Trial Outcomes & Findings for Investigation of Pharmacodynamic Effects of Dabigatran and Ticagrelor and Assessment of Ticagrelor Interaction Potential With Dabigatran (NCT NCT01595854)

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

36 participants

Primary outcome timeframe

-1/-0.5, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours

Results posted on

2013-08-22

Participant Flow

Participant milestones

Participant milestones
Measure	Dabigatran Etexilate 220 mg - Part 1 A single dose of dabigatran etexilate 220 mg (2 capsules of 110 mg), using a washed blood test.	Ticagrelor 180 mg - Part 1 A single dose of ticagrelor coated tablets 180 mg (2 tablets of 90 mg), using a washed blood test.	Dabigatran Etexilate 220 mg - Part 2 A single dose of dabigatran etexilate 220 mg (2 capsules of 110 mg), using a shed blood test.	Ticagrelor 180 mg - Part 2 A single dose of ticagrelor coated tablets 180 mg (2 tablets of 90 mg), using a shed blood test	Dabigatran Etexilate/Multiple Dose Ticagrelor Crossover-Part 3 A randomised, two-period, cross-over trial, the two treatments administered were * A single dose of dabigatran etexilate 75 mg * Ticagrelor coated tablets dosed for four days; 180 mg loading dose on day 1, 90 mg twice daily on day 2 and 3, 90 mg on day 4. Co-administered is a single dose of 75 mg Dabigatran etexilate on days 1 and 4. Between treatment periods there was a washout period of at least 4 days.
Overall Study STARTED	8	4	8	4	12
Overall Study COMPLETED	8	4	8	4	12
Overall Study NOT COMPLETED	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Investigation of Pharmacodynamic Effects of Dabigatran and Ticagrelor and Assessment of Ticagrelor Interaction Potential With Dabigatran

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dabigatran Etexilate 220 mg - Part 1 n=8 Participants A single dose of dabigatran etexilate 220 mg (2 capsules of 110 mg), using a washed blood test.	Ticagrelor 180 mg - Part 1 n=4 Participants A single dose of ticagrelor coated tablets 180 mg (2 tablets of 90 mg), using a washed blood test.	Dabigatran Etexilate 220 mg - Part 2 n=8 Participants A single dose of dabigatran etexilate 220 mg (2 capsules of 110 mg), using a shed blood test.	Ticagrelor 180 mg - Part 2 n=4 Participants A single dose of ticagrelor coated tablets 180 mg (2 tablets of 90 mg), using a shed blood test	Dabigatran Etexilate / Multiple Dose Ticagrelor - Part 3 n=12 Participants A randomised two-period cross-over trial, the two treatments administered were * A single dose of dabigatran etexilate 75 mg * Ticagrelor coated tablets dosed for four days; 180 mg loading dose on day 1, 90 mg twice daily on day 2 and 3, 90 mg on day 4. Co-administered with a single dose of 75 mg Dabigatran etexilate on days 1 and 4. Between treatment periods there was a washout period of at least 4 days.	Total n=36 Participants Total of all reporting groups
Age Continuous	30.6 years STANDARD_DEVIATION 7.7 • n=5 Participants	29.8 years STANDARD_DEVIATION 11.4 • n=7 Participants	33.6 years STANDARD_DEVIATION 9.1 • n=5 Participants	33.3 years STANDARD_DEVIATION 6.3 • n=4 Participants	30.2 years STANDARD_DEVIATION 7.2 • n=21 Participants	31.3 years STANDARD_DEVIATION 8.2 • n=8 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants	4 Participants n=4 Participants	12 Participants n=21 Participants	36 Participants n=8 Participants

PRIMARY outcome

Timeframe: -1/-0.5, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours

Population: Pharmacokinetic (PK) set defined as all subjects of Part 3 who received at least 1 dose of trial medication and provided at least 1 observation for at least 1 PK endpoint without important protocol violations relevant to the evaluation of bioavailability.

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

Outcome measures

Outcome measures
Measure	Dabi 75 mg n=12 Participants A single dose of Dabigatran etexilate (Dabi) 75 mg.	Dabi + Ticagrelor LD n=12 Participants A single dose of 75 mg Dabigatran coadministered with a loading dose (LD) of 180 mg ticagrelor coated tablets (T).	Dabi + Ticagrelor MD n=12 Participants A single dose of 75 mg Dabigatran coadministered with a morning dose of multiple dose (MD) ticagrelor.	Ticagrelor 180 mg - Part 2 A single dose of Ticagrelor coated tablets 180 mg (2 tablets of 90 mg), using a shed blood test.	Dabigatran 75 mg - Part 3 A single dose of Dabigatran etexilate 75 mg	Dabigatran + Ticagrelor - Part 3 Ticagrelor coated tablets dosed for four days; 180 mg loading dose on day 1, 90 mg twice daily on day 2 and 3, 90 mg on day 4. Co-administered is a single dose of 75 mg Dabigatran etexilate on days 1 and 4.
Total Dabigatran (Dabi): Area Under the Curve 0 to Infinity (AUC0-∞)	281.05 ng*h/mL Geometric Coefficient of Variation 104	485.48 ng*h/mL Geometric Coefficient of Variation 40.5	410.46 ng*h/mL Geometric Coefficient of Variation 53.1	—	—	—

PRIMARY outcome

Timeframe: -1/-0.5, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours

Population: Pharmacokinetic (PK) set defined as all subjects of Part 3 who received at least 1 dose of trial medication and provided at least 1 observation for at least 1 PK endpoint without important protocol violations relevant to the evaluation of bioavailability.

Maximum measured concentration of total dabigatran in plasma, per period.

Outcome measures

Outcome measures
Measure	Dabi 75 mg n=12 Participants A single dose of Dabigatran etexilate (Dabi) 75 mg.	Dabi + Ticagrelor LD n=12 Participants A single dose of 75 mg Dabigatran coadministered with a loading dose (LD) of 180 mg ticagrelor coated tablets (T).	Dabi + Ticagrelor MD n=12 Participants A single dose of 75 mg Dabigatran coadministered with a morning dose of multiple dose (MD) ticagrelor.	Ticagrelor 180 mg - Part 2 A single dose of Ticagrelor coated tablets 180 mg (2 tablets of 90 mg), using a shed blood test.	Dabigatran 75 mg - Part 3 A single dose of Dabigatran etexilate 75 mg	Dabigatran + Ticagrelor - Part 3 Ticagrelor coated tablets dosed for four days; 180 mg loading dose on day 1, 90 mg twice daily on day 2 and 3, 90 mg on day 4. Co-administered is a single dose of 75 mg Dabigatran etexilate on days 1 and 4.
Total Dabigatran: Maximum Measured Concentration (Cmax)	31.47 ng/mL Geometric Coefficient of Variation 130	61.30 ng/mL Geometric Coefficient of Variation 42.9	49.11 ng/mL Geometric Coefficient of Variation 64.8	—	—	—

SECONDARY outcome

Timeframe: From screening until the end-of-study examination

Population: Treated set

The number of participants with drug related adverse events