Pharmacokinetics of Bictegravir in Adults With Normal and Impaired Renal Function

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

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.

Study Overview

• Status: Completed
• Conditions: HIV
• Intervention / Treatment: Drug: Bictegravir

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 1

Contacts and Locations

Study Locations

• New Zealand
  • Christchurch, New Zealand, 8011
    • Christchurch Clinical Studies Trust
  • Auckland
    • Grafton, Auckland, New Zealand, 1010
      • Auckland Clinical Studies Limited
• United States
  • Florida
    • DeLand, Florida, United States, 32720
      • Avail Clinical Research
    • Miami, Florida, United States, 33014-3616
      • Clinical Pharmacology of Miami, Inc.
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center
  • Minnesota
    • Saint Paul, Minnesota, United States, 55114
      • Prism Clinical Research
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • New Orleans Center for Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Gilead Sciences

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2015
• Primary Completion (Actual): July 6, 2015
• Study Completion (Actual): July 13, 2015

Study Registration Dates

• First Submitted: March 17, 2015
• First Submitted That Met QC Criteria: March 23, 2015
• First Posted (Estimate): March 27, 2015

Study Record Updates

• Last Update Posted (Actual): October 11, 2019
• Last Update Submitted That Met QC Criteria: September 20, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Phase 1; Renally Impaired
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency
• Other Study ID Numbers: GS-US-141-1479; 2015-000898-12 (EudraCT Number)

Drug and device information, study documents

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