Influence of Ribavirin on the Initial Virological Response in Treatment Naïve Patients With Hepatitis C Genotype 1 Infection

Browse trials for

• Hepatitis A 2,710
• Hepatitis C 2,321
• Hepatitis C, Chronic 1,073
• Hepatitis 3,381

Hepatitis A

2,710 studies on the registry are indexed under Hepatitis A; 142 are open to participants now.

This study's enrollment of 68 is below the median of 100 across 1,887 interventional studies indexed under Hepatitis A.

Lead sponsor

Hoffmann-La Roche is the lead sponsor of 2,061 studies on the registry; 85 are open to participants now.

Of its 319 completed or terminated interventional studies of FDA-regulated products, 239 (75%) have results posted.

Study arms

• Experimental
  Pegylated Interferon (PEG-IFN) alfa-2a

  Participants with chronic hepatitis C, genotype 1, received pegylated interferon (PEG-IFN) alfa-2a monotherapy for 6 weeks. Thereafter, all participants received combination therapy with PEG-IFN alfa-2a plus ribavirin for 12 weeks.

  Drug: Pegylated Interferon (PEG-IFN) alfa-2a · Drug: Ribavirin

• Placebo comparator
  Placebo

  Participants with chronic hepatitis C, genotype 1, received ribavirin matching placebo for 6 weeks. Thereafter, all participants received combination therapy with PEG-IFN alfa-2a plus ribavirin for 12 weeks.

  Drug: Pegylated Interferon (PEG-IFN) alfa-2a · Drug: Placebo · Drug: Ribavirin

• Experimental
  Ribavirin

  Participants with chronic hepatitis C, genotype 1, received ribavirin monotherapy for 6 weeks. Thereafter, all participants received combination therapy with PEG-IFN alfa-2a plus ribavirin for 12 weeks.

  Drug: Pegylated Interferon (PEG-IFN) alfa-2a · Drug: Ribavirin

Interventions

• DrugPegylated Interferon (PEG-IFN) alfa-2a

  Pegylated interferon (PEG-IFN) alfa-2a (40 kilodalton \[KD\]) 180 microgram (mcg) subcutaneously (SC) weekly, for 6 weeks during monotherapy and/or 12 weeks during combination therapy.

  Also known as: Pegasys®

• DrugPlacebo

  Ribavirin matching placebo orally (PO) twice daily for 6 weeks.

• DrugRibavirin

  Ribavirin, 1000 mg orally (PO) (400 mg in the morning \[=2 tablets\] and 600 mg in the evening \[=3 tablets\]) in participants with a body weight less than 75 kilogram (kg) or 1200 mg PO (600 mg at each time =3 tablets, in the morning and evening, respectively) in participants with a body weight greater than or equal to 75 kg, PO daily for 6 weeks during monotherapy and/or 12 weeks during combination therapy.

  Also known as: Copegus®

Primary outcomes

1. Log Likelihood Median Values of Hepatitis C-Virus (HCV) Kinetic Models for Quantitative HCV Ribonucleic Acid (RNA) Measurement With Various Assumptions of Ribavirin Mechanism of Action

   To investigate possible action mechanisms, three different models were fitted to viruskinetic data and evaluated using related log-likelihood function values. These models were designed assuming individual effects with respect to infectiousness (model 1), virus production (model 2) or degradation of infected cells rate (model 3). The following viruskinetic parameters were fitted in each model: initial viral load, loss rate of infected cells (delta), effectivity of interferon with respect to a pharmacokinetic-pharmacodynamic model. A lower log likelihood function value indicates a lesser fit for the model.

   Time frame: Up to Day 126

Secondary outcomes

1. Score in Quality of Life Assessed Using Short Form-36 (SF-36) Health Questionnaire

   SF-36 is a psychometric scale to quantify health conditions. This psychometric scale has 8 dimensions of the subjective health status and consists of 36 individual items that have a varying number of related item scores (ranging from "yes/no" up to a 6-point scale). At first the raw scores were determined by summation over all items and weighted accordingly. Afterwards the raw scores were transformed to ranges of 0-100 with 100 being the highest level of health and compared to published reference scales. The following eight dimensions of subjective health conditions were considered: physical functioning index, role physical index, pain, general health perception, vitality, social functioning index, role emotional index and mental health index. The SF36 questionnaire had to be answered by the patients at screening before monotherapy, after monotherapy and at the end of the study (=end of combination therapy).

   Time frame: At screening (Days -56 to -1), at end of monotherapy (Week 6) and at end of combination therapy (Week 18)

2. Percentage of Participants With Treatment Response

   HCV-RNA level was measured at each visit by a central laboratory. Treatment response was estimated applying the following definitions of response/non-response: 1) Adequate first phase decline: HCV RNA decline ≥ 0.5 log10 International Units/milliliter (IU/mL) from time 0 to 48 hours of PEG-IFN treatment (PEG-IFN arm: day 0 - day 2; placebo and ribavirin arm: day 42-day 44), 2) Rapid virologic response: HCV RNA \< 15 IU/mL (=detection limit) on day 70, 3) Complete early virologic response: HCV RNA \< 15 IU/mL on day 126, 4) Partial early virologic response (log decrease): HCV RNA decrease ≥ 2 log10 IU/mL from day 0 to day 126, 5) Partial early virologic response (cut off): HCV RNA \<30000 IU/mL on day 126, 6) Non-response: HCV RNA decrease \<2 log10 IU/mL from day 0 to day 126, 7) Null-response: HCV RNA decrease \<1 log10 IU/mL from day 0 to day 28 and from day 0 to day 70 for PEG-IFN arm and placebo / ribavirin arm, respectively.

   Time frame: Up to Day 126

3. Area Under the Concentration-Time Curve (AUC) of Ribavirin

   Evaluation of ribavirin arm after Day 0. Evaluation of placebo and PEG-IFN arms after Day 42.

   Time frame: From Day 0 at 0 hour (hr), 12 hr, 24 hr, 36 hr, 48 hr, 60 hr and 72 hr, Day 42 at 0 hr, 12 hr, 24 hr and 36 hr and at each visit up to Day 126.

4. Maximum Concentration (Cmax) of Ribavirin

   Cmax was obtained directly from the concentration-time data. Evaluation of ribavirin arm after day 0. Evaluation of placebo and PEG-IFN arms after day 42.

   Time frame: From Day 0 at 0 hour (hr), 12 hr, 24 hr, 36 hr, 48 hr, 60 hr and 72 hr, Day 42 at 0 hr, 12 hr, 24 hr and 36 hr and at each visit up to Day 126.

5. Time to Maximum Concentration (Tmax) of Ribavirin

   Tmax was obtained directly from the concentration-time data. Evaluation of ribavirin arm after day 0. Evaluation of placebo and PEG-IFN arms after day 42.

   Time frame: From Day 0 at 0 hour (hr), 12 hr, 24 hr, 36 hr, 48 hr, 60 hr and 72 hr, Day 42 at 0 hr, 12 hr, 24 hr and 36 hr and at each visit up to Day 126.

6. Area Under the Concentration-Time Curve (AUC) of PEG-IFN

   Evaluation of PEG-IFN arm after Day 0. Evaluation of ribavirin and placebo arms after Day 42.

   Time frame: From Day 0 at 0 hour (hr), 24 hr, 48 hr and 72 hr, Day 42 at 0 hr and 24 hr and at approximately every other visit up to Day 126

7. Maximum Concentration (Cmax) of PEG-IFN

   Cmax was obtained directly from the concentration-time data. Evaluation of PEG-IFN arm after day 0. Evaluation of ribavirin and placebo arms after day 42.

   Time frame: From Day 0 at 0 hour (hr), 24 hr, 48 hr and 72 hr, Day 42 at 0 hr and 24 hr and at approximately every other visit up to Day 126

8. Time to Maximum Concentration (Tmax) of PEG-IFN

   Tmax was obtained directly from the concentration-time data. Evaluation of PEG-IFN arm after day 0. Evaluation of ribavirin and placebo arms after day 42.

   Time frame: From Day 0 at 0 hour (hr), 24 hr, 48 hr and 72 hr, Day 42 at 0 hr and 24 hr and at approximately every other visit up to Day 126

9. Area Under the Concentration-Time Curve (AUC) of Glutamate-Pyruvate Transaminase (GPT)

   Time frame: From Day 0 at 0 hour (hr), 12 hr, 24 hr, 36 hr, 48 hr, 60 hr and 72 hr, Day 42 at 0 hr, 12 hr, 24 hr and 36 hr and at each visit up to Day 126.

10. Maximum Concentration (Cmax) of GPT

    Cmax was obtained directly from the concentration-time data.

    Time frame: From Day 0 at 0 hour (hr), 12 hr, 24 hr, 36 hr, 48 hr, 60 hr and 72 hr, Day 42 at 0 hr, 12 hr, 24 hr and 36 hr and at each visit up to Day 126.

11. Time to Maximum Concentration (Tmax) of GPT

    Tmax was obtained directly from the concentration-time data.

    Time frame: From Day 0 at 0 hour (hr), 12 hr, 24 hr, 36 hr, 48 hr, 60 hr and 72 hr, Day 42 at 0 hr, 12 hr, 24 hr and 36 hr and at each visit up to Day 126.

Baseline characteristics