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

Study Overview
=================
Brief 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.

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

Conditions
-----------------
Thrombosis

Intervention / Treatment
-----------------
* Drug: dabigatran etexilate
* Drug: rivaroxaban


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

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

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hemophilia B