HealthyPhase 1NCT03155893
A Study to Evaluate the Cardiac Safety of a Single Dose of AL-335 Administered on a Background of Simeprevir and Odalasvir and of Repeated Doses of Odalasvir Administered Alone in Healthy Participants
A Phase 1 study of Healthy, run by Janssen Research & Development, LLC at 1 site in United States.
Trial summary
The main purpose of this study is to assess the effect of a single supratherapeutic dose of AL-335 administered on top of multiple doses of odalasvir (ODV) and simeprevir (SMV) versus placebo on QT/QT interval corrected for heart rate (QTc) interval changes, using intersection-union test (IUT) analysis (Panel 1); to… Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 59 participants
- Where
- 1 siteUnited States
- Study dates
- 12 May 2017to 27 Oct 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Participants must sign and date an informed consent form (ICF) indicating that he or she understands the purpose of, and the procedures required for, the study and is willing to participate in the study
- Participant must be healthy on the basis of physical examination, medical history, vital signs, and laboratory tests performed at screening
- Participant must have a blood pressure (supine after at least 5 minutes rest) between 90 and 140 millimeters of mercury (mmHg) systolic, inclusive, and no higher than 90 mmHg diastolic
- Participant must have a 12-lead electrocardiogram (ECG) (based on the mean value of triplicate ECG parameters) consistent with normal cardiac conduction and function at screening
- Participant must have an echocardiogram at screening with left ventricular ejection fraction (LVEF) greater than or equal to (>=)55 percent (%). Participant should not have any other echocardiogram finding suggestive of clinically relevant cardiomyopathy
- Female participant must have a negative highly sensitive urine pregnancy test at Day -2 (Panel 1) or Day -4 (Panel 2)
Who cannot join
- Participant has a history of liver or renal insufficiency, significant cardiac, vascular, pulmonary, gastrointestinal (such as significant diarrhea, gastric stasis, constipation, or gastrointestinal surgery that in the investigator's opinion could influence drug absorption or bioavailability), endocrine, neurologic, hematologic, rheumatologic, psychiatric, neoplastic, or metabolic disturbances
- Participant with a history of clinically relevant heart rhythm disturbances including atrial, junctional, re-entry, and ventricular tachycardia, and heart blocks
- Participant with unusual T-wave morphology (such as bifid T-wave) likely to interfere with corrected QT (QTc) measurements
- Participant with a past history of sick sinus syndrome, heart arrhythmias (example, extrasystolic rhythms or tachycardia at rest). Isolated extrasystolic beats are not exclusionary; risk factors associated with Torsade de Pointes (TdP) such as hypokalemia; family history of short/long QT syndrome; sudden unexplained death (including sudden infant death syndrome in a first-degree relative [that is, sibling, offspring, or biological parent])
- Participant with any skin condition likely to interfere with electrocardiogram (ECG) electrode placement or adhesion
- Participant with a breast implant or a history of thoracic surgery likely to cause abnormality of the electrical conduction through thoracic tissues
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Double-blind, Double-dummy, Placebo- and Positive-controlled Study to Evaluate the Cardiac Safety of a Single Dose of AL-335 Administered on a Background of Simeprevir and Odalasvir and of Repeated Doses of Odalasvir Administered Alone in Healthy Subjects
The main purpose of this study is to assess the effect of a single supratherapeutic dose of AL-335 administered on top of multiple doses of odalasvir (ODV) and simeprevir (SMV) versus placebo on QT/QT interval corrected for heart rate (QTc) interval changes, using intersection-union test (IUT) analysis (Panel 1); to assess the effect of ODV on QT/QTc and PR interval changes after multiple supratherapeutic doses of ODV using an exposure-response (ER) approach (Panel 2); and to assess the effect of multiple supratherapeutic doses of ODV on echocardiographic left ventricular ejection fraction (LVEF) (Panel 2) in healthy participants.
- Conditions
- Healthy
- Being tested
- ODV Placebo (Matching 25 mg ODV), ODV Placebo (Matching 200 mg ODV), ODV Placebo (Matching 125 mg ODV), ODV Placebo (Matching 100 mg ODV), SMV Placebo (Matching 150 mg SMV)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ODV Placebo (Matching 25 mg ODV)Drug
Participants will receive ODV placebo (matching 25 [mg] ODV [1*25 mg tablet]) once daily in Treatment A and B from Day 1 to 16 and Treatment C on Day 1.
ODV Placebo (Matching 200 mg ODV)Drug
Participants will receive ODV placebo (matching 200 mg ODV [4*50 mg tablets]) on Days 1 and 2 in Treatment E.
ODV Placebo (Matching 125 mg ODV)Drug
Participants will receive ODV placebo (matching 125 mg ODV [2*50 mg tablets + 1*25 mg tablets]) orally once daily on Days 3 to 7 in Treatment E.
ODV Placebo (Matching 100 mg ODV)Drug
Participants will receive ODV placebo (matching 100 mg ODV [2*50 mg tablets] orally once daily on Days 8 to 14 in Treatment E.
SMV Placebo (Matching 150 mg SMV)Drug
Participants will receive SMV Placebo (matching 150 mg SMV [2*75 mg capsules]) orally once daily administered from Day 1 to 16 in Treatment A, B and on Day 1 in Treatment C.
AL-335 Placebo (matching 1200 mg AL-335)Drug
Participants will receive a single dose of AL-335 placebo (matching 1200 mg AL-335 [3*400 mg tablets]) administered orally on Day 15 in Treatment A and B.
Moxifloxacin Placebo (matching 400 mg moxifloxacin)Drug
Participants will receive a single dose of moxifloxacin placebo (matching 400 mg moxifloxacin [1*400 mg capsule]) administered orally on Day 1, 15 and 16 in Treatment A, on Day 1, 2 and 15 in Treatment B and on Day 1, 2, 15 and 16 in Treatment C.
ODV 25 mgDrug
Participants will receive ODV 25 mg orally once daily administered on Days 2 to 16 in Treatment C.
ODV 200 mgDrug
Participants will receive ODV 200 mg (4*50 mg tablets) orally once daily will be administered on Days 1 and 2 in Treatment F.
ODV 125 mgDrug
Participants will receive ODV 125 mg (2*50 mg tablets + 1*25 mg tablets) once daily administered on Days 3 to 7 in Treatment F.
ODV 100 mgDrug
Participants will receive ODV 100 mg (2*50 mg tablets) orally once daily administered on Days 8 to 14 in Treatment F.
SMV 150 mgDrug
Participants will receive SMV 150 mg (2*75 mg capsules) orally once daily administered on Days 2 to 16 in Treatment C.
AL-335 1200 mgDrug
Participants will receive a single oral dose of AL-335 1200 mg (3*400 mg tablets) administered on Day 15 in Treatment C.
| Study group | Role | What they receive |
|---|---|---|
| Panel 1: Treatment A | Experimental | Participants will receive odalasvir (ODV) placebo (matching 25 milligram [mg] ODV [1*25 mg tablet]) and simeprevir (SMV) placebo (matching 150 mg SMV [2*75 mg capsules]) once daily from Day 1 to 16 along with single dose of AL-335 placebo (matching 1200 milligram [mg] AL-335 [3*400 mg tablets]) on Day 15 and moxifloxacin placebo (matching 400 mg moxifloxacin [1*400 mg capsule]) as a single dose on Day 1, 15 and 16 along with moxifloxacin 400 mg (1*400 mg capsule) single dose on Day 2 orally under fed conditions. Receives: Drug: ODV Placebo (Matching 25 mg ODV); Drug: SMV Placebo (Matching 150 mg SMV); Drug: AL-335 Placebo (matching 1200 mg AL-335); Drug: Moxifloxacin Placebo (matching 400 mg moxifloxacin) |
| Panel 1: Treatment B | Experimental | Participants will receive odalasvir (ODV) placebo (matching 25 milligram [mg] ODV [1*25 mg tablet]) and simeprevir (SMV) placebo (matching 150 mg SMV [2*75 mg capsules]) once daily from Day 1 to 16 along with single dose of AL-335 placebo (matching 1200 milligram [mg] AL-335 [3*400 mg tablets]) on Day 15 and moxifloxacin placebo (matching 400 mg moxifloxacin [1*400 mg capsule]) as a single dose on Day 1, 2 and 15 along with moxifloxacin 400 mg (1*400 mg capsule) single dose on Day 16 orally under fed conditions. Receives: Drug: ODV Placebo (Matching 25 mg ODV); Drug: SMV Placebo (Matching 150 mg SMV); Drug: AL-335 Placebo (matching 1200 mg AL-335); Drug: Moxifloxacin Placebo (matching 400 mg moxifloxacin) |
| Panel 1: Treatment C | Experimental | Participants will receive odalasvir (ODV) placebo (matching 25 milligram [mg] ODV [1*25 mg tablet]) and simeprevir (SMV) placebo (matching 150 mg SMV [2*75 mg capsules]) once daily on Day 1 and moxifloxacin placebo (matching 400 mg moxifloxacin [1*400 mg capsule]) as a single dose on Day 1, 2, 15 and 16 along with ODV 25 mg (1*25 mg tablet) and SMV 150 mg (2*75 mg capsule) once daily on Day 2 to 16 and AL-335 1200 mg (3*400 mg tablet) single dose on Day 15 orally under fed conditions. Receives: Drug: ODV Placebo (Matching 25 mg ODV); Drug: SMV Placebo (Matching 150 mg SMV); Drug: Moxifloxacin Placebo (matching 400 mg moxifloxacin); Drug: ODV 25 mg; Drug: SMV 150 mg; Drug: AL-335 1200 mg |
| Panel 2: Treatment E | Placebo comparator | Participants will receive ODV placebo (matching 200 mg ODV [4*50 mg tablets]) on Days 1 and 2; ODV placebo (matching 125 mg ODV [2*50 mg tablets + 1*25 mg tablets]) on Days 3 to 7; and ODV placebo (matching 100 mg ODV [2*50 mg tablets] on Days 8 to 14, orally once daily under fed conditions. Receives: Drug: ODV Placebo (Matching 200 mg ODV); Drug: ODV Placebo (Matching 125 mg ODV); Drug: ODV Placebo (Matching 100 mg ODV) |
| Panel 2: Treatment F | Experimental | Participants will receive ODV 200 mg (4*50 mg tablets) on Days 1 and 2; ODV 125 mg (2*50 mg tablets + 1*25 mg tablets) on Days 3 to 7, and ODV 100 mg (2*50 mg tablets) on Days 8 to 14, orally once daily under fed conditions. Receives: Drug: ODV 200 mg; Drug: ODV 125 mg; Drug: ODV 100 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Panel 1:Effect of AL-335 Single Supratherapeutic Dose on QT/QTc Interval Change on top of Multiple Doses of ODV and SMV Vs. Placebo Using IUT Analysis at Day 16
Intersection-union test (IUT) analysis will be performed to evaluate the effect of AL-335 on QT/QTc interval changes after a single supratherapeutic dose of AL-335 on top of multiple doses of odalasvir (ODV) and simeprevir (SMV) versus placebo.
Measured: Baseline (Day 1), Day 15
Panel 2: Effect of ODV on QT/QTc Interval Change From Baseline After Multiple Supratherapeutic Doses of ODV Using ER Approach at Day 14
Exposure-response (ER) analysis will be performed to evaluate the effect of ODV on QT/QTc interval changes after multiple supratherapeutic doses of ODV.
Measured: Baseline (Day -3), Day 14
Panel 2: Effect of ODV on QT/QTc Interval Change From Baseline After Multiple Supratherapeutic Doses of ODV Using ER Approach at Day 15
ER analysis will be performed to evaluate the effect of ODV on QT/QTc interval changes after multiple supratherapeutic doses of ODV.
Measured: Baseline (Day -3), Day 15
Panel 2: Effect of ODV on QT/QTc Interval Change From Baseline After Multiple Supratherapeutic Doses of ODV Using ER Approach at Day 16
ER analysis will be performed to evaluate the effect of ODV on QT/QTc interval changes after multiple supratherapeutic doses of ODV.
Measured: Baseline (Day -3), Day 16
Panel 2: Effect of ODV on PR Interval Change From Baseline After Multiple Supratherapeutic Doses of ODV Using ER Approach at Day 14
ER analysis will be performed to evaluate the effect of ODV on PR interval changes after multiple supratherapeutic doses of ODV.
Measured: Baseline (Day -3), Day 14
Panel 2: Effect of ODV on PR Interval Change From Baseline After Multiple Supratherapeutic Doses of ODV Using ER Approach at Day 15
ER analysis will be performed to evaluate the effect of ODV on PR interval changes after multiple supratherapeutic doses of ODV.
Measured: Baseline (Day -3), Day 15
Panel 2: Effect of ODV on PR Interval Change From Baseline After Multiple Supratherapeutic Doses of ODV Using ER Approach at Day 16
ER analysis will be performed to evaluate the effect of ODV on PR interval changes after multiple supratherapeutic doses of ODV.
Measured: Baseline (Day -3), Day 16
Panel 2: Effect of Multiple Supratherapeutic Doses of ODV on Change From Baseline in Echocardiographic Left Ventricular Ejection Fraction (LVEF) at Day 10
Echocardiogram measurements will be performed to evaluate the effect of multiple supratherapeutic doses of ODV on change in echocardiographic LVEF. The baseline for echocardiographic LVEF will be the average of Days -2 and -1.
Measured: Baseline (Day -2 and -1), Day 10
Panel 2: Effect of Multiple Supratherapeutic Doses of ODV on Change From Baseline in Echocardiographic Left Ventricular Ejection Fraction (LVEF) at Day 14
Echocardiogram measurements will be performed to evaluate the effect of multiple supratherapeutic doses of ODV on change in echocardiographic LVEF. The baseline for echocardiographic LVEF will be the average of Days -2 and -1.
Measured: Baseline (Day -2 and -1), Day 14
Panel 2: Effect of Multiple Supratherapeutic Doses of ODV on Change From Baseline in Echocardiographic Left Ventricular Ejection Fraction (LVEF) at Day 28
Echocardiogram measurements will be performed to evaluate the effect of multiple supratherapeutic doses of ODV on change in echocardiographic LVEF. The baseline for echocardiographic LVEF will be the average of Days -2 and -1.
Measured: Baseline (Day -2 and -1), Day 28
Secondary outcomes (20)
Panel 1: Maximum Observed Analyte Concentration (Cmax) of AL-335 and its 2 metabolites ALS-022399 and ALS-022227
The Cmax is the maximum observed analyte concentration.
Measured: Panel 1, Day 15: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours postdose
Panel 1: Time to Reach the Maximum Observed Analyte Concentration (Tmax) of AL-335 and its 2 metabolites ALS-022399 and ALS-022227
The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.
Measured: Panel 1, Day 15: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours postdose
Panel 1: Area Under the Analyte Concentration-time Curve From Time 0 to 24 Hours Postdose (AUC24) of AL-335 and its 2 metabolites ALS-022399 and ALS-022227
AUC24 is defined as area under the analyte concentration-time curve from time 0 to 24 hours postdose.
