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

• ClinicalTrials.gov Identifier: NCT01229254
• Recruitment Status: Completed
• First Posted: October 27, 2010
• Results First Posted: September 18, 2017
• Last Update Posted: September 18, 2017
• Sponsor: Portola Pharmaceuticals
• Information provided by (Responsible Party): Portola Pharmaceuticals

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Atrial Fibrillation; Atrial Flutter	Drug: Amiodarone; Drug: Betrixaban 60 mg; Drug: Betrixaban 90 mg; Drug: Betrixaban 30 mg	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 189 participants
• 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
• Study Start Date: September 2010
• Actual Primary Completion Date: December 2010
• Actual Study Completion Date: April 2011

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. 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 :

1. 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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• 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
• Other Study ID Numbers: 006-00
• First Posted: October 27, 2010
• 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