Pharmacokinetics of Bictegravir in Adults With Normal and Impaired Renal Function

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the pharmacokinetic (PK) profile of oral bictegravir (formerly GS-9883) in adults with impaired renal function relative to matched, healthy controls with normal renal function. Each participant in the renal impairment groups will be matched for age (± 10 years), gender, and body mass index [BMI (± 20%, 18 ≤ BMI ≤ 40 kg/m^2)] with a participant in the control group.

Official Title
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A Phase 1, Open-Label, Parallel-Group, Adaptive Single-dose Study to Evaluate the Pharmacokinetics of GS-9883 in Subjects With Normal and Impaired Renal Function

Conditions
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HIV

Intervention / Treatment
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* Drug: Bictegravir


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: All Individuals: Must have a calculated BMI from 18 to 40 kg/m^2, inclusive, at screening Individuals with impaired renal function Chronic stable renal impairment without recent clinical change Mild: Creatinine clearance (CrCl) = 60 - 89 mL/min Moderate: CrCl = 30 - 59 mL/min Severe: CrCl = 15 - 29 mL/min Healthy individuals CrCl ≥ 90 mL/min Key Exclusion Criteria: All Individuals: Pregnant or lactating females HIV positive or chronic hepatitis B infected Individuals with impaired renal function Chronic liver disease Dialysis or anticipated use of dialysis Renal transplant Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Severe Renal Impairment<br>Participants with severe renal impairment and matched healthy controls will receive a single dose of bictegravir. | Drug: Bictegravir<br>* 75 mg tablet administered orally<br>* Other names: GS-9883;|
| Experimental: Moderate Renal Impairment<br>Participants with moderate renal impairment and matched healthy controls will receive a single dose of bictegravir. | Drug: Bictegravir<br>* 75 mg tablet administered orally<br>* Other names: GS-9883;|
| Experimental: Mild Renal Impairment<br>Participants with mild renal impairment and matched healthy controls will receive a single dose of bictegravir. | Drug: Bictegravir<br>* 75 mg tablet administered orally<br>* Other names: GS-9883;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic (PK) Parameter: AUCinf of Bictegravir (Total) | AUCinf is defined as the area under the plasma concentration versus time curve extrapolated to infinite time. | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96, 120 and 144 hours postdose on Day 1 | 
| PK Parameter: AUCinf of Bictegravir (Free) | Free AUCinf was calculated based on unbound plasma bictegravir (AUCinf × percentage unbound bictegravir ÷ 100 for each participant). | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96, 120 and 144 hours postdose on Day 1 | 
| PK Parameter: AUClast of Bictegravir (Total) | AUClast is defined as the area under the plasma concentration versus time curve from time zero to the last quantifiable concentration. | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96, 120 and 144 hours postdose on Day 1 | 
| PK Parameter: AUClast of Bictegravir (Free) | Free AUClast was calculated based on unbound plasma bictegravir (AUClast × percentage unbound bictegravir ÷ 100 for each participant). | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96, 120 and 144 hours postdose on Day 1 | 
| PK Parameter: Cmax of Bictegravir (Total) | Cmax is defined as the maximum observed plasma concentration of drug. | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96, 120 and 144 hours postdose on Day 1 | 
| PK Parameter: Cmax of Bictegravir (Free) | Free Cmax was calculated based on unbound plasma bictegravir (Cmax × percentage unbound bictegravir ÷ 100 for each participant). | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96, 120 and 144 hours postdose on Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Experienced Treatment-Emergent Adverse Events | Treatment-emergent adverse events (TEAEs) are defined as any adverse events (AEs) with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug or any AEs leading to premature discontinuation of study drug. | First dose date to Day 31 | 
| Percentage of Participants Who Experienced Treatment-Emergent Laboratory Abnormalities | A treatment-emergent graded laboratory abnormality was defined as an increase of at least 1 abnormality grade from the predose assessment and occurring after the predose visit and on or before the date of the administration of study drug plus 30 days. The most severe graded abnormality from all tests was counted for each participant. Toxicity grade was defined as follows: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, and Grade 4 = Life-threatening. | First dose date to Day 31 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 1, Renally Impaired