Trial Outcomes & Findings for Pharmacokinetics of Bictegravir in Adults With Normal and Impaired Renal Function (NCT NCT02400307)
NCT ID: NCT02400307
Last Updated: 2019-10-11
Results Overview
AUCinf is defined as the area under the plasma concentration versus time curve extrapolated to infinite time.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
19 participants
Primary outcome timeframe
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
Results posted on
2019-10-11
Participant Flow
Participants were enrolled at study sites in the United States and New Zealand. The first participant was screened on 17 April 2015. The last study visit occurred on 13 July 2015.
49 participants were screened. No participants were enrolled in the moderate or mild renal impairment adaptive cohorts as a review showed that PK data collected were sufficient to detect any differences between the 2 renal function groups.
Participant milestones
| Measure |
Severe Renal Impairment
Participants with severe renal impairment (CrCl = 15 - 29 mL/min) received a single dose of bictegravir 75 mg tablet orally on Day 1 under fed conditions
|
Normal Renal Function
Matched healthy control participants with normal renal function (CrCl ≥ 90 mL/min) received a single dose of bictegravir 75 mg tablet orally on Day 1 under fed conditions
|
|---|---|---|
|
Overall Study
STARTED
|
11
|
8
|
|
Overall Study
COMPLETED
|
10
|
8
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
Severe Renal Impairment
Participants with severe renal impairment (CrCl = 15 - 29 mL/min) received a single dose of bictegravir 75 mg tablet orally on Day 1 under fed conditions
|
Normal Renal Function
Matched healthy control participants with normal renal function (CrCl ≥ 90 mL/min) received a single dose of bictegravir 75 mg tablet orally on Day 1 under fed conditions
|
|---|---|---|
|
Overall Study
Enrolled and Never Dosed
|
1
|
0
|
Baseline Characteristics
Pharmacokinetics of Bictegravir in Adults With Normal and Impaired Renal Function
Baseline characteristics by cohort
| Measure |
Severe Renal Impairment
n=10 Participants
Participants with severe renal impairment (CrCl = 15 - 29 mL/min) received a single dose of bictegravir 75 mg tablet orally on Day 1 under fed conditions
|
Normal Renal Function
n=8 Participants
Matched healthy control participants with normal renal function (CrCl ≥ 90 mL/min) received a single dose of bictegravir 75 mg tablet orally on Day 1 under fed conditions
|
Total
n=18 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
62 years
STANDARD_DEVIATION 15.6 • n=5 Participants
|
56 years
STANDARD_DEVIATION 14.7 • n=7 Participants
|
59 years
STANDARD_DEVIATION 15.1 • n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
7 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
7 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96, 120 and 144 hours postdose on Day 1Population: The PK Analysis Set included participants who took the single dose of bictegravir and had at least 1 nonmissing postdose concentration value for bictegravir.
AUCinf is defined as the area under the plasma concentration versus time curve extrapolated to infinite time.
Outcome measures
| Measure |
Severe Renal Impairment
n=10 Participants
Participants with severe renal impairment (CrCl = 15 - 29 mL/min) received a single dose of bictegravir 75 mg tablet orally on Day 1 under fed conditions
|
Normal Renal Function
n=8 Participants
Matched healthy control participants with normal renal function (CrCl ≥ 90 mL/min) received a single dose of bictegravir 75 mg tablet orally on Day 1 under fed conditions
|
|---|---|---|
|
Pharmacokinetic (PK) Parameter: AUCinf of Bictegravir (Total)
|
138169.7 h*ng/mL
Standard Deviation 61291.27
|
170105.6 h*ng/mL
Standard Deviation 42213.18
|
PRIMARY outcome
Timeframe: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96, 120 and 144 hours postdose on Day 1Population: Participants in the PK Analysis Set were analyzed.
Free AUCinf was calculated based on unbound plasma bictegravir (AUCinf × percentage unbound bictegravir ÷ 100 for each participant).
Outcome measures
| Measure |
Severe Renal Impairment
n=10 Participants
Participants with severe renal impairment (CrCl = 15 - 29 mL/min) received a single dose of bictegravir 75 mg tablet orally on Day 1 under fed conditions
|
Normal Renal Function
n=8 Participants
Matched healthy control participants with normal renal function (CrCl ≥ 90 mL/min) received a single dose of bictegravir 75 mg tablet orally on Day 1 under fed conditions
|
|---|---|---|
|
PK Parameter: AUCinf of Bictegravir (Free)
|
830.6 h*ng/mL
Standard Deviation 266.59
|
824.5 h*ng/mL
Standard Deviation 203.49
|
PRIMARY outcome
Timeframe: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96, 120 and 144 hours postdose on Day 1Population: Participants in the PK Analysis Set were analyzed.
AUClast is defined as the area under the plasma concentration versus time curve from time zero to the last quantifiable concentration.
Outcome measures
| Measure |
Severe Renal Impairment
n=10 Participants
Participants with severe renal impairment (CrCl = 15 - 29 mL/min) received a single dose of bictegravir 75 mg tablet orally on Day 1 under fed conditions
|
Normal Renal Function
n=8 Participants
Matched healthy control participants with normal renal function (CrCl ≥ 90 mL/min) received a single dose of bictegravir 75 mg tablet orally on Day 1 under fed conditions
|
|---|---|---|
|
PK Parameter: AUClast of Bictegravir (Total)
|
136956.4 h*ng/mL
Standard Deviation 60557.34
|
168876.8 h*ng/mL
Standard Deviation 41706.37
|
PRIMARY outcome
Timeframe: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96, 120 and 144 hours postdose on Day 1Population: Participants in the PK Analysis Set were analyzed.
Free AUClast was calculated based on unbound plasma bictegravir (AUClast × percentage unbound bictegravir ÷ 100 for each participant).
Outcome measures
| Measure |
Severe Renal Impairment
n=10 Participants
Participants with severe renal impairment (CrCl = 15 - 29 mL/min) received a single dose of bictegravir 75 mg tablet orally on Day 1 under fed conditions
|
Normal Renal Function
n=8 Participants
Matched healthy control participants with normal renal function (CrCl ≥ 90 mL/min) received a single dose of bictegravir 75 mg tablet orally on Day 1 under fed conditions
|
|---|---|---|
|
PK Parameter: AUClast of Bictegravir (Free)
|
822.5 h*ng/mL
Standard Deviation 263.22
|
818.6 h*ng/mL
Standard Deviation 201.18
|
PRIMARY outcome
Timeframe: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96, 120 and 144 hours postdose on Day 1Population: Participants in the PK Analysis Set were analyzed.
Cmax is defined as the maximum observed plasma concentration of drug.
Outcome measures
| Measure |
Severe Renal Impairment
n=10 Participants
Participants with severe renal impairment (CrCl = 15 - 29 mL/min) received a single dose of bictegravir 75 mg tablet orally on Day 1 under fed conditions
|
Normal Renal Function
n=8 Participants
Matched healthy control participants with normal renal function (CrCl ≥ 90 mL/min) received a single dose of bictegravir 75 mg tablet orally on Day 1 under fed conditions
|
|---|---|---|
|
PK Parameter: Cmax of Bictegravir (Total)
|
5977.0 ng/mL
Standard Deviation 2079.57
|
7227.5 ng/mL
Standard Deviation 2135.56
|
PRIMARY outcome
Timeframe: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96, 120 and 144 hours postdose on Day 1Population: Participants in the PK Analysis Set were analyzed.
Free Cmax was calculated based on unbound plasma bictegravir (Cmax × percentage unbound bictegravir ÷ 100 for each participant).
Outcome measures
| Measure |
Severe Renal Impairment
n=10 Participants
Participants with severe renal impairment (CrCl = 15 - 29 mL/min) received a single dose of bictegravir 75 mg tablet orally on Day 1 under fed conditions
|
Normal Renal Function
n=8 Participants
Matched healthy control participants with normal renal function (CrCl ≥ 90 mL/min) received a single dose of bictegravir 75 mg tablet orally on Day 1 under fed conditions
|
|---|---|---|
|
PK Parameter: Cmax of Bictegravir (Free)
|
37.7 ng/mL
Standard Deviation 8.15
|
35.0 ng/mL
Standard Deviation 9.94
|
SECONDARY outcome
Timeframe: First dose date to Day 31Population: The Safety Analysis Set included participants who received the single dose of study drug.
