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

NCT03155893 | Completed Phase 1 FDA Drug

• 2 other identifiers: CR10833264294178HPC1012
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

Brief 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

Healthy

Outcome Measures

Primary Outcomes (10)

• 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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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

  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

  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

  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

  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

  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

Study Arms (5)

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.

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.

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.

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.

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.

Drug: ODV 200 mg; Drug: ODV 125 mg; Drug: ODV 100 mg

Interventions

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.

Panel 1: Treatment A; Panel 1: Treatment B; Panel 1: Treatment C

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.

Panel 2: 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.

Panel 2: 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.

Panel 2: 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.

Panel 1: Treatment A; Panel 1: Treatment B; Panel 1: 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.

Panel 1: Treatment A; Panel 1: Treatment 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.

Panel 1: Treatment A; Panel 1: Treatment B; Panel 1: Treatment C

ODV 25 mg DRUG

Participants will receive ODV 25 mg orally once daily administered on Days 2 to 16 in Treatment C.

Panel 1: Treatment C

ODV 200 mg DRUG

Participants will receive ODV 200 mg (4\*50 mg tablets) orally once daily will be administered on Days 1 and 2 in Treatment F.

Panel 2: Treatment F

ODV 125 mg DRUG

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.

Panel 2: Treatment F

ODV 100 mg DRUG

Participants will receive ODV 100 mg (2\*50 mg tablets) orally once daily administered on Days 8 to 14 in Treatment F.

Panel 2: Treatment F

SMV 150 mg DRUG

Participants will receive SMV 150 mg (2\*75 mg capsules) orally once daily administered on Days 2 to 16 in Treatment C.

Panel 1: Treatment C

AL-335 1200 mg DRUG

Participants will receive a single oral dose of AL-335 1200 mg (3\*400 mg tablets) administered on Day 15 in Treatment C.

Panel 1: Treatment C

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (1)

Celerion

Tempe, Arizona, 85283, United States

Location

MeSH Terms

Interventions

Desvenlafaxine Succinate; adafosbuvir; Moxifloxacin

Intervention Hierarchy (Ancestors)

Cyclohexanols; Hexanols; Fatty Alcohols; Alcohols; Organic Chemicals; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Lipids; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2017
• First Posted: May 16, 2017
• Study Start: May 12, 2017
• Primary Completion: October 27, 2017
• Study Completion: October 27, 2017
• Last Updated: November 14, 2017

Record last verified: 2017-11

Locations

US (1)