Trial Outcomes & Findings for A Rollover Study of BI 201335 in Combination With Pegylated Interferon-alpha and Ribavirin in Treatment-experienced Genotype 1 Hepatitis C Infected Patients (NCT NCT01330316)

Last Updated: 2016-06-30

Results Overview

The primary endpoint was SVR12, defined as a plasma Hepatitis C virus (HCV) Ribonucleic acid (RNA) level \<25 IU/mL (undetected) 12 weeks after the originally planned treatment duration.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

119 participants

Primary outcome timeframe

12 weeks post treatment, up to 60 weeks

Results posted on

2016-06-30

Participant Flow

This was a multi-national, open-label trial enrolling two cohorts of patients with chronic Hepatitis C Virus (HCV) infection of genotype 1 (GT-1) who were randomized to the placebo arm (+ Pegylated interferon α-2a/ Ribavirin) and experienced virologic failure in one of the 1220.7 (NCT01358864), 1220.30 (NCT01343888), 1220.47 (NCT01297270) trials.

Eligible patients who entered the rollover trial within 14 weeks of their last study visit in one of the predecessor trials were not required to do a screening visit (treatment start: Day 1). Eligible patients who were outside of this 14-week window were required to do a screening visit (Visit 1) and started treatment at Visit 2 (Day 1).

Participant milestones

Participant milestones
Measure	Relapse Faldaprevir (FDV) 240 mg once daily combined with Pegylated interferon α-2a (PegIFN)/ Ribavirin (RBV) for 24 weeks was administered for relapser patients. At week 24, patients who did not achieve early treatment success (ETS) continue with an additional 24 weeks of PegIFN/RBV. ETS is defined as Hepatitis C virus(HCV) Ribonucleic Acid (RNA) \<25 Internalional Units (IU)/millilitre (ml) (detected or undetected) at week 4 and \<25 IU/ml (undetected) at week 8. Patients who had undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) levels at the end of treatment in one of the previous studies (see recruitment details) but had detectable levels in subsequent assessments are called relapser.	Non-relapse Faldaprevir (FDV) 240mg once daily combined with Pegylated interferon α-2a (PegIFN)/ Ribavirin (RBV) for 24 weeks, followed by an additional 24 weeks of PegIFN/RBV for non-relapser patients. Non-relapser are non-responder (null and partial) and breakthrough patients. Null responders are patients who did not achieve \> 2 log10 decrease in HCV RNA from baseline during the treatment period. Partial non-responders are patients who achieved \> 2 log10 decrease in HCV RNA from baseline but who never achieved an undetectable level of HCV RNA. Breakthrough are patients who achieved an undetectable HCV RNA during the treatment period but had detectable HCV RNA at the end of treatment.
Overall Study STARTED	43	75
Overall Study COMPLETED	41	60
Overall Study NOT COMPLETED	2	15

Reasons for withdrawal

Reasons for withdrawal
Measure	Relapse Faldaprevir (FDV) 240 mg once daily combined with Pegylated interferon α-2a (PegIFN)/ Ribavirin (RBV) for 24 weeks was administered for relapser patients. At week 24, patients who did not achieve early treatment success (ETS) continue with an additional 24 weeks of PegIFN/RBV. ETS is defined as Hepatitis C virus(HCV) Ribonucleic Acid (RNA) \<25 Internalional Units (IU)/millilitre (ml) (detected or undetected) at week 4 and \<25 IU/ml (undetected) at week 8. Patients who had undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) levels at the end of treatment in one of the previous studies (see recruitment details) but had detectable levels in subsequent assessments are called relapser.	Non-relapse Faldaprevir (FDV) 240mg once daily combined with Pegylated interferon α-2a (PegIFN)/ Ribavirin (RBV) for 24 weeks, followed by an additional 24 weeks of PegIFN/RBV for non-relapser patients. Non-relapser are non-responder (null and partial) and breakthrough patients. Null responders are patients who did not achieve \> 2 log10 decrease in HCV RNA from baseline during the treatment period. Partial non-responders are patients who achieved \> 2 log10 decrease in HCV RNA from baseline but who never achieved an undetectable level of HCV RNA. Breakthrough are patients who achieved an undetectable HCV RNA during the treatment period but had detectable HCV RNA at the end of treatment.
Overall Study Adverse Event	2	2
Overall Study Lack of Efficacy	0	10
Overall Study Lost to Follow-up	0	1
Overall Study Withdrawal by Subject	0	1
Overall Study other than above	0	1

Baseline Characteristics

A Rollover Study of BI 201335 in Combination With Pegylated Interferon-alpha and Ribavirin in Treatment-experienced Genotype 1 Hepatitis C Infected Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Relapse n=43 Participants FDV 240 mg once daily combined with PegIFN/RBV for 24 weeks. At week 24, if the patients did not achieve ETS the patients received an additional 24 weeks of PegIFN/RBV.	Non-relapse n=75 Participants FDV 240mg once daily combined with PegIFN/RBV for 24 weeks, followed by an additional 24 weeks of PegIFN/RBV.	Total n=118 Participants Total of all reporting groups
Age, Continuous	55.4 years STANDARD_DEVIATION 7.38 • n=5 Participants	53.4 years STANDARD_DEVIATION 9.46 • n=7 Participants	54.1 years STANDARD_DEVIATION 8.78 • n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	25 Participants n=7 Participants	41 Participants n=5 Participants
Sex: Female, Male Male	27 Participants n=5 Participants	50 Participants n=7 Participants	77 Participants n=5 Participants

PRIMARY outcome

Timeframe: 12 weeks post treatment, up to 60 weeks

Population: FAS

The primary endpoint was SVR12, defined as a plasma Hepatitis C virus (HCV) Ribonucleic acid (RNA) level \<25 IU/mL (undetected) 12 weeks after the originally planned treatment duration.

Outcome measures

Outcome measures
Measure	Relapse n=43 Participants FDV 240 mg once daily combined with PegIFN/RBV for 24 weeks. At week 24, if the patients did not achieve ETS the patients received an additional 24 weeks of PegIFN/RBV.	Non-relapse n=75 Participants FDV 240mg once daily combined with PegIFN/RBV for 24 weeks, followed by an additional 24 weeks of PegIFN/RBV.
Sustained Virological Response (SVR): Plasma HCV RNA Level < 25 IU/mL	95.3 percentage of participants Interval 89.1 to 100.0	54.7 percentage of participants Interval 43.4 to 65.9

SECONDARY outcome

Timeframe: 24 weeks post treatment, up to 72 weeks

Population: FAS

Sustained virologic response 24 weeks, defined as a plasma HCV RNA level \< 25 IU/mL (undetected) 24 weeks after the originally planned treatment duration.

Outcome measures

Outcome measures
Measure	Relapse n=43 Participants FDV 240 mg once daily combined with PegIFN/RBV for 24 weeks. At week 24, if the patients did not achieve ETS the patients received an additional 24 weeks of PegIFN/RBV.	Non-relapse n=75 Participants FDV 240mg once daily combined with PegIFN/RBV for 24 weeks, followed by an additional 24 weeks of PegIFN/RBV.
Sustained Virological Response After 24 Weeks of Treatment Discontinuation (SVR24)	95.3 percentage of participants Interval 89.1 to 100.0	54.7 percentage of participants Interval 43.4 to 65.9

SECONDARY outcome

Timeframe: week 4 and week 8

Population: FAS

ETS, defined as a plasma HCV RNA level \<25 IU/mL (detected or undetected) at week 4 and HCV RNA \<25 IU/mL (undetected) at week 8.

Outcome measures

Outcome measures
Measure	Relapse n=43 Participants FDV 240 mg once daily combined with PegIFN/RBV for 24 weeks. At week 24, if the patients did not achieve ETS the patients received an additional 24 weeks of PegIFN/RBV.	Non-relapse n=75 Participants FDV 240mg once daily combined with PegIFN/RBV for 24 weeks, followed by an additional 24 weeks of PegIFN/RBV.
Early Treatment Success (ETS)	97.7 percentage of participants	65.3 percentage of participants

SECONDARY outcome

Timeframe: Week 24 for relapsers with ETS; Week 48 for relapsers without ETS, and non-relapsers

Population: FAS

This will be presented as the number of patients in/not in normal range from baseline EoT. SVR12 is sustained virological response 12 weeks post-treatment.

Outcome measures

Outcome measures
Measure	Relapse n=43 Participants FDV 240 mg once daily combined with PegIFN/RBV for 24 weeks. At week 24, if the patients did not achieve ETS the patients received an additional 24 weeks of PegIFN/RBV.	Non-relapse n=75 Participants FDV 240mg once daily combined with PegIFN/RBV for 24 weeks, followed by an additional 24 weeks of PegIFN/RBV.
Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) SVR12 = No	2 participants	34 participants
Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) SVR12 = No, Baseline Normal to EOT Normal	0 participants	11 participants
Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) SVR12 = No, Baseline Elevated to EOT Normal	2 participants	9 participants
Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) SVR12 = Yes	41 participants	41 participants
Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) SVR12 = Yes, Baseline Normal to EOT Normal	12 participants	10 participants
Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) SVR12 = Yes, Baseline Elevated to EOT Normal	16 participants	15 participants

SECONDARY outcome

Timeframe: 48 weeks for relapsers with ETS; 60 weeks for non-relapsers and relapsers without ETS

Population: FAS

This will be presented as the number of patients in/not in normal range from baseline to 12 weeks post treatment. SVR12 is sustained virological response 12 weeks post-treatment.

Outcome measures

Outcome measures
Measure	Relapse n=43 Participants FDV 240 mg once daily combined with PegIFN/RBV for 24 weeks. At week 24, if the patients did not achieve ETS the patients received an additional 24 weeks of PegIFN/RBV.	Non-relapse n=75 Participants FDV 240mg once daily combined with PegIFN/RBV for 24 weeks, followed by an additional 24 weeks of PegIFN/RBV.
Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at 12 Weeks Post-treatment. SVR12 = Yes	41 participants	41 participants
Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at 12 Weeks Post-treatment. SVR12 = Yes, Baseline Normal to SVR12 Normal	12 participants	11 participants
Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at 12 Weeks Post-treatment. SVR12 = Yes, Baseline Elevated to SVR12 Normal	27 participants	27 participants
Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at 12 Weeks Post-treatment. SVR12 = No	2 participants	34 participants
Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at 12 Weeks Post-treatment. SVR12 = No, Baseline Normal to SVR12 Normal	0 participants	8 participants
Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at 12 Weeks Post-treatment. SVR12 = No, Baseline Elevated to SVR12 Normal	1 participants	2 participants

SECONDARY outcome

Timeframe: Week 24 for relapsers with ETS; Week 48 for relapsers without ETS, and non-relapsers.

Population: FAS

This will be presented as the number of patients in/not in normal range from baseline to EoT. SVR12 is sustained virological response 12 weeks post-treatment.

Outcome measures

Outcome measures
Measure	Relapse n=43 Participants FDV 240 mg once daily combined with PegIFN/RBV for 24 weeks. At week 24, if the patients did not achieve ETS the patients received an additional 24 weeks of PegIFN/RBV.	Non-relapse n=75 Participants FDV 240mg once daily combined with PegIFN/RBV for 24 weeks, followed by an additional 24 weeks of PegIFN/RBV.
Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) SVR12 = Yes	41 participants	41 participants
Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) SVR12 = Yes, Baseline Normal to EOT Normal	15 participants	13 participants
Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) SVR12 = Yes, Baseline Elevated to EOT Normal	14 participants	11 participants
Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) SVR12 = No	2 participants	34 participants
Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) SVR12 = No, Baseline Normal to EOT Normal	1 participants	12 participants
Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) SVR12 = No, Baseline Elevated to EOT Normal	1 participants	7 participants

SECONDARY outcome

Timeframe: Week 48 for relapsers with ETS; Week 48 for relapsers without ETS, and non-relapsers

Population: FAS

This will be presented as the number of patients in/not in normal range from baseline to 12 weeks post treatment. SVR12 is sustained virological response 12 weeks post-treatment.

Outcome measures

Outcome measures
Measure	Relapse n=43 Participants FDV 240 mg once daily combined with PegIFN/RBV for 24 weeks. At week 24, if the patients did not achieve ETS the patients received an additional 24 weeks of PegIFN/RBV.	Non-relapse n=75 Participants FDV 240mg once daily combined with PegIFN/RBV for 24 weeks, followed by an additional 24 weeks of PegIFN/RBV.
Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at 12 Weeks Post-treatment. SVR12 = No	2 participants	34 participants
Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at 12 Weeks Post-treatment. SVR12 = Yes	41 participants	41 participants
Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at 12 Weeks Post-treatment. SVR12 = Yes, Baseline Normal to SVR12 Normal	15 participants	14 participants
Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at 12 Weeks Post-treatment. SVR12 = Yes, Baseline Elevated to SVR12 Normal	22 participants	24 participants
Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at 12 Weeks Post-treatment. SVR12 = No, Baseline Normal to SVR12 Normal	1 participants	10 participants
Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at 12 Weeks Post-treatment. SVR12 = No, Baseline Elevated to SVR12 Normal	0 participants	3 participants

SECONDARY outcome

Timeframe: from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days

Population: FAS

This outcome measure will be presented as the percentage of subjects with any adverse event (AE). Percentages are calculated using total number of subjects per treatment cohort as the denominator. The intensity of all AEs was evaluated according to the DAIDS (Division of Acquired Immunodeficiency Syndrome) grading scale with AEs of mild, moderate, or severe intensity receiving Grades 1, 2, or 3, respectively. Adverse events judged potentially life threatening received a Grade 4 assessment.

Outcome measures

Outcome measures
Measure	Relapse n=43 Participants FDV 240 mg once daily combined with PegIFN/RBV for 24 weeks. At week 24, if the patients did not achieve ETS the patients received an additional 24 weeks of PegIFN/RBV.	Non-relapse n=75 Participants FDV 240mg once daily combined with PegIFN/RBV for 24 weeks, followed by an additional 24 weeks of PegIFN/RBV.
Occurrence of Adverse Events (Overall and by DAIDS Grade) Overall	90.7 percentage of participants	93.3 percentage of participants
Occurrence of Adverse Events (Overall and by DAIDS Grade) Subjects with DAIDS Grade 2, 3 or 4 AEs	65.1 percentage of participants	56.0 percentage of participants
Occurrence of Adverse Events (Overall and by DAIDS Grade) Subjects with DAIDS Grade 3 or 4 AEs	27.9 percentage of participants	17.3 percentage of participants
Occurrence of Adverse Events (Overall and by DAIDS Grade) Subjects with DAIDS Grade 4 AEs	7.0 percentage of participants	1.3 percentage of participants

SECONDARY outcome

Timeframe: from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days

Population: FAS

This outcome measure will be presented as the percentage of subjects with adverse events leading to discontinuation of Faldaprevir and all study medication. Percentages are calculated using total number of subjects per treatment cohort as the denominator.

Outcome measures

Outcome measures
Measure	Relapse n=43 Participants FDV 240 mg once daily combined with PegIFN/RBV for 24 weeks. At week 24, if the patients did not achieve ETS the patients received an additional 24 weeks of PegIFN/RBV.	Non-relapse n=75 Participants FDV 240mg once daily combined with PegIFN/RBV for 24 weeks, followed by an additional 24 weeks of PegIFN/RBV.
Occurrence of Adverse Events Leading to Treatment Discontinuation discontinuation of all study medication	2.3 percentage of participants	0.0 percentage of participants
Occurrence of Adverse Events Leading to Treatment Discontinuation discontinuation of faldaprevir	4.7 percentage of participants	2.7 percentage of participants

SECONDARY outcome

Timeframe: from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days

Population: FAS

This outcome measure will be presented as the percentage of subjects with any serious adverse event (SAE). Percentages are calculated using total number of subjects per treatment cohort as the denominator.

Outcome measures

Outcome measures
Measure	Relapse n=43 Participants FDV 240 mg once daily combined with PegIFN/RBV for 24 weeks. At week 24, if the patients did not achieve ETS the patients received an additional 24 weeks of PegIFN/RBV.	Non-relapse n=75 Participants FDV 240mg once daily combined with PegIFN/RBV for 24 weeks, followed by an additional 24 weeks of PegIFN/RBV.
Occurrence of Serious Adverse Events (SAEs)	2.3 percentage of participants	8.0 percentage of participants

SECONDARY outcome

Timeframe: from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days

Population: FAS

This outcome measure will be presented as the percentage of subjects with any drug-related AEs as assessed by the investigator. Percentages are calculated using total number of subjects per treatment cohort as the denominator.

Outcome measures

Outcome measures
Measure	Relapse n=43 Participants FDV 240 mg once daily combined with PegIFN/RBV for 24 weeks. At week 24, if the patients did not achieve ETS the patients received an additional 24 weeks of PegIFN/RBV.	Non-relapse n=75 Participants FDV 240mg once daily combined with PegIFN/RBV for 24 weeks, followed by an additional 24 weeks of PegIFN/RBV.
Occurrence of Drug-related AEs as Assessed by the Investigator	88.4 percentage of participants	88.0 percentage of participants

SECONDARY outcome

Timeframe: baseline (day 1, after first dose of randomised treatment) up to 7 days after the last intake of study

Population: FAS

This Outcome measure will be presented as summary of the percentage of patients with worst on-treatment Division of Acquired Immunodeficiency Syndrome (DAIDS) grade laboratory abnormalities for selected analytes (Haemoglobin, Alanine aminotransaminase (ALT), Aspartate aminotransaminase (AST) and Bilirubin total) with particular relevance to patients with HCV.

Outcome measures

Outcome measures
Measure	Relapse n=43 Participants FDV 240 mg once daily combined with PegIFN/RBV for 24 weeks. At week 24, if the patients did not achieve ETS the patients received an additional 24 weeks of PegIFN/RBV.	Non-relapse n=75 Participants FDV 240mg once daily combined with PegIFN/RBV for 24 weeks, followed by an additional 24 weeks of PegIFN/RBV.
Laboratory Test Abnormalities by DAIDS Grades Bilirubin, total, Grade 2	32.6 percentage of participants	37.3 percentage of participants
Laboratory Test Abnormalities by DAIDS Grades Bilirubin, total, Grade 3	39.5 percentage of participants	29.3 percentage of participants
Laboratory Test Abnormalities by DAIDS Grades Bilirubin, total, Grade 4	11.6 percentage of participants	13.3 percentage of participants
Laboratory Test Abnormalities by DAIDS Grades Haemoglobin, Grade 2	14.0 percentage of participants	18.9 percentage of participants
Laboratory Test Abnormalities by DAIDS Grades Haemoglobin, Grade 3	11.6 percentage of participants	8.1 percentage of participants
Laboratory Test Abnormalities by DAIDS Grades Haemoglobin, Grade 4	0.0 percentage of participants	0.0 percentage of participants
Laboratory Test Abnormalities by DAIDS Grades ALT, Grade 2	7.0 percentage of participants	6.7 percentage of participants
Laboratory Test Abnormalities by DAIDS Grades ALT, Grade 3	2.3 percentage of participants	4.0 percentage of participants
Laboratory Test Abnormalities by DAIDS Grades ALT, Grade 4	2.3 percentage of participants	0.0 percentage of participants
Laboratory Test Abnormalities by DAIDS Grades AST, Grade 2	4.7 percentage of participants	10.7 percentage of participants
Laboratory Test Abnormalities by DAIDS Grades AST, Grade 3	2.3 percentage of participants	2.7 percentage of participants
Laboratory Test Abnormalities by DAIDS Grades AST, Grade 4	2.3 percentage of participants	0.0 percentage of participants

SECONDARY outcome

Timeframe: baseline (the last observed measurement prior to administration of any randomised study medication), week 4, week 12 (after start of treatment)

Population: FAS

This outcome measure will be presented as the mean value and the standard deviation at baseline, week 4, week 12, the minimum (min) value on treatment, maximum (max) value on treatment and last measured value on treatment. Analytes with particular relevance for patients with HCF have been selected: Haemoglobin, Alanine aminotransaminase (ALT), Aspartate aminotransaminase (AST) and Bilirubin total. In this outcome measure Haemoglobin is presented.

Outcome measures

Outcome measures
Measure	Relapse n=43 Participants FDV 240 mg once daily combined with PegIFN/RBV for 24 weeks. At week 24, if the patients did not achieve ETS the patients received an additional 24 weeks of PegIFN/RBV.	Non-relapse n=75 Participants FDV 240mg once daily combined with PegIFN/RBV for 24 weeks, followed by an additional 24 weeks of PegIFN/RBV.
Changes From Baseline in Laboratory Test Values Over Time [Haemoglobin] Baseline (N=43, 74)	14.8 gram (g)/decilitre (dL) Standard Deviation 1.3	14.8 gram (g)/decilitre (dL) Standard Deviation 1.4
Changes From Baseline in Laboratory Test Values Over Time [Haemoglobin] week 4 (N=41, 69)	12.6 gram (g)/decilitre (dL) Standard Deviation 1.6	12.7 gram (g)/decilitre (dL) Standard Deviation 1.4
Changes From Baseline in Laboratory Test Values Over Time [Haemoglobin] week 12 (N=43, 66)	11.7 gram (g)/decilitre (dL) Standard Deviation 1.6	11.5 gram (g)/decilitre (dL) Standard Deviation 1.5
Changes From Baseline in Laboratory Test Values Over Time [Haemoglobin] min value on treatment (N=43, 74)	11.1 gram (g)/decilitre (dL) Standard Deviation 1.5	11.3 gram (g)/decilitre (dL) Standard Deviation 1.7
Changes From Baseline in Laboratory Test Values Over Time [Haemoglobin] max value on treatment (N=43, 74)	13.7 gram (g)/decilitre (dL) Standard Deviation 1.2	14.0 gram (g)/decilitre (dL) Standard Deviation 1.4
Changes From Baseline in Laboratory Test Values Over Time [Haemoglobin] last value on treatment (N=43, 74)	11.4 gram (g)/decilitre (dL) Standard Deviation 1.5	11.8 gram (g)/decilitre (dL) Standard Deviation 1.6

SECONDARY outcome

Timeframe: baseline (the last observed measurement prior to administration of any randomised study medication), week 4, week 12 (after start of treatment)

Population: FAS

Outcome measures

Outcome measures
Measure	Relapse n=43 Participants FDV 240 mg once daily combined with PegIFN/RBV for 24 weeks. At week 24, if the patients did not achieve ETS the patients received an additional 24 weeks of PegIFN/RBV.	Non-relapse n=75 Participants FDV 240mg once daily combined with PegIFN/RBV for 24 weeks, followed by an additional 24 weeks of PegIFN/RBV.
Changes From Baseline in Laboratory Test Values Over Time [ALT] Baseline (N=43, 75)	72 Units (U)/Litre (L) Standard Deviation 79	88 Units (U)/Litre (L) Standard Deviation 63
Changes From Baseline in Laboratory Test Values Over Time [ALT] week 4 (N=43, 73)	51 Units (U)/Litre (L) Standard Deviation 71	57 Units (U)/Litre (L) Standard Deviation 49
Changes From Baseline in Laboratory Test Values Over Time [ALT] week 12 (N=43, 67)	43 Units (U)/Litre (L) Standard Deviation 40	55 Units (U)/Litre (L) Standard Deviation 62
Changes From Baseline in Laboratory Test Values Over Time [ALT] min value on treatment (N=43, 75)	30 Units (U)/Litre (L) Standard Deviation 20	39 Units (U)/Litre (L) Standard Deviation 38
Changes From Baseline in Laboratory Test Values Over Time [ALT] max value on treatment (N=43, 75)	68 Units (U)/Litre (L) Standard Deviation 91	70 Units (U)/Litre (L) Standard Deviation 62
Changes From Baseline in Laboratory Test Values Over Time [ALT] last value on treatment (N=43, 75)	40 Units (U)/Litre (L) Standard Deviation 26	54 Units (U)/Litre (L) Standard Deviation 52

SECONDARY outcome

Timeframe: baseline (the last observed measurement prior to administration of any randomised study medication), week 4, week 12 (after start of treatment)

Population: FAS

Outcome measures

Outcome measures
Measure	Relapse n=43 Participants FDV 240 mg once daily combined with PegIFN/RBV for 24 weeks. At week 24, if the patients did not achieve ETS the patients received an additional 24 weeks of PegIFN/RBV.	Non-relapse n=75 Participants FDV 240mg once daily combined with PegIFN/RBV for 24 weeks, followed by an additional 24 weeks of PegIFN/RBV.
Changes From Baseline in Laboratory Test Values Over Time [AST] Baseline (N=43, 75)	54 U/L Standard Deviation 41	68 U/L Standard Deviation 42
Changes From Baseline in Laboratory Test Values Over Time [AST] week 4 (N=43, 73)	48 U/L Standard Deviation 71	46 U/L Standard Deviation 33
Changes From Baseline in Laboratory Test Values Over Time [AST] week 12 (N=43, 67)	41 U/L Standard Deviation 37	48 U/L Standard Deviation 45
Changes From Baseline in Laboratory Test Values Over Time [AST] min value on treatment (N=43, 75)	30 U/L Standard Deviation 16	35 U/L Standard Deviation 25
Changes From Baseline in Laboratory Test Values Over Time [AST] max value on treatment (N=43, 75)	63 U/L Standard Deviation 89	62 U/L Standard Deviation 50
Changes From Baseline in Laboratory Test Values Over Time [AST] last value on treatment (N=43, 75)	40 U/L Standard Deviation 23	49 U/L Standard Deviation 39

