Hepatitis CPhase 1NCT01537900

A Multiple Dose Study of Grazoprevir (MK-5172) in Hepatitis C-Infected Participants (MK-5172-010)

A Phase 1 study testing Grazoprevir in people with 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

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Hepatitis C
What is being tested?: Grazoprevir
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 4 participants
Where: No sites listed yet
Study dates: 1 Oct 2013to 31 Jul 2014
Phase: Phase 1
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
No healthy volunteers
Adult, Older adult

Who may be able to join

has a Body Mass Index (BMI) ≥18.5 kg/m² and ≤36.0 kg/m²
has chronic compensated, genotype 1 HCV infection
has no cirrhosis of the liver as confirmed by FibroSure®/Fibro Test® and/or local country procedure (e.g. transient elastography/Fibroscan)
does not require anticoagulants, nonsteroidal anti-inflammatory agents, and aspirin for at least fourteen (14) days preceding the initial liver biopsy and continuing throughout the entire study
if is a female participant of reproductive potential, is willing to use 2 medically acceptable forms of contraception for 2 weeks prior to start of treatment through 2 weeks after last study treatment
if is a male participant with a partner(s) of reproductive potential, is willing to use 2 medically acceptable forms of contraception from first dose to 90 days after last dose

Who cannot join

has a history of stroke, chronic seizures, or major neurological disorder
has received previous treatment with a direct-acting antiviral (DAA)
has evidence of high grade bridging fibrosis from prior liver biopsy within 3 years of study entry
has evidence or history of chronic hepatitis not caused by HCV infection including but not limited to non-HCV viral hepatitis, nonalcoholic steatohepatitis (NASH), drug-induced hepatitis, or autoimmune hepatitis
has clinical or laboratory evidence of cirrhosis or other advanced liver disease
has decompensated liver disease as indicated by a history of ascites, hepatic encephalopathy, or bleeding esophageal varices

Show all 19Show fewer

has been diagnosed with, or suspected of having, hepatocellular carcinoma (HCC)
has clinically significant abnormality on an electrocardiogram (ECG)
is co-infected with human immunodeficiency virus (HIV)
is positive for Hepatitis B surface antigen (HBsAg) or other evidence of active Hepatitis B infection
has a history of gastric bypass surgery, bowel resection or other disorder that may interfere with absorption
has a history of clinically significant uncontrolled endocrine, gastrointestinal, cardiovascular, hematological, immunological, renal, respiratory, or genitourinary abnormalities or diseases
has clinically significant neoplastic disease
uses alcohol to excess, defined as greater than 3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer [354 mL], wine [118 mL], or distilled spirits [29.5 mL]) per day
is a current regular user (including use of any illicit drugs) or history of drug (including alcohol) abuse within the last 3 months
has undergone surgery, donation of 1 unit of blood (approximately 500 mL) or participation in another investigational study within a period of 4 weeks prior to the screening visit
has a history of multiple and/or severe allergies, or anaphylactic reaction or intolerability to prescription or nonprescription drugs or food
is pregnant or lactating
is expecting to donate eggs or sperm

About this study

Official title: A Multiple Dose Study to Evaluate Pharmacokinetics and Hepatitis C Virus RNA Dynamics Following Administration of MK-5172 in Hepatitis C Infected Patients

The goal of this study was to compare hepatic pharmacokinetics (PK) derived from liver tissue to plasma PK after administration of grazoprevir (MK-5172) to participants with chronic hepatitis C virus (HCV) infection. Participants will be randomized to one of four different liver ultrasound-guided Fine Needle Aspirate (FNA) schedules (at 4-, 8-, 24-, or 72-hours after the Day 7 dose).

Conditions: Hepatitis C
Being tested: Grazoprevir
Medical subject headings: Hepatitis C

What participants receive

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

GrazoprevirDrug
Also called MK-5172
GZR 100 mg tablet by mouth q.d. for 7 days.

Study groups in NCT01537900
Study group	Role	What they receive
Grazoprevir 100 mg	Experimental	Participants received GZR 100 mg once daily (q.d.) for 7 days. Liver FNA was performed on Day 7. Receives: Drug: Grazoprevir

What is being measured

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

Estimated Area Under the Liver Concentration-time Curve for 24 Hours Post-dose (AUC[H]0-24hr) of Grazoprevir
Each participant was assigned to undergo Fine Needle Aspiration (FNA) to obtain liver tissue at different time points. Specifically, one participant underwent FNA at 4 hr post-dose only, another participant underwent FNA at 8 hr post-dose only, and a third participant underwent FNA at 24 hr post-dose only. (The fourth participant underwent FNA at 72 hr post-dose and therefore was not included in the calculation of AUC0-24hr.) Therefore, in calculating AUC0-24hr, there were only 3 data points: 1 data point at 4 hr post-dose, 1 data point at 8 hr post-dose, and 1 data point at 24 hr post-dose. The model assumed that drug concentration was at steady-state, and that the concentration at 24 hr post-dose was equal to the concentration at 0 hr post-dose.
Measured: 4, 8, and 24 hours post-dose on Day 7
Hepatic Concentration of GZR (C[H]Xhr)
C(H)Xhr of GZR was expressed as liver concentration (μmol GZR/L liver) using the concentration of the extracted liver sample (mass of the liver biopsy/0.2 mL solvent), and assuming that liver has the specific gravity of water (1 g/mL). The arithmetic mean C(H)Xhr concentration is based on the means of 4 FNA passes per participant in all 4 participants.
Measured: 4, 8, 24, and 72 hours post-dose on Day 7
Apparent Terminal Hepatic Half-life (t[H]½ ) of GZR
t(H)1/2 is a measure of the time required for the maximum post-dose liver concentration of GZR to decrease by 50%.
Measured: 4, 8, 24, and 72 hours post-dose on Day 7

Secondary outcomes (5)

Plasma AUC[0-24 hr] of GZR
AUC0-24hr is a measure of the mean concentration of drug in plasma after dosing to 24 hours post-dose.
Measured: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose on Day 7
Maximum Plasma Concentration (Cmax) of GZR
Cmax is a measure of the maximum plasma concentration post-dose.
Measured: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose on Day 7
Lowest Plasma Concentration (Ctrough) of GZR
Ctrough is a measure of drug concentration 24 hours post-dose.
Measured: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose on Day 7
Time to Maximum Plasma Concentration (Tmax) of GZR
Tmax is a measure of time to reach maximum post-dose plasma drug concentration.
Measured: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose on Day 7
Plasma t½ of GZR
t1/2 is a measure of time for the maximum plasma concentration of GZR to decrease by 50%.
Measured: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose on Day 7

Timeline

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

1 Oct 201331 Jul 2014

First posted23 Feb 2012 (estimated)
Study start1 Oct 2013
Primary completion31 Jul 2014
Study completion31 Jul 2014

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 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
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 4 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01537900
Sponsor's protocol ID: 5172-010
Other IDs: 2011-000435-83
Status last verified: Aug 2018
First submitted: 17 Feb 2012
Last updated: 14 Sep 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: 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

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Study at a glance

From the registry record, last updated by the sponsor on 14 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multiple Dose Study to Evaluate Pharmacokinetics and Hepatitis C Virus RNA Dynamics Following Administration of MK-5172 in Hepatitis C Infected Patients
ClinicalTrials.gov ID: NCT01537900
Acronym / sponsor ID: 5172-010
Conditions: Hepatitis C
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 4 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 1 Oct 2013 (actual)
Primary completion: 31 Jul 2014 (actual)
Study completion: 31 Jul 2014 (actual)
First posted: 23 Feb 2012 (estimated)
Results: Posted 4 Mar 2016

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: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Grazoprevir 100 mg	Experimental	Drug: GrazoprevirParticipants received GZR 100 mg once daily (q.d.) for 7 days. Liver FNA was performed on Day 7.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

has a Body Mass Index (BMI) ≥18.5 kg/m² and ≤36.0 kg/m²
has chronic compensated, genotype 1 HCV infection
has no cirrhosis of the liver as confirmed by FibroSure®/Fibro Test® and/or local country procedure (e.g. transient elastography/Fibroscan)
does not require anticoagulants, nonsteroidal anti-inflammatory agents, and aspirin for at least fourteen (14) days preceding the initial liver biopsy and continuing throughout the entire study
if is a female participant of reproductive potential, is willing to use 2 medically acceptable forms of contraception for 2 weeks prior to start of treatment through 2 weeks after last study treatment

Key exclusion criteria (19 listed)

has a history of stroke, chronic seizures, or major neurological disorder
has received previous treatment with a direct-acting antiviral (DAA)
has evidence of high grade bridging fibrosis from prior liver biopsy within 3 years of study entry
has evidence or history of chronic hepatitis not caused by HCV infection including but not limited to non-HCV viral hepatitis, nonalcoholic steatohepatitis (NASH), drug-induced hepatitis, or autoimmune hepatitis
has clinical or laboratory evidence of cirrhosis or other advanced liver disease

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
GrazoprevirAlso: MK-5172GZR 100 mg tablet by mouth q.d. for 7 days.	Drug	Grazoprevir 100 mg

Primary outcome

Estimated Area Under the Liver Concentration-time Curve for 24 Hours Post-dose (AUC[H]0-24hr) of Grazoprevir
Time frame: 4, 8, and 24 hours post-dose on Day 7
Each participant was assigned to undergo Fine Needle Aspiration (FNA) to obtain liver tissue at different time points. Specifically, one participant underwent FNA at 4 hr post-dose only, another participant underwent FNA at 8 hr post-dose only, and a third participant underwent FNA at 24 hr post-dose only. (The fourth participant underwent FNA at 72 hr post-dose and therefore was not included in the calculation of AUC0-24hr.) Therefore, in calculating AUC0-24hr, there were only 3 data points: 1 data point at 4 hr post-dose, 1 data point at 8 hr post-dose, and 1 data point at 24 hr post-dose. The model assumed that drug concentration was at steady-state, and that the concentration at 24 hr post-dose was equal to the concentration at 0 hr post-dose.
Hepatic Concentration of GZR (C[H]Xhr)
Time frame: 4, 8, 24, and 72 hours post-dose on Day 7
C(H)Xhr of GZR was expressed as liver concentration (μmol GZR/L liver) using the concentration of the extracted liver sample (mass of the liver biopsy/0.2 mL solvent), and assuming that liver has the specific gravity of water (1 g/mL). The arithmetic mean C(H)Xhr concentration is based on the means of 4 FNA passes per participant in all 4 participants.
Apparent Terminal Hepatic Half-life (t[H]½ ) of GZR
Time frame: 4, 8, 24, and 72 hours post-dose on Day 7
t(H)1/2 is a measure of the time required for the maximum post-dose liver concentration of GZR to decrease by 50%.

5 secondary outcomes

Plasma AUC[0-24 hr] of GZR
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose on Day 7
Maximum Plasma Concentration (Cmax) of GZR
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose on Day 7
Lowest Plasma Concentration (Ctrough) of GZR
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose on Day 7
Time to Maximum Plasma Concentration (Tmax) of GZR
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose on Day 7
Plasma t½ of GZR
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose on Day 7

Results and safety

Results posted to the registry on 4 Mar 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Grazoprevir 100 mg	4	4

Primary outcome: Estimated Area Under the Liver Concentration-time Curve for 24 Hours Post-dose (AUC[H]0-24hr) of Grazoprevir

Time frame: 4, 8, and 24 hours post-dose on Day 7. Number. Unit: µM*hr

Measure	Grazoprevir 100 mg n = 3
Value	19800

Population analysed: The per protocol population (PPP) includes all participants (4, 8, and 24 hr time points) who complied with the protocol sufficiently to ensure that the data were likely to exhibit the effects of treatment. As each data point was obtained from unique participants, there is no measure of variability.

Primary outcome: Hepatic Concentration of GZR (C[H]Xhr)

Time frame: 4, 8, 24, and 72 hours post-dose on Day 7. Mean (Standard Deviation). Unit: µM

Measure	Grazoprevir 100 mg n = 4
Hepatic concentration at 4 hours (C[H]4hr)	390 (186)
Hepatic concentration at 8 hours (C[H]8hr)	1340 (1335)
Hepatic concentration at 24 hours (C[H]24hr)	575 (505)
Hepatic concentration at 72 hours (C[H]72hr)	434 (108)

Population analysed: The PPP includes all participants who complied with the protocol sufficiently to ensure that the data were likely to exhibit the effects of treatment.

Primary outcome: Apparent Terminal Hepatic Half-life (t[H]½ ) of GZR

Time frame: 4, 8, 24, and 72 hours post-dose on Day 7

Population analysed: Apparent t(h)1/2 could not be estimated due to insufficient data in the terminal phase.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: From Screening up to 14 days after final dose (up to Day 21). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Grazoprevir 100 mg	1 of 4 (25%)	1 of 4 (25%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 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 study testing Grazoprevir in people with 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 6 inclusion and 19 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 14 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 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.

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 4 Mar 2016). 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?

Estimated Area Under the Liver Concentration-time Curve for 24 Hours Post-dose (AUC[H]0-24hr) of Grazoprevir (time frame: 4, 8, and 24 hours post-dose on Day 7). The study lists 3 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 NCT01537900.

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 14 Sep 2018.