Trial Outcomes & Findings for Bioequivalence of Two Different Capsule Types of Dabigatran (NCT NCT01290757)

NCT ID: NCT01290757

Last Updated: 2014-05-19

Results Overview

Area under the concentration-time curve of total dabigatran in plasma from time 0 to the time of the last quantifiable data point, adjusted for treatment, period and sequence (all fixed effects), and random subject effect.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 180 participants
• Primary outcome timeframe: 60 hours
• Results posted on: 2014-05-19

Participant Flow

In this crossover study, subjects were randomly assigned to one of the 2 sequences, with 2 treatment arms. In general terms, Ref-Test-Ref-Test and Test-Ref-Test-Ref. The aim was bioequivalence comparing (Ref) Dabigatran 150mg in the currently approved capsule shell (Qualicaps) to the test of Dabigatran 150mg in a new shell (Capsugel).

Participant milestones

Measure	Sequence: Qualicaps - Capsugel - Qualicaps - Capsugel Dabigatran 150mg in currently approved Qualicaps, followed by Dabigatran 150mg in new Capsugel, followed by Dabigatran 150mg in currently approved Qualicaps, followed by Dabigatran 150mg in new Capsugel (RTRT)	Sequence: Capsugel - Qualicaps - Capsugel - Qualicaps Dabigatran 150mg in new Capsugel, followed by Dabigatran 150mg in currently approved Qualicaps, followed by Dabigatran 150mg in new Capsugel, followed by Dabigatran 150mg in currently approved Qualicaps (TRTR)
Overall Study STARTED	90	90
Overall Study COMPLETED	88	88
Overall Study NOT COMPLETED	2	2

Reasons for withdrawal

Measure	Sequence: Qualicaps - Capsugel - Qualicaps - Capsugel Dabigatran 150mg in currently approved Qualicaps, followed by Dabigatran 150mg in new Capsugel, followed by Dabigatran 150mg in currently approved Qualicaps, followed by Dabigatran 150mg in new Capsugel (RTRT)	Sequence: Capsugel - Qualicaps - Capsugel - Qualicaps Dabigatran 150mg in new Capsugel, followed by Dabigatran 150mg in currently approved Qualicaps, followed by Dabigatran 150mg in new Capsugel, followed by Dabigatran 150mg in currently approved Qualicaps (TRTR)
Overall Study Adverse Event	1	0
Overall Study Protocol Violation	1	1
Overall Study Other	0	1

Baseline Characteristics

Bioequivalence of Two Different Capsule Types of Dabigatran

Baseline characteristics by cohort

Measure	Sequence: Qualicaps - Capsugel - Qualicaps - Capsugel n=90 Participants Dabigatran 150mg in currently approved Qualicaps, followed by Dabigatran 150mg in new Capsugel, followed by Dabigatran 150mg in currently approved Qualicaps, followed by Dabigatran 150mg in new Capsugel (RTRT)	Sequence: Capsugel - Qualicaps - Capsugel - Qualicaps n=90 Participants Dabigatran 150mg in new Capsugel, followed by Dabigatran 150mg in currently approved Qualicaps, followed by Dabigatran 150mg in new Capsugel, followed by Dabigatran 150mg in currently approved Qualicaps (TRTR)	Total n=180 Participants Total of all reporting groups
Age, Continuous	39.8 Years STANDARD_DEVIATION 10.1 • n=5 Participants	39.4 Years STANDARD_DEVIATION 9.1 • n=7 Participants	39.6 Years STANDARD_DEVIATION 9.6 • n=5 Participants
Sex: Female, Male Female	46 Participants n=5 Participants	47 Participants n=7 Participants	93 Participants n=5 Participants
Sex: Female, Male Male	44 Participants n=5 Participants	43 Participants n=7 Participants	87 Participants n=5 Participants

PRIMARY outcome

Timeframe: 60 hours

Population: This subject set, the pharmacokinetic set (PKS), includes all subjects of the treated set who provide at least one evaluable observation for at least one of the three PK endpoints of total dabigatran, which is obtained in a period without important protocol violations relevant to the evaluation of bioequivalence.

Area under the concentration-time curve of total dabigatran in plasma from time 0 to the time of the last quantifiable data point, adjusted for treatment, period and sequence (all fixed effects), and random subject effect.

Outcome measures

Measure	Capsugel n=179 Participants Dabigatran 150mg in new Capsugel	Qualicaps n=180 Participants Dabigatran 150mg in currently approved Qualicaps
Area Under the Curve 0 to tz (AUC0-tz) of Total Dabigatran	1147.64 ng*hr/mL Geometric Coefficient of Variation 32.32	908.48 ng*hr/mL Geometric Coefficient of Variation 49.83

PRIMARY outcome

Timeframe: 60 hours

Population: PKS

Adjusted for treatment, period and sequence (all fixed effects), and random subject effect.

Outcome measures

Measure	Capsugel n=179 Participants Dabigatran 150mg in new Capsugel	Qualicaps n=180 Participants Dabigatran 150mg in currently approved Qualicaps
Maximum Measured Concentration (Cmax) of Total Dabigatran in Plasma	134.44 ng/mL Geometric Coefficient of Variation 31.10	107.13 ng/mL Geometric Coefficient of Variation 49.67

SECONDARY outcome

Timeframe: 60 hours

Population: PKS

Area under the concentration-time curve of total dabigatran in plasma over the time interval from 0 extrapolated to infinity. Adjusted for treatment, period and sequence (all fixed effects), and random subject effect.

Outcome measures

Measure	Capsugel n=179 Participants Dabigatran 150mg in new Capsugel	Qualicaps n=180 Participants Dabigatran 150mg in currently approved Qualicaps
Area Under the Curve 0 to Infinity (AUC0-∞) of Total Dabigatran.	1175.05 ng*hr/mL Geometric Coefficient of Variation 30.81	941.99 ng*hr/mL Geometric Coefficient of Variation 46.53

SECONDARY outcome

Timeframe: 60 hours

Population: PKS

Area under the concentration-time curve of free dabigatran in plasma from time 0 to the time of the last quantifiable data point. Adjusted for treatment, period and sequence (all fixed effects), and random subject effect.

Outcome measures

Measure	Capsugel n=179 Participants Dabigatran 150mg in new Capsugel	Qualicaps n=180 Participants Dabigatran 150mg in currently approved Qualicaps
AUC0-tz of Free Dabigatran.	856.31 ng*hr/mL Geometric Coefficient of Variation 33.15	678.43 ng*hr/mL Geometric Coefficient of Variation 50.85

SECONDARY outcome

Timeframe: 60 hours

Population: PKS

Adjusted for treatment, period and sequence (all fixed effects), and random subject effect.

Outcome measures

Measure	Capsugel n=179 Participants Dabigatran 150mg in new Capsugel	Qualicaps n=180 Participants Dabigatran 150mg in currently approved Qualicaps
Cmax of Free Dabigatran in Plasma.	106.66 ng/mL Geometric Coefficient of Variation 31.34	85.12 ng/mL Geometric Coefficient of Variation 50.33

SECONDARY outcome

Timeframe: 60 hours

Population: PKS

Area under the concentration-time curve of free dabigatran in plasma over the time interval from 0 extrapolated to infinity. Adjusted for treatment, period and sequence (all fixed effects), and random subject effect.

Outcome measures

Measure	Capsugel n=179 Participants Dabigatran 150mg in new Capsugel	Qualicaps n=180 Participants Dabigatran 150mg in currently approved Qualicaps
AUC0-∞ of Free Dabigatran.	888.86 ng*hr/mL Geometric Coefficient of Variation 31.20	714.01 ng*hr/mL Geometric Coefficient of Variation 47.16

Adverse Events

Qualicaps

Serious events: 0 serious events

Other events: 37 other events

Deaths: 0 deaths

Capsugel

Serious events: 0 serious events

Other events: 34 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Qualicaps n=180 participants at risk Dabigatran 150mg in Qualicaps	Capsugel n=180 participants at risk Dabigatran 150mg in Capsugel
Nervous system disorders Headache	20.6% 37/180 • Approximately 7 days	18.9% 34/180 • Approximately 7 days

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim Pharmaceuticals

Phone: 1-800-243-0127

Email: clintriage.rdg@boehringer-ingelheim.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER