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Dose-Ranging Study of Sofosbuvir in Combination With Pegylated Interferon and Ribavirin in Treatment Naïve GT 1 HCV Patients

A Multi-center, Double-Blind, Parallel Group, Randomized, Placebo-Controlled, Dose Ranging Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Following Oral Administration of PSI-7977 in Combination With Standard of Care (Pegylated Interferon and Ribavirin) in Treatment-Naïve Patients With Chronic HCV Infection Genotype 1

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01054729
Enrollment
64
Registered
2010-01-22
Start date
2010-01-31
Completion date
2011-08-31
Last updated
2014-04-17

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Hepatitis C

Keywords

Chronic Hepatitis C infection Genotype 1, HCV, GT1, GT 1

Brief summary

Participants with genotype 1 HCV infection were randomized to 1 of 3 sofosbuvir doses (100 mg, 200 mg, or 400 mg) or matching placebo once daily based upon stratification for IL28B status (CC or CT/TT). Placebo tablets were administered to participants receiving 100 mg active sofosbuvir (3 placebo tablets) and 200 mg active sofosbuvir (2 placebo tablets) in order to maintain the study blind. Participants received sofosbuvir/matching placebo from Day 0 to 27. Participants also received treatment with PEG+RBV starting on Day 0 of the study which continued for 48 weeks. Participants were evaluated for sustained virologic response (SVR) for an additional 24 weeks following completion of study treatment.

Interventions

DRUGSofosbuvir

Sofosbuvir tablet(s) administered orally once daily

DRUGPlacebo

Placebo to match sofosbuvir administered orally once daily

DRUGPEG

Pegylated interferon alfa-2a (PEG) 180 μg was administered once weekly by subcutaneous injection.

DRUGRBV

Ribavirin (RBV) tablets were administered orally in a divided daily dose according to package insert weight-based dosing recommendations (\< 75kg = 1000 mg and ≥ 75 kg = 1200 mg).

Sponsors

Gilead Sciences
Lead SponsorINDUSTRY

Study design

Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No

Inclusion criteria

* Treatment-naive males and females, 18-65 years of age * Genotype 1 HCV infection * Negative pregnancy test for females of childbearing age * Females of childbearing age and males with female partners of childbearing age must use two forms of contraception during treatment and following the last dose of ribavirin in accordance with locally approved label for ribavirin

Exclusion criteria

* Hepatitis B or HIV infection * Pregnant or breast feeding females or male partners of pregnant females * Previous interferon or ribavirin-based therapy or investigational anti-HCV agent * History or evidence of medical condition associated with chronic liver disease other than HCV

Design outcomes

Primary

MeasureTime frameDescription
Percentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment PeriodBaseline to Week 4Adverse events (AEs) occurring during the sofosbuvir treatment period were summarized across the participant population. A participant was counted once if they had a qualifying event.