Measured: Panel 1, Day 15: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours postdose
Panel 1: Area Under the Analyte Concentration-time Curve from Time 0 to the Time of the Last Measurable Concentration (AUClast) of AL-335 and its 2 metabolites ALS-022399 and ALS-022227
AUClast is defined as area under the analyte concentration-time curve from time 0 to the time of the last measurable (non-below quantification limit [BQL]) concentration.
Measured: Panel 1, Day 15: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours postdose
Panel 1: Apparent Terminal Elimination Half-life (t1/2term) of AL-335 and its 2 metabolites ALS-022399 and ALS-022227
Apparent terminal elimination half-life is defined as 0.693/lambda(z).
Measured: Panel 1, Day 15: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours postdose
Panel 1: Apparent Terminal Elimination Rate Constant (Lambda[z]) of AL-335 and its 2 metabolites ALS-022399 and ALS-022227
Lambda(z) is defined as apparent terminal elimination rate constant, determined by linear regression using the terminal log-linear phase of the log transformed concentration versus time curve.
Measured: Panel 1, Day 15: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours postdose
Panel 1: Area Under the Analyte Concentration-time Curve From Time 0 to Infinite Time (AUC[0-infinity]) of AL-335 and its 2 metabolites ALS-022399 and ALS-022227
The AUC (0-infinity) is the area under the analyte concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z); wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.
Measured: Panel 1, Day 15: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours postdose
Panel 1 and 2: Maximum Observed Analyte Concentration (Cmax) of ODV
The Cmax is the maximum observed analyte concentration.
Measured: Panel 1, Days 14 and 15: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours postdose; Panel 2, Day 14: predose, 1, 3, 4, 5, 6, 7, 8, 10, 12, 24, 28, 32, 36, 48, 52, 56, 60, and 72 hours postdose
Panel 1 and 2: Time to Reach the Maximum Observed Analyte Concentration (Tmax) of ODV
The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.
Measured: Panel 1, Days 14 and 15: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours postdose; Panel 2, Day 14: predose, 1, 3, 4, 5, 6, 7, 8, 10, 12, 24, 28, 32, 36, 48, 52, 56, 60, and 72 hours postdose
Panel 1 and 2: Minimum Observed Analyte Concentration (Cmin) of ODV
The Cmin is a minimum observed analyte concentration.
Measured: Panel 1, Days 14 and 15: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours postdose; Panel 2, Day 14: predose, 1, 3, 4, 5, 6, 7, 8, 10, 12, 24, 28, 32, 36, 48, 52, 56, 60, and 72 hours postdose
Panel 1 and 2: Observed Analyte Concentration Just Prior to the Beginning of a Dosing Interval (Ctrough) of ODV
The Ctrough is the observed analyte concentration just prior to the beginning of a dosing interval.
Measured: Panel 1: Predose on Days 14 and 15; Panel 2: Predose on Day 14
Panel 1 and 2: Area Under the Analyte Concentration-time Curve From Time 0 to 24 hours Postdose (AUC24) of ODV
AUC24 is defined as area under the analyte concentration-time curve from time 0 to 24 hours postdose.
Measured: Panel 1, Days 14 and 15: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours postdose; Panel 2, Day 14: predose, 1, 3, 4, 5, 6, 7, 8, 10, 12 and 24 hours postdose
Panel 2: Observed Analyte Concentration of ODV
Observed analyte concentration of ODV will be assessed on Days 10, 14 and 28.
Measured: Panel 2, Days 10 and 14: 6 and 8 hours postdose; Day 28: 6 and 8 hours
Panel 1: Maximum Observed Analyte Concentration (Cmax) of SMV
The Cmax is the maximum observed analyte concentration.
Measured: Panel 1, Days 14 and 15: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours postdose
Panel 1: Time to Reach the Maximum Observed Analyte Concentration (Tmax) of SMV
The tmax is defined as actual sampling time to reach maximum observed analyte concentration.
Measured: Panel 1, Days 14 and 15: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours postdose
Panel 1: Minimum Observed Analyte Concentration (Cmin) of SMV
The Cmin is the minimum observed analyte concentration.
Measured: Panel 1, Days 14 and 15: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours postdose
Panel 1: Observed Analyte Concentration Just Prior to the Beginning of a Dosing Interval (Ctrough) of SMV
The Ctrough is the observed analyte concentration just prior to the beginning of a dosing interval.
Measured: Panel 1: Predose on Days 14 and 15
Panel 1: Area Under the Analyte Concentration-time Curve From Time 0 to 24 hours Postdose (AUC24) of SMV
AUC24 is defined as area under the analyte concentration-time curve from time 0 to 24 hours postdose.
Measured: Panel 1, Days 14 and 15: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours postdose
Panel 1 and 2: Number of Participants With Adverse Events as a Measure of Safety and Tolerability
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Measured: Up to Day 49 (Panel 1) and Day 66 (Panel 2)
Panel 1: Effect of Moxifloxacin on the QT/QTc Interval Change From Baseline at Day 2 and 16
The effect of moxifloxacin on the QT/QTc Interval changes will be assessed for assay sensitivity.
Measured: Baseline (Day 1), Days 2 and 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2017
- Study start12 May 2017
- Primary completion27 Oct 2017
- Study completion27 Oct 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by Janssen Research & Development, 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
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 59 participants (actual)
Sponsor and investigators
- Lead sponsor
- Janssen Research & Development, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Janssen Research & Development, LLC Clinical Trial, Study director, Janssen Research & Development, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03155893
- Sponsor's protocol ID
- CR108332
- Other IDs
- 64294178HPC1012
- Status last verified
- Nov 2017
- First submitted
- 15 May 2017
- Last updated
- 14 Nov 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Double-dummy, Placebo- and Positive-controlled Study to Evaluate the Cardiac Safety of a Single Dose of AL-335 Administered on a Background of Simeprevir and Odalasvir and of Repeated Doses of Odalasvir Administered Alone in Healthy Subjects
- ClinicalTrials.gov ID
- NCT03155893
- Acronym / sponsor ID
- CR108332
- Conditions
- Healthy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 59 participants (actual)
- Lead sponsor
- Janssen Research & Development, LLCIndustry (pharma, biotech, devices)
- Study start
- 12 May 2017 (actual)
- Primary completion
- 27 Oct 2017 (actual)
- Study completion
- 27 Oct 2017 (actual)
- First posted
- 16 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main purpose of this study is to assess the effect of a single supratherapeutic dose of AL-335 administered on top of multiple doses of odalasvir (ODV) and simeprevir (SMV) versus placebo on QT/QT interval corrected for heart rate (QTc) interval changes, using intersection-union test (IUT) analysis (Panel 1); to assess the effect of ODV on QT/QTc and PR interval changes after multiple supratherapeutic doses of ODV using an exposure-response (ER) approach (Panel 2); and to assess the effect of multiple supratherapeutic doses of ODV on echocardiographic left ventricular ejection fraction (LVEF) (Panel 2) in healthy participants.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Panel 1: Treatment A | Experimental | Drug: ODV Placebo (Matching 25 mg ODV), Drug: SMV Placebo (Matching 150 mg SMV), Drug: AL-335 Placebo (matching 1200 mg AL-335), Drug: Moxifloxacin Placebo (matching 400 mg moxifloxacin)Participants will receive odalasvir (ODV) placebo (matching 25 milligram [mg] ODV [1*25 mg tablet]) and simeprevir (SMV) placebo (matching 150 mg SMV [2*75 mg capsules]) once daily from Day 1 to 16 along with single dose of AL-335 placebo (matching 1200 milligram [mg] AL-335 [3*400 mg tablets]) on Day 15 and moxifloxacin placebo (matching 400 mg moxifloxacin [1*400 mg capsule]) as a single dose on Day 1, 15 and 16 along with moxifloxacin 400 mg (1*400 mg capsule) single dose on Day 2 orally under fed conditions. |
| Panel 1: Treatment B | Experimental | Drug: ODV Placebo (Matching 25 mg ODV), Drug: SMV Placebo (Matching 150 mg SMV), Drug: AL-335 Placebo (matching 1200 mg AL-335), Drug: Moxifloxacin Placebo (matching 400 mg moxifloxacin)Participants will receive odalasvir (ODV) placebo (matching 25 milligram [mg] ODV [1*25 mg tablet]) and simeprevir (SMV) placebo (matching 150 mg SMV [2*75 mg capsules]) once daily from Day 1 to 16 along with single dose of AL-335 placebo (matching 1200 milligram [mg] AL-335 [3*400 mg tablets]) on Day 15 and moxifloxacin placebo (matching 400 mg moxifloxacin [1*400 mg capsule]) as a single dose on Day 1, 2 and 15 along with moxifloxacin 400 mg (1*400 mg capsule) single dose on Day 16 orally under fed conditions. |
| Panel 1: Treatment C | Experimental | Drug: ODV Placebo (Matching 25 mg ODV), Drug: SMV Placebo (Matching 150 mg SMV), Drug: Moxifloxacin Placebo (matching 400 mg moxifloxacin), Drug: ODV 25 mg, Drug: SMV 150 mg, Drug: AL-335 1200 mgParticipants will receive odalasvir (ODV) placebo (matching 25 milligram [mg] ODV [1*25 mg tablet]) and simeprevir (SMV) placebo (matching 150 mg SMV [2*75 mg capsules]) once daily on Day 1 and moxifloxacin placebo (matching 400 mg moxifloxacin [1*400 mg capsule]) as a single dose on Day 1, 2, 15 and 16 along with ODV 25 mg (1*25 mg tablet) and SMV 150 mg (2*75 mg capsule) once daily on Day 2 to 16 and AL-335 1200 mg (3*400 mg tablet) single dose on Day 15 orally under fed conditions. |
| Panel 2: Treatment E | Placebo comparator | Drug: ODV Placebo (Matching 200 mg ODV), Drug: ODV Placebo (Matching 125 mg ODV), Drug: ODV Placebo (Matching 100 mg ODV)Participants will receive ODV placebo (matching 200 mg ODV [4*50 mg tablets]) on Days 1 and 2; ODV placebo (matching 125 mg ODV [2*50 mg tablets + 1*25 mg tablets]) on Days 3 to 7; and ODV placebo (matching 100 mg ODV [2*50 mg tablets] on Days 8 to 14, orally once daily under fed conditions. |
| Panel 2: Treatment F | Experimental | Drug: ODV 200 mg, Drug: ODV 125 mg, Drug: ODV 100 mgParticipants will receive ODV 200 mg (4*50 mg tablets) on Days 1 and 2; ODV 125 mg (2*50 mg tablets + 1*25 mg tablets) on Days 3 to 7, and ODV 100 mg (2*50 mg tablets) on Days 8 to 14, orally once daily under fed conditions. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Participants must sign and date an informed consent form (ICF) indicating that he or she understands the purpose of, and the procedures required for, the study and is willing to participate in the study
- Participant must be healthy on the basis of physical examination, medical history, vital signs, and laboratory tests performed at screening
- Participant must have a blood pressure (supine after at least 5 minutes rest) between 90 and 140 millimeters of mercury (mmHg) systolic, inclusive, and no higher than 90 mmHg diastolic
- Participant must have a 12-lead electrocardiogram (ECG) (based on the mean value of triplicate ECG parameters) consistent with normal cardiac conduction and function at screening
- Participant must have an echocardiogram at screening with left ventricular ejection fraction (LVEF) greater than or equal to (>=)55 percent (%). Participant should not have any other echocardiogram finding suggestive of clinically relevant cardiomyopathy
Key exclusion criteria (6 listed)
- Participant has a history of liver or renal insufficiency, significant cardiac, vascular, pulmonary, gastrointestinal (such as significant diarrhea, gastric stasis, constipation, or gastrointestinal surgery that in the investigator's opinion could influence drug absorption or bioavailability), endocrine, neurologic, hematologic, rheumatologic, psychiatric, neoplastic, or metabolic disturbances
- Participant with a history of clinically relevant heart rhythm disturbances including atrial, junctional, re-entry, and ventricular tachycardia, and heart blocks
- Participant with unusual T-wave morphology (such as bifid T-wave) likely to interfere with corrected QT (QTc) measurements
- Participant with a past history of sick sinus syndrome, heart arrhythmias (example, extrasystolic rhythms or tachycardia at rest). Isolated extrasystolic beats are not exclusionary; risk factors associated with Torsade de Pointes (TdP) such as hypokalemia; family history of short/long QT syndrome; sudden unexplained death (including sudden infant death syndrome in a first-degree relative [that is, sibling, offspring, or biological parent])
- Participant with any skin condition likely to interfere with electrocardiogram (ECG) electrode placement or adhesion
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 |
|---|---|---|
| ODV Placebo (Matching 25 mg ODV)Participants will receive ODV placebo (matching 25 [mg] ODV [1*25 mg tablet]) once daily in Treatment A and B from Day 1 to 16 and Treatment C on Day 1. | Drug | Panel 1: Treatment A, Panel 1: Treatment B, Panel 1: Treatment C |
| ODV Placebo (Matching 200 mg ODV)Participants will receive ODV placebo (matching 200 mg ODV [4*50 mg tablets]) on Days 1 and 2 in Treatment E. | Drug | Panel 2: Treatment E |
| ODV Placebo (Matching 125 mg ODV)Participants will receive ODV placebo (matching 125 mg ODV [2*50 mg tablets + 1*25 mg tablets]) orally once daily on Days 3 to 7 in Treatment E. | Drug | Panel 2: Treatment E |
| ODV Placebo (Matching 100 mg ODV)Participants will receive ODV placebo (matching 100 mg ODV [2*50 mg tablets] orally once daily on Days 8 to 14 in Treatment E. | Drug | Panel 2: Treatment E |
| SMV Placebo (Matching 150 mg SMV)Participants will receive SMV Placebo (matching 150 mg SMV [2*75 mg capsules]) orally once daily administered from Day 1 to 16 in Treatment A, B and on Day 1 in Treatment C. | Drug | Panel 1: Treatment A, Panel 1: Treatment B, Panel 1: Treatment C |
| AL-335 Placebo (matching 1200 mg AL-335)Participants will receive a single dose of AL-335 placebo (matching 1200 mg AL-335 [3*400 mg tablets]) administered orally on Day 15 in Treatment A and B. | Drug | Panel 1: Treatment A, Panel 1: Treatment B |
| Moxifloxacin Placebo (matching 400 mg moxifloxacin)Participants will receive a single dose of moxifloxacin placebo (matching 400 mg moxifloxacin [1*400 mg capsule]) administered orally on Day 1, 15 and 16 in Treatment A, on Day 1, 2 and 15 in Treatment B and on Day 1, 2, 15 and 16 in Treatment C. | Drug | Panel 1: Treatment A, Panel 1: Treatment B, Panel 1: Treatment C |
| ODV 25 mgParticipants will receive ODV 25 mg orally once daily administered on Days 2 to 16 in Treatment C. | Drug | Panel 1: Treatment C |
| ODV 200 mgParticipants will receive ODV 200 mg (4*50 mg tablets) orally once daily will be administered on Days 1 and 2 in Treatment F. | Drug | Panel 2: Treatment F |
| ODV 125 mgParticipants will receive ODV 125 mg (2*50 mg tablets + 1*25 mg tablets) once daily administered on Days 3 to 7 in Treatment F. | Drug | Panel 2: Treatment F |
| ODV 100 mgParticipants will receive ODV 100 mg (2*50 mg tablets) orally once daily administered on Days 8 to 14 in Treatment F. | Drug | Panel 2: Treatment F |
| SMV 150 mgParticipants will receive SMV 150 mg (2*75 mg capsules) orally once daily administered on Days 2 to 16 in Treatment C. | Drug | Panel 1: Treatment C |
| AL-335 1200 mgParticipants will receive a single oral dose of AL-335 1200 mg (3*400 mg tablets) administered on Day 15 in Treatment C. | Drug | Panel 1: Treatment C |
Primary outcome
Panel 1:Effect of AL-335 Single Supratherapeutic Dose on QT/QTc Interval Change on top of Multiple Doses of ODV and SMV Vs. Placebo Using IUT Analysis at Day 16
Time frame: Baseline (Day 1), Day 15
Intersection-union test (IUT) analysis will be performed to evaluate the effect of AL-335 on QT/QTc interval changes after a single supratherapeutic dose of AL-335 on top of multiple doses of odalasvir (ODV) and simeprevir (SMV) versus placebo.
Panel 2: Effect of ODV on QT/QTc Interval Change From Baseline After Multiple Supratherapeutic Doses of ODV Using ER Approach at Day 14
Time frame: Baseline (Day -3), Day 14
Exposure-response (ER) analysis will be performed to evaluate the effect of ODV on QT/QTc interval changes after multiple supratherapeutic doses of ODV.
Panel 2: Effect of ODV on QT/QTc Interval Change From Baseline After Multiple Supratherapeutic Doses of ODV Using ER Approach at Day 15
Time frame: Baseline (Day -3), Day 15
ER analysis will be performed to evaluate the effect of ODV on QT/QTc interval changes after multiple supratherapeutic doses of ODV.
Panel 2: Effect of ODV on QT/QTc Interval Change From Baseline After Multiple Supratherapeutic Doses of ODV Using ER Approach at Day 16
Time frame: Baseline (Day -3), Day 16
ER analysis will be performed to evaluate the effect of ODV on QT/QTc interval changes after multiple supratherapeutic doses of ODV.
Panel 2: Effect of ODV on PR Interval Change From Baseline After Multiple Supratherapeutic Doses of ODV Using ER Approach at Day 14
Time frame: Baseline (Day -3), Day 14
ER analysis will be performed to evaluate the effect of ODV on PR interval changes after multiple supratherapeutic doses of ODV.
Panel 2: Effect of ODV on PR Interval Change From Baseline After Multiple Supratherapeutic Doses of ODV Using ER Approach at Day 15
Time frame: Baseline (Day -3), Day 15
ER analysis will be performed to evaluate the effect of ODV on PR interval changes after multiple supratherapeutic doses of ODV.
Panel 2: Effect of ODV on PR Interval Change From Baseline After Multiple Supratherapeutic Doses of ODV Using ER Approach at Day 16
Time frame: Baseline (Day -3), Day 16
ER analysis will be performed to evaluate the effect of ODV on PR interval changes after multiple supratherapeutic doses of ODV.
Panel 2: Effect of Multiple Supratherapeutic Doses of ODV on Change From Baseline in Echocardiographic Left Ventricular Ejection Fraction (LVEF) at Day 10
Time frame: Baseline (Day -2 and -1), Day 10
Echocardiogram measurements will be performed to evaluate the effect of multiple supratherapeutic doses of ODV on change in echocardiographic LVEF. The baseline for echocardiographic LVEF will be the average of Days -2 and -1.
Panel 2: Effect of Multiple Supratherapeutic Doses of ODV on Change From Baseline in Echocardiographic Left Ventricular Ejection Fraction (LVEF) at Day 14
Time frame: Baseline (Day -2 and -1), Day 14
Echocardiogram measurements will be performed to evaluate the effect of multiple supratherapeutic doses of ODV on change in echocardiographic LVEF. The baseline for echocardiographic LVEF will be the average of Days -2 and -1.
Panel 2: Effect of Multiple Supratherapeutic Doses of ODV on Change From Baseline in Echocardiographic Left Ventricular Ejection Fraction (LVEF) at Day 28
Time frame: Baseline (Day -2 and -1), Day 28
Echocardiogram measurements will be performed to evaluate the effect of multiple supratherapeutic doses of ODV on change in echocardiographic LVEF. The baseline for echocardiographic LVEF will be the average of Days -2 and -1.
