A Study to Evaluate the Effect of Severe Renal Impairment on the Single-dose Pharmacokinetics of Odalasvir

An Open-label Study to Evaluate the Effect of Severe Renal Impairment on the Single-dose Pharmacokinetics of Odalasvir

The main purpose of this study is to evaluate the pharmacokinetics (PK) of a single oral dose of odalasvir (ODV) in participants with severe renal impairment and compare with the PK in matched participants with normal renal function.

Study Overview

• Status: Completed
• Conditions: Renal Insufficiency
• Intervention / Treatment: Drug: Odalasvir

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center
  • Tennessee
    • Knoxville, Tennessee, United States, 37923
      • New Orleans Center for Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Cohorts 1 and 2:

• Participant must have a body mass index (BMI; weight in kilogram (kg) divided by the square of height in meters) of 18 to 36 kilogram per meter square (kg/m^2), extremes included, and a body weight not less than 50.0 kg
• Participant must be willing and able to adhere to the prohibitions and restrictions specified in the protocol
• Male Participant must agree not to donate sperm from enrollment (Day 1) in the study until at least 30 days after receiving the study drug
• Female Participant, except if postmenopausal, must have a negative serum (beta human chorionic gonadotropin [beta hCG]) pregnancy test at screening and negative highly sensitive urine pregnancy test at Day -1

Cohort 1:

• Participant must have severe renal impairment not requiring dialysis, defined as an estimated glomerular filtration rate (eGFR) less than (<) 30 milliLiter per minute (mL/min)/1.73 m^2
• Participant must have stable renal function that is no significant change in renal function as evidenced by the (mean) screening serum creatinine value within +/-25 percent (%) from the determination obtained at least 3 months prior to screening, and expected to remain stable during the study, and not be planning to initiate dialysis during the study period
• Participant must be otherwise healthy except for renal impairment and its underlying disease states and mild comorbidities and participant must be medically stable on the basis of physical examination, medical history, vital signs, 12-lead electrocardiogram (ECG), and clinical laboratory tests performed at screening. If there are abnormalities or results outside the normal reference ranges, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable for the population under study. This determination must be recorded in the participant's source documents and initialed by the investigator

Cohort 2:

• Participant must be healthy on the basis of physical examination, medical history, vital signs, 12-lead ECG, and clinical laboratory tests performed at screening
• Participant must have an eGFR greater than or equal to (>=) 90 mL/min/1.73 m^2

Exclusion Criteria:

Cohorts 1 and 2:

• Participant has a history of any illness (unrelated to renal impairment or its underlying disease, as appropriate) that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the participant. This may include but is not limited to history of relevant drug or food allergies, history of cardiovascular or central nervous system disease, history or presence of clinically significant pathology, chronic skin disease, or history of mental disease
• Participant who is on a vegetarian diet or who takes creatine supplements, and who has a non-standard muscle mass, example amputation, malnutrition, muscle wasting, or extremely muscular (body building)
• Participant has a history of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti HCV) positive, or other clinically active liver disease, or tests positive for HBsAg or anti-HCV at screening
• Participant has a history of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV at screening
• Participant who smokes more than 10 cigarettes or 2 cigars or 2 pipes per day from within 3 months before screening until the end of the study
• Participant is a woman who is pregnant, or breast-feeding, or planning to become pregnant from signing of the informed consent form (ICF) onwards until 30 days after study drug administration
• Participant is a man who plans to father a child while enrolled in this study (Day 1) until 30 days after study drug administration

Cohort 1:

• Participant requires dialysis
• Participant with imminent renal replacement therapy (that is, during the study period)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 (Severe Renal Impairment): Odalasvir; Participants will receive single oral dose of odalasvir 25 milligram (mg) under fed conditions (standard breakfast) on Day 1.	Drug: Odalasvir; Participants will receive odalasvir 25 mg tablet, orally.
Experimental: Cohort 2 (Normal Renal Function): Odalasvir; Participants will receive single oral dose of odalasvir 25 milligram (mg) under fed conditions (standard breakfast) on Day 1.	Drug: Odalasvir; Participants will receive odalasvir 25 mg tablet, orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma Concentration (Cmax) of Odalasvir	The Cmax is the maximum observed plasma analyte concentration.	Predose and 1, 3, 4, 5, 6, 7, 8, 12, 16, 24, 36, 48, 60, 72, 96 120, 144, 168, and 312 hours postdose
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Odalasvir	The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.	Predose and 1, 3, 4, 5, 6, 7, 8, 12, 16, 24, 36, 48, 60, 72, 96 120, 144, 168, and 312 hours postdose
Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24]) of Odalasvir	The AUC (0-24) is the area under the plasma concentration-time curve from time zero to 24 hours.	Predose and 1, 3, 4, 5, 6, 7, 8, 12, 16, 24, 36, 48, 60, 72, 96 120, 144, 168, and 312 hours postdose
Area Under the Plasma Concentration-Time Curve From Time Zero to 72 Hours (AUC[0-72]) of Odalasvir	The AUC (0-72) is the area under the plasma concentration-time curve from time zero to 72 hours.	Predose and 1, 3, 4, 5, 6, 7, 8, 12, 16, 24, 36, 48, 60, 72, 96 120, 144, 168, and 312 hours postdose
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0-last]) of Odalasvir	The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time.	Predose and 1, 3, 4, 5, 6, 7, 8, 12, 16, 24, 36, 48, 60, 72, 96 120, 144, 168, and 312 hours postdose
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Odalasvir	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(0-last) and C(last)/lambda(z); wherein AUC(0-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.	Predose and 1, 3, 4, 5, 6, 7, 8, 12, 16, 24, 36, 48, 60, 72, 96 120, 144, 168, and 312 hours postdose
Apparent Elimination Half-Life (t1/2) of Odalasvir	Elimination half-life associated with the terminal slope Lambda (z) of the semi logarithmic drug concentration-time curve, calculated as 0.693/Lambda (z).	Predose and 1, 3, 4, 5, 6, 7, 8, 12, 16, 24, 36, 48, 60, 72, 96 120, 144, 168, and 312 hours postdose
Apparent Volume of Distribution (Vd/F) of Odalasvir	The Vd/F is defined as Dose/[Lambda (z)*AUC (0-infinity)].	Predose and 1, 3, 4, 5, 6, 7, 8, 12, 16, 24, 36, 48, 60, 72, 96 120, 144, 168, and 312 hours postdose
Total Apparent Oral Clearance (CL/F) of Odalasvir	The CL/F is defined as Dose/AUC (0-infinity).	Predose and 1, 3, 4, 5, 6, 7, 8, 12, 16, 24, 36, 48, 60, 72, 96 120, 144, 168, and 312 hours postdose

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Adverse Events as a Measure of Safety and Tolerability	Baseline, up to follow-up (30 to 35 days after study drug intake)

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): November 9, 2016
• Primary Completion (Actual): April 9, 2018
• Study Completion (Actual): April 9, 2018

Study Registration Dates

• First Submitted: November 9, 2016
• First Submitted That Met QC Criteria: November 9, 2016
• First Posted (Estimate): November 11, 2016

Study Record Updates

• Last Update Posted (Actual): May 17, 2018
• Last Update Submitted That Met QC Criteria: May 14, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Anti-Infective Agents; Antiviral Agents; Odalasvir
• Other Study ID Numbers: CR108242; 64294178HPC1014 (Other Identifier: Janssen Research & Development, LLC)

Drug and device information, study documents

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