Healthy
Conditions
Brief summary
The objective of this study is to evaluate the effect of multiple doses of BI 207127 combined with faldaprevir on cardiac safety parameters in healthy subjects
Interventions
DRUGBI 207127
Medium dose oral administration
DRUGFaldaprevir placebo
DRUGFaldaprevir
Medium dose oral administration
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male and female subjects * Subjects must be able to understand and comply with study requirements * Age =18 and =55 years * BMI range: =18.5 and =29.9 kg/m2
Exclusion criteria
\- any relevant deviation from healthy conditions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Mean Placebo-corrected QTcN Change From Baseline Between 1 to 24 Hours on Day 1 for the Combination Therapy | 20min,15min and 10min prior to drug administration on day -2 (baseline) and 1h (hours), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h and 24h after drug adminstration on day 1 | Maximum mean placebo-corrected QT interval corrected for heart rate according to a parabolic population model (QTcN) change from baseline between 1 to 24 hours on Day 1 for the combination therapy is estimated. QTcN denotes the population heart rate corrected QT interval length, based on a parabolic model. 'Baseline' denotes the mean of the pre-dose ECG measurements prior to (first) dose at Visits 2, 3 or 4, determined separately for each treatment period. 'Global baseline' refers to the mean of all available period baseline values. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Mean Placebo-corrected QTcN Change From Baseline Between 1 to 6 Hours on Day 1 for the Moxifloxacin Treatment | 20min,15min and 10min prior to drug administration on day -2 (baseline) and 1h (hours), 2h, 3h, 4h, 5h and 6h after drug adminstration on day 1 | Maximum mean placebo-corrected QTcN change from baseline between 1 to 6 hours on Day 1 for the Moxifloxacin treatment is estimated. QTcN denotes the population heart rate corrected QT interval length, based on a parabolic model. 'Baseline' denotes the mean of the pre-dose ECG measurements prior to (first) dose at Visits 2, 3 or 4, determined separately for each treatment period. 'Global baseline' refers to the mean of all available period baseline values. |
| Maximum Mean Placebo-corrected HR Change From Baseline Between 1 to 24 Hours on Day 1 for the Combination Therapy | 20min,15min and 10min prior to drug administration on day -2 (baseline) and 1h (hours), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h and 24h after drug adminstration on day 1 | Maximum mean placebo-corrected heart rate (HR) change from baseline between 1 to 24 hours on Day 1 for the combination therapy is estimated. HR was derived from the RR interval. |
| Minimum Mean Placebo-corrected HR (Heart Rate) Change From Baseline Between 1 to 24 Hours on Day 1 for the Combination Therapy | 20min,15min and 10min prior to drug administration on day -2 (baseline) and 1h (hours), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h and 24h after drug adminstration on day 1 | Minimum mean placebo-corrected HR (heart rate) change from baseline between 1 to 24 hours on Day 1 for the combination therapy is estimated. HR was derived from the RR interval. |
Countries
Germany
Participant flow
Pre-assignment details
After an initial screening (Visit 1) within Day -23 and Day -3 prior of the first treatment period, subjects meeting all inclusion and none of the exclusion criteria participated in Visits 2 to 5.
Participants by arm
| Arm | Count |
|---|---|
| Overall Study This study is randomised, single-blind, 3-period crossover having 3 treatments, BI 207127 and Faldaprevir for 3 days (Days -2 to 1), placebo to BI 207127 plus placebo to Faldaprevir for 3 days (Days -2 to 1) and Moxifloxacin 400 mg as single dose (Day 1). | 48 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Other than stated above | 6 | 5 | 6 | 6 | 6 | 6 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Continuous | 37.5 Years STANDARD_DEVIATION 8.8 |
| Sex: Female, Male Female | 24 Participants |
| Sex: Female, Male Male | 24 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 | 17 / 32 | 4 / 31 | 7 / 32 |
| serious Total, serious adverse events | 0 / 32 | 0 / 31 | 0 / 32 |
Outcome results
Primary
Maximum Mean Placebo-corrected QTcN Change From Baseline Between 1 to 24 Hours on Day 1 for the Combination Therapy
Maximum mean placebo-corrected QT interval corrected for heart rate according to a parabolic population model (QTcN) change from baseline between 1 to 24 hours on Day 1 for the combination therapy is estimated. QTcN denotes the population heart rate corrected QT interval length, based on a parabolic model. 'Baseline' denotes the mean of the pre-dose ECG measurements prior to (first) dose at Visits 2, 3 or 4, determined separately for each treatment period. 'Global baseline' refers to the mean of all available period baseline values.
Time frame: 20min,15min and 10min prior to drug administration on day -2 (baseline) and 1h (hours), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h and 24h after drug adminstration on day 1
Population: Electrocardiogram (ECG) analysis set (ECGS): all subjects in the treated set who had at least 1 baseline and post-baseline assessment for at least 1 ECG endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BI 207127+ Faldaprevir | Maximum Mean Placebo-corrected QTcN Change From Baseline Between 1 to 24 Hours on Day 1 for the Combination Therapy | -0.47 ms | Standard Error 1.65 |
| Placebo to BI 207127 + Placebo to Faldaprevir | Maximum Mean Placebo-corrected QTcN Change From Baseline Between 1 to 24 Hours on Day 1 for the Combination Therapy | -8.37 ms | Standard Error 1.64 |
90% CI: [5.37, 10.43]
Secondary
Maximum Mean Placebo-corrected HR Change From Baseline Between 1 to 24 Hours on Day 1 for the Combination Therapy
Maximum mean placebo-corrected heart rate (HR) change from baseline between 1 to 24 hours on Day 1 for the combination therapy is estimated. HR was derived from the RR interval.
Time frame: 20min,15min and 10min prior to drug administration on day -2 (baseline) and 1h (hours), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h and 24h after drug adminstration on day 1
Population: ECG analysis set (ECGS)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BI 207127+ Faldaprevir | Maximum Mean Placebo-corrected HR Change From Baseline Between 1 to 24 Hours on Day 1 for the Combination Therapy | -3.47 bpm | Standard Error 0.88 |
| Placebo to BI 207127 + Placebo to Faldaprevir | Maximum Mean Placebo-corrected HR Change From Baseline Between 1 to 24 Hours on Day 1 for the Combination Therapy | -3.64 bpm | Standard Error 0.88 |
Comparison: No formal hypothesis testing was done.90% CI: [-1.38, 1.73]
Secondary
Maximum Mean Placebo-corrected QTcN Change From Baseline Between 1 to 6 Hours on Day 1 for the Moxifloxacin Treatment
Maximum mean placebo-corrected QTcN change from baseline between 1 to 6 hours on Day 1 for the Moxifloxacin treatment is estimated. QTcN denotes the population heart rate corrected QT interval length, based on a parabolic model. 'Baseline' denotes the mean of the pre-dose ECG measurements prior to (first) dose at Visits 2, 3 or 4, determined separately for each treatment period. 'Global baseline' refers to the mean of all available period baseline values.
Time frame: 20min,15min and 10min prior to drug administration on day -2 (baseline) and 1h (hours), 2h, 3h, 4h, 5h and 6h after drug adminstration on day 1
Population: ECG analysis set (ECGS)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BI 207127+ Faldaprevir | Maximum Mean Placebo-corrected QTcN Change From Baseline Between 1 to 6 Hours on Day 1 for the Moxifloxacin Treatment | 14.95 ms | Standard Error 1.84 |
| Placebo to BI 207127 + Placebo to Faldaprevir | Maximum Mean Placebo-corrected QTcN Change From Baseline Between 1 to 6 Hours on Day 1 for the Moxifloxacin Treatment | 2.25 ms | Standard Error 1.74 |
Comparison: No formal hypothesis testing was done.90% CI: [9.32, 16.08]
Secondary
Minimum Mean Placebo-corrected HR (Heart Rate) Change From Baseline Between 1 to 24 Hours on Day 1 for the Combination Therapy
Minimum mean placebo-corrected HR (heart rate) change from baseline between 1 to 24 hours on Day 1 for the combination therapy is estimated. HR was derived from the RR interval.
Time frame: 20min,15min and 10min prior to drug administration on day -2 (baseline) and 1h (hours), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h and 24h after drug adminstration on day 1
Population: ECG analysis set (ECGS)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BI 207127+ Faldaprevir | Minimum Mean Placebo-corrected HR (Heart Rate) Change From Baseline Between 1 to 24 Hours on Day 1 for the Combination Therapy | -0.68 bpm | Standard Error 0.88 |
| Placebo to BI 207127 + Placebo to Faldaprevir | Minimum Mean Placebo-corrected HR (Heart Rate) Change From Baseline Between 1 to 24 Hours on Day 1 for the Combination Therapy | 3.74 bpm | Standard Error 0.87 |
Comparison: No formal hypothesis testing was done.90% CI: [-5.98, -2.87]