Chronic Hepatitis CPhase 1/2NCT01974687

Single and Multiple Dose Study of Uprifosbuvir (MK-3682/IDX21437) in Healthy and Hepatitis C Virus (HCV)-Infected Participants (MK-3682-001)

A Phase 1/2 study testing Uprifosbuvir and Itraconazole in people with Chronic Hepatitis C, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This is a multi-part study to evaluate the safety, tolerability, and pharmacokinetics (PK) of uprifosbuvir (MK-3682/IDX21437) in healthy participants and in participants infected with Hepatitis C virus (HCV) genotype (GT)1-GT6. The effect of food on the PK of uprifosbuvir will be evaluated. Read more about this study

Who is it for?: Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for: Chronic Hepatitis C
What is being tested?: Uprifosbuvir and Itraconazole
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 178 participants
Where: No sites listed yet
Study dates: 31 Oct 2013to 11 Sep 2015
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

All Participants:
of childbearing potential must have agreed to use a double method of birth control (one of which must be a barrier) from Screening through at least 90 days after the last dose of the study drug
must not have consumed grapefruit or grapefruit juice within 7 days of Day -1 and throughout the study
HCV Participants:
documented clinical history compatible with chronic hepatitis C.
have not received direct-acting antiviral treatment for hepatitis C infection
has HCV Genotype 1, 2, 3, 4, 5 or 6

Who cannot join

All Participants:
pregnant or breastfeeding
co-infected with hepatitis B virus (HBV) and/or human immunodeficiency virus (HIV).
decompensated liver disease
other clinically significant medical conditions or laboratory abnormalities.

About this study

Official title: A Phase I/IIa Study Assessing Single and Multiple Doses of IDX21437 in Healthy and HCV-Infected Subjects

Conditions: Chronic Hepatitis C
Being tested: Uprifosbuvir, Placebo, Itraconazole
Keywords: Hepatitis C virus, HCV
Medical subject headings: Hepatitis C, Chronic, Hepatitis C

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

UprifosbuvirDrug
Also called MK-3682/IDX21437
Uprifosbuvir 5 mg, 25 mg, or 50 mg capsule, or 150 mg tablet, administered by mouth.
PlaceboDrug
Matching placebo to uprifosbuvir capsule administered by mouth.
ItraconazoleDrug
Also called Sporanox®
Itraconazole is supplied as 10 mg/mL oral solution or 100 mg capsules administered by mouth.

Study groups in NCT01974687
Study group	Role	What they receive
Group A: Healthy	Experimental	Healthy participants will receive sequentially higher doses of uprifosbuvir (10 mg - 300 mg) capsules or matching placebo capsules once daily (QD) on Day 1 (Cohorts 1a-3a, 5a), Days 1 and 7 (Cohort 4a), or Day 1 - Day 7 (Cohort 6a). Dosing of next cohort will be based on review of available safety and PK data. Dosing will occur under fasted conditions with the exception of Cohort 4a, in which drug administration will occur under both fasted and fed conditions. Receives: Drug: Uprifosbuvir; Drug: Placebo
Group B: GT1 HCV-infected, treatment naive on Day 1	Experimental	HCV GT1 participants with no prior direct-acting antiviral (DAA) exposure will receive a single dose of uprifosbuvir (10 mg - 300 mg) for 1 day across sequential dose cohorts. Dosing will commence following review of available safety and PK data from respective dose cohorts in Group A. All dosing will occur under fasted conditions. Receives: Drug: Uprifosbuvir
Group C: GT1 HCV-infected on Days 1-7	Experimental	HCV GT1 participants will receive uprifosbuvir (50 mg - 400 mg in capsules or 300 mg or 450 mg in tablets) or matching placebo capsules QD for 7 days. Dosing will commence following review of available safety and PK data of Group A. Fed vs. fasted dosing will be dependent on food effect results from Group A. Receives: Drug: Uprifosbuvir; Drug: Placebo
Group D: GT2 through GT6 HCV-infected on Days 1-7	Experimental	HCV GT2 - GT6 participants will receive uprifosbuvir (50 mg - 300 mg) capsules QD for 7 days. Dosing will commence following review of available safety and PK data from Group A. Fed vs. fasted dosing will be dependent on food effect results from Group A. Receives: Drug: Uprifosbuvir
Group E: GT1 HCV-infected on Days 1-7, mild hepatic impairment	Experimental	HCV GT1 participants with mildly impaired hepatic function will receive uprifosbuvir (150 mg - 450 mg) capsules QD for 1 or 7 days. Dosing of subsequent cohorts will be based on review of available safety and PK data. Fed vs. fasted dosing will be dependent on food effect results from Group A. Receives: Drug: Uprifosbuvir
Group F: GT1 HCV-infected on Days 1-7, + Itraconazole	Experimental	HCV GT1 participants will receive itraconazole 200 mg twice daily (BID) on Day -5 and itraconazole 200 mg QD from Day -4 to Day 11. Participants will also be co-administered uprifosbuvir 300 mg from Day 1 to Day 7. Receives: Drug: Itraconazole

What is being measured

The primary outcome is the main question the study is designed to answer.

Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (AE)
An AE was defined as any untoward medical occurrence in a participant administered study drug, and that does not necessarily have a causal relationship with the study drug(s). An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug(s), whether or not related to study drug(s). The percentage of participants who experienced at least one AE is presented.
Measured: Up to 42 days
Percentage of Participants Who Experienced at Least One Treatment-emergent Serious AE (SAE)
An SAE was defined as any untoward medical occurrence that at any dose that: resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. The percentage of participants who experienced at least one SAE is presented.
Measured: Up to 42 days
Percentage of Participants Who Experienced a Treatment-emergent Dose-limiting Toxicity (DLT)
A DLT was defined as any of the following events: Any SAE considered by the investigator to be at least reasonably or possibly related to study drug; Any Grade 3 clinical AE considered by the investigator to be at least reasonably or possibly related to study drug; Any Grade 3 confirmed laboratory abnormalities considered by the investigator to be at least reasonably or possibly related to study drug, except for asymptomatic Grade ¾ cholesterol and triglyceride; Any clinical or laboratory AE of any intensity that is considered by the investigator to be at least reasonably or possibly related to study drug that necessitates permanent discontinuation of study drug; Confirmed increase in QT interval corrected for heart rate using Fridericia's (QTcF) formula ≥60 msec over Baseline or an absolute QTcF ≥500 msec.
Measured: Up to 13 days
Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality
Laboratory abnormalities were graded using the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events. Treatment-emergent AEs (TEAEs)were graded as: Grade 1: Mild TEAE as Worst Severity; Grade 2: Moderate TEAE as Worst Severity; Grade 3: Severe TEAE as Worst Severity; Grade 4: Potentially Life-Threatening TEAE as Worst Severity; Grade 5: TEAE Leading to Death. The percentage of participants who experienced at least one Grade 1, 2, 3, 4 or 5 laboratory abnormality is presented.
Measured: Up to 42 days
Percentage of Participants Who Discontinued Study Drug Due to a Treatment-emergent AE
The percentage of participants who discontinued study drug due to an AE is presented.
Measured: Up to 14 days
Area Under the Plasma Drug Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A)
AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration. All participants were fasted.
Measured: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
AUC0-t of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a)
AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration.
Measured: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
AUC0-t of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Healthy Participants (Group A - Cohort 6a)
AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration.
Measured: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
AUC0-t of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B)
AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration.
Measured: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
AUC0-t of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D)
AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration.
Measured: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
AUC0-t of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C)
AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration.
Measured: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
AUC0-t of Uprifosbuvir After Single Dose of Uprifosbuvir as Capsule Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 1e)
AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration.
Measured: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
AUC0-t of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e)
AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration.
Measured: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
AUC0-t of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Tablet Formulation in Genotype 1, HCV-Infected Participants, With Itraconazole (Group F)
AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration.
Measured: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Maximum (Peak) Observed Plasma Drug Concentration (Cmax) of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A)
Maximum observed plasma drug concentration was obtained. All participants were fasted.
Measured: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Cmax of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a)
Maximum observed plasma drug concentration was obtained.
Measured: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Cmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Healthy Participants (Group A - Cohort 6a)
Maximum observed plasma drug concentration was obtained.
Measured: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Cmax of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B)
Maximum observed plasma drug concentration was obtained.
Measured: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Cmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D)
Maximum observed plasma drug concentration was obtained. All participants were fasted.
Measured: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Cmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C)
Maximum observed plasma drug concentration was obtained.
Measured: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Cmax of Uprifosbuvir After Single Dose of Uprifosbuvir as Capsule Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 1e)
Maximum observed plasma drug concentration was obtained.
Measured: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Cmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e)
Maximum observed plasma drug concentration was obtained.
Measured: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Cmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Tablet Formulation in Genotype 1, HCV-Infected Participants, With Itraconazole (Group F)
Maximum observed plasma drug concentration was obtained.
Measured: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Time to Maximum Plasma Concentration (Tmax) of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A)
Time to maximum plasma concentration was obtained. All participants were fasted.
Measured: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Tmax of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a)
Time to maximum plasma concentration was obtained.
Measured: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Tmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Healthy Participants (Group A - Cohort 6a)
Maximum observed plasma drug concentration was obtained.
Measured: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Tmax of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-infected Participants (Group B)
Time to maximum plasma concentration was obtained.
Measured: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Tmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-infected Participants (Groups C and D)
Time to maximum plasma concentration was obtained.
Measured: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Tmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-infected Participants (Group C)
Time to maximum plasma concentration was obtained.
Measured: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Tmax of Uprifosbuvir After Singe Dose of Uprifosbuvir as Capsule Formulation in Genotype 1, HCV-infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 1e)
Time to maximum plasma concentration was obtained.
Measured: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Tmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e)
AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration.
Measured: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Tmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-infected Participants, With Itraconazole (Group F)
Time to maximum plasma concentration was obtained.
Measured: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Observed Terminal Half-Life (t1/2) of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A)
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained. All participants were fasted.
Measured: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
t1/2 of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a)
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
Measured: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
t1/2 of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-infected Participants (Group B)
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
Measured: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
t1/2 of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-infected Participants (Groups C and D)
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
Measured: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
t1/2 of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-infected Participants (Group C)
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
Measured: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
t1/2 of Uprifosbuvir After Single Dose of Uprifosbuvir as Capsule Formulation in Genotype 1, HCV-infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 1e)
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
Measured: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
t1/2 of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e)
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
Measured: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
t1/2 of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-infected Participants, With Itraconazole (Group F)
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
Measured: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
AUC0-inf of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A)
Area under the drug concentration-time curve from time zero to infinity for M6, a metabolite of uprifosbuvir, estimated as AUC0-t + Cest/λz, where λz is the terminal elimination rate constant, calculated for the first dose only. All participants were fasted.
Measured: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
AUC0-inf of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a)
Area under the drug concentration-time curve from time zero to infinity estimated as AUC0-t + Cest/λz, where λz is the terminal elimination rate constant, calculated for the first dose only.
Measured: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
AUC0-inf of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Healthy Participants (Group A - Cohort 6a)
Area under the drug concentration-time curve from time zero to infinity estimated as AUC0-t + Cest/λz, where λz is the terminal elimination rate constant, calculated for the first dose only.
Measured: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
AUC0-inf of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B)
Area under the drug concentration-time curve from time zero to infinity estimated as AUC0-t + Cest/λz, where λz is the terminal elimination rate constant, calculated for the first dose only.
Measured: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
AUC0-inf of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D)
Area under the drug concentration-time curve from time zero to infinity estimated as AUC0-t + Cest/λz, where λz is the terminal elimination rate constant, calculated for the first dose only.
Measured: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
AUC0-inf of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C)
Area under the drug concentration-time curve from time zero to infinity estimated as AUC0-t + Cest/λz, where λz is the terminal elimination rate constant, calculated for the first dose only.
Measured: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
AUC0-inf of M6 After Single Dose of Uprifosbuvir as Capsule Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 1e)
Area under the drug concentration-time curve from time zero to infinity estimated as AUC0-t + Cest/λz, where λz is the terminal elimination rate constant, calculated for the first dose only.
Measured: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
AUC0-inf of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e)
Area under the drug concentration-time curve from time zero to infinity estimated as AUC0-t + Cest/λz, where λz is the terminal elimination rate constant, calculated for the first dose only.
Measured: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
AUC0-inf of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants, With Itraconazole (Group F)
Area under the drug concentration-time curve from time zero to infinity estimated as AUC0-t + Cest/λz, where λz is the terminal elimination rate constant, calculated for the first dose only.
Measured: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Cmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A)
Maximum observed plasma drug concentration was obtained. All participants were fasted.
Measured: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Cmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a)
Maximum observed plasma drug concentration was obtained.
Measured: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Cmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Healthy Participants (Group A - Cohort 6a)
Maximum observed plasma drug concentration was obtained.
Measured: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Cmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B)
Maximum observed plasma drug concentration was obtained.
Measured: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Cmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D)
Maximum observed plasma drug concentration was obtained.
Measured: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Cmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C)
Maximum observed plasma drug concentration was obtained.
Measured: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Cmax of M6 After Single Dose of Uprifosbuvir as Capsule Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 1e)
Maximum observed plasma drug concentration was obtained.
Measured: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Cmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e)
Maximum observed plasma drug concentration was obtained.
Measured: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Cmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants, With Itraconazole (Group F)
Maximum observed plasma drug concentration was obtained.
Measured: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Tmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A)
Time to maximum plasma concentration was obtained. All participants were fasted.
Measured: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Tmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a)
Time to maximum plasma concentration was obtained.
Measured: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Tmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Healthy Participants (Group A - Cohort 6a)
Time to maximum plasma concentration was obtained.
Measured: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Tmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B)
Time to maximum plasma concentration was obtained.
Measured: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Tmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D)
Time to maximum plasma concentration was obtained.
Measured: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Tmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C)
Time to maximum plasma concentration was obtained.
Measured: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Tmax of M6 After Single Dose of Uprifosbuvir as Capsule Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 1e)
Time to maximum plasma concentration was obtained.
Measured: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Tmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1,HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e)
Time to maximum plasma concentration was obtained.
Measured: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Tmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants, With Itraconazole (Group F)
Time to maximum plasma concentration was obtained.
Measured: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
t1/2 of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A)
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained. All participants were fasted.
Measured: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
t1/2 of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a)
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
Measured: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
t1/2 of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Healthy Participants (Group A - Cohort 6a)
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
Measured: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
t1/2 of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B)
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
Measured: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
t1/2 of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D)
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
Measured: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
t1/2 of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C)
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
Measured: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
t1/2 of M6 After Single Dose of Uprifosbuvir as Capsule Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 1e)
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
Measured: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
t1/2 of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e)
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
Measured: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
t1/2 of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants, With Itraconazole (Group F)
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
Measured: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Cumulative Urine Excretion of Unchanged Uprifosbuvir in Healthy Participants (Group A)
Cumulative urine excretion of unchanged MK-3682 in healthy participants was obtained. All participants were fasted.
Measured: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Cumulative Urine Excretion of Unchanged M6 in Healthy Participants (Group A)
Cumulative urine excretion of unchanged M6 in healthy participants was obtained. All participants were fasted.
Measured: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Reduction in HCV RNA From Baseline on Day 8 Following Uprifosbuvir 50-450 mg for 7 Days in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D)
Reduction in HCV RNA from baseline on Day 8 following uprifosbuvir 50-450 mg for 7 Days in Genotype 1, 2 and 3, HCV-infected participants was obtained.
Measured: Baseline and Day 8
Maximum Reduction in log10 HCV RNA From Baseline - Normal Participants (From Groups B and C) vs. Mild Hepatic Impairment Participants (Group E)
Reduction in HCV RNA from baseline on Day 8 following uprifosbuvir 50-450 mg for 7 Days in Genotype (Gt) 1, HCV-infected participants was obtained.
Measured: Baseline and 28 days after last dose of study drug (Up to 42 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

31 Oct 201311 Sep 2015

First posted1 Nov 2013 (estimated)
Study start31 Oct 2013
Primary completion2 Sep 2015
Study completion11 Sep 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Chronic Hepatitis CStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 178 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01974687
Sponsor's protocol ID: 3682-001
Other IDs: U1111-1149-5611, IDX-04B-001, 2013-004043-23, MK-3682-001
Status last verified: Sep 2018
First submitted: 28 Oct 2013
Last updated: 13 Sep 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

RecruitingObservational study
Evaluation of Patients With Liver Disease
Hepatitis D, Hepatitis C
Active, not recruitingPhase 4
People With CHC Who Achieved a Sustained Virological Response Following Therapy With Direct Acting Antiviral Agents
Diabetes Mellitus, Hepatitis C, Chronic
RecruitingObservational study
"Constitution of a Biological Collection to Establish Preclinical Translational Models for the Study of Tumors and Chronic Liver Diseases".
Chronic Liver Disease and Cirrhosis, Liver Cancer
Active, not recruitingPhase 4
Sofosbuvir/Velpatasvir Treatment of Chronic Hepatitis C During Pregnancy
Hepatitis C, Chronic, Pregnancy; Infection
Enrolling by invitationObservational study
Comparative Autoantibody and Immunologic Cell Marker Study
Autoimmune Diseases, Lupus Erythematosus, Systemic

All Chronic Hepatitis C trials

Study at a glance

From the registry record, last updated by the sponsor on 13 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I/IIa Study Assessing Single and Multiple Doses of IDX21437 in Healthy and HCV-Infected Subjects
ClinicalTrials.gov ID: NCT01974687
Acronym / sponsor ID: 3682-001
Conditions: Chronic Hepatitis C
Keywords: Hepatitis C virus, HCV
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 178 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 31 Oct 2013 (actual)
Primary completion: 2 Sep 2015 (actual)
Study completion: 11 Sep 2015 (actual)
First posted: 1 Nov 2013 (estimated)
Results: Posted 13 Sep 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 6

Arm	Type	Receives
Group A: Healthy	Experimental	Drug: Uprifosbuvir, Drug: PlaceboHealthy participants will receive sequentially higher doses of uprifosbuvir (10 mg - 300 mg) capsules or matching placebo capsules once daily (QD) on Day 1 (Cohorts 1a-3a, 5a), Days 1 and 7 (Cohort 4a), or Day 1 - Day 7 (Cohort 6a). Dosing of next cohort will be based on review of available safety and PK data. Dosing will occur under fasted conditions with the exception of Cohort 4a, in which drug administration will occur under both fasted and fed conditions.
Group B: GT1 HCV-infected, treatment naive on Day 1	Experimental	Drug: UprifosbuvirHCV GT1 participants with no prior direct-acting antiviral (DAA) exposure will receive a single dose of uprifosbuvir (10 mg - 300 mg) for 1 day across sequential dose cohorts. Dosing will commence following review of available safety and PK data from respective dose cohorts in Group A. All dosing will occur under fasted conditions.
Group C: GT1 HCV-infected on Days 1-7	Experimental	Drug: Uprifosbuvir, Drug: PlaceboHCV GT1 participants will receive uprifosbuvir (50 mg - 400 mg in capsules or 300 mg or 450 mg in tablets) or matching placebo capsules QD for 7 days. Dosing will commence following review of available safety and PK data of Group A. Fed vs. fasted dosing will be dependent on food effect results from Group A.
Group D: GT2 through GT6 HCV-infected on Days 1-7	Experimental	Drug: UprifosbuvirHCV GT2 - GT6 participants will receive uprifosbuvir (50 mg - 300 mg) capsules QD for 7 days. Dosing will commence following review of available safety and PK data from Group A. Fed vs. fasted dosing will be dependent on food effect results from Group A.
Group E: GT1 HCV-infected on Days 1-7, mild hepatic impairment	Experimental	Drug: UprifosbuvirHCV GT1 participants with mildly impaired hepatic function will receive uprifosbuvir (150 mg - 450 mg) capsules QD for 1 or 7 days. Dosing of subsequent cohorts will be based on review of available safety and PK data. Fed vs. fasted dosing will be dependent on food effect results from Group A.
Group F: GT1 HCV-infected on Days 1-7, + Itraconazole	Experimental	Drug: ItraconazoleHCV GT1 participants will receive itraconazole 200 mg twice daily (BID) on Day -5 and itraconazole 200 mg QD from Day -4 to Day 11. Participants will also be co-administered uprifosbuvir 300 mg from Day 1 to Day 7.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

of childbearing potential must have agreed to use a double method of birth control (one of which must be a barrier) from Screening through at least 90 days after the last dose of the study drug
must not have consumed grapefruit or grapefruit juice within 7 days of Day -1 and throughout the study
documented clinical history compatible with chronic hepatitis C.
have not received direct-acting antiviral treatment for hepatitis C infection
has HCV Genotype 1, 2, 3, 4, 5 or 6

Key exclusion criteria (5 listed)

pregnant or breastfeeding
co-infected with hepatitis B virus (HBV) and/or human immunodeficiency virus (HIV).
decompensated liver disease
other clinically significant medical conditions or laboratory abnormalities.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
UprifosbuvirAlso: MK-3682/IDX21437Uprifosbuvir 5 mg, 25 mg, or 50 mg capsule, or 150 mg tablet, administered by mouth.	Drug	Group A: Healthy, Group B: GT1 HCV-infected, treatment naive on Day 1, Group C: GT1 HCV-infected on Days 1-7, Group D: GT2 through GT6 HCV-infected on Days 1-7, Group E: GT1 HCV-infected on Days 1-7, mild hepatic impairment
PlaceboMatching placebo to uprifosbuvir capsule administered by mouth.	Drug	Group A: Healthy, Group C: GT1 HCV-infected on Days 1-7
ItraconazoleAlso: Sporanox®Itraconazole is supplied as 10 mg/mL oral solution or 100 mg capsules administered by mouth.	Drug	Group F: GT1 HCV-infected on Days 1-7, + Itraconazole

