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Evaluate the Pharmacokinetics and Safety of MK-4448 in Participants With Nonvalvular Atrial Fibrillation or Atrial Flutter

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01229254
First Posted: October 27, 2010
Last Update Posted: September 18, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Portola Pharmaceuticals
  Purpose
The primary purpose of this study is to optimize drug exposure in the target population.

Condition Intervention Phase
Atrial Fibrillation Atrial Flutter Drug: Amiodarone Drug: Betrixaban 60 mg Drug: Betrixaban 90 mg Drug: Betrixaban 30 mg Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Portola Pharmaceuticals:

Primary Outcome Measures:
  • Steady-state C12 hr on Days 14, 18, and 21 After Weight-based Dosing [ Time Frame: Days 14, 18, and 21 of the PK period ]
    Betrixaban PK concentration at 12 hr on Days 14, 18, and 21 in low and high weight groups


Secondary Outcome Measures:
  • Steady-state C12 hr on Days 14, 18, and 21 After Weight and Amiodarone-based Dosing [ Time Frame: Days 14, 18, and 21 of the PK period ]
    Betrixaban PK concentration at 12 hr on Days 14, 18, and 21 in amiodarone, low and high weight groups


Enrollment: 189
Study Start Date: September 2010
Study Completion Date: April 2011
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Amiodarone
Participants on betrixaban 30 mg and concomitant baseline amiodarone
Drug: Amiodarone
Patients on Amiodarone
Drug: Betrixaban 30 mg
Betrixaban 30 mg once a day with food on Day 0 through Day 25 with concomitant amiodarone treatment.
Other Name: MK-4448
Experimental: Betrixaban 60 mg
Participants with lower weights
Drug: Betrixaban 60 mg
Betrixaban 60 mg once a day with food on Day 0 through Day 25
Other Name: MK-4448
Experimental: Betrixaban 90 mg
Participants with higher weights
Drug: Betrixaban 90 mg
Betrixaban 90 mg once a day with food on Day 0 through Day 25
Other Name: MK-4448

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
No Contacts or Locations Provided
  More Information

Responsible Party: Portola Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01229254     History of Changes
Other Study ID Numbers: 006-00
First Submitted: September 9, 2010
First Posted: October 27, 2010
Results First Submitted: July 21, 2017
Results First Posted: September 18, 2017
Last Update Posted: September 18, 2017
Last Verified: July 2017

Keywords provided by Portola Pharmaceuticals:
Betrixaban
MK-4448
nonvalvular atrial fibrillation

Additional relevant MeSH terms:
Atrial Fibrillation
Atrial Flutter
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Amiodarone
Betrixaban
Anti-Arrhythmia Agents
Vasodilator Agents
Potassium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Sodium Channel Blockers
Cytochrome P-450 CYP1A2 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Cytochrome P-450 CYP2C9 Inhibitors
Cytochrome P-450 CYP2D6 Inhibitors
Cytochrome P-450 CYP3A Inhibitors
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Anticoagulants