A Study to Investigate Biomarkers After Single Doses of Anticoagulants in Healthy Young Male and Healthy Elderly Participants (MK-0000-216 AM1)

A Randomized Clinical Trial to Validate Novel Biomarker Approaches After Single Doses of Anticoagulants in Healthy Young Male Subjects and in Healthy Elderly Subjects

This is a study to investigate biomarkers after single oral doses of the anticoagulant agents dabigatran etexilate and rivaroxaban in healthy young male subjects and in healthy elderly subjects.

Study Overview

• Status: Completed
• Conditions: Thrombosis
• Intervention / Treatment: Drug: dabigatran etexilate; Drug: rivaroxaban

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion criteria for non-hemophilia participants:

Panel A

- Male or female between 65 to 85 years of age

Panel B

- Male between 18 to 45 years of age

Both Panels

• Weight of ≥50 kg and ≤110 kg
• In good health
• No clinically significant abnormality on electrocardiogram (ECG)
• Nonsmoker and/or has not used nicotine or nicotine-containing products for at least approximately 6 months

Exclusion criteria for non-hemophilia participants:

• History of stroke, chronic seizures, or major neurological disorder
• History of clinically significant endocrine, gastrointestinal (including peptic ulcer disease), cardiovascular, hematological, hepatic, immunological, renal, respiratory, or genitourinary abnormalities or diseases
• History of malignant neoplastic disease, with the exception of adequately treated non-melanomatous skin carcinoma or other malignancies that have been successfully treated ≥10 years prior to the study
• History of a thrombotic or platelet-related disorder including prior deep venous thrombosis or pulmonary embolus
• Use of warfarin, coumadin, heparin, aspirin, dabigatran etexilate, rivaroxaban or dipyridamole within 2 weeks
• History of poor wound healing
• Unable to refrain from or anticipates the use of any medication, including aspirin and aspirin-containing products, all non-steroidal anti-inflammatory drug (NSAID)-containing products (including pain, cold and allergy products, etc.) and including prescription and non-prescription drugs or herbal remedies (such as St. John's Wort [Hypericum perforatum]) beginning approximately 2 weeks (or 5 half-lives) prior to initiation of the treatment periods, throughout the study until the post-study visit
• Consumption of excessive amounts of alcohol, defined as greater than 3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer [284 mL/10 ounces], wine [125 mL/4 ounces], or distilled spirits [25 mL/1 ounce]) per day
• Consumption of excessive amounts, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, or other caffeinated beverages per day
• Major surgery, donation or loss of 1 unit of blood (approximately 500 mL) or participation in another investigational study within 4 weeks
• History of significant multiple and/or severe allergies (including latex allergy), or an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food, including dabigatran etexilate and rivaroxaban
• Current regular user (including illicit drugs or has a history of drug [including alcohol] abuse within approximately 6 months
• History (including family history if hereditary) or symptoms of clinically relevant bleeding disorder
• Organic lesion at risk of bleeding (e.g., aneurysm, cavernous hemangioma, arterio-venous malformation)
• History of frequent epistaxis or has recurrent or active gingivitis or hemorrhoids

Inclusion criteria for hemophilia participants:

• Male with diagnosis of hemophilia B between 18 to 64 years of age
• Weight of ≥110 lbs and ≤300 lbs
• Has not received clotting factor in the 7 days prior to blood sampling
• No active bleeding event
• No procedure or surgery in the past 8 weeks
• Judged to be in good health based on medical history
• Has not smoked more than 2 cigarettes per day for at least approximately 1 week prior; has not smoked a pipe or cigar or chewed tobacco for at least 3 days prior
• Can refrain from the use of all NSAIDs (e.g., Advil, Aleve, aspirin), all NSAID-containing products (including pain, cold, and allergy products, etc.), herbal meds or drugs for 7 days prior to the date of study procedure

Exclusion criteria for hemophilia participants:

• Clinically significant endocrine, gastrointestinal (including peptic ulcer disease), cardiovascular, hematological (except factor IX deficiency), immunological, renal, respiratory, neurological or genitourinary abnormalities or diseases
• History of malignant neoplastic disease, with the exception of adequately treated non-melanomatous skin carcinoma or other malignancies that have been successfully treated ≥10 years prior to the study
• Consumption of excessive amounts of alcohol, defined as greater than 3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer [284 mL/10 ounces], wine [125 mL/4 ounces], or distilled spirits [25 mL/1 ounce]) within 24 hours prior to study procedures
• Major surgery, donation or loss of 1 unit of blood (approximately 500 mL) or participation in another investigational study within 7 days prior to the date of study procedures
• Current regular user (including illicit drugs or has a history of drug [including alcohol] abuse within approximately 6 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dabigatran; Single 150-mg dose of dabigatran etexilate	Drug: dabigatran etexilate; dabigatran etexilate, orally, as 2 x 75-mg capsules (150 mg), single administration
Experimental: Rivaroxaban; Single 20-mg dose of rivaroxaban	Drug: rivaroxaban; rivaroxaban, orally, as 2 x 10-mg tablets (20 mg), single administration
No Intervention: No intervention; No study drug will be administered

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Endogenous thrombin potential by Thrombin Generation Assay (TGA)-2a assay	From up to 2 hours pre-dose to up to 24 hours post-dose
Level of fibrin degradation product (D-dimer)	From up to 2 hours pre-dose to up to 24 hours post-dose
Level of fibrinopeptide A (FPA)	From up to 2 hours pre-dose to up to 24 hours post-dose
Level of prothrombin split products (F1+2)	From up to 2 hours pre-dose to up to 24 hours post-dose
Level of thrombin-antithrombin complex (TAT)	From up to 2 hours pre-dose to up to 24 hours post-dose

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: June 3, 2011
• First Submitted That Met QC Criteria: June 21, 2011
• First Posted (Estimate): June 23, 2011

Study Record Updates

• Last Update Posted (Estimate): October 2, 2015
• Last Update Submitted That Met QC Criteria: October 1, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: Hemophilia B
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thrombosis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Rivaroxaban; Dabigatran
• Other Study ID Numbers: 0000-216