Hepatitis C
Conditions
Brief summary
The objective of this trial is to collect evidence for the safety and efficacy of 24 weeks of treatment with BI 201335 240 mg in combination with 24 or 48 weeks of Pegylated Interferon (PegIFN) and ribavirin (RBV) in treatment experienced patients who have been withdrawn from PegIFN and RBV treatment due to lack of efficacy in the 1220.7, 1220.30 and 1220.47 trials.
Interventions
DRUGBI 201335
BI 201335 for 24 weeks
DRUGPegIFN/RBV
PegIFN/RBV for 48 weeks
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Chronic hepatitis C infection of GT-1 in patients who failed prior treatment with PegIFN and RBV in the 1220.7, 1220.30 and 1220.47 trials of the BI 201335 Phase III program. 1. Patients from trials 1220.7, 1220.30 and 1220.47 of BI 201335 who have failed treatment with PegIFN/RBV in the placebo groups due to protocol-defined criteria of treatment failure (i.e. either non-response on treatment or relapse after end of treatment \[EOT\]). 2. Patients must have received at least 4 weeks of assigned trial medication and been compliant with all study procedures. 3. Female patients: * with documented hysterectomy, * who have had both ovaries removed, * with documented tubal ligation, * who are post-menopausal with last menstrual period at least 12 months prior to screening, or * of childbearing potential with a negative serum pregnancy test at screening and Day 1, that, if sexually active, agree to use one of the appropriate medically accepted methods of birth control from the date of screening until 7 months after the last dose of RBV in addition to the consistent and correct use of a condom. Patients must agree not to breast-feed at any time from the date of screening until 7 months after the last dose of RBV. Medically accepted methods of contraception for females in this trial are ethinyl estradiol-containing contraceptives, diaphragm with spermicide substance, intra-uterine device and cervical cap. or Male patients: * who are documented to be sterile, or * who are without pregnant female partner(s) and consistently and correctly use a condom while their female partner(s) (if of child-bearing potential) agree to use one of the appropriate medically accepted methods of birth control from the date of screening until 7 months after the last dose of ribavirin. It is in the responsibility of the male patient to ensure that his partner(s) is not pregnant prior to screening into the study or becomes pregnant during the treatment and the observation phase. Female partners of childbearing potential must perform monthly pregnancy tests from the date of screening until 7 months after the last dose of ribavirin (tests will be provided by the sponsor). 4. Signed informed consent form prior to trial participation.
Exclusion criteria
1. Evidence of acute or chronic liver disease due to causes other than chronic HCV infection. Incidental steatosis diagnosed by biopsy is not an
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sustained Virological Response (SVR): Plasma HCV RNA Level < 25 IU/mL | 12 weeks post treatment, up to 60 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Early Treatment Success (ETS) | week 4 and week 8 | 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. |
| Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) | Week 24 for relapsers with ETS; Week 48 for relapsers without ETS, and non-relapsers | 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. |
| Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at 12 Weeks Post-treatment. | 48 weeks for relapsers with ETS; 60 weeks for non-relapsers and relapsers without ETS | 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. |
| Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) | Week 24 for relapsers with ETS; Week 48 for relapsers without ETS, and non-relapsers. | 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. |
| Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at 12 Weeks Post-treatment. | Week 48 for relapsers with ETS; Week 48 for relapsers without ETS, and non-relapsers | 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. |
| Occurrence of Adverse Events (Overall and by DAIDS Grade) | from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days | 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. |
| Occurrence of Adverse Events Leading to Treatment Discontinuation | from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days | 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. |
| Sustained Virological Response After 24 Weeks of Treatment Discontinuation (SVR24) | 24 weeks post treatment, up to 72 weeks | Sustained virologic response 24 weeks, defined as a plasma HCV RNA level \< 25 IU/mL (undetected) 24 weeks after the originally planned treatment duration. |
| Occurrence of Drug-related AEs as Assessed by the Investigator | from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days | 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. |
| Laboratory Test Abnormalities by DAIDS Grades | baseline (day 1, after first dose of randomised treatment) up to 7 days after the last intake of study | 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. |
| Changes From Baseline in Laboratory Test Values Over Time [Haemoglobin] | baseline (the last observed measurement prior to administration of any randomised study medication), week 4, week 12 (after start of treatment) | 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. |
| Changes From Baseline in Laboratory Test Values Over Time [ALT] | baseline (the last observed measurement prior to administration of any randomised study medication), week 4, week 12 (after start of treatment) | 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 ALT is presented. |
| Changes From Baseline in Laboratory Test Values Over Time [AST] | baseline (the last observed measurement prior to administration of any randomised study medication), week 4, week 12 (after start of treatment) | 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 AST is presented. |
| Changes From Baseline in Laboratory Test Values Over Time [Bilirubin Total] | baseline (the last observed measurement prior to administration of any randomised study medication), week 4, week 12 (after start of treatment) | 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 Bilirubin total is presented. |
| Occurrence of Serious Adverse Events (SAEs) | from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days | 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. |
Countries
Austria, Belgium, Canada, France, Germany, Japan, Portugal, Romania, Russia, South Korea, Spain, Switzerland, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
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.
Pre-assignment details
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).
Participants by arm
| Arm | Count |
|---|---|
| Relapse 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. | 43 |
| Non-relapse FDV 240mg once daily combined with PegIFN/RBV for 24 weeks, followed by an additional 24 weeks of PegIFN/RBV. | 75 |
| Total | 118 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 |
| Overall Study | Lack of Efficacy | 0 | 10 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | other than above | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Relapse | Non-relapse | Total |
|---|---|---|---|
| Age, Continuous | 55.4 years STANDARD_DEVIATION 7.38 | 53.4 years STANDARD_DEVIATION 9.46 | 54.1 years STANDARD_DEVIATION 8.78 |
| Sex: Female, Male Female | 16 Participants | 25 Participants | 41 Participants |
| Sex: Female, Male Male | 27 Participants | 50 Participants | 77 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 38 / 43 | 68 / 75 |
| serious Total, serious adverse events | 1 / 43 | 6 / 75 |
Outcome results
Primary
Sustained Virological Response (SVR): Plasma HCV RNA Level < 25 IU/mL
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.
Time frame: 12 weeks post treatment, up to 60 weeks
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Relapse | Sustained Virological Response (SVR): Plasma HCV RNA Level < 25 IU/mL | 95.3 percentage of participants |
| Non-relapse | Sustained Virological Response (SVR): Plasma HCV RNA Level < 25 IU/mL | 54.7 percentage of participants |
Secondary
Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at 12 Weeks Post-treatment.
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.
Time frame: 48 weeks for relapsers with ETS; 60 weeks for non-relapsers and relapsers without ETS
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Relapse | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at 12 Weeks Post-treatment. | SVR12 = Yes | 41 participants |
| Relapse | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at 12 Weeks Post-treatment. | SVR12 = Yes, Baseline Normal to SVR12 Normal | 12 participants |
| Relapse | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at 12 Weeks Post-treatment. | SVR12 = Yes, Baseline Elevated to SVR12 Normal | 27 participants |
| Relapse | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at 12 Weeks Post-treatment. | SVR12 = No | 2 participants |
| Relapse | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at 12 Weeks Post-treatment. | SVR12 = No, Baseline Normal to SVR12 Normal | 0 participants |
| Relapse | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at 12 Weeks Post-treatment. | SVR12 = No, Baseline Elevated to SVR12 Normal | 1 participants |
| Non-relapse | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at 12 Weeks Post-treatment. | SVR12 = No, Baseline Normal to SVR12 Normal | 8 participants |
| Non-relapse | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at 12 Weeks Post-treatment. | SVR12 = Yes | 41 participants |
| Non-relapse | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at 12 Weeks Post-treatment. | SVR12 = No | 34 participants |
| Non-relapse | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at 12 Weeks Post-treatment. | SVR12 = Yes, Baseline Normal to SVR12 Normal | 11 participants |
| Non-relapse | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at 12 Weeks Post-treatment. | SVR12 = No, Baseline Elevated to SVR12 Normal | 2 participants |
| Non-relapse | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at 12 Weeks Post-treatment. | SVR12 = Yes, Baseline Elevated to SVR12 Normal | 27 participants |
Secondary
Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT)
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.
Time frame: Week 24 for relapsers with ETS; Week 48 for relapsers without ETS, and non-relapsers
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Relapse | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) | SVR12 = Yes | 41 participants |
| Relapse | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) | SVR12 = Yes, Baseline Normal to EOT Normal | 12 participants |
| Relapse | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) | SVR12 = Yes, Baseline Elevated to EOT Normal | 16 participants |
| Relapse | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) | SVR12 = No | 2 participants |
| Relapse | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) | SVR12 = No, Baseline Normal to EOT Normal | 0 participants |
| Relapse | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) | SVR12 = No, Baseline Elevated to EOT Normal | 2 participants |
| Non-relapse | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) | SVR12 = No, Baseline Normal to EOT Normal | 11 participants |
| Non-relapse | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) | SVR12 = Yes | 41 participants |
| Non-relapse | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) | SVR12 = No | 34 participants |
| Non-relapse | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) | SVR12 = Yes, Baseline Normal to EOT Normal | 10 participants |
| Non-relapse | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) | SVR12 = No, Baseline Elevated to EOT Normal | 9 participants |
| Non-relapse | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) | SVR12 = Yes, Baseline Elevated to EOT Normal | 15 participants |
Secondary
Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at 12 Weeks Post-treatment.
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.
Time frame: Week 48 for relapsers with ETS; Week 48 for relapsers without ETS, and non-relapsers
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Relapse | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at 12 Weeks Post-treatment. | SVR12 = No, Baseline Normal to SVR12 Normal | 1 participants |
| Relapse | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at 12 Weeks Post-treatment. | SVR12 = Yes, Baseline Normal to SVR12 Normal | 15 participants |
| Relapse | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at 12 Weeks Post-treatment. | SVR12 = Yes, Baseline Elevated to SVR12 Normal | 22 participants |
| Relapse | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at 12 Weeks Post-treatment. | SVR12 = No | 2 participants |
| Relapse | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at 12 Weeks Post-treatment. | SVR12 = No, Baseline Elevated to SVR12 Normal | 0 participants |
| Relapse | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at 12 Weeks Post-treatment. | SVR12 = Yes | 41 participants |
| Non-relapse | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at 12 Weeks Post-treatment. | SVR12 = No, Baseline Elevated to SVR12 Normal | 3 participants |
| Non-relapse | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at 12 Weeks Post-treatment. | SVR12 = Yes | 41 participants |
| Non-relapse | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at 12 Weeks Post-treatment. | SVR12 = No | 34 participants |
| Non-relapse | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at 12 Weeks Post-treatment. | SVR12 = Yes, Baseline Normal to SVR12 Normal | 14 participants |
| Non-relapse | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at 12 Weeks Post-treatment. | SVR12 = No, Baseline Normal to SVR12 Normal | 10 participants |
| Non-relapse | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at 12 Weeks Post-treatment. | SVR12 = Yes, Baseline Elevated to SVR12 Normal | 24 participants |
Secondary
Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT)
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.
Time frame: Week 24 for relapsers with ETS; Week 48 for relapsers without ETS, and non-relapsers.
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Relapse | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) | SVR12 = Yes | 41 participants |
| Relapse | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) | SVR12 = Yes, Baseline Normal to EOT Normal | 15 participants |
| Relapse | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) | SVR12 = Yes, Baseline Elevated to EOT Normal | 14 participants |
| Relapse | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) | SVR12 = No | 2 participants |
| Relapse | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) | SVR12 = No, Baseline Normal to EOT Normal | 1 participants |
| Relapse | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) | SVR12 = No, Baseline Elevated to EOT Normal | 1 participants |
| Non-relapse | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) | SVR12 = No, Baseline Normal to EOT Normal | 12 participants |
| Non-relapse | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) | SVR12 = Yes | 41 participants |
| Non-relapse | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) | SVR12 = No | 34 participants |
| Non-relapse | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) | SVR12 = Yes, Baseline Normal to EOT Normal | 13 participants |
| Non-relapse | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) | SVR12 = No, Baseline Elevated to EOT Normal | 7 participants |
| Non-relapse | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) | SVR12 = Yes, Baseline Elevated to EOT Normal | 11 participants |
Secondary
Changes From Baseline in Laboratory Test Values Over Time [ALT]
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 ALT is presented.
Time frame: baseline (the last observed measurement prior to administration of any randomised study medication), week 4, week 12 (after start of treatment)
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Relapse | Changes From Baseline in Laboratory Test Values Over Time [ALT] | Baseline (N=43, 75) | 72 Units (U)/Litre (L) | Standard Deviation 79 |
| Relapse | Changes From Baseline in Laboratory Test Values Over Time [ALT] | week 4 (N=43, 73) | 51 Units (U)/Litre (L) | Standard Deviation 71 |
| Relapse | Changes From Baseline in Laboratory Test Values Over Time [ALT] | week 12 (N=43, 67) | 43 Units (U)/Litre (L) | Standard Deviation 40 |
| Relapse | 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 |
| Relapse | 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 |
| Relapse | 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 |
| Non-relapse | Changes From Baseline in Laboratory Test Values Over Time [ALT] | max value on treatment (N=43, 75) | 70 Units (U)/Litre (L) | Standard Deviation 62 |
| Non-relapse | Changes From Baseline in Laboratory Test Values Over Time [ALT] | Baseline (N=43, 75) | 88 Units (U)/Litre (L) | Standard Deviation 63 |
| Non-relapse | Changes From Baseline in Laboratory Test Values Over Time [ALT] | min value on treatment (N=43, 75) | 39 Units (U)/Litre (L) | Standard Deviation 38 |
| Non-relapse | Changes From Baseline in Laboratory Test Values Over Time [ALT] | week 4 (N=43, 73) | 57 Units (U)/Litre (L) | Standard Deviation 49 |
| Non-relapse | Changes From Baseline in Laboratory Test Values Over Time [ALT] | last value on treatment (N=43, 75) | 54 Units (U)/Litre (L) | Standard Deviation 52 |
| Non-relapse | Changes From Baseline in Laboratory Test Values Over Time [ALT] | week 12 (N=43, 67) | 55 Units (U)/Litre (L) | Standard Deviation 62 |
Secondary
Changes From Baseline in Laboratory Test Values Over Time [AST]
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 AST is presented.
Time frame: baseline (the last observed measurement prior to administration of any randomised study medication), week 4, week 12 (after start of treatment)
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Relapse | Changes From Baseline in Laboratory Test Values Over Time [AST] | Baseline (N=43, 75) | 54 U/L | Standard Deviation 41 |
| Relapse | Changes From Baseline in Laboratory Test Values Over Time [AST] | week 4 (N=43, 73) | 48 U/L | Standard Deviation 71 |
| Relapse | Changes From Baseline in Laboratory Test Values Over Time [AST] | week 12 (N=43, 67) | 41 U/L | Standard Deviation 37 |
| Relapse | Changes From Baseline in Laboratory Test Values Over Time [AST] | min value on treatment (N=43, 75) | 30 U/L | Standard Deviation 16 |
| Relapse | Changes From Baseline in Laboratory Test Values Over Time [AST] | max value on treatment (N=43, 75) | 63 U/L | Standard Deviation 89 |
| Relapse | Changes From Baseline in Laboratory Test Values Over Time [AST] | last value on treatment (N=43, 75) | 40 U/L | Standard Deviation 23 |
| Non-relapse | Changes From Baseline in Laboratory Test Values Over Time [AST] | max value on treatment (N=43, 75) | 62 U/L | Standard Deviation 50 |
| Non-relapse | Changes From Baseline in Laboratory Test Values Over Time [AST] | Baseline (N=43, 75) | 68 U/L | Standard Deviation 42 |
| Non-relapse | Changes From Baseline in Laboratory Test Values Over Time [AST] | min value on treatment (N=43, 75) | 35 U/L | Standard Deviation 25 |
| Non-relapse | Changes From Baseline in Laboratory Test Values Over Time [AST] | week 4 (N=43, 73) | 46 U/L | Standard Deviation 33 |
| Non-relapse | Changes From Baseline in Laboratory Test Values Over Time [AST] | last value on treatment (N=43, 75) | 49 U/L | Standard Deviation 39 |
| Non-relapse | Changes From Baseline in Laboratory Test Values Over Time [AST] | week 12 (N=43, 67) | 48 U/L | Standard Deviation 45 |
Secondary
Changes From Baseline in Laboratory Test Values Over Time [Bilirubin Total]
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 Bilirubin total is presented.
Time frame: baseline (the last observed measurement prior to administration of any randomised study medication), week 4, week 12 (after start of treatment)
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Relapse | Changes From Baseline in Laboratory Test Values Over Time [Bilirubin Total] | Baseline (N=43, 75) | 0.5 milligram (mg)/dL | Standard Deviation 0.2 |
| Relapse | 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 |
| Relapse | 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 |
| Relapse | 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 |
| Relapse | 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 |
| Relapse | 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 |
| Non-relapse | Changes From Baseline in Laboratory Test Values Over Time [Bilirubin Total] | max value on treatment (N=43, 75) | 3.5 milligram (mg)/dL | Standard Deviation 2.2 |
| Non-relapse | Changes From Baseline in Laboratory Test Values Over Time [Bilirubin Total] | Baseline (N=43, 75) | 0.5 milligram (mg)/dL | Standard Deviation 0.2 |
| Non-relapse | 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 1.5 |
| Non-relapse | Changes From Baseline in Laboratory Test Values Over Time [Bilirubin Total] | week 4 (N=43, 74) | 2.6 milligram (mg)/dL | Standard Deviation 1.7 |
| Non-relapse | 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 1.9 |
| Non-relapse | Changes From Baseline in Laboratory Test Values Over Time [Bilirubin Total] | week 12 (N=43, 67) | 2.7 milligram (mg)/dL | Standard Deviation 1.9 |
Secondary
Changes From Baseline in Laboratory Test Values Over Time [Haemoglobin]
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.
Time frame: baseline (the last observed measurement prior to administration of any randomised study medication), week 4, week 12 (after start of treatment)
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Relapse | Changes From Baseline in Laboratory Test Values Over Time [Haemoglobin] | Baseline (N=43, 74) | 14.8 gram (g)/decilitre (dL) | Standard Deviation 1.3 |
| Relapse | 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 |
| Relapse | 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 |
| Relapse | 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 |
| Relapse | 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 |
| Relapse | 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 |
| Non-relapse | Changes From Baseline in Laboratory Test Values Over Time [Haemoglobin] | max value on treatment (N=43, 74) | 14.0 gram (g)/decilitre (dL) | Standard Deviation 1.4 |
| Non-relapse | Changes From Baseline in Laboratory Test Values Over Time [Haemoglobin] | Baseline (N=43, 74) | 14.8 gram (g)/decilitre (dL) | Standard Deviation 1.4 |
| Non-relapse | Changes From Baseline in Laboratory Test Values Over Time [Haemoglobin] | min value on treatment (N=43, 74) | 11.3 gram (g)/decilitre (dL) | Standard Deviation 1.7 |
| Non-relapse | Changes From Baseline in Laboratory Test Values Over Time [Haemoglobin] | week 4 (N=41, 69) | 12.7 gram (g)/decilitre (dL) | Standard Deviation 1.4 |
| Non-relapse | Changes From Baseline in Laboratory Test Values Over Time [Haemoglobin] | last value on treatment (N=43, 74) | 11.8 gram (g)/decilitre (dL) | Standard Deviation 1.6 |
| Non-relapse | Changes From Baseline in Laboratory Test Values Over Time [Haemoglobin] | week 12 (N=43, 66) | 11.5 gram (g)/decilitre (dL) | Standard Deviation 1.5 |
Secondary
Early Treatment Success (ETS)
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.
Time frame: week 4 and week 8
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Relapse | Early Treatment Success (ETS) | 97.7 percentage of participants |
| Non-relapse | Early Treatment Success (ETS) | 65.3 percentage of participants |
Secondary
Laboratory Test Abnormalities by DAIDS Grades
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.
Time frame: baseline (day 1, after first dose of randomised treatment) up to 7 days after the last intake of study
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Relapse | Laboratory Test Abnormalities by DAIDS Grades | Haemoglobin, Grade 3 | 11.6 percentage of participants |
| Relapse | Laboratory Test Abnormalities by DAIDS Grades | AST, Grade 2 | 4.7 percentage of participants |
| Relapse | Laboratory Test Abnormalities by DAIDS Grades | ALT, Grade 2 | 7.0 percentage of participants |
| Relapse | Laboratory Test Abnormalities by DAIDS Grades | AST, Grade 3 | 2.3 percentage of participants |
| Relapse | Laboratory Test Abnormalities by DAIDS Grades | Haemoglobin, Grade 2 | 14.0 percentage of participants |
| Relapse | Laboratory Test Abnormalities by DAIDS Grades | AST, Grade 4 | 2.3 percentage of participants |
| Relapse | Laboratory Test Abnormalities by DAIDS Grades | ALT, Grade 3 | 2.3 percentage of participants |
| Relapse | Laboratory Test Abnormalities by DAIDS Grades | Bilirubin, total, Grade 2 | 32.6 percentage of participants |
| Relapse | Laboratory Test Abnormalities by DAIDS Grades | Haemoglobin, Grade 4 | 0.0 percentage of participants |
| Relapse | Laboratory Test Abnormalities by DAIDS Grades | Bilirubin, total, Grade 3 | 39.5 percentage of participants |
| Relapse | Laboratory Test Abnormalities by DAIDS Grades | ALT, Grade 4 | 2.3 percentage of participants |
| Relapse | Laboratory Test Abnormalities by DAIDS Grades | Bilirubin, total, Grade 4 | 11.6 percentage of participants |
| Non-relapse | Laboratory Test Abnormalities by DAIDS Grades | Bilirubin, total, Grade 4 | 13.3 percentage of participants |
| Non-relapse | Laboratory Test Abnormalities by DAIDS Grades | Haemoglobin, Grade 2 | 18.9 percentage of participants |
| Non-relapse | Laboratory Test Abnormalities by DAIDS Grades | Haemoglobin, Grade 3 | 8.1 percentage of participants |
| Non-relapse | Laboratory Test Abnormalities by DAIDS Grades | Haemoglobin, Grade 4 | 0.0 percentage of participants |
| Non-relapse | Laboratory Test Abnormalities by DAIDS Grades | ALT, Grade 2 | 6.7 percentage of participants |
| Non-relapse | Laboratory Test Abnormalities by DAIDS Grades | ALT, Grade 3 | 4.0 percentage of participants |
| Non-relapse | Laboratory Test Abnormalities by DAIDS Grades | ALT, Grade 4 | 0.0 percentage of participants |
| Non-relapse | Laboratory Test Abnormalities by DAIDS Grades | AST, Grade 2 | 10.7 percentage of participants |
| Non-relapse | Laboratory Test Abnormalities by DAIDS Grades | AST, Grade 3 | 2.7 percentage of participants |
| Non-relapse | Laboratory Test Abnormalities by DAIDS Grades | AST, Grade 4 | 0.0 percentage of participants |
| Non-relapse | Laboratory Test Abnormalities by DAIDS Grades | Bilirubin, total, Grade 2 | 37.3 percentage of participants |
| Non-relapse | Laboratory Test Abnormalities by DAIDS Grades | Bilirubin, total, Grade 3 | 29.3 percentage of participants |
Secondary
Occurrence of Adverse Events Leading to Treatment Discontinuation
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.
Time frame: from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Relapse | Occurrence of Adverse Events Leading to Treatment Discontinuation | discontinuation of faldaprevir | 4.7 percentage of participants |
| Relapse | Occurrence of Adverse Events Leading to Treatment Discontinuation | discontinuation of all study medication | 2.3 percentage of participants |
| Non-relapse | Occurrence of Adverse Events Leading to Treatment Discontinuation | discontinuation of faldaprevir | 2.7 percentage of participants |
| Non-relapse | Occurrence of Adverse Events Leading to Treatment Discontinuation | discontinuation of all study medication | 0.0 percentage of participants |
Secondary
Occurrence of Adverse Events (Overall and by DAIDS Grade)
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.
Time frame: from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Relapse | Occurrence of Adverse Events (Overall and by DAIDS Grade) | Overall | 90.7 percentage of participants |
| Relapse | Occurrence of Adverse Events (Overall and by DAIDS Grade) | Subjects with DAIDS Grade 2, 3 or 4 AEs | 65.1 percentage of participants |
| Relapse | Occurrence of Adverse Events (Overall and by DAIDS Grade) | Subjects with DAIDS Grade 3 or 4 AEs | 27.9 percentage of participants |
| Relapse | Occurrence of Adverse Events (Overall and by DAIDS Grade) | Subjects with DAIDS Grade 4 AEs | 7.0 percentage of participants |
| Non-relapse | Occurrence of Adverse Events (Overall and by DAIDS Grade) | Subjects with DAIDS Grade 4 AEs | 1.3 percentage of participants |
| Non-relapse | Occurrence of Adverse Events (Overall and by DAIDS Grade) | Overall | 93.3 percentage of participants |
| Non-relapse | Occurrence of Adverse Events (Overall and by DAIDS Grade) | Subjects with DAIDS Grade 3 or 4 AEs | 17.3 percentage of participants |
| Non-relapse | Occurrence of Adverse Events (Overall and by DAIDS Grade) | Subjects with DAIDS Grade 2, 3 or 4 AEs | 56.0 percentage of participants |
Secondary
Occurrence of Drug-related AEs as Assessed by the Investigator
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.
Time frame: from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Relapse | Occurrence of Drug-related AEs as Assessed by the Investigator | 88.4 percentage of participants |
| Non-relapse | Occurrence of Drug-related AEs as Assessed by the Investigator | 88.0 percentage of participants |
Secondary
Occurrence of Serious Adverse Events (SAEs)
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.
Time frame: from first intake of study medication until 30 days after discontinuing faldaprevir, up to a maximum of 213 days
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Relapse | Occurrence of Serious Adverse Events (SAEs) | 2.3 percentage of participants |
| Non-relapse | Occurrence of Serious Adverse Events (SAEs) | 8.0 percentage of participants |
Secondary
Sustained Virological Response After 24 Weeks of Treatment Discontinuation (SVR24)
Sustained virologic response 24 weeks, defined as a plasma HCV RNA level \< 25 IU/mL (undetected) 24 weeks after the originally planned treatment duration.
Time frame: 24 weeks post treatment, up to 72 weeks
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Relapse | Sustained Virological Response After 24 Weeks of Treatment Discontinuation (SVR24) | 95.3 percentage of participants |
| Non-relapse | Sustained Virological Response After 24 Weeks of Treatment Discontinuation (SVR24) | 54.7 percentage of participants |