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

Phase 2CompletedNCT01958281

Gilead Sciences38 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

HCV Infection

Interventions

SOFDRUG

Tablet(s) administered orally once daily

RBVDRUG

200 mg tablet administered orally once daily

LDV/SOFDRUG

90/400 mg fixed-dose combination (FDC) tablet administered orally once daily

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key 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 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.

Locations (10)

Unnamed facility

San Francisco, California, United States

Unnamed facility

Miami, Florida, United States

Unnamed facility

Chicago, Illinois, United States

Unnamed facility

Detroit, Michigan, United States

Outcomes

Primary Outcomes

Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)

SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment.

Time frame: Posttreatment Week 12

Percentage of Participants Experiencing Treatment-Emergent Adverse Events

Time frame: Up to 24 weeks plus 30 days

Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities

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.

Time frame: Up to 24 weeks plus 30 days

Percentage of Participants Experiencing Clinically Significant 12-lead Electrocardiogram (ECG) Abnormalities

Time frame: Up to 24 weeks plus 30 days

Percentage of Participants Experiencing Treatment-Emergent Adverse Events Associated With Vital Sign Abnormalities

Time frame: 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)

AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2

PK Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)

AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

Data from ClinicalTrials.gov

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Secondary Outcomes

Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4)

SVR4 was defined as HCV RNA \< LLOQ at 4 weeks after stopping study treatment.

Time frame: Posttreatment Week 4

Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24)

SVR4 was defined as HCV RNA \< LLOQ at 24 weeks after stopping study treatment.

Time frame: Posttreatment Week 24

Percentage of Participants With Overall Virologic Failure

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.

Time frame: Up to Posttreatment Week 24

PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)

AUClast is defined as the concentration of drug from time zero to the last observable concentration.

Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2

PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)

AUClast is defined as the concentration of drug from time zero to the last observable concentration.

Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12

PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)

AUClast is defined as the concentration of drug from time zero to the last observable concentration.

Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4

PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)

Clast is defined as the last observable concentration of drug.

Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2

PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)

Clast is defined as the last observable concentration of drug.

Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12

PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)

Clast is defined as the last observable concentration of drug.

Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4

PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)

Tmax is defined as the time (observed time point) of Cmax.

Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2

PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)

Tmax is defined as the time (observed time point) of Cmax.

Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12

PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)

Tmax is defined as the time (observed time point) of Cmax.

Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4

PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)

Tlast is defined as the time (observed time point) of Clast.

Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2

PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)

Tlast is defined as the time (observed time point) of Clast.

Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12

PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)

Tlast is defined as the time (observed time point) of Clast.

Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4

PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 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.

Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2

PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 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.

Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12

PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)

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.

Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4

PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)

t1/2 is defined as the estimate of the terminal elimination half-life of the drug.

Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2

PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)

t1/2 is defined as the estimate of the terminal elimination half-life of the drug.

Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12

PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)

t1/2 is defined as the estimate of the terminal elimination half-life of the drug.

Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4