Evaluate the Pharmacokinetics and Safety of MK-4448 in Participants With Nonvalvular Atrial Fibrillation (Study MK-4448-006)

This study has been completed.
Sponsor:
Collaborator:
Portola Pharmaceuticals
Information provided by:
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01229254
First received: September 9, 2010
Last updated: June 22, 2011
Last verified: June 2011
  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 Group
Drug: Betrixaban 60 mg
Drug: Betrixaban 90 mg
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: 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 Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Steady-state plasma concentrations in the lower weight and the higher weight participant groups [ Time Frame: Days 14 through 21 ] [ Designated as safety issue: No ]
    The betrixaban steady-state PK is the endpoint of interest. Measurement is an average concentration from 3 timepoints: Days 14, 18 and 21.


Secondary Outcome Measures:
  • Steady-state geometric mean plasma concentrations for the 3 combined arms. [ Time Frame: Days 14, 18 and 21 ] [ Designated as safety issue: No ]
    The steady-state geometric mean plasma concentrations will be evaluated for the 3 arms of betrixaban treatment combined.


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 Group
Participants on betrixaban 30 mg and concomitant baseline amiodarone
Drug: Amiodarone Group
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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • In the opinion of the investigator, participant requires long term anticoagulation for stroke prevention in AF.
  • Men and women ≥18 years of age.
  • Participant has current NVAF or atrial flutter or ECG or Holter documentation within past 12 months.
  • Participant has an 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
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, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Vice President, Late State Development Group Leader, Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01229254     History of Changes
Other Study ID Numbers: MK-4448-006
Study First Received: September 9, 2010
Last Updated: June 22, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Merck Sharp & Dohme Corp.:
Betrixaban
MK-4448
nonvalvular atrial fibrillation

Additional relevant MeSH terms:
Atrial Fibrillation
Atrial Flutter
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Amiodarone
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents

ClinicalTrials.gov processed this record on July 22, 2014