Hepatitis C, Chronic
Conditions
Brief summary
To evaluate the drug-drug interactions between BI 201335 and BI 207127 as well as their combined effect on CYP probe drug substrates and on tenofovir and raltegravir in treatment naive or prior treatment relapse patients with chronic hepatitis C infection.
Interventions
DRUGmidazolam
CYP3A probe drug
DRUGBI 201335
HCV protease inhibitor
DRUGtenofovir
nucleoside analogue
DRUGcaffeine
CYP1A2 probe drug
DRUGtolbutamide
CYP2C9 probe drug
DRUGpegylated interferon
HCV treatment
DRUGBI 207127
HCV polymerase inhibitor
DRUGribavirin
HCV treatment
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Chronic hepatitis C genotype 1 infection, diagnosed at least 6 months prior to screening 2. Treatment naive or confirmed prior treatment relapse or partial response following treatment with interferon and ribavirin 3. Age 18 to 70 years 4. HCV RNA (Hepatitis C Virus RiboNucleic Acid) = 1,000 IU/mL at screening 5. Liver biopsy or fibroscan to exclude cirrhosis
Exclusion criteria
1. Hepatitis C Virus (HCV) infection of mixed genotype; Hepatitis B Virus (HBV) or Human Immunodeficiency Virus (HIV) co-infection 2. Evidence of acute or chronic liver disease due to causes other than chronic HCV infection, 3. Decompensated liver disease, or history of decompensated liver disease, 4. Body weight \< 40 or \> 125 kg, 5. Clinical evidence of significant or unstable cardiovascular disease, chronic pulmonary disease, history or evidence of retinopathy or clinically significant ophthalmological disorder 6. Pre-existing psychiatric condition that could interfere with the subject's participation in and completion of the study 7. Laboratory parameters disorders (thalassemia major, sickle cell anemia or glucose 6 phosphate dehydrogenase deficit) 8. Hemoglobin \< 12 g/dL for women and \< 13 g/dL for men 9. Patients who have been previously treated with at least one dose of any antiviral or immunomodulatory drug other than interferon alfa or ribavirin for acute or chronic HCV infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC 0-12hr of Raltegravir | PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9 and 17 | Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 12 hours. |
| Cmax of Faldaprevir (BI 201335) | PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66. | Maximum concentration of an analyte in plasma |
| C24hr of Faldaprevir (BI 201335) | PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66. | Concentration of an analyte in plasma at 24 hours |
| Area Under the Concentration-time Curve (AUC) of Faldaprevir (BI 201335) From 0 to 24 Hours | PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66. | Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 24 hours |
| Cmax of Deleobuvir (BI 207127) | PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66. | Maximum concentration of an analyte in plasma |
| C6hr of Deleobuvir (BI 207127) | PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66. | Concentration of an analyte in plasma at 6 hours |
| AUC 0-6hr of Deleobuvir (BI 207127) | PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66. | Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 6 hours |
| Cmax of Deleobuvir Metabolite Acyl-glucuronide (BI 208333) | PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66. | Maximum concentration of an analyte in plasma |
| C6hr of Deleobuvir Metabolite Acyl-glucuronide (BI 208333) | PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66. | Concentration of an analyte in plasma at 6 hours |
| AUC 0-6hr of Deleobuvir Metabolite Acyl-glucuronide (BI 208333) | PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66. | Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 6 hours |
| Cmax of Deleobuvir Reduction Metabolite CD 6168 | PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66. | Maximum concentration of an analyte in plasma |
| C6hr of Deleobuvir Reduction Metabolite CD 6168 | PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66. | Concentration of an analyte in plasma at 6 hours |
| AUC 0-6hr of Deleobuvir Reduction Metabolite CD 6168 | PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66. | Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 6 hours |
| Cmax of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide) | PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66. | Maximum concentration of an analyte in plasma |
| C6hr of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide) | PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66. | Concentration of an analyte in plasma at 6 hours |
| AUC 0-6hr of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide) | PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66. | Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 6 hours |
| Cmax of Caffeine | 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66. | Maximum concentration of an analyte in plasma |
| Cmax of 1-OH-Midazolam (1-hydroxy-midazolam) | 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66. | Maximum concentration of an analyte in plasma |
| AUC 0-infinity of Caffeine | 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66. | Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity. |
| Cmax of Tolbutamide | 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66. | Maximum concentration of an analyte in plasma |
| AUC 0-infinity of Tolbutamide | 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66. | Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity. |
| Cmax of Midazolam | 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66. | Maximum concentration of an analyte in plasma |
| AUC 0-infinity of Midazolam | 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66. | Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity. |
| AUC 0-infinity of 1-OH-Midazolam (1-hydroxy-midazolam) | 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66. | Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity. |
| Cmax of Tenofovir | PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9 and 17 | Maximum concentration of an analyte in plasma. |
| C24hr of Tenofovir | PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9 and 17 | Concentration of an analyte in plasma at 24 hours. |
| AUC 0-24hr of Tenofovir | PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9 and 17 | Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 24 hours. |
| Cmax of Raltegravir | PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9 and 17 | Maximum concentration of an analyte in plasma. |
| C12hr of Raltegravir | PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9 and 17 | Concentration of an analyte in plasma at 12 hours. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Sustained Virological Response (SVR12) | 12 weeks post treatment | Sustained virologic response (SVR12): Plasma Hepatitis C virus Ribonucleic acid (HCV RNA) level \<25 IU/mL(international units per millilitre) undetectable at 12 weeks after the end of treatment. SVR12 was analyzed in a descriptive manner using frequency of participants who achieved SVR12. |
Countries
Canada, Germany, United States
Participant flow
Recruitment details
72 patients were treated and analysed.
Pre-assignment details
This was randomised (Groups A and B only), controlled, open-label, parallel-group (Groups A to E), multi-centre trial in treatment-naive patients and patients with prior treatment relapse or partial responders with Genotype 1 (GT1) chronic Hepatitis C infection.
Participants by arm
| Arm | Count |
|---|---|
| Group A 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a(PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group A the effect of DBV on FDV, the effect of FDV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined. | 16 |
| Group B 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a (PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group B the effect of FDV on DBV, the effect of DBV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined. | 19 |
| Group C 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with tenofovir tablet 300mg daily on days 1-17. | 16 |
| Group D 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily with probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). | 14 |
| Group E 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with raltegravir tablet 400mg twice daily on days 1-17. | 7 |
| Total | 72 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 2 | 0 | 1 |
| Overall Study | Lack of Efficacy | 0 | 2 | 2 | 1 | 2 |
| Overall Study | Lost to Follow-up | 1 | 1 | 0 | 0 | 0 |
| Overall Study | Other reason not defined above | 0 | 0 | 0 | 3 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Group A | Group B | Group C | Group D | Group E | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 48.2 Years STANDARD_DEVIATION 12.3 | 53.6 Years STANDARD_DEVIATION 9.3 | 53.1 Years STANDARD_DEVIATION 9.5 | 48.4 Years STANDARD_DEVIATION 12.7 | 52.1 Years STANDARD_DEVIATION 10.4 | 51.1 Years STANDARD_DEVIATION 10.9 |
| Sex: Female, Male Female | 7 Participants | 8 Participants | 5 Participants | 7 Participants | 1 Participants | 28 Participants |
| Sex: Female, Male Male | 9 Participants | 11 Participants | 11 Participants | 7 Participants | 6 Participants | 44 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 16 / 16 | 19 / 19 | 16 / 16 | 14 / 14 | 5 / 7 |
| serious Total, serious adverse events | 0 / 16 | 0 / 19 | 1 / 16 | 2 / 14 | 0 / 7 |
Outcome results
Primary
Area Under the Concentration-time Curve (AUC) of Faldaprevir (BI 201335) From 0 to 24 Hours
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 24 hours
Time frame: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
Population: The pharmacokinetic set (PKS): included all patients in the treated set who provided at least one observation for at least one primary (PK) endpoint without important protocol violations relevant to the evaluation of PK. This endpoint was not planned to be analysed for groups C, D and E.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group A | Area Under the Concentration-time Curve (AUC) of Faldaprevir (BI 201335) From 0 to 24 Hours | Day 9 (N=15,0) | 45600 ng*h/mL | Geometric Coefficient of Variation 54.5 |
| Group A | Area Under the Concentration-time Curve (AUC) of Faldaprevir (BI 201335) From 0 to 24 Hours | Day 17 (N=14,19) | 138000 ng*h/mL | Geometric Coefficient of Variation 62.1 |
| Group A | Area Under the Concentration-time Curve (AUC) of Faldaprevir (BI 201335) From 0 to 24 Hours | Day 66 (N=13,15) | 56200 ng*h/mL | Geometric Coefficient of Variation 58.2 |
| Group B | Area Under the Concentration-time Curve (AUC) of Faldaprevir (BI 201335) From 0 to 24 Hours | Day 9 (N=15,0) | NA ng*h/mL | — |
| Group B | Area Under the Concentration-time Curve (AUC) of Faldaprevir (BI 201335) From 0 to 24 Hours | Day 17 (N=14,19) | 173000 ng*h/mL | Geometric Coefficient of Variation 60.8 |
| Group B | Area Under the Concentration-time Curve (AUC) of Faldaprevir (BI 201335) From 0 to 24 Hours | Day 66 (N=13,15) | 97300 ng*h/mL | Geometric Coefficient of Variation 114 |
Comparison: Day 17 vs. Day 9p-value: 190% CI: [250.93, 374.26]ANOVA
Comparison: Day 66 vs. Day 9p-value: 0.618590% CI: [104.26, 161.71]ANOVA
Primary
AUC 0-12hr of Raltegravir
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 12 hours.
Time frame: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9 and 17
Population: PKS. Due to Boehringer Ingelheim's decision not to pursue the development of this substance, the extent of the statistical analysis was limited to selected endpoints. No further analysis is planned for the endpoints which were not related to patient efficacy or safety.
Primary
AUC 0-24hr of Tenofovir
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 24 hours.
Time frame: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9 and 17
Population: PKS. Due to Boehringer Ingelheim's decision not to pursue the development of this substance, the extent of the statistical analysis was limited to selected endpoints. No further analysis is planned for the endpoints which were not related to patient efficacy or safety.
Primary
AUC 0-6hr of Deleobuvir (BI 207127)
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 6 hours
Time frame: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
Population: The pharmacokinetic set (PKS): included all patients in the treated set who provided at least one observation for at least one primary (PK) endpoint without important protocol violations relevant to the evaluation of PK. This endpoint was not planned to be analysed for groups C, D and E.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group A | AUC 0-6hr of Deleobuvir (BI 207127) | Day 9 (N=0, 17) | NA nmol*h/L | — |
| Group A | AUC 0-6hr of Deleobuvir (BI 207127) | Day 17 (N=14, 19) | 119000 nmol*h/L | Geometric Coefficient of Variation 73.7 |
| Group A | AUC 0-6hr of Deleobuvir (BI 207127) | Day 66 (N=13, 15) | 36200 nmol*h/L | Geometric Coefficient of Variation 89 |
| Group B | AUC 0-6hr of Deleobuvir (BI 207127) | Day 9 (N=0, 17) | 41100 nmol*h/L | Geometric Coefficient of Variation 93.7 |
| Group B | AUC 0-6hr of Deleobuvir (BI 207127) | Day 17 (N=14, 19) | 135000 nmol*h/L | Geometric Coefficient of Variation 65 |
| Group B | AUC 0-6hr of Deleobuvir (BI 207127) | Day 66 (N=13, 15) | 59200 nmol*h/L | Geometric Coefficient of Variation 129 |
Comparison: Day 17 vs. Day 9p-value: 190% CI: [256.24, 406.34]ANOVA
Comparison: Day 66 vs. Day 9p-value: 0.746190% CI: [97.83, 217.69]ANOVA
Primary
AUC 0-6hr of Deleobuvir Metabolite Acyl-glucuronide (BI 208333)
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 6 hours
Time frame: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
Population: The pharmacokinetic set (PKS): included all patients in the treated set who provided at least one observation for at least one primary (PK) endpoint without important protocol violations relevant to the evaluation of PK. This endpoint was not planned to be analysed for groups C, D and E.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group A | AUC 0-6hr of Deleobuvir Metabolite Acyl-glucuronide (BI 208333) | Day 9 (N=0, 17) | NA nmol*h/L | — |
| Group A | AUC 0-6hr of Deleobuvir Metabolite Acyl-glucuronide (BI 208333) | Day 17 (N=14, 19) | 61800 nmol*h/L | Geometric Coefficient of Variation 97.9 |
| Group A | AUC 0-6hr of Deleobuvir Metabolite Acyl-glucuronide (BI 208333) | Day 66 (N=13, 15) | 15000 nmol*h/L | Geometric Coefficient of Variation 81.2 |
| Group B | AUC 0-6hr of Deleobuvir Metabolite Acyl-glucuronide (BI 208333) | Day 9 (N=0, 17) | 24300 nmol*h/L | Geometric Coefficient of Variation 131 |
| Group B | AUC 0-6hr of Deleobuvir Metabolite Acyl-glucuronide (BI 208333) | Day 17 (N=14, 19) | 98800 nmol*h/L | Geometric Coefficient of Variation 124 |
| Group B | AUC 0-6hr of Deleobuvir Metabolite Acyl-glucuronide (BI 208333) | Day 66 (N=13, 15) | 27600 nmol*h/L | Geometric Coefficient of Variation 128 |
Comparison: Day 17 vs. Day 9p-value: 190% CI: [332.19, 490.99]ANOVA
Comparison: Day 66 vs. Day 9p-value: 0.396890% CI: [75.38, 181.47]ANOVA
Primary
AUC 0-6hr of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide)
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 6 hours
Time frame: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
Population: The pharmacokinetic set (PKS): included all patients in the treated set who provided at least one observation for at least one primary (PK) endpoint without important protocol violations relevant to the evaluation of PK. This endpoint was not planned to be analysed for groups C, D and E.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group A | AUC 0-6hr of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide) | Day 9 (N=0, 17) | NA nmol*h/L | — |
| Group A | AUC 0-6hr of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide) | Day 17 (N=14, 19) | 2980 nmol*h/L | Geometric Coefficient of Variation 151 |
| Group A | AUC 0-6hr of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide) | Day 66 (N=13, 15) | 1620 nmol*h/L | Geometric Coefficient of Variation 133 |
| Group B | AUC 0-6hr of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide) | Day 9 (N=0, 17) | 893 nmol*h/L | Geometric Coefficient of Variation 142 |
| Group B | AUC 0-6hr of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide) | Day 17 (N=14, 19) | 5700 nmol*h/L | Geometric Coefficient of Variation 123 |
| Group B | AUC 0-6hr of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide) | Day 66 (N=13, 15) | 3510 nmol*h/L | Geometric Coefficient of Variation 143 |
Comparison: Day 17 vs. Day 9p-value: 190% CI: [471.42, 779.74]ANOVA
Comparison: Day 66 vs. Day 9p-value: 0.999490% CI: [233.48, 611.91]ANOVA
Primary
AUC 0-6hr of Deleobuvir Reduction Metabolite CD 6168
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 6 hours
Time frame: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
Population: The pharmacokinetic set (PKS): included all patients in the treated set who provided at least one observation for at least one primary (PK) endpoint without important protocol violations relevant to the evaluation of PK. This endpoint was not planned to be analysed for groups C, D and E.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group A | AUC 0-6hr of Deleobuvir Reduction Metabolite CD 6168 | Day 9 (N=0, 17) | NA nmol*h/L | — |
| Group A | AUC 0-6hr of Deleobuvir Reduction Metabolite CD 6168 | Day 17 (N=14, 19) | 41700 nmol*h/L | Geometric Coefficient of Variation 130 |
| Group A | AUC 0-6hr of Deleobuvir Reduction Metabolite CD 6168 | Day 66 (N=13, 15) | 19300 nmol*h/L | Geometric Coefficient of Variation 134 |
| Group B | AUC 0-6hr of Deleobuvir Reduction Metabolite CD 6168 | Day 9 (N=0, 17) | 13300 nmol*h/L | Geometric Coefficient of Variation 123 |
| Group B | AUC 0-6hr of Deleobuvir Reduction Metabolite CD 6168 | Day 17 (N=14, 19) | 62200 nmol*h/L | Geometric Coefficient of Variation 82.7 |
| Group B | AUC 0-6hr of Deleobuvir Reduction Metabolite CD 6168 | Day 66 (N=13, 15) | 39100 nmol*h/L | Geometric Coefficient of Variation 133 |
Comparison: Day 17 vs. Day 9p-value: 190% CI: [357.02, 610.66]ANOVA
Comparison: Day 66 vs. Day 9p-value: 0.997290% CI: [187.22, 476.15]ANOVA
Primary
AUC 0-infinity of 1-OH-Midazolam (1-hydroxy-midazolam)
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity.
Time frame: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.
Population: PKS. This endpoint was not planned to be analysed for groups C, D and E
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group A | AUC 0-infinity of 1-OH-Midazolam (1-hydroxy-midazolam) | Day 1 (N=16, 19) | 23.6 nmol*h/L | Geometric Coefficient of Variation 59.8 |
| Group A | AUC 0-infinity of 1-OH-Midazolam (1-hydroxy-midazolam) | Day 9 (N=15, 17) | 24.2 nmol*h/L | Geometric Coefficient of Variation 35.9 |
| Group A | AUC 0-infinity of 1-OH-Midazolam (1-hydroxy-midazolam) | Day 17 (N=14, 19) | 23.5 nmol*h/L | Geometric Coefficient of Variation 37.4 |
| Group A | AUC 0-infinity of 1-OH-Midazolam (1-hydroxy-midazolam) | Day 66 (N=13, 13) | 18.3 nmol*h/L | Geometric Coefficient of Variation 26.7 |
| Group B | AUC 0-infinity of 1-OH-Midazolam (1-hydroxy-midazolam) | Day 66 (N=13, 13) | 20.8 nmol*h/L | Geometric Coefficient of Variation 46.1 |
| Group B | AUC 0-infinity of 1-OH-Midazolam (1-hydroxy-midazolam) | Day 1 (N=16, 19) | 26.0 nmol*h/L | Geometric Coefficient of Variation 65.2 |
| Group B | AUC 0-infinity of 1-OH-Midazolam (1-hydroxy-midazolam) | Day 17 (N=14, 19) | 22.8 nmol*h/L | Geometric Coefficient of Variation 49.8 |
| Group B | AUC 0-infinity of 1-OH-Midazolam (1-hydroxy-midazolam) | Day 9 (N=15, 17) | 28.5 nmol*h/L | Geometric Coefficient of Variation 63.9 |
Comparison: Day 9 vs. Day 1p-value: 0.115990% CI: [77.89, 135.39]ANOVA
Comparison: Day 17 vs. Day 1p-value: 0.065190% CI: [78.33, 127.64]ANOVA
Comparison: Day 66 vs. Day 1p-value: 0.565890% CI: [62.5, 98.07]ANOVA
Comparison: Day 9 vs. Day 1p-value: 0.128690% CI: [87.46, 133.99]ANOVA
Comparison: Day 17 vs. Day 1p-value: 0.189890% CI: [73.56, 104.3]ANOVA
Comparison: Day 66 vs. Day 1p-value: 0.557590% CI: [61.81, 99.51]ANOVA
Primary
AUC 0-infinity of Caffeine
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity.
Time frame: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.
Population: PKS. This endpoint was not planned to be analysed for groups C, D and E
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group A | AUC 0-infinity of Caffeine | Day 1 (N=16, 19) | 54900 ng*h/mL | Geometric Coefficient of Variation 130 |
| Group A | AUC 0-infinity of Caffeine | Day 9 (N=15, 15) | 42100 ng*h/mL | Geometric Coefficient of Variation 96 |
| Group A | AUC 0-infinity of Caffeine | Day 17 (N=14, 19) | 71900 ng*h/mL | Geometric Coefficient of Variation 169 |
| Group A | AUC 0-infinity of Caffeine | Day 66 (N=13, 15) | 120000 ng*h/mL | Geometric Coefficient of Variation 220 |
| Group B | AUC 0-infinity of Caffeine | Day 66 (N=13, 15) | 159000 ng*h/mL | Geometric Coefficient of Variation 138 |
| Group B | AUC 0-infinity of Caffeine | Day 1 (N=16, 19) | 77500 ng*h/mL | Geometric Coefficient of Variation 119 |
| Group B | AUC 0-infinity of Caffeine | Day 17 (N=14, 19) | 170000 ng*h/mL | Geometric Coefficient of Variation 203 |
| Group B | AUC 0-infinity of Caffeine | Day 9 (N=15, 15) | 142000 ng*h/mL | Geometric Coefficient of Variation 109 |
Comparison: Day 9 vs. Day 1p-value: 0.103790% CI: [77.39, 100.89]ANOVA
Comparison: Day 17 vs. Day 1p-value: 0.872390% CI: [111.06, 227.93]ANOVA
Comparison: Day 66 vs. Day 1p-value: 0.98390% CI: [150.65, 447.21]ANOVA
Comparison: Day 9 vs. Day 1p-value: 0.968990% CI: [129.52, 207.52]ANOVA
Comparison: Day 17 vs. Day 1p-value: 0.993390% CI: [153.84, 314.26]ANOVA
Comparison: Day 66 vs. Day 1p-value: 0.986590% CI: [145.88, 315.09]ANOVA
Primary
AUC 0-infinity of Midazolam
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity.
Time frame: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.
Population: PKS. This endpoint was not planned to be analysed for groups C, D and E
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group A | AUC 0-infinity of Midazolam | Day 1 (N=16, 19) | 79.7 nmol*h/L | Geometric Coefficient of Variation 59.1 |
| Group A | AUC 0-infinity of Midazolam | Day 9 (N=15, 17) | 117 nmol*h/L | Geometric Coefficient of Variation 58.2 |
| Group A | AUC 0-infinity of Midazolam | Day 17 (N=14, 19) | 127 nmol*h/L | Geometric Coefficient of Variation 50.2 |
| Group A | AUC 0-infinity of Midazolam | Day 66 (N=13, 15) | 75.5 nmol*h/L | Geometric Coefficient of Variation 46.7 |
| Group B | AUC 0-infinity of Midazolam | Day 66 (N=13, 15) | 95.6 nmol*h/L | Geometric Coefficient of Variation 41.6 |
| Group B | AUC 0-infinity of Midazolam | Day 1 (N=16, 19) | 107 nmol*h/L | Geometric Coefficient of Variation 40.7 |
| Group B | AUC 0-infinity of Midazolam | Day 17 (N=14, 19) | 140 nmol*h/L | Geometric Coefficient of Variation 51.8 |
| Group B | AUC 0-infinity of Midazolam | Day 9 (N=15, 17) | 130 nmol*h/L | Geometric Coefficient of Variation 66.9 |
Comparison: Day 9 vs. Day 1p-value: 0.994190% CI: [134.79, 170.64]ANOVA
Comparison: Day 17 vs. Day 1p-value: 0.992690% CI: [137.91, 193.64]ANOVA
Comparison: Day 66 vs. Day 1p-value: 0.039290% CI: [81.2, 118.63]ANOVA
Comparison: Day 9 vs. Day 1p-value: 0.437490% CI: [99.15, 151.55]ANOVA
Comparison: Day 17 vs. Day 1p-value: 0.64790% CI: [107.57, 158.18]ANOVA
Comparison: Day 66 vs. Day 1p-value: 0.237290% CI: [70.32, 109.54]ANOVA
Primary
AUC 0-infinity of Tolbutamide
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity.
Time frame: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.
Population: PKS. This endpoint was not planned to be analysed for groups C, D and E
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group A | AUC 0-infinity of Tolbutamide | Day 1 (N=16, 19) | 1940000 nmol*h/L | Geometric Coefficient of Variation 42.5 |
| Group A | AUC 0-infinity of Tolbutamide | Day 9 (N=13, 17) | 1800000 nmol*h/L | Geometric Coefficient of Variation 41.3 |
| Group A | AUC 0-infinity of Tolbutamide | Day 17 (N=14, 18) | 1520000 nmol*h/L | Geometric Coefficient of Variation 36.4 |
| Group A | AUC 0-infinity of Tolbutamide | Day 66 (N=12, 15) | 1330000 nmol*h/L | Geometric Coefficient of Variation 40.1 |
| Group B | AUC 0-infinity of Tolbutamide | Day 66 (N=12, 15) | 1390000 nmol*h/L | Geometric Coefficient of Variation 33.2 |
| Group B | AUC 0-infinity of Tolbutamide | Day 1 (N=16, 19) | 2220000 nmol*h/L | Geometric Coefficient of Variation 29.4 |
| Group B | AUC 0-infinity of Tolbutamide | Day 17 (N=14, 18) | 1410000 nmol*h/L | Geometric Coefficient of Variation 27.9 |
| Group B | AUC 0-infinity of Tolbutamide | Day 9 (N=13, 17) | 1940000 nmol*h/L | Geometric Coefficient of Variation 36.5 |
Comparison: Day 9 vs. Day 1p-value: 0.000590% CI: [90.15, 106.91]ANOVA
Comparison: Day 17 vs. Day 1p-value: 0.363890% CI: [75.19, 87.82]ANOVA
Comparison: Day 66 vs. Day 1p-value: 0.897590% CI: [60.44, 83.22]ANOVA
Comparison: Day 9 vs. Day 1p-value: 0.114490% CI: [77.62, 96.11]ANOVA
Comparison: Day 17 vs. Day 1p-value: 190% CI: [60.42, 69.2]ANOVA
Comparison: Day 66 vs. Day 1p-value: 0.998890% CI: [57.19, 71.07]ANOVA
Primary
C12hr of Raltegravir
Concentration of an analyte in plasma at 12 hours.
Time frame: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9 and 17
Population: PKS. Due to Boehringer Ingelheim's decision not to pursue the development of this substance, the extent of the statistical analysis was limited to selected endpoints. No further analysis is planned for the endpoints which were not related to patient efficacy or safety.
Primary
C24hr of Faldaprevir (BI 201335)
Concentration of an analyte in plasma at 24 hours
Time frame: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
Population: The pharmacokinetic set (PKS): included all patients in the treated set who provided at least one observation for at least one primary (PK) endpoint without important protocol violations relevant to the evaluation of PK. This endpoint was not planned to be analysed for groups C, D and E.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group A | C24hr of Faldaprevir (BI 201335) | Day 9 (N=15,0) | 983 ng/mL | Geometric Coefficient of Variation 65.5 |
| Group A | C24hr of Faldaprevir (BI 201335) | Day 17 (N=14,19) | 3670 ng/mL | Geometric Coefficient of Variation 90.4 |
| Group A | C24hr of Faldaprevir (BI 201335) | Day 66 (N=13,14) | 1140 ng/mL | Geometric Coefficient of Variation 107 |
| Group B | C24hr of Faldaprevir (BI 201335) | Day 9 (N=15,0) | NA ng/mL | — |
| Group B | C24hr of Faldaprevir (BI 201335) | Day 17 (N=14,19) | 5410 ng/mL | Geometric Coefficient of Variation 91.6 |
| Group B | C24hr of Faldaprevir (BI 201335) | Day 66 (N=13,14) | 2580 ng/mL | Geometric Coefficient of Variation 135 |
Comparison: Day 17 vs. Day 9p-value: 190% CI: [317.01, 458.19]ANOVA
Comparison: Day 66 vs. Day 9p-value: 0.471890% CI: [94.66, 161.51]ANOVA
Primary
C24hr of Tenofovir
Concentration of an analyte in plasma at 24 hours.
Time frame: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9 and 17
Population: PKS. Due to Boehringer Ingelheim's decision not to pursue the development of this substance, the extent of the statistical analysis was limited to selected endpoints. No further analysis is planned for the endpoints which were not related to patient efficacy or safety.
Primary
C6hr of Deleobuvir (BI 207127)
Concentration of an analyte in plasma at 6 hours
Time frame: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
Population: The pharmacokinetic set (PKS): included all patients in the treated set who provided at least one observation for at least one primary (PK) endpoint without important protocol violations relevant to the evaluation of PK. This endpoint was not planned to be analysed for groups C, D and E.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group A | C6hr of Deleobuvir (BI 207127) | Day 9 (N=0, 17) | NA nmol/L | — |
| Group A | C6hr of Deleobuvir (BI 207127) | Day 17 (N=14, 19) | 17900 nmol/L | Geometric Coefficient of Variation 84.2 |
| Group A | C6hr of Deleobuvir (BI 207127) | Day 66 (N=13, 14) | 5080 nmol/L | Geometric Coefficient of Variation 108 |
| Group B | C6hr of Deleobuvir (BI 207127) | Day 9 (N=0, 17) | 5800 nmol/L | Geometric Coefficient of Variation 129 |
| Group B | C6hr of Deleobuvir (BI 207127) | Day 17 (N=14, 19) | 20800 nmol/L | Geometric Coefficient of Variation 83.8 |
| Group B | C6hr of Deleobuvir (BI 207127) | Day 66 (N=13, 14) | 10100 nmol/L | Geometric Coefficient of Variation 133 |
Comparison: Day 17 vs. Day 9p-value: 190% CI: [269.12, 454.93]ANOVA
Comparison: Day 66 vs. Day 9p-value: 0.953390% CI: [125.95, 247.5]ANOVA
Primary
C6hr of Deleobuvir Metabolite Acyl-glucuronide (BI 208333)
Concentration of an analyte in plasma at 6 hours
Time frame: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
Population: The pharmacokinetic set (PKS): included all patients in the treated set who provided at least one observation for at least one primary (PK) endpoint without important protocol violations relevant to the evaluation of PK. This endpoint was not planned to be analysed for groups C, D and E.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group A | C6hr of Deleobuvir Metabolite Acyl-glucuronide (BI 208333) | Day 66 (N=13, 14) | 2740 nmol/L | Geometric Coefficient of Variation 85.9 |
| Group A | C6hr of Deleobuvir Metabolite Acyl-glucuronide (BI 208333) | Day 9 (N=0, 17) | NA nmol/L | — |
| Group A | C6hr of Deleobuvir Metabolite Acyl-glucuronide (BI 208333) | Day 17 (N=14, 19) | 11200 nmol/L | Geometric Coefficient of Variation 83.7 |
| Group B | C6hr of Deleobuvir Metabolite Acyl-glucuronide (BI 208333) | Day 9 (N=0, 17) | 4330 nmol/L | Geometric Coefficient of Variation 154 |
| Group B | C6hr of Deleobuvir Metabolite Acyl-glucuronide (BI 208333) | Day 17 (N=14, 19) | 17500 nmol/L | Geometric Coefficient of Variation 119 |
| Group B | C6hr of Deleobuvir Metabolite Acyl-glucuronide (BI 208333) | Day 66 (N=13, 14) | 5780 nmol/L | Geometric Coefficient of Variation 132 |
Comparison: Day 17 vs. Day 9p-value: 190% CI: [330.79, 478.22]ANOVA
Comparison: Day 66 vs. Day 9p-value: 0.734690% CI: [99.49, 203.44]ANOVA
Primary
C6hr of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide)
Concentration of an analyte in plasma at 6 hours
Time frame: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
Population: The pharmacokinetic set (PKS): included all patients in the treated set who provided at least one observation for at least one primary (PK) endpoint without important protocol violations relevant to the evaluation of PK. This endpoint was not planned to be analysed for groups C, D and E.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group A | C6hr of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide) | Day 9 (N=0, 17) | NA nmol/L | — |
| Group A | C6hr of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide) | Day 17 (N=14, 19) | 508 nmol/L | Geometric Coefficient of Variation 138 |
| Group A | C6hr of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide) | Day 66 (N=13, 14) | 295 nmol/L | Geometric Coefficient of Variation 128 |
| Group B | C6hr of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide) | Day 9 (N=0, 17) | 159 nmol/L | Geometric Coefficient of Variation 165 |
| Group B | C6hr of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide) | Day 17 (N=14, 19) | 962 nmol/L | Geometric Coefficient of Variation 117 |
| Group B | C6hr of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide) | Day 66 (N=13, 14) | 712 nmol/L | Geometric Coefficient of Variation 143 |
Comparison: Day 17 vs. Day 9p-value: 190% CI: [447.49, 725.57]ANOVA
Comparison: Day 66 vs. Day 9p-value: 0.999990% CI: [286.81, 680.82]ANOVA
Primary
C6hr of Deleobuvir Reduction Metabolite CD 6168
Concentration of an analyte in plasma at 6 hours
Time frame: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
Population: The pharmacokinetic set (PKS): included all patients in the treated set who provided at least one observation for at least one primary (PK) endpoint without important protocol violations relevant to the evaluation of PK. This endpoint was not planned to be analysed for groups C, D and E.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group A | C6hr of Deleobuvir Reduction Metabolite CD 6168 | Day 9 (N=0, 17) | NA nmol/L | — |
| Group A | C6hr of Deleobuvir Reduction Metabolite CD 6168 | Day 17 (N=14, 19) | 6980 nmol/L | Geometric Coefficient of Variation 128 |
| Group A | C6hr of Deleobuvir Reduction Metabolite CD 6168 | Day 66 (N=13, 14) | 3360 nmol/L | Geometric Coefficient of Variation 139 |
| Group B | C6hr of Deleobuvir Reduction Metabolite CD 6168 | Day 9 (N=0, 17) | 2250 nmol/L | Geometric Coefficient of Variation 137 |
| Group B | C6hr of Deleobuvir Reduction Metabolite CD 6168 | Day 17 (N=14, 19) | 10200 nmol/L | Geometric Coefficient of Variation 81 |
| Group B | C6hr of Deleobuvir Reduction Metabolite CD 6168 | Day 66 (N=13, 14) | 7460 nmol/L | Geometric Coefficient of Variation 123 |
Comparison: Day 17 vs. Day 9p-value: 190% CI: [343.67, 590.57]ANOVA
Comparison: Day 66 vs. Day 9p-value: 0.999690% CI: [229.22, 510.13]ANOVA
Primary
Cmax of 1-OH-Midazolam (1-hydroxy-midazolam)
Maximum concentration of an analyte in plasma
Time frame: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.
Population: PKS. This endpoint was not planned to be analysed for groups C, D and E
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group A | Cmax of 1-OH-Midazolam (1-hydroxy-midazolam) | Day 1 (N=16, 19) | 5.57 nmol/L | Geometric Coefficient of Variation 36.4 |
| Group A | Cmax of 1-OH-Midazolam (1-hydroxy-midazolam) | Day 9 (N=15, 17) | 6.50 nmol/L | Geometric Coefficient of Variation 46.3 |
| Group A | Cmax of 1-OH-Midazolam (1-hydroxy-midazolam) | Day 17 (N=14, 19) | 6.46 nmol/L | Geometric Coefficient of Variation 42.7 |
| Group A | Cmax of 1-OH-Midazolam (1-hydroxy-midazolam) | Day 66 (N=13, 15) | 5.05 nmol/L | Geometric Coefficient of Variation 45.6 |
| Group B | Cmax of 1-OH-Midazolam (1-hydroxy-midazolam) | Day 66 (N=13, 15) | 4.67 nmol/L | Geometric Coefficient of Variation 45.2 |
| Group B | Cmax of 1-OH-Midazolam (1-hydroxy-midazolam) | Day 1 (N=16, 19) | 6.68 nmol/L | Geometric Coefficient of Variation 67.1 |
| Group B | Cmax of 1-OH-Midazolam (1-hydroxy-midazolam) | Day 17 (N=14, 19) | 5.02 nmol/L | Geometric Coefficient of Variation 50.5 |
| Group B | Cmax of 1-OH-Midazolam (1-hydroxy-midazolam) | Day 9 (N=15, 17) | 6.52 nmol/L | Geometric Coefficient of Variation 46.9 |
Comparison: Day 9 vs. Day 1p-value: 0.151990% CI: [106.49, 130]ANOVA
Comparison: Day17 vs. Day 1p-value: 0.282790% CI: [96.06, 142.52]ANOVA
Comparison: Day 66 vs. Day 1p-value: 0.132690% CI: [74.38, 114.07]ANOVA
Comparison: Day 9 vs. Day 1p-value: 0.043290% CI: [80.63, 113.24]ANOVA
Comparison: Day 17 vs. Day 1p-value: 0.736790% CI: [63.64, 88.82]ANOVA
Comparison: Day 66 vs. Day 1p-value: 0.854790% CI: [56.84, 86.56]ANOVA
Primary
Cmax of Caffeine
Maximum concentration of an analyte in plasma
Time frame: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.
Population: PKS. This endpoint was not planned to be analysed for groups C, D and E
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group A | Cmax of Caffeine | Day 1 (N=16, 19) | 5170 ng/mL | Geometric Coefficient of Variation 46.2 |
| Group A | Cmax of Caffeine | Day 9 (N=15, 17) | 4890 ng/mL | Geometric Coefficient of Variation 57.7 |
| Group A | Cmax of Caffeine | Day 17 (N=14, 19) | 4830 ng/mL | Geometric Coefficient of Variation 47.5 |
| Group A | Cmax of Caffeine | Day 66 (N=13, 15) | 5590 ng/mL | Geometric Coefficient of Variation 49.6 |
| Group B | Cmax of Caffeine | Day 66 (N=13, 15) | 6450 ng/mL | Geometric Coefficient of Variation 32.4 |
| Group B | Cmax of Caffeine | Day 1 (N=16, 19) | 5340 ng/mL | Geometric Coefficient of Variation 38.2 |
| Group B | Cmax of Caffeine | Day 17 (N=14, 19) | 6530 ng/mL | Geometric Coefficient of Variation 52.3 |
| Group B | Cmax of Caffeine | Day 9 (N=15, 17) | 7220 ng/mL | Geometric Coefficient of Variation 37.1 |
Comparison: Day 9 vs. Day 1p-value: 0.0590% CI: [80, 117.69]ANOVA
Comparison: Day 17 vs. Day 1p-value: 0.056490% CI: [79.37, 118.79]ANOVA
Comparison: Day 66 vs. Day 1p-value: 0.237590% CI: [92.36, 141.66]ANOVA
Comparison: Day 9 vs. Day 1p-value: 0.908290% CI: [121.63, 159]ANOVA
Comparison: Day 17 vs. Day 1p-value: 0.411190% CI: [104.11, 143.84]ANOVA
Comparison: Day 66 vs. Day 1p-value: 0.371990% CI: [104.24, 141.45]ANOVA
Primary
Cmax of Deleobuvir (BI 207127)
Maximum concentration of an analyte in plasma
Time frame: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
Population: The pharmacokinetic set (PKS): included all patients in the treated set who provided at least one observation for at least one primary (PK) endpoint without important protocol violations relevant to the evaluation of PK. This endpoint was not planned to be analysed for groups C, D and E.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group A | Cmax of Deleobuvir (BI 207127) | Day 9 (N=0, 17) | NA nmol/L | — |
| Group A | Cmax of Deleobuvir (BI 207127) | Day 17 (N=14, 19) | 27000 nmol/L | Geometric Coefficient of Variation 64.6 |
| Group A | Cmax of Deleobuvir (BI 207127) | Day 66 (N=13, 15) | 10100 nmol/L | Geometric Coefficient of Variation 78.2 |
| Group B | Cmax of Deleobuvir (BI 207127) | Day 9 (N=0, 17) | 10900 nmol/L | Geometric Coefficient of Variation 85.3 |
| Group B | Cmax of Deleobuvir (BI 207127) | Day 17 (N=14, 19) | 31400 nmol/L | Geometric Coefficient of Variation 45.8 |
| Group B | Cmax of Deleobuvir (BI 207127) | Day 66 (N=13, 15) | 16000 nmol/L | Geometric Coefficient of Variation 100 |
Comparison: Day 17 vs. Day 9p-value: 190% CI: [228.51, 357.97]ANOVA
Comparison: Day 66 vs. Day 9p-value: 0.82190% CI: [106.81, 211.91]ANOVA
Primary
Cmax of Deleobuvir Metabolite Acyl-glucuronide (BI 208333)
Maximum concentration of an analyte in plasma
Time frame: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
Population: The pharmacokinetic set (PKS): included all patients in the treated set who provided at least one observation for at least one primary (PK) endpoint without important protocol violations relevant to the evaluation of PK. This endpoint was not planned to be analysed for groups C, D and E.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group A | Cmax of Deleobuvir Metabolite Acyl-glucuronide (BI 208333) | Day 9 (N=0, 17) | NA nmol/L | — |
| Group A | Cmax of Deleobuvir Metabolite Acyl-glucuronide (BI 208333) | Day 17 (N=14, 19) | 12700 nmol/L | Geometric Coefficient of Variation 89.4 |
| Group A | Cmax of Deleobuvir Metabolite Acyl-glucuronide (BI 208333) | Day 66 (N=13, 15) | 3790 nmol/L | Geometric Coefficient of Variation 66.9 |
| Group B | Cmax of Deleobuvir Metabolite Acyl-glucuronide (BI 208333) | Day 9 (N=0, 17) | 5620 nmol/L | Geometric Coefficient of Variation 119 |
| Group B | Cmax of Deleobuvir Metabolite Acyl-glucuronide (BI 208333) | Day 17 (N=14, 19) | 20200 nmol/L | Geometric Coefficient of Variation 111 |
| Group B | Cmax of Deleobuvir Metabolite Acyl-glucuronide (BI 208333) | Day 66 (N=13, 15) | 6550 nmol/L | Geometric Coefficient of Variation 98.3 |
Comparison: Day 17 vs. Day 9p-value: 190% CI: [298.13, 422.83]ANOVA
Comparison: Day 66 vs. Day 9p-value: 0.433790% CI: [83.68, 174.01]ANOVA
Primary
Cmax of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide)
Maximum concentration of an analyte in plasma
Time frame: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
Population: The pharmacokinetic set (PKS): included all patients in the treated set who provided at least one observation for at least one primary (PK) endpoint without important protocol violations relevant to the evaluation of PK. This endpoint was not planned to be analysed for groups C, D and E.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group A | Cmax of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide) | Day 9 (N=0, 17) | NA nmol/L | — |
| Group A | Cmax of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide) | Day 17 (N=14, 19) | 596 nmol/L | Geometric Coefficient of Variation 143 |
| Group A | Cmax of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide) | Day 66 (N=13, 15) | 386 nmol/L | Geometric Coefficient of Variation 111 |
| Group B | Cmax of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide) | Day 9 (N=0, 17) | 203 nmol/L | Geometric Coefficient of Variation 135 |
| Group B | Cmax of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide) | Day 17 (N=14, 19) | 1130 nmol/L | Geometric Coefficient of Variation 115 |
| Group B | Cmax of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide) | Day 66 (N=13, 15) | 806 nmol/L | Geometric Coefficient of Variation 125 |
Comparison: Day 17 vs. Day 9p-value: 190% CI: [415.88, 672.75]ANOVA
Comparison: Day 66 vs. Day 9p-value: 0.999890% CI: [251.56, 586.16]ANOVA
Primary
Cmax of Deleobuvir Reduction Metabolite CD 6168
Maximum concentration of an analyte in plasma
Time frame: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
Population: The pharmacokinetic set (PKS): included all patients in the treated set who provided at least one observation for at least one primary (PK) endpoint without important protocol violations relevant to the evaluation of PK. This endpoint was not planned to be analysed for groups C, D and E.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group A | Cmax of Deleobuvir Reduction Metabolite CD 6168 | Day 9 (N=0, 17) | NA nmol/L | — |
| Group A | Cmax of Deleobuvir Reduction Metabolite CD 6168 | Day 17 (N=14, 19) | 8520 nmol/L | Geometric Coefficient of Variation 119 |
| Group A | Cmax of Deleobuvir Reduction Metabolite CD 6168 | Day 66 (N=13, 15) | 4510 nmol/L | Geometric Coefficient of Variation 117 |
| Group B | Cmax of Deleobuvir Reduction Metabolite CD 6168 | Day 9 (N=0, 17) | 3040 nmol/L | Geometric Coefficient of Variation 115 |
| Group B | Cmax of Deleobuvir Reduction Metabolite CD 6168 | Day 17 (N=14, 19) | 12400 nmol/L | Geometric Coefficient of Variation 70.9 |
| Group B | Cmax of Deleobuvir Reduction Metabolite CD 6168 | Day 66 (N=13, 15) | 8880 nmol/L | Geometric Coefficient of Variation 111 |
Comparison: Day 17 vs. Day 9p-value: 190% CI: [315.15, 529.9]ANOVA
Comparison: Day 66 vs. Day 9p-value: 0.999390% CI: [204.61, 443.35]ANOVA
Primary
Cmax of Faldaprevir (BI 201335)
Maximum concentration of an analyte in plasma
Time frame: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.
Population: The pharmacokinetic set (PKS): included all patients in the treated set who provided at least one observation for at least one primary (PK) endpoint without important protocol violations relevant to the evaluation of PK. This endpoint was not planned to be analysed for groups C, D and E.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group A | Cmax of Faldaprevir (BI 201335) | Day 9 (N=15,0) | 3520 ng/mL | Geometric Coefficient of Variation 54.8 |
| Group A | Cmax of Faldaprevir (BI 201335) | Day 17 (N=14,14) | 8780 ng/mL | Geometric Coefficient of Variation 47.5 |
| Group A | Cmax of Faldaprevir (BI 201335) | Day 66 (N=13,15) | 4410 ng/mL | Geometric Coefficient of Variation 48.7 |
| Group B | Cmax of Faldaprevir (BI 201335) | Day 9 (N=15,0) | NA ng/mL | — |
| Group B | Cmax of Faldaprevir (BI 201335) | Day 17 (N=14,14) | 9950 ng/mL | Geometric Coefficient of Variation 51 |
| Group B | Cmax of Faldaprevir (BI 201335) | Day 66 (N=13,15) | 6690 ng/mL | Geometric Coefficient of Variation 78.8 |
Comparison: Day 17 vs. Day 9p-value: 190% CI: [205.54, 307.43]ANOVA
Comparison: Day 66 vs. Day 9p-value: 0.651490% CI: [105.4, 163.57]ANOVA
Primary
Cmax of Midazolam
Maximum concentration of an analyte in plasma
Time frame: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.
Population: PKS. This endpoint was not planned to be analysed for groups C, D and E
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group A | Cmax of Midazolam | Day 1 (N=16, 19) | 21.1 nmol/L | Geometric Coefficient of Variation 38.3 |
| Group A | Cmax of Midazolam | Day 9 (N=15, 17) | 29.9 nmol/L | Geometric Coefficient of Variation 34.7 |
| Group A | Cmax of Midazolam | Day 17 (N=14, 19) | 31.9 nmol/L | Geometric Coefficient of Variation 36.6 |
| Group A | Cmax of Midazolam | Day 66 (N=13, 15) | 21.3 nmol/L | Geometric Coefficient of Variation 34 |
| Group B | Cmax of Midazolam | Day 66 (N=13, 15) | 23.2 nmol/L | Geometric Coefficient of Variation 40.4 |
| Group B | Cmax of Midazolam | Day 1 (N=16, 19) | 23.8 nmol/L | Geometric Coefficient of Variation 41.2 |
| Group B | Cmax of Midazolam | Day 17 (N=14, 19) | 28.8 nmol/L | Geometric Coefficient of Variation 46.9 |
| Group B | Cmax of Midazolam | Day 9 (N=15, 17) | 29.8 nmol/L | Geometric Coefficient of Variation 44.3 |
Comparison: Day 9 vs. Day 1p-value: 0.974990% CI: [128.3, 163.36]ANOVA
Comparison: Day 17 vs. Day 1p-value: 0.970390% CI: [128.6, 181.89]ANOVA
Comparison: Day 66 vs. Day 1p-value: 0.0590% CI: [84.85, 124.99]ANOVA
Comparison: Day 9 vs. Day 1p-value: 0.469790% CI: [107.91, 142.99]ANOVA
Comparison: Day 17 vs. Day 1p-value: 0.290690% CI: [108.47, 134.38]ANOVA
Comparison: Day 66 vs. Day 1p-value: 0.04690% CI: [80.33, 109.86]ANOVA
Primary
Cmax of Raltegravir
Maximum concentration of an analyte in plasma.
Time frame: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9 and 17
Population: PKS. Due to Boehringer Ingelheim's decision not to pursue the development of this substance, the extent of the statistical analysis was limited to selected endpoints. No further analysis is planned for the endpoints which were not related to patient efficacy or safety.
Primary
Cmax of Tenofovir
Maximum concentration of an analyte in plasma.
Time frame: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9 and 17
Population: PKS. Due to Boehringer Ingelheim's decision not to pursue the development of this substance, the extent of the statistical analysis was limited to selected endpoints. No further analysis is planned for the endpoints which were not related to patient efficacy or safety.
Primary
Cmax of Tolbutamide
Maximum concentration of an analyte in plasma
Time frame: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.
Population: PKS. This endpoint was not planned to be analysed for groups C, D and E
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group A | Cmax of Tolbutamide | Day 1 (N=16, 19) | 152000 nmol/L | Geometric Coefficient of Variation 30.8 |
| Group A | Cmax of Tolbutamide | Day 9 (N=15, 17) | 146000 nmol/L | Geometric Coefficient of Variation 28.1 |
| Group A | Cmax of Tolbutamide | Day 17 (N=14, 19) | 130000 nmol/L | Geometric Coefficient of Variation 24.7 |
| Group A | Cmax of Tolbutamide | Day 66 (N=13, 15) | 110000 nmol/L | Geometric Coefficient of Variation 32.3 |
| Group B | Cmax of Tolbutamide | Day 66 (N=13, 15) | 127000 nmol/L | Geometric Coefficient of Variation 25 |
| Group B | Cmax of Tolbutamide | Day 1 (N=16, 19) | 170000 nmol/L | Geometric Coefficient of Variation 18.6 |
| Group B | Cmax of Tolbutamide | Day 17 (N=14, 19) | 126000 nmol/L | Geometric Coefficient of Variation 32 |
| Group B | Cmax of Tolbutamide | Day 9 (N=15, 17) | 158000 nmol/L | Geometric Coefficient of Variation 22.8 |
Comparison: Day 9 vs. Day 1p-value: 0.001590% CI: [87.77, 105.13]ANOVA
Comparison: Day 17 vs. Day 1p-value: 0.161790% CI: [76.32, 95.57]ANOVA
Comparison: Day 66 vs. Day 1p-value: 0.89390% CI: [65.03, 82.54]ANOVA
Comparison: Day 9 vs. Day 1p-value: 0.000590% CI: [86.67, 98.13]ANOVA
Comparison: Day 17 vs. Day 1p-value: 0.864690% CI: [65.55, 83.39]ANOVA
Comparison: Day 66 vs. Day 1p-value: 0.837890% CI: [68.15, 83.45]ANOVA
Secondary
Number of Participants With Sustained Virological Response (SVR12)
Sustained virologic response (SVR12): Plasma Hepatitis C virus Ribonucleic acid (HCV RNA) level \<25 IU/mL(international units per millilitre) undetectable at 12 weeks after the end of treatment. SVR12 was analyzed in a descriptive manner using frequency of participants who achieved SVR12.
Time frame: 12 weeks post treatment
Population: Treated set (TRT): This subject set includes all patients who were dispensed trial medication and were documented to have taken at least one dose of trial drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group A | Number of Participants With Sustained Virological Response (SVR12) | 13 Participants |
| Group B | Number of Participants With Sustained Virological Response (SVR12) | 13 Participants |
| Group C | Number of Participants With Sustained Virological Response (SVR12) | 11 Participants |
| Group D | Number of Participants With Sustained Virological Response (SVR12) | 10 Participants |
| Group E | Number of Participants With Sustained Virological Response (SVR12) | 3 Participants |