- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02171039
Relative Bioavailability of Dabigatran and Atorvastatin in Healthy Male and Female Volunteers
August 29, 2018 updated by: Boehringer Ingelheim
Relative Bioavailability of Dabigatran and Atorvastatin After 150 mg BID Dabigatran Etexilate and Atorvastatin at 80 mg QD Alone or Following Concomitant Multiple Oral Administrations in Healthy Male and Female Volunteers (an Open-label, Randomised, Multiple-dose, Three-way Crossover Study)
To investigate the bioavailability of dabigatran with and without concomitant administration of atorvastatin and the bioavailability of atorvastatin with and without concomitant administration of dabigatran etexilate
Study Overview
Study Type
Interventional
Enrollment (Actual)
24
Phase
- Phase 1
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 65 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
Healthy males and females according to the following criteria:
Based upon a complete medical history, including the physical examination, vital signs (BP, PR), 12-lead ECG, clinical laboratory tests
- Age ≥18 and ≤65 years
- BMI ≥18.5 and BMI ≤29.9 kg/m2 (Body Mass Index)
- Liver transaminases (ALT; aspartate aminotransferase (AST); GGT) and creatin kinase (CK) are to be within the normal range
- Haemoglobin values within the normal range
- Signed and dated written informed consent prior to admission to the study in accordance with GCP and the local legislation.
Exclusion Criteria:
- Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
- Relevant surgery of gastrointestinal tract
- History of any bleeding disorder or acute blood coagulation defect
- History or presence of acute liver disease
- History or presence of myopathy
- Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
- History of relevant orthostatic hypotension, fainting spells or blackouts
- Chronic or relevant acute infections
- History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator
- Intake of drugs with a long half-life (>24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial
- 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
- Participation in another trial with an investigational drug within two months prior to administration or during the trial
- Alcohol abuse (more than 60 g/day)
- Drug abuse
- Within 5 days of study medication no intake of grapefruit, grapefruit juice, or products containing grapefruit juice, Seville oranges, garlic supplements, or St. John's Wort
- Blood donation (more than 100 mL within four weeks prior to administration o during the trial)
- Excessive physical activities (within one week prior to administration or during the trial)
- Any laboratory value outside the reference range that is of clinical relevance
- Inability to comply with dietary regimen of study centre
- Females of child bearing potential who are pregnant, breast feeding or who are either not surgically sterile or are sexually active and not using an acceptable form of contraception as either the oral contraceptives since at least two months or the double barrier method, i.e. intrauterine device with spermicide and condom for the male partner
- Male subjects will not agree to minimise the risk of female partners becoming pregnant from the first dosing day until 3 months after the completion of the post study medical. Acceptable methods of contraception comprises barrier contraception and a medically accepted contraceptive method for the female partner (intra-uterine device with spermicide, hormonal contraceptive since at least two month)
- Planned surgeries within four weeks following the end-of study examination
- Intake of medication, which influences the blood clotting, i.e., acetylsalicylic acid, cumarin etc.
- The subject is not able to understand and comply with protocol requirements, instructions and protocol-stated restrictions
- Vulnerable subjects (e.g. persons kept in detention).
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: dabigatran plus atorvastatin
|
|
Active Comparator: dabigatran
|
|
Active Comparator: atorvastatin
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Area under the concentration-time curve of the analyte in plasma at steady state over one dosing interval ( AUCτ,ss)
Time Frame: Day 4
|
Day 4
|
Maximum concentration of the analyte in plasma at steady state (Cmax,ss)
Time Frame: 2 hours before and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours after drug administration on day 4
|
2 hours before and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours after drug administration on day 4
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Area under the concentration-time curve of the analyte in plasma from the time point 0 after the last dose at steady state to the last quantifiable analyte plasma concentration within the uniform dosing interval τ (AUC0-tz,ss)
Time Frame: Up to day 7 after administration
|
Up to day 7 after administration
|
Time of last measurable concentration of the analyte in plasma within the dosing interval τ at steady state (tz,ss)
Time Frame: Up to day 7 after administration
|
Up to day 7 after administration
|
Time from last dosing to the maximum concentration of the analyte in plasma at steady state (tmax,ss)
Time Frame: Up to day 7 after administration
|
Up to day 7 after administration
|
Apparent clearance of the analyte in the plasma at steady state after extravascular multiple dose administration (CL/Fss)
Time Frame: Up to day 7 after administration
|
Up to day 7 after administration
|
Minimum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ (Cmin,ss)
Time Frame: 2 hours before and 0,5, 1, 1,5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours after drug administration
|
2 hours before and 0,5, 1, 1,5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours after drug administration
|
Time from last dosing to the minimum concentration of the analyte in plasma at steady state over a uniform dosing interval τ (tmin,ss )
Time Frame: Up to day 7 after administration
|
Up to day 7 after administration
|
Pre-dose concentration of the analyte in plasma at steady state immediately before administration of the next dose (Cpre,ss)
Time Frame: 2 hours before drug administration on day 1, 2, 3 and 4
|
2 hours before drug administration on day 1, 2, 3 and 4
|
Mean residence time of the analyte in the body at steady state after p.o. administration (MRTp.o.,ss)
Time Frame: Up to day 7 after administration
|
Up to day 7 after administration
|
Apparent volume of distribution during the terminal phase λz at steady state following an extravascular administration (Vz/Fss)
Time Frame: Up to day 7 after administration
|
Up to day 7 after administration
|
Amount of analyte that was eliminated in urine at steady state over an uniform dosing interval τ (Aeτ,ss)
Time Frame: Day 4 and 5 after administration
|
Day 4 and 5 after administration
|
Fraction of parent drug eliminated in urine at steady state over a uniform dosing interval τ (feτ,ss)
Time Frame: Day 4 and 5 after administration
|
Day 4 and 5 after administration
|
Renal clearance of the analyte at steady state determined over the dosing interval τ (CLR,ss)
Time Frame: Day 4 and 5 after administration
|
Day 4 and 5 after administration
|
Maximum effect ratio at steady state (ERmax_ss) for activated thrombin time (aPTT) and ecarin clotting time (ECT)
Time Frame: Up to day 7 after administration
|
Up to day 7 after administration
|
Area under the effect curve (baseline corrected) (AUECτ,ss) for aPTT and ECT
Time Frame: Day 4 and 5
|
Day 4 and 5
|
Change from baseline in blood pressure and puls rate (BP, PR)
Time Frame: Baseline, day 78
|
Baseline, day 78
|
Change from baseline in physical examination
Time Frame: Baseline, day 78
|
Baseline, day 78
|
Change from baseline in 12-lead electrocardiogram
Time Frame: Baseline, day 78
|
Baseline, day 78
|
Change from baseline in clinical laboratory tests
Time Frame: Baseline, day 78
|
Baseline, day 78
|
Number of Participants with Serious and Non-Serious Adverse Events
Time Frame: Up to day 78
|
Up to day 78
|
Assessment of tolerability by investigator on a four point scale (good, satisfactory, not satisfactory, bad)
Time Frame: Day 78
|
Day 78
|
Ecarin clotting time (ECT) prolongation at trough (ER(pre,ss))
Time Frame: Up to day 7 after administration
|
Up to day 7 after administration
|
Amount of total active HMG-CoA reductase inhibitors in plasma
Time Frame: Up to day 7 after administration
|
Up to day 7 after administration
|
Activated partial thromboplastin time (aPTT) prolongation at trough (ER(pre,ss))
Time Frame: Up to day 7 after administration
|
Up to day 7 after administration
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
June 1, 2006
Primary Completion (Actual)
August 1, 2006
Study Completion
December 7, 2022
Study Registration Dates
First Submitted
June 20, 2014
First Submitted That Met QC Criteria
June 20, 2014
First Posted (Estimate)
June 23, 2014
Study Record Updates
Last Update Posted (Actual)
August 31, 2018
Last Update Submitted That Met QC Criteria
August 29, 2018
Last Verified
August 1, 2018
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 1160.58
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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