Sofosbuvir Plus Ribavirin, or Ledipasvir/Sofosbuvir in Adults With HCV Infection and Renal Insufficiency

Phase 2

Completed

• Conditions: HCV Infection
• Interventions: Drug: LDV/SOF; Drug: SOF; Drug: RBV

• Registration Number: NCT01958281
• Lead Sponsor: Gilead Sciences

Brief Summary

The primary objectives of this study are to evaluate the safety and efficacy of sofosbuvir (SOF) plus ribavirin (RBV) for 24 weeks and ledipasvir/sofosbuvir (LDV/SOF) for 12 weeks, and to evaluate the steady state pharmacokinetics (PK) of SOF and its metabolites and LDV in participants with genotype (GT) 1, 3, or 4 hepatitis C virus (HCV) infection who have chronic renal insufficiency (impaired kidney function).

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design

Study Timeline

• Study First Submitted: 2013-10-06
• Study First Submitted QC: 2013-10-06
• Study Start: 2013-10-07
• Study First Posted: 2013-10-09
• Primary Completion: 2017-07-18
• Study Completion: 2017-10-19
• Status Verified: 2018-07
• Results First Submitted: 2018-07-13
• Results First Submitted QC: 2018-07-13
• Last Update Submitted: 2018-07-13
• Results First Posted: 2018-08-08
• Last Update Posted: 2018-08-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 38

Inclusion Criteria

• Cohorts 1 and 2: chronic genotype 1 or 3 HCV infection
• Cohort 3: chronic genotype 1 or 4 HCV infection
• HCV RNA ≥ 10^4 IU/mL at screening
• Screening labs within defined thresholds
• Cirrhosis determination at screening

Key

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Exclusion Criteria

• Females who are pregnant or nursing or males who have a pregnant partner
• Prior null response to pegylated interferon (Peg-IFN)+RBV therapy (Cohorts 1 and 2) or for individuals with cirrhosis, prior treatment failure with IFN-based therapy not resulting from treatment intolerance (Cohort 3)
• Current of prior history of hepatic decompensation
• Infection with hepatitis B virus (HBV) or HIV
• History of clinically significant illness (including psychiatric or cardiac) or any other medical disorder that may interfere with individual's treatment and/or adherence to the protocol

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
LDV/SOF (Cohort 3)	LDV/SOF	Participants with genotype 1 or 4 HCV infection will receive LDV/SOF once daily for 12 weeks.
SOF 400 mg + RBV 200 mg (Cohort 2)	SOF	Participants with genotype 1 or 3 HCV infection will receive SOF 400 mg (4 × 100 mg tablets or 1 × 400 mg tablet) plus RBV once daily for 24 weeks.
SOF 200 mg + RBV 200 mg (Cohort 1)	SOF	Participants with genotype 1 or 3 HCV infection will receive SOF 200 mg (2 × 100 mg tablets) plus RBV once daily for 24 weeks.
SOF 200 mg + RBV 200 mg (Cohort 1)	RBV	Participants with genotype 1 or 3 HCV infection will receive SOF 200 mg (2 × 100 mg tablets) plus RBV once daily for 24 weeks.
SOF 400 mg + RBV 200 mg (Cohort 2)	RBV	Participants with genotype 1 or 3 HCV infection will receive SOF 400 mg (4 × 100 mg tablets or 1 × 400 mg tablet) plus RBV once daily for 24 weeks.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Experiencing Treatment-Emergent Adverse Events	Up to 24 weeks plus 30 days
Pharmacokinetic (PK) Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2	AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4	Cmax is defined as the maximum concentration of drug.
PK Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4	AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12	Cmax is defined as the maximum concentration of drug.
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities	Up to 24 weeks plus 30 days	Treatment-emergent laboratory abnormalities were defined as values that increased by at least 1 toxicity grade from baseline at any time postbaseline up to the date of last dose of study drug plus 30 days.
Percentage of Participants Experiencing Clinically Significant 12-lead Electrocardiogram (ECG) Abnormalities	Up to 24 weeks plus 30 days
PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2	Cmax is defined as the maximum concentration of drug.
PK Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12	AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4	Ctau is defined as the observed drug concentration at the end of the dosing interval.
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)	Posttreatment Week 12	SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment.
Percentage of Participants Experiencing Treatment-Emergent Adverse Events Associated With Vital Sign Abnormalities	Up to 24 weeks plus 30 days
PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2	Ctau is defined as the observed drug concentration at the end of the dosing interval.
PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12	Ctau is defined as the observed drug concentration at the end of the dosing interval.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24)	Posttreatment Week 24	SVR4 was defined as HCV RNA \< LLOQ at 24 weeks after stopping study treatment.
Percentage of Participants With Overall Virologic Failure	Up to Posttreatment Week 24	Virologic failure was defined as: * On-treatment virologic failure: * Breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA \< LLOQ while on treatment), or; * Rebound (confirmed \> 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), or; * Non-response (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment); * Virologic relapse: * Confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA \< LLOQ at last on-treatment visit.
PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2	λz is defined as the terminal elimination rate constant, estimated by linear regression of the terminal elimination phase of the log plasma concentration of drug versus time curve of the drug.
PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2	t1/2 is defined as the estimate of the terminal elimination half-life of the drug.
PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12	t1/2 is defined as the estimate of the terminal elimination half-life of the drug.
PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2	AUClast is defined as the concentration of drug from time zero to the last observable concentration.
PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4	AUClast is defined as the concentration of drug from time zero to the last observable concentration.
PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2	Clast is defined as the last observable concentration of drug.
PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12	Clast is defined as the last observable concentration of drug.
PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12	Tlast is defined as the time (observed time point) of Clast.
PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4	t1/2 is defined as the estimate of the terminal elimination half-life of the drug.
PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4	Clast is defined as the last observable concentration of drug.
PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2	Tmax is defined as the time (observed time point) of Cmax.
PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4	Tmax is defined as the time (observed time point) of Cmax.
PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4	Tlast is defined as the time (observed time point) of Clast.
PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12	λz is defined as the terminal elimination rate constant, estimated by linear regression of the terminal elimination phase of the log plasma concentration of drug versus time curve of the drug.
Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4)	Posttreatment Week 4	SVR4 was defined as HCV RNA \< LLOQ at 4 weeks after stopping study treatment.
PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12	AUClast is defined as the concentration of drug from time zero to the last observable concentration.
PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12	Tmax is defined as the time (observed time point) of Cmax.
PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2	Tlast is defined as the time (observed time point) of Clast.
PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4	λz is defined as the terminal elimination rate constant, estimated by linear regression of the terminal elimination phase of the log plasma concentration of drug versus time curve of the drug.