Secondary

MeasureTime frameDescription
Change in Circulating HCV RNA at Week 4Baseline to Week 4—
Percentage of Participants With Rapid Virologic Response at Week 4Week 4Rapid virologic response (RVR) was defined as HCV RNA below the limit of detection (LOD \[15 IU/mL\]) at Week 4.
Percentage of Participants With Sustained Virologic Response (SVR) at 12 and 24 Weeks After Last Dose of PEG+RBV Following Completion of 48 Weeks of TreatmentPost-treatment Weeks 12 and 24SVR at 12 weeks (SVR12) and 24 weeks (SVR24) was defined as HCV RNA \< LOD 12 and 24 weeks after last dose of PEG+RBV, respectively, following completion of 48 weeks of treatment (4 weeks of sofosbuvir or matching placebo and PEG+RBV, followed by an additional 44 weeks of PEG+RBV).
Plasma Pharmacokinetics of Sofosbuvir: Cmax at Day 0Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdoseThe Cmax of sofosbuvir was measured at Day 0 following a single dose of sofosbuvir. Cmax is defined as the maximum concentration of drug.
Plasma Pharmacokinetics of Sofosbuvir: Cmax at Day 27Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)The Cmax of sofosbuvir was measured at Day 27 following continuous dosing of sofosbuvir.
Plasma Pharmacokinetics of Sofosbuvir: AUCinf at Day 0Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdoseThe AUCinf of sofosbuvir was analyzed at Day 0 (following a single dose of sofosbuvir). AUCinf is defined as the concentration of drug (area under the plasma concentration versus time curve) extrapolated to infinite time.
Plasma Pharmacokinetics of Sofosbuvir: AUCtau at Day 27Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)The AUCtau of sofosbuvir was analyzed at Day 27 (following continuous dosing of sofosbuvir). AUCtau is defined as the concentration of drug (area under the plasma concentration versus time curve) over the dosing interval.
Percentage of Participants Who Developed Resistance to SofosbuvirBaseline to Week 4—
Plasma Pharmacokinetics of GS-331007: Cmax at Day 27Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)The Cmax of GS-331007 was measured at Day 27 following continuous dosing of sofosbuvir.
Plasma Pharmacokinetics of GS-331007: AUCinf at Day 0Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdoseThe AUCinf of GS-331007 was analyzed at Day 0 (following a single dose of sofosbuvir).
Plasma Pharmacokinetics of GS-331007: AUCtau at Day 27Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)The AUCtau of GS-331007 was analyzed at Day 27 (following continuous dosing of sofosbuvir).
Plasma Pharmacokinetics of GS-566500: Cmax at Day 0Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdoseThe Cmax of GS-566500 was measured at Day 0 following a single dose of sofosbuvir. GS-566500 is one of the major metabolites of sofosbuvir.
Plasma Pharmacokinetics of GS-566500: Cmax at Day 27Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)The Cmax of GS-566500 was measured at Day 27 following continuous dosing of sofosbuvir.
Plasma Pharmacokinetics of GS-566500: AUCinf at Day 0Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdoseThe AUCinf of GS-566500 was analyzed at Day 0 (following a single dose of sofosbuvir).
Plasma Pharmacokinetics of GS-566500: AUCtau at Day 27Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)The AUCtau of GS-566500 was analyzed at Day 27 (following continuous dosing of sofosbuvir).
Plasma Pharmacokinetics of GS-331007: Cmax at Day 0Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdoseThe Cmax of GS-331007 was measured at Day 0 following a single dose of sofosbuvir. GS-331007 is the predominant circulating metabolite of sofosbuvir.

Countries

Puerto Rico, United States

Participant flow

Recruitment details

Subjects were enrolled at a total of 7 study sites in the United States. The first participant was screened on 18 January 2010. The last participant observation was on 25 August 2011.

Pre-assignment details

143 participants were screened and 64 were randomized; 63 participants were treated, and comprise the Safety Analysis Set.

Participants by arm

ArmCount
Sofosbuvir 100 mg+PEG+RBV
Sofosbuvir 100 mg for 28 days plus PEG+RBV for 48 weeks
16
Sofosbuvir 200 mg+PEG+RBV
Sofosbuvir 200 mg for 28 days plus PEG+RBV for 48 weeks
18
Sofosbuvir 400 mg+PEG+RBV
Sofosbuvir 400 mg for 28 days plus PEG+RBV for 48 weeks
15
Placebo+PEG+RBV
Placebo to match sofosbuvir for 28 days plus PEG+RBV for 48 weeks
14
Total63

Withdrawals & dropouts

PeriodReasonFG000FG001FG002FG003
Overall StudyAdverse Event1121
Overall StudyLack of Efficacy0001
Overall StudyLost to Follow-up0100
Overall StudyLost to Follow-up, Later Contacted Site0100
Overall StudyNon-responder1011
Overall StudyPEG/RBV Non-responder1010
Overall StudyPersonal/Obligations0100
Overall StudyRandomized but Not Treated0100
Overall StudySubject moved0010
Overall StudyWithdrawal by Subject1010

