Trial Outcomes & Findings for Drug-interaction Trial in Healthy Subjects With Oral Administration of Empagliflozin (BI 10773), Rifampicin and Probenecid (NCT NCT01634100)
NCT ID: NCT01634100
Last Updated: 2014-07-03
Results Overview
Area under the concentration-time curve of total empagliflozin (empa) in plasma over the time interval from 0 extrapolated to infinity.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
18 participants
Primary outcome timeframe
15 minutes (min) prior to the first dose and 20min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h and 72h after the first dose
Results posted on
2014-07-03
Participant Flow
This was a randomised, 3-way crossover trial. 18 patients were randomised to one of six treatment sequences and treated. It was an open label trial in which each treatment period lasted 4 days with a washout period of at least 7 days between each.
Participant milestones
| Measure |
Empa Alone / Empa + Rifampicin / Empa + Probenecid
Patients were administered three treatments in the following order:
* Empa Alone (A single dose of 10mg of empagliflozin (empa))
* Empa + Rifampicin (A single dose of 10mg empagliflozin (empa) combined with a single dose of 600 mg rifampicin)
* Empa + Probenecid (A single dose of 10mg empagliflozin (empa) in the morning of day 1 combined with 500 mg of probenecid given twice daily for four days from day -1 to day 3)
|
Empa Alone / Empa + Probenecid / Empa + Rifampicin
Patients were administered three treatments in the following order:
* Empa Alone (A single dose of 10mg of empagliflozin (empa))
* Empa + Probenecid (A single dose of 10mg empagliflozin (empa) in the morning of day 1 combined with 500 mg of probenecid given twice daily for four days from day -1 to day 3)
* Empa + Rifampicin (A single dose of 10mg empagliflozin (empa) combined with a single dose of 600 mg rifampicin)
|
Empa + Rifampicin / Empa Alone / Empa + Probenecid
Patients were administered three treatments in the following order:
* Empa + Rifampicin (A single dose of 10mg empagliflozin (empa) combined with a single dose of 600 mg rifampicin)
* Empa Alone (A single dose of 10mg of empagliflozin (empa))
* Empa + Probenecid (A single dose of 10mg empagliflozin (empa) in the morning of day 1 combined with 500 mg of probenecid given twice daily for four days from day -1 to day 3)
|
Empa + Rifampicin / Empa + Probenecid / Empa Alone
Patients were administered three treatments in the following order:
* Empa + Rifampicin (A single dose of 10mg empagliflozin (empa) combined with a single dose of 600 mg rifampicin)
* Empa + Probenecid (A single dose of 10mg empagliflozin (empa) in the morning of day 1 combined with 500 mg of probenecid given twice daily for four days from day -1 to day 3)
* Empa Alone (A single dose of 10mg of empagliflozin (empa))
|
Empa + Probenecid / Empa Alone / Empa + Rifampicin
Patients were administered three treatments in the following order:
* Empa + Probenecid (A single dose of 10mg empagliflozin (empa) in the morning of day 1 combined with 500 mg of probenecid given twice daily for four days from day -1 to day 3)
* Empa Alone (A single dose of 10mg of empagliflozin (empa))
* Empa + Rifampicin (A single dose of 10mg empagliflozin (empa) combined with a single dose of 600 mg rifampicin)
|
Empa + Probenecid / Empa + Rifampicin / Empa Alone
Patients were administered three treatments in the following order:
* Empa + Probenecid (A single dose of 10mg empagliflozin (empa) in the morning of day 1 combined with 500 mg of probenecid given twice daily for four days from day -1 to day 3)
* Empa + Rifampicin (A single dose of 10mg empagliflozin (empa) combined with a single dose of 600 mg rifampicin)
* Empa Alone (A single dose of 10mg of empagliflozin (empa))
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
3
|
3
|
3
|
3
|
3
|
3
|
|
Overall Study
Received Empa Alone
|
3
|
3
|
3
|
3
|
3
|
3
|
|
Overall Study
Received Empa + Rifampicin
|
3
|
3
|
3
|
3
|
3
|
3
|
|
Overall Study
Received Empa + Probenecid
|
2
|
3
|
2
|
3
|
3
|
3
|
|
Overall Study
COMPLETED
|
2
|
3
|
2
|
3
|
3
|
3
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
1
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Empa Alone / Empa + Rifampicin / Empa + Probenecid
Patients were administered three treatments in the following order:
* Empa Alone (A single dose of 10mg of empagliflozin (empa))
* Empa + Rifampicin (A single dose of 10mg empagliflozin (empa) combined with a single dose of 600 mg rifampicin)
* Empa + Probenecid (A single dose of 10mg empagliflozin (empa) in the morning of day 1 combined with 500 mg of probenecid given twice daily for four days from day -1 to day 3)
|
Empa Alone / Empa + Probenecid / Empa + Rifampicin
Patients were administered three treatments in the following order:
* Empa Alone (A single dose of 10mg of empagliflozin (empa))
* Empa + Probenecid (A single dose of 10mg empagliflozin (empa) in the morning of day 1 combined with 500 mg of probenecid given twice daily for four days from day -1 to day 3)
* Empa + Rifampicin (A single dose of 10mg empagliflozin (empa) combined with a single dose of 600 mg rifampicin)
|
Empa + Rifampicin / Empa Alone / Empa + Probenecid
Patients were administered three treatments in the following order:
* Empa + Rifampicin (A single dose of 10mg empagliflozin (empa) combined with a single dose of 600 mg rifampicin)
* Empa Alone (A single dose of 10mg of empagliflozin (empa))
* Empa + Probenecid (A single dose of 10mg empagliflozin (empa) in the morning of day 1 combined with 500 mg of probenecid given twice daily for four days from day -1 to day 3)
|
Empa + Rifampicin / Empa + Probenecid / Empa Alone
Patients were administered three treatments in the following order:
* Empa + Rifampicin (A single dose of 10mg empagliflozin (empa) combined with a single dose of 600 mg rifampicin)
* Empa + Probenecid (A single dose of 10mg empagliflozin (empa) in the morning of day 1 combined with 500 mg of probenecid given twice daily for four days from day -1 to day 3)
* Empa Alone (A single dose of 10mg of empagliflozin (empa))
|
Empa + Probenecid / Empa Alone / Empa + Rifampicin
Patients were administered three treatments in the following order:
* Empa + Probenecid (A single dose of 10mg empagliflozin (empa) in the morning of day 1 combined with 500 mg of probenecid given twice daily for four days from day -1 to day 3)
* Empa Alone (A single dose of 10mg of empagliflozin (empa))
* Empa + Rifampicin (A single dose of 10mg empagliflozin (empa) combined with a single dose of 600 mg rifampicin)
|
Empa + Probenecid / Empa + Rifampicin / Empa Alone
Patients were administered three treatments in the following order:
* Empa + Probenecid (A single dose of 10mg empagliflozin (empa) in the morning of day 1 combined with 500 mg of probenecid given twice daily for four days from day -1 to day 3)
* Empa + Rifampicin (A single dose of 10mg empagliflozin (empa) combined with a single dose of 600 mg rifampicin)
* Empa Alone (A single dose of 10mg of empagliflozin (empa))
|
|---|---|---|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
1
|
0
|
0
|
0
|
Baseline Characteristics
Drug-interaction Trial in Healthy Subjects With Oral Administration of Empagliflozin (BI 10773), Rifampicin and Probenecid
Baseline characteristics by cohort
| Measure |
Study Overall
n=18 Participants
This was a randomised, 3-way crossover trial. 18 patients were randomised to one of six treatment sequences and treated. It was an open label trial in which each treatment period lasted 4 days with a washout period of at least 7 days between each.
|
|---|---|
|
Age, Continuous
|
32.7 years
STANDARD_DEVIATION 11.4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 15 minutes (min) prior to the first dose and 20min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h and 72h after the first dosePopulation: Pharmacokinetic (PK) set: The PK analysis set includes all subjects who took at least 1 dose of investigational treatment and provided at least 1 evaluable observation for at least 1 primary PK endpoint in at least 1 treatment period without any important protocol violations relevant to the evaluation of PK.
Area under the concentration-time curve of total empagliflozin (empa) in plasma over the time interval from 0 extrapolated to infinity.
Outcome measures
| Measure |
Empa Alone
n=18 Participants
A single dose of 10mg of empagliflozin (empa).
|
Empa + Rifampicin
n=18 Participants
A single dose of 10mg empagliflozin (empa) combined with a single dose of 600 mg rifampicin.
|
Empa + Probenecid
n=16 Participants
A single dose of 10mg empagliflozin (empa) in the morning of day 1 combined with 500 mg of probenecid given twice daily for four days from day -1 to day 3.
|
|---|---|---|---|
|
Total Empagliflozin: Area Under the Curve 0 to Infinity (AUC0-∞)
|
2240 nmol*h/L
Geometric Coefficient of Variation 28.1
|
3020 nmol*h/L
Geometric Coefficient of Variation 28.2
|
3400 nmol*h/L
Geometric Coefficient of Variation 28.7
|
PRIMARY outcome
Timeframe: 15 minutes (min) prior to the first dose and 20min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h and 72h after the first dosePopulation: Pharmacokinetic (PK) set: The PK analysis set includes all subjects who took at least 1 dose of investigational treatment and provided at least 1 evaluable observation for at least 1 primary PK endpoint in at least 1 treatment period without any important protocol violations relevant to the evaluation of PK.
Maximum measured concentration of total empa in plasma, per period.
Outcome measures
| Measure |
Empa Alone
n=18 Participants
A single dose of 10mg of empagliflozin (empa).
|
Empa + Rifampicin
n=18 Participants
A single dose of 10mg empagliflozin (empa) combined with a single dose of 600 mg rifampicin.
|
Empa + Probenecid
n=16 Participants
A single dose of 10mg empagliflozin (empa) in the morning of day 1 combined with 500 mg of probenecid given twice daily for four days from day -1 to day 3.
|
|---|---|---|---|
|
Total Empa: Maximum Measured Concentration (Cmax)
|
301 nmol/L
Geometric Coefficient of Variation 31.6
|
527 nmol/L
Geometric Coefficient of Variation 27.5
|
373 nmol/L
Geometric Coefficient of Variation 30.9
|
SECONDARY outcome
Timeframe: 15 minutes (min) prior to the first dose and 20min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h and 72h after the first dosePopulation: Pharmacokinetic (PK) set: The PK analysis set includes all subjects who took at least 1 dose of investigational treatment and provided at least 1 evaluable observation for at least 1 primary PK endpoint in at least 1 treatment period without any important protocol violations relevant to the evaluation of PK.
Area under the concentration-time curve of total empagliflozin (empa) in plasma over the time interval from 0 extrapolated to the time of last the quantifiable data point.
Outcome measures
| Measure |
Empa Alone
n=18 Participants
A single dose of 10mg of empagliflozin (empa).
|
Empa + Rifampicin
n=18 Participants
A single dose of 10mg empagliflozin (empa) combined with a single dose of 600 mg rifampicin.
|
Empa + Probenecid
n=16 Participants
A single dose of 10mg empagliflozin (empa) in the morning of day 1 combined with 500 mg of probenecid given twice daily for four days from day -1 to day 3.
|
|---|---|---|---|
|
Total Empagliflozin: Area Under the Curve 0 to Time of Last Quantifiable Data Point (AUC0-tz)
|
2200 nmol*h/L
Geometric Coefficient of Variation 28.6
|
3000 nmol*h/L
Geometric Coefficient of Variation 28.4
|
3350 nmol*h/L
Geometric Coefficient of Variation 29.1
|
Adverse Events
Empa Alone
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Empa + Rifampicin
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Empa + Probenecid
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Empa Alone
n=18 participants at risk
A single dose of 10mg of empagliflozin (empa).
|
Empa + Rifampicin
n=18 participants at risk
A single dose of 10mg empagliflozin (empa) combined with a single dose of 600 mg rifampicin.
|
Empa + Probenecid
n=16 participants at risk
A single dose of 10mg empagliflozin (empa) in the morning of day 1 combined with 500 mg of probenecid given twice daily for four days from day -1 to day 3.
|
|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
5.6%
1/18 • Treatment period until end of washout period/end of study examination, up to 29 days
|
0.00%
0/18 • Treatment period until end of washout period/end of study examination, up to 29 days
|
0.00%
0/16 • Treatment period until end of washout period/end of study examination, up to 29 days
|
|
Gastrointestinal disorders
Nausea
|
11.1%
2/18 • Treatment period until end of washout period/end of study examination, up to 29 days
|
16.7%
3/18 • Treatment period until end of washout period/end of study examination, up to 29 days
|
12.5%
2/16 • Treatment period until end of washout period/end of study examination, up to 29 days
|
|
Gastrointestinal disorders
Vomiting
|
11.1%
2/18 • Treatment period until end of washout period/end of study examination, up to 29 days
|
16.7%
3/18 • Treatment period until end of washout period/end of study examination, up to 29 days
|
6.2%
1/16 • Treatment period until end of washout period/end of study examination, up to 29 days
|
|
Injury, poisoning and procedural complications
Muscle strain
|
0.00%
0/18 • Treatment period until end of washout period/end of study examination, up to 29 days
|
0.00%
0/18 • Treatment period until end of washout period/end of study examination, up to 29 days
|
6.2%
1/16 • Treatment period until end of washout period/end of study examination, up to 29 days
|
|
Nervous system disorders
Dizziness
|
0.00%
0/18 • Treatment period until end of washout period/end of study examination, up to 29 days
|
11.1%
2/18 • Treatment period until end of washout period/end of study examination, up to 29 days
|
0.00%
0/16 • Treatment period until end of washout period/end of study examination, up to 29 days
|
|
Nervous system disorders
Headache
|
16.7%
3/18 • Treatment period until end of washout period/end of study examination, up to 29 days
|
27.8%
5/18 • Treatment period until end of washout period/end of study examination, up to 29 days
|
18.8%
3/16 • Treatment period until end of washout period/end of study examination, up to 29 days
|
|
Nervous system disorders
Presyncope
|
5.6%
1/18 • Treatment period until end of washout period/end of study examination, up to 29 days
|
0.00%
0/18 • Treatment period until end of washout period/end of study examination, up to 29 days
|
0.00%
0/16 • Treatment period until end of washout period/end of study examination, up to 29 days
|
|
Nervous system disorders
Sciatica
|
0.00%
0/18 • Treatment period until end of washout period/end of study examination, up to 29 days
|
5.6%
1/18 • Treatment period until end of washout period/end of study examination, up to 29 days
|
0.00%
0/16 • Treatment period until end of washout period/end of study examination, up to 29 days
|
|
Vascular disorders
Haematoma
|
5.6%
1/18 • Treatment period until end of washout period/end of study examination, up to 29 days
|
0.00%
0/18 • Treatment period until end of washout period/end of study examination, up to 29 days
|
0.00%
0/16 • Treatment period until end of washout period/end of study examination, up to 29 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 Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.
- Publication restrictions are in place
Restriction type: OTHER