SECONDARY outcome

Timeframe: baseline (the last observed measurement prior to administration of any randomised study medication), week 4, week 12 (after start of treatment)

Population: FAS

Outcome measures

Outcome measures
Measure	Relapse n=43 Participants FDV 240 mg once daily combined with PegIFN/RBV for 24 weeks. At week 24, if the patients did not achieve ETS the patients received an additional 24 weeks of PegIFN/RBV.	Non-relapse n=75 Participants FDV 240mg once daily combined with PegIFN/RBV for 24 weeks, followed by an additional 24 weeks of PegIFN/RBV.
Changes From Baseline in Laboratory Test Values Over Time [Bilirubin Total] Baseline (N=43, 75)	0.5 milligram (mg)/dL Standard Deviation 0.2	0.5 milligram (mg)/dL Standard Deviation 0.2
Changes From Baseline in Laboratory Test Values Over Time [Bilirubin Total] week 4 (N=43, 74)	2.8 milligram (mg)/dL Standard Deviation 1.6	2.6 milligram (mg)/dL Standard Deviation 1.7
Changes From Baseline in Laboratory Test Values Over Time [Bilirubin Total] week 12 (N=43, 67)	2.7 milligram (mg)/dL Standard Deviation 1.8	2.7 milligram (mg)/dL Standard Deviation 1.9
Changes From Baseline in Laboratory Test Values Over Time [Bilirubin Total] min value on treatment (N=43, 75)	1.9 milligram (mg)/dL Standard Deviation 1.3	1.9 milligram (mg)/dL Standard Deviation 1.5
Changes From Baseline in Laboratory Test Values Over Time [Bilirubin Total] max value on treatment (N=43, 75)	3.6 milligram (mg)/dL Standard Deviation 2.1	3.5 milligram (mg)/dL Standard Deviation 2.2
Changes From Baseline in Laboratory Test Values Over Time [Bilirubin Total] last value on treatment (N=43, 75)	2.6 milligram (mg)/dL Standard Deviation 1.8	2.6 milligram (mg)/dL Standard Deviation 1.9

Adverse Events

Relapse

Serious events: 1 serious events

Other events: 38 other events

Deaths: 0 deaths

Non-relapse

Serious events: 6 serious events

Other events: 68 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Relapse n=43 participants at risk FDV 240 mg once daily combined with PegIFN/RBV for 24 weeks. At week 24, if the patients did not achieve ETS the patients received an additional 24 weeks of PegIFN/RBV.	Non-relapse n=75 participants at risk FDV 240mg once daily combined with PegIFN/RBV for 24 weeks, followed by an additional 24 weeks of PegIFN/RBV.
Gastrointestinal disorders Ascites	0.00% 0/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	1.3% 1/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Gastrointestinal disorders Diarrhoea	0.00% 0/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	1.3% 1/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Gastrointestinal disorders Mallory-Weiss syndrome	2.3% 1/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	0.00% 0/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Hepatobiliary disorders Hepatic failure	2.3% 1/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	0.00% 0/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Infections and infestations Gastroenteritis	0.00% 0/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	1.3% 1/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Infections and infestations Oral fungal infection	0.00% 0/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	1.3% 1/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Infections and infestations Pneumonia	2.3% 1/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	0.00% 0/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Metabolism and nutrition disorders Decreased appetite	0.00% 0/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	1.3% 1/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Metabolism and nutrition disorders Dehydration	0.00% 0/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	1.3% 1/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	1.3% 1/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Nervous system disorders Presyncope	0.00% 0/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	1.3% 1/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	1.3% 1/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days

Other adverse events

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim

Phone: 1-800-243-0127

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Other - Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Relapse n=43 participants at risk FDV 240 mg once daily combined with PegIFN/RBV for 24 weeks. At week 24, if the patients did not achieve ETS the patients received an additional 24 weeks of PegIFN/RBV.	Non-relapse n=75 participants at risk FDV 240mg once daily combined with PegIFN/RBV for 24 weeks, followed by an additional 24 weeks of PegIFN/RBV.
Blood and lymphatic system disorders Anaemia	20.9% 9/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	26.7% 20/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Blood and lymphatic system disorders Neutropenia	4.7% 2/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	9.3% 7/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Blood and lymphatic system disorders Thrombocytopenia	2.3% 1/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	6.7% 5/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Eye disorders Dry eye	2.3% 1/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	5.3% 4/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Gastrointestinal disorders Abdominal discomfort	0.00% 0/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	5.3% 4/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Gastrointestinal disorders Abdominal pain	14.0% 6/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	4.0% 3/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Gastrointestinal disorders Abdominal pain upper	4.7% 2/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	10.7% 8/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Gastrointestinal disorders Diarrhoea	32.6% 14/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	28.0% 21/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Gastrointestinal disorders Dry mouth	0.00% 0/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	5.3% 4/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Gastrointestinal disorders Dyspepsia	4.7% 2/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	6.7% 5/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Gastrointestinal disorders Nausea	51.2% 22/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	45.3% 34/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Gastrointestinal disorders Stomatitis	7.0% 3/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	2.7% 2/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Gastrointestinal disorders Vomiting	25.6% 11/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	20.0% 15/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
General disorders Asthenia	16.3% 7/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	17.3% 13/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
General disorders Chills	7.0% 3/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	2.7% 2/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
General disorders Fatigue	32.6% 14/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	14.7% 11/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
General disorders Influenza like illness	11.6% 5/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	5.3% 4/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
General disorders Malaise	2.3% 1/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	8.0% 6/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
General disorders Pyrexia	9.3% 4/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	10.7% 8/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Hepatobiliary disorders Hyperbilirubinaemia	27.9% 12/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	8.0% 6/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Hepatobiliary disorders Jaundice	11.6% 5/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	13.3% 10/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Infections and infestations Urinary tract infection	7.0% 3/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	1.3% 1/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Investigations Haemoglobin decreased	7.0% 3/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	1.3% 1/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Investigations Weight decreased	7.0% 3/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	4.0% 3/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Metabolism and nutrition disorders Decreased appetite	7.0% 3/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	21.3% 16/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Musculoskeletal and connective tissue disorders Arthralgia	4.7% 2/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	5.3% 4/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	5.3% 4/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Musculoskeletal and connective tissue disorders Muscle spasms	4.7% 2/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	5.3% 4/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Musculoskeletal and connective tissue disorders Myalgia	7.0% 3/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	12.0% 9/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Nervous system disorders Dizziness	7.0% 3/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	6.7% 5/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Nervous system disorders Dysgeusia	4.7% 2/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	5.3% 4/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Nervous system disorders Headache	23.3% 10/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	20.0% 15/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Psychiatric disorders Depression	7.0% 3/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	5.3% 4/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Psychiatric disorders Insomnia	11.6% 5/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	18.7% 14/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Psychiatric disorders Irritability	4.7% 2/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	8.0% 6/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Respiratory, thoracic and mediastinal disorders Cough	11.6% 5/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	14.7% 11/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Respiratory, thoracic and mediastinal disorders Dyspnoea	9.3% 4/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	4.0% 3/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	4.7% 2/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	5.3% 4/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Skin and subcutaneous tissue disorders Alopecia	9.3% 4/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	8.0% 6/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Skin and subcutaneous tissue disorders Dry skin	9.3% 4/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	10.7% 8/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Skin and subcutaneous tissue disorders Eczema	2.3% 1/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	6.7% 5/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Skin and subcutaneous tissue disorders Photosensitivity reaction	7.0% 3/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	1.3% 1/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Skin and subcutaneous tissue disorders Pruritus	30.2% 13/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	30.7% 23/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Skin and subcutaneous tissue disorders Rash	27.9% 12/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	28.0% 21/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Vascular disorders Hypertension	7.0% 3/43 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days	1.3% 1/75 • from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days