Thrombosis
Conditions
Keywords
Hemophilia B
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.
Interventions
DRUGdabigatran etexilate
dabigatran etexilate, orally, as 2 x 75-mg capsules (150 mg), single administration
DRUGrivaroxaban
rivaroxaban, orally, as 2 x 10-mg tablets (20 mg), single administration
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| 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 |
Outcome results
None listed