A Triple Combination Therapy Study of Boceprevir, Pegasys and Copegus in Previously Untreated Patients With Genotype 1 Chronic Hepatitis C

SVR at 12 weeks after EOT was defined as an undetectable HCV RNA viral load obtained 12 weeks following completion of treatment. HCV RNA viral load was measured using the Roche COBAS TaqMan 2.0 HCV Test, with a lower limit of detection (LOD) of 10 to 15 international units per milliliter (IU/mL). The percentage of participants with SVR was calculated as [number of participants with undetectable HCV RNA at 12 weeks after EOT divided by the number of participants analyzed] multiplied by 100.

SVR at 24 weeks after EOT was defined as an undetectable HCV RNA viral load obtained 24 weeks following completion of treatment. HCV RNA viral load was measured using the Roche COBAS TaqMan 2.0 HCV Test, with a lower LOD of 10 to 15 IU/mL. The percentage of participants with SVR was calculated as [number of participants with undetectable HCV RNA at 24 weeks after EOT divided by the number of participants analyzed] multiplied by 100.

HCV RNA levels were obtained routinely during and after treatment. Mean HCV RNA levels were calculated by averaging the HCV RNA levels among all participants analyzed at each collection timepoint and expressed in log10 IU/mL.

HCV RNA levels were obtained routinely during and after treatment. The percentage of participants with undetectable HCV RNA viral load (ie, virological response) was calculated as [number of participants with undetectable HCV RNA at each timepoint divided by the number of participants analyzed] multiplied by 100.

HCV RNA levels were obtained routinely during and after treatment. Reductions in HCV RNA viral load by 1-log, 2-log, or 3-log increments were determined relative to Baseline HCV RNA. Each increment represents a reduction greater than or equal to (≥) the specified log value, including results for which HCV RNA was below the limit of quantification (25 IU/mL). The percentage of participants with each log reduction in HCV RNA was calculated as [number of participants with log reduction divided by the number of participants analyzed] multiplied by 100.

Virological relapse was defined as a detectable post-treatment HCV RNA viral load following a previously undetectable EOT level (ie, virological response). The percentage of participants with virological relapse was calculated as [number of participants meeting the above criteria divided by the number of participants analyzed] multiplied by 100.

Virological breakthrough was defined as an HCV RNA viral load greater than (>) 1000 IU/mL following a previously undetectable level at any time during treatment (ie, virological response). Participants who ultimately achieved an EOT response were not considered for virological breakthrough. The percentage of participants with virological breakthrough was calculated as [number of participants meeting the above criteria divided by the number of participants analyzed] multiplied by 100.

Virological rebound was defined as an HCV RNA viral load >1000 IU/mL and a ≥1-log increase from nadir following a decline in HCV RNA from Baseline at any time during treatment (ie, on-treatment decline). Participants who ultimately achieved an EOT response were not considered for virological rebound. The percentage of participants with virological rebound was calculated as [number of participants meeting the above criteria divided by the number of participants analyzed] multiplied by 100.

Treatment was to be discontinued for participants who met prespecified criteria, termed the futility rule, after 12 or 24 weeks of treatment. Participants were discontinued from treatment for one of the following reasons: HCV RNA viral load ≥100 IU/mL (Week 12) or a detectable HCV RNA viral load (Week 24). HCV RNA viral load was measured using the Roche COBAS TaqMan 2.0 HCV Test, with a lower LOD of 10 to 15 IU/mL. The percentage of participants with treatment discontinued for each reason was calculated as [number of participants meeting one of the above criteria divided by the number of participants analyzed] multiplied by 100.

The duration of treatment with each study drug was determined as the time from treatment start until the last dose of PEG-IFN, RBV, or boceprevir. Median duration of treatment was determined using the actual duration of treatment among individual participants and expressed in weeks.

Dose modifications for each study drug included any dose reduction, treatment interruption, or premature withdrawal. Adverse event (AE)-related reasons were documented, as well as reasons related to insufficient efficacy ('Poor efficacy') or other safety-related reasons ('Safety/other'). The percentage of participants with a dose modification documented for each reason was calculated as [number of participants with dose modification divided by the number of participants analyzed] multiplied by 100.

The frequency of missed treatments was examined using the number of administrations received as a percentage of target administrations for each study drug. The maximum number of possible administrations was considered in terms of once-weekly injections with PEG-IFN and in terms of treatment days with RBV and boceprevir. The percentage of target administrations each participant received was separated into ranges of <60%, 60 to <80%, 80 to <95%, and ≥95% for each study drug. The percentage of participants who received each range of target administrations was calculated as [number of participants in each range divided by the number of participants analyzed] multiplied by 100.

Dose modifications for each study drug included any dose reduction, treatment interruption, or premature withdrawal. The percentage of participants with a safety-related dose modification (eg, modification due to adverse event or laboratory abnormality) of any study drug was calculated as [number of participants with dose modification divided by the number of participants analyzed] multiplied by 100.

Dose modifications for each study drug included any dose reduction, treatment interruption, or premature withdrawal. Median time to safety-related dose modification (eg, modification due to adverse event or laboratory abnormality) of any study drug was estimated using Kaplan-Meier and expressed in weeks.

Use of concomitant hematopoietic stimulants (such as epoetin) during the 48-week treatment period and/or within 24 weeks of follow-up was documented. The percentage of participants using concomitant hematopoietic stimulants was calculated as [number of participants reporting concomitant use divided by the number of participants analyzed] multiplied by 100.

The prevalence of concomitant disease at any time from Screening through the end of follow-up was documented. The percentage of participants with a concomitant disease was calculated as [number of participants reporting or diagnosed with concomitant disease divided by the number of participants analyzed] multiplied by 100. Diseases documented for ≥5% of participants included hypertension, diabetes mellitus, hypothyroidism, and vitamin D deficiency as reported here.

Use of concomitant prescription or nonprescription medications during the 48-week treatment period and/or within 24 weeks of follow-up was documented. The percentage of participants using concomitant medications was calculated as [number of participants reporting concomitant use divided by the number of participants analyzed] multiplied by 100. Medication classes reported by >10% of participants included analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), antihistamines, corticosteroids, proton pump inhibitors, vitamins and minerals, and beta-adrenoceptor blocking agents as reported here.