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.
Outcome measures
| Measure |
Severe Renal Impairment
n=10 Participants
Participants with severe renal impairment (CrCl = 15 - 29 mL/min) received a single dose of bictegravir 75 mg tablet orally on Day 1 under fed conditions
|
Normal Renal Function
n=8 Participants
Matched healthy control participants with normal renal function (CrCl ≥ 90 mL/min) received a single dose of bictegravir 75 mg tablet orally on Day 1 under fed conditions
|
|---|---|---|
|
Percentage of Participants Who Experienced Treatment-Emergent Adverse Events
|
20.0 percentage of participants
|
25.0 percentage of participants
|
SECONDARY outcome
Timeframe: First dose date to Day 31Population: Participants in the Safety Analysis Set were analyzed.
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.
Outcome measures
| Measure |
Severe Renal Impairment
n=10 Participants
Participants with severe renal impairment (CrCl = 15 - 29 mL/min) received a single dose of bictegravir 75 mg tablet orally on Day 1 under fed conditions
|
Normal Renal Function
n=8 Participants
Matched healthy control participants with normal renal function (CrCl ≥ 90 mL/min) received a single dose of bictegravir 75 mg tablet orally on Day 1 under fed conditions
|
|---|---|---|
|
Percentage of Participants Who Experienced Treatment-Emergent Laboratory Abnormalities
Grade 1
|
20.0 percentage of participants
|
25.0 percentage of participants
|
|
Percentage of Participants Who Experienced Treatment-Emergent Laboratory Abnormalities
Grade 2
|
40.0 percentage of participants
|
25.0 percentage of participants
|
|
Percentage of Participants Who Experienced Treatment-Emergent Laboratory Abnormalities
Grade 3
|
40.0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants Who Experienced Treatment-Emergent Laboratory Abnormalities
Grade 4
|
0 percentage of participants
|
0 percentage of participants
|
Adverse Events
Severe Renal Impairment
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Normal Renal Function
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Severe Renal Impairment
n=10 participants at risk
Participants with severe renal impairment (CrCl = 15 - 29 mL/min) received a single dose of bictegravir 75 mg tablet orally on Day 1 under fed conditions
|
Normal Renal Function
n=8 participants at risk
Matched healthy control participants with normal renal function (CrCl ≥ 90 mL/min) received a single dose of bictegravir 75 mg tablet orally on Day 1 under fed conditions
|
|---|---|---|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/10 • First dose date to Day 31
The Safety Analysis Set included participants who received the single dose of bictegravir.
|
12.5%
1/8 • First dose date to Day 31
The Safety Analysis Set included participants who received the single dose of bictegravir.
|
|
Gastrointestinal disorders
Nausea
|
10.0%
1/10 • First dose date to Day 31
The Safety Analysis Set included participants who received the single dose of bictegravir.
|
0.00%
0/8 • First dose date to Day 31
The Safety Analysis Set included participants who received the single dose of bictegravir.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
10.0%
1/10 • First dose date to Day 31
The Safety Analysis Set included participants who received the single dose of bictegravir.
|
0.00%
0/8 • First dose date to Day 31
The Safety Analysis Set included participants who received the single dose of bictegravir.
|
|
Nervous system disorders
Headache
|
0.00%
0/10 • First dose date to Day 31
The Safety Analysis Set included participants who received the single dose of bictegravir.
|
12.5%
1/8 • First dose date to Day 31
The Safety Analysis Set included participants who received the single dose of bictegravir.
|
|
Skin and subcutaneous tissue disorders
Ecchymosis
|
10.0%
1/10 • First dose date to Day 31
The Safety Analysis Set included participants who received the single dose of bictegravir.
|
0.00%
0/8 • First dose date to Day 31
The Safety Analysis Set included participants who received the single dose of bictegravir.
|
Additional Information
Gilead Clinical Study Information Center
Gilead Sciences
Phone: 1-833-445-3230 (GILEAD-0)
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: * The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or * The study has been completed at all study sites for at least 2 years
- Publication restrictions are in place
Restriction type: OTHER