Trial Outcomes & Findings for Study to Evaluate the Pharmacokinetics of Velpatasvir in Participants With Normal Renal Function and Severe Renal Impairment (NCT NCT02002767)

Results Overview

AUClast is defined as the area under the plasma concentration versus time curve from time zero to the last quantifiable concentration.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

19 participants

Primary outcome timeframe

Pre-dose (≤ 5 min), 0.5, 1, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 18, 24, 48, 72, 96, and 120 hours post-dose on Day 1

Results posted on

2020-11-16

Participant Flow

Participants were enrolled at study sites in United Stated and New Zealand. The first participant was screened on 16 December 2013. The last study visit occurred on 09 June 2014.

46 participants were screened.

Participant milestones

Participant milestones
Measure	Normal Renal Function Participants with normal renal function received velpatasvir 100 mg administered orally with a light breakfast on Day 1.	Severe Renal Impairment Participants with severe renal impairment received velpatasvir 100 mg administered orally with a light breakfast on Day 1.
Overall Study STARTED	9	10
Overall Study COMPLETED	9	10
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study to Evaluate the Pharmacokinetics of Velpatasvir in Participants With Normal Renal Function and Severe Renal Impairment

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Normal Renal Function n=9 Participants Participants with normal renal function received velpatasvir 100 mg administered orally with a light breakfast on Day 1.	Severe Renal Impairment n=10 Participants Participants with severe renal impairment received velpatasvir 100 mg administered orally with a light breakfast on Day 1.	Total n=19 Participants Total of all reporting groups
Age, Continuous	66 years STANDARD_DEVIATION 3.7 • n=5 Participants	71 years STANDARD_DEVIATION 4.0 • n=7 Participants	68 years STANDARD_DEVIATION 4.7 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized White	8 Participants n=5 Participants	8 Participants n=7 Participants	16 Participants n=5 Participants

PRIMARY outcome

Timeframe: Pre-dose (≤ 5 min), 0.5, 1, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 18, 24, 48, 72, 96, and 120 hours post-dose on Day 1

Population: The PK analysis set included all enrolled and treated participants who have evaluable PK profiles for velpatasvir.

AUClast is defined as the area under the plasma concentration versus time curve from time zero to the last quantifiable concentration.

Outcome measures

Outcome measures
Measure	Normal Renal Function n=9 Participants Participants with normal renal function received velpatasvir 100 mg administered orally with a light breakfast on Day 1.	Severe Renal Impairment n=10 Participants Participants with severe renal impairment received velpatasvir 100 mg administered orally with a light breakfast on Day 1.
Pharmacokinetic (PK) Parameter of Velpatasvir: AUClast	5597.8 h*ng/mL Standard Deviation 1749.18	7971.7 h*ng/mL Standard Deviation 2531.09

PRIMARY outcome

Timeframe: Pre-dose (≤ 5 min), 0.5, 1, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 18, 24, 48, 72, 96, and 120 hours post-dose on Day 1

Population: Participants in the PK Analysis Set were analyzed.

AUCinf is defined as the area under the plasma concentration versus time curve extrapolated to infinite time.

Outcome measures

Outcome measures
Measure	Normal Renal Function n=9 Participants Participants with normal renal function received velpatasvir 100 mg administered orally with a light breakfast on Day 1.	Severe Renal Impairment n=10 Participants Participants with severe renal impairment received velpatasvir 100 mg administered orally with a light breakfast on Day 1.
PK Parameter of Velpatasvir: AUCinf	5651.6 h*ng/mL Standard Deviation 1763.12	8108.3 h*ng/mL Standard Deviation 2628.18

PRIMARY outcome

Timeframe: Pre-dose (≤ 5 min), 0.5, 1, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 18, 24, 48, 72, 96, and 120 hours post-dose on Day 1

Population: Participants in the PK Analysis Set were analyzed.

Cmax is defined as the maximum observed plasma concentration of drug.