Primary outcome

Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (AE)
Time frame: Up to 42 days
An AE was defined as any untoward medical occurrence in a participant administered study drug, and that does not necessarily have a causal relationship with the study drug(s). An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug(s), whether or not related to study drug(s). The percentage of participants who experienced at least one AE is presented.
Percentage of Participants Who Experienced at Least One Treatment-emergent Serious AE (SAE)
Time frame: Up to 42 days
An SAE was defined as any untoward medical occurrence that at any dose that: resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. The percentage of participants who experienced at least one SAE is presented.
Percentage of Participants Who Experienced a Treatment-emergent Dose-limiting Toxicity (DLT)
Time frame: Up to 13 days
A DLT was defined as any of the following events: Any SAE considered by the investigator to be at least reasonably or possibly related to study drug; Any Grade 3 clinical AE considered by the investigator to be at least reasonably or possibly related to study drug; Any Grade 3 confirmed laboratory abnormalities considered by the investigator to be at least reasonably or possibly related to study drug, except for asymptomatic Grade ¾ cholesterol and triglyceride; Any clinical or laboratory AE of any intensity that is considered by the investigator to be at least reasonably or possibly related to study drug that necessitates permanent discontinuation of study drug; Confirmed increase in QT interval corrected for heart rate using Fridericia's (QTcF) formula ≥60 msec over Baseline or an absolute QTcF ≥500 msec.
Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality
Time frame: Up to 42 days
Laboratory abnormalities were graded using the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events. Treatment-emergent AEs (TEAEs)were graded as: Grade 1: Mild TEAE as Worst Severity; Grade 2: Moderate TEAE as Worst Severity; Grade 3: Severe TEAE as Worst Severity; Grade 4: Potentially Life-Threatening TEAE as Worst Severity; Grade 5: TEAE Leading to Death. The percentage of participants who experienced at least one Grade 1, 2, 3, 4 or 5 laboratory abnormality is presented.
Percentage of Participants Who Discontinued Study Drug Due to a Treatment-emergent AE
Time frame: Up to 14 days
The percentage of participants who discontinued study drug due to an AE is presented.
Area Under the Plasma Drug Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A)
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration. All participants were fasted.
AUC0-t of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a)
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration.
AUC0-t of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Healthy Participants (Group A - Cohort 6a)
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration.
AUC0-t of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B)
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration.
AUC0-t of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D)
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration.
AUC0-t of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C)
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration.
AUC0-t of Uprifosbuvir After Single Dose of Uprifosbuvir as Capsule Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 1e)
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration.
AUC0-t of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e)
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration.
AUC0-t of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Tablet Formulation in Genotype 1, HCV-Infected Participants, With Itraconazole (Group F)
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration.
Maximum (Peak) Observed Plasma Drug Concentration (Cmax) of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A)
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Maximum observed plasma drug concentration was obtained. All participants were fasted.
Cmax of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a)
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Maximum observed plasma drug concentration was obtained.
Cmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Healthy Participants (Group A - Cohort 6a)
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Maximum observed plasma drug concentration was obtained.
Cmax of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B)
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Maximum observed plasma drug concentration was obtained.
Cmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D)
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Maximum observed plasma drug concentration was obtained. All participants were fasted.
Cmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C)
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Maximum observed plasma drug concentration was obtained.
Cmax of Uprifosbuvir After Single Dose of Uprifosbuvir as Capsule Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 1e)
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Maximum observed plasma drug concentration was obtained.
Cmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e)
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Maximum observed plasma drug concentration was obtained.
Cmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Tablet Formulation in Genotype 1, HCV-Infected Participants, With Itraconazole (Group F)
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Maximum observed plasma drug concentration was obtained.
Time to Maximum Plasma Concentration (Tmax) of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A)
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Time to maximum plasma concentration was obtained. All participants were fasted.
Tmax of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a)
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Time to maximum plasma concentration was obtained.
Tmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Healthy Participants (Group A - Cohort 6a)
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Maximum observed plasma drug concentration was obtained.
Tmax of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-infected Participants (Group B)
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Time to maximum plasma concentration was obtained.
Tmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-infected Participants (Groups C and D)
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Time to maximum plasma concentration was obtained.
Tmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-infected Participants (Group C)
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Time to maximum plasma concentration was obtained.
Tmax of Uprifosbuvir After Singe Dose of Uprifosbuvir as Capsule Formulation in Genotype 1, HCV-infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 1e)
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Time to maximum plasma concentration was obtained.
Tmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e)
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration.
Tmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-infected Participants, With Itraconazole (Group F)
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Time to maximum plasma concentration was obtained.
Observed Terminal Half-Life (t1/2) of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A)
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained. All participants were fasted.
t1/2 of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a)
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
t1/2 of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-infected Participants (Group B)
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
t1/2 of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-infected Participants (Groups C and D)
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
t1/2 of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-infected Participants (Group C)
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
t1/2 of Uprifosbuvir After Single Dose of Uprifosbuvir as Capsule Formulation in Genotype 1, HCV-infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 1e)
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
t1/2 of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e)
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
t1/2 of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-infected Participants, With Itraconazole (Group F)
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
AUC0-inf of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A)
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Area under the drug concentration-time curve from time zero to infinity for M6, a metabolite of uprifosbuvir, estimated as AUC0-t + Cest/λz, where λz is the terminal elimination rate constant, calculated for the first dose only. All participants were fasted.
AUC0-inf of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a)
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Area under the drug concentration-time curve from time zero to infinity estimated as AUC0-t + Cest/λz, where λz is the terminal elimination rate constant, calculated for the first dose only.
AUC0-inf of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Healthy Participants (Group A - Cohort 6a)
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Area under the drug concentration-time curve from time zero to infinity estimated as AUC0-t + Cest/λz, where λz is the terminal elimination rate constant, calculated for the first dose only.
AUC0-inf of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B)
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Area under the drug concentration-time curve from time zero to infinity estimated as AUC0-t + Cest/λz, where λz is the terminal elimination rate constant, calculated for the first dose only.
AUC0-inf of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D)
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Area under the drug concentration-time curve from time zero to infinity estimated as AUC0-t + Cest/λz, where λz is the terminal elimination rate constant, calculated for the first dose only.
AUC0-inf of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C)
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Area under the drug concentration-time curve from time zero to infinity estimated as AUC0-t + Cest/λz, where λz is the terminal elimination rate constant, calculated for the first dose only.
AUC0-inf of M6 After Single Dose of Uprifosbuvir as Capsule Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 1e)
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Area under the drug concentration-time curve from time zero to infinity estimated as AUC0-t + Cest/λz, where λz is the terminal elimination rate constant, calculated for the first dose only.
AUC0-inf of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e)
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Area under the drug concentration-time curve from time zero to infinity estimated as AUC0-t + Cest/λz, where λz is the terminal elimination rate constant, calculated for the first dose only.
AUC0-inf of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants, With Itraconazole (Group F)
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Area under the drug concentration-time curve from time zero to infinity estimated as AUC0-t + Cest/λz, where λz is the terminal elimination rate constant, calculated for the first dose only.
Cmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A)
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Maximum observed plasma drug concentration was obtained. All participants were fasted.
Cmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a)
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Maximum observed plasma drug concentration was obtained.
Cmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Healthy Participants (Group A - Cohort 6a)
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Maximum observed plasma drug concentration was obtained.
Cmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B)
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Maximum observed plasma drug concentration was obtained.
Cmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D)
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Maximum observed plasma drug concentration was obtained.
Cmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C)
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Maximum observed plasma drug concentration was obtained.
Cmax of M6 After Single Dose of Uprifosbuvir as Capsule Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 1e)
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Maximum observed plasma drug concentration was obtained.
Cmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e)
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Maximum observed plasma drug concentration was obtained.
Cmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants, With Itraconazole (Group F)
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Maximum observed plasma drug concentration was obtained.
Tmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A)
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Time to maximum plasma concentration was obtained. All participants were fasted.
Tmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a)
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Time to maximum plasma concentration was obtained.
Tmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Healthy Participants (Group A - Cohort 6a)
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Time to maximum plasma concentration was obtained.
Tmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B)
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Time to maximum plasma concentration was obtained.
Tmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D)
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Time to maximum plasma concentration was obtained.
Tmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C)
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Time to maximum plasma concentration was obtained.
Tmax of M6 After Single Dose of Uprifosbuvir as Capsule Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 1e)
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Time to maximum plasma concentration was obtained.
Tmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1,HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e)
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Time to maximum plasma concentration was obtained.
Tmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants, With Itraconazole (Group F)
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Time to maximum plasma concentration was obtained.
t1/2 of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A)
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained. All participants were fasted.
t1/2 of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a)
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
t1/2 of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Healthy Participants (Group A - Cohort 6a)
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
t1/2 of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B)
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
t1/2 of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D)
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
t1/2 of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C)
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
t1/2 of M6 After Single Dose of Uprifosbuvir as Capsule Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 1e)
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
t1/2 of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e)
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
t1/2 of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants, With Itraconazole (Group F)
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
Cumulative Urine Excretion of Unchanged Uprifosbuvir in Healthy Participants (Group A)
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Cumulative urine excretion of unchanged MK-3682 in healthy participants was obtained. All participants were fasted.
Cumulative Urine Excretion of Unchanged M6 in Healthy Participants (Group A)
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Cumulative urine excretion of unchanged M6 in healthy participants was obtained. All participants were fasted.
Reduction in HCV RNA From Baseline on Day 8 Following Uprifosbuvir 50-450 mg for 7 Days in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D)
Time frame: Baseline and Day 8
Reduction in HCV RNA from baseline on Day 8 following uprifosbuvir 50-450 mg for 7 Days in Genotype 1, 2 and 3, HCV-infected participants was obtained.
Maximum Reduction in log10 HCV RNA From Baseline - Normal Participants (From Groups B and C) vs. Mild Hepatic Impairment Participants (Group E)
Time frame: Baseline and 28 days after last dose of study drug (Up to 42 days)
Reduction in HCV RNA from baseline on Day 8 following uprifosbuvir 50-450 mg for 7 Days in Genotype (Gt) 1, HCV-infected participants was obtained.

