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

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01595854
• Collaborator: (none)
• Enrollment: 36
• Location: 1
• Arms: 4
• Duration (Months): 1
• Patients Per Site Per Month: 35.3

Study Details

Study Description

Brief Summary

Evaluation of potential ticagrelor effects on dabigatran exposure and evaluation of two new pharmacodynamic methods

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: dabigatran etexilate; Drug: Ticagrelor; Drug: Ticagrelor; Drug: dabigatran etexilate; Drug: dabigatran etexilate	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Investigation of Pharmacodynamic Effects of Dabigatran and Ticagrelor (Part 1 and 2, Open, Non-randomised, 2 Parallel Groups) and Assessment of Ticagrelor Interaction Potential With Dabigatran (Part 3, Open, Randomised, Two-period Cross-over) in Healthy Male Subjects
• Study Start Date: May 1, 2012
• Actual Primary Completion Date: Jun 1, 2012
• Actual Study Completion Date: Jun 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Test 2 (part 3) low dose dabigatran + high dose ticagrelor	Drug: Ticagrelor; high dose ticagrelor; Drug: dabigatran etexilate; medium dose dabigatran
Active Comparator: Test 1 (part 1 + 2) high dose ticagrelor	Drug: Ticagrelor; high dose ticagrelor
Experimental: Reference 1 (part 1 + 2) medium dose dabigatran	Drug: dabigatran etexilate; medium dose dabigatran
Experimental: Reference 2 (part 3) low dose dabigatran	Drug: dabigatran etexilate; low dose dabigatran

Outcome Measures

Primary Outcome Measures

1. Total Dabigatran (Dabi): Area Under the Curve 0 to Infinity (AUC0-∞) [-1/-0.5, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours]

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

2. Total Dabigatran: Maximum Measured Concentration (Cmax) [-1/-0.5, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours]

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

Secondary Outcome Measures

1. Number of Participants With Drug Related Adverse Events [From screening until the end-of-study examination]

   The number of participants with drug related adverse events

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Inclusion criteria:

1. Healthy male subjects

Exclusion criteria:

1. Any relevant deviation from healthy conditions

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	1160.141.1 Boehringer Ingelheim Investigational Site	Biberach		Germany

Sponsors and Collaborators

• Boehringer Ingelheim

Investigators

• Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT01595854
• Other Study ID Numbers: 1160.141; 2012-000874-42
• First Posted: May 10, 2012
• Last Update Posted: Aug 22, 2013
• Last Verified: Jun 1, 2013

• Additional relevant MeSH terms: Dabigatran; Ticagrelor

Study Results

Participant Flow

Arm/Group Title	Dabigatran Etexilate 220 mg - Part 1	Ticagrelor 180 mg - Part 1	Dabigatran Etexilate 220 mg - Part 2	Ticagrelor 180 mg - Part 2	Dabigatran Etexilate/Multiple Dose Ticagrelor Crossover-Part 3
Arm/Group Description	A single dose of dabigatran etexilate 220 mg (2 capsules of 110 mg), using a washed blood test.	A single dose of ticagrelor coated tablets 180 mg (2 tablets of 90 mg), using a washed blood test.	A single dose of dabigatran etexilate 220 mg (2 capsules of 110 mg), using a shed blood test.	A single dose of ticagrelor coated tablets 180 mg (2 tablets of 90 mg), using a shed blood test	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.
Period Title: Overall Study
STARTED	8	4	8	4	12
COMPLETED	8	4	8	4	12
NOT COMPLETED	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Dabigatran Etexilate 220 mg - Part 1	Ticagrelor 180 mg - Part 1	Dabigatran Etexilate 220 mg - Part 2	Ticagrelor 180 mg - Part 2	Dabigatran Etexilate / Multiple Dose Ticagrelor - Part 3	Total
Arm/Group Description	A single dose of dabigatran etexilate 220 mg (2 capsules of 110 mg), using a washed blood test.	A single dose of ticagrelor coated tablets 180 mg (2 tablets of 90 mg), using a washed blood test.	A single dose of dabigatran etexilate 220 mg (2 capsules of 110 mg), using a shed blood test.	A single dose of ticagrelor coated tablets 180 mg (2 tablets of 90 mg), using a shed blood test	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 of all reporting groups
Overall Participants	8	4	8	4	12	36
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	30.6 (7.7)	29.8 (11.4)	33.6 (9.1)	33.3 (6.3)	30.2 (7.2)	31.3 (8.2)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Male	8 100%	4 100%	8 100%	4 100%	12 100%	36 100%

Outcome Measures

1. Primary Outcome

Title	Total Dabigatran (Dabi): Area Under the Curve 0 to Infinity (AUC0-∞)
Description	Area under the concentration-time curve of the analyte in plasma, over the time interval from 0 extrapolated to infinity, of dabigatran.
Time Frame	-1/-0.5, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Dabi 75 mg	Dabi + Ticagrelor LD	Dabi + Ticagrelor MD
Arm/Group Description	A single dose of Dabigatran etexilate (Dabi) 75 mg.	A single dose of 75 mg Dabigatran coadministered with a loading dose (LD) of 180 mg ticagrelor coated tablets (T).	A single dose of 75 mg Dabigatran coadministered with a morning dose of multiple dose (MD) ticagrelor.
Measure Participants	12	12	12
Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL]	281.05 (104)	485.48 (40.5)	410.46 (53.1)

2. Primary Outcome

Title	Total Dabigatran: Maximum Measured Concentration (Cmax)
Description	Maximum measured concentration of total dabigatran in plasma, per period.
Time Frame	-1/-0.5, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Dabi 75 mg	Dabi + Ticagrelor LD	Dabi + Ticagrelor MD
Arm/Group Description	A single dose of Dabigatran etexilate (Dabi) 75 mg.	A single dose of 75 mg Dabigatran coadministered with a loading dose (LD) of 180 mg ticagrelor coated tablets (T).	A single dose of 75 mg Dabigatran coadministered with a morning dose of multiple dose (LD) ticagrelor.
Measure Participants	12	12	12
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	31.47 (130)	61.30 (42.9)	49.11 (64.8)

3. Secondary Outcome

Title	Number of Participants With Drug Related Adverse Events
Description	The number of participants with drug related adverse events
Time Frame	From screening until the end-of-study examination

Outcome Measure Data

Analysis Population Description

Treated set

Arm/Group Title	Dabigatran 220 mg - Part 1	Ticagrelor 180 mg - Part 1	Dabigatran 220 mg - Part 2	Ticagrelor 180 mg - Part 2	Dabigatran 75 mg - Part 3	Dabigatran + Ticagrelor - Part 3
Arm/Group Description	A single dose of Dabigatran etexilate 220 mg (2 capsules of 110 mg), using a washed blood test.	A single dose of Ticagrelor coated tablets 180 mg (2 tablets of 90 mg), using a washed blood test.	A single dose of Dabigatran etexilate 220 mg (2 capsules of 110 mg), using a shed blood test.	A single dose of Ticagrelor coated tablets 180 mg (2 tablets of 90 mg), using a shed blood test.	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.
Measure Participants	8	4	8	4	12	12
Number [participants]	0 0%	0 0%	0 0%	0 0%	0 0%	1 2.8%

Adverse Events

Time Frame	3 to 10 days after last dosing
Arm/Group Title	Dabigatran Etexilate 220 mg - Part 1		Ticagrelor 180 mg - Part 1		Dabigatran Etexilate 220 mg - Part 2		Ticagrelor 180 mg - Part 2		Dabi 75 mg - Part 3		Multiple Dose Ticagrelor - Part 3
Arm/Group Description	A single dose of dabigatran etexilate 220 mg (2 capsules of 110 mg), using a washed blood test.		A single dose of ticagrelor coated tablets 180 mg (2 tablets of 90 mg), using a washed blood test.		A single dose of dabigatran etexilate 220 mg (2 capsules of 110 mg), using a shed blood test.		A single dose of ticagrelor coated tablets 180 mg (2 tablets of 90 mg), using a shed blood test		A single dose of dabigatran etexilate (Dabi) 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.
All Cause Mortality
	Dabigatran Etexilate 220 mg - Part 1		Ticagrelor 180 mg - Part 1		Dabigatran Etexilate 220 mg - Part 2		Ticagrelor 180 mg - Part 2		Dabi 75 mg - Part 3		Multiple Dose Ticagrelor - Part 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Dabigatran Etexilate 220 mg - Part 1		Ticagrelor 180 mg - Part 1		Dabigatran Etexilate 220 mg - Part 2		Ticagrelor 180 mg - Part 2		Dabi 75 mg - Part 3		Multiple Dose Ticagrelor - Part 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/4 (0%)		0/8 (0%)		0/4 (0%)		0/12 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Dabigatran Etexilate 220 mg - Part 1		Ticagrelor 180 mg - Part 1		Dabigatran Etexilate 220 mg - Part 2		Ticagrelor 180 mg - Part 2		Dabi 75 mg - Part 3		Multiple Dose Ticagrelor - Part 3
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/8 (12.5%)		0/4 (0%)		0/8 (0%)		0/4 (0%)		2/12 (16.7%)		3/12 (25%)
Gastrointestinal disorders
Nausea	0/8 (0%)		0/4 (0%)		0/8 (0%)		0/4 (0%)		0/12 (0%)		1/12 (8.3%)
Infections and infestations
Gastrointestinal infection	1/8 (12.5%)		0/4 (0%)		0/8 (0%)		0/4 (0%)		0/12 (0%)		0/12 (0%)
Musculoskeletal and connective tissue disorders
Neck pain	0/8 (0%)		0/4 (0%)		0/8 (0%)		0/4 (0%)		1/12 (8.3%)		1/12 (8.3%)
Skin and subcutaneous tissue disorders
Erythema	0/8 (0%)		0/4 (0%)		0/8 (0%)		0/4 (0%)		0/12 (0%)		1/12 (8.3%)
Rash	0/8 (0%)		0/4 (0%)		0/8 (0%)		0/4 (0%)		1/12 (8.3%)		0/12 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

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.