Trial Outcomes & Findings for The Influence of Febuxostat on Coronary Artery Endothelial Dysfunction in Participants With Chronic Stable Angina (NCT NCT01763996)
NCT ID: NCT01763996
Last Updated: 2016-04-13
Results Overview
Coronary artery flow was measured using magnetic resonance imaging (MRI) at rest and during sustained isometric (static) handgrip exercises. Data at the end of each treatment period was combined for the febuxostat and the placebo arms. A positive change from Baseline indicates improvement.
COMPLETED
PHASE4
30 participants
Baseline and at the end of each 6 week treatment period (Week 6 and Week 12)
2016-04-13
Participant Flow
Participants took part in the study at one investigative site in the United States from 29 May 2013 (first participant signed the formed consent form) to 14 April 2015.
Participants with a diagnosis of chronic stable angina were enrolled in one of 2 sequence cross-over arms: (1) febuxostat 80 mg for 6 weeks then placebo for 6 weeks, or (2) placebo for 6 weeks then febuxostat 80 mg for 6 weeks.
Participant milestones
| Measure |
Sequence 1: Febuxostat 80 mg + Placebo
Febuxostat 80 mg, capsules, orally, once daily for 6 weeks in Period 1, followed by febuxostat placebo-matching capsules, orally, once daily for up to 6 weeks in Period 2.
|
Sequence 2: Placebo + Febuxostat 80 mg
Febuxostat placebo-matching capsules, orally, once daily for 6 weeks in Period 1, followed by febuxostat 80 mg, capsules, orally, once daily for up to 6 weeks in Period 2.
|
|---|---|---|
|
Treatment Period 1
STARTED
|
15
|
15
|
|
Treatment Period 1
COMPLETED
|
15
|
15
|
|
Treatment Period 1
NOT COMPLETED
|
0
|
0
|
|
Treatment Period 2
STARTED
|
15
|
15
|
|
Treatment Period 2
COMPLETED
|
15
|
14
|
|
Treatment Period 2
NOT COMPLETED
|
0
|
1
|
Reasons for withdrawal
| Measure |
Sequence 1: Febuxostat 80 mg + Placebo
Febuxostat 80 mg, capsules, orally, once daily for 6 weeks in Period 1, followed by febuxostat placebo-matching capsules, orally, once daily for up to 6 weeks in Period 2.
|
Sequence 2: Placebo + Febuxostat 80 mg
Febuxostat placebo-matching capsules, orally, once daily for 6 weeks in Period 1, followed by febuxostat 80 mg, capsules, orally, once daily for up to 6 weeks in Period 2.
|
|---|---|---|
|
Treatment Period 2
Adverse Event
|
0
|
1
|
Baseline Characteristics
The Influence of Febuxostat on Coronary Artery Endothelial Dysfunction in Participants With Chronic Stable Angina
Baseline characteristics by cohort
| Measure |
All Participants
n=30 Participants
All participants who were randomized and received study drug (febuxostat 80 mg and placebo) during the study.
|
|---|---|
|
Age, Continuous
|
59 years
STANDARD_DEVIATION 7.7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
27 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
African-American
|
5 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
25 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
30 participants
n=5 Participants
|
|
Height
|
176 cm
STANDARD_DEVIATION 7.7 • n=5 Participants
|
|
Weight
|
87.8 kg
STANDARD_DEVIATION 16 • n=5 Participants
|
|
Body Mass Index (BMI)
|
28.3 kg/m^2
STANDARD_DEVIATION 4.12 • n=5 Participants
|
|
Left Ventricular Ejection Fraction
|
56.8 percent
STANDARD_DEVIATION 9.24 • n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and at the end of each 6 week treatment period (Week 6 and Week 12)Population: Participants from the Full Analysis Set, all randomized participants who received at least one dose of study drug, with data available.
Coronary artery flow was measured using magnetic resonance imaging (MRI) at rest and during sustained isometric (static) handgrip exercises. Data at the end of each treatment period was combined for the febuxostat and the placebo arms. A positive change from Baseline indicates improvement.
Outcome measures
| Measure |
Placebo
n=29 Participants
Febuxostat placebo-matching capsules, orally, once daily for up to 6 weeks in Period 1 or 2.
|
Febuxostat 80 mg
n=29 Participants
Febuxostat 80 mg, capsules, orally, once daily for up to 6 weeks in Period 1 or 2.
|
|---|---|---|
|
Change in Coronary Artery Flow From Rest to Isometric Handgrip (IHG) Exercise at the End of the Administration of Febuxostat and Placebo
|
8.8 mL/min
Interval 0.4 to 17.28
|
10.7 mL/min
Interval 2.23 to 19.11
|
SECONDARY outcome
Timeframe: Baseline and at the end of each 6 week treatment period (Week 6 and Week 12)Population: Participants from the Full Analysis Set, all randomized participants who received at least one dose of study drug, with data available.
Coronary artery cross-sectional area was measured by MRI at rest and during sustained isometric (static) handgrip exercise. Data at the end of each treatment period was combined for the febuxostat and the placebo arms. A positive change from Baseline indicates improvement.