Results and safety

Results posted to the registry on 13 Sep 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Group A: Uprifosbuvir 10 mg (Cohort 1a)	6	6
Group A: Uprifosbuvir 25 mg (Cohort 2a)	6	6
Group A: Uprifosbuvir 150 mg (Cohort 4a)	6	6
Group A: Uprifosbuvir 300 mg (Cohort 5a)	6	6
Group A: Placebo (Cohort 6a)	2	2
Group A: Uprifosbuvir 300 mg (Cohort 6a)	6	6
Group B: Uprifosbuvir 10 mg (Cohort 1b)	3	3
Group B: Uprifosbuvir 25 mg (Cohort 2b)	3	3
Group B: Uprifosbuvir 50 mg (Cohort 3b)	3	3
Group B: Uprifosbuvir 150 mg (Cohort 4b)	3	3
Group B: Uprifosbuvir 300 mg (Cohort 5b)	3	3
Groups C & D: Uprifosbuvir 50 mg (Capsule)	13	11
Groups C & D: Uprifosbuvir 150 mg (Capsule)	13	10
Groups C & D: Uprifosbuvir 250 mg (Capsule)	10	8
Groups C & D: Uprifosbuvir 300 mg (Capsule)	19	18
Groups C & D: Uprifosbuvir 400 mg (Capsule)	9	8
Groups C & D: Uprifosbuvir 300 mg (Tablet)	9	8
Groups C & D: Uprifosbuvir 450 mg (Tablet)	11	8
Groups C & D: Placebo (Pooled)	9	9
Group E: Uprifosbuvir 150 mg (Cohort 1e)	3	3
Group E: Uprifosbuvir 300 mg (Cohort 2e)	3	3
Group E: Uprifosbuvir 450 mg (Cohort 3e)	8	8
Group F: Uprifosbuvir 300 mg (Tablet)	8	8
Group A: Uprifosbuvir 50 mg (Cohort 3a)	6	6
Group A: Placebo (Cohorts 1a-5a - Pooled)	10	10

Primary outcome: Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (AE)

Time frame: Up to 42 days. Number. Unit: Percentage of Participants

Measure	Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) n = 10	Group A: Uprifosbuvir 10 mg (Cohort 1a) n = 6	Group A: Uprifosbuvir 25 mg (Cohort 2a) n = 6	Group A: Uprifosbuvir 50 mg (Cohort 3a) n = 6	Group A: Uprifosbuvir 150 mg (Cohort 4a) (Fasted and Fed) n = 6	Group A: Uprifosbuvir 300 mg (Cohort 5a) n = 6	Group A: Uprifosbuvir 300 mg (Cohort 6a) n = 6	Group A: Placebo (Cohort 6a) n = 2	Group B: Uprifosbuvir 10 mg (Cohort 1b) n = 3	Group B: Uprifosbuvir 25 mg (Cohort 2b) n = 3	Group B: Uprifosbuvir 50 mg (Cohort 3b) n = 3	Group B: Uprifosbuvir 150 mg (Cohort 4b) n = 3	Group B: Uprifosbuvir 300 mg (Cohort 5b) n = 3	Groups C & D: Uprifosbuvir 50 mg (Capsule) n = 11	Groups C & D: Uprifosbuvir 150 mg (Capsule) n = 10	Groups C & D: Uprifosbuvir 250 mg (Capsule) n = 8	Groups C & D: Uprifosbuvir 300 mg (Capsule) n = 18	Groups C & D: Uprifosbuvir 400 mg (Capsule) n = 8	Groups C & D: Uprifosbuvir 300 mg (Tablet) n = 8	Groups C & D: Uprifosbuvir 450 mg (Tablet) n = 8	Groups C & D: Placebo (Pooled) n = 9	Group E: Uprifosbuvir 150 mg (Cohort 1e) n = 3	Group E: Uprifosbuvir 300 mg (Cohort 2e) n = 3	Group E: Uprifosbuvir 450 mg (Cohort 3e) n = 8	Group F: Uprifosbuvir 300 mg (Tablet)

Primary outcome: Percentage of Participants Who Experienced at Least One Treatment-emergent Serious AE (SAE)

Time frame: Up to 42 days. Number. Unit: Percentage of Participants

Measure	Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) n = 10	Group A: Uprifosbuvir 10 mg (Cohort 1a) n = 6	Group A: Uprifosbuvir 25 mg (Cohort 2a) n = 6	Group A: Uprifosbuvir 50 mg (Cohort 3a) n = 6	Group A: Uprifosbuvir 150 mg (Cohort 4a) (Fasted and Fed) n = 6	Group A: Uprifosbuvir 300 mg (Cohort 5a) n = 6	Group A: Uprifosbuvir 300 mg (Cohort 6a) n = 6	Group A: Placebo (Cohort 6a) n = 2	Group B: Uprifosbuvir 10 mg (Cohort 1b) n = 3	Group B: Uprifosbuvir 25 mg (Cohort 2b) n = 3	Group B: Uprifosbuvir 50 mg (Cohort 3b) n = 3	Group B: Uprifosbuvir 150 mg (Cohort 4b) n = 3	Group B: Uprifosbuvir 300 mg (Cohort 5b) n = 3	Groups C & D: Uprifosbuvir 50 mg (Capsule) n = 11	Groups C & D: Uprifosbuvir 150 mg (Capsule) n = 10	Groups C & D: Uprifosbuvir 250 mg (Capsule) n = 8	Groups C & D: Uprifosbuvir 300 mg (Capsule) n = 18	Groups C & D: Uprifosbuvir 400 mg (Capsule) n = 8	Groups C & D: Uprifosbuvir 300 mg (Tablet) n = 8	Groups C & D: Uprifosbuvir 450 mg (Tablet) n = 8	Groups C & D: Placebo (Pooled) n = 9	Group E: Uprifosbuvir 150 mg (Cohort 1e) n = 3	Group E: Uprifosbuvir 300 mg (Cohort 2e) n = 3	Group E: Uprifosbuvir 450 mg (Cohort 3e) n = 8	Group F: Uprifosbuvir 300 mg (Tablet)

Primary outcome: Percentage of Participants Who Experienced a Treatment-emergent Dose-limiting Toxicity (DLT)

Time frame: Up to 13 days. Number. Unit: Percentage of Participants

Measure	Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) n = 10	Group A: Uprifosbuvir 10 mg (Cohort 1a) n = 6	Group A: Uprifosbuvir 25 mg (Cohort 2a) n = 6	Group A: Uprifosbuvir 50 mg (Cohort 3a) n = 6	Group A: Uprifosbuvir 150 mg (Cohort 4a) (Fasted and Fed) n = 6	Group A: Uprifosbuvir 300 mg (Cohort 5a) n = 6	Group A: Uprifosbuvir 300 mg (Cohort 6a) n = 6	Group A: Placebo (Cohort 6a) n = 2	Group B: Uprifosbuvir 10 mg (Cohort 1b) n = 3	Group B: Uprifosbuvir 25 mg (Cohort 2b) n = 3	Group B: Uprifosbuvir 50 mg (Cohort 3b) n = 3	Group B: Uprifosbuvir 150 mg (Cohort 4b) n = 3	Group B: Uprifosbuvir 300 mg (Cohort 5b) n = 3	Groups C & D: Uprifosbuvir 50 mg (Capsule) n = 11	Groups C & D: Uprifosbuvir 150 mg (Capsule) n = 10	Groups C & D: Uprifosbuvir 250 mg (Capsule) n = 8	Groups C & D: Uprifosbuvir 300 mg (Capsule) n = 18	Groups C & D: Uprifosbuvir 400 mg (Capsule) n = 8	Groups C & D: Uprifosbuvir 300 mg (Tablet) n = 8	Groups C & D: Uprifosbuvir 450 mg (Tablet) n = 8	Groups C & D: Placebo (Pooled) n = 9	Group E: Uprifosbuvir 150 mg (Cohort 1e) n = 3	Group E: Uprifosbuvir 300 mg (Cohort 2e) n = 3	Group E: Uprifosbuvir 450 mg (Cohort 3e) n = 8	Group F: Uprifosbuvir 300 mg (Tablet)

Primary outcome: Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality

Time frame: Up to 42 days. Number. Unit: Percentage of Participants

Measure	Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) n = 10	Group A: Uprifosbuvir 10 mg (Cohort 1a) n = 6	Group A: Uprifosbuvir 25 mg (Cohort 2a) n = 6	Group A: Uprifosbuvir 50 mg (Cohort 3a) n = 6	Group A: Uprifosbuvir 150 mg (Cohort 4a) (Fasted and Fed) n = 6	Group A: Uprifosbuvir 300 mg (Cohort 5a) n = 6	Group A: Uprifosbuvir 300 mg (Cohort 6a) n = 6	Group A: Placebo (Cohort 6a) n = 2	Group B: Uprifosbuvir 10 mg (Cohort 1b) n = 3	Group B: Uprifosbuvir 25 mg (Cohort 2b) n = 3	Group B: Uprifosbuvir 50 mg (Cohort 3b) n = 3	Group B: Uprifosbuvir 150 mg (Cohort 4b) n = 3	Group B: Uprifosbuvir 300 mg (Cohort 5b) n = 3	Groups C & D: Uprifosbuvir 50 mg (Capsule) n = 11	Groups C & D: Uprifosbuvir 150 mg (Capsule) n = 10	Groups C & D: Uprifosbuvir 250 mg (Capsule) n = 8	Groups C & D: Uprifosbuvir 300 mg (Capsule) n = 18	Groups C & D: Uprifosbuvir 400 mg (Capsule) n = 8	Groups C & D: Uprifosbuvir 300 mg (Tablet) n = 8	Groups C & D: Uprifosbuvir 450 mg (Tablet) n = 8	Groups C & D: Placebo (Pooled) n = 9	Group E: Uprifosbuvir 150 mg (Cohort 1e) n = 3	Group E: Uprifosbuvir 300 mg (Cohort 2e) n = 3	Group E: Uprifosbuvir 450 mg (Cohort 3e) n = 8	Group F: Uprifosbuvir 300 mg (Tablet)

Adverse events

Time frame: Up to 42 days (28 days after last study drug administration). Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Group A: Placebo (Cohort 1a - Cohort 5a - Pooled)	0 of 10 (0%)	5 of 10 (50%)	Not reported
Group A: Uprifosbuvir 10 mg (Cohort 1a)	0 of 6 (0%)	0 of 6 (0%)	Not reported
Group A: Uprifosbuvir 25 mg (Cohort 2a)	0 of 6 (0%)	2 of 6 (33.3%)	Not reported
Group A: Uprifosbuvir 50 mg (Cohort 3a)	0 of 6 (0%)	2 of 6 (33.3%)	Not reported
Group A: Uprifosbuvir 150 mg (Cohort 4a)	0 of 6 (0%)	4 of 6 (66.7%)	Not reported
Group A: Uprifosbuvir 300 mg (Cohort 5a)	0 of 6 (0%)	3 of 6 (50%)	Not reported
Group A: Placebo (Cohort 6a)	0 of 2 (0%)	1 of 2 (50%)	Not reported
Group A: Uprifosbuvir 300 mg (Cohort 6a)	0 of 6 (0%)	2 of 6 (33.3%)	Not reported
Group B: Uprifosbuvir 10 mg (Cohort 1b)	0 of 3 (0%)	1 of 3 (33.3%)	Not reported
Group B: Uprifosbuvir 25 mg (Cohort 2b)	0 of 3 (0%)	2 of 3 (66.7%)	Not reported
Group B: Uprifosbuvir 50 mg (Cohort 3b)	0 of 3 (0%)	1 of 3 (33.3%)	Not reported
Group B: Uprifosbuvir 150 mg (Cohort 4b)	0 of 3 (0%)	2 of 3 (66.7%)	Not reported
Group B: Uprifosbuvir 300 mg (Cohort 5b)	0 of 3 (0%)	2 of 3 (66.7%)	Not reported
Groups C & D: Uprifosbuvir 50 mg (Capsule)	0 of 11 (0%)	8 of 11 (72.7%)	Not reported
Groups C & D: Uprifosbuvir 150 mg (Capsule)	0 of 10 (0%)	7 of 10 (70%)	Not reported
Groups C & D: Uprifosbuvir 250 mg (Capsule)	0 of 8 (0%)	7 of 8 (87.5%)	Not reported
Groups C & D: Uprifosbuvir 300 mg (Capsule)	0 of 18 (0%)	8 of 18 (44.4%)

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Sep 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Yes. https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Uprifosbuvir and Itraconazole in people with Chronic Hepatitis C, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Sep 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (AE) (time frame: Up to 42 days). The study lists 80 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01974687.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Sep 2018.

Grade 1	50.00	16.7	16.7	50.0	33.3	33.3	50.0	0.0	66.7	33.3	66.7	66.7	45.5	60.0	37.5	33.3	0.0	37.5	25.0	33.3	100.0	12.5	0.0
Grade 2	0.0	16.7	16.7	16.7	16.7	0.0	0.0	0.0	0.0	0.0	0.0	33.3	18.2	0.0	50.0	5.6	62.5	37.5	25.0	33.3	0.0	37.5	37.5
Grade 3	0.0	0.0	0.0	0.0	0.0	0.0	0.0	33.3	0.0	0.0	0.0	0.0	9.1	10.0	0.0	5.6	0.0	0.0	0.0	0.0	0.0	12.5	0.0
Grade 4	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	12.5	0.0	0.0	0.0	0.0
Grade 5	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0