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A Safety And Pharmacokinetic Study of Setrobuvir Alone and In Combination With Ritonavir-Boosted Danoprevir in Subjects With Mild Hepatic Impairment Compared to Healthy Controls

This study has been completed.
Information provided by (Responsible Party):
Hoffmann-La Roche Identifier:
First received: October 23, 2012
Last updated: November 1, 2016
Last verified: November 2016
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.

Condition Intervention Phase
Healthy Volunteer
Drug: danoprevir
Drug: ritonavir
Drug: setrobuvir
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: 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

Resource links provided by NLM:

Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Safety: Incidence of adverse events [ Time Frame: approximately 40 days ]
  • Pharmacokinetics: Maximum plasma concentration at steady-state (Css,max) [ Time Frame: up to 16 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 ]
  • Pharmacokinetics: Plasma concentration at steady-state 12 hours post-dose (Css, 12h) [ Time Frame: up to 16 days ]

Secondary Outcome Measures:
  • Pharmacokinetics: Time to maximum plasma concentration (tmax) [ Time Frame: up to 16 days ]
  • Pharmacokinetics: Elimination half-life (t1/2) [ Time Frame: up to 16 days ]
  • Pharmacokinetics: Apparent oral clearance at steady-state (CLss/F) [ Time Frame: up to 16 days ]
  • Pharmacokinetics: Cumulative amount excreted at steady-state (Aess) [ Time Frame: up to 16 days ]
  • Pharmacokinetics: Fraction of orally administered drug excreted into urine (fe/f) [ Time Frame: up to 16 days ]
  • Pharmacokinetics of danoprevir in combination with setrobuvir: Area under the concentration-time curve (AUC) [ Time Frame: up to 12 days ]
  • Pharmacokinetics of ritonavir in combination with setrobuvir: Area under the concentration-time curve (AUC) [ Time Frame: up to 12 days ]

Enrollment: 18
Study Start Date: November 2012
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A: setrobuvir Drug: setrobuvir
200 mg orally every 12 hours
Experimental: B: setrobuvir + DNV/r Drug: danoprevir
100 mg orally every 12 hours
Drug: ritonavir
100 mg orally every 12 hours
Drug: setrobuvir
200 mg orally every 12 hours


Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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
  • Healthy subjects only:

Any clinically significant concomitant disease or condition that could interfere with, or for which the treatment might interfere with, the conduct of the study, absorption of medication, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study Positive screening test for HBsAg or HCV antibody

  • Subjects with hepatic impairment only:

Severe ascites at screening or Day -1 History of or current severe hepatic encephalopathy (Grade 3 or higher) Biliary liver cirrhosis or other causes of hepatic impairment not related to parenchymal disorder and/or disease of the liver Positive screening test for HCV antigen

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Please refer to this study by its identifier: NCT01714154

Balatonfuered, Hungary, 8230
Budapest, Hungary, 1076
Warszawa, Poland, 01-201
Sponsors and Collaborators
Hoffmann-La Roche
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche Identifier: NCT01714154     History of Changes
Other Study ID Numbers: NP28326
2012-002283-28 ( EudraCT Number )
Study First Received: October 23, 2012
Last Updated: November 1, 2016

Additional relevant MeSH terms:
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Anti-Bacterial Agents processed this record on May 24, 2017