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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.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01714154
First received: October 23, 2012
Last updated: November 3, 2014
Last verified: November 2014
  Purpose

This multi-center, fixed-sequence, open-label, multiple-dose, 2-period study wil l evaluate the safety, tolerability and pharmacokinetics of setrobuvir alone or in combination with ritonavir-boosted danoprevir in subjects with mild hepatic i mpairment compared to healthy controls. All subjects will receive multiple doses of setrobuvir orally for 10 days in Period 1 and multiple doses of setrobuvir p lus 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
Endpoint Classification: Pharmacokinetics Study
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 ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Maximum plasma concentration at steady-state (Css,max) [ Time Frame: up to 16 days ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Plasma concentration at steady-state 12 hours post-dose (Css, 12h) [ Time Frame: up to 16 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pharmacokinetics: Time to maximum plasma concentration (tmax) [ Time Frame: up to 16 days ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Elimination half-life (t1/2) [ Time Frame: up to 16 days ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Apparent oral clearance at steady-state (CLss/F) [ Time Frame: up to 16 days ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Cumulative amount excreted at steady-state (Aess) [ Time Frame: up to 16 days ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Fraction of orally administered drug excreted into urine (fe/f) [ Time Frame: up to 16 days ] [ Designated as safety issue: No ]
  • Pharmacokinetics of danoprevir in combination with setrobuvir: Area under the concentration-time curve (AUC) [ Time Frame: up to 12 days ] [ Designated as safety issue: No ]
  • Pharmacokinetics of ritonavir in combination with setrobuvir: Area under the concentration-time curve (AUC) [ Time Frame: up to 12 days ] [ Designated as safety issue: No ]

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

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  • 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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01714154

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

No publications provided

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01714154     History of Changes
Other Study ID Numbers: NP28326, 2012-002283-28
Study First Received: October 23, 2012
Last Updated: November 3, 2014
Health Authority: Hungary: National Institute for Quality and Organizational Development in Healthcare and Medicines

Additional relevant MeSH terms:
Ritonavir
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
HIV Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protease Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014