Pharmacokinetics of Bictegravir in Adults With Normal and Impaired Renal Function

Phase 1

Completed

• Conditions: HIV
• Interventions: Drug: Bictegravir

• Registration Number: NCT02400307
• Lead Sponsor: Gilead Sciences

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-03-17
• Study First Submitted QC: 2015-03-23
• Study First Posted: 2015-03-27
• Study Start: 2015-04-17
• Primary Completion: 2015-07-06
• Study Completion: 2015-07-13
• Status Verified: 2019-09
• Results First Submitted: 2019-09-20
• Results First Submitted QC: 2019-09-20
• Last Update Submitted: 2019-09-20
• Results First Posted: 2019-10-11
• Last Update Posted: 2019-10-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 19

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Severe Renal Impairment	Bictegravir	Participants with severe renal impairment and matched healthy controls will receive a single dose of bictegravir.
Moderate Renal Impairment	Bictegravir	Participants with moderate renal impairment and matched healthy controls will receive a single dose of bictegravir.
Mild Renal Impairment	Bictegravir	Participants with mild renal impairment and matched healthy controls will receive a single dose of bictegravir.

Primary Outcome Measures

Name	Time	Method
Pharmacokinetic (PK) Parameter: AUCinf of Bictegravir (Total)	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	AUCinf is defined as the area under the plasma concentration versus time curve extrapolated to infinite time.
PK Parameter: AUCinf of Bictegravir (Free)	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	Free AUCinf was calculated based on unbound plasma bictegravir (AUCinf × percentage unbound bictegravir ÷ 100 for each participant).
PK Parameter: AUClast of Bictegravir (Total)	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	AUClast is defined as the area under the plasma concentration versus time curve from time zero to the last quantifiable concentration.
PK Parameter: AUClast of Bictegravir (Free)	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	Free AUClast was calculated based on unbound plasma bictegravir (AUClast × percentage unbound bictegravir ÷ 100 for each participant).
PK Parameter: Cmax of Bictegravir (Total)	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	Cmax is defined as the maximum observed plasma concentration of drug.
PK Parameter: Cmax of Bictegravir (Free)	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	Free Cmax was calculated based on unbound plasma bictegravir (Cmax × percentage unbound bictegravir ÷ 100 for each participant).

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Who Experienced Treatment-Emergent Adverse Events	First dose date to Day 31	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.
Percentage of Participants Who Experienced Treatment-Emergent Laboratory Abnormalities	First dose date to Day 31	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.

Trial Locations

Locations (7)

Avail Clinical Research; 🇺🇸 DeLand, Florida, United States

Clinical Pharmacology of Miami, Inc.; 🇺🇸 Miami, Florida, United States

Orlando Clinical Research Center; 🇺🇸 Orlando, Florida, United States

Prism Clinical Research; 🇺🇸 Saint Paul, Minnesota, United States

Auckland Clinical Studies Limited; 🇳🇿 Grafton, Auckland, New Zealand

Christchurch Clinical Studies Trust; 🇳🇿 Christchurch, New Zealand

New Orleans Center for Clinical Research; 🇺🇸 Knoxville, Tennessee, United States