CompletedNCT03155893Updated Nov 14, 2017

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 interventional study of ODV Placebo (Matching 25 mg ODV) and ODV Placebo (Matching 200 mg ODV) in Healthy, sponsored by Janssen Research & Development, LLC. Completed at 1 site in United States. Open to participants aged 18 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2017-11-14.

Sponsored by Janssen Research & Development, LLC · Phase 1, Interventional, and Other

From the registry’s dates

Primary completion was Oct 2017, 8 years 11 months ago, and no results have been posted to the registry.

Phase: Phase 1
Study type: Interventional
Enrollment: 59
Allocation: Randomized
Ages: 18 Years to 55 Years
Sex: All

Study 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 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 studied

Healthy

In context

Lead sponsor

Janssen Research & Development, LLC is the lead sponsor of 912 studies on the registry; 76 are open to participants now.

Of its 278 completed or terminated interventional studies of FDA-regulated products, 131 (47%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 55 Years
Sexes eligible: All
Accepts healthy volunteers: Yes

Inclusion criteria

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)

Exclusion criteria

Exclusion Criteria:

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

Study design

Phase: Phase 1
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Double (Participant, Investigator)
Enrollment: 59 participants (actual)

Study arms

Experimental
Panel 1: Treatment A
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.
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)
Experimental
Panel 1: Treatment B
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.
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)
Experimental
Panel 1: Treatment C
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.
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
Placebo comparator
Panel 2: Treatment E
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.
Drug: ODV Placebo (Matching 200 mg ODV) · Drug: ODV Placebo (Matching 125 mg ODV) · Drug: ODV Placebo (Matching 100 mg ODV)
Experimental
Panel 2: Treatment F
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.
Drug: ODV 200 mg · Drug: ODV 125 mg · Drug: ODV 100 mg

Interventions

DrugODV 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.
DrugODV 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.
DrugODV 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.
DrugODV 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.
DrugSMV 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.
DrugAL-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.
DrugMoxifloxacin 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.
DrugODV 25 mg
Participants will receive ODV 25 mg orally once daily administered on Days 2 to 16 in Treatment C.
DrugODV 200 mg
Participants will receive ODV 200 mg (4\*50 mg tablets) orally once daily will be administered on Days 1 and 2 in Treatment F.
DrugODV 125 mg
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.
DrugODV 100 mg
Participants will receive ODV 100 mg (2\*50 mg tablets) orally once daily administered on Days 8 to 14 in Treatment F.
DrugSMV 150 mg
Participants will receive SMV 150 mg (2\*75 mg capsules) orally once daily administered on Days 2 to 16 in Treatment C.
DrugAL-335 1200 mg
Participants will receive a single oral dose of AL-335 1200 mg (3\*400 mg tablets) administered on Day 15 in Treatment C.

What researchers measure

Primary outcomes

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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Baseline (Day -2 and -1), Day 28

Secondary outcomes

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.
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
The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.
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
AUC24 is defined as area under the analyte concentration-time curve from time 0 to 24 hours postdose.
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
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.
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
Apparent terminal elimination half-life is defined as 0.693/lambda(z).
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
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.
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
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.
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
The Cmax is the maximum observed analyte concentration.
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
The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.
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
The Cmin is a minimum observed analyte concentration.
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
The Ctrough is the observed analyte concentration just prior to the beginning of a dosing interval.
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
AUC24 is defined as area under the analyte concentration-time curve from time 0 to 24 hours postdose.
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
Observed analyte concentration of ODV will be assessed on Days 10, 14 and 28.
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
The Cmax is the maximum observed analyte concentration.
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
The tmax is defined as actual sampling time to reach maximum observed analyte concentration.
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
The Cmin is the minimum observed analyte concentration.
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
The Ctrough is the observed analyte concentration just prior to the beginning of a dosing interval.
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
AUC24 is defined as area under the analyte concentration-time curve from time 0 to 24 hours postdose.
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
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.
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
The effect of moxifloxacin on the QT/QTc Interval changes will be assessed for assay sensitivity.
Time frame: Baseline (Day 1), Days 2 and 16

Study locations

1 site

Celerion
Tempe, Arizona 85283, United States

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Nov 14, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT03155893
Lead sponsor: Janssen Research & Development, LLC
Responsible party: Sponsor
First posted: May 16, 2017
Start date: May 12, 2017
Primary completion: Oct 27, 2017
Completion: Oct 27, 2017
Last update: Nov 14, 2017

Study contacts

Janssen Research & Development, LLC Clinical Trial

study director · Janssen Research & Development, LLC

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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