Hepatitis C, Chronic
Conditions
Brief summary
This study will evaluate the pharmacokinetics (area under the curve \[AUC\], maximum concentration \[Cmax\], and other parameters) and tolerability of peginterferon alfa-2a and ribavirin combination therapy following single and multiple doses in participants with CHC infection and moderate to severe renal impairment or end-stage renal disease (ESRD) receiving hemodialysis. The anticipated time on study treatment is up to 48 weeks, and the target sample size is 48 individuals.
Interventions
DRUGPeginterferon alfa-2a
Peginterferon alfa-2a will be administered for 12 to 48 weeks. The dose will range from 135 mcg (Group C) to 180 mcg (Groups A, B, and D) once weekly via SC route.
DRUGRibavirin
Ribavirin will be administered for 12 to 48 weeks. The total daily dosage will range from 200 mg (Group C) to 1200 mg (Group D), depending upon CrCl and participant-specific factors.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Adults 18 to 65 years of age * CHC infection as shown on enzyme-linked immunosorbent assay (ELISA) and radioimmunoblot assay (RIBA) or quantifiable hepatitis C virus (HCV) ribonucleic acid (RNA) greater than (\>) 2000 copies per milliliter (copies/mL) * Use of two forms of contraception during study and 6 months after the study in both men and women * Normal renal function (creatinine clearance \[CrCl\] \>80 milliliters per minute \[mL/min\]), moderate renal impairment (CrCl 30 to 50 mL/min), severe renal impairment (CrCl less than \[\<\] 30 mL/min), or ESRD requiring hemodialysis * Patients with ESRD must have been undergoing hemodialysis for at least 2 months
Exclusion criteria
* Women who are pregnant or breastfeeding * Male partners of women who are pregnant * Conditions associated with decompensated and/or chronic liver disease * Human immunodeficiency virus (HIV) infection * Interferon or ribavirin treatment within the previous 3 months * Poor hematologic function, including unstable hemoglobin * Significant comorbidity or severe illness which would make the participant unsuitable for the study * Acute renal failure
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Clearance (CL/F) of peginterferon alfa-2a | Pre-dose (0 hours) and 0.5, 1, 3, 5, 8, 12, 24, 72, 120, and 168 hours post-dose during Weeks 1 and 12 |
| CL/F of ribavirin | Pre-dose (0 hours) and 0.5, 1, 3, 5, 8, 12, 24, 72, 120, and 168 hours post-dose during Weeks 1 and 12 |
| Percentage of participants with undetectable HCV RNA level | Week 12 |
| Cmax of ribavirin | Pre-dose (0 hours) and 0.5, 1, 3, 5, 8, 12, 24, 72, 120, and 168 hours post-dose during Weeks 1 and 12 |
| AUC of ribavirin | Pre-dose (0 hours) and 0.5, 1, 3, 5, 8, 12, 24, 72, 120, and 168 hours post-dose during Weeks 1 and 12 |
| AUC of peginterferon alfa-2a | Pre-dose (0 hours) and 0.5, 1, 3, 5, 8, 12, 24, 72, 120, and 168 hours post-dose during Weeks 1 and 12 |
| Cmax of peginterferon alfa-2a | Pre-dose (0 hours) and 0.5, 1, 3, 5, 8, 12, 24, 72, 120, and 168 hours post-dose during Weeks 1 and 12 |
Secondary
| Measure | Time frame |
|---|---|
| Tmax of ribavirin | Pre-dose (0 hours) and 0.5, 1, 3, 5, 8, 12, 24, 72, 120, and 168 hours post-dose during Weeks 1 and 12 |
| Plasma concentration of ribavirin | Pre-dose (0 hours) and 0.5, 1, 3, 5, 8, 12, 24, 72, 120, and 168 hours post-dose during Weeks 1 and 12 |
| Percentage of participants with adverse events (AEs) | From Baseline to Week 12 (or up to Week 48 if treatment continued) |
| Percentage of participants with a dose modification or premature withdrawal for safety reasons | From Baseline to Week 12 (or up to Week 48 if treatment continued) |
| Time of maximum concentration (Tmax) of peginterferon alfa-2a | Pre-dose (0 hours) and 0.5, 1, 3, 5, 8, 12, 24, 72, 120, and 168 hours post-dose during Weeks 1 and 12 |
Countries
Brazil, France, New Zealand, Sweden, United States
Outcome results
None listed