Atrial FibrillationPhase 2NCT01229254

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

A Phase 2 study testing Amiodarone, Betrixaban 60 mg and Betrixaban 90 mg in people with Atrial Fibrillation and Atrial Flutter, run by Portola Pharmaceuticals.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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

Who is it for?: Ages 18 years and older
Conditions the study is for: Atrial Fibrillation, Atrial Flutter
What is being tested?: Amiodarone, Betrixaban 60 mg and Betrixaban 90 mg
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 189 participants
Where: No sites listed yet
Study dates: Sep 2010to Apr 2011
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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

Show all 27Show fewer

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.

About this study

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

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

Conditions: Atrial Fibrillation, Atrial Flutter
Being tested: Amiodarone, Betrixaban 60 mg, Betrixaban 90 mg, Betrixaban 30 mg
Keywords: Betrixaban, MK-4448, nonvalvular atrial fibrillation
Medical subject headings: Atrial Fibrillation, Atrial Flutter

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AmiodaroneDrug
Patients on Amiodarone
Betrixaban 60 mgDrug
Also called MK-4448
Betrixaban 60 mg once a day with food on Day 0 through Day 25
Betrixaban 90 mgDrug
Also called MK-4448
Betrixaban 90 mg once a day with food on Day 0 through Day 25
Betrixaban 30 mgDrug
Also called MK-4448
Betrixaban 30 mg once a day with food on Day 0 through Day 25 with concomitant amiodarone treatment.

Study groups in NCT01229254
Study group	Role	What they receive
Amiodarone	Experimental	Participants on betrixaban 30 mg and concomitant baseline amiodarone Receives: Drug: Amiodarone; Drug: Betrixaban 30 mg
Betrixaban 60 mg	Experimental	Participants with lower weights Receives: Drug: Betrixaban 60 mg
Betrixaban 90 mg	Experimental	Participants with higher weights Receives: Drug: Betrixaban 90 mg

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: 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
Betrixaban PK concentration at 12 hr on Days 14, 18, and 21 in amiodarone, low and high weight groups
Measured: Days 14, 18, and 21 of the PK period

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2010Apr 2011

First posted27 Oct 2010 (estimated)
Study startSep 2010
Primary completionDec 2010
Study completionApr 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Atrial FibrillationStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 189 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01229254
Sponsor's protocol ID: 006-00
Status last verified: Aug 2023
First submitted: 9 Sep 2010
Last updated: 7 Aug 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

Active, not recruiting
Horizon 360 Protocol for the Treatment of Paroxysmal Atrial Fibrillation With the Sphere-360™ Catheter and Affera™ Mapping and Ablation System (Horizon 360)
Paroxysmal AF
Active, not recruitingObservational study
Concomitant Left Atrial Appendage Closure and Pulsed Field Ablation-Asia
Concomitant Procedures, Atrial Fibrillation
Active, not recruiting
CONVERGE Post-Approval Study (PAS)
Chronic Atrial Fibrillation
Recruiting
Early Closure of Left Atrial Appendage for Patients With Atrial Fibrillation and Ischemic Stroke Despite Anticoagulation Therapy
Ischemic Stroke, Atrial Fibrillation
RecruitingPhase 2
Safety in Adult Participants With Atrial Fibrillation Who Are Treated With Anticoagulation
Atrial Fibrillation (AF)

All Atrial Fibrillation trials

Study at a glance

From the registry record, last updated by the sponsor on 7 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT01229254
Acronym / sponsor ID: 006-00
Conditions: Atrial Fibrillation, Atrial Flutter
Keywords: Betrixaban, MK-4448, nonvalvular atrial fibrillation
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 189 participants (actual)
Lead sponsor: Portola PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: Sep 2010
Primary completion: Dec 2010 (actual)
Study completion: Apr 2011 (actual)
First posted: 27 Oct 2010 (estimated)
Results: Posted 18 Sep 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Amiodarone	Experimental	Drug: Amiodarone, Drug: Betrixaban 30 mgParticipants on betrixaban 30 mg and concomitant baseline amiodarone
Betrixaban 60 mg	Experimental	Drug: Betrixaban 60 mgParticipants with lower weights
Betrixaban 90 mg	Experimental	Drug: Betrixaban 90 mgParticipants with higher weights

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

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.

Key exclusion criteria (27 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
AmiodaronePatients on Amiodarone	Drug	Amiodarone
Betrixaban 60 mgAlso: MK-4448Betrixaban 60 mg once a day with food on Day 0 through Day 25	Drug	Betrixaban 60 mg
Betrixaban 90 mgAlso: MK-4448Betrixaban 90 mg once a day with food on Day 0 through Day 25	Drug	Betrixaban 90 mg
Betrixaban 30 mgAlso: MK-4448Betrixaban 30 mg once a day with food on Day 0 through Day 25 with concomitant amiodarone treatment.	Drug	Amiodarone

Primary outcome

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

1 secondary outcome

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

Results and safety

Results posted to the registry on 18 Sep 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Betrixaban 30 mg (+Amiodarone)	42	27
Betrixaban 60 mg (<80 kg)	74	58
Betrixaban 90 mg (≥80 kg)	73	61

Primary outcome: 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. Geometric least squares mean (90% Confidence Interval). Unit: ng/mL

Measure	Betrixaban 30 mg (+Amiodarone) n = 0	Betrixaban 60 mg (<80 kg) n = 68	Betrixaban 90 mg (≥80 kg) n = 69
Value	–	7.870 (6.654 to 9.307)	10.517 (8.903 to 12.423)

Betrixaban 60 mg (<80 kg): Ratio of geometric least-squares means: 0.748 (90% CI 0.591 to 0.948)

Population analysed: Per protocol analysis set, which includes all allocated patients who received at least one dose of study treatment and who were ≥ 90% compliant with study treatment, took study treatment within 24 hours prior to steadystate blood sampling, had at least two post steady-state blood samples collected, and not on amiodarone.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Maximum of 24 weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Betrixaban 30 mg (+Amiodarone)	6 of 42 (14.3%)	18 of 42 (42.9%)	Not reported
Betrixaban 60 mg (<80 kg)	13 of 74 (17.6%)	34 of 74 (45.9%)	Not reported
Betrixaban 90 mg (≥80 kg)	6 of 73 (8.2%)	35 of 73 (47.9%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Atrial Fibrillation

Active, not recruiting
Horizon 360 Protocol for the Treatment of Paroxysmal Atrial Fibrillation With the Sphere-360™ Catheter and Affera™ Mapping and Ablation System (Horizon 360)
Paroxysmal AF
Active, not recruitingObservational study
Concomitant Left Atrial Appendage Closure and Pulsed Field Ablation-Asia
Concomitant Procedures, Atrial Fibrillation
Active, not recruiting
CONVERGE Post-Approval Study (PAS)
Chronic Atrial Fibrillation
Recruiting
Early Closure of Left Atrial Appendage for Patients With Atrial Fibrillation and Ischemic Stroke Despite Anticoagulation Therapy
Ischemic Stroke, Atrial Fibrillation
RecruitingPhase 2
Safety in Adult Participants With Atrial Fibrillation Who Are Treated With Anticoagulation
Atrial Fibrillation (AF)

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Amiodarone, Betrixaban 60 mg and Betrixaban 90 mg in people with Atrial Fibrillation and Atrial Flutter, run by Portola Pharmaceuticals.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Sep 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01229254.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2023.