Dabigatran in an Interaction Probe Drug Cocktail (D-cocktail)

An Open-label Crossover Trial Assessing the Value of Dabigatran in a Drug Interaction Cocktail in Healthy Young Volunteers

Four periods of oral dosing following overnight fasting (1. known metabolic probe drug cocktail consisting of caffeine, diclofenac, esomeprazole, metoprolol, midazolam; 2. dabigatran + cocktail; 3. dabigatran alone; 4. clarithromycin 3 days + cocktail + dabigatran). Blood samples collected for pharmacokinetics over 24 h. Washout between periods. Adverse events, haematology and clinical chemistry recorded.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Caffeine; Drug: Diclofenac; Drug: Esomeprazole; Drug: Metoprolol; Drug: Midazolam; Drug: Dabigatran; Drug: Clarithromycin

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• Finland
  • Turku, Finland, 20520
    • Teutori CPRU

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Healthy
• Weight at least 50 kg and body mass index 19 - 30 kg m-2
• Normal clinical laboratory profiles
• No childbearing potential or use of adequate contraceptive measures

Exclusion Criteria:

• Blood loss >300 ml within 2 months prior to the first dosing day
• Pregnancy, breastfeeding
• Allergy or hypersensitivity to caffeine, diclofenac, esomeprazole, metoprolol, midazolam, dabigatran or clarithromycin or to excipients in the pharmaceutical products
• Infection with HIV, HBV or HCV
• Participation in the preceding 3 months or concomitantly in any clinical drug study
• Suspected current drug or alcohol abuse
• History of drug or alcohol abuse.
• Concomitant medication with the exception of hormonal contraception.
• Positive result in urine test for drug abuse.
• Nicotine consumption equivalent to >5 cigarettes per day

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: Caffeine; probe; Drug: Diclofenac; probe; Drug: Esomeprazole; probe; Drug: Metoprolol; probe; Drug: Midazolam; probe; Drug: Dabigatran; probe; Drug: Clarithromycin; perpetrator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC of dabigatran in plasma	Exposure ratio for dabigatran in combination and dabigatran alone	24 h

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of subjects with adverse events	23 days

Collaborators and Investigators

• Sponsor: Turku University Hospital
• Investigators: Principal Investigator: Petri Vainio, MD PhD, Turku University Hospital

Study record dates

Study Major Dates

• Study Start: February 1, 2015
• Primary Completion (Actual): September 1, 2016
• Study Completion (Actual): June 1, 2017

Study Registration Dates

• First Submitted: January 30, 2015
• First Submitted That Met QC Criteria: February 6, 2015
• First Posted (Estimate): February 12, 2015

Study Record Updates

• Last Update Posted (Actual): August 14, 2018
• Last Update Submitted That Met QC Criteria: August 10, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Anti-Infective Agents; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Purinergic Antagonists; Purinergic Agents; Gastrointestinal Agents; Protease Inhibitors; Anti-Bacterial Agents; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Protein Synthesis Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Anti-Ulcer Agents; Proton Pump Inhibitors; Phosphodiesterase Inhibitors; Purinergic P1 Receptor Antagonists; Central Nervous System Stimulants; Sympatholytics; Adrenergic beta-1 Receptor Antagonists; Midazolam; Dabigatran; Diclofenac; Clarithromycin; Metoprolol; Caffeine; Esomeprazole
• Other Study ID Numbers: T162/2014; 2014-003628-38 (EudraCT Number)