Clinical trial NCT01290757: Bioequivalence of Two Different Capsule Types of Dabigatran
Official title: Bioequivalence of Two Different Capsule Types of 150 mg Dabigatran Etexilate Made From Two Different Drug Product Batches, Following Oral Administration in Healthy Male and Female Volunteers (Open-label, Randomised, Single Dose, Replicate Design in a Two Treatments, Four Periods Crossover Phase I Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2011-02-07
Enrollment: 180
Sex: ALL
Minimum age (years): 21
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The objective of this Phase I trial is to demonstrate the bioequivalence of two capsules of dabigatran etexilate made from two different drug product batches.

The reference batch is dabigatran etexilate hard capsules 150 mg using the currently approved capsule shell (Qualicaps). The test batch is dabigatran etexilate 150 mg hard capsules using a new capsule shell (Capsugel). The test batch is the drug product intended for future commercial use.


Eligibility criteria: Inclusion criteria:

1. Healthy males and females according to the following criteria: Based upon a complete medical history, including the physical examination, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead electrocardiogram (ECG), clinical laboratory tests
2. Age =21 and = 55 years
3. Body Mass Index (BMI) =18.5 and BMI = 29.9 kg/m\^2
4. Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and the local legislation

Exclusion criteria:

1. Clinically relevant gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
2. Clinically relevant surgery of gastrointestinal tract or evidence of significant gastrointestinal motility problems that could affect absorption of the drug
3. Diseases of the central nervous system (included but not limited to any kind of seizures, stroke or psychiatric disorders) within the past 6 month
4. Any history or evidence of blood dyscrasia, hemorrhagic diathesis, severe thrombocytopenia, cerebrovascular hemorrhage, bleeding tendencies associated with active ulceration or overt bleeding of gastrointestinal, respiratory or genitourinary tract or any disease or condition with hemorrhagic tendencies
5. History of relevant orthostatic hypotension, fainting spells or blackouts
6. Chronic or relevant acute infections
7. History of allergy/hypersensitivity (including drug allergy in particular to study drug or its excipients) which is deemed relevant to the trial as judged by the investigator
8. Use of drugs which might reasonably influence the results of the trial based on the knowledge at the time of protocol preparation within 10 days prior to administration or during the trial
9. Alcohol abuse (more than 20 g/day)
10. Drug abuse
11. Any laboratory value outside the reference range that is of clinical relevance (especially hemoglobin, thrombocytes, prothrombin time (PT) and Activated Partial Thromboplastin Time (Measure of the clotting time) (aPTT) or positive drug or virus screening
12. Planned surgeries within four weeks following the end-of study examination
13. Recent or contemplated diagnostic or therapeutic procedures with potential for uncontrollable bleeding within 14 days before or after end-of study examination

Primary outcomes:
measure: Area Under the Curve 0 to tz (AUC0-tz) of Total Dabigatran
timeFrame: 60 hours
measure: Maximum Measured Concentration (Cmax) of Total Dabigatran in Plasma
timeFrame: 60 hours
Secondary outcomes:
measure: Area Under the Curve 0 to Infinity (AUC0-∞) of Total Dabigatran.
timeFrame: 60 hours
measure: AUC0-tz of Free Dabigatran.
timeFrame: 60 hours
measure: Cmax of Free Dabigatran in Plasma.
timeFrame: 60 hours
measure: AUC0-∞ of Free Dabigatran.
timeFrame: 60 hours
Other outcomes:
Locations:
city: Mannheim
country: Germany
facility: 1160.117.1 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: