Trial Outcomes & Findings for Investigation of Drug-drug Interaction of Dabigatran and Ticagrelor (NCT NCT01734772)

Results Overview

Area under the concentration-time curve of dabigatran etexilate in plasma at steady state over the uniform dosing interval τ (AUCτ,ss).

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

48 participants

Primary outcome timeframe

47.55, 48.30,49, 49.30,50,50.30,51,52,54,56, 60 hours

Results posted on

2014-05-05

Participant Flow

Participant milestones

Participant milestones
Measure	Part 1 In part 1, 110 mg dabigatran etexilate were dosed twice daily to steady state and a dabigatran PK profile was taken on day 3 (reference). On the day after the reference treatment, ticagrelor treatment was added starting with the concomitant administration of a 180 mg ticagrelor loading dose followed by 90 mg ticagrelor twice daily. Dabigatran PK profiles were taken on day 1 of the test treatment and day 4 of the test treatment.	Part 2 In part 2, 110 mg dabigatran etexilate were dosed twice daily to steady state and a dabigatran PK profile was taken on day 3 (reference). On the day after the reference treatment, 180 mg ticagrelor were given 2 hours after the morning dose of 110 mg dabigatran etexilate and dabigatran PK profile were taken on this day 1 of the test treatment.
Overall Study STARTED	24	24
Overall Study COMPLETED	23	21
Overall Study NOT COMPLETED	1	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Part 1 In part 1, 110 mg dabigatran etexilate were dosed twice daily to steady state and a dabigatran PK profile was taken on day 3 (reference). On the day after the reference treatment, ticagrelor treatment was added starting with the concomitant administration of a 180 mg ticagrelor loading dose followed by 90 mg ticagrelor twice daily. Dabigatran PK profiles were taken on day 1 of the test treatment and day 4 of the test treatment.	Part 2 In part 2, 110 mg dabigatran etexilate were dosed twice daily to steady state and a dabigatran PK profile was taken on day 3 (reference). On the day after the reference treatment, 180 mg ticagrelor were given 2 hours after the morning dose of 110 mg dabigatran etexilate and dabigatran PK profile were taken on this day 1 of the test treatment.
Overall Study Adverse Event	1	2
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Investigation of Drug-drug Interaction of Dabigatran and Ticagrelor

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part 1 n=24 Participants In part 1, 110 mg dabigatran etexilate were dosed twice daily to steady state and a dabigatran PK profile was taken on day 3 (reference). On the day after the reference treatment, ticagrelor treatment was added starting with the concomitant administration of a 180 mg ticagrelor loading dose followed by 90 mg ticagrelor twice daily. Dabigatran PK profiles were taken on day 1 of the test treatment and day 4 of the test treatment.	Part 2 n=24 Participants In part 2, 110 mg dabigatran etexilate were dosed twice daily to steady state and a dabigatran PK profile was taken on day 3 (reference). On the day after the reference treatment, 180 mg ticagrelor were given 2 hours after the morning dose of 110 mg dabigatran etexilate and dabigatran PK profile were taken on this day 1 of the test treatment.	Total n=48 Participants Total of all reporting groups
Age, Continuous	28.0 years STANDARD_DEVIATION 7.2 • n=5 Participants	28.6 years STANDARD_DEVIATION 7.1 • n=7 Participants	28.3 years STANDARD_DEVIATION 7.15 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	24 Participants n=5 Participants	24 Participants n=7 Participants	48 Participants n=5 Participants

PRIMARY outcome

Timeframe: 47.55, 48.30,49, 49.30,50,50.30,51,52,54,56, 60 hours

Population: Pharmacokinetic set: This subject set included all subjects in the TS who provided at least 1 observation for at least 1 PK endpoint without important protocol violations relevant to the evaluation of bioavailability and who had not vomiting at or before 2 times the median tmax,ss of the trial medications on PK study days of both trial parts.

Area under the concentration-time curve of dabigatran etexilate in plasma at steady state over the uniform dosing interval τ (AUCτ,ss).

Outcome measures

Outcome measures
Measure	Dabigratan Etexilate 110mg Bid Alone - Part 1 n=24 Participants Dabigatran Etexilate 110mg twice daily (bid) for 3 days	Dabigatran Etexilate 110mg Bid + Ticagrelor 180 mg - Part 1 n=23 Participants Single loading dose of Ticagrelor 180 mg on day 1 together with Dabigatran Etexilate 110mg bid.	Dabigatran Etexilate 110mg Bid + Ticagrelor 90mg Bid - Part 1 n=23 Participants Multiple dosing of 90 mg bid on days 2 and 3 and 90mg on day 4 together with Dabigatran Etexilate 110mg bid on days 2 and 3 and 110mg in the morning on day 4.	Dabigratan Etexilate 110mg Bid Alone - Part 2 n=23 Participants Dabigatran Etexilate 110mg twice daily (bid) for 3 days	Dabigatran Etexilate 110mg Bid + Ticagrelor 180 mg - Part 2 n=21 Participants Dabigatran Etexilate 110mg morning dose followed by 180mg Ticagrelor 2 hours later.
Total Dabigatran: Area Under the Concentration-time Curve at Steady State Over the Uniform Dosing Interval τ (AUCτ,ss)	551 ng*h/mL Geometric Coefficient of Variation 59.0	817 ng*h/mL Geometric Coefficient of Variation 43.3	689 ng*h/mL Geometric Coefficient of Variation 55.1	660 ng*h/mL Geometric Coefficient of Variation 39.6	844 ng*h/mL Geometric Coefficient of Variation 43.4

PRIMARY outcome

Timeframe: 47.55, 48.30,49, 49.30,50,50.30,51,52,54,56, 60 hours

Population: Pharmacokinetic set: This subject set included all subjects in the TS who provided at least 1 observation for at least 1 PK endpoint without important protocol violations relevant to the evaluation of bioavailability and who had not vomiting at or before 2 times the median tmax,ss of the trial medications on PK study days of both trial parts.

Maximum measured concentration of the analyte in plasma at steady state (Cmax,ss).