Outcome measures

Outcome measures
Measure	Normal Renal Function n=9 Participants Participants with normal renal function received velpatasvir 100 mg administered orally with a light breakfast on Day 1.	Severe Renal Impairment n=10 Participants Participants with severe renal impairment received velpatasvir 100 mg administered orally with a light breakfast on Day 1.
PK Parameter of Velpatasvir: Cmax	702.7 ng/mL Standard Deviation 197.20	732.4 ng/mL Standard Deviation 176.19

SECONDARY outcome

Timeframe: First dose date plus 30 days

Population: The Safety Analysis Set included participants who were enrolled and received at least 1 dose of study drug.

Treatment-emergent adverse events (TEAEs) were 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.

Outcome measures

Outcome measures
Measure	Normal Renal Function n=9 Participants Participants with normal renal function received velpatasvir 100 mg administered orally with a light breakfast on Day 1.	Severe Renal Impairment n=10 Participants Participants with severe renal impairment received velpatasvir 100 mg administered orally with a light breakfast on Day 1.
Percentage of Participants Experiencing Treatment-Emergent Adverse Events	0 percentage of participants	20 percentage of participants

SECONDARY outcome

Timeframe: First dose date plus 30 days

Population: Participants in the Safety Analysis Set were analyzed.

A treatment-emergent laboratory abnormality was defined as an increase of at least 1 abnormality grade from baseline and occurring after the first dose of study drug and within 30 days after last study drug administration. The severity of laboratory abnormalities was assessed as Grade 0, 1 (mild), 2 (moderate), 3 (severe), or 4 (potentially life threatening).

Outcome measures

Outcome measures
Measure	Normal Renal Function n=9 Participants Participants with normal renal function received velpatasvir 100 mg administered orally with a light breakfast on Day 1.	Severe Renal Impairment n=10 Participants Participants with severe renal impairment received velpatasvir 100 mg administered orally with a light breakfast on Day 1.
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities Grade 1	33.3 percentage of participants	20 percentage of participants
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities Grade 2	0 percentage of participants	30 percentage of participants
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities Grade 3	0 percentage of participants	30 percentage of participants
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities Grade 4	0 percentage of participants	10 percentage of participants

SECONDARY outcome

Timeframe: 2 or 3 hours post-dose on Day 1

Population: Participants in the PK Analysis Set were analyzed.

Mean velpatasvir protein binding (percentage free and percentage bound) was determined in all participants at 2 or 3 hours post-dose. Protein binding was assessed at Tmax whenever possible or at the time point closest to Tmax for each participant.

Outcome measures

Outcome measures
Measure	Normal Renal Function n=9 Participants Participants with normal renal function received velpatasvir 100 mg administered orally with a light breakfast on Day 1.	Severe Renal Impairment n=10 Participants Participants with severe renal impairment received velpatasvir 100 mg administered orally with a light breakfast on Day 1.
Percentage Protein Binding of Velpatasvir Free Protein Percentage	0.29 percentage of plasma protein binding Standard Deviation 0.012	0.29 percentage of plasma protein binding Standard Deviation 0.012
Percentage Protein Binding of Velpatasvir Bound Protein Percentage	99.71 percentage of plasma protein binding Standard Deviation 0.012	99.71 percentage of plasma protein binding Standard Deviation 0.012

Adverse Events

Normal Renal Function

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Severe Renal Impairment

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Normal Renal Function n=9 participants at risk Participants with normal renal function received velpatasvir 100 mg administered orally with a light breakfast on Day 1.	Severe Renal Impairment n=10 participants at risk Participants with severe renal impairment received velpatasvir 100 mg administered orally with a light breakfast on Day 1.
General disorders Vessel puncture site haemorrhage	0.00% 0/9 • First dose date plus 30 days The Safety Analysis Set included participants who were enrolled and received at least 1 dose of study drug.	10.0% 1/10 • First dose date plus 30 days The Safety Analysis Set included participants who were enrolled and received at least 1 dose of study drug.
Nervous system disorders Dizziness	0.00% 0/9 • First dose date plus 30 days The Safety Analysis Set included participants who were enrolled and received at least 1 dose of study drug.	10.0% 1/10 • First dose date plus 30 days The Safety Analysis Set included participants who were enrolled and received at least 1 dose of study drug.

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