Safety and Pharmacokinetics of Quinidine Alone and in Combination With Dabigatran Etexilate

Boehringer Ingelheim

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: dabigatran etexilate; Drug: quinidine

Study type: Interventional

Funder types: Industry

Identifiers

NCT02171624

1160.90

Details and patient eligibility

About

Open-label, two-way crossover design with a quinidine sulfate run-in period followed by a randomised sequence of dabigatran etexilate plus quinidine sulfate or dabigatran etexilate alone to evaluate the safety of co-administration of dabigatran etexilate and quinidine. and the pharmacokinetic interaction between quinidine and dabigatran etexilate.

Enrollment: 42 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Healthy male and female subjects
• Age ≥18 and Age ≤55 years
• Body Mass Index (BMI) ≥18.5 and BMI <30 kg/m2
• Signed and dated written informed consent prior to admission to the study in accordance with GCP and the local legislation.

Exclusion criteria

• Any finding of the medical examination (including Blood Pressure (BP), Pulse Rate (PR) and Electrocardiogram (ECG)) deviating from normal and of clinical relevance

• Any evidence of a clinically relevant concomitant disease

• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders

• Surgery of the gastrointestinal tract (except appendectomy)

• 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 relevant allergy/hypersensitivity (including allergy to drug or its excipients)

• 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 or that prolong the QT/QTc interval 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 thirty days prior to administration or during the trial

• Inability to refrain from smoking on trial days Smoker (>10 cigarettes or >3 cigars or >3 pipes/day)

• Alcohol abuse (more than 60 g/day)

• 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

• Inability to comply with dietary regimen of trial site

• A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 ms)

• A history of additional risk factors for Torsades de Pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)

• Taking drugs which are known P-gp and/or CYP3A4 inhibitors or inducers (verapamil, phenothiazine antipsychotics, macrolide antibiotics (clarithromycin, erythromycin), antifungal drugs, antiviral drugs (protease inhibitors like nelfinavir) or St. John´s Wort) within the last 4 weeks before screening

• Taking drugs which are known CYP2D6 substrates (antidepressants, antiarrhythmics, beta blockers) within the last 2 weeks before screening

• For female subjects:

  • Pregnancy or planning to become pregnant within 2 months of study completion
  • Positive pregnancy test
  • No adequate contraception e.g., sterilisation, IUD (intrauterine device), have not been using a barrier method of contraception for at least 3 months prior to participation in the study
  • Are not willing or are unable to use a reliable method of barrier contraception (such as diaphragm with spermicidal cream/jelly or condoms with spermicidal foam), during and up to 2 months after completion/termination of the trial
  • Chronic use of oral contraception or hormone replacement containing ethinyl estradiol as the only method of contraception
  • Partner is unwilling to use condoms
  • Currently lactating

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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42 participants in 2 patient groups

dabigatran etexilate

Experimental group

Description:

quinidine run-in, followed by dabigatran+quinine and dabigatran alone in randomized order

Treatment:

Drug: quinidine

Drug: dabigatran etexilate

quinidine

Experimental group

Description:

quinidine run-in, followed by dabigatran+quinine and dabigatran alone in randomized order

Treatment:

Drug: quinidine

Drug: dabigatran etexilate