Clinical trial NCT01229254: Evaluate the Pharmacokinetics and Safety of MK-4448 in Participants With Nonvalvular Atrial Fibrillation or Atrial Flutter
Official title: A Phase II, Open-label, Dose Exposure Confirmation Study to Evaluate the Pharmacokinetics and Safety and Tolerability of Betrixaban (MK-4448) in Adult Patients With Nonvalvular Atrial Fibrillation or Atrial Flutter
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Atrial Fibrillation
Atrial Flutter
Keywords: Betrixaban
MK-4448
nonvalvular atrial fibrillation
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2010-10-27
Enrollment: 189
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary purpose of this study is to optimize drug exposure in the target population.


Eligibility criteria: Inclusion Criteria:

* In the opinion of the investigator, participant requires long term anticoagulation for stroke prevention in atrial flutter (AF).
* Men and women ≥18 years of age.
* Participant has current non-valvular atrial fibrillation (NVAF) or AF or electrocardiogram (ECG) or Holter documentation within past 12 months.
* Participant has an international normalized ratio (INR) ≤ 2.2 at allocation (Visit 2).
* A participant who is of reproductive potential agrees to remain abstinent or use (or have their partner use) 2 acceptable methods of birth control for the duration of the study. Acceptable methods of birth control are: intrauterine device (IUD), diaphragm with spermicide, condom, vasectomy, and hormonal contraception.
* Participant understands the study procedures and risks involved with the study, and voluntarily agree to participate by giving written informed consent.

Exclusion Criteria:

General

* Participant is currently participating in another drug study or has received an investigational drug within 30 days prior to enrollment.
* Participant is a woman who is pregnant, lactating or of child-bearing potential who refuses to use a medically acceptable form of contraception throughout the study.
* Participant has a body weight less than 40 kg (88 lbs) or greater than 200 kg (440 lbs).
* Participant routinely consumes more than 2 alcoholic drinks per day (average \>14 alcoholic drinks per week) or greater than 5 drinks within 2 hours on occasion.

Prohibited Medical Conditions

* Participant has any condition or situation which, in the opinion of the investigator, might pose a risk to the participant or interfere with participation in the study.
* Conditions associated with an increased risk of bleeding Active bleeding.
* Conditions other than AF that require chronic anticoagulation.
* Severe aortic and mitral valvular disease requiring surgical intervention.
* Previous known history of coagulopathy (e.g.: Factor V Leiden, Protein C Deficiency, Protein S Deficiency, Antiphospholipid Syndrome, etc.).
* Active infective endocarditis.
* Participant has history of familial long QT interval (the QT interval is the portion of an electrocardiogram (ECG) between the onset of the Q wave and the end of the T wave, representing the total time for ventricular depolarization and repolarization) syndrome or prolonged Bazett-corrected QT interval (QTcB) (males \> 470 msec; females \>480 msec) at baseline as measured on a 12-lead ECG.
* Participant has serious pulmonary, hepatic, metabolic, gastrointestinal, central nervous system (CNS) or psychiatric disease, end-stage disease states, or any other disease that could interfere with the conduct or validity of the study or compromise participant safety.
* Participant has a history of malignancy ≤ 5 years prior to signing informed consent, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer (melanoma, leukemia, lymphoma and myeloproliferative disorders of any duration are excluded).
* Participant has a history of mental instability, drug/alcohol abuse within the past 5 years, or major psychiatric illness not adequately controlled and stable on pharmacotherapy.
* Participant has reversible causes of atrial fibrillation (i.e.: cardiac surgery, pulmonary embolism, untreated hyperthyroidism).
* Participant is to undergo pulmonary vein isolation or surgery for treatment of AF.
* Participant had a severe, disabling stroke within the previous 6 months, any stroke within the previous 14 days, thromboembolism within previous 30 days or a transient ischemic attack (TIA) within 3 days prior to Visit 1.
* Participant requires renal replacement therapies (hemo- or peritoneal dialysis).
* Participant has any of a list of defined laboratory abnormalities.

Prohibited Medications

* Anti-platelet agents other than aspirin within 10 days prior to Visit 1 (excluding maintenance dose clopidogrel, prasugrel or ticlopidine) or fibrinolytic agents within 30 days prior to Visit 1.
* Aspirin greater than 162 mg/day.
* Daily non-steroidal anti-inflammatory drug (NSAID) use.
* Dronedarone, verapamil or ketoconazole.
* Vitamin K antagonists (VKA) or other anticoagulants.

Primary outcomes:
measure: Steady-state C12 hr on Days 14, 18, and 21 After Weight-based Dosing
timeFrame: Days 14, 18, and 21 of the PK period
Secondary outcomes:
measure: Steady-state C12 hr on Days 14, 18, and 21 After Weight and Amiodarone-based Dosing
timeFrame: Days 14, 18, and 21 of the PK period
Other outcomes:
Locations:
Study officials:
References: