A Study to Evaluate the Effect of Renal Impairment on the Pharmacokinetics of AL-335

An Open-label, Single-dose Study to Evaluate the Effect of Renal Impairment on the Single-dose Pharmacokinetics of AL-335

The purpose of this study is to evaluate the pharmacokinetics (PK) of a single oral dose of AL-335 in participants with various degrees of impaired renal function (mild, moderate, and severe) compared to participants with normal renal function.

Study Overview

• Status: Completed
• Conditions: Renal Insufficiency
• Intervention / Treatment: Drug: AL-335

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Orlando, Florida, United States
  • Tennessee
    • Knoxville, Tennessee, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Cohorts 1-4:

• 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
• Participants must agree to follow all requirements that must be met during the study as noted in the Inclusion and Exclusion Criteria (eg, contraceptive requirements)
• Female participant must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for a period of 30 days after study drug administration
• 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

Cohorts 1-3:

• Participant must have stable renal function
• Participant must be otherwise healthy except for the 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
• Participants must have an estimated glomerular filtration rate (eGFR) less than (<) 90 milliLiter per minute per 1.73 meter square (mL/min/1.73m^2). Mild renal impairment (eGFR 60 to <90 mL/min/1.73m^2); moderate renal impairment (eGFR 30 to <60 mL/min/1.73m^2); severe renal impairment (eGFR <30 mL/min/1.73m^2 not requiring dialysis)

Cohort 4:

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

Exclusion Criteria:

Cohorts 1-4:

• 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 (eg), 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.

Cohorts 1-3:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AL-335 (Cohort 1); Participants with mild impaired renal function will receive a single oral dose of AL-335 800 milligram (mg) (given as 2*400-mg tablets).	Drug: AL-335; Participants with various degrees of impaired renal function (mild [Cohort 1], moderate [Cohort 2], severe [Cohort 3]) and normal renal function (Cohort 4) will receive a single oral dose of AL-335 800 mg (given as 2*400-mg tablets).
Experimental: AL-335 (Cohort 2); Participants with moderate impaired renal function will receive a single oral dose of AL-335 800 mg (given as 2*400-mg tablets).	Drug: AL-335; Participants with various degrees of impaired renal function (mild [Cohort 1], moderate [Cohort 2], severe [Cohort 3]) and normal renal function (Cohort 4) will receive a single oral dose of AL-335 800 mg (given as 2*400-mg tablets).
Experimental: AL-335 (Cohort 3); Participants with severe impaired renal function will receive a single oral dose of AL-335 800 mg (given as 2*400-mg tablets).	Drug: AL-335; Participants with various degrees of impaired renal function (mild [Cohort 1], moderate [Cohort 2], severe [Cohort 3]) and normal renal function (Cohort 4) will receive a single oral dose of AL-335 800 mg (given as 2*400-mg tablets).
Experimental: AL-335 (Cohort 4); Participants with normal renal function will receive a single oral dose of AL-335 800 mg (given as 2*400-mg tablets).	Drug: AL-335; Participants with various degrees of impaired renal function (mild [Cohort 1], moderate [Cohort 2], severe [Cohort 3]) and normal renal function (Cohort 4) will receive a single oral dose of AL-335 800 mg (given as 2*400-mg tablets).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Concentration (Cmax) of AL-335	The Cmax is the maximum observed concentration of analyte (AL-335).	Pre-dose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 28, 32, 36, 48, 60, and 72 hours post-dose
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)	The AUClast is the area under the analyte (AL-335) concentration-time curve from time zero (0) to time of the last quantifiable concentration.	Pre-dose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 28, 32, 36, 48, 60, and 72 hours post-dose
Area Under the Concentration-Time Curve From Time Zero to Infinite Time (AUCinfinity)	The AUCinfinity 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.	Pre-dose, and at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 28, 32, 36, 48, 60, and 72 hours post-dose

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): September 13, 2016
• Primary Completion (Actual): August 8, 2017
• Study Completion (Actual): August 16, 2017

Study Registration Dates

• First Submitted: September 6, 2016
• First Submitted That Met QC Criteria: September 6, 2016
• First Posted (Estimate): September 9, 2016

Study Record Updates

• Last Update Posted (Actual): December 20, 2017
• Last Update Submitted That Met QC Criteria: December 18, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Anti-Infective Agents; Antiviral Agents; Adafosbuvir
• Other Study ID Numbers: CR108225; 64294178HPC1009 (Other Identifier: Janssen Research & Development, LLC)

Drug and device information, study documents

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