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

Healthy Volunteer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01714154
• Other study ID #: NP28326
• Secondary ID: 2012-002283-28
• Status: Completed
• Phase: Phase 1
• First received: October 23, 2012
• Last updated: November 1, 2016
• Start date: November 2012
• Est. completion date: May 2013

Study information

• Verified date: November 2016
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: Hungary: National Institute for Quality and Organizational Development in Healthcare and Medicines
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: May 2013
• Est. primary completion date: May 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Healthy Volunteer

Intervention

Drug:
• danoprevir
100 mg orally every 12 hours
• ritonavir
100 mg orally every 12 hours
• setrobuvir
200 mg orally every 12 hours

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

Hungary,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety: Incidence of adverse events		approximately 40 days	No
Primary	Pharmacokinetics: Maximum plasma concentration at steady-state (Css,max)		up to 16 days	No
Primary	Pharmacokinetics: Total area under the concentration-time curve form time 0 to 12 hours post-dose at steady-state (AUCss,0-12h)		up to 16 days	No
Primary	Pharmacokinetics: Plasma concentration at steady-state 12 hours post-dose (Css, 12h)		up to 16 days	No
Secondary	Pharmacokinetics: Time to maximum plasma concentration (tmax)		up to 16 days	No
Secondary	Pharmacokinetics: Elimination half-life (t1/2)		up to 16 days	No
Secondary	Pharmacokinetics: Apparent oral clearance at steady-state (CLss/F)		up to 16 days	No
Secondary	Pharmacokinetics: Cumulative amount excreted at steady-state (Aess)		up to 16 days	No
Secondary	Pharmacokinetics: Fraction of orally administered drug excreted into urine (fe/f)		up to 16 days	No
Secondary	Pharmacokinetics of danoprevir in combination with setrobuvir: Area under the concentration-time curve (AUC)		up to 12 days	No
Secondary	Pharmacokinetics of ritonavir in combination with setrobuvir: Area under the concentration-time curve (AUC)		up to 12 days	No