Investigation of the Impact of Concomitant Use of Multiple Doses of Clopidogrel With Multiple Doses of Dabigatran Etexilate on the Pharmacokinetic and Pharmacodynamic Parameters in Healthy Male Subjects

NCT02171598 | Completed Phase 1

• 1 other identifier: 1160.83
• Study Type: interventional
• Target: 44
• Locations: 0 countries
• Sites: N/A

Brief Summary

The primary objective of the study (Main Part 2) was to investigate whether and to which extent a combination of multiple oral doses (steady state conditions) of 75 mg of clopidogrel q.d. (after a loading dose of 300 mg) and multiple doses of 150 mg of dabigatran etexilate b.i.d. at steady state affects pharmacokinetic and pharmacodynamic parameters of dabigatran etexilate and clopidogrel. The objective of the preceding Pilot Part 1 of the study was to explore the effect of a single dose of 300 mg clopidogrel administered after multiple doses of 75 mg and 150 mg dabigatran had reached steady state, regarding safety as well as pharmacokinetic and pharmacodynamic parameters. The Main Part 3 of the study moreover was to compare intra-individually the effects of a single dose of 600 mg clopidogrel with the same dose, 600 mg clopidogrel, given additionally to multiple doses of 150 mg dabigatran in steady state condition with respect to safety and pharmacokinetic and pharmacodynamic parameters.

Conditions

Healthy

Outcome Measures

Primary Outcomes (6)

• AUCτ,ss (area under the concentration-time curve of the analyte in plasma over one dosing interval at steady state)

  for total dabigatran, clopidogrel and the inactive metabolite SR26334

  up to 19 days

• AUC0-24,1 (area under the concentration-time curve of the analyte in plasma over one dosing interval after the loading dose)

  for clopidogrel and the inactive metabolite SR26334

  up to 19 days

• Cmax,ss (maximum measured concentration of the analyte in plasma at steady state)

  for total dabigatran, clopidogrel and the inactive metabolite SR26334

  up to 19 days

• Cmax,1 (maximum measured concentration of the analyte in plasma after the loading dose)

  for total dabigatran, clopidogrel and the inactive metabolite SR26334

  up to 19 days

• AUECIPA,0-24 (area under the effect curve of inhibition of platelet aggregation after the first dose of clopidogrel)

  up to 19 days

• Emax,IPA,0-24 (maximum percentage change - compared to baseline - in adenosine diphosphate-induced platelet aggregation after the loading dose of clopidogrel)

  baseline, up to 19 days

Secondary Outcomes (26)

• tmax (time from dosing to the maximum concentration of the analyte in plasma)

  up to 8 weeks

• AUC0-infinity (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)

  up to 8 weeks

• AUC0-tz (area under the concentration-time curve of the analyte in plasma from the time point 0 to the last quantifiable analyte plasma concentration)

  up to 8 weeks

• λz (terminal rate constant in plasma)

  up to 8 weeks

• t1/2 (terminal half-life of the analyte in plasma)

  up to 8 weeks

Study Arms (3)

Fixed sequence 1

EXPERIMENTAL

multiple-dose, fixed-sequence with 2 periods of 4 days separated by a washout period of at least 14 days. A single dose of 300 mg clopidogrel will be given on top of 75 mg or 150 mg dabigatran in steady state.

Drug: Clopidogrel; Drug: Dabigatran high dose; Drug: Dabigatran low dose

Crossover

EXPERIMENTAL

clopidogrel + dabigatran / clopidogrel / dabigatran in randomized order

Drug: Clopidogrel; Drug: Dabigatran high dose; Drug: Dabigatran low dose

Fixed sequence 2

EXPERIMENTAL

intra-individual comparison with the fixed sequence of a single dose of 600mg clopidogrel alone and the combination of dabigatran 150 mg in steady state plus single dose of 600 mg clopidogrel

Drug: Clopidogrel; Drug: Dabigatran high dose

Interventions

Clopidogrel DRUG

Crossover; Fixed sequence 1; Fixed sequence 2

Dabigatran high dose DRUG

Crossover; Fixed sequence 1; Fixed sequence 2

Dabigatran low dose DRUG

Crossover; Fixed sequence 1

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male subjects according to the following criteria: Based upon a complete medical history, including the physical examination, vital signs (blood pressure, pulse rate), body temperature, 12-lead electrocardiogram, clinical laboratory tests
• Age ≥18 and Age ≤40 years
• Body mass index (BMI) ≥18.5 and ≤29.9 kg/m2 (Body Mass Index)
• Signed and dated written informed consent prior to admission to the study in accordance with GCP and the local legislation.

You may not qualify if:

• Any gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
• Subjects who in the investigator's judgement are perceived as having an increased risk of bleeding, for example because of:
• Hemorrhagic disorders or bleeding diathesis
• Occult blood in faeces or haematuria
• Trauma or surgery within the last month or as long as an excessive risk of bleeding persists after these events, or planned surgery during trial participation
• History of arteriovenous malformation or aneurysm
• History of gastroduodenal ulcer disease, gastrointestinal haemorrhage and haemorrhoids
• History of intracranial, intraocular, spinal, retroperitoneal, or atraumatic intraarticular bleeding
• Use of drugs that may interfere with haemostasis during trial conduct (e.g.acetyl salicylic acid or other non-steroidal anti-inflammatory drugs)
• Relevant surgery of gastrointestinal tract
• 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 any medication within four weeks of first dosing

Sponsors & Collaborators

• Boehringer Ingelheim: lead

MeSH Terms

Interventions

Clopidogrel; Dabigatran

Intervention Hierarchy (Ancestors)

Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Benzimidazoles

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2014
• First Posted: June 24, 2014
• Study Start: February 1, 2009
• Primary Completion: July 1, 2009
• Last Updated: June 24, 2014

Record last verified: 2014-06