HealthyPhase 1NCT02171533
Relative Bioavailability of Single Oral Doses of Dabigatran Etexilate With or Without Oral Administration of Verapamil in Two Different Dosages in Healthy Male and Female Volunteers
A Phase 1 study testing dabigatran, Verapamil and Verapamil ER in people with Healthy, run by Boehringer Ingelheim.
Trial summary
To investigate whether and to what extent the P-glycoprotein inhibitor (P-gp) verapamil affects the pharmacokinetic parameters of dabigatran with verapamil given at different dosages, in different formulations (immediate release (IR) and extended release (ER)), and in different intervals in relation to the dabigatran… Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- dabigatran, Verapamil and Verapamil ER
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- No sites listed yet
- Study dates
- Jun 2008to Aug 2008
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
- Age ≥18 and ≤55 years
- Body mass index (BMI) ≥18.5 and BMI ≤29.9 kg/m2
- Signed and dated written informed consent prior to admission to the study in accordance with GCP and the local legislation
Who cannot join
- 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
- 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
Show all 24Show fewer
- History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator
- Pulse rate below 50 bpm and or systolic blood pressure <90 mm Hg at screening. ECG: PR >170 ms (Part 1), AV block ≥1st degree (Part 2) at screening
- Use of drugs which might reasonably influence the results of the trial based on the knowledge at the time of protocol preparation within four weeks prior to administration or during the trial, especially intake of medication, which influences the blood clotting, i.e., acetylsalicylic acid, cumarin etc.
- Participation in another trial with an investigational drug within two months prior to administration or during the trial
- Smoker (more than 15 cigarettes or 3 cigars or 3 pipes per day)
- Alcohol abuse (more than 60 g/day for men and more than 40 g/day for women)
- Drug abuse
- Blood donation (more than 100 mL within four weeks prior to administration or 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
- Planned surgeries within four weeks following the end-of study examination
- The subject is not able to understand and comply with protocol requirements, instructions, protocol-stated restrictions and dietary regimen of study centre
- For male subjects:
- Male subjects who do 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)
- For female subjects:
- Pregnancy / positive pregnancy test, or planning to become pregnant during the study or within 1 month of study completion
- No adequate contraception during the study and until 1 month of study completion, i.e. implants, injectables, combined oral contraceptives, IUD (intrauterine device), sexual abstinence (for at least 1 month prior to enrolment), vasectomised partner (vasectomy performed at least 1 year prior to enrolment), or surgical sterilisation (incl. hysterectomy). Females, who have not a vasectomised partner, are not sexually abstinent or surgically sterile will be asked to additionally use barrier contraception methods (e.g. condom, diaphragm with spermicide)
- Lactation period
About this study
Official title: Relative Bioavailability of Single Oral Doses of 150 mg Dabigatran Etexilate With or Without Oral Administration of Verapamil in Two Different Dosages (240 mg and 480 mg Daily) (Open-label, Fixed-sequence Design), and Relative Bioavailability of Single Oral Doses of 150 mg Dabigatran Etexilate Given With or Without Single Oral Doses of 120 mg (IR) or 240 mg (ER) of Verapamil Administered at Different Time Points Relative to Dabigatran Etexilate Dosing in Healthy Male and Female Volunteers (Open-label, Randomised, Five-way Crossover Design, Phase I Study)
To investigate whether and to what extent the P-glycoprotein inhibitor (P-gp) verapamil affects the pharmacokinetic parameters of dabigatran with verapamil given at different dosages, in different formulations (immediate release (IR) and extended release (ER)), and in different intervals in relation to the dabigatran dose.
- Conditions
- Healthy
- Being tested
- dabigatran, Verapamil, Verapamil ER
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
dabigatranDrug
VerapamilDrug
Verapamil ERDrug
| Study group | Role | What they receive |
|---|---|---|
| Fixed sequence | Experimental | Treatments will be given in a fixed sequence Receives: Drug: dabigatran; Drug: Verapamil |
| Crossover | Experimental | Treatments will be given in randomized sequences Receives: Drug: dabigatran; Drug: Verapamil; Drug: Verapamil ER |
What is being measured
The primary outcome is the main question the study is designed to answer.
AUC0-infinity (area under the concentration-time curve of total dabigatran over the time interval from 0 extrapolated to infinity)
Measured: up to 107 hours
Cmax (maximum measured concentration of total dabigatran)
Measured: up to 107 hours
Secondary outcomes (31)
AUC0-infinity (area under the concentration-time curve of free dabigatran over the time interval from 0 extrapolated to infinity)
Measured: up to 107 hours
Cmax (maximum measured concentration of free dabigatran)
Measured: up to 107 hours
AUC0-infinity (area under the concentration-time curve of verapamil over the time interval from 0 extrapolated to infinity)
Measured: up to 107 hours
Cmax (maximum measured concentration of verapamil)
Measured: up to 107 hours
AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point)
Measured: up to 107 hours
AUC0-24 (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 24 h after the administration)
Measured: up to 107 hours
tmax (time from dosing to the maximum concentration of the analyte in plasma)
Measured: up to 107 hours
λz (terminal rate constant in plasma)
Measured: up to 107 hours
t1/2 (terminal half-life of the analyte in plasma)
Measured: up to 107 hours
MRTpo (mean residence time of the analyte in the body after oral administration)
Measured: up to 107 hours
CL/F (apparent clearance of the analyte in the plasma after extravascular administration)
Measured: up to 107 hours
Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose)
Measured: up to 107 hours
AUCτ,ss (area under the concentration-time curve of verapamil within the uniform dosing interval τ)
Measured: up to 107 hours
AUC0-tz,ss (area under the concentration-time curve of verapamil 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)
Measured: up to 107 hours
Cmax,ss (maximum concentration of verapamil at steady state)
Measured: up to 107 hours
tz,ss (time of last measureable concentration of verapamil within the dosing interval τ at steady state)
Measured: up to 107 hours
tmax,ss (time from last dosing to the maximum concentration of verapamil at steady state on day 4)
Measured: up to 107 hours
CL/F,ss (apparent clearance of verapamil at steady state after extravascular multiple dose administration)
Measured: up to 107 hours
Cmin,ss (minimum measured concentration of verapamil at steady state over a uniform dosing interval τ)
Measured: up to 107 hours
tmin,ss (time from last dosing to the minimum concentration of verapamil at steady state over a uniform dosing interval τ)
Measured: up to 107 hours
Cpre,ss (predose concentration of verapamil at steady state immediately before administration of the next dose)
Measured: up to 107 hours
Cavg (Average concentration of verapamil at steady state)
Measured: up to 107 hours
MRTpo,ss (mean residence time of verapamil in the body at steady state after oral administration)
Measured: up to 107 hours
Vz/F,ss (apparent volume of distribution during the terminal phase λz at steady state following an extravascular administration)
Measured: up to 107 hours
Ae0-24 (amount of dabigatran that is eliminated in urine from the time interval 0-24h)
Measured: up to 107 hours
fe0-24 (fraction of administered drug excreted unchanged in urine from time point 0- 24h)
Measured: up to 107 hours
CLR0-24 (renal clearance of dabigatran from the time point 0 until the time point 24h )
Measured: up to 107 hours
AUEC0-24 (area under the effect curve)
for ecarin clotting time and thrombin time
Measured: up to 107 hours
ERmax (maximum effect ratio)
for ecarin clotting time and thrombin time
Measured: up to 107 hours
Occurence of Adverse Events
Measured: within 5 days after last drug administration
Assessment of Tolerability by investigator
Measured: within 5 days after last drug administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2014 (estimated)
- Study startJun 2008
- Primary completionAug 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by Boehringer IngelheimThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boehringer Ingelheim
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02171533
- Sponsor's protocol ID
- 1160.74
- Status last verified
- Jun 2014
- First submitted
- 20 Jun 2014
- Last updated
- 24 Jun 2014
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Relative Bioavailability of Single Oral Doses of 150 mg Dabigatran Etexilate With or Without Oral Administration of Verapamil in Two Different Dosages (240 mg and 480 mg Daily) (Open-label, Fixed-sequence Design), and Relative Bioavailability of Single Oral Doses of 150 mg Dabigatran Etexilate Given With or Without Single Oral Doses of 120 mg (IR) or 240 mg (ER) of Verapamil Administered at Different Time Points Relative to Dabigatran Etexilate Dosing in Healthy Male and Female Volunteers (Open-label, Randomised, Five-way Crossover Design, Phase I Study)
- ClinicalTrials.gov ID
- NCT02171533
- Acronym / sponsor ID
- 1160.74
- Conditions
- Healthy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- Jun 2008
- Primary completion
- Aug 2008 (actual)
- First posted
- 24 Jun 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To investigate whether and to what extent the P-glycoprotein inhibitor (P-gp) verapamil affects the pharmacokinetic parameters of dabigatran with verapamil given at different dosages, in different formulations (immediate release (IR) and extended release (ER)), and in different intervals in relation to the dabigatran dose.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fixed sequence | Experimental | Drug: dabigatran, Drug: VerapamilTreatments will be given in a fixed sequence |
| Crossover | Experimental | Drug: dabigatran, Drug: Verapamil, Drug: Verapamil ERTreatments will be given in randomized sequences |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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
- Age ≥18 and ≤55 years
- Body mass index (BMI) ≥18.5 and BMI ≤29.9 kg/m2
- Signed and dated written informed consent prior to admission to the study in accordance with GCP and the local legislation
Key exclusion criteria (24 listed)
- 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
- Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
- History of relevant orthostatic hypotension, fainting spells or blackouts
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| dabigatran | Drug | Crossover, Fixed sequence |
| Verapamil | Drug | Crossover, Fixed sequence |
| Verapamil ER | Drug | Crossover |
Primary outcome
AUC0-infinity (area under the concentration-time curve of total dabigatran over the time interval from 0 extrapolated to infinity)
Time frame: up to 107 hours
Cmax (maximum measured concentration of total dabigatran)
Time frame: up to 107 hours
31 secondary outcomes
AUC0-infinity (area under the concentration-time curve of free dabigatran over the time interval from 0 extrapolated to infinity)
Time frame: up to 107 hours
Cmax (maximum measured concentration of free dabigatran)
Time frame: up to 107 hours
AUC0-infinity (area under the concentration-time curve of verapamil over the time interval from 0 extrapolated to infinity)
Time frame: up to 107 hours
Cmax (maximum measured concentration of verapamil)
Time frame: up to 107 hours
AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point)
Time frame: up to 107 hours
AUC0-24 (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 24 h after the administration)
Time frame: up to 107 hours
tmax (time from dosing to the maximum concentration of the analyte in plasma)
Time frame: up to 107 hours
λz (terminal rate constant in plasma)
Time frame: up to 107 hours
t1/2 (terminal half-life of the analyte in plasma)
Time frame: up to 107 hours
MRTpo (mean residence time of the analyte in the body after oral administration)
Time frame: up to 107 hours
CL/F (apparent clearance of the analyte in the plasma after extravascular administration)
Time frame: up to 107 hours
Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose)
Time frame: up to 107 hours
AUCτ,ss (area under the concentration-time curve of verapamil within the uniform dosing interval τ)
Time frame: up to 107 hours
AUC0-tz,ss (area under the concentration-time curve of verapamil 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)
Time frame: up to 107 hours
Cmax,ss (maximum concentration of verapamil at steady state)
Time frame: up to 107 hours
tz,ss (time of last measureable concentration of verapamil within the dosing interval τ at steady state)
Time frame: up to 107 hours
tmax,ss (time from last dosing to the maximum concentration of verapamil at steady state on day 4)
Time frame: up to 107 hours
CL/F,ss (apparent clearance of verapamil at steady state after extravascular multiple dose administration)
Time frame: up to 107 hours
Cmin,ss (minimum measured concentration of verapamil at steady state over a uniform dosing interval τ)
Time frame: up to 107 hours
tmin,ss (time from last dosing to the minimum concentration of verapamil at steady state over a uniform dosing interval τ)
Time frame: up to 107 hours
Cpre,ss (predose concentration of verapamil at steady state immediately before administration of the next dose)
Time frame: up to 107 hours
Cavg (Average concentration of verapamil at steady state)
Time frame: up to 107 hours
MRTpo,ss (mean residence time of verapamil in the body at steady state after oral administration)
Time frame: up to 107 hours
Vz/F,ss (apparent volume of distribution during the terminal phase λz at steady state following an extravascular administration)
Time frame: up to 107 hours
Ae0-24 (amount of dabigatran that is eliminated in urine from the time interval 0-24h)
Time frame: up to 107 hours
fe0-24 (fraction of administered drug excreted unchanged in urine from time point 0- 24h)
Time frame: up to 107 hours
CLR0-24 (renal clearance of dabigatran from the time point 0 until the time point 24h )
Time frame: up to 107 hours
AUEC0-24 (area under the effect curve)
Time frame: up to 107 hours
ERmax (maximum effect ratio)
Time frame: up to 107 hours
Occurence of Adverse Events
Time frame: within 5 days after last drug administration
Assessment of Tolerability by investigator
Time frame: within 5 days after last drug administration
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2014.
Related trials for Healthy
Recruiting
THE EFFECTS OF GAME-BASED EXERCISE PROGRAMS
Physical Activity, Body Image
Not yet recruitingPhase 1
A Phase I Study of GLR2053 Tablets in Chinese Healthy Adult Participants
Atopic Dermatitis
Recruiting
Colon-delivered Riboflavin and Gut Microbiota Composition
Microbiome Dysbiosis, Gut Health
Not yet recruiting
Neuroergonomic Analysis of a Brain-Computer Interface Device (BCI)
Healthy Volunteers - Male and Female
RecruitingPhase 1
First-in-Human Trial to Assess REGN20423 in Healthy Adult Participants and Adult Participants With Atopic Dermatitis
Healthy Volunteer, Atopic Dermatitis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing dabigatran, Verapamil and Verapamil ER in people with Healthy, run by Boehringer Ingelheim.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Jun 2014. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
AUC0-infinity (area under the concentration-time curve of total dabigatran over the time interval from 0 extrapolated to infinity) (time frame: up to 107 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jun 2014.