Healthy
Conditions
Brief summary
The purpose of this trial is to investigate the effect of food with different fat content and of gastric pH increase (mediated by multiple dosing of omeprazole) on the relative bioavailability of deleobuvir.
Interventions
DRUGBI 207127 high fat
BI 207127 as a single dose after a high fat breakfast
DRUGBI 207127 with Omeprazole
BI 207127 as a single dose after 4 days treatment of Omeprazole 40 mg once a day
DRUGBI 207127
BI 207127 as a single dose in fasted state
DRUGBI 207127 low fat
BI 207127 as a single dose after a low fat breakfast
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy males or females according to the investigators assessment, as based on the following criteria: a complete medical history including a physical examination, vital signs (BP, PR), 12-lead ECG, and clinical laboratory tests. Subjects will be either Caucasian or Japanese (first generation Japanese: born in Japan with parents of Japanese descent, and not more than 5 years out of Japan, documented by medical interview and by appropriate materials - e.g. passport, birth certificate, etc) * Age 20 to 35 years (incl.) * BMI 18.5 to 25 kg/m2 (incl.)
Exclusion criteria
* Any finding in the medical examination (including BP, PR or ECG) deviating from normal and judged clinically relevant by the investigator * Repeated measurement of systolic blood pressure greater than 140 mm Hg or diastolic blood pressure greater than 90 mm Hg * Any laboratory value outside the reference range that the investigator considers to be of clinical relevance * Any evidence of a concomitant disease judged clinically relevant by the investigator * Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders * Surgery of the gastrointestinal tract that could interfere with kinetics of the study drug(s) * Diseases of the central nervous system (such as epilepsy), other neurological disorders or psychiatric disorders
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC(0-tz) | 1 hour (h) before drug administration and 30 minutes (min), 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h and 48h after drug administration | Area under the concentration-time curve of deleobuvir in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) |
| Cmax | 1 hour (h) before drug administration and 30 minutes (min), 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h and 48h after drug administration | Maximum measured concentration of deleobuvir in plasma (Cmax) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC(0-inf) | 1 hour (h) before drug administration and 30 minutes (min), 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h and 48h after drug administration | Area under the concentration-time curve of deleobuvir in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf) |
Countries
Germany
Participant flow
Recruitment details
It was planned that 16 healthy Caucasian subjects (males and females, at least one third of each sex) and 16 healthy Japanese subjects (both males + females, at least one third of each sex) would enter the study. They were recruited from the volunteers' pool of the trial site. Due to early study termination, no Japanese subjects were randomised.
Pre-assignment details
All subjects were screened for eligibility to participate in the trial. Subjects attended specialist sites which would then ensure that the subject met all strictly implemented inclusion/exclusion criteria. Subjects were not to be randomised to trial treatment if any one of the specific entry criteria were violated.
Participants by arm
| Arm | Count |
|---|---|
| Dele Fasted / Dele High Fat / Dele + OMP / Dele Low Fat Dele fasted, followed by a washout phase, followed by Dele after a standardised high-fat, high- calorie meal, followed by a washout phase, followed by Dele after a 4 days pre-treatment with a 40 mg Omeprazole (OMP) gastro-resistant hard capsule once daily, followed by a washout phase, followed by Dele after a standardised low-fat meal.
Each Dele intake is a single dose of 3x 200mg Dele film-coated tablets after an overnight fast of at least 10 h.
The duration of a washout phase was at least 6 days. | 4 |
| Dele High Fat / Dele Low Fat / Dele Fasted / Dele + OMP Dele after a standardised high-fat, high-calorie meal, followed by a washout phase, followed by Dele after a standardised low-fat meal, followed by a washout phase, followed by Dele fasted, followed by a washout phase, followed by Dele after a 4 days pre-treatment with a 40 mg OMP gastro-resistant hard capsule once daily.
Each Dele intake is a single dose of 3x 200mg Dele film-coated tablets after an overnight fast of at least 10 h.
The duration of a washout phase was at least 6 days. | 4 |
| Dele Low Fat / Dele + OMP / Dele High Fat / Dele Fasted Dele after a standardised low-fat meal, followed by a washout phase, followed by Dele after a 4 days pre-treatment with a 40 mg OMP gastro-resistant hard capsule once daily, followed by a washout phase, followed by Dele after a standardised high-fat, high-calorie meal, followed by a washout phase, followed by Dele fasted.
Each Dele intake is a single dose of 3x 200mg Dele film-coated tablets after an overnight fast of at least 10 h.
The duration of a washout phase was at least 6 days. | 4 |
| Dele + OMP / Dele Fasted / Dele Low Fat / Dele High Fat Dele after a 4 days pre-treatment with a 40 mg OMP gastro-resistant hard capsule once daily, followed by a washout phase, followed by Dele fasted, followed by a washout phase, followed by Dele after a standardised low-fat meal, followed by a washout phase, followed by Dele after a standardised high-fat, high-calorie meal.
Each Dele intake is a single dose of 3x 200mg Dele film-coated tablets after an overnight fast of at least 10 h.
The duration of a washout phase was at least 6 days. | 4 |
| Total | 16 |
Baseline characteristics
| Characteristic | Dele Fasted / Dele High Fat / Dele + OMP / Dele Low Fat | Dele High Fat / Dele Low Fat / Dele Fasted / Dele + OMP | Dele Low Fat / Dele + OMP / Dele High Fat / Dele Fasted | Dele + OMP / Dele Fasted / Dele Low Fat / Dele High Fat | Total |
|---|---|---|---|---|---|
| Age, Continuous | 29.3 years STANDARD_DEVIATION 3 | 25.3 years STANDARD_DEVIATION 1 | 32.3 years STANDARD_DEVIATION 2.9 | 27.8 years STANDARD_DEVIATION 3 | 28.6 years STANDARD_DEVIATION 3.5 |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 3 Participants | 0 Participants | 7 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 1 Participants | 4 Participants | 9 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 | 2 / 11 | 1 / 10 | 4 / 12 | 7 / 10 | 0 / 10 |
| serious Total, serious adverse events | 0 / 11 | 0 / 10 | 0 / 12 | 0 / 10 | 0 / 10 |
Outcome results
Primary
AUC(0-tz)
Area under the concentration-time curve of deleobuvir in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz)
Time frame: 1 hour (h) before drug administration and 30 minutes (min), 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h and 48h after drug administration
Population: Pharmacokinetic set (PKS): included all subjects in the Treated Set who provided at least 1 observation for at least 1 primary pharmacokinetic (PK) endpoint that was not affected by important protocol violations relevant to the evaluation of PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dele Fasted | AUC(0-tz) | 9790 nmol*h/L | Geometric Coefficient of Variation 60.2 |
| Dele High Fat | AUC(0-tz) | 16900 nmol*h/L | Geometric Coefficient of Variation 98.8 |
| Dele Low Fat | AUC(0-tz) | 14200 nmol*h/L | Geometric Coefficient of Variation 46.8 |
| Dele + OMP | AUC(0-tz) | 15800 nmol*h/L | Geometric Coefficient of Variation 72.1 |
Comparison: The difference between the expected means for log(Dele low fat) and log(Dele fasted) was estimated by the differences in the adjusted means (Least Squares Means), and a 2 sided 90% confidence interval (CI) based on the t-distribution was computed.~These were then back transformed. The estimation model included effects accounting for the following sources of variation: 'sequence', 'subjects within sequence', 'period', and 'treatment'.p-value: 0.394490% CI: [63.52, 211.11]ANOVA
Primary
Cmax
Maximum measured concentration of deleobuvir in plasma (Cmax)
Time frame: 1 hour (h) before drug administration and 30 minutes (min), 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h and 48h after drug administration
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dele Fasted | Cmax | 2140 nmol/L | Geometric Coefficient of Variation 60.1 |
| Dele High Fat | Cmax | 3930 nmol/L | Geometric Coefficient of Variation 92.5 |
| Dele Low Fat | Cmax | 3160 nmol/L | Geometric Coefficient of Variation 52.2 |
| Dele + OMP | Cmax | 3190 nmol/L | Geometric Coefficient of Variation 90.2 |
Comparison: The difference between the expected means for log(Dele low fat) and log(Dele fasted) was estimated by the differences in the adjusted means (Least Squares Means), and a 2 sided 90% CI based on the t-distribution was computed.~These were then back transformed. This estimation model included effects accounting for the following sources of variation: 'sequence', 'subjects within sequence', 'period', and 'treatment'.p-value: 0.367490% CI: [74.803, 176.281]ANOVA
Secondary
AUC(0-inf)
Area under the concentration-time curve of deleobuvir in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf)
Time frame: 1 hour (h) before drug administration and 30 minutes (min), 1h, 1h 30min, 2h, 2h 30min, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h and 48h after drug administration
Population: PKS - Due to premature discontinuation of the study, this endpoint was not evaluated.