Trial Outcomes & Findings for Drug-drug Interaction of Empagliflozin (BI 10773) and Simvastatin (NCT NCT01304329)
NCT ID: NCT01304329
Last Updated: 2014-07-28
Results Overview
Area under the concentration-time curve of empagliflozin (empa) in plasma over the time interval from 0 extrapolated to infinity. The geometric mean (gMean) and geometric coefficient of variation (gCV) are adjusted values.
COMPLETED
PHASE1
18 participants
0 hours (h), 20minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration
2014-07-28
Participant Flow
This was a randomised, open label, 3 period crossover study. Treatment periods were separated by a washout period of at least 7 days.
Participant milestones
| Measure |
Empa Alone / Simvastatin Alone / Empa Plus Sim
Patients were administered three treatments in the following order:
* A single dose of empagliflozin 25mg
* A single dose of simvastatin 40mg
* A single dose of empagliflozin 25mg together with 40mg simvastatin
|
Empa Alone / Empa Plus Sim / Simvastatin Alone
Patients were administered three treatments in the following order:
* A single dose of empagliflozin 25mg
* A single dose of empagliflozin 25mg together with 40mg simvastatin
* A single dose of simvastatin 40mg
|
Simvastatin Alone / Empa Alone / Empa Plus Sim
Patients were administered three treatments in the following order:
* A single dose of simvastatin 40mg
* A single dose of empagliflozin 25mg
* A single dose of empagliflozin 25mg together with 40mg simvastatin
|
Simvastatin Alone / Empa Plus Sim / Empa Alone
Patients were administered three treatments in the following order:
* A single dose of simvastatin 40mg
* A single dose of empagliflozin 25mg together with 40mg simvastatin
* A single dose of empagliflozin 25mg
|
Empa Plus Sim / Empa Alone / Simvastatin Alone
Patients were administered three treatments in the following order:
* A single dose of empagliflozin 25mg together with 40mg simvastatin
* A single dose of empagliflozin 25mg
* A single dose of simvastatin 40mg
|
Empa Plus Sim / Simvastatin Alone / Empa Alone
Patients were administered three treatments in the following order:
* A single dose of empagliflozin 25mg together with 40mg simvastatin
* A single dose of simvastatin 40mg
* A single dose of empagliflozin 25mg
|
|---|---|---|---|---|---|---|
|
First Intervention (3 Days)
STARTED
|
3
|
3
|
3
|
3
|
3
|
3
|
|
First Intervention (3 Days)
COMPLETED
|
3
|
3
|
3
|
3
|
3
|
3
|
|
First Intervention (3 Days)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Second Intervention (3 Days)
STARTED
|
3
|
3
|
3
|
3
|
3
|
3
|
|
Second Intervention (3 Days)
COMPLETED
|
3
|
3
|
3
|
3
|
3
|
3
|
|
Second Intervention (3 Days)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Third Intervention (3 Days)
STARTED
|
3
|
3
|
3
|
3
|
3
|
3
|
|
Third Intervention (3 Days)
COMPLETED
|
3
|
2
|
3
|
3
|
3
|
3
|
|
Third Intervention (3 Days)
NOT COMPLETED
|
0
|
1
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Empa Alone / Simvastatin Alone / Empa Plus Sim
Patients were administered three treatments in the following order:
* A single dose of empagliflozin 25mg
* A single dose of simvastatin 40mg
* A single dose of empagliflozin 25mg together with 40mg simvastatin
|
Empa Alone / Empa Plus Sim / Simvastatin Alone
Patients were administered three treatments in the following order:
* A single dose of empagliflozin 25mg
* A single dose of empagliflozin 25mg together with 40mg simvastatin
* A single dose of simvastatin 40mg
|
Simvastatin Alone / Empa Alone / Empa Plus Sim
Patients were administered three treatments in the following order:
* A single dose of simvastatin 40mg
* A single dose of empagliflozin 25mg
* A single dose of empagliflozin 25mg together with 40mg simvastatin
|
Simvastatin Alone / Empa Plus Sim / Empa Alone
Patients were administered three treatments in the following order:
* A single dose of simvastatin 40mg
* A single dose of empagliflozin 25mg together with 40mg simvastatin
* A single dose of empagliflozin 25mg
|
Empa Plus Sim / Empa Alone / Simvastatin Alone
Patients were administered three treatments in the following order:
* A single dose of empagliflozin 25mg together with 40mg simvastatin
* A single dose of empagliflozin 25mg
* A single dose of simvastatin 40mg
|
Empa Plus Sim / Simvastatin Alone / Empa Alone
Patients were administered three treatments in the following order:
* A single dose of empagliflozin 25mg together with 40mg simvastatin
* A single dose of simvastatin 40mg
* A single dose of empagliflozin 25mg
|
|---|---|---|---|---|---|---|
|
Third Intervention (3 Days)
Adverse Event
|
0
|
1
|
0
|
0
|
0
|
0
|
Baseline Characteristics
Drug-drug Interaction of Empagliflozin (BI 10773) and Simvastatin
Baseline characteristics by cohort
| Measure |
Study Overall
n=18 Participants
This was a randomised, 3-period, crossover trial. The trial was open label. The three treatments were separated by a washout period of at least 7 days.
|
|---|---|
|
Age, Continuous
|
35.9 years
STANDARD_DEVIATION 8.8 • n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 0 hours (h), 20minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administrationPopulation: Pharmacokinetic (PK) set: PK set included all evaluable subjects who took at least one dose of investigational treatment and provided at least one observation for at least one primary PK endpoint without important protocol violations relevant to the evaluation of PK.
Area under the concentration-time curve of empagliflozin (empa) in plasma over the time interval from 0 extrapolated to infinity. The geometric mean (gMean) and geometric coefficient of variation (gCV) are adjusted values.
Outcome measures
| Measure |
Empa Alone
n=18 Participants
25mg empagliflozin (empa) alone
|
Empa Plus Sim
n=18 Participants
25 mg empagliflozin (empa) together with 40 mg simvastatin (sim)
|
|---|---|---|
|
Empa: Area Under the Curve 0 to Infinity (AUC0-∞)
|
5571.70 nmol*h/L
Geometric Coefficient of Variation 5.4
|
5685.69 nmol*h/L
Geometric Coefficient of Variation 5.4
|
PRIMARY outcome
Timeframe: 0 hours (h), 20minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administrationPopulation: Pharmacokinetic (PK) set: PK set included all evaluable subjects who took at least one dose of investigational treatment and provided at least one observation for at least one primary PK endpoint without important protocol violations relevant to the evaluation of PK.
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity. Simvastatin acid is an active metabolite of simvastatin. The geometric mean (gMean) and geometric coefficient of variation (gCV) are adjusted values.
Outcome measures
| Measure |
Empa Alone
n=17 Participants
25mg empagliflozin (empa) alone
|
Empa Plus Sim
n=18 Participants
25 mg empagliflozin (empa) together with 40 mg simvastatin (sim)
|
|---|---|---|
|
Simvastatin: Area Under the Curve 0 to Infinity (AUC0-∞)
AUC of simvastatin
|
33.51 ng*h/mL
Geometric Coefficient of Variation 40.4
|
33.93 ng*h/mL
Geometric Coefficient of Variation 40.4
|
|
Simvastatin: Area Under the Curve 0 to Infinity (AUC0-∞)
AUC of simvastatin acid
|
16.83 ng*h/mL
Geometric Coefficient of Variation 25.5
|
17.65 ng*h/mL
Geometric Coefficient of Variation 25.5
|
PRIMARY outcome
Timeframe: 0 hours (h), 20minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administrationPopulation: Pharmacokinetic (PK) set: PK set included all evaluable subjects who took at least one dose of investigational treatment and provided at least one observation for at least one primary PK endpoint without important protocol violations relevant to the evaluation of PK.
Maximum measured concentration of the analyte in plasma, per period. The geometric mean and geometric coefficient of variation (gCV) are adjusted values
Outcome measures
| Measure |
Empa Alone
n=18 Participants
25mg empagliflozin (empa) alone
|
Empa Plus Sim
n=18 Participants
25 mg empagliflozin (empa) together with 40 mg simvastatin (sim)
|
|---|---|---|
|
Empa: Maximum Measured Concentration (Cmax)
|
774.06 nmol/L
Geometric Coefficient of Variation 21.1
|
847.49 nmol/L
Geometric Coefficient of Variation 21.1
|
PRIMARY outcome
Timeframe: 0 hours (h), 20minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administrationPopulation: Pharmacokinetic (PK) set: PK set included all evaluable subjects who took at least one dose of investigational treatment and provided at least one observation for at least one primary PK endpoint without important protocol violations relevant to the evaluation of PK.
Maximum measured concentration of the analyte in plasma, per period. The geometric mean and geometric coefficient of variation (gCV) are adjusted values.
Outcome measures
| Measure |
Empa Alone
n=17 Participants
25mg empagliflozin (empa) alone
|
Empa Plus Sim
n=18 Participants
25 mg empagliflozin (empa) together with 40 mg simvastatin (sim)
|
|---|---|---|
|
Simvastatin: Maximum Measured Concentration (Cmax)
Cmax of simvastatin
|
7.88 ng/mL
Geometric Coefficient of Variation 41.7
|
7.65 ng/mL
Geometric Coefficient of Variation 41.7
|
|
Simvastatin: Maximum Measured Concentration (Cmax)
Cmax of simvastatin acid
|
1.51 ng/mL
Geometric Coefficient of Variation 22.7
|
1.47 ng/mL
Geometric Coefficient of Variation 22.7
|
SECONDARY outcome
Timeframe: 0 hours (h), 20minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administrationPopulation: Pharmacokinetic (PK) set: PK set included all evaluable subjects who took at least one dose of investigational treatment and provided at least one observation for at least one primary PK endpoint without important protocol violations relevant to the evaluation of PK.
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point. The geometric mean and geometric coefficient of variation (gCV) are adjusted values.
Outcome measures
| Measure |
Empa Alone
n=18 Participants
25mg empagliflozin (empa) alone
|
Empa Plus Sim
n=18 Participants
25 mg empagliflozin (empa) together with 40 mg simvastatin (sim)
|
|---|---|---|
|
Empa: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz)
|
5481.31 nmol*h/L
Geometric Coefficient of Variation 5.8
|
5619.60 nmol*h/L
Geometric Coefficient of Variation 5.8
|
SECONDARY outcome
Timeframe: 0 hours (h), 20minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administrationPopulation: Pharmacokinetic (PK) set: PK set included all evaluable subjects who took at least one dose of investigational treatment and provided at least one observation for at least one primary PK endpoint without important protocol violations relevant to the evaluation of PK.
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point. The geometric mean and geometric coefficient of variation (gCV) are adjusted values.
Outcome measures
| Measure |
Empa Alone
n=17 Participants
25mg empagliflozin (empa) alone
|
Empa Plus Sim
n=18 Participants
25 mg empagliflozin (empa) together with 40 mg simvastatin (sim)
|
|---|---|---|
|
Simvastatin: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz)
AUC of simvastatin
|
31.82 ng*h/mL
Geometric Coefficient of Variation 41.7
|
32.57 ng*h/mL
Geometric Coefficient of Variation 41.7
|
|
Simvastatin: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz)
AUC of simvastatin acid
|
14.86 ng*h/mL
Geometric Coefficient of Variation 24.8
|
16.53 ng*h/mL
Geometric Coefficient of Variation 24.8
|
Adverse Events
Empa Alone
Simvastatin Alone
Empa Plus Sim
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Empa Alone
n=18 participants at risk
25mg empagliflozin (empa) alone
|
Simvastatin Alone
n=17 participants at risk
40 mg simvastatin alone
|
Empa Plus Sim
n=18 participants at risk
25 mg empagliflozin (empa) together with 40 mg simvastatin (sim)
|
|---|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/18 • First administration of trial medication until next administration of trial medication or up to post-study visit, up to 36 days
|
5.9%
1/17 • First administration of trial medication until next administration of trial medication or up to post-study visit, up to 36 days
|
0.00%
0/18 • First administration of trial medication until next administration of trial medication or up to post-study visit, up to 36 days
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/18 • First administration of trial medication until next administration of trial medication or up to post-study visit, up to 36 days
|
0.00%
0/17 • First administration of trial medication until next administration of trial medication or up to post-study visit, up to 36 days
|
5.6%
1/18 • First administration of trial medication until next administration of trial medication or up to post-study visit, up to 36 days
|
|
Infections and infestations
Nasopharyngitis
|
11.1%
2/18 • First administration of trial medication until next administration of trial medication or up to post-study visit, up to 36 days
|
0.00%
0/17 • First administration of trial medication until next administration of trial medication or up to post-study visit, up to 36 days
|
5.6%
1/18 • First administration of trial medication until next administration of trial medication or up to post-study visit, up to 36 days
|
|
Infections and infestations
Oral herpes
|
5.6%
1/18 • First administration of trial medication until next administration of trial medication or up to post-study visit, up to 36 days
|
0.00%
0/17 • First administration of trial medication until next administration of trial medication or up to post-study visit, up to 36 days
|
0.00%
0/18 • First administration of trial medication until next administration of trial medication or up to post-study visit, up to 36 days
|
|
Infections and infestations
Purulence
|
0.00%
0/18 • First administration of trial medication until next administration of trial medication or up to post-study visit, up to 36 days
|
0.00%
0/17 • First administration of trial medication until next administration of trial medication or up to post-study visit, up to 36 days
|
5.6%
1/18 • First administration of trial medication until next administration of trial medication or up to post-study visit, up to 36 days
|
|
Injury, poisoning and procedural complications
Laceration
|
0.00%
0/18 • First administration of trial medication until next administration of trial medication or up to post-study visit, up to 36 days
|
5.9%
1/17 • First administration of trial medication until next administration of trial medication or up to post-study visit, up to 36 days
|
0.00%
0/18 • First administration of trial medication until next administration of trial medication or up to post-study visit, up to 36 days
|
|
Nervous system disorders
Headache
|
22.2%
4/18 • First administration of trial medication until next administration of trial medication or up to post-study visit, up to 36 days
|
11.8%
2/17 • First administration of trial medication until next administration of trial medication or up to post-study visit, up to 36 days
|
11.1%
2/18 • First administration of trial medication until next administration of trial medication or up to post-study visit, up to 36 days
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/18 • First administration of trial medication until next administration of trial medication or up to post-study visit, up to 36 days
|
0.00%
0/17 • First administration of trial medication until next administration of trial medication or up to post-study visit, up to 36 days
|
5.6%
1/18 • First administration of trial medication until next administration of trial medication or up to post-study visit, up to 36 days
|
Additional Information
Boehringer Ingelheim Call Center
Boehringer Ingelheim Pharmaceuticals
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place