Healthy
Conditions
Brief summary
Obtain interaction data between BI 201335 and Efavirenz to guide dosing for each drug when administered together. To predict drug interaction between BI 201335 and Cyp 3A4 y using Midazolam as cyp 3A4 probe , Efavirenz as enzyme inducer and BI 201335 as enzyme inhibitor.
Interventions
DRUGlow dose
efavirenz single dosing once daily
DRUGnormal dose
efavirenz once daily
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Healthy volunteers age 18- 55 BMI (Body Mass Index) 18.5 - 29.9
Exclusion criteria
1. Any finding on medical examination and ECG (Electrocardiography) deviating from normal 2. Active diseases 3. History of photosensitivity or rash
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Group A - Efavirenz: Cmax | 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 24:00, 48:00, 72:00, 96:00, 120:00, 144:00 hours(h) after administration of Efavirenz | Maximum plasma concentration (Cmax) of Efavirenz calculated for subjects in sequence group A (240 mg Faldaprevir+50 mg Efavirenz) |
| Group A - Efavirenz: AUC0-∞ | 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 24:00, 48:00, 72:00, 96:00, 120:00, 144:00 h after administration of Efavirenz | Area under the concentration-time curve of the analyte in plasma over the time interval 0 to infinity of Efavirenz calculated for subjects in sequence group A (240 mg Faldaprevir+50 mg Efavirenz) |
| Group B - Faldaprevir: Cmax,ss | 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00 h after first administration of Faldaprevir | Maximum plasma concentration at steady state of Faldaprevir calculated for subjects in sequence group B (600 mg Efavirenz+240 mg Faldaprevir+7.5 mg Midazolam) |
| Group B - Faldaprevir: AUC0-12h,ss | 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00 h after first administration of Faldaprevir | Area under the concentration-time curve of Faldaprevir at steady state over the time interval 0 to 12h calculated for subjects in sequence group B (600 mg Efavirenz+240 mg Faldaprevir+7.5 mg Midazolam) |
| Group B - Faldaprevir: C12,ss | 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00 h after first administration of Faldaprevir | Plasma concentration 12 h after dosing of Faldaprevir at steady state calculated for subjects in sequence group B (600 mg Efavirenz+240 mg Faldaprevir+7.5 mg Midazolam) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Group B - Faldaprevir: Tmax,ss | 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00 h after administration of Faldaprevir | Time of maximum concentration of Faldaprevir on Day 9 and 10 at steady state, calculated for patients in sequence group B (600 mg Efavirenz+240 mg Faldaprevir+7.5 mg Midazolam) |
| Group B - Midazolam: Cmax | 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 14:00, 24:00 h after administration of Midazolam | Maximum plasma concentration of Midazolam on days 1, 9 and 18, calculated for subjects in sequence group B (600 mg Efavirenz+240 mg Faldaprevir+7.5 mg Midazolam) |
| Group B - Midazolam: Tmax | 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 14:00, 24:00 h after administration of Midazolam | Time of maximum concentration after a single dose of Midazolam on days 1, 9 and 18, calculated for subjects in sequence group B (600 mg Efavirenz+240 mg Faldaprevir+7.5 mg Midazolam) |
| Group A - Faldaprevir: Cmax,ss | 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00 h after administration of Faldaprevir | Maximum plasma concentration of Faldaprevir on day 14 at steady state, calculated for subjects in sequence group A (240 mg Faldaprevir+50 mg Efavirenz) |
| Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Physical Examination and ECG | From first treatment administration (Day 1) up to Day 24 | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Physical Examination and ECG. New abnormal findings or worsening of baseline conditions were reported as Adverse Events. |
| Group A - Number of Participants With Drug Related Adverse Events | From Day 1 up to 30 days after last treatment (Days 1,2,3,4,5,6,7,8,11,13,14,15,16,17,18,19,20,24) | Number of participants with investigator-defined drug related adverse events (AE) in sequence group A. AEs occurring up to 5 days after last intake of Faldaprevir on day 19 were assigned to Efavirenz+Faldaprevir treatment. AEs were assessed throughout the trial. During the outpatient portion of the trial, assessment of AEs was monitored by telephone. |
| Group B - Number of Participants With Drug Related Adverse Events | From Day 1 up to 30 days after last treatment (Days 1,2,6,8,9,10,11,14,17,18,19,24) | Number of participants with investigator-defined drug related adverse events (AE) in sequence group B. AEs occurring up to 5 days after last intake of Faldaprevir were assigned to Faldaprevir+Midazolam+Efavirenz treatment. AEs were assessed throughout the trial. During the outpatient portion of the trial, assessment of AEs was monitored by telephone. |
| Group B - Midazolam: AUC0-∞ | 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 14:00, 24:00 h after administration of Midazolam | Area under the concentration-time curve of of Midazolam over the time interval 0 to infinity on days 1, 9 and 18, calculated for subjects in sequence group B (600 mg Efavirenz+240 mg Faldaprevir+7.5 mg Midazolam) |
| Group A - Faldaprevir: Tmax,ss | 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00 h after administration of Faldaprevir | Time of maximum concentration of Faldaprevir on day 14 at steady state, calculated for subjects in sequence group A (240 mg Faldaprevir+50 mg Efavirenz) |
| Group A - Faldaprevir: AUC0-12h,ss | 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00 h after administration of Faldaprevir | Area under the concentration-time curve of Faldaprevir over the time interval 0-12h on day 14 at steady state, calculated for subjects in sequence group A (240 mg Faldaprevir+50 mg Efavirenz) |
| Group A - Faldaprevir: C12,ss | 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00 h after administration of Faldaprevir | Plasma concentration 12 h after dosing of Faldaprevir on day 14 at steady state, calculated for subjects in sequence group A (240 mg Faldaprevir+50 mg Efavirenz) |
| Group A - Efavirenz: Tmax | 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00 h after administration of Efavirenz | Time of maximum concentration of Efavirenz on day 14, calculated for subjects in sequence group A (240 mg Faldaprevir+50 mg Efavirenz) |
Countries
Switzerland
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group A: 240 mg Faldaprevir+50 mg Efavirenz Faldaprevir (soft gel capsule): Loading dose (480 mg) on day 7 followed by 240 mg doses twice a day until day 19.
Efavirenz (film-coated tablet): Single dose (50 mg) on day 1 and 14.
oral administration with water after food intake. | 14 |
| Group B: 600 mg Efavirenz+240 mg Feldaprevir+7.5 mg Midazolam Faldaprevir (soft gel capsule): Loading dose (480 mg) on day 2 followed by 240 mg doses twice a day until day 18.
Efavirenz (film-coated tablet): 600 mg on days 10 to 18 once a day. Midazolam (tablet): Single dose (7.5 mg) on day 1, 9 and 18.
oral administration with water after food intake. | 15 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | Group A: 240 mg Faldaprevir+50 mg Efavirenz | Group B: 600 mg Efavirenz+240 mg Feldaprevir+7.5 mg Midazolam | Total |
|---|---|---|---|
| Age, Continuous | 39.4 years STANDARD_DEVIATION 10.7 | 33.1 years STANDARD_DEVIATION 11.6 | 36.1 years STANDARD_DEVIATION 11.5 |
| Sex: Female, Male Female | 8 Participants | 6 Participants | 14 Participants |
| Sex: Female, Male Male | 6 Participants | 9 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 14 | 13 / 14 | 11 / 13 | 1 / 15 | 14 / 15 | 6 / 15 | 15 / 15 |
| serious Total, serious adverse events | 0 / 14 | 0 / 14 | 0 / 13 | 0 / 15 | 0 / 15 | 0 / 15 | 0 / 15 |
Outcome results
Primary
Group A - Efavirenz: AUC0-∞
Area under the concentration-time curve of the analyte in plasma over the time interval 0 to infinity of Efavirenz calculated for subjects in sequence group A (240 mg Faldaprevir+50 mg Efavirenz)
Time frame: 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 24:00, 48:00, 72:00, 96:00, 120:00, 144:00 h after administration of Efavirenz
Population: all subjects entered in sequence group A of the PK set.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 50 mg Efavirenz | Group A - Efavirenz: AUC0-∞ | 36100.0 nmol*h/L | Geometric Coefficient of Variation 30.3 |
| 50 mg Efavirenz+240 mg Faldaprevir | Group A - Efavirenz: AUC0-∞ | 40700.0 nmol*h/L | Geometric Coefficient of Variation 28.8 |
Comparison: relative bioavailability comparison (50 mg Efavirenz+240 mg Faldaprevir : 50 mg Efavirenz) of Efavirenz90% CI: [101.87, 132.35]ANOVA
Primary
Group A - Efavirenz: Cmax
Maximum plasma concentration (Cmax) of Efavirenz calculated for subjects in sequence group A (240 mg Faldaprevir+50 mg Efavirenz)
Time frame: 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 24:00, 48:00, 72:00, 96:00, 120:00, 144:00 hours(h) after administration of Efavirenz
Population: all subjects entered in sequence group A of the PK set. Pharmacokinetic (PK) set: This subject set included all subjects of the treated set who provided evaluable data for at least1 observation for at least 1 primary PK endpoint in any trial period without important protocol violations.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 50 mg Efavirenz | Group A - Efavirenz: Cmax | 771.0 nmol/L | Geometric Coefficient of Variation 29.1 |
| 50 mg Efavirenz+240 mg Faldaprevir | Group A - Efavirenz: Cmax | 809.0 nmol/L | Geometric Coefficient of Variation 19.9 |
Comparison: relative bioavailability comparison (50 mg Efavirenz+240 mg Faldaprevir : 50 mg Efavirenz) of Efavirenz90% CI: [90.81, 122.82]ANOVA
Primary
Group B - Faldaprevir: AUC0-12h,ss
Area under the concentration-time curve of Faldaprevir at steady state over the time interval 0 to 12h calculated for subjects in sequence group B (600 mg Efavirenz+240 mg Faldaprevir+7.5 mg Midazolam)
Time frame: 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00 h after first administration of Faldaprevir
Population: all subjects entered in sequence group B of the PK set.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 50 mg Efavirenz | Group B - Faldaprevir: AUC0-12h,ss | 225000.0 ng*h/mL | Geometric Coefficient of Variation 91.1 |
| 50 mg Efavirenz+240 mg Faldaprevir | Group B - Faldaprevir: AUC0-12h,ss | 146000.0 ng*h/mL | Geometric Coefficient of Variation 148 |
Comparison: relative bioavailability comparison (7.5 mg Midazolam+240 mg Faldaprevir+600 mg Efavirenz : 7.5 mg Midazolam+240 mg Faldaprevir) of Faldaprevir90% CI: [53.32, 79.16]ANOVA
Primary
Group B - Faldaprevir: C12,ss
Plasma concentration 12 h after dosing of Faldaprevir at steady state calculated for subjects in sequence group B (600 mg Efavirenz+240 mg Faldaprevir+7.5 mg Midazolam)
Time frame: 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00 h after first administration of Faldaprevir
Population: all subjects entered in sequence group B of the PK set.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 50 mg Efavirenz | Group B - Faldaprevir: C12,ss | 14700.0 ng/mL | Geometric Coefficient of Variation 119 |
| 50 mg Efavirenz+240 mg Faldaprevir | Group B - Faldaprevir: C12,ss | 7650.0 ng/mL | Geometric Coefficient of Variation 277 |
Comparison: relative bioavailability comparison (7.5 mg Midazolam+240 mg Faldaprevir+600 mg Efavirenz : 7.5 mg Midazolam+240 mg Faldaprevir) of Faldaprevir90% CI: [40.47, 72.88]ANOVA
Primary
Group B - Faldaprevir: Cmax,ss
Maximum plasma concentration at steady state of Faldaprevir calculated for subjects in sequence group B (600 mg Efavirenz+240 mg Faldaprevir+7.5 mg Midazolam)
Time frame: 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00 h after first administration of Faldaprevir
Population: all subjects entered in sequence group B of the PK set.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 50 mg Efavirenz | Group B - Faldaprevir: Cmax,ss | 24000.0 ng/mL | Geometric Coefficient of Variation 76.4 |
| 50 mg Efavirenz+240 mg Faldaprevir | Group B - Faldaprevir: Cmax,ss | 17200.0 ng/mL | Geometric Coefficient of Variation 111 |
Comparison: relative bioavailability comparison (7.5 mg Midazolam+240 mg Faldaprevir+600 mg Efavirenz : 7.5 mg Midazolam+240 mg Faldaprevir) of Faldaprevir90% CI: [61.46, 83.95]ANOVA
Secondary
Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Physical Examination and ECG
Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Physical Examination and ECG. New abnormal findings or worsening of baseline conditions were reported as Adverse Events.
Time frame: From first treatment administration (Day 1) up to Day 24
Population: treated set: All subjects who were dispensed study medication and were documented to have taken at least 1 dose of trial medication
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 50 mg Efavirenz | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Physical Examination and ECG | Weight decreased | 1 participants |
| 50 mg Efavirenz | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Physical Examination and ECG | Hepatic enzyme increased | 0 participants |
| 50 mg Efavirenz+240 mg Faldaprevir | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Physical Examination and ECG | Weight decreased | 0 participants |
| 50 mg Efavirenz+240 mg Faldaprevir | Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Physical Examination and ECG | Hepatic enzyme increased | 1 participants |
Secondary
Group A - Efavirenz: Tmax
Time of maximum concentration of Efavirenz on day 14, calculated for subjects in sequence group A (240 mg Faldaprevir+50 mg Efavirenz)
Time frame: 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00 h after administration of Efavirenz
Population: All patients entered in sequence group A of the PK set
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| 50 mg Efavirenz | Group A - Efavirenz: Tmax | Day 1: Efavirenz | 3.00 hours | Full Range 1.41 |
| 50 mg Efavirenz | Group A - Efavirenz: Tmax | Day 14: Efavirenz+Faldaprevir (N=13) | 3.03 hours | — |
Secondary
Group A - Faldaprevir: AUC0-12h,ss
Area under the concentration-time curve of Faldaprevir over the time interval 0-12h on day 14 at steady state, calculated for subjects in sequence group A (240 mg Faldaprevir+50 mg Efavirenz)
Time frame: 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00 h after administration of Faldaprevir
Population: All patients entered in sequence group A of the PK set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 50 mg Efavirenz | Group A - Faldaprevir: AUC0-12h,ss | 341000 ng*h/mL | Geometric Coefficient of Variation 27.2 |
Secondary
Group A - Faldaprevir: C12,ss
Plasma concentration 12 h after dosing of Faldaprevir on day 14 at steady state, calculated for subjects in sequence group A (240 mg Faldaprevir+50 mg Efavirenz)
Time frame: 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00 h after administration of Faldaprevir
Population: All patients entered in sequence group A of the PK set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 50 mg Efavirenz | Group A - Faldaprevir: C12,ss | 23900 ng/mL | Geometric Coefficient of Variation 27.7 |
Secondary
Group A - Faldaprevir: Cmax,ss
Maximum plasma concentration of Faldaprevir on day 14 at steady state, calculated for subjects in sequence group A (240 mg Faldaprevir+50 mg Efavirenz)
Time frame: 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00 h after administration of Faldaprevir
Population: All patients entered in sequence group A of the PK set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 50 mg Efavirenz | Group A - Faldaprevir: Cmax,ss | 34600.0 ng/mL | Geometric Coefficient of Variation 26 |
Secondary
Group A - Faldaprevir: Tmax,ss
Time of maximum concentration of Faldaprevir on day 14 at steady state, calculated for subjects in sequence group A (240 mg Faldaprevir+50 mg Efavirenz)
Time frame: 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00 h after administration of Faldaprevir
Population: All patients entered in sequence sequence group A of the PK set
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| 50 mg Efavirenz | Group A - Faldaprevir: Tmax,ss | 3.00 hours | Full Range 0.836 |
Secondary
Group A - Number of Participants With Drug Related Adverse Events
Number of participants with investigator-defined drug related adverse events (AE) in sequence group A. AEs occurring up to 5 days after last intake of Faldaprevir on day 19 were assigned to Efavirenz+Faldaprevir treatment. AEs were assessed throughout the trial. During the outpatient portion of the trial, assessment of AEs was monitored by telephone.
Time frame: From Day 1 up to 30 days after last treatment (Days 1,2,3,4,5,6,7,8,11,13,14,15,16,17,18,19,20,24)
Population: all subjects entered in sequence group A of the treated set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 50 mg Efavirenz | Group A - Number of Participants With Drug Related Adverse Events | 2 participants |
| 50 mg Efavirenz+240 mg Faldaprevir | Group A - Number of Participants With Drug Related Adverse Events | 13 participants |
| Efavirenz+Faldaprevir | Group A - Number of Participants With Drug Related Adverse Events | 11 participants |
| Total On-treatment | Group A - Number of Participants With Drug Related Adverse Events | 13 participants |
Secondary
Group B - Faldaprevir: Tmax,ss
Time of maximum concentration of Faldaprevir on Day 9 and 10 at steady state, calculated for patients in sequence group B (600 mg Efavirenz+240 mg Faldaprevir+7.5 mg Midazolam)
Time frame: 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00 h after administration of Faldaprevir
Population: All patients entered in sequence group B of the PK set
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 50 mg Efavirenz | Group B - Faldaprevir: Tmax,ss | Day 9: Midazolam+Faldaprevir | 3.00 hours |
| 50 mg Efavirenz | Group B - Faldaprevir: Tmax,ss | Day 18: Midazolam+Faldaprevir+Efavirenz (N=14) | 2.02 hours |
Secondary
Group B - Midazolam: AUC0-∞
Area under the concentration-time curve of of Midazolam over the time interval 0 to infinity on days 1, 9 and 18, calculated for subjects in sequence group B (600 mg Efavirenz+240 mg Faldaprevir+7.5 mg Midazolam)
Time frame: 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 14:00, 24:00 h after administration of Midazolam
Population: all subjects entered in sequence group B of the PK set.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 50 mg Efavirenz | Group B - Midazolam: AUC0-∞ | Day 1: Midazolam | 278 nmol*h/L | Geometric Coefficient of Variation 28.3 |
| 50 mg Efavirenz | Group B - Midazolam: AUC0-∞ | Day 9: Midazolam+Faldaprevir | 624 nmol*h/L | Geometric Coefficient of Variation 54.3 |
| 50 mg Efavirenz | Group B - Midazolam: AUC0-∞ | Day 18: Midazolam+Faldaprevir+Efavirenz (N=14) | 110 nmol*h/L | Geometric Coefficient of Variation 88.1 |
Secondary
Group B - Midazolam: Cmax
Maximum plasma concentration of Midazolam on days 1, 9 and 18, calculated for subjects in sequence group B (600 mg Efavirenz+240 mg Faldaprevir+7.5 mg Midazolam)
Time frame: 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 14:00, 24:00 h after administration of Midazolam
Population: all subjects entered in sequence group B of the PK set.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 50 mg Efavirenz | Group B - Midazolam: Cmax | Day 1: Midazolam | 110.0 nmol/L | Geometric Coefficient of Variation 45.6 |
| 50 mg Efavirenz | Group B - Midazolam: Cmax | Day 9: Midazolam+Faldaprevir | 121.0 nmol/L | Geometric Coefficient of Variation 46.1 |
| 50 mg Efavirenz | Group B - Midazolam: Cmax | Day 18: Midazolam+Faldaprevir+Efavirenz (N=14) | 44.9 nmol/L | Geometric Coefficient of Variation 101 |
Secondary
Group B - Midazolam: Tmax
Time of maximum concentration after a single dose of Midazolam on days 1, 9 and 18, calculated for subjects in sequence group B (600 mg Efavirenz+240 mg Faldaprevir+7.5 mg Midazolam)
Time frame: 0:00, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 14:00, 24:00 h after administration of Midazolam
Population: all subjects entered in sequence group B of the PK set.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| 50 mg Efavirenz | Group B - Midazolam: Tmax | Day 18: Midazolam+Faldaprevir+Efavirenz (N=14) | 0.74 hours | Full Range 59 |
| 50 mg Efavirenz | Group B - Midazolam: Tmax | Day 1: Midazolam | 1.00 hours | Full Range 47 |
| 50 mg Efavirenz | Group B - Midazolam: Tmax | Day 9: Midazolam+Faldaprevir | 1.00 hours | Full Range 59.7 |
Secondary
Group B - Number of Participants With Drug Related Adverse Events
Number of participants with investigator-defined drug related adverse events (AE) in sequence group B. AEs occurring up to 5 days after last intake of Faldaprevir were assigned to Faldaprevir+Midazolam+Efavirenz treatment. AEs were assessed throughout the trial. During the outpatient portion of the trial, assessment of AEs was monitored by telephone.
Time frame: From Day 1 up to 30 days after last treatment (Days 1,2,6,8,9,10,11,14,17,18,19,24)
Population: all subjects entered in sequence group B of the treated set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 50 mg Efavirenz | Group B - Number of Participants With Drug Related Adverse Events | 1 participants |
| 50 mg Efavirenz+240 mg Faldaprevir | Group B - Number of Participants With Drug Related Adverse Events | 14 participants |
| Efavirenz+Faldaprevir | Group B - Number of Participants With Drug Related Adverse Events | 3 participants |
| Total On-treatment | Group B - Number of Participants With Drug Related Adverse Events | 14 participants |
| Total On-treatment | Group B - Number of Participants With Drug Related Adverse Events | 15 participants |