NCT01714154
Completed
Phase 1
A Multi Center, Sequential, Open-Label, Multiple-Dose Study of Setrobuvir (STV) Alone and With Co-Administration of Ritonavir-boosted Danoprevir to Evaluate the Safety, Tolerability and Pharmacokinetics of STV, DNV, and Ritonavir (RTV) in Subjects With Mild Hepatic Impairment Compared to Healthy Controls
ConditionsHealthy Volunteer
Overview
- Phase
- Phase 1
- Intervention
- setrobuvir
- Conditions
- Healthy Volunteer
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 18
- Primary Endpoint
- Pharmacokinetics: Plasma concentration at steady-state 12 hours post-dose (Css, 12h)
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
This multi-center, fixed-sequence, open-label, multiple-dose, 2-period study will evaluate the safety, tolerability and pharmacokinetics of setrobuvir alone or in combination with ritonavir-boosted danoprevir in subjects with mild hepatic impairment compared to healthy controls. All subjects will receive multiple doses of setrobuvir orally for 10 days in Period 1 and multiple doses of setrobuvir plus ritonavir-boosted danoprevir orally for 10 days in Period 2, with a washout phase of at least 9 days between treatments.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male and female adults, 18-65 years of age, inclusive
- •Weight \>/= 45.0 kg
- •Body mass index (BMI) 18.0 - 35.0 kg/m2, inclusive
- •Females of childbearing potential and males and their female partners of childbearing potential must agree to use two forms of non-hormonal contraception as defined by protocol
- •Subjects with a history of substance abuse may be enrolled provided they have not abused drugs or alcohol for at least 6 months
- •Healthy subjects only:
- •Medical history without major recent or ongoing pathology Laboratory values at screening and Day -1 within the normal range or showing no clinically relevant deviations
- •Subjects with hepatic impairment only:
- •Stable mild liver disease (Child-Pugh A) of cryptogenic, post-hepatic, hepatitis B/C, or alcoholic origin Stable hepatic impairment defined as no clinically significant change in disease status within the last 30 days Must be on stable dose of medication and/or treatment regimen at least 2 weeks before dosing of study medication
Exclusion Criteria
- •Pregnant or lactating women or males with female partners who are pregnant or lactating
- •Active infection or febrile illness \</= 10 days prior to the first dose of study medication
- •Uncontrolled/untreated hypertension
- •Inadequate renal function
- •Positive urine drug screen or positive breath alcohol test at screening and on Day -1 of each period
- •An average alcohol intake of more than 2 units per day or 14 units per week until 48 hours prior to enrollment
- •History of any significant drug-related allergy or hepatotoxicity
- •Participation in other clinical studies with an investigational drug or new chemical entity within 3 months (6 months for biologic therapies) prior to the first dose of study medication
- •Positive for HIV infection
- •Any clinically significant cardiovascular or cerebrovascular disease
Arms & Interventions
A: setrobuvir
Intervention: setrobuvir
B: setrobuvir + DNV/r
Intervention: danoprevir
B: setrobuvir + DNV/r
Intervention: ritonavir
B: setrobuvir + DNV/r
Intervention: setrobuvir
Outcomes
Primary Outcomes
Pharmacokinetics: Plasma concentration at steady-state 12 hours post-dose (Css, 12h)
Time Frame: up to 16 days
Pharmacokinetics: Maximum plasma concentration at steady-state (Css,max)
Time Frame: up to 16 days
Safety: Incidence of adverse events
Time Frame: approximately 40 days
Pharmacokinetics: Total area under the concentration-time curve form time 0 to 12 hours post-dose at steady-state (AUCss,0-12h)
Time Frame: up to 16 days
Secondary Outcomes
- Pharmacokinetics: Apparent oral clearance at steady-state (CLss/F)(up to 16 days)
- Pharmacokinetics: Cumulative amount excreted at steady-state (Aess)(up to 16 days)
- Pharmacokinetics of danoprevir in combination with setrobuvir: Area under the concentration-time curve (AUC)(up to 12 days)
- Pharmacokinetics: Elimination half-life (t1/2)(up to 16 days)
- Pharmacokinetics: Time to maximum plasma concentration (tmax)(up to 16 days)
- Pharmacokinetics: Fraction of orally administered drug excreted into urine (fe/f)(up to 16 days)
- Pharmacokinetics of ritonavir in combination with setrobuvir: Area under the concentration-time curve (AUC)(up to 12 days)
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