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

NCT01229254 | Completed Phase 2 Results

• 1 other identifier: 006-00
• Study Type: interventional
• Target: 189
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

Atrial Fibrillation; Atrial Flutter

Keywords

Betrixaban; MK-4448; nonvalvular atrial fibrillation

Outcome Measures

Primary Outcomes (1)

• Steady-state C12 hr on Days 14, 18, and 21 After Weight-based Dosing

  Betrixaban PK concentration at 12 hr on Days 14, 18, and 21 in low and high weight groups

  Days 14, 18, and 21 of the PK period

Secondary Outcomes (1)

• Steady-state C12 hr on Days 14, 18, and 21 After Weight and Amiodarone-based Dosing

  Days 14, 18, and 21 of the PK period

Study Arms (3)

Amiodarone

EXPERIMENTAL

Participants on betrixaban 30 mg and concomitant baseline amiodarone

Drug: Amiodarone; Drug: Betrixaban 30 mg

Betrixaban 60 mg

EXPERIMENTAL

Participants with lower weights

Drug: Betrixaban 60 mg

Betrixaban 90 mg

EXPERIMENTAL

Participants with higher weights

Drug: Betrixaban 90 mg

Interventions

Amiodarone DRUG

Patients on Amiodarone

Amiodarone

Betrixaban 60 mg DRUG

Betrixaban 60 mg once a day with food on Day 0 through Day 25

Also known as: MK-4448

Betrixaban 60 mg

Betrixaban 90 mg DRUG

Betrixaban 90 mg once a day with food on Day 0 through Day 25

Also known as: MK-4448

Betrixaban 90 mg

Betrixaban 30 mg DRUG

Betrixaban 30 mg once a day with food on Day 0 through Day 25 with concomitant amiodarone treatment.

Also known as: MK-4448

Amiodarone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Portola Pharmaceuticals: lead

MeSH Terms

Conditions

Atrial Fibrillation; Atrial Flutter

Interventions

Amiodarone; betrixaban

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Head of Clinical Development
• Organization: Portola Pharmaceuticals, Inc.

650-246-7000

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2010
• First Posted: October 27, 2010
• Study Start: September 1, 2010
• Primary Completion: December 1, 2010
• Study Completion: April 1, 2011
• Last Updated: August 7, 2023
• Results First Posted: September 18, 2017

Record last verified: 2023-08