Bioequivalence of Two Different Capsule Types of Dabigatran

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)

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Dabigatran etexilate; Drug: Dabigatran etexilate

• Study Type: Interventional
• Enrollment (Actual): 180
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Mannheim, Germany
    • 1160.117.1 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dabigatran etexilate 150 mg (T); Capsugel (T), oral administration	Drug: Dabigatran etexilate; 150 mg Capsugel (T); Drug: Dabigatran etexilate; 150 mg Qualicaps (R)
Experimental: Dabigatran etexilate 150 mg (R); Qualicaps (R), oral administration	Drug: Dabigatran etexilate; 150 mg Capsugel (T); Drug: Dabigatran etexilate; 150 mg Qualicaps (R)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve 0 to tz (AUC0-tz) of Total Dabigatran	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.	60 hours
Maximum Measured Concentration (Cmax) of Total Dabigatran in Plasma	Adjusted for treatment, period and sequence (all fixed effects), and random subject effect.	60 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve 0 to Infinity (AUC0-∞) of Total Dabigatran.	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.	60 hours
AUC0-tz of Free Dabigatran.	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.	60 hours
Cmax of Free Dabigatran in Plasma.	Adjusted for treatment, period and sequence (all fixed effects), and random subject effect.	60 hours
AUC0-∞ of Free Dabigatran.	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.	60 hours

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): April 1, 2011

Study Registration Dates

• First Submitted: February 2, 2011
• First Submitted That Met QC Criteria: February 4, 2011
• First Posted (Estimate): February 7, 2011

Study Record Updates

• Last Update Posted (Estimate): May 19, 2014
• Last Update Submitted That Met QC Criteria: May 8, 2014
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Dabigatran
• Other Study ID Numbers: 1160.117; 2010-022966-28 (EudraCT Number: EudraCT)