Trial Outcomes & Findings for Drug Interaction Study of Digoxin and BI 10773 (NCT NCT01306175)

Results Overview

Area under the concentration-time curve of digoxin in plasma over the time interval from 0 extrapolated to infinity.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

20 participants

Primary outcome timeframe

1.5 hours (h) prior to the first dose and 20 minutes (min), 40 min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 48h, 72h, 96h after the first dose

Results posted on

2014-06-17

Participant Flow

Participant milestones

Participant milestones
Measure	Study Total This was a randomised, two-period cross-over trial, the two treatments administered were * A single dose of 0.5mg digoxin on day 1 * empagliflozin (Empa) 25 mg once daily on days 1 to 8 combined with a single dose of 0.5 mg digoxin on day 5 Between treatment periods there was a washout period of at least 14 days.
First Intervention STARTED	20
First Intervention COMPLETED	20
First Intervention NOT COMPLETED	0
Washout Period of at Least 14 Days STARTED	20
Washout Period of at Least 14 Days COMPLETED	20
Washout Period of at Least 14 Days NOT COMPLETED	0
Second Intervention STARTED	20
Second Intervention COMPLETED	20
Second Intervention NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Drug Interaction Study of Digoxin and BI 10773

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Study Total n=20 Participants This was a randomised, two-period, cross-over trial, the two treatments administered were * A single dose of digoxin 0.5 mg on day 1 * Empagliflozin (Empa) 25 mg once daily on days 1 to 8 combined with a single dose of 0.5 mg digoxin on day 5 Between treatment periods there was a washout period of at least 14 days.
Age, Continuous	34.3 years STANDARD_DEVIATION 8.1 • n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants

PRIMARY outcome

Timeframe: 1.5 hours (h) prior to the first dose and 20 minutes (min), 40 min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 48h, 72h, 96h after the first dose

Population: Pharmacokinetic (PK) set comprised all evaluable subjects who took at least 1 dose of study medication with at least 1 observation for at least 1 primary PK endpoint without any important protocol violations relevant to the PK evaluation. One subject was excluded from the PK set because the pre-dose plasma concentration of digoxin was \>5% of Cmax.

Area under the concentration-time curve of digoxin in plasma over the time interval from 0 extrapolated to infinity.

Outcome measures

Outcome measures
Measure	Digoxin Alone n=20 Participants A single dose of digoxin 0.5 mg on day 1.	Digoxin and Empa n=19 Participants Empagliflozin (Empa) 25 mg once daily on days 1 to 8 combined with a single dose of 0.5 mg digoxin on day 5.
Digoxin: Area Under the Curve 0 to Infinity (AUC0-∞)	37.8 ng-h/mL Geometric Coefficient of Variation 23.2	39.9 ng-h/mL Geometric Coefficient of Variation 26.0

PRIMARY outcome

Timeframe: 1.5 hours (h) prior to the first dose and 20 minutes (min), 40 min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 48h, 72h, 96h after the first dose

Population: Pharmacokinetic (PK) set comprised all evaluable subjects who took at least 1 dose of study medication with at least 1 observation for at least 1 primary PK endpoint without any important protocol violations relevant to the PK evaluation. One subject was excluded from the PK set because the pre-dose plasma concentration of digoxin was \>5% of Cmax.

Maximum measured concentration of digoxin, per period.

Outcome measures

Outcome measures
Measure	Digoxin Alone n=20 Participants A single dose of digoxin 0.5 mg on day 1.	Digoxin and Empa n=19 Participants Empagliflozin (Empa) 25 mg once daily on days 1 to 8 combined with a single dose of 0.5 mg digoxin on day 5.
Digoxin: Maximum Measured Concentration (Cmax)	1.97 ng/mL Geometric Coefficient of Variation 43.3	2.25 ng/mL Geometric Coefficient of Variation 33.8

SECONDARY outcome

Timeframe: 1.5 hours (h) prior to the first dose and 20 minutes (min), 40 min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 48h, 72h, 96h after the first dose

Population: Pharmacokinetic (PK) set comprised all evaluable subjects who took at least 1 dose of study medication with at least 1 observation for at least 1 primary PK endpoint without any important protocol violations relevant to the PK evaluation. One subject was excluded from the PK set because the pre-dose plasma concentration of digoxin was \>5% of Cmax.

Area under the concentration-time curve of digoxin in plasma over the time interval from 0 extrapolated to the time of the last quantifiable data point.

Outcome measures

Outcome measures
Measure	Digoxin Alone n=20 Participants A single dose of digoxin 0.5 mg on day 1.	Digoxin and Empa n=19 Participants Empagliflozin (Empa) 25 mg once daily on days 1 to 8 combined with a single dose of 0.5 mg digoxin on day 5.
Digoxin: Area Under the Curve 0 to Last Quantifiable Data Point (AUC0-tz)	24.8 ng*h/mL Geometric Coefficient of Variation 24.8	28.4 ng*h/mL Geometric Coefficient of Variation 24.3

Adverse Events

Digoxin Alone

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Digoxin and Empa

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Digoxin Alone n=20 participants at risk A single dose of digoxin 0.5 mg on day 1.	Digoxin and Empa n=20 participants at risk Empagliflozin (Empa) 25 mg once daily on days 1 to 8 combined with a single dose of 0.5 mg digoxin on day 5.
General disorders Fatigue	10.0% 2/20 • First administration of trial medication until 7 days after last administration of trial medication for Digoxin and BI 10773 + Digoxin, 30 days	0.00% 0/20 • First administration of trial medication until 7 days after last administration of trial medication for Digoxin and BI 10773 + Digoxin, 30 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
Publication restrictions are in place