Healthy
Conditions
Brief summary
The objective of the current trial is to evaluate safety, tolerability and pharmacokinetics of different multiple doses of BI 207127 BID and multiple doses of BI 207127 combined with faldaprevir in healthy male and female subjects.
Interventions
DRUGBI 207127 + faldaprevir
fixed dose combination
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
1\. healthy male and female subjects
Exclusion criteria
1\. Any relevant deviation from healthy conditions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax and Cmax,ss of Faldaprevir (Combined Treatment Part) | After the first administration of Deleobuvir+Faldaprevir on Day 1 and after the last administration on Day 16 at 0 (5 min before administration on Day 16), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8,12, 24 h after drug administration in the morning. | Maximum measured concentration of Faldaprevir on Day 1 and at steady state on Day 16. |
| C(12h) and C(12h,ss) of CD 6168 (Combined Treatment Part) | After the first administration of Deleobuvir+Faldaprevir on Day 1 and after the last administration on Day 16 at 0 (5 min before administration on Day 16), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8,12 h after drug administration in the morning. | Concentration of CD 6168 at the end of the dosing interval 0 to 12 h on Day 1 and at steady state on Day 16. CD 6168 is a major metabolite of Deleobuvir. |
| AUC(0-12h) and AUC(0-12h,ss) of BI 208333 (Combined Treatment Part) | After the first administration of Deleobuvir+Faldaprevir on Day 1 and after the last administration on Day 16 at 0 (5 min before administration on Day 16), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8,12 h after drug administration in the morning. | Area under the concentration-time curve of BI 208333 over the uniform dosing interval 0 to 12 h on Day 1 and at steady state on Day 16. BI 208333 is a major metabolite of Deleobuvir. |
| Cmax and Cmax,ss of BI 208333 (Combined Treatment Part) | After the first administration of Deleobuvir+Faldaprevir on Day 1 and after the last administration on Day 16 at 0 (5 min before administration on Day 16), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8,12 h after drug administration in the morning. | Maximum measured concentration of BI 208333 on Day 1 and at steady state on Day 16. BI 208333 is a major metabolite of Deleobuvir. |
| C(12h) and C(12h,ss) of BI 208333 (Combined Treatment Part) | After the first administration of Deleobuvir+Faldaprevir on Day 1 and after the last administration on Day 16 at 0 (5 min before administration on Day 16), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8,12 h after drug administration in the morning. | Concentration of BI 208333 at the end of the dosing interval 0 to 12 h on Day 1 and at steady state on Day 16. BI 208333 is a major metabolite of Deleobuvir. |
| AUC(0-12h) and AUC(0-12h,ss) of CD 6168 Acylglucuronide (Combined Treatment Part) | After the first administration of Deleobuvir+Faldaprevir on Day 1 and after the last administration on Day 16 at 0 (5 min before administration on Day 16), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8,12 h after drug administration in the morning. | Area under the concentration-time curve of CD 6168 acylglucuronide over the uniform dosing interval 0 to 12 h on Day 1 and at steady state on Day 16. CD 6168 acylglucuronide is a metabolite of Deleobuvir. |
| Cmax and Cmax,ss of CD 6168 Acylglucuronide (Combined Treatment Part) | After the first administration of Deleobuvir+Faldaprevir on Day 1 and after the last administration on Day 16 at 0 (5 min before administration on Day 16), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8,12 h after drug administration in the morning. | Maximum measured concentration of CD 6168 acylglucuronide on Day 1 and at steady state on Day 16. CD 6168 acylglucuronide is a metabolite of Deleobuvir. |
| C(12h) and C(12h,ss) of CD 6168 Acylglucuronide (Combined Treatment Part) | After the first administration of Deleobuvir+Faldaprevir on Day 1 and after the last administration on Day 16 at 0 (5 min before administration on Day 16), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8,12 h after drug administration in the morning. | Concentration of CD 6168 acylglucuronide at the end of the dosing interval 0 to 12 h on Day 1 and at steady state on Day 16. CD 6168 acylglucuronide is a metabolite of Deleobuvir. |
| AUC(0-24h) and AUC(0-24h,ss) of Faldaprevir (Combined Treatment Part) | After the first administration of Deleobuvir+Faldaprevir on Day 1 and after the last administration on Day 16 at 0 (5 min before administration on Day 16), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8,12 h after drug administration in the morning. | Area under the concentration-time curve of Faldaprevir over the uniform dosing interval 0 to 24 h on Day 1 and at steady state on Day 16. |
| Number of Healthy Subjects With AEs (Multiple Rising Dose Part) | From first drug administration (Day 1) until end of trial examination (15 to 21 days after first administration) | Number of healthy subjects with any adverse event (AE) during the on-treatment period. |
| AUC(0-12h) and AUC(0-12h,ss) of Deleobuvir (Combined Treatment Part) | After the first administration of Deleobuvir+Faldaprevir on Day 1 and after the last administration on Day 16 at 0 (5 min before administration on Day 16), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8,12 hours (h) after drug administration in the morning. | Area under the concentration-time curve (AUC) of Deleobuvir over the uniform dosing interval 0 to 12 h (hours) on Day 1 and at steady state on Day 16. |
| Cmax and Cmax,ss of Deleobuvir (Combined Treatment Part) | After the first administration of Deleobuvir+Faldaprevir on Day 1 and after the last administration on Day 16 at 0 (5 min before administration on Day 16), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8,12 h after drug administration in the morning. | Maximum measured concentration of Deleobuvir on Day 1 and at steady state on Day 16. |
| C(12h) and C(12h,ss) of Deleobuvir (Combined Treatment Part) | After the first administration of Deleobuvir+Faldaprevir on Day 1 and after the last administration on Day 16 at 0 (5 min before administration on Day 16), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8,12 h after drug administration in the morning. | Concentration of Deleobuvir at the end of the dosing interval 0 to 12 h on Day 1 and at steady state on Day 16. |
| AUC(0-12h) and AUC(0-12h,ss) of CD 6168 (Combined Treatment Part) | After the first administration of Deleobuvir+Faldaprevir on Day 1 and after the last administration on Day 16 at 0 (5 min before administration on Day 16), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8,12 h after drug administration in the morning. | Area under the concentration-time curve of CD 6168 over the uniform dosing interval 0 to 12 h on Day 1 and at steady state on Day 16. CD 6168 is a major metabolite of Deleobuvir. |
| Cmax and Cmax,ss of CD 6168 (Combined Treatment Part) | After the first administration of Deleobuvir+Faldaprevir on Day 1 and after the last administration on Day 16 at 0 (5 min before administration on Day 16), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8,12 h after drug administration in the morning. | Maximum measured concentration of CD 6168 on Day 1 and at steady state on Day 16. CD 6168 is a major metabolite of Deleobuvir. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax and Cmax,ss of Deleobuvir (Multiple Rising Dose Part) | After the first administration of Deleobuvir on Day 1 and after the last administration on Day 9: at 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8,12 h after drug administration in the morning. | Maximum measured concentration of Deleobuvir on Day 1 and at steady state on Day 9. |
| AUC(0-12h) and AUC(0-12h,ss) of CD 6168 (Multiple Rising Dose Part) | After the first administration of Deleobuvir on Day 1 and after the last administration on Day 9: at 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8,12 h after drug administration in the morning. | Area under the concentration-time curve of CD 6168 over the uniform dosing interval 0 to 12 h on Day 1 and at steady state on Day 9. CD 6168 is a major metabolite of Deleobuvir. |
| Cmax and Cmax,ss of CD 6168 (Multiple Rising Dose Part) | After the first administration of Deleobuvir on Day 1 and after the last administration on Day 9: at 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8,12 h after drug administration in the morning. | Maximum measured concentration of CD 6168 on Day 1 and at steady state on Day 9. CD 6168 is a major metabolite of Deleobuvir. |
| AUC(0-12h) and AUC(0-12h,ss) of BI 208333 (Multiple Rising Dose Part) | After the first administration of Deleobuvir on Day 1 and after the last administration on Day 9: at 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8,12 h after drug administration in the morning. | Area under the concentration-time curve of BI 208333 over the uniform dosing interval 0 to 12 h on Day 1 and at steady state on Day 9. BI 208333 is a major metabolite of Deleobuvir. |
| Cmax and Cmax,ss of BI 208333 (Multiple Rising Dose Part) | After the first administration of Deleobuvir on Day 1 and after the last administration on Day 9: at 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8,12 h after drug administration in the morning. | Maximum measured concentration of BI 208333 on Day 1 and at steady state on Day 9. BI 208333 is a major metabolite of Deleobuvir. |
| AUC(0-12h) and AUC(0-12h,ss) of CD 6168 Acylglucuronide (Multiple Rising Dose Part) | After the first administration of Deleobuvir on Day 1 and after the last administration on Day 9: at 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8,12 h after drug administration in the morning. | Area under the concentration-time curve of CD 6168 acylglucuronide over the uniform dosing interval 0 to 12 h on Day 1 and at steady state on Day 9. CD 6168 acylglucuronide is a metabolite of Deleobuvir. |
| Cmax and Cmax,ss of CD 6168 Acylglucuronide (Multiple Rising Dose Part) | After the first administration of Deleobuvir on Day 1 and after the last administration on Day 9: at 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8,12 h after drug administration in the morning. | Maximum measured concentration of CD 6168 acylglucuronide on Day 1 and at steady state on Day 9. CD 6168 acylglucuronide is a metabolite of Deleobuvir. |
| AUC(0-12h) and AUC(0-12h,ss) of Deleobuvir (Multiple Rising Dose Part) | After the first administration of Deleobuvir on Day 1 and after the last administration on Day 9: at 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8,12 h after drug administration in the morning. | Area under the concentration-time curve of Deleobuvir over the uniform dosing interval 0 to 12 h on Day 1 and at steady state on Day 9. |
Countries
Germany
Participant flow
Pre-assignment details
The 600mg dose cohort was to be started at least 6 days after the 400mg dose cohort was completed and the combined treatment cohort (600mg Deleobuvir + 120mg Faldaprevir) was started after the evaluation of key safety and tolerability data of the individual treatments.
Participants by arm
| Arm | Count |
|---|---|
| 400 mg Deleobuvir 400 mg Deleobuvir administered twice daily for 9 days. Oral administration with 240 mL of water under fed conditions. Low dose of multiple rising dose part. | 8 |
| 600 mg Deleobuvir 600 mg Deleobuvir administered twice daily for 9 days. Oral administration with 240 mL of water under fed conditions. High dose of multiple rising dose part. | 8 |
| 600 mg Deleobuvir + 120 mg Faldaprevir 600 mg Deleobuvir administered twice daily and 120 mg Faldaprevir administered once daily for 16 days.
Oral administration with 240 mL of water under fed conditions. Combined treatment part; conducted after multiple rising dose part. | 16 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | 400 mg Deleobuvir | 600 mg Deleobuvir | 600 mg Deleobuvir + 120 mg Faldaprevir | Total |
|---|---|---|---|---|
| Age, Continuous | 39.5 years STANDARD_DEVIATION 10.4 | 37.3 years STANDARD_DEVIATION 5.1 | 38.3 years STANDARD_DEVIATION 10.6 | 38.3 years STANDARD_DEVIATION 9.3 |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 6 Participants | 13 Participants |
| Sex: Female, Male Male | 5 Participants | 4 Participants | 10 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 8 | 5 / 8 | 9 / 16 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 16 |
Outcome results
Primary
AUC(0-12h) and AUC(0-12h,ss) of BI 208333 (Combined Treatment Part)
Area under the concentration-time curve of BI 208333 over the uniform dosing interval 0 to 12 h on Day 1 and at steady state on Day 16. BI 208333 is a major metabolite of Deleobuvir.
Time frame: After the first administration of Deleobuvir+Faldaprevir on Day 1 and after the last administration on Day 16 at 0 (5 min before administration on Day 16), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8,12 h after drug administration in the morning.
Population: PKS including patients with available data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 400 mg Deleobuvir | AUC(0-12h) and AUC(0-12h,ss) of BI 208333 (Combined Treatment Part) | AUC(0-12h) on Day 1 | 9130 nmol*h/L | Geometric Coefficient of Variation 46.9 |
| 400 mg Deleobuvir | AUC(0-12h) and AUC(0-12h,ss) of BI 208333 (Combined Treatment Part) | AUC(0-12h,ss) on Day 16 | 13600 nmol*h/L | Geometric Coefficient of Variation 71.1 |
Primary
AUC(0-12h) and AUC(0-12h,ss) of CD 6168 Acylglucuronide (Combined Treatment Part)
Area under the concentration-time curve of CD 6168 acylglucuronide over the uniform dosing interval 0 to 12 h on Day 1 and at steady state on Day 16. CD 6168 acylglucuronide is a metabolite of Deleobuvir.
Time frame: After the first administration of Deleobuvir+Faldaprevir on Day 1 and after the last administration on Day 16 at 0 (5 min before administration on Day 16), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8,12 h after drug administration in the morning.
Population: PKS including patients with available data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 400 mg Deleobuvir | AUC(0-12h) and AUC(0-12h,ss) of CD 6168 Acylglucuronide (Combined Treatment Part) | AUC(0-12h) on Day 1 | 511 nmol*h/L | Geometric Coefficient of Variation 69.9 |
| 400 mg Deleobuvir | AUC(0-12h) and AUC(0-12h,ss) of CD 6168 Acylglucuronide (Combined Treatment Part) | AUC(0-12h,ss) on Day 16 | 3560 nmol*h/L | Geometric Coefficient of Variation 120 |
Primary
AUC(0-12h) and AUC(0-12h,ss) of CD 6168 (Combined Treatment Part)
Area under the concentration-time curve of CD 6168 over the uniform dosing interval 0 to 12 h on Day 1 and at steady state on Day 16. CD 6168 is a major metabolite of Deleobuvir.
Time frame: After the first administration of Deleobuvir+Faldaprevir on Day 1 and after the last administration on Day 16 at 0 (5 min before administration on Day 16), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8,12 h after drug administration in the morning.
Population: PKS including patients with available data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 400 mg Deleobuvir | AUC(0-12h) and AUC(0-12h,ss) of CD 6168 (Combined Treatment Part) | AUC(0-12h) on Day 1 | 6080 nmol*h/L | Geometric Coefficient of Variation 55 |
| 400 mg Deleobuvir | AUC(0-12h) and AUC(0-12h,ss) of CD 6168 (Combined Treatment Part) | AUC(0-12h,ss) on Day 16 | 38100 nmol*h/L | Geometric Coefficient of Variation 76 |
Primary
AUC(0-12h) and AUC(0-12h,ss) of Deleobuvir (Combined Treatment Part)
Area under the concentration-time curve (AUC) of Deleobuvir over the uniform dosing interval 0 to 12 h (hours) on Day 1 and at steady state on Day 16.
Time frame: After the first administration of Deleobuvir+Faldaprevir on Day 1 and after the last administration on Day 16 at 0 (5 min before administration on Day 16), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8,12 hours (h) after drug administration in the morning.
Population: PKS. The pharmacokinetic set (PKS) included all subjects of the treated set who provided at least 1 observation for at least 1 pharmacokinetic endpoint without important protocol violations relevant for the statistical evaluation of pharmacokinetic endpoints. Including patients with available data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 400 mg Deleobuvir | AUC(0-12h) and AUC(0-12h,ss) of Deleobuvir (Combined Treatment Part) | AUC(0-12h) on Day 1 | 37500 nmol*h/L | Geometric Coefficient of Variation 49.4 |
| 400 mg Deleobuvir | AUC(0-12h) and AUC(0-12h,ss) of Deleobuvir (Combined Treatment Part) | AUC(0-12h,ss) on Day 16 | 51400 nmol*h/L | Geometric Coefficient of Variation 57.2 |
Primary
AUC(0-24h) and AUC(0-24h,ss) of Faldaprevir (Combined Treatment Part)
Area under the concentration-time curve of Faldaprevir over the uniform dosing interval 0 to 24 h on Day 1 and at steady state on Day 16.
Time frame: After the first administration of Deleobuvir+Faldaprevir on Day 1 and after the last administration on Day 16 at 0 (5 min before administration on Day 16), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8,12 h after drug administration in the morning.
Population: PKS including patients with available data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 400 mg Deleobuvir | AUC(0-24h) and AUC(0-24h,ss) of Faldaprevir (Combined Treatment Part) | AUC(0-12h) on Day 1 | 44800 nmol*h/L | Geometric Coefficient of Variation 23.6 |
| 400 mg Deleobuvir | AUC(0-24h) and AUC(0-24h,ss) of Faldaprevir (Combined Treatment Part) | AUC(0-12h,ss) on Day 16 | 66200 nmol*h/L | Geometric Coefficient of Variation 46.1 |
Primary
C(12h) and C(12h,ss) of BI 208333 (Combined Treatment Part)
Concentration of BI 208333 at the end of the dosing interval 0 to 12 h on Day 1 and at steady state on Day 16. BI 208333 is a major metabolite of Deleobuvir.
Time frame: After the first administration of Deleobuvir+Faldaprevir on Day 1 and after the last administration on Day 16 at 0 (5 min before administration on Day 16), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8,12 h after drug administration in the morning.
Population: PKS including patients with available data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 400 mg Deleobuvir | C(12h) and C(12h,ss) of BI 208333 (Combined Treatment Part) | C(12h) on Day 1 | 520 nmol/L | Geometric Coefficient of Variation 80.8 |
| 400 mg Deleobuvir | C(12h) and C(12h,ss) of BI 208333 (Combined Treatment Part) | C(12h,ss) on Day 16 | 447 nmol/L | Geometric Coefficient of Variation 101 |
Primary
C(12h) and C(12h,ss) of CD 6168 Acylglucuronide (Combined Treatment Part)
Concentration of CD 6168 acylglucuronide at the end of the dosing interval 0 to 12 h on Day 1 and at steady state on Day 16. CD 6168 acylglucuronide is a metabolite of Deleobuvir.
Time frame: After the first administration of Deleobuvir+Faldaprevir on Day 1 and after the last administration on Day 16 at 0 (5 min before administration on Day 16), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8,12 h after drug administration in the morning.
Population: PKS including patients with available data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 400 mg Deleobuvir | C(12h) and C(12h,ss) of CD 6168 Acylglucuronide (Combined Treatment Part) | C(12h) on Day 1 | 56.4 nmol/L | Geometric Coefficient of Variation 67.1 |
| 400 mg Deleobuvir | C(12h) and C(12h,ss) of CD 6168 Acylglucuronide (Combined Treatment Part) | C(12h,ss) on Day 16 | 178.0 nmol/L | Geometric Coefficient of Variation 122 |
Primary
C(12h) and C(12h,ss) of CD 6168 (Combined Treatment Part)
Concentration of CD 6168 at the end of the dosing interval 0 to 12 h on Day 1 and at steady state on Day 16. CD 6168 is a major metabolite of Deleobuvir.
Time frame: After the first administration of Deleobuvir+Faldaprevir on Day 1 and after the last administration on Day 16 at 0 (5 min before administration on Day 16), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8,12 h after drug administration in the morning.
Population: PKS including patients with available data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 400 mg Deleobuvir | C(12h) and C(12h,ss) of CD 6168 (Combined Treatment Part) | C(12h) on Day 1 | 488 nmol/L | Geometric Coefficient of Variation 67.5 |
| 400 mg Deleobuvir | C(12h) and C(12h,ss) of CD 6168 (Combined Treatment Part) | C(12h,ss) on Day 16 | 1650 nmol/L | Geometric Coefficient of Variation 102 |
Primary
C(12h) and C(12h,ss) of Deleobuvir (Combined Treatment Part)
Concentration of Deleobuvir at the end of the dosing interval 0 to 12 h on Day 1 and at steady state on Day 16.
Time frame: After the first administration of Deleobuvir+Faldaprevir on Day 1 and after the last administration on Day 16 at 0 (5 min before administration on Day 16), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8,12 h after drug administration in the morning.
Population: PKS including patients with available data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 400 mg Deleobuvir | C(12h) and C(12h,ss) of Deleobuvir (Combined Treatment Part) | C(12h) on Day 1 | 1090 nmol/L | Geometric Coefficient of Variation 69.3 |
| 400 mg Deleobuvir | C(12h) and C(12h,ss) of Deleobuvir (Combined Treatment Part) | C(12h,ss) on Day 16 | 1000 nmol/L | Geometric Coefficient of Variation 85.9 |
Primary
Cmax and Cmax,ss of BI 208333 (Combined Treatment Part)
Maximum measured concentration of BI 208333 on Day 1 and at steady state on Day 16. BI 208333 is a major metabolite of Deleobuvir.
Time frame: After the first administration of Deleobuvir+Faldaprevir on Day 1 and after the last administration on Day 16 at 0 (5 min before administration on Day 16), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8,12 h after drug administration in the morning.
Population: PKS including patients with available data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 400 mg Deleobuvir | Cmax and Cmax,ss of BI 208333 (Combined Treatment Part) | Cmax on Day 1 | 1450 nmol/L | Geometric Coefficient of Variation 40 |
| 400 mg Deleobuvir | Cmax and Cmax,ss of BI 208333 (Combined Treatment Part) | Cmax,ss on Day 16 (N=14) | 2060 nmol/L | Geometric Coefficient of Variation 57.6 |
Primary
Cmax and Cmax,ss of CD 6168 Acylglucuronide (Combined Treatment Part)
Maximum measured concentration of CD 6168 acylglucuronide on Day 1 and at steady state on Day 16. CD 6168 acylglucuronide is a metabolite of Deleobuvir.
Time frame: After the first administration of Deleobuvir+Faldaprevir on Day 1 and after the last administration on Day 16 at 0 (5 min before administration on Day 16), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8,12 h after drug administration in the morning.
Population: PKS including patients with available data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 400 mg Deleobuvir | Cmax and Cmax,ss of CD 6168 Acylglucuronide (Combined Treatment Part) | Cmax on Day 1 | 83.9 nmol/L | Geometric Coefficient of Variation 63.7 |
| 400 mg Deleobuvir | Cmax and Cmax,ss of CD 6168 Acylglucuronide (Combined Treatment Part) | Cmax,ss on Day 16 (N=14) | 457.0 nmol/L | Geometric Coefficient of Variation 106 |
Primary
Cmax and Cmax,ss of CD 6168 (Combined Treatment Part)
Maximum measured concentration of CD 6168 on Day 1 and at steady state on Day 16. CD 6168 is a major metabolite of Deleobuvir.
Time frame: After the first administration of Deleobuvir+Faldaprevir on Day 1 and after the last administration on Day 16 at 0 (5 min before administration on Day 16), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8,12 h after drug administration in the morning.
Population: PKS including patients with available data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 400 mg Deleobuvir | Cmax and Cmax,ss of CD 6168 (Combined Treatment Part) | Cmax on Day 1 | 902 nmol/L | Geometric Coefficient of Variation 49.2 |
| 400 mg Deleobuvir | Cmax and Cmax,ss of CD 6168 (Combined Treatment Part) | Cmax,ss on Day 16 | 4860 nmol/L | Geometric Coefficient of Variation 60.5 |
Primary
Cmax and Cmax,ss of Deleobuvir (Combined Treatment Part)
Maximum measured concentration of Deleobuvir on Day 1 and at steady state on Day 16.
Time frame: After the first administration of Deleobuvir+Faldaprevir on Day 1 and after the last administration on Day 16 at 0 (5 min before administration on Day 16), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8,12 h after drug administration in the morning.
Population: PKS including patients with available data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 400 mg Deleobuvir | Cmax and Cmax,ss of Deleobuvir (Combined Treatment Part) | Cmax on Day 1 | 6930 nmol/L | Geometric Coefficient of Variation 47.9 |
| 400 mg Deleobuvir | Cmax and Cmax,ss of Deleobuvir (Combined Treatment Part) | Cmax,ss on Day 16 (N=14) | 9710 nmol/L | Geometric Coefficient of Variation 43.3 |
Primary
Cmax and Cmax,ss of Faldaprevir (Combined Treatment Part)
Maximum measured concentration of Faldaprevir on Day 1 and at steady state on Day 16.
Time frame: After the first administration of Deleobuvir+Faldaprevir on Day 1 and after the last administration on Day 16 at 0 (5 min before administration on Day 16), 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8,12, 24 h after drug administration in the morning.
Population: PKS including patients with available data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 400 mg Deleobuvir | Cmax and Cmax,ss of Faldaprevir (Combined Treatment Part) | Cmax on Day 1 | 4060.0 nmol/L | Geometric Coefficient of Variation 25 |
| 400 mg Deleobuvir | Cmax and Cmax,ss of Faldaprevir (Combined Treatment Part) | Cmax,ss on Day 16 (N=14) | 5940.0 nmol/L | Geometric Coefficient of Variation 32.3 |
Primary
Number of Healthy Subjects With AEs (Multiple Rising Dose Part)
Number of healthy subjects with any adverse event (AE) during the on-treatment period.
Time frame: From first drug administration (Day 1) until end of trial examination (15 to 21 days after first administration)
Population: Treated Set. The treated set included all subjects who were documented to have taken at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 400 mg Deleobuvir | Number of Healthy Subjects With AEs (Multiple Rising Dose Part) | 6 participants |
| 600 mg Deleobuvir | Number of Healthy Subjects With AEs (Multiple Rising Dose Part) | 5 participants |
Secondary
AUC(0-12h) and AUC(0-12h,ss) of BI 208333 (Multiple Rising Dose Part)
Area under the concentration-time curve of BI 208333 over the uniform dosing interval 0 to 12 h on Day 1 and at steady state on Day 9. BI 208333 is a major metabolite of Deleobuvir.
Time frame: After the first administration of Deleobuvir on Day 1 and after the last administration on Day 9: at 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8,12 h after drug administration in the morning.
Population: PKS including patients with available data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 400 mg Deleobuvir | AUC(0-12h) and AUC(0-12h,ss) of BI 208333 (Multiple Rising Dose Part) | AUC(0-12h) on Day 1 | 3940 nmol*h/L | Geometric Coefficient of Variation 38.7 |
| 400 mg Deleobuvir | AUC(0-12h) and AUC(0-12h,ss) of BI 208333 (Multiple Rising Dose Part) | AUC(0-12h,ss) on Day 9 | 2840 nmol*h/L | Geometric Coefficient of Variation 51.7 |
| 600 mg Deleobuvir | AUC(0-12h) and AUC(0-12h,ss) of BI 208333 (Multiple Rising Dose Part) | AUC(0-12h) on Day 1 | 6060 nmol*h/L | Geometric Coefficient of Variation 57.1 |
| 600 mg Deleobuvir | AUC(0-12h) and AUC(0-12h,ss) of BI 208333 (Multiple Rising Dose Part) | AUC(0-12h,ss) on Day 9 | 5270 nmol*h/L | Geometric Coefficient of Variation 102 |
Secondary
AUC(0-12h) and AUC(0-12h,ss) of CD 6168 Acylglucuronide (Multiple Rising Dose Part)
Area under the concentration-time curve of CD 6168 acylglucuronide over the uniform dosing interval 0 to 12 h on Day 1 and at steady state on Day 9. CD 6168 acylglucuronide is a metabolite of Deleobuvir.
Time frame: After the first administration of Deleobuvir on Day 1 and after the last administration on Day 9: at 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8,12 h after drug administration in the morning.
Population: PKS including patients with available data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 400 mg Deleobuvir | AUC(0-12h) and AUC(0-12h,ss) of CD 6168 Acylglucuronide (Multiple Rising Dose Part) | AUC(0-12h) on Day 1 | 155 nmol*h/L | Geometric Coefficient of Variation 27.2 |
| 400 mg Deleobuvir | AUC(0-12h) and AUC(0-12h,ss) of CD 6168 Acylglucuronide (Multiple Rising Dose Part) | AUC(0-12h,ss) on Day 9 (N=6, 7) | 256 nmol*h/L | Geometric Coefficient of Variation 42.7 |
| 600 mg Deleobuvir | AUC(0-12h) and AUC(0-12h,ss) of CD 6168 Acylglucuronide (Multiple Rising Dose Part) | AUC(0-12h) on Day 1 | 342 nmol*h/L | Geometric Coefficient of Variation 66 |
| 600 mg Deleobuvir | AUC(0-12h) and AUC(0-12h,ss) of CD 6168 Acylglucuronide (Multiple Rising Dose Part) | AUC(0-12h,ss) on Day 9 (N=6, 7) | 701 nmol*h/L | Geometric Coefficient of Variation 94 |
Secondary
AUC(0-12h) and AUC(0-12h,ss) of CD 6168 (Multiple Rising Dose Part)
Area under the concentration-time curve of CD 6168 over the uniform dosing interval 0 to 12 h on Day 1 and at steady state on Day 9. CD 6168 is a major metabolite of Deleobuvir.
Time frame: After the first administration of Deleobuvir on Day 1 and after the last administration on Day 9: at 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8,12 h after drug administration in the morning.
Population: PKS including patients with available data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 400 mg Deleobuvir | AUC(0-12h) and AUC(0-12h,ss) of CD 6168 (Multiple Rising Dose Part) | AUC(0-12h) on Day 1 | 1690 nmol*h/L | Geometric Coefficient of Variation 56 |
| 400 mg Deleobuvir | AUC(0-12h) and AUC(0-12h,ss) of CD 6168 (Multiple Rising Dose Part) | AUC(0-12h,ss) on Day 9 | 2810 nmol*h/L | Geometric Coefficient of Variation 63.1 |
| 600 mg Deleobuvir | AUC(0-12h) and AUC(0-12h,ss) of CD 6168 (Multiple Rising Dose Part) | AUC(0-12h) on Day 1 | 2920 nmol*h/L | Geometric Coefficient of Variation 88.3 |
| 600 mg Deleobuvir | AUC(0-12h) and AUC(0-12h,ss) of CD 6168 (Multiple Rising Dose Part) | AUC(0-12h,ss) on Day 9 | 6960 nmol*h/L | Geometric Coefficient of Variation 106 |
Secondary
AUC(0-12h) and AUC(0-12h,ss) of Deleobuvir (Multiple Rising Dose Part)
Area under the concentration-time curve of Deleobuvir over the uniform dosing interval 0 to 12 h on Day 1 and at steady state on Day 9.
Time frame: After the first administration of Deleobuvir on Day 1 and after the last administration on Day 9: at 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8,12 h after drug administration in the morning.
Population: PKS including patients with available data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 400 mg Deleobuvir | AUC(0-12h) and AUC(0-12h,ss) of Deleobuvir (Multiple Rising Dose Part) | AUC(0-12h) on Day 1 | 8210 nmol*h/L | Geometric Coefficient of Variation 45.5 |
| 400 mg Deleobuvir | AUC(0-12h) and AUC(0-12h,ss) of Deleobuvir (Multiple Rising Dose Part) | AUC(0-12h,ss) on Day 9 | 6160 nmol*h/L | Geometric Coefficient of Variation 45.2 |
| 600 mg Deleobuvir | AUC(0-12h) and AUC(0-12h,ss) of Deleobuvir (Multiple Rising Dose Part) | AUC(0-12h) on Day 1 | 18000 nmol*h/L | Geometric Coefficient of Variation 77.6 |
| 600 mg Deleobuvir | AUC(0-12h) and AUC(0-12h,ss) of Deleobuvir (Multiple Rising Dose Part) | AUC(0-12h,ss) on Day 9 | 18500 nmol*h/L | Geometric Coefficient of Variation 93.3 |
Secondary
Cmax and Cmax,ss of BI 208333 (Multiple Rising Dose Part)
Maximum measured concentration of BI 208333 on Day 1 and at steady state on Day 9. BI 208333 is a major metabolite of Deleobuvir.
Time frame: After the first administration of Deleobuvir on Day 1 and after the last administration on Day 9: at 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8,12 h after drug administration in the morning.
Population: PKS including patients with available data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 400 mg Deleobuvir | Cmax and Cmax,ss of BI 208333 (Multiple Rising Dose Part) | Cmax on Day 1 | 766 nmol/L | Geometric Coefficient of Variation 41.5 |
| 400 mg Deleobuvir | Cmax and Cmax,ss of BI 208333 (Multiple Rising Dose Part) | Cmax,ss on Day 9 | 576 nmol/L | Geometric Coefficient of Variation 44.4 |
| 600 mg Deleobuvir | Cmax and Cmax,ss of BI 208333 (Multiple Rising Dose Part) | Cmax on Day 1 | 1050 nmol/L | Geometric Coefficient of Variation 54.2 |
| 600 mg Deleobuvir | Cmax and Cmax,ss of BI 208333 (Multiple Rising Dose Part) | Cmax,ss on Day 9 | 983 nmol/L | Geometric Coefficient of Variation 82.4 |
Secondary
Cmax and Cmax,ss of CD 6168 Acylglucuronide (Multiple Rising Dose Part)
Maximum measured concentration of CD 6168 acylglucuronide on Day 1 and at steady state on Day 9. CD 6168 acylglucuronide is a metabolite of Deleobuvir.
Time frame: After the first administration of Deleobuvir on Day 1 and after the last administration on Day 9: at 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8,12 h after drug administration in the morning.
Population: PKS including patients with available data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 400 mg Deleobuvir | Cmax and Cmax,ss of CD 6168 Acylglucuronide (Multiple Rising Dose Part) | Cmax on Day 1 | 27.3 nmol/L | Geometric Coefficient of Variation 36.8 |
| 400 mg Deleobuvir | Cmax and Cmax,ss of CD 6168 Acylglucuronide (Multiple Rising Dose Part) | Cmax,ss on Day 9 | 33.3 nmol/L | Geometric Coefficient of Variation 61.3 |
| 600 mg Deleobuvir | Cmax and Cmax,ss of CD 6168 Acylglucuronide (Multiple Rising Dose Part) | Cmax on Day 1 | 57.9 nmol/L | Geometric Coefficient of Variation 61 |
| 600 mg Deleobuvir | Cmax and Cmax,ss of CD 6168 Acylglucuronide (Multiple Rising Dose Part) | Cmax,ss on Day 9 | 116.0 nmol/L | Geometric Coefficient of Variation 80.6 |
Secondary
Cmax and Cmax,ss of CD 6168 (Multiple Rising Dose Part)
Maximum measured concentration of CD 6168 on Day 1 and at steady state on Day 9. CD 6168 is a major metabolite of Deleobuvir.
Time frame: After the first administration of Deleobuvir on Day 1 and after the last administration on Day 9: at 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8,12 h after drug administration in the morning.
Population: PKS including patients with available data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 400 mg Deleobuvir | Cmax and Cmax,ss of CD 6168 (Multiple Rising Dose Part) | Cmax on Day 1 | 329 nmol/L | Geometric Coefficient of Variation 60.5 |
| 400 mg Deleobuvir | Cmax and Cmax,ss of CD 6168 (Multiple Rising Dose Part) | Cmax,ss on Day 9 | 451 nmol/L | Geometric Coefficient of Variation 66.3 |
| 600 mg Deleobuvir | Cmax and Cmax,ss of CD 6168 (Multiple Rising Dose Part) | Cmax on Day 1 | 516 nmol/L | Geometric Coefficient of Variation 92.7 |
| 600 mg Deleobuvir | Cmax and Cmax,ss of CD 6168 (Multiple Rising Dose Part) | Cmax,ss on Day 9 | 1130 nmol/L | Geometric Coefficient of Variation 90.9 |
Secondary
Cmax and Cmax,ss of Deleobuvir (Multiple Rising Dose Part)
Maximum measured concentration of Deleobuvir on Day 1 and at steady state on Day 9.
Time frame: After the first administration of Deleobuvir on Day 1 and after the last administration on Day 9: at 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8,12 h after drug administration in the morning.
Population: PKS including patients with available data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 400 mg Deleobuvir | Cmax and Cmax,ss of Deleobuvir (Multiple Rising Dose Part) | Cmax on Day 1 | 2010 nmol/L | Geometric Coefficient of Variation 41.5 |
| 400 mg Deleobuvir | Cmax and Cmax,ss of Deleobuvir (Multiple Rising Dose Part) | Cmax,ss on Day 9 | 1380 nmol/L | Geometric Coefficient of Variation 48.3 |
| 600 mg Deleobuvir | Cmax and Cmax,ss of Deleobuvir (Multiple Rising Dose Part) | Cmax on Day 1 | 3740 nmol/L | Geometric Coefficient of Variation 79.4 |
| 600 mg Deleobuvir | Cmax and Cmax,ss of Deleobuvir (Multiple Rising Dose Part) | Cmax,ss on Day 9 | 3650 nmol/L | Geometric Coefficient of Variation 91.6 |