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

NCT01714154 | Completed Phase 1

• 2 other identifiers: NP283262012-002283-28
• Study Type: interventional
• Target: 18
• Locations: 2 countries
• Sites: 3

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.

Conditions

Healthy Volunteer

Outcome Measures

Primary Outcomes (4)

• Safety: Incidence of adverse events

  approximately 40 days

• Pharmacokinetics: Maximum plasma concentration at steady-state (Css,max)

  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)

  up to 16 days

• Pharmacokinetics: Plasma concentration at steady-state 12 hours post-dose (Css, 12h)

  up to 16 days

Secondary Outcomes (7)

• Pharmacokinetics: Time to maximum plasma concentration (tmax)

  up to 16 days

• Pharmacokinetics: Elimination half-life (t1/2)

  up to 16 days

• 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: Fraction of orally administered drug excreted into urine (fe/f)

  up to 16 days

Study Arms (2)

A: setrobuvir

EXPERIMENTAL

Drug: setrobuvir

B: setrobuvir + DNV/r

EXPERIMENTAL

Drug: danoprevir; Drug: ritonavir; Drug: setrobuvir

Interventions

danoprevir DRUG

100 mg orally every 12 hours

B: setrobuvir + DNV/r

ritonavir DRUG

100 mg orally every 12 hours

B: setrobuvir + DNV/r

setrobuvir DRUG

200 mg orally every 12 hours

A: setrobuvir; B: setrobuvir + DNV/r

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (3)

Unknown Facility

Balatonfüred, 8230, Hungary

Location

Unknown Facility

Budapest, 1076, Hungary

Location

Unknown Facility

Warsaw, 01-201, Poland

Location

MeSH Terms

Interventions

danoprevir; Ritonavir; setrobuvir

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2012
• First Posted: October 25, 2012
• Study Start: November 1, 2012
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: November 2, 2016

Record last verified: 2016-11

Locations

PL (1); HU (2)