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

Thrombosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01379300
• Other study ID #: 0000-216
• Status: Completed
• Phase: Phase 1
• First received: June 3, 2011
• Last updated: October 1, 2015
• Start date: May 2011
• Est. completion date: December 2011

Study information

• Verified date: October 2015
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health Products
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: December 2011
• Est. primary completion date: December 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Thrombosis

Intervention

Drug:
• dabigatran etexilate
dabigatran etexilate, orally, as 2 x 75-mg capsules (150 mg), single administration
• rivaroxaban
rivaroxaban, orally, as 2 x 10-mg tablets (20 mg), single administration

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Endogenous thrombin potential by Thrombin Generation Assay (TGA)-2a assay		From up to 2 hours pre-dose to up to 24 hours post-dose	No
Primary	Level of fibrin degradation product (D-dimer)		From up to 2 hours pre-dose to up to 24 hours post-dose	No
Primary	Level of fibrinopeptide A (FPA)		From up to 2 hours pre-dose to up to 24 hours post-dose	No
Primary	Level of prothrombin split products (F1+2)		From up to 2 hours pre-dose to up to 24 hours post-dose	No
Primary	Level of thrombin-antithrombin complex (TAT)		From up to 2 hours pre-dose to up to 24 hours post-dose	No