AzTrials
AzTrials

AnginaPhase 2NCT01549977

Effect of Febuxostat Compared to Placebo on Exercise Tolerance in Participants With Chronic Stable Angina

A Phase 2 study testing Febuxostat in people with Angina, run by Takeda at 21 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

The purpose of this study is to evaluate the effect of febuxostat, once daily (QD), compared to placebo as an add on to stable anti-anginal therapy, on the total exercise time of participants with Chronic Stable Angina. Read more about this study

Who is it for?
Ages 18 to 85 years
Conditions the study is for
Angina
What is being tested?
Febuxostat
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
1 participants
Where
21 sitesUnited States
Study dates
Jul 2012to Nov 2012
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 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
  • The participant or, when applicable, the participant's legally acceptable representative, signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
  • The participant has an serum urate (sUA) ≥5.0 mg/dL.
  • The participant has a history of angina, defined as:
  • Minimum of 3-month history of stable angina (at least 2 episodes of chest pain or anginal equivalent in the past 30 days); AND
  • Receiving at least one chronic anti-ischemic medication(s), including beta blockers, calcium channel blockers and long acting nitrates (doses must be stable for at least 30 days prior to Screening [Day -21]); AND
Show all 20Show fewer
  • Coronary artery disease, as defined by:
  • ≥50 % stenosis of ≥1 major coronary artery confirmed by angiography; OR
  • Documented prior myocardial infarction (MI) by enzymes/electrocardiogram (ECG) changes; OR
  • Documented myocardial imaging stress test; OR
  • Prior history of coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI) greater than 3 months prior to Screening Day -21.
  • The participant has estimated glomerular filtration rate (eGFR) >30 mL/min by Modification of Diet in Renal Disease (MDRD) at the Screening visit Day -21.
  • The participant has a normal/controlled blood pressure at Day 1/Randomization, as defined by the mean of three sitting blood pressures not exceeding 140/90.
  • The participant is male or female and aged 18 to 85 years, inclusive.
  • A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent throughout the duration of the study.
  • Participant is on stable (30 days) medication doses prescribed for any underlying medical condition (ie; hypertension, angina) and will remain on stable doses throughout the study duration.
  • Participant is able to take, in an ongoing manner, nitroglycerine for anginal symptoms.
  • Symptom-limited exercise duration, during ETT at Day -14 and Day -7, on the modified Bruce Protocol.
  • Exercise duration for the two ETTs at Day -14 and Day -7 did not differ by more than 20% of the longer of the two times, and did not differ by more than 60 seconds. To be confirmed by the Core ECG Lab prior to the subject being randomized.
  • Definite ECG signs of ischemia during the ETT at both Day -14 and Day -7 (i.e., 1 additional mm of horizontal or down-sloping ST-segment depression beyond baseline and ≥1 mm below the isoelectric line) are present in at least one standard ECG lead during ETT. The Day -7 ≥1 mm ST-segment depression must be verified by the Core ECG Lab prior to participant being randomized.

Who cannot join

  • The participant has received any investigational compound within 30 days prior to Screening Day -21.
  • The participant has received allopurinol or febuxostat in a previous clinical study or as a therapeutic agent.
  • The participant has gout or secondary hyperuricemia (e.g., due to myeloproliferative disorder, or organ transplant) or has experienced a gout flare.
  • The participant has a history of xanthinuria.
  • The participant is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (e.g., spouse, parent, child, sibling) or may consent under duress.
  • The participant has a history of hypersensitivity or allergies to febuxostat or nitroglycerine.
Show all 38Show fewer
  • The participant has hemoglobin <10 g/L at Screening Day -21.
  • The participant has a systolic blood pressure of less than 100 mmHg.
  • The participant has a blood pressure of greater than 200/100 at any Screening or Run-in visit.
  • The participant has a history or clinical manifestations of a significant medical condition that might affect his/her ability to complete the study.
  • The participant has any of the following at any Screening or Run-in visit:
  • Resting ST-segment depression ≥1 mm in any lead.
  • Left bundle-branch block.
  • New York Heart Association Class III or IV heart failure.
  • Acute coronary syndrome or a coronary revascularization procedure within 3 months of Screening.
  • Wolff-Parkinson-White syndrome.
  • Pacemaker or implantable cardioverter defibrillator.
  • Arrhythmias (i.e., SVT, atrial fibrillation/flutter, VT, or rate related bundle branch blocks).
  • Left ventricular hypertrophy with repolarization abnormalities.
  • The participant has a recent history (within the last 3 months) of myocardial infarction, heart failure, coronary artery bypass graft, percutaneous coronary intervention, hypertensive encephalopathy, cerebrovascular accident, or transient ischemic attack.
  • The participant has a contraindication for using nitrates (severe anemia, increased intracranial pressure, and those with a known sensitivity or hypersensitivity to nitroglycerin or its ingredients, or other nitrates or nitrites; concomitant use either regularly and/or intermittently, with phosphodiesterase type 5 (PDE5) inhibitors).
  • The participant has unstable angina that:
  • Occurs when the participant is at rest.
  • Is prolonged, usually greater than 20 minutes.
  • Occurs with increasing in intensity, duration, and/or frequency.
  • Responds poorly to nitroglycerin (i.e., does not go away after three doses of nitroglycerin or returns after the nitroglycerin helped at first).
  • The participant is unable to exercise sufficiently to complete ETT due to leg claudication, arthritis, deconditioning, or associated pulmonary disease.
  • The participant has severe or critical valvular disease documented by echocardiogram, or congenital heart disease.
  • The participant has left ventricular ejection fraction (LVEF) less than 35%, as documented by echocardiogram or angiography.
  • The participant has clinically significant cardiac conduction defects (i.e., second- or third-degree atrioventricular block, sick sinus syndrome or a QTc >500 msec) at Day -21.
  • The participant has active acute myocarditis/pericarditis within the 3 months prior to Screening Day -21.
  • The participant has hypertrophic cardiomyopathy.
  • The participant has an alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level of greater than 2.0 times the upper limit of normal, has active liver disease, or jaundice.
  • The participant has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 5 years prior to the Screening Visit.
  • The participant is required or expected to require excluded medications digoxin and digoxin-containing compounds.
  • If female, the participant is pregnant or lactating or intending to become pregnant before, during, or within 1 month after participating in this study; or intending to donate ova during such time period.
  • The participant has participated in another clinical study within the past 30 days.
  • The participant has a history of extracorporeal external counterpulsation treatment for chronic stable angina within 3 months prior to screening visit.

Trial locations and contacts

21 sites in 1 country.

21 sites in 1 country

United States21 sites

  • Study site

    Carmichael, California

  • Study site

    City of Saint Peters, Missouri

  • Study site

    Columbus, Ohio

  • Study site

    Dunwoody, Georgia

  • Study site

    Fresno, California

  • Study site

    Irvine, California

  • Study site

    Lexington, Kentucky

  • Study site

    Lyndhurst, Ohio

  • Study site

    Madison, Wisconsin

  • Study site

    Manassas, Virginia

  • Study site

    Oklahoma City, Oklahoma

  • Study site

    Paramount, California

  • Study site

    Port Orchard, Washington

  • Study site

    Sacramento, California

  • Study site

    Salisbury, North Carolina

  • Study site

    San Antonio, Texas

  • Study site

    San Diego, California

  • Study site

    St Louis, Missouri

  • Study site

    Suwanee, Georgia

  • Study site

    Tampa, Florida

  • Study site

    Tipton, Pennsylvania

Other trials in United States

About this study

Official title: A Phase 2, Double-Blind, Placebo-Controlled Study to Assess the Effect of Febuxostat 80 mg Once Daily Compared to Placebo on Exercise Tolerance in Subjects With Chronic Stable Angina

The purpose of this study is to evaluate the effect of febuxostat, once daily (QD), compared to placebo as an add on to stable anti-anginal therapy, on the total exercise time of participants with Chronic Stable Angina.

Read the detailed description

This is a phase 2 multicenter, randomized, placebo-controlled double-blind study. This study is comprised of a single-blind placebo run-in qualifying phase lasting approximately 3 weeks and a double-blind treatment phase lasting 12 weeks. A safety follow-up visit is scheduled for 2 weeks after last dose of study drug.

All participants will undergo 3 visits during a 3 week, run-in phase (Days -21 to Day 1). During the run-in phase, all participants will receive single-blind placebo. Two exercise treadmill tests (ETTs) will be conducted using the modified Bruce Protocol at Day -14 and at Day -7. The results from the Day -7 ETT will be considered as Baseline.

A total of approximately 100 participants will be randomized 1:1 to receive either febuxostat 80 mg once daily (QD) or placebo QD in a double-blind treatment for 12 weeks, and 5 more visits.

All participants will complete the Seattle Angina Questionnaire (SAQ) and Euroqol 5 dimension (EQ-5D) quality-of-life measurements at Day 1, Week 6 and Week 12/Early Termination (ET) Visit. The investigator will also rate the overall severity of the participant's angina at each visit based on the Canadian Cardiovascular Society Grading of Angina (CCSGA).

This 12-week phase 2 proof-of-concept study was designed to assess the effect of febuxostat as an add-on to stable anti-anginal therapy on the total exercise time of participants with chronic stable angina and a serum urate ≥5 mg/dL. At this time, Takeda has decided to terminate the study for business reasons.

Conditions
Angina
Being tested
Febuxostat, Placebo
Keywords
Drug Therapy
Medical subject headings
Angina Pectoris

What participants receive

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

  • FebuxostatDrug

    Also called TMX-67, Uloric

    Febuxostat tablets

  • PlaceboDrug

    Febuxostat placebo-matching tablets

Study groups in NCT01549977
Study groupRoleWhat they receive
Febuxostat 80 mgExperimentalFebuxostat 80 mg, tablets, orally, once daily for up to 12 weeks.
Receives: Drug: Febuxostat
PlaceboPlacebo comparatorFebuxostat placebo-matching tablets, orally, once daily for up to 12 weeks.
Receives: Drug: Placebo

What is being measured

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

  1. Change From Baseline in Exercise Treadmill Testing (ETT) Duration at Week 12

    The change between the duration of ETT at Week 12 relative to Baseline. ETTs were conducted using the modified Bruce Protocol. Participants exercised on a treadmill, starting at 1.7 mph and 0% incline. The intensity of exercise (speed and/or incline) was increased at 3 minute intervals.

    Measured: Baseline and Week 12

Secondary outcomes (4)

  1. Change From Baseline in Time to Onset of Angina During ETT at Week 12

    The change between the time to onset of angina during the exercise treadmill test (ETT) at Week 12 relative to Baseline.

    Measured: Baseline and Week 12

  2. Change From Baseline in Time to Onset of ≥1 mm ST-segment Depression During ETT at Week 12

    The change between the time to onset of ≥1 mm ST-segment depression during exercise treadmill test (ETT) at Week 12 relative to Baseline. ST-segment is measured by electrocardiography (ECG) and represents the interval between ventricular depolarization and repolarization.

    Measured: Baseline and Week 12

  3. Change From Baseline in Maximum ST-segment Depression During ETT at Week 12

    The change between the maximum ST-segment depression during ETT at Week 12 relative to Baseline. ST-segment is measured by electrocardiography (ECG) and represents the interval between ventricular depolarization and repolarization.

    Measured: Baseline and Week 12

  4. Percentage of Participants Stopping ETT Due to Angina at Week 12

    The percentage of participants who had to stop exercise treatment testing (ETT) due to experiencing angina symptoms at Week 12.

    Measured: Week 12

Timeline

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

  1. First posted9 Mar 2012 (estimated)
  2. Study startJul 2012
  3. Primary completionNov 2012
  4. Study completionNov 2012

Why it stopped: Business Decision (please see below)

Resources

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
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
1 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01549977
Sponsor's protocol ID
TMX-67_207
Other IDs
U1111-1125-1278
Status last verified
Oct 2013
First submitted
6 Mar 2012
Last updated
20 Dec 2013
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Febuxostat in people with Angina, run by Takeda at 21 sites in United States.

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 20 inclusion and 38 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: stopped early, as of the sponsor's last update on 20 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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 20 Dec 2013). 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?

Change From Baseline in Exercise Treadmill Testing (ETT) Duration at Week 12 (time frame: Baseline and Week 12). 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 NCT01549977.

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 20 Dec 2013.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in