20 secondary outcomes
Panel 1: Maximum Observed Analyte Concentration (Cmax) of AL-335 and its 2 metabolites ALS-022399 and ALS-022227
Time frame: Panel 1, Day 15: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours postdose
Panel 1: Time to Reach the Maximum Observed Analyte Concentration (Tmax) of AL-335 and its 2 metabolites ALS-022399 and ALS-022227
Time frame: Panel 1, Day 15: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours postdose
Panel 1: Area Under the Analyte Concentration-time Curve From Time 0 to 24 Hours Postdose (AUC24) of AL-335 and its 2 metabolites ALS-022399 and ALS-022227
Time frame: Panel 1, Day 15: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours postdose
Panel 1: Area Under the Analyte Concentration-time Curve from Time 0 to the Time of the Last Measurable Concentration (AUClast) of AL-335 and its 2 metabolites ALS-022399 and ALS-022227
Time frame: Panel 1, Day 15: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours postdose
Panel 1: Apparent Terminal Elimination Half-life (t1/2term) of AL-335 and its 2 metabolites ALS-022399 and ALS-022227
Time frame: Panel 1, Day 15: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours postdose
Panel 1: Apparent Terminal Elimination Rate Constant (Lambda[z]) of AL-335 and its 2 metabolites ALS-022399 and ALS-022227
Time frame: Panel 1, Day 15: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours postdose
Panel 1: Area Under the Analyte Concentration-time Curve From Time 0 to Infinite Time (AUC[0-infinity]) of AL-335 and its 2 metabolites ALS-022399 and ALS-022227
Time frame: Panel 1, Day 15: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours postdose
Panel 1 and 2: Maximum Observed Analyte Concentration (Cmax) of ODV
Time frame: Panel 1, Days 14 and 15: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours postdose; Panel 2, Day 14: predose, 1, 3, 4, 5, 6, 7, 8, 10, 12, 24, 28, 32, 36, 48, 52, 56, 60, and 72 hours postdose
Panel 1 and 2: Time to Reach the Maximum Observed Analyte Concentration (Tmax) of ODV
Time frame: Panel 1, Days 14 and 15: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours postdose; Panel 2, Day 14: predose, 1, 3, 4, 5, 6, 7, 8, 10, 12, 24, 28, 32, 36, 48, 52, 56, 60, and 72 hours postdose
Panel 1 and 2: Minimum Observed Analyte Concentration (Cmin) of ODV
Time frame: Panel 1, Days 14 and 15: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours postdose; Panel 2, Day 14: predose, 1, 3, 4, 5, 6, 7, 8, 10, 12, 24, 28, 32, 36, 48, 52, 56, 60, and 72 hours postdose
Panel 1 and 2: Observed Analyte Concentration Just Prior to the Beginning of a Dosing Interval (Ctrough) of ODV
Time frame: Panel 1: Predose on Days 14 and 15; Panel 2: Predose on Day 14
Panel 1 and 2: Area Under the Analyte Concentration-time Curve From Time 0 to 24 hours Postdose (AUC24) of ODV
Time frame: Panel 1, Days 14 and 15: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours postdose; Panel 2, Day 14: predose, 1, 3, 4, 5, 6, 7, 8, 10, 12 and 24 hours postdose
Panel 2: Observed Analyte Concentration of ODV
Time frame: Panel 2, Days 10 and 14: 6 and 8 hours postdose; Day 28: 6 and 8 hours
Panel 1: Maximum Observed Analyte Concentration (Cmax) of SMV
Time frame: Panel 1, Days 14 and 15: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours postdose
Panel 1: Time to Reach the Maximum Observed Analyte Concentration (Tmax) of SMV
Time frame: Panel 1, Days 14 and 15: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours postdose
Panel 1: Minimum Observed Analyte Concentration (Cmin) of SMV
Time frame: Panel 1, Days 14 and 15: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours postdose
Panel 1: Observed Analyte Concentration Just Prior to the Beginning of a Dosing Interval (Ctrough) of SMV
Time frame: Panel 1: Predose on Days 14 and 15
Panel 1: Area Under the Analyte Concentration-time Curve From Time 0 to 24 hours Postdose (AUC24) of SMV
Time frame: Panel 1, Days 14 and 15: Predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 and 24 hours postdose
Panel 1 and 2: Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Time frame: Up to Day 49 (Panel 1) and Day 66 (Panel 2)
Panel 1: Effect of Moxifloxacin on the QT/QTc Interval Change From Baseline at Day 2 and 16
Time frame: Baseline (Day 1), Days 2 and 16
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 2017.
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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.
Janssen Research & Development, LLC Clinical Trial study director
Janssen Research & Development, LLC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study of Healthy, run by Janssen Research & Development, LLC at 1 site in United States.
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 6 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 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Panel 1:Effect of AL-335 Single Supratherapeutic Dose on QT/QTc Interval Change on top of Multiple Doses of ODV and SMV Vs. Placebo Using IUT Analysis at Day 16 (time frame: Baseline (Day 1), Day 15). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Nov 2017.