Baseline characteristics

CharacteristicSofosbuvir 100 mg+PEG+RBVSofosbuvir 200 mg+PEG+RBVSofosbuvir 400 mg+PEG+RBVPlacebo+PEG+RBVTotal
Age, Continuous44.4 years
STANDARD_DEVIATION 10.1
44.4 years
STANDARD_DEVIATION 8.34
44.9 years
STANDARD_DEVIATION 8.43
46.6 years
STANDARD_DEVIATION 11.44
45.0 years
STANDARD_DEVIATION 9.38
Alanine Aminotransferase (ALT)69.0 IU/L
STANDARD_DEVIATION 29.69
72.6 IU/L
STANDARD_DEVIATION 46.45
95.4 IU/L
STANDARD_DEVIATION 75.86
70.0 IU/L
STANDARD_DEVIATION 40.73
76.2 IU/L
STANDARD_DEVIATION 50.08
Ethnicity (NIH/OMB)
Hispanic or Latino
7 Participants9 Participants8 Participants4 Participants28 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
9 Participants9 Participants7 Participants10 Participants35 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants0 Participants0 Participants
HCV RNA Level (IU/mL)
≤ 800,000
1 participants3 participants3 participants4 participants11 participants
HCV RNA Level (IU/mL)
> 800,000
15 participants15 participants12 participants10 participants52 participants
Hepatitis C (HCV) RNA6.64 log10 IU/mL
STANDARD_DEVIATION 0.476
6.28 log10 IU/mL
STANDARD_DEVIATION 0.813
6.49 log10 IU/mL
STANDARD_DEVIATION 0.602
6.48 log10 IU/mL
STANDARD_DEVIATION 0.666
6.47 log10 IU/mL
STANDARD_DEVIATION 0.655
IL28b Genotype
CC
4 participants5 participants4 participants4 participants17 participants
IL28b Genotype
CT/TT
12 participants13 participants11 participants10 participants46 participants
Liver Biopsy Fibrosis Score
Bridging Fibrosis
0 participants2 participants1 participants1 participants4 participants
Liver Biopsy Fibrosis Score
Cirrhosis
0 participants0 participants0 participants0 participants0 participants
Liver Biopsy Fibrosis Score
None or Minimal Fibrosis
5 participants6 participants5 participants4 participants20 participants
Liver Biopsy Fibrosis Score
Portal Fibrosis
11 participants10 participants9 participants9 participants39 participants
Race/Ethnicity, Customized
American Indian or Alaska native
0 participants0 participants1 participants0 participants1 participants
Race/Ethnicity, Customized
Black or African American
1 participants2 participants2 participants0 participants5 participants
Race/Ethnicity, Customized
White
15 participants16 participants12 participants14 participants57 participants
Sex: Female, Male
Female
5 Participants8 Participants4 Participants3 Participants20 Participants
Sex: Female, Male
Male
11 Participants10 Participants11 Participants11 Participants43 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
deaths
Total, all-cause mortality
— / —— / —— / —— / —
other
Total, other adverse events
14 / 1618 / 1813 / 1513 / 14
serious
Total, serious adverse events
1 / 160 / 183 / 151 / 14

Outcome results

Primary

Percentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment Period

Adverse events (AEs) occurring during the sofosbuvir treatment period were summarized across the participant population. A participant was counted once if they had a qualifying event.

Time frame: Baseline to Week 4

Population: Safety Analysis Set: participants were randomized and received at least 1 dose of study drug

ArmMeasureGroupValue (NUMBER)
Sofosbuvir 100 mg+PEG+RBVPercentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment PeriodGrade 3 or higher AE0.0 percentage of participants
Sofosbuvir 100 mg+PEG+RBVPercentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment PeriodAE leading to drug discontinuation/interruption0.0 percentage of participants
Sofosbuvir 100 mg+PEG+RBVPercentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment PeriodAny AE87.5 percentage of participants
Sofosbuvir 100 mg+PEG+RBVPercentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment PeriodDrug-related AE12.5 percentage of participants
Sofosbuvir 100 mg+PEG+RBVPercentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment PeriodSerious AE0.0 percentage of participants
Sofosbuvir 200 mg+PEG+RBVPercentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment PeriodGrade 3 or higher AE0.0 percentage of participants
Sofosbuvir 200 mg+PEG+RBVPercentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment PeriodAE leading to drug discontinuation/interruption0.0 percentage of participants
Sofosbuvir 200 mg+PEG+RBVPercentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment PeriodDrug-related AE27.8 percentage of participants
Sofosbuvir 200 mg+PEG+RBVPercentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment PeriodAny AE83.3 percentage of participants
Sofosbuvir 200 mg+PEG+RBVPercentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment PeriodSerious AE0.0 percentage of participants
Sofosbuvir 400 mg+PEG+RBVPercentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment PeriodGrade 3 or higher AE0.0 percentage of participants
Sofosbuvir 400 mg+PEG+RBVPercentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment PeriodAny AE86.7 percentage of participants
Sofosbuvir 400 mg+PEG+RBVPercentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment PeriodDrug-related AE33.3 percentage of participants
Sofosbuvir 400 mg+PEG+RBVPercentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment PeriodAE leading to drug discontinuation/interruption0.0 percentage of participants
Sofosbuvir 400 mg+PEG+RBVPercentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment PeriodSerious AE0.0 percentage of participants
Placebo+PEG+RBVPercentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment PeriodAE leading to drug discontinuation/interruption0.0 percentage of participants
Placebo+PEG+RBVPercentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment PeriodDrug-related AE42.9 percentage of participants
Placebo+PEG+RBVPercentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment PeriodAny AE85.7 percentage of participants
Placebo+PEG+RBVPercentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment PeriodGrade 3 or higher AE0.0 percentage of participants
Placebo+PEG+RBVPercentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment PeriodSerious AE0.0 percentage of participants
Secondary

Change in Circulating HCV RNA at Week 4

Time frame: Baseline to Week 4

Population: Safety Analysis Set

ArmMeasureValue (MEAN)Dispersion
Sofosbuvir 100 mg+PEG+RBVChange in Circulating HCV RNA at Week 4-5.323 log10 IU/mLStandard Deviation 0.6642
Sofosbuvir 200 mg+PEG+RBVChange in Circulating HCV RNA at Week 4-5.081 log10 IU/mLStandard Deviation 0.8068
Sofosbuvir 400 mg+PEG+RBVChange in Circulating HCV RNA at Week 4-5.346 log10 IU/mLStandard Deviation 0.613
Placebo+PEG+RBVChange in Circulating HCV RNA at Week 4-2.8 log10 IU/mLStandard Deviation 1.6034
Secondary

Percentage of Participants Who Developed Resistance to Sofosbuvir

Time frame: Baseline to Week 4

Population: Participants in the Safety Analysis Set who received a regimen containing sofosbuvir were analyzed.

ArmMeasureValue (NUMBER)
Sofosbuvir 100 mg+PEG+RBVPercentage of Participants Who Developed Resistance to Sofosbuvir0.0 percentage of participants
Sofosbuvir 200 mg+PEG+RBVPercentage of Participants Who Developed Resistance to Sofosbuvir0.0 percentage of participants
Sofosbuvir 400 mg+PEG+RBVPercentage of Participants Who Developed Resistance to Sofosbuvir0.0 percentage of participants
Secondary

Percentage of Participants With Rapid Virologic Response at Week 4

Rapid virologic response (RVR) was defined as HCV RNA below the limit of detection (LOD \[15 IU/mL\]) at Week 4.

Time frame: Week 4

Population: Safety Analysis Set

ArmMeasureValue (NUMBER)
Sofosbuvir 100 mg+PEG+RBVPercentage of Participants With Rapid Virologic Response at Week 487.5 percentage of participants
Sofosbuvir 200 mg+PEG+RBVPercentage of Participants With Rapid Virologic Response at Week 494.4 percentage of participants
Sofosbuvir 400 mg+PEG+RBVPercentage of Participants With Rapid Virologic Response at Week 493.3 percentage of participants
Placebo+PEG+RBVPercentage of Participants With Rapid Virologic Response at Week 421.4 percentage of participants
Secondary

Percentage of Participants With Sustained Virologic Response (SVR) at 12 and 24 Weeks After Last Dose of PEG+RBV Following Completion of 48 Weeks of Treatment

SVR at 12 weeks (SVR12) and 24 weeks (SVR24) was defined as HCV RNA \< LOD 12 and 24 weeks after last dose of PEG+RBV, respectively, following completion of 48 weeks of treatment (4 weeks of sofosbuvir or matching placebo and PEG+RBV, followed by an additional 44 weeks of PEG+RBV).

Time frame: Post-treatment Weeks 12 and 24

Population: Safety Analysis Set

ArmMeasureGroupValue (NUMBER)
Sofosbuvir 100 mg+PEG+RBVPercentage of Participants With Sustained Virologic Response (SVR) at 12 and 24 Weeks After Last Dose of PEG+RBV Following Completion of 48 Weeks of TreatmentSVR1256.3 percentage of participants
Sofosbuvir 100 mg+PEG+RBVPercentage of Participants With Sustained Virologic Response (SVR) at 12 and 24 Weeks After Last Dose of PEG+RBV Following Completion of 48 Weeks of TreatmentSVR2456.3 percentage of participants
Sofosbuvir 200 mg+PEG+RBVPercentage of Participants With Sustained Virologic Response (SVR) at 12 and 24 Weeks After Last Dose of PEG+RBV Following Completion of 48 Weeks of TreatmentSVR2483.3 percentage of participants
Sofosbuvir 200 mg+PEG+RBVPercentage of Participants With Sustained Virologic Response (SVR) at 12 and 24 Weeks After Last Dose of PEG+RBV Following Completion of 48 Weeks of TreatmentSVR1272.2 percentage of participants
Sofosbuvir 400 mg+PEG+RBVPercentage of Participants With Sustained Virologic Response (SVR) at 12 and 24 Weeks After Last Dose of PEG+RBV Following Completion of 48 Weeks of TreatmentSVR1286.7 percentage of participants
Sofosbuvir 400 mg+PEG+RBVPercentage of Participants With Sustained Virologic Response (SVR) at 12 and 24 Weeks After Last Dose of PEG+RBV Following Completion of 48 Weeks of TreatmentSVR2480.0 percentage of participants
Placebo+PEG+RBVPercentage of Participants With Sustained Virologic Response (SVR) at 12 and 24 Weeks After Last Dose of PEG+RBV Following Completion of 48 Weeks of TreatmentSVR1250.0 percentage of participants
Placebo+PEG+RBVPercentage of Participants With Sustained Virologic Response (SVR) at 12 and 24 Weeks After Last Dose of PEG+RBV Following Completion of 48 Weeks of TreatmentSVR2442.9 percentage of participants
Secondary

Plasma Pharmacokinetics of GS-331007: AUCinf at Day 0

The AUCinf of GS-331007 was analyzed at Day 0 (following a single dose of sofosbuvir).

Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose

Population: Participants in the Safety Analysis Set with available data and who received a regimen containing sofosbuvir were analyzed.

ArmMeasureValue (MEAN)Dispersion
Sofosbuvir 100 mg+PEG+RBVPlasma Pharmacokinetics of GS-331007: AUCinf at Day 02173.18 h*ng/mLStandard Deviation 852.32
Sofosbuvir 200 mg+PEG+RBVPlasma Pharmacokinetics of GS-331007: AUCinf at Day 03984.88 h*ng/mLStandard Deviation 895.69
Sofosbuvir 400 mg+PEG+RBVPlasma Pharmacokinetics of GS-331007: AUCinf at Day 07559.91 h*ng/mLStandard Deviation 3065.23
Secondary

Plasma Pharmacokinetics of GS-331007: AUCtau at Day 27

The AUCtau of GS-331007 was analyzed at Day 27 (following continuous dosing of sofosbuvir).

Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)

Population: Participants in the Safety Analysis Set with available data and who received a regimen containing sofosbuvir were analyzed.

ArmMeasureValue (MEAN)Dispersion
Sofosbuvir 100 mg+PEG+RBVPlasma Pharmacokinetics of GS-331007: AUCtau at Day 272256.81 h*ng/mLStandard Deviation 982.4
Sofosbuvir 200 mg+PEG+RBVPlasma Pharmacokinetics of GS-331007: AUCtau at Day 273389.23 h*ng/mLStandard Deviation 832.01
Sofosbuvir 400 mg+PEG+RBVPlasma Pharmacokinetics of GS-331007: AUCtau at Day 277398.99 h*ng/mLStandard Deviation 2633.7
Secondary

Plasma Pharmacokinetics of GS-331007: Cmax at Day 0

The Cmax of GS-331007 was measured at Day 0 following a single dose of sofosbuvir. GS-331007 is the predominant circulating metabolite of sofosbuvir.

Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose

Population: Participants in the Safety Analysis Set with available data and who received a regimen containing sofosbuvir were analyzed.

ArmMeasureValue (MEAN)Dispersion
Sofosbuvir 100 mg+PEG+RBVPlasma Pharmacokinetics of GS-331007: Cmax at Day 0197.32 ng/mLStandard Deviation 88.68
Sofosbuvir 200 mg+PEG+RBVPlasma Pharmacokinetics of GS-331007: Cmax at Day 0357.33 ng/mLStandard Deviation 99.88
Sofosbuvir 400 mg+PEG+RBVPlasma Pharmacokinetics of GS-331007: Cmax at Day 0662.13 ng/mLStandard Deviation 214.76
Secondary

Plasma Pharmacokinetics of GS-331007: Cmax at Day 27

The Cmax of GS-331007 was measured at Day 27 following continuous dosing of sofosbuvir.

Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)

Population: Participants in the Safety Analysis Set with available data and who received a regimen containing sofosbuvir were analyzed.

ArmMeasureValue (MEAN)Dispersion
Sofosbuvir 100 mg+PEG+RBVPlasma Pharmacokinetics of GS-331007: Cmax at Day 27233.79 ng/mLStandard Deviation 105.02
Sofosbuvir 200 mg+PEG+RBVPlasma Pharmacokinetics of GS-331007: Cmax at Day 27357.38 ng/mLStandard Deviation 109.91
Sofosbuvir 400 mg+PEG+RBVPlasma Pharmacokinetics of GS-331007: Cmax at Day 27717.23 ng/mLStandard Deviation 208.62
Secondary

Plasma Pharmacokinetics of GS-566500: AUCinf at Day 0

The AUCinf of GS-566500 was analyzed at Day 0 (following a single dose of sofosbuvir).

Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose

Population: Participants in the Safety Analysis Set with available data and who received a regimen containing sofosbuvir were analyzed.

ArmMeasureValue (MEAN)Dispersion
Sofosbuvir 100 mg+PEG+RBVPlasma Pharmacokinetics of GS-566500: AUCinf at Day 0266.22 h*ng/mLStandard Deviation 122.4
Sofosbuvir 200 mg+PEG+RBVPlasma Pharmacokinetics of GS-566500: AUCinf at Day 0645.95 h*ng/mLStandard Deviation 228.09
Sofosbuvir 400 mg+PEG+RBVPlasma Pharmacokinetics of GS-566500: AUCinf at Day 01315.94 h*ng/mLStandard Deviation 618.96
Secondary

Plasma Pharmacokinetics of GS-566500: AUCtau at Day 27

The AUCtau of GS-566500 was analyzed at Day 27 (following continuous dosing of sofosbuvir).

Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)

Population: Participants in the Safety Analysis Set with available data and who received a regimen containing sofosbuvir were analyzed.

ArmMeasureValue (MEAN)Dispersion
Sofosbuvir 100 mg+PEG+RBVPlasma Pharmacokinetics of GS-566500: AUCtau at Day 27262.00 h*ng/mLStandard Deviation 120.64
Sofosbuvir 200 mg+PEG+RBVPlasma Pharmacokinetics of GS-566500: AUCtau at Day 27571.95 h*ng/mLStandard Deviation 156.59
Sofosbuvir 400 mg+PEG+RBVPlasma Pharmacokinetics of GS-566500: AUCtau at Day 271072.91 h*ng/mLStandard Deviation 327.09
Secondary

Plasma Pharmacokinetics of GS-566500: Cmax at Day 0

The Cmax of GS-566500 was measured at Day 0 following a single dose of sofosbuvir. GS-566500 is one of the major metabolites of sofosbuvir.

Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose

Population: Participants in the Safety Analysis Set with available data and who received a regimen containing sofosbuvir were analyzed.

ArmMeasureValue (MEAN)Dispersion
Sofosbuvir 100 mg+PEG+RBVPlasma Pharmacokinetics of GS-566500: Cmax at Day 069.99 ng/mLStandard Deviation 35.98
Sofosbuvir 200 mg+PEG+RBVPlasma Pharmacokinetics of GS-566500: Cmax at Day 0145.51 ng/mLStandard Deviation 31.95
Sofosbuvir 400 mg+PEG+RBVPlasma Pharmacokinetics of GS-566500: Cmax at Day 0293.35 ng/mLStandard Deviation 92.75
Secondary

Plasma Pharmacokinetics of GS-566500: Cmax at Day 27

The Cmax of GS-566500 was measured at Day 27 following continuous dosing of sofosbuvir.

Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)

Population: Participants in the Safety Analysis Set with available data and who received a regimen containing sofosbuvir were analyzed.

ArmMeasureValue (MEAN)Dispersion
Sofosbuvir 100 mg+PEG+RBVPlasma Pharmacokinetics of GS-566500: Cmax at Day 2764.75 ng/mLStandard Deviation 38.51
Sofosbuvir 200 mg+PEG+RBVPlasma Pharmacokinetics of GS-566500: Cmax at Day 27132.72 ng/mLStandard Deviation 49.33
Sofosbuvir 400 mg+PEG+RBVPlasma Pharmacokinetics of GS-566500: Cmax at Day 27237.46 ng/mLStandard Deviation 51.66
Secondary

Plasma Pharmacokinetics of Sofosbuvir: AUCinf at Day 0

The AUCinf of sofosbuvir was analyzed at Day 0 (following a single dose of sofosbuvir). AUCinf is defined as the concentration of drug (area under the plasma concentration versus time curve) extrapolated to infinite time.

Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose

Population: Participants in the Safety Analysis Set with available data and who received a regimen containing sofosbuvir were analyzed.

ArmMeasureValue (MEAN)Dispersion
Sofosbuvir 100 mg+PEG+RBVPlasma Pharmacokinetics of Sofosbuvir: AUCinf at Day 0280.19 h*ng/mLStandard Deviation 199.54
Sofosbuvir 200 mg+PEG+RBVPlasma Pharmacokinetics of Sofosbuvir: AUCinf at Day 0585.56 h*ng/mLStandard Deviation 342.53
Sofosbuvir 400 mg+PEG+RBVPlasma Pharmacokinetics of Sofosbuvir: AUCinf at Day 01867.24 h*ng/mLStandard Deviation 959.3
Secondary

Plasma Pharmacokinetics of Sofosbuvir: AUCtau at Day 27

The AUCtau of sofosbuvir was analyzed at Day 27 (following continuous dosing of sofosbuvir). AUCtau is defined as the concentration of drug (area under the plasma concentration versus time curve) over the dosing interval.

Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)

Population: Participants in the Safety Analysis Set with available data and who received a regimen containing sofosbuvir were analyzed.

ArmMeasureValue (MEAN)Dispersion
Sofosbuvir 100 mg+PEG+RBVPlasma Pharmacokinetics of Sofosbuvir: AUCtau at Day 27375.70 h*ng/mLStandard Deviation 203.13
Sofosbuvir 200 mg+PEG+RBVPlasma Pharmacokinetics of Sofosbuvir: AUCtau at Day 27732.27 h*ng/mLStandard Deviation 297.19
Sofosbuvir 400 mg+PEG+RBVPlasma Pharmacokinetics of Sofosbuvir: AUCtau at Day 272011.23 h*ng/mLStandard Deviation 988.25
Secondary

Plasma Pharmacokinetics of Sofosbuvir: Cmax at Day 0

The Cmax of sofosbuvir was measured at Day 0 following a single dose of sofosbuvir. Cmax is defined as the maximum concentration of drug.

Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose

Population: Participants in the Safety Analysis Set with available data and who received a regimen containing sofosbuvir were analyzed.

ArmMeasureValue (MEAN)Dispersion
Sofosbuvir 100 mg+PEG+RBVPlasma Pharmacokinetics of Sofosbuvir: Cmax at Day 0218.08 ng/mLStandard Deviation 181.54
Sofosbuvir 200 mg+PEG+RBVPlasma Pharmacokinetics of Sofosbuvir: Cmax at Day 0332.26 ng/mLStandard Deviation 215.53
Sofosbuvir 400 mg+PEG+RBVPlasma Pharmacokinetics of Sofosbuvir: Cmax at Day 01257.50 ng/mLStandard Deviation 736.36
Secondary

Plasma Pharmacokinetics of Sofosbuvir: Cmax at Day 27

The Cmax of sofosbuvir was measured at Day 27 following continuous dosing of sofosbuvir.

Time frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)

Population: Participants in the Safety Analysis Set with available data and who received a regimen containing sofosbuvir were analyzed.

ArmMeasureValue (MEAN)Dispersion
Sofosbuvir 100 mg+PEG+RBVPlasma Pharmacokinetics of Sofosbuvir: Cmax at Day 27253.54 ng/mLStandard Deviation 171.1
Sofosbuvir 200 mg+PEG+RBVPlasma Pharmacokinetics of Sofosbuvir: Cmax at Day 27475.14 ng/mLStandard Deviation 358.88
Sofosbuvir 400 mg+PEG+RBVPlasma Pharmacokinetics of Sofosbuvir: Cmax at Day 271355.65 ng/mLStandard Deviation 853.85

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026