Trial Outcomes & Findings for Effect of Food and Increased Gastric pH Value on Bioavailability of a Single Dose of BI 207127 in Healthy Caucasian and Japanese Subjects (NCT NCT01983566)
NCT ID: NCT01983566
Last Updated: 2016-05-16
Results Overview
Area under the concentration-time curve of deleobuvir in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz)
Recruitment status
TERMINATED
Study phase
PHASE1
Target enrollment
16 participants
Primary outcome timeframe
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
Results posted on
2016-05-16
Participant Flow
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.
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.
Participant milestones
| Measure |
Dele Fasted / Dele High Fat / Dele + OMP / Dele Low Fat
Each subject received a single dose of 3 x 200 mg Deleobuvir (Dele) film-coated tablets after an overnight fast of at least 10 hours (h), followed by a washout phase of at least 6 days; then each subject received a single dose of 3 x 200 mg Dele film-coated tablets after a standardised high-fat, high-calorie meal after an overnight fast of at least 10 h, followed by a washout phase of at least 6 days; then each subject received a single dose of 3 x 200 mg Dele film-coated tablets after an overnight fast of at least 10 h after 4 days of pre-treatment with a 40 mg Omeprazole (OMP) gastro-resistant hard capsule once daily, followed by a washout phase of at least 6 days; then each subject received a single dose of 3 x 200 mg Dele film-coated tablets after a standardised low-fat meal after an overnight fast of at least 10 h.
All medications were administered oral with 240 mL of water.
|
Dele High Fat / Dele Low Fat / Dele Fasted / Dele + OMP
Each subject received a single dose of 3 x 200 mg Dele film-coated tablets after a standardised high-fat, high-calorie meal after an overnight fast of at least 10 h, followed by a washout phase of at least 6 days; then each subject received a single dose of 3 x 200 mg Dele film-coated tablets after a standardised low-fat meal after an overnight fast of at least 10 h, followed by a washout phase of at least 6 days; then each subject received a single dose of 3 x 200 mg Dele film-coated tablets after an overnight fast of at least 10 h, followed by a washout phase of at least 6 days; then each subject received a single dose of 3 x 200 mg Dele film-coated tablets after an overnight fast of at least 10 h after 4 days of pre-treatment with a 40 mg OMP gastro-resistant hard capsule once daily.
All medications were administered oral with 240 mL of water.
|
Dele Low Fat / Dele + OMP / Dele High Fat / Dele Fasted
Each subject received a single dose of 3 x 200 mg Dele film-coated tablets after a standardised low-fat meal after an overnight fast of at least 10 h, followed by a washout phase of at least 6 days; then each subject received a single dose of 3 x 200 mg Dele film-coated tablets after an overnight fast of at least 10 h after 4 days of pre-treatment with a 40 mg OMP gastro-resistant hard capsule once daily, followed by a washout phase of at least 6 days; then each subject received a single dose of 3 x 200 mg Dele film-coated tablets after a standardised high-fat, high-calorie meal after an overnight fast of at least 10 h, followed by a washout phase of at least 6 days; then each subject received a single dose of 3 x 200 mg Dele film-coated tablets after an overnight fast of at least 10 h.
All medications were administered oral with 240 mL of water.
|
Dele + OMP / Dele Fasted / Dele Low Fat / Dele High Fat
Each subject received a single dose of 3 x 200 mg Dele film-coated tablets after an overnight fast of at least 10 h after 4 days of pre-treatment with a 40 mg OMP gastro-resistant hard capsule once daily, followed by a washout phase of at least 6 days; then each subject received a single dose of 3 x 200 mg Dele film-coated tablets after an overnight fast of at least 10 h, followed by a washout phase of at least 6 days; then each subject received a single dose of 3 x 200 mg Dele film-coated tablets after a standardised low-fat meal after an overnight fast of at least 10 h, followed by a washout phase of at least 6 days; then each subject received a single dose of 3 x 200 mg Dele film-coated tablets after a standardised high-fat, high-calorie meal after an overnight fast of at least 10 h.
All medications were administered oral with 240 mL of water.
|
|---|---|---|---|---|
|
Test Period 1
STARTED
|
4
|
4
|
4
|
4
|
|
Test Period 1
COMPLETED
|
4
|
4
|
4
|
4
|
|
Test Period 1
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Wash-Out 1
STARTED
|
4
|
4
|
4
|
4
|
|
Wash-Out 1
COMPLETED
|
4
|
4
|
4
|
4
|
|
Wash-Out 1
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Test Period 2
STARTED
|
4
|
4
|
4
|
4
|
|
Test Period 2
COMPLETED
|
4
|
4
|
4
|
4
|
|
Test Period 2
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Wash-Out 2
STARTED
|
2
|
3
|
2
|
4
|
|
Wash-Out 2
COMPLETED
|
2
|
3
|
2
|
4
|
|
Wash-Out 2
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Test Period 3
STARTED
|
2
|
3
|
2
|
4
|
|
Test Period 3
COMPLETED
|
2
|
3
|
2
|
4
|
|
Test Period 3
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Wash-Out 3
STARTED
|
0
|
0
|
0
|
0
|
|
Wash-Out 3
COMPLETED
|
0
|
0
|
0
|
0
|
|
Wash-Out 3
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Test Period 4
STARTED
|
0
|
0
|
0
|
0
|
|
Test Period 4
COMPLETED
|
0
|
0
|
0
|
0
|
|
Test Period 4
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Effect of Food and Increased Gastric pH Value on Bioavailability of a Single Dose of BI 207127 in Healthy Caucasian and Japanese Subjects
Baseline characteristics by cohort
| Measure |
Dele Fasted / Dele High Fat / Dele + OMP / Dele Low Fat
n=4 Participants
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.
|
Dele High Fat / Dele Low Fat / Dele Fasted / Dele + OMP
n=4 Participants
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.
|
Dele Low Fat / Dele + OMP / Dele High Fat / Dele Fasted
n=4 Participants
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.
|
Dele + OMP / Dele Fasted / Dele Low Fat / Dele High Fat
n=4 Participants
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.
|
Total
n=16 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
29.3 years
STANDARD_DEVIATION 3.0 • n=99 Participants
|
25.3 years
STANDARD_DEVIATION 1.0 • n=107 Participants
|
32.3 years
STANDARD_DEVIATION 2.9 • n=206 Participants
|
27.8 years
STANDARD_DEVIATION 3.0 • n=7 Participants
|
28.6 years
STANDARD_DEVIATION 3.5 • n=31 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
7 Participants
n=31 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
4 Participants
n=7 Participants
|
9 Participants
n=31 Participants
|
PRIMARY outcome
Timeframe: 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 administrationPopulation: 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.
Area under the concentration-time curve of deleobuvir in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz)
Outcome measures
| Measure |
Dele Fasted
n=11 Participants
Each subject received a single dose of 3 x 200 mg Dele film-coated tablets after an overnight fast of at least 10 h.
The tablets were administered oral with 240 mL of water.
|
Dele High Fat
n=10 Participants
Each subject received a single dose of 3 x 200 mg Dele film-coated tablets after a standardised high-fat, high-calorie meal after an overnight fast of at least 10 h.
The tablets were administered oral with 240 mL of water.
|
Dele Low Fat
n=12 Participants
Each subject received a single dose of 3 x 200 mg Dele film-coated tablets after a standardised low-fat meal after an overnight fast of at least 10 h.
The tablets were administered oral with 240 mL of water.
|
Dele + OMP
n=10 Participants
Each subject received a single dose of 3 x 200 mg Dele film-coated tablets after an overnight fast of at least 10 h after 4 days of pre-treatment with a 40 mg Omeprazole (OMP) gastro-resistant hard capsule once daily.
All medications were administered oral with 240 mL of water.
|
|---|---|---|---|---|
|
AUC(0-tz)
|
9790 nmol*h/L
Geometric Coefficient of Variation 60.2
|
16900 nmol*h/L
Geometric Coefficient of Variation 98.8
|
14200 nmol*h/L
Geometric Coefficient of Variation 46.8
|
15800 nmol*h/L
Geometric Coefficient of Variation 72.1
|
PRIMARY outcome
Timeframe: 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 administrationPopulation: PKS
Maximum measured concentration of deleobuvir in plasma (Cmax)
Outcome measures
| Measure |
Dele Fasted
n=11 Participants
Each subject received a single dose of 3 x 200 mg Dele film-coated tablets after an overnight fast of at least 10 h.
The tablets were administered oral with 240 mL of water.
|
Dele High Fat
n=10 Participants
Each subject received a single dose of 3 x 200 mg Dele film-coated tablets after a standardised high-fat, high-calorie meal after an overnight fast of at least 10 h.
The tablets were administered oral with 240 mL of water.
|
Dele Low Fat
n=12 Participants
Each subject received a single dose of 3 x 200 mg Dele film-coated tablets after a standardised low-fat meal after an overnight fast of at least 10 h.
The tablets were administered oral with 240 mL of water.
|
Dele + OMP
n=10 Participants
Each subject received a single dose of 3 x 200 mg Dele film-coated tablets after an overnight fast of at least 10 h after 4 days of pre-treatment with a 40 mg Omeprazole (OMP) gastro-resistant hard capsule once daily.
All medications were administered oral with 240 mL of water.
|
|---|---|---|---|---|
|
Cmax
|
2140 nmol/L
Geometric Coefficient of Variation 60.1
|
3930 nmol/L
Geometric Coefficient of Variation 92.5
|
3160 nmol/L
Geometric Coefficient of Variation 52.2
|
3190 nmol/L
Geometric Coefficient of Variation 90.2
|
SECONDARY outcome
Timeframe: 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 administrationPopulation: PKS - Due to premature discontinuation of the study, this endpoint was not evaluated.
Area under the concentration-time curve of deleobuvir in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf)
Outcome measures
Outcome data not reported
Adverse Events
Dele Fasted
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Dele High Fat
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Dele Low Fat
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Dele + OMP
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
OMP Alone
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Dele Fasted
n=11 participants at risk
Each subject received a single dose of 3 x 200 mg Dele film-coated tablets after an overnight fast of at least 10 h.
The tablets were administered oral with 240 mL of water.
|
Dele High Fat
n=10 participants at risk
Each subject received a single dose of 3 x 200 mg Dele film-coated tablets after a standardised high-fat, high-calorie meal after an overnight fast of at least 10 h.
The tablets were administered oral with 240 mL of water.
|
Dele Low Fat
n=12 participants at risk
Each subject received a single dose of 3 x 200 mg Dele film-coated tablets after a standardised low-fat meal after an overnight fast of at least 10 h.
The tablets were administered oral with 240 mL of water.
|
Dele + OMP
n=10 participants at risk
Each subject received a single dose of 3 x 200 mg Dele film-coated tablets after an overnight fast of at least 10 h after 4 days of pre-treatment with a 40 mg Omeprazole (OMP) gastro-resistant hard capsule once daily.
All medications were administered oral with 240 mL of water.
|
OMP Alone
n=10 participants at risk
One gastro-resistant hard capsule of Omeprazole (OMP) (40 mg) once daily in the evening for 4 days administered oral with 240 mL of water.
|
|---|---|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/11 • From the time of first administration of the respective treatment until start of the next treatment or until the day after the termination date (or until 3 days after administration of last study drug, whichever occurred later), up to 37 days.
|
0.00%
0/10 • From the time of first administration of the respective treatment until start of the next treatment or until the day after the termination date (or until 3 days after administration of last study drug, whichever occurred later), up to 37 days.
|
0.00%
0/12 • From the time of first administration of the respective treatment until start of the next treatment or until the day after the termination date (or until 3 days after administration of last study drug, whichever occurred later), up to 37 days.
|
10.0%
1/10 • From the time of first administration of the respective treatment until start of the next treatment or until the day after the termination date (or until 3 days after administration of last study drug, whichever occurred later), up to 37 days.
|
0.00%
0/10 • From the time of first administration of the respective treatment until start of the next treatment or until the day after the termination date (or until 3 days after administration of last study drug, whichever occurred later), up to 37 days.
|
|
Nervous system disorders
Syncope
|
0.00%
0/11 • From the time of first administration of the respective treatment until start of the next treatment or until the day after the termination date (or until 3 days after administration of last study drug, whichever occurred later), up to 37 days.
|
10.0%
1/10 • From the time of first administration of the respective treatment until start of the next treatment or until the day after the termination date (or until 3 days after administration of last study drug, whichever occurred later), up to 37 days.
|
0.00%
0/12 • From the time of first administration of the respective treatment until start of the next treatment or until the day after the termination date (or until 3 days after administration of last study drug, whichever occurred later), up to 37 days.
|
0.00%
0/10 • From the time of first administration of the respective treatment until start of the next treatment or until the day after the termination date (or until 3 days after administration of last study drug, whichever occurred later), up to 37 days.
|
0.00%
0/10 • From the time of first administration of the respective treatment until start of the next treatment or until the day after the termination date (or until 3 days after administration of last study drug, whichever occurred later), up to 37 days.
|
|
Nervous system disorders
Dizziness
|
0.00%
0/11 • From the time of first administration of the respective treatment until start of the next treatment or until the day after the termination date (or until 3 days after administration of last study drug, whichever occurred later), up to 37 days.
|
0.00%
0/10 • From the time of first administration of the respective treatment until start of the next treatment or until the day after the termination date (or until 3 days after administration of last study drug, whichever occurred later), up to 37 days.
|
8.3%
1/12 • From the time of first administration of the respective treatment until start of the next treatment or until the day after the termination date (or until 3 days after administration of last study drug, whichever occurred later), up to 37 days.
|
0.00%
0/10 • From the time of first administration of the respective treatment until start of the next treatment or until the day after the termination date (or until 3 days after administration of last study drug, whichever occurred later), up to 37 days.
|
0.00%
0/10 • From the time of first administration of the respective treatment until start of the next treatment or until the day after the termination date (or until 3 days after administration of last study drug, whichever occurred later), up to 37 days.
|
|
Gastrointestinal disorders
Nausea
|
18.2%
2/11 • From the time of first administration of the respective treatment until start of the next treatment or until the day after the termination date (or until 3 days after administration of last study drug, whichever occurred later), up to 37 days.
|
0.00%
0/10 • From the time of first administration of the respective treatment until start of the next treatment or until the day after the termination date (or until 3 days after administration of last study drug, whichever occurred later), up to 37 days.
|
16.7%
2/12 • From the time of first administration of the respective treatment until start of the next treatment or until the day after the termination date (or until 3 days after administration of last study drug, whichever occurred later), up to 37 days.
|
50.0%
5/10 • From the time of first administration of the respective treatment until start of the next treatment or until the day after the termination date (or until 3 days after administration of last study drug, whichever occurred later), up to 37 days.
|
0.00%
0/10 • From the time of first administration of the respective treatment until start of the next treatment or until the day after the termination date (or until 3 days after administration of last study drug, whichever occurred later), up to 37 days.
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/11 • From the time of first administration of the respective treatment until start of the next treatment or until the day after the termination date (or until 3 days after administration of last study drug, whichever occurred later), up to 37 days.
|
0.00%
0/10 • From the time of first administration of the respective treatment until start of the next treatment or until the day after the termination date (or until 3 days after administration of last study drug, whichever occurred later), up to 37 days.
|
0.00%
0/12 • From the time of first administration of the respective treatment until start of the next treatment or until the day after the termination date (or until 3 days after administration of last study drug, whichever occurred later), up to 37 days.
|
10.0%
1/10 • From the time of first administration of the respective treatment until start of the next treatment or until the day after the termination date (or until 3 days after administration of last study drug, whichever occurred later), up to 37 days.
|
0.00%
0/10 • From the time of first administration of the respective treatment until start of the next treatment or until the day after the termination date (or until 3 days after administration of last study drug, whichever occurred later), up to 37 days.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
9.1%
1/11 • From the time of first administration of the respective treatment until start of the next treatment or until the day after the termination date (or until 3 days after administration of last study drug, whichever occurred later), up to 37 days.
|
0.00%
0/10 • From the time of first administration of the respective treatment until start of the next treatment or until the day after the termination date (or until 3 days after administration of last study drug, whichever occurred later), up to 37 days.
|
0.00%
0/12 • From the time of first administration of the respective treatment until start of the next treatment or until the day after the termination date (or until 3 days after administration of last study drug, whichever occurred later), up to 37 days.
|
0.00%
0/10 • From the time of first administration of the respective treatment until start of the next treatment or until the day after the termination date (or until 3 days after administration of last study drug, whichever occurred later), up to 37 days.
|
0.00%
0/10 • From the time of first administration of the respective treatment until start of the next treatment or until the day after the termination date (or until 3 days after administration of last study drug, whichever occurred later), up to 37 days.
|
|
General disorders
Fatigue
|
0.00%
0/11 • From the time of first administration of the respective treatment until start of the next treatment or until the day after the termination date (or until 3 days after administration of last study drug, whichever occurred later), up to 37 days.
|
0.00%
0/10 • From the time of first administration of the respective treatment until start of the next treatment or until the day after the termination date (or until 3 days after administration of last study drug, whichever occurred later), up to 37 days.
|
16.7%
2/12 • From the time of first administration of the respective treatment until start of the next treatment or until the day after the termination date (or until 3 days after administration of last study drug, whichever occurred later), up to 37 days.
|
0.00%
0/10 • From the time of first administration of the respective treatment until start of the next treatment or until the day after the termination date (or until 3 days after administration of last study drug, whichever occurred later), up to 37 days.
|
0.00%
0/10 • From the time of first administration of the respective treatment until start of the next treatment or until the day after the termination date (or until 3 days after administration of last study drug, whichever occurred later), up to 37 days.
|
|
Nervous system disorders
Headache
|
9.1%
1/11 • From the time of first administration of the respective treatment until start of the next treatment or until the day after the termination date (or until 3 days after administration of last study drug, whichever occurred later), up to 37 days.
|
0.00%
0/10 • From the time of first administration of the respective treatment until start of the next treatment or until the day after the termination date (or until 3 days after administration of last study drug, whichever occurred later), up to 37 days.
|
8.3%
1/12 • From the time of first administration of the respective treatment until start of the next treatment or until the day after the termination date (or until 3 days after administration of last study drug, whichever occurred later), up to 37 days.
|
10.0%
1/10 • From the time of first administration of the respective treatment until start of the next treatment or until the day after the termination date (or until 3 days after administration of last study drug, whichever occurred later), up to 37 days.
|
0.00%
0/10 • From the time of first administration of the respective treatment until start of the next treatment or until the day after the termination date (or until 3 days after administration of last study drug, whichever occurred later), up to 37 days.
|
Additional Information
Boehringer Ingelheim Call Center
Boehringer Ingelheim Pharmaceuticals
Phone: 1-800-243-0127
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Other - Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER