Study to Investigate the Pharmacokinetics, Safety and Tolerability of Odalasvir and AL-335 in Healthy Japanese Participants

A Phase 1, Double-blind, Placebo-controlled, Randomized, Single Ascending Dose Study to Investigate the Pharmacokinetics, Safety and Tolerability of Odalasvir and AL-335 in Healthy Japanese Subjects

The purpose of this study is to investigate the pharmacokinetics (PK), safety and tolerability following single oral administration of ascending doses of odalasvir (ODV) in healthy Japanese participants (Panel 1) and to investigate the PK, safety and tolerability following single oral administration of ascending doses of AL-335 in healthy Japanese participants (Panel 2; Sequential Design).

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: Odalasvir (ODV); Drug: AL-335

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Surrey, United Kingdom

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participant must be a Japanese participant who has resided outside Japan for no more than 5 years and whose parents and grandparents are Japanese as determined by participant's verbal report
• Participant must have a body mass index (BMI: weight in kilogram [kg] divided by the square of height in meters) of 18.0 to 30.0 kilogram per meter square (kg/m^2), extremes included and a body weight not less than 50.0 kilogram (kg)
• Participant must be healthy on the basis of physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at Screening. If there are abnormalities, the participant may be included only if the Investigator judges the abnormalities or deviations from normal to be not clinically significant. This determination must be recorded in the participant's source documents and initialed by the Investigator
• Participant must have a blood pressure (after the participant supine for 5 minutes) between 90 and 140 millimeter of mercury (mmHg) systolic, inclusive, and no higher than 90 mmHg diastolic. If blood pressure is out of range, up to 2 repeated assessments are permitted
• Female participant must agree to not donate eggs (ova, oocytes) for the purpose of assisted reproduction during the study and for a period of 60 days (Panel 1) or 30 days (Panel 2) after study drug administration or until the last follow-up visit, whichever occurs later

Exclusion Criteria:

• Participant has a history of liver or renal insufficiency (estimated creatinine clearance below 80 milliliters per minute [mL/min]); significant cardiac, vascular, pulmonary, gastrointestinal (such as significant diarrhea, gastric stasis, or constipation that in the Investigator's opinion could influence drug absorption or bioavailability), endocrine, neurologic, hematologic, rheumatologic, psychiatric, neoplastic or metabolic disturbances
• Participant has any condition for which, in the opinion of the Investigator, participation would not be in the best interest of the participant (for example, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments
• Participant with a past history of heart arrhythmias (for example, extra systolic beats or tachycardia at rest); risk factors associated with Torsade de Pointes such as hypokalemia or family history of short/long QT syndrome or sudden unexplained death (including sudden infant death syndrome) in a first-degree relative [for example, sibling, offspring, or biological parent])
• Participant with any history of clinically significant skin disease such as, but not limited to, dermatitis, eczema, drug rash, psoriasis, food allergy, or urticaria
• Participant has known allergies, hypersensitivity, or intolerance to odalasvir (ODV) or AL-335 or its excipients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Panel 1: Treatment A; Participants will receive odalasvir (ODV) 50 milligram (mg) (n=8) or placebo (n=2) on Day 1.	Drug: Placebo; Matching placebo will be administered.; Drug: Odalasvir (ODV); ODV 50 mg (1 tablet) in Treatment A, 100 mg (2 tablets of 50 mg) in Treatment B and 300 mg (6 tablets of 50 mg) in Treatment C.
Experimental: Panel 1: Treatment B; Participants will receive ODV 100 mg (n=8) or placebo (n=2) on Day 1.	Drug: Placebo; Matching placebo will be administered.; Drug: Odalasvir (ODV); ODV 50 mg (1 tablet) in Treatment A, 100 mg (2 tablets of 50 mg) in Treatment B and 300 mg (6 tablets of 50 mg) in Treatment C.
Experimental: Panel 1: Treatment C; Participants will receive ODV 300 mg (n=8) or placebo (n=2) on Day 1.	Drug: Placebo; Matching placebo will be administered.; Drug: Odalasvir (ODV); ODV 50 mg (1 tablet) in Treatment A, 100 mg (2 tablets of 50 mg) in Treatment B and 300 mg (6 tablets of 50 mg) in Treatment C.
Experimental: Panel 2: Treatment D; Participants will receive AL-335 400 mg (n=8) or placebo (n=2) on Day 1 of Period 1. Each treatment period will be separated by a washout period of 7 days.	Drug: Placebo; Matching placebo will be administered.; Drug: AL-335; AL-335 400 mg (1 tablet) in Treatment D, 800 mg (2 tablets of 400 mg) in Treatment E and 1200 mg (3 tablets of 400 mg) in Treatment F.
Experimental: Panel 2: Treatment E; Participants will receive AL-335 800 mg (n=8) or placebo (n=2) on Day 1 of Period 2. Each treatment period will be separated by a washout period of 7 days.	Drug: Placebo; Matching placebo will be administered.; Drug: AL-335; AL-335 400 mg (1 tablet) in Treatment D, 800 mg (2 tablets of 400 mg) in Treatment E and 1200 mg (3 tablets of 400 mg) in Treatment F.
Experimental: Panel 2: Treatment F; Participants will receive AL-335 1,200 mg (n=8) or placebo (n=2) on Day 1 of Period 3. Each treatment period will be separated by a washout period of 7 days.	Drug: Placebo; Matching placebo will be administered.; Drug: AL-335; AL-335 400 mg (1 tablet) in Treatment D, 800 mg (2 tablets of 400 mg) in Treatment E and 1200 mg (3 tablets of 400 mg) in Treatment F.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Concentration (Cmax) of Odalasvir (ODV)	The Cmax is the maximum observed analyte concentration.	From Day 1 to Day 14 after intake of ODV
Time to Reach Maximum Observed Concentration (Tmax) of ODV	The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.	From Day 1 to Day 14 after intake of ODV
Area Under the Concentration-Time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of ODV	The (AUC [0-last]) is the area under the analyte concentration-time curve from time 0 to time of the last quantifiable concentration.	From Day 1 to Day 50-55 after intake of ODV
Elimination Rate Constant (Lambda[z]) of ODV	Lambda(z) is first order elimination rate constant associated with the terminal portion of the curve, determined as the negative slope of the terminal log-linear phase of the drug concentration-time curve.	From Day 1 to Day 50-55 after intake of ODV
Elimination Half-Life (t1/2) of ODV	Elimination half-life (t[1/2]) is associated with the terminal slope (lambda [z]) of the semi-logarithmic drug concentration-time curve, calculated as 0.693/lambda(z).	From Day 1 to Day 50-55 after intake of ODV
Area Under the Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of ODV	The AUC (0-infinity) is the area under the plasma 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.	From Day 1 to Day 50-55 after intake of ODV
Number of Participants With Adverse Events (AE) as a Measure of Safety and Tolerability for ODV		Up to 50-55 days after intake of ODV
Maximum Observed Concentration (Cmax) of AL-335	The Cmax is the maximum observed analyte concentration.	From Day 1 to Day 4 after intake of AL-335
Time to Reach Maximum Observed Concentration (Tmax) of AL-335	The Tmax is defined as actual sampling time to reach maximum observed concentration.	From Day 1 to Day 4 after intake of AL-335
Area Under the Concentration-Time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of AL-335	The (AUC [0-last]) is the area under the concentration-time curve from time 0 to time of the last quantifiable concentration.	From Day 1 to Day 4 after intake of AL-335
Elimination Rate Constant (Lambda[z]) of AL-335	Lambda(z) is first order elimination rate constant associated with the terminal portion of the curve, determined as the negative slope of the terminal log-linear phase of the drug concentration-time curve.	From Day 1 to Day 4 after intake of AL-335
Elimination Half-Life (t1/2) of AL-335	Elimination half-life (t[1/2]) is associated with the terminal slope (lambda [z]) of the semi-logarithmic drug concentration-time curve, calculated as 0.693/lambda(z).	From Day 1 to Day 4 after intake of AL-335
Area Under the Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) of AL-335	The AUC (0-infinity) is the area under the plasma 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.	From Day 1 to Day 4 after intake of AL-335
Number of Participants With Adverse Events (AE) as a Measure of Safety and Tolerability for AL-335		Up to 30 to 35 days after last intake of AL-335

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research and Developement, LLC Clinical Trial, Janssen Research and Developement, LLC

Study record dates

Study Major Dates

• Study Start (Actual): June 14, 2016
• Primary Completion (Actual): September 9, 2016
• Study Completion (Actual): September 30, 2016

Study Registration Dates

• First Submitted: June 10, 2016
• First Submitted That Met QC Criteria: June 29, 2016
• First Posted (Estimate): July 4, 2016

Study Record Updates

• Last Update Posted (Actual): March 29, 2018
• Last Update Submitted That Met QC Criteria: March 28, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Anti-Infective Agents; Antiviral Agents; Odalasvir
• Other Study ID Numbers: CR108178; 64294178HPC1005 (Other Identifier: Janssen Research & Development, LLC); 2015-005639-42 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No