Trial Outcomes & Findings for This Trial Evaluates Safety, Pharmacokinetic Profile and Anti-viral Response of BI 207127 and BI 201335 for Patients With Chronic Hepatitis C (NCT NCT01528735)

NCT ID: NCT01528735

Last Updated: 2016-04-13

Results Overview

Number of patients with investigator defined drug-related Adverse Events

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

25 participants

Primary outcome timeframe

From first dose of study medication until 30 days after last dose of study medication, up to 199 days

Results posted on

2016-04-13

Participant Flow

Participant milestones

Participant milestones
Measure	600mg Deleobuvir and 80mg Faldaprevir Patients received 8 weeks of 600mg twice daily (bid) deleobuvir and 80 mg once daily (qd) faldaprevir (faldap) in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).	600mg Deleobuvir and 120mg Faldaprevir Patients received 8 weeks of 600mg twice daily (bid.) deleobuvir and 120 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).
Treatment Period 1: Faldap/Del/RBV STARTED	12	13
Treatment Period 1: Faldap/Del/RBV COMPLETED	11	12
Treatment Period 1: Faldap/Del/RBV NOT COMPLETED	1	1
Treatment Period 2: Faldap/PegIFN/RBV STARTED	11	12
Treatment Period 2: Faldap/PegIFN/RBV COMPLETED	10	12
Treatment Period 2: Faldap/PegIFN/RBV NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	600mg Deleobuvir and 80mg Faldaprevir Patients received 8 weeks of 600mg twice daily (bid) deleobuvir and 80 mg once daily (qd) faldaprevir (faldap) in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).	600mg Deleobuvir and 120mg Faldaprevir Patients received 8 weeks of 600mg twice daily (bid.) deleobuvir and 120 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).
Treatment Period 1: Faldap/Del/RBV Adverse Event	1	1
Treatment Period 2: Faldap/PegIFN/RBV Withdrawal by Subject	1	0

Baseline Characteristics

This Trial Evaluates Safety, Pharmacokinetic Profile and Anti-viral Response of BI 207127 and BI 201335 for Patients With Chronic Hepatitis C

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	600mg Deleobuvir and 80mg Faldaprevir n=12 Participants Patients received 8 weeks of 600mg twice daily (bid) deleobuvir and 80 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).	600mg Deleobuvir and 120mg Faldaprevir n=13 Participants Patients received 8 weeks of 600mg twice daily (bid.) deleobuvir and 120 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).	Total n=25 Participants Total of all reporting groups
Age, Continuous	57.7 years STANDARD_DEVIATION 7.38 • n=5 Participants	55.5 years STANDARD_DEVIATION 8.42 • n=7 Participants	56.5 years STANDARD_DEVIATION 7.85 • n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	8 Participants n=7 Participants	16 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants

PRIMARY outcome

Timeframe: From first dose of study medication until 30 days after last dose of study medication, up to 199 days

Population: Treated Set which included all patients who were dispensed study medication and were documented to have taken at least one dose of study medication.

Number of patients with investigator defined drug-related Adverse Events

Outcome measures

Outcome measures
Measure	600mg Deleobuvir and 80mg Faldaprevir n=12 Participants Patients received 8 weeks of 600mg twice daily (bid) deleobuvir and 80 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).	600mg Deleobuvir and 120mg Faldaprevir n=13 Participants Patients received 8 weeks of 600mg twice daily (bid.) deleobuvir and 120 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).
Number of Patients With Drug-related Adverse Events	12 participants	13 participants

SECONDARY outcome

Timeframe: 4 weeks

Population: Full analysis set which included all patients with at least 1 on-treatment value of HCV RNA viral load

Percentage of participants with plasma HCV RNA (hepatitis C virus (HCV) ribonucleic acid (RNA)) level \<25 IU/mL (undetected or detected) at week 4.

Outcome measures

Outcome measures
Measure	600mg Deleobuvir and 80mg Faldaprevir n=12 Participants Patients received 8 weeks of 600mg twice daily (bid) deleobuvir and 80 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).	600mg Deleobuvir and 120mg Faldaprevir n=13 Participants Patients received 8 weeks of 600mg twice daily (bid.) deleobuvir and 120 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).
Percentage of Participants With Virological Response at Week 4	91.7 percentage of participants	92.3 percentage of participants

SECONDARY outcome

Timeframe: 8 weeks

Population: Full analysis set which included all patients with at least 1 on-treatment value of HCV RNA viral load

Percentage of participants with plasma HCV RNA (hepatitis C virus ribonucleic acid ) level \<25 IU/mL (undetected or detected) at week 8.

Outcome measures

Outcome measures
Measure	600mg Deleobuvir and 80mg Faldaprevir n=12 Participants Patients received 8 weeks of 600mg twice daily (bid) deleobuvir and 80 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).	600mg Deleobuvir and 120mg Faldaprevir n=13 Participants Patients received 8 weeks of 600mg twice daily (bid.) deleobuvir and 120 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).
Percentage of Participants With Virological Response at Week 8	91.7 percentage of participants	100.0 percentage of participants

SECONDARY outcome

Timeframe: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57

Population: Pharmacokinetic (PK) analysis set which included all evaluable patients. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.

Maximum measured concentration of BI 207127 (Deleobuvir) in plasma following the morning dose of Nth day (Cmax,N).

Outcome measures

Outcome measures
Measure	600mg Deleobuvir and 80mg Faldaprevir n=11 Participants Patients received 8 weeks of 600mg twice daily (bid) deleobuvir and 80 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).	600mg Deleobuvir and 120mg Faldaprevir n=13 Participants Patients received 8 weeks of 600mg twice daily (bid.) deleobuvir and 120 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).
Maximum Measured Concentration (Cmax) of Deleobuvir Day 1 (N=9, 12)	12800 nmol/L Geometric Coefficient of Variation 57.3	18800 nmol/L Geometric Coefficient of Variation 55.8
Maximum Measured Concentration (Cmax) of Deleobuvir Day 11 (N=11, 12)	30100 nmol/L Geometric Coefficient of Variation 71.6	50300 nmol/L Geometric Coefficient of Variation 35.4
Maximum Measured Concentration (Cmax) of Deleobuvir Day 57 (N=11, 13)	18800 nmol/L Geometric Coefficient of Variation 61.0	41900 nmol/L Geometric Coefficient of Variation 51.6

SECONDARY outcome

Timeframe: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57

Population: PK analysis set which included all evaluable patients. A patient was considered to be not evaluable if the patient had a protocol violation relevant to the evaluation of pharmacokinetics or had insufficient data.

Time from last dosing to the maximum concentration of Deleobuvir (BI 207127) in plasma after the morning dose of Nth day (Tmax,N).

Outcome measures

Outcome measures
Measure	600mg Deleobuvir and 80mg Faldaprevir n=11 Participants Patients received 8 weeks of 600mg twice daily (bid) deleobuvir and 80 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).	600mg Deleobuvir and 120mg Faldaprevir n=13 Participants Patients received 8 weeks of 600mg twice daily (bid.) deleobuvir and 120 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).
Time From Last Dosing to the Maximum Concentration (Tmax) of Deleobuvir Day 57 (N=11, 13)	4.00 hours Interval 1.83 to 6.05	3.98 hours Interval 1.97 to 6.08
Time From Last Dosing to the Maximum Concentration (Tmax) of Deleobuvir Day 1 (N=9, 12)	3.97 hours Interval 3.83 to 6.02	5.03 hours Interval 1.97 to 7.87
Time From Last Dosing to the Maximum Concentration (Tmax) of Deleobuvir Day 11 (N=11, 12)	3.92 hours Interval 1.92 to 5.92	3.94 hours Interval 1.9 to 6.0

SECONDARY outcome

Timeframe: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57

Area under the concentration time curve (AUC) of the analyte in plasma after the morning dose on the Nth day (AUCτ,N) and at steady state (AUCτ,ss), over a uniform dosing interval τ.

Outcome measures

Outcome measures
Measure	600mg Deleobuvir and 80mg Faldaprevir n=11 Participants Patients received 8 weeks of 600mg twice daily (bid) deleobuvir and 80 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).	600mg Deleobuvir and 120mg Faldaprevir n=13 Participants Patients received 8 weeks of 600mg twice daily (bid.) deleobuvir and 120 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).
Area Under the Curve (AUC) of Deleobuvir Day 57 (N=10, 13)	111000 nmol*h/L Geometric Coefficient of Variation 102	326000 nmol*h/L Geometric Coefficient of Variation 64.8
Area Under the Curve (AUC) of Deleobuvir Day 1 (N=9, 12)	77500 nmol*h/L Geometric Coefficient of Variation 57.0	118000 nmol*h/L Geometric Coefficient of Variation 59.8
Area Under the Curve (AUC) of Deleobuvir Day 11 (N=11, 12)	216000 nmol*h/L Geometric Coefficient of Variation 104	404000 nmol*h/L Geometric Coefficient of Variation 52.3

SECONDARY outcome

Timeframe: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57

Maximum measured concentration of Faldaprevir (BI 201335 ZW) in plasma following the morning dose of Nth day (Cmax,N).

Outcome measures

Outcome measures
Measure	600mg Deleobuvir and 80mg Faldaprevir n=11 Participants Patients received 8 weeks of 600mg twice daily (bid) deleobuvir and 80 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).	600mg Deleobuvir and 120mg Faldaprevir n=13 Participants Patients received 8 weeks of 600mg twice daily (bid.) deleobuvir and 120 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).
Maximum Measured Concentration (Cmax) of Faldaprevir Day 11 (N=11, 12)	8530 ng/mL Geometric Coefficient of Variation 76.0	20400 ng/mL Geometric Coefficient of Variation 39.7
Maximum Measured Concentration (Cmax) of Faldaprevir Day 57 (N=11, 13)	4750 ng/mL Geometric Coefficient of Variation 65.1	18700 ng/mL Geometric Coefficient of Variation 59.0
Maximum Measured Concentration (Cmax) of Faldaprevir Day 1 (N=9, 12)	3380 ng/mL Geometric Coefficient of Variation 43.9	6440 ng/mL Geometric Coefficient of Variation 46.9

SECONDARY outcome

Timeframe: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57

Time from last dosing to the maximum concentration of Faldaprevir (BI 201335 ZW) in plasma after the morning dose of Nth day (Tmax,N).

Outcome measures

Outcome measures
Measure	600mg Deleobuvir and 80mg Faldaprevir n=11 Participants Patients received 8 weeks of 600mg twice daily (bid) deleobuvir and 80 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).	600mg Deleobuvir and 120mg Faldaprevir n=13 Participants Patients received 8 weeks of 600mg twice daily (bid.) deleobuvir and 120 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).
Time From Last Dosing to the Maximum Concentration (Tmax) of Faldaprevir Day 1 (N=9, 12)	3.97 hours Interval 3.83 to 6.02	5.98 hours Interval 3.97 to 23.8
Time From Last Dosing to the Maximum Concentration (Tmax) of Faldaprevir Day 11 (N=11, 12)	3.92 hours Interval 1.92 to 9.83	4.00 hours Interval 1.9 to 9.8
Time From Last Dosing to the Maximum Concentration (Tmax) of Faldaprevir Day 57 (N=11, 13)	3.92 hours Interval 1.83 to 6.05	3.97 hours Interval 1.97 to 7.93

SECONDARY outcome

Timeframe: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57

Area under the concentration time curve (AUC) of the analyte in plasma after the morning dose on the Nth day (AUCτ,N) and at steady state (AUCτ,ss), over a uniform dosing interval τ.

Outcome measures

Outcome measures
Measure	600mg Deleobuvir and 80mg Faldaprevir n=11 Participants Patients received 8 weeks of 600mg twice daily (bid) deleobuvir and 80 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).	600mg Deleobuvir and 120mg Faldaprevir n=13 Participants Patients received 8 weeks of 600mg twice daily (bid.) deleobuvir and 120 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).
Area Under the Curve (AUC) of Faldaprevir Day 11 (N=11, 10)	119000 ng*h/mL Geometric Coefficient of Variation 113	360000 ng*h/mL Geometric Coefficient of Variation 50.8
Area Under the Curve (AUC) of Faldaprevir Day 57 (N=10, 11)	58700 ng*h/mL Geometric Coefficient of Variation 115	291000 ng*h/mL Geometric Coefficient of Variation 78.5
Area Under the Curve (AUC) of Faldaprevir Day 1 (N=9, 9)	42900 ng*h/mL Geometric Coefficient of Variation 53.0	107000 ng*h/mL Geometric Coefficient of Variation 36.4

SECONDARY outcome

Timeframe: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57

Maximum measured concentration of BI 208333 (a metabolite of Deleobuvir) in plasma following the morning dose of Nth day (Cmax,N).

Outcome measures

Outcome measures
Measure	600mg Deleobuvir and 80mg Faldaprevir n=11 Participants Patients received 8 weeks of 600mg twice daily (bid) deleobuvir and 80 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).	600mg Deleobuvir and 120mg Faldaprevir n=13 Participants Patients received 8 weeks of 600mg twice daily (bid.) deleobuvir and 120 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).
Maximum Measured Concentration (Cmax) of BI 208333 Day 11 (N=11, 12)	11100 nmol/L Geometric Coefficient of Variation 92.5	20800 nmol/L Geometric Coefficient of Variation 80.5
Maximum Measured Concentration (Cmax) of BI 208333 Day 57 (N=11, 13)	4630 nmol/L Geometric Coefficient of Variation 74.0	14600 nmol/L Geometric Coefficient of Variation 92.7
Maximum Measured Concentration (Cmax) of BI 208333 Day 1 (N=9, 12)	2600 nmol/L Geometric Coefficient of Variation 64.2	3630 nmol/L Geometric Coefficient of Variation 76.8

SECONDARY outcome

Timeframe: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57

Time from last dosing to the maximum concentration of BI 208333 (a metabolite of Deleobuvir) in plasma after the morning dose of Nth day (Tmax,N).

Outcome measures

Outcome measures
Measure	600mg Deleobuvir and 80mg Faldaprevir n=11 Participants Patients received 8 weeks of 600mg twice daily (bid) deleobuvir and 80 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).	600mg Deleobuvir and 120mg Faldaprevir n=13 Participants Patients received 8 weeks of 600mg twice daily (bid.) deleobuvir and 120 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).
Time From Last Dosing to the Maximum Concentration (Tmax) of BI 208333 Day 1 (N=9, 12)	6.00 hours Interval 3.97 to 8.0	7.80 hours Interval 4.05 to 10.0
Time From Last Dosing to the Maximum Concentration (Tmax) of BI 208333 Day 11 (N=11, 12)	5.90 hours Interval 3.83 to 7.98	3.99 hours Interval 1.83 to 8.0
Time From Last Dosing to the Maximum Concentration (Tmax) of BI 208333 Day 57 (N=11, 13)	5.97 hours Interval 3.87 to 6.13	5.98 hours Interval 3.97 to 10.0

SECONDARY outcome

Timeframe: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57

Area under the concentration time curve (AUC) of the analyte in plasma after the morning dose on the Nth day (AUCτ,N) and at steady state (AUCτ,ss), over a uniform dosing interval τ.

Outcome measures

Outcome measures
Measure	600mg Deleobuvir and 80mg Faldaprevir n=11 Participants Patients received 8 weeks of 600mg twice daily (bid) deleobuvir and 80 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).	600mg Deleobuvir and 120mg Faldaprevir n=13 Participants Patients received 8 weeks of 600mg twice daily (bid.) deleobuvir and 120 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).
Area Under the Curve (AUC) of BI 208333 Day 11 (N=11, 12)	94200 nmol*h/L Geometric Coefficient of Variation 137	210000 nmol*h/L Geometric Coefficient of Variation 82.9
Area Under the Curve (AUC) of BI 208333 Day 1 (N=9, 12)	19900 nmol*h/L Geometric Coefficient of Variation 67.5	26000 nmol*h/L Geometric Coefficient of Variation 69.5
Area Under the Curve (AUC) of BI 208333 Day 57 (N=10, 13)	38400 nmol*h/L Geometric Coefficient of Variation 109	141000 nmol*h/L Geometric Coefficient of Variation 112

SECONDARY outcome

Timeframe: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on days 1, 11 and 57

Maximum measured concentration of CD 6168 (a metabolite of Deleobuvir) in plasma following the morning dose of Nth day (Cmax,N).

Outcome measures

Outcome measures
Measure	600mg Deleobuvir and 80mg Faldaprevir n=11 Participants Patients received 8 weeks of 600mg twice daily (bid) deleobuvir and 80 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).	600mg Deleobuvir and 120mg Faldaprevir n=13 Participants Patients received 8 weeks of 600mg twice daily (bid.) deleobuvir and 120 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).
Maximum Measured Concentration (Cmax) of CD 6168 Day 1 (N=9, 12)	1640 nmol/L Geometric Coefficient of Variation 73.7	1920 nmol/L Geometric Coefficient of Variation 75.5
Maximum Measured Concentration (Cmax) of CD 6168 Day 11 (N=11, 12)	12200 nmol/L Geometric Coefficient of Variation 144	23400 nmol/L Geometric Coefficient of Variation 40.4
Maximum Measured Concentration (Cmax) of CD 6168 Day 57 (N=11, 13)	7150 nmol/L Geometric Coefficient of Variation 109	21000 nmol/L Geometric Coefficient of Variation 62.3

SECONDARY outcome

Timeframe: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57

Time from last dosing to the maximum concentration of CD 6168 (a metabolite of Deleobuvir) in plasma after the morning dose of Nth day (Tmax,N).

Outcome measures

Outcome measures
Measure	600mg Deleobuvir and 80mg Faldaprevir n=11 Participants Patients received 8 weeks of 600mg twice daily (bid) deleobuvir and 80 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).	600mg Deleobuvir and 120mg Faldaprevir n=13 Participants Patients received 8 weeks of 600mg twice daily (bid.) deleobuvir and 120 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).
Time From Last Dosing to the Maximum Concentration (Tmax) of CD 6168 Day 57 (N=11, 13)	5.83 hours Interval 3.85 to 6.13	4.10 hours Interval 1.97 to 11.8
Time From Last Dosing to the Maximum Concentration (Tmax) of CD 6168 Day 1 (N=9, 12)	8.00 hours Interval 6.0 to 11.9	9.81 hours Interval 5.97 to 11.8
Time From Last Dosing to the Maximum Concentration (Tmax) of CD 6168 Day 11 (N=11, 12)	3.95 hours Interval 1.83 to 9.83	3.94 hours Interval 1.9 to 6.0

SECONDARY outcome

Timeframe: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57

Area under the concentration time curve (AUC) of the analyte in plasma after the morning dose on the Nth day (AUCτ,N) and at steady state (AUCτ,ss), over a uniform dosing interval τ.

Outcome measures

Outcome measures
Measure	600mg Deleobuvir and 80mg Faldaprevir n=11 Participants Patients received 8 weeks of 600mg twice daily (bid) deleobuvir and 80 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).	600mg Deleobuvir and 120mg Faldaprevir n=13 Participants Patients received 8 weeks of 600mg twice daily (bid.) deleobuvir and 120 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).
Area Under the Curve (AUC) of CD 6168 Day 1 (N=8, 10)	11200 nmol*h/L Geometric Coefficient of Variation 82.7	13200 nmol*h/L Geometric Coefficient of Variation 75.1
Area Under the Curve (AUC) of CD 6168 Day 11 (N=11, 12)	111000 nmol*h/L Geometric Coefficient of Variation 177	234000 nmol*h/L Geometric Coefficient of Variation 47.5
Area Under the Curve (AUC) of CD 6168 Day 57 (N=10, 12)	61400 nmol*h/L Geometric Coefficient of Variation 157	191000 nmol*h/L Geometric Coefficient of Variation 73.3

SECONDARY outcome

Timeframe: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on days 1, 11 and 57

Maximum measured concentration of CD 6168-AG (a metabolite of Deleobuvir) in plasma following the morning dose of Nth day (Cmax,N). AG=acylglucuronide.

Outcome measures

Outcome measures
Measure	600mg Deleobuvir and 80mg Faldaprevir n=11 Participants Patients received 8 weeks of 600mg twice daily (bid) deleobuvir and 80 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).	600mg Deleobuvir and 120mg Faldaprevir n=13 Participants Patients received 8 weeks of 600mg twice daily (bid.) deleobuvir and 120 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).
Maximum Measured Concentration (Cmax) of CD 6168-AG Day 11 (N=11, 12)	691 nmol/L Geometric Coefficient of Variation 132	2020 nmol/L Geometric Coefficient of Variation 71.7
Maximum Measured Concentration (Cmax) of CD 6168-AG Day 57 (N=11, 13)	455 nmol/L Geometric Coefficient of Variation 97.6	1780 nmol/L Geometric Coefficient of Variation 75.3
Maximum Measured Concentration (Cmax) of CD 6168-AG Day 1 (N=9, 12)	73.7 nmol/L Geometric Coefficient of Variation 81.3	106 nmol/L Geometric Coefficient of Variation 85.2

SECONDARY outcome

Timeframe: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57

Time from last dosing to the maximum concentration of CD 6168-AG (a metabolite of Deleobuvir) in plasma after the morning dose of Nth day (Tmax,N). AG=acylglucuronide.

Outcome measures

Outcome measures
Measure	600mg Deleobuvir and 80mg Faldaprevir n=11 Participants Patients received 8 weeks of 600mg twice daily (bid) deleobuvir and 80 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).	600mg Deleobuvir and 120mg Faldaprevir n=13 Participants Patients received 8 weeks of 600mg twice daily (bid.) deleobuvir and 120 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).
Time From Last Dosing to the Maximum Concentration (Tmax) of CD 6168-AG Day 1 (N=9, 12)	8.00 hours Interval 7.8 to 11.8	9.93 hours Interval 7.95 to 11.8
Time From Last Dosing to the Maximum Concentration (Tmax) of CD 6168-AG Day 11 (N=11, 12)	5.90 hours Interval 1.85 to 9.83	4.96 hours Interval 2.0 to 9.83
Time From Last Dosing to the Maximum Concentration (Tmax) of CD 6168-AG Day 57 (N=11, 13)	5.85 hours Interval 3.85 to 6.13	6.08 hours Interval 4.0 to 11.8

SECONDARY outcome

Timeframe: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57

Area under the concentration time curve (AUC) of the analyte in plasma after the morning dose on the Nth day (AUCτ,N) and at steady state (AUCτ,ss), over a uniform dosing interval τ. AG=acylglucuronide.

Outcome measures

Outcome measures
Measure	600mg Deleobuvir and 80mg Faldaprevir n=11 Participants Patients received 8 weeks of 600mg twice daily (bid) deleobuvir and 80 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).	600mg Deleobuvir and 120mg Faldaprevir n=13 Participants Patients received 8 weeks of 600mg twice daily (bid.) deleobuvir and 120 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).
Area Under the Curve (AUC) of CD 6168-AG Day 1	NA nmol*h/L Geometric Coefficient of Variation NA Not calculated because parameters of 2/3rds of the subjects cannot be derived due to limitation of the data or vomiting.	NA nmol*h/L Geometric Coefficient of Variation NA Not calculated because parameters of 2/3rds of the subjects cannot be derived due to limitation of the data or vomiting.
Area Under the Curve (AUC) of CD 6168-AG Day 11 (N=11, 12)	6460 nmol*h/L Geometric Coefficient of Variation 152	20700 nmol*h/L Geometric Coefficient of Variation 76.6
Area Under the Curve (AUC) of CD 6168-AG Day 57 (N=10, 12)	4110 nmol*h/L Geometric Coefficient of Variation 122	17700 nmol*h/L Geometric Coefficient of Variation 87.2

SECONDARY outcome

Timeframe: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h and 11h 50min after drug administration on days 1 and 57

Maximum measured concentration of ribavirin (RBV) in plasma following the morning dose of Nth day (Cmax,N).

Outcome measures

Outcome measures
Measure	600mg Deleobuvir and 80mg Faldaprevir n=11 Participants Patients received 8 weeks of 600mg twice daily (bid) deleobuvir and 80 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).	600mg Deleobuvir and 120mg Faldaprevir n=13 Participants Patients received 8 weeks of 600mg twice daily (bid.) deleobuvir and 120 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).
Maximum Measured Concentration (Cmax) of RBV Day 1 (N=9, 13)	537 ng/mL Geometric Coefficient of Variation 27.1	601 ng/mL Geometric Coefficient of Variation 58.1
Maximum Measured Concentration (Cmax) of RBV Day 57 (N=9, 11)	2560 ng/mL Geometric Coefficient of Variation 21.8	2740 ng/mL Geometric Coefficient of Variation 31.8

SECONDARY outcome

Timeframe: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h and 11h 50min after drug administration on days 1 and 57

Time from last dosing to the maximum concentration of ribavirin (RBV) in plasma after the morning dose of Nth day (Tmax,N).

Outcome measures

Outcome measures
Measure	600mg Deleobuvir and 80mg Faldaprevir n=11 Participants Patients received 8 weeks of 600mg twice daily (bid) deleobuvir and 80 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).	600mg Deleobuvir and 120mg Faldaprevir n=13 Participants Patients received 8 weeks of 600mg twice daily (bid.) deleobuvir and 120 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).
Time From Last Dosing to the Maximum Concentration (Tmax) of RBV Day 1 (N=9, 13)	2.00 hours Interval 1.82 to 4.02	3.95 hours Interval 1.87 to 6.05
Time From Last Dosing to the Maximum Concentration (Tmax) of RBV Day 57 (N=9, 11)	2.08 hours Interval 1.83 to 4.13	2.03 hours Interval 1.95 to 4.0

SECONDARY outcome

Timeframe: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h and 11h 50min after drug administration on days 1 and 57

Area under the concentration time curve (AUC) of ribavirin (RBV) in plasma after the morning dose on the Nth day (AUCτ,N) and at steady state (AUCτ,ss), over a uniform dosing interval τ.

Outcome measures

Outcome measures
Measure	600mg Deleobuvir and 80mg Faldaprevir n=11 Participants Patients received 8 weeks of 600mg twice daily (bid) deleobuvir and 80 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).	600mg Deleobuvir and 120mg Faldaprevir n=13 Participants Patients received 8 weeks of 600mg twice daily (bid.) deleobuvir and 120 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).
Area Under the Curve (AUC) of RBV Day 1 (N=9, 13)	3410 ng*h/mL Geometric Coefficient of Variation 19.0	3730 ng*h/mL Geometric Coefficient of Variation 57.6
Area Under the Curve (AUC) of RBV Day 57 (N=8, 10)	25700 ng*h/mL Geometric Coefficient of Variation 22.7	27600 ng*h/mL Geometric Coefficient of Variation 39.1

SECONDARY outcome

Timeframe: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57

Accumulation ratio of BI 207127 (Deleobuvir) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of Cmax after the morning dose of the Nth day and after the first dose (RA,Cmax,N), and ratio of the Cmax,ss of Deleobuvir versus itself (RA,Cmax,Met,ss).

Outcome measures

Outcome measures
Measure	600mg Deleobuvir and 80mg Faldaprevir n=11 Participants Patients received 8 weeks of 600mg twice daily (bid) deleobuvir and 80 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).	600mg Deleobuvir and 120mg Faldaprevir n=13 Participants Patients received 8 weeks of 600mg twice daily (bid.) deleobuvir and 120 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).
Cmax Accumulation Ratio (RA,Cmax,N) of Deleobuvir RA,Cmax,57 (N=11, 13)	1.46 Ratio Geometric Coefficient of Variation 53.2	2.20 Ratio Geometric Coefficient of Variation 53.6
Cmax Accumulation Ratio (RA,Cmax,N) of Deleobuvir RA,Cmax,Met,ss (N=11, 13)	1.00 Ratio Geometric Coefficient of Variation 0	1.00 Ratio Geometric Coefficient of Variation 0
Cmax Accumulation Ratio (RA,Cmax,N) of Deleobuvir RA,Cmax,11 (N=11, 12)	2.33 Ratio Geometric Coefficient of Variation 50.9	2.68 Ratio Geometric Coefficient of Variation 47.3

SECONDARY outcome

Timeframe: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57

Accumulation ratio of BI 207127 (Deleobuvir) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of AUC after the morning dose of the Nth day and after the first dose (RA,AUC,N), and ratio of the AUC,ss of Deleobuvir versus itself (RA,AUC,Met,ss).

Outcome measures

Outcome measures
Measure	600mg Deleobuvir and 80mg Faldaprevir n=11 Participants Patients received 8 weeks of 600mg twice daily (bid) deleobuvir and 80 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).	600mg Deleobuvir and 120mg Faldaprevir n=13 Participants Patients received 8 weeks of 600mg twice daily (bid.) deleobuvir and 120 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).
AUC Accumulation Ratio of Deleobuvir RA,AUC,11 (N=11, 12)	2.60 Ratio Geometric Coefficient of Variation 62.5	3.43 Ratio Geometric Coefficient of Variation 43.3
AUC Accumulation Ratio of Deleobuvir RA,AUC,57 (N=10, 13)	1.21 Ratio Geometric Coefficient of Variation 71.3	2.74 Ratio Geometric Coefficient of Variation 58.9
AUC Accumulation Ratio of Deleobuvir RA,AUC,tau,Met,ss (N=10, 13)	1.00 Ratio Geometric Coefficient of Variation 0	1.00 Ratio Geometric Coefficient of Variation 0

SECONDARY outcome

Timeframe: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on day 57

Mean residence time of BI 207127 (Deleobuvir) in the body after oral administration at steady state (MRTpo,ss).

Outcome measures

Outcome measures
Measure	600mg Deleobuvir and 80mg Faldaprevir n=10 Participants Patients received 8 weeks of 600mg twice daily (bid) deleobuvir and 80 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).	600mg Deleobuvir and 120mg Faldaprevir n=13 Participants Patients received 8 weeks of 600mg twice daily (bid.) deleobuvir and 120 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).
Mean Residence Time (MRTpo,ss) of Deleobuvir	6.65 hours Geometric Coefficient of Variation 39.0	12.6 hours Geometric Coefficient of Variation 52.2

SECONDARY outcome

Timeframe: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on day 57

Apparent clearance of BI 207127 (Deleobuvir) in plasma following extravascular administration on the 57th day (CL/F,ss).

Outcome measures

Outcome measures
Measure	600mg Deleobuvir and 80mg Faldaprevir n=10 Participants Patients received 8 weeks of 600mg twice daily (bid) deleobuvir and 80 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).	600mg Deleobuvir and 120mg Faldaprevir n=13 Participants Patients received 8 weeks of 600mg twice daily (bid.) deleobuvir and 120 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).
Apparent Clearance (CL/F,ss) of Deleobuvir	8.25 Litres per hour Geometric Coefficient of Variation 102	2.81 Litres per hour Geometric Coefficient of Variation 64.8

SECONDARY outcome

Timeframe: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 11 and 57

Predose measured concentration of BI 207127 (Deleobuvir) in plasma before the morning dose of the Nth day (Cpre,N) and at steady state (Cpre,ss).

Outcome measures

Outcome measures
Measure	600mg Deleobuvir and 80mg Faldaprevir n=11 Participants Patients received 8 weeks of 600mg twice daily (bid) deleobuvir and 80 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).	600mg Deleobuvir and 120mg Faldaprevir n=13 Participants Patients received 8 weeks of 600mg twice daily (bid.) deleobuvir and 120 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).
Predose Measured Concentration of Deleobuvir Cpre,11 (N=9, 12)	10700 nmol/L Geometric Coefficient of Variation 217	23500 nmol/L Geometric Coefficient of Variation 61.1
Predose Measured Concentration of Deleobuvir Cpre,ss (N=11, 13)	3280 nmol/L Geometric Coefficient of Variation 234	16599 nmol/L Geometric Coefficient of Variation 109

SECONDARY outcome

Timeframe: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57

Accumulation ratio of Faldaprevir (BI 201335 ZW) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of Cmax after the morning dose of the Nth day and after the first dose (RA,Cmax,N).

Outcome measures

Outcome measures
Measure	600mg Deleobuvir and 80mg Faldaprevir n=11 Participants Patients received 8 weeks of 600mg twice daily (bid) deleobuvir and 80 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).	600mg Deleobuvir and 120mg Faldaprevir n=13 Participants Patients received 8 weeks of 600mg twice daily (bid.) deleobuvir and 120 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).
Cmax Accumulation Ratio (RA,Cmax,N) of Faldaprevir RA,Cmax,11 (N=11, 12)	2.72 Ratio Geometric Coefficient of Variation 56.1	3.17 Ratio Geometric Coefficient of Variation 55.4
Cmax Accumulation Ratio (RA,Cmax,N) of Faldaprevir RA,Cmax,57 (N=11, 13)	1.51 Ratio Geometric Coefficient of Variation 68.0	3.00 Ratio Geometric Coefficient of Variation 81.7

SECONDARY outcome

Timeframe: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57

Accumulation ratio of Faldaprevir (BI 201335 ZW) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of AUC after the morning dose of the Nth day and after the first dose (RA,AUC,N).

Outcome measures

Outcome measures
Measure	600mg Deleobuvir and 80mg Faldaprevir n=11 Participants Patients received 8 weeks of 600mg twice daily (bid) deleobuvir and 80 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).	600mg Deleobuvir and 120mg Faldaprevir n=13 Participants Patients received 8 weeks of 600mg twice daily (bid.) deleobuvir and 120 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).
AUC Accumulation Ratio of Faldaprevir RA,AUC,57 (N=10, 9)	1.28 Ratio Geometric Coefficient of Variation 96.6	2.26 Ratio Geometric Coefficient of Variation 57.6
AUC Accumulation Ratio of Faldaprevir RA, AUC,11 (N=11, 9)	2.88 Ratio Geometric Coefficient of Variation 73.0	3.31 Ratio Geometric Coefficient of Variation 43.3

SECONDARY outcome

Timeframe: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on day 57

Mean residence time of Faldaprevir (BI 201335 ZW) in the body after oral administration at steady state (MRTpo,ss). This endpoint was not analysed as the parameter was not calculable for all patients in both treatment groups.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on day 57

Apparent clearance of Faldaprevir (BI 201335 ZW) in plasma following extravascular administration on the 57th day (CL/F,ss).

Outcome measures

Outcome measures
Measure	600mg Deleobuvir and 80mg Faldaprevir n=10 Participants Patients received 8 weeks of 600mg twice daily (bid) deleobuvir and 80 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).	600mg Deleobuvir and 120mg Faldaprevir n=11 Participants Patients received 8 weeks of 600mg twice daily (bid.) deleobuvir and 120 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).
Apparent Clearance (CL/F,ss) of Faldaprevir	22.7 mL/min Geometric Coefficient of Variation 114	6.87 mL/min Geometric Coefficient of Variation 78.5

SECONDARY outcome

Timeframe: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 11 and 57

Predose measured concentration of Faldaprevir (BI 201335 ZW) in plasma before the morning dose of the Nth day (Cpre,N) and at steady state (Cpre,ss).

Outcome measures

Outcome measures
Measure	600mg Deleobuvir and 80mg Faldaprevir n=11 Participants Patients received 8 weeks of 600mg twice daily (bid) deleobuvir and 80 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).	600mg Deleobuvir and 120mg Faldaprevir n=13 Participants Patients received 8 weeks of 600mg twice daily (bid.) deleobuvir and 120 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).
Predose Measured Concentration of Faldaprevir Cpre,11 (N=9, 12)	4250 ng/mL Geometric Coefficient of Variation 143	13800 ng/mL Geometric Coefficient of Variation 47.5
Predose Measured Concentration of Faldaprevir Cpre,ss (N=11, 12)	1540 ng/mL Geometric Coefficient of Variation 176	9980 ng/mL Geometric Coefficient of Variation 92.6

SECONDARY outcome

Timeframe: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57

Accumulation ratio of BI 208333 (a metabolite of Deleobuvir) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of Cmax after the morning dose of the Nth day and after the first dose (RA,Cmax,N), and ratio of the Cmax,ss of BI 208333 versus Cmax,ss of Deleobuvir (RA,Cmax,Met,ss).

Outcome measures

Outcome measures
Measure	600mg Deleobuvir and 80mg Faldaprevir n=11 Participants Patients received 8 weeks of 600mg twice daily (bid) deleobuvir and 80 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).	600mg Deleobuvir and 120mg Faldaprevir n=13 Participants Patients received 8 weeks of 600mg twice daily (bid.) deleobuvir and 120 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).
Cmax Accumulation Ratio of BI 208333 RA,Cmax,11 (N=11, 12)	3.82 Ratio Geometric Coefficient of Variation 81.2	5.73 Ratio Geometric Coefficient of Variation 36.2
Cmax Accumulation Ratio of BI 208333 RA,Cmax,57 (N=11, 13)	1.60 Ratio Geometric Coefficient of Variation 85.2	3.99 Ratio Geometric Coefficient of Variation 61.2
Cmax Accumulation Ratio of BI 208333 RA,Cmax,Met,ss (N=11, 13)	0.345 Ratio Geometric Coefficient of Variation 24.1	0.349 Ratio Geometric Coefficient of Variation 64.0

SECONDARY outcome

Timeframe: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 1, 11 and 57

Accumulation ratio of BI 208333 (a metabolite of Deleobuvir) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of AUC after the morning dose of the Nth day and after the first dose (RA,AUC,N), and ratio of the AUC,ss of BI 208333 versus AUC,ss of Deleobuvir (RA,AUC,Met,ss).

Outcome measures

Outcome measures
Measure	600mg Deleobuvir and 80mg Faldaprevir n=11 Participants Patients received 8 weeks of 600mg twice daily (bid) deleobuvir and 80 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).	600mg Deleobuvir and 120mg Faldaprevir n=13 Participants Patients received 8 weeks of 600mg twice daily (bid.) deleobuvir and 120 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).
AUC Accumulation Ratio of BI 208333 RA,AUC,11 (N=11, 12)	4.16 Ratio Geometric Coefficient of Variation 106	8.10 Ratio Geometric Coefficient of Variation 39.6
AUC Accumulation Ratio of BI 208333 RA,AUC,57 (N=110 13)	1.48 Ratio Geometric Coefficient of Variation 137	4.92 Ratio Geometric Coefficient of Variation 60.9
AUC Accumulation Ratio of BI 208333 RA,AUC,tau,Met,ss (N=10, 13)	0.345 Ratio Geometric Coefficient of Variation 24.1	0.431 Ratio Geometric Coefficient of Variation 57.9

SECONDARY outcome

Timeframe: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on day 57

Mean residence time of BI 208333 (a metabolite of Deleobuvir) in the body after oral administration at steady state (MRTpo,ss). This endpoint was not analysed as the parameter was not calculable for all patients in both treatment groups.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and 23h 50min after drug administration on days 11 and 57

Predose measured concentration of BI 208333 (a metabolite of Deleobuvir) in plasma before the morning dose of the Nth day (Cpre,N) and at steady state (Cpre,ss).

Outcome measures

Outcome measures
Measure	600mg Deleobuvir and 80mg Faldaprevir n=11 Participants Patients received 8 weeks of 600mg twice daily (bid) deleobuvir and 80 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).	600mg Deleobuvir and 120mg Faldaprevir n=13 Participants Patients received 8 weeks of 600mg twice daily (bid.) deleobuvir and 120 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).
Predose Measured Concentration of BI 208333 Cpre,ss (N=11, 13)	1630 nmol/L Geometric Coefficient of Variation 241	10700 nmol/L Geometric Coefficient of Variation 125
Predose Measured Concentration of BI 208333 Cpre,11 (N=9, 13)	7450 nmol/L Geometric Coefficient of Variation 186	16800 nmol/L Geometric Coefficient of Variation 87.1

SECONDARY outcome

Timeframe: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on days 1, 11 and 57

Accumulation ratio of CD 6168 (a metabolite of Deleobuvir) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of Cmax after the morning dose of the Nth day and after the first dose (RA,Cmax,N), and ratio of the Cmax,ss of CD 6168 versus Cmax,ss of Deleobuvir (RA,Cmax,Met,ss).

Outcome measures

Outcome measures
Measure	600mg Deleobuvir and 80mg Faldaprevir n=11 Participants Patients received 8 weeks of 600mg twice daily (bid) deleobuvir and 80 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).	600mg Deleobuvir and 120mg Faldaprevir n=13 Participants Patients received 8 weeks of 600mg twice daily (bid.) deleobuvir and 120 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).
Cmax Accumulation Ratio of CD 6168 RA,Cmax,11 (N=10, 12)	8.34 Ratio Geometric Coefficient of Variation 78.5	12.2 Ratio Geometric Coefficient of Variation 71.8
Cmax Accumulation Ratio of CD 6168 RA,Cmax,57 (N=11, 13)	4.90 Ratio Geometric Coefficient of Variation 75.4	10.9 Ratio Geometric Coefficient of Variation 82.5
Cmax Accumulation Ratio of CD 6168 RA,Cmax,Met,ss (N=11, 13)	0.380 Ratio Geometric Coefficient of Variation 47.7	0.500 Ratio Geometric Coefficient of Variation 34.6

SECONDARY outcome

Timeframe: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on days 1, 11 and 57

Accumulation ratio of CD 6168 (a metabolite of Deleobuvir) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of AUC after the morning dose of the Nth day and after the first dose (RA,AUC,N), and ratio of the AUC,ss of CD 6168 versus AUC,ss of Deleobuvir (RA,AUC,Met,ss).

Outcome measures

Outcome measures
Measure	600mg Deleobuvir and 80mg Faldaprevir n=11 Participants Patients received 8 weeks of 600mg twice daily (bid) deleobuvir and 80 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).	600mg Deleobuvir and 120mg Faldaprevir n=13 Participants Patients received 8 weeks of 600mg twice daily (bid.) deleobuvir and 120 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).
AUC Accumulation Ratio of CD 6168 RA,AUC,11 (N=10, 10)	9.57 Ratio Geometric Coefficient of Variation 74.9	17.0 Ratio Geometric Coefficient of Variation 75.4
AUC Accumulation Ratio of CD 6168 RA,AUC,57 (N=9, 11)	5.14 Ratio Geometric Coefficient of Variation 106	14.2 Ratio Geometric Coefficient of Variation 92.5
AUC Accumulation Ratio of CD 6168 RA,AUC,tau,Met,ss (N=10, 12)	0.552 Ratio Geometric Coefficient of Variation 48.0	0.600 Ratio Geometric Coefficient of Variation 24.6

SECONDARY outcome

Timeframe: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on day 57

Mean residence time of CD 6168 (a metabolite of Deleobuvir) in the body after oral administration at steady state (MRTpo,ss). This endpoint was not analysed as the parameter was not calculable for all patients in both treatment groups.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on days 11 and 57

Predose measured concentration of CD 6168 (a metabolite of Deleobuvir) in plasma before the morning dose of the Nth day (Cpre,N) and at steady state (Cpre,ss).

Outcome measures

Outcome measures
Measure	600mg Deleobuvir and 80mg Faldaprevir n=11 Participants Patients received 8 weeks of 600mg twice daily (bid) deleobuvir and 80 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).	600mg Deleobuvir and 120mg Faldaprevir n=13 Participants Patients received 8 weeks of 600mg twice daily (bid.) deleobuvir and 120 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).
Predose Measured Concentration of CD 6168 Cpre,11 (N=9, 13)	9610 nmol/L Geometric Coefficient of Variation 246	17600 nmol/L Geometric Coefficient of Variation 76.7
Predose Measured Concentration of CD 6168 Cpre,ss (N=11, 13)	3190 nmol/L Geometric Coefficient of Variation 279	13100 nmol/L Geometric Coefficient of Variation 82.6

SECONDARY outcome

Timeframe: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on days 1, 11 and 57

Accumulation ratio of CD 6168-AG (a metabolite of Deleobuvir) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of Cmax after the morning dose of the Nth day and after the first dose (RA,Cmax,N), and ratio of the Cmax,ss of CD 6168-AG versus Cmax,ss of Deleobuvir (RA,Cmax,Met,ss). AG=acylglucuronide.

Outcome measures

Outcome measures
Measure	600mg Deleobuvir and 80mg Faldaprevir n=11 Participants Patients received 8 weeks of 600mg twice daily (bid) deleobuvir and 80 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).	600mg Deleobuvir and 120mg Faldaprevir n=13 Participants Patients received 8 weeks of 600mg twice daily (bid.) deleobuvir and 120 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).
Cmax Accumulation Ratio of CD 6168-AG RA,Cmax,57 (N=11, 13)	7.11 Ratio Geometric Coefficient of Variation 109	17.2 Ratio Geometric Coefficient of Variation 89.8
Cmax Accumulation Ratio of CD 6168-AG RA,Cmax,Met,ss (N=11, 13)	0.0242 Ratio Geometric Coefficient of Variation 45.4	0.0424 Ratio Geometric Coefficient of Variation 53.9
Cmax Accumulation Ratio of CD 6168-AG RA,Cmax,11 (N=11, 8)	10.8 Ratio Geometric Coefficient of Variation 105	NA Ratio Geometric Coefficient of Variation NA Not calculable as per Boehringer Ingelheim internal rules summary statistics are not calculated when less than 2/3rds of patients have available data.

SECONDARY outcome

Timeframe: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on days 1, 11 and 57

Accumulation ratio of CD 6168-AG (a metabolite of Deleobuvir) in plasma after the administration of the Nth day over a uniform dosing interval tau, expressed as a ratio of AUC after the morning dose of the Nth day and after the first dose (RA,AUC,N), and ratio of the AUC,ss of CD 6168-AG versus AUC,ss of Deleobuvir (RA,AUC,Met,ss). AG=acylglucuronide.

Outcome measures

Outcome measures
Measure	600mg Deleobuvir and 80mg Faldaprevir n=11 Participants Patients received 8 weeks of 600mg twice daily (bid) deleobuvir and 80 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).	600mg Deleobuvir and 120mg Faldaprevir n=13 Participants Patients received 8 weeks of 600mg twice daily (bid.) deleobuvir and 120 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).
AUC Accumulation Ratio of CD 6168-AG RA,AUC,11 (N=11, 8)	16.7 Ratio Geometric Coefficient of Variation 122	NA Ratio Geometric Coefficient of Variation NA Not calculable as per Boehringer Ingelheim internal rules summary statistics are not calculated when less than 2/3rds of patients have available data.
AUC Accumulation Ratio of CD 6168-AG RA,AUC,57 (N=9, 8)	8.06 Ratio Geometric Coefficient of Variation 163	NA Ratio Geometric Coefficient of Variation NA Not calculable as per Boehringer Ingelheim internal rules summary statistics are not calculated when less than 2/3rds of patients have available data.
AUC Accumulation Ratio of CD 6168-AG RA,AUC,tau,Met,ss (N=10, 12)	0.0369 Ratio Geometric Coefficient of Variation 36.6	0.0557 Ratio Geometric Coefficient of Variation 46.2

SECONDARY outcome

Timeframe: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on day 57

Mean residence time of CD 6168-AG (a metabolite of Deleobuvir) in the body after oral administration at steady state (MRTpo,ss). AG=acylglucuronide. This endpoint was not analysed as the parameter was not calculable for all patients in both treatment groups.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h, 11h 50min and and 23h 50min after drug administration on days 11 and 57

Predose measured concentration of CD 6168-AG (a metabolite of Deleobuvir) in plasma before the morning dose of the Nth day (Cpre,N) and at steady state (Cpre,ss). AG=acylglucuronide.

Outcome measures

Outcome measures
Measure	600mg Deleobuvir and 80mg Faldaprevir n=11 Participants Patients received 8 weeks of 600mg twice daily (bid) deleobuvir and 80 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).	600mg Deleobuvir and 120mg Faldaprevir n=13 Participants Patients received 8 weeks of 600mg twice daily (bid.) deleobuvir and 120 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).
Predose Measured Concentration of CD 6168-AG Cpre,11 (N=9, 13)	566 nmol/L Geometric Coefficient of Variation 154	1630 nmol/L Geometric Coefficient of Variation 73.9
Predose Measured Concentration of CD 6168-AG Cpre,ss (N=11, 13)	211 nmol/L Geometric Coefficient of Variation 197	1350 nmol/L Geometric Coefficient of Variation 82.8

SECONDARY outcome

Timeframe: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h and 11h 50min after drug administration on days 1 and 57

Accumulation ratio of ribavirin (RBV) in plasma after the administration of the 57th day over a uniform dosing interval tau, expressed as a ratio of AUC after the morning dose of the 57th day and after the first dose (RA,AUC,57).

Outcome measures

Outcome measures
Measure	600mg Deleobuvir and 80mg Faldaprevir n=8 Participants Patients received 8 weeks of 600mg twice daily (bid) deleobuvir and 80 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).	600mg Deleobuvir and 120mg Faldaprevir n=10 Participants Patients received 8 weeks of 600mg twice daily (bid.) deleobuvir and 120 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).
AUC Accumulation Ratio of RBV	8.03 Ratio Geometric Coefficient of Variation 17.5	6.89 Ratio Geometric Coefficient of Variation 60.8

SECONDARY outcome

Timeframe: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h and 11h 50min after drug administration on days 1 and 57

Accumulation ratio of ribavirin (RBV) in plasma after the administration of the 57th day over a uniform dosing interval tau, expressed as a ratio of Cmax after the morning dose of the 57th day and after the first dose (RA,Cmax,57).

Outcome measures

Outcome measures
Measure	600mg Deleobuvir and 80mg Faldaprevir n=9 Participants Patients received 8 weeks of 600mg twice daily (bid) deleobuvir and 80 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).	600mg Deleobuvir and 120mg Faldaprevir n=11 Participants Patients received 8 weeks of 600mg twice daily (bid.) deleobuvir and 120 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).
Cmax Accumulation Ratio (RA,Cmax,57) of RBV	5.05 Ratio Geometric Coefficient of Variation 22.5	4.89 Ratio Geometric Coefficient of Variation 67.6

SECONDARY outcome

Timeframe: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h and 11h 50min after drug administration on day 57

Mean residence time of ribavirin (RBV) in the body after oral administration at steady state (MRTpo,ss). This endpoint was not analysed as the parameter was not calculable for all patients in both treatment groups.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 10 minutes (min) before drug administration and 2 hours (h), 4h, 6h, 8h, 10h and 11h 50min after drug administration on days 11 and 57

Predose measured concentration of ribavirin (RBV) in plasma before the morning dose of the Nth day (Cpre,N) and at steady state (Cpre,ss).

Outcome measures

Outcome measures
Measure	600mg Deleobuvir and 80mg Faldaprevir n=11 Participants Patients received 8 weeks of 600mg twice daily (bid) deleobuvir and 80 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).	600mg Deleobuvir and 120mg Faldaprevir n=13 Participants Patients received 8 weeks of 600mg twice daily (bid.) deleobuvir and 120 mg once daily (qd) faldaprevir in combination with standard weight-based dose of ribavirin (RBV). Followed by 24 weeks of 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV).
Predose Measured Concentration of RBV Cpre,11 (N=9, 13)	1400 ng/mL Geometric Coefficient of Variation 26.8	1290 ng/mL Geometric Coefficient of Variation 31.8
Predose Measured Concentration of RBV Cpre,ss (N=10, 12)	2080 ng/mL Geometric Coefficient of Variation 25.6	2110 ng/mL Geometric Coefficient of Variation 38.6

Adverse Events

Faldap/Del/RBV:80mg Faldap and 600mg Del.

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Faldap/Del/RBV:120mg Faldap and 600mg Del.

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Faldap/pegIFN/RBV:80mg Faldap and 600mg Del.

Serious events: 1 serious events

Other events: 11 other events

Deaths: 0 deaths

Faldap/pegIFN/RBV:120mg Faldap and 600mg Del.

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Faldap/Del/RBV:80mg Faldap and 600mg Del. n=12 participants at risk Patients received 8 weeks of 600mg twice daily (bid) deleobuvir (del) and 80 mg once daily (qd) faldaprevir (faldap) in combination with standard weight-based dose of ribavirin (RBV)	Faldap/Del/RBV:120mg Faldap and 600mg Del. n=13 participants at risk Patients received 8 weeks of 600mg twice daily (bid.) deleobuvir (del) and 120 mg once daily (qd) faldaprevir (faldap) in combination with standard weight-based dose of ribavirin (RBV)	Faldap/pegIFN/RBV:80mg Faldap and 600mg Del. n=11 participants at risk Patients received 24 weeks 120 mg once daily (qd) faldaprevir (faldap) in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV), following treatment of 8 weeks of 600mg twice daily (bid) deleobuvir (del) and 80 mg once daily (qd) faldaprevir (faldap) in combination with standard weight-based dose of ribavirin (RBV).	Faldap/pegIFN/RBV:120mg Faldap and 600mg Del. n=12 participants at risk Patients received 24 weeks 120 mg once daily (qd) faldaprevir in combination with once weekly subcutaneous injection of 180 μg pegylated interferon alfa-2a (PegIFN) and standard weight-based dose of ribavirin (RBV), following treatment of 8 weeks of 600mg twice daily (bid.) deleobuvir (del) and 120 mg once daily (qd) faldaprevir (faldap) in combination with standard weight-based dose of ribavirin (RBV).
Infections and infestations Gastroenteritis viral	0.00% 0/12 • From first dose of study medication until 30 days after last dose of study medication, up to 199 days	0.00% 0/13 • From first dose of study medication until 30 days after last dose of study medication, up to 199 days	9.1% 1/11 • From first dose of study medication until 30 days after last dose of study medication, up to 199 days	0.00% 0/12 • From first dose of study medication until 30 days after last dose of study medication, up to 199 days

Other adverse events

Additional Information

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Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
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