Outcome measures
| Measure |
Placebo
n=29 Participants
Febuxostat placebo-matching capsules, orally, once daily for up to 6 weeks in Period 1 or 2.
|
Febuxostat 80 mg
n=29 Participants
Febuxostat 80 mg, capsules, orally, once daily for up to 6 weeks in Period 1 or 2.
|
|---|---|---|
|
Change in Coronary Artery Cross-Sectional Area From Rest to IHG Exercise at the End of the Administration of Febuxostat and Placebo
|
0.45 mm^2
Interval -0.177 to 1.074
|
0.03 mm^2
Interval -0.595 to 0.656
|
SECONDARY outcome
Timeframe: Baseline and at the end of each 6 week treatment period (Week 6 and Week 12)Population: Participants from the Full Analysis Set, all randomized participants who received at least one dose of study drug, with data available.
Coronary flow velocity was measured by MRI at rest and during sustained isometric (static) handgrip exercise. Data at the end of each treatment period was combined for the febuxostat and the placebo arms. A positive change from Baseline indicates improvement.
Outcome measures
| Measure |
Placebo
n=29 Participants
Febuxostat placebo-matching capsules, orally, once daily for up to 6 weeks in Period 1 or 2.
|
Febuxostat 80 mg
n=29 Participants
Febuxostat 80 mg, capsules, orally, once daily for up to 6 weeks in Period 1 or 2.
|
|---|---|---|
|
Change in Coronary Flow Velocity From Rest to IHG Exercise at the End of the Administration of Febuxostat and Placebo
|
1.6 cm/second
Interval -0.1 to 3.4
|
2.2 cm/second
Interval 0.43 to 3.93
|
SECONDARY outcome
Timeframe: Baseline and at the end of each 6 week treatment period (Week 6 and Week 12)Population: Participants from the Full Analysis Set, all randomized participants who received at least one dose of study drug, who used nitroglycerin.
Coronary artery flow was measured by MRI before and following administration of nitroglycerin under the tongue. Data at the end of each treatment period was combined for the febuxostat and the placebo arms. A positive change from Baseline indicates improvement.
Outcome measures
| Measure |
Placebo
n=11 Participants
Febuxostat placebo-matching capsules, orally, once daily for up to 6 weeks in Period 1 or 2.
|
Febuxostat 80 mg
n=15 Participants
Febuxostat 80 mg, capsules, orally, once daily for up to 6 weeks in Period 1 or 2.
|
|---|---|---|
|
Change in Coronary Artery Flow Following the Administration of Sublingual Nitroglycerin at the End of the Administration of Febuxostat and Placebo
|
17.0 mL/min
Interval -6.0 to 39.98
|
13.0 mL/min
Interval -2.53 to 28.43
|
SECONDARY outcome
Timeframe: Baseline and at the end of each 6 week treatment period (Week 6 and Week 12)Population: Participants from the Full Analysis Set, all randomized participants who received at least one dose of study drug, who used nitroglycerin.
Coronary artery cross sectional area was measured by MRI before and following administration of nitroglycerin under the tongue. Data at the end of each treatment period was combined for the febuxostat and the placebo arms. A positive change from Baseline indicates improvement.
Outcome measures
| Measure |
Placebo
n=11 Participants
Febuxostat placebo-matching capsules, orally, once daily for up to 6 weeks in Period 1 or 2.
|
Febuxostat 80 mg
n=15 Participants
Febuxostat 80 mg, capsules, orally, once daily for up to 6 weeks in Period 1 or 2.
|
|---|---|---|
|
Change in Coronary Artery Cross Sectional Area Following the Administration of Sublingual Nitroglycerin at the End of the Administration of Febuxostat and Placebo
|
3.35 mm^2
Interval 1.449 to 5.244
|
2.86 mm^2
Interval 1.582 to 4.138
|
SECONDARY outcome
Timeframe: Baseline and at the end of each 6 week treatment period (Week 6 and Week 12)Population: Participants from the Full Analysis Set, all randomized participants who received at least one dose of study drug, who used nitroglycerin.
Coronary flow velocity was measured by MRI before and following administration of nitroglycerin under the tongue. Data at the end of each treatment period was combined for the febuxostat and the placebo arms. A positive change from Baseline indicates improvement.
Outcome measures
| Measure |
Placebo
n=11 Participants
Febuxostat placebo-matching capsules, orally, once daily for up to 6 weeks in Period 1 or 2.
|
Febuxostat 80 mg
n=15 Participants
Febuxostat 80 mg, capsules, orally, once daily for up to 6 weeks in Period 1 or 2.
|
|---|---|---|
|
Change in Coronary Flow Velocity Following the Administration of Sublingual Nitroglycerin at the End of the Administration of Febuxostat and Placebo
|
-0.95 cm/second
Interval -4.12 to 2.213
|
-0.66 cm/second
Interval -2.792 to 1.472
|
SECONDARY outcome
Timeframe: Baseline and at the end of each 6 week treatment period (Week 6 and Week 12)Population: Participants from the Full Analysis Set, all randomized participants who received at least one dose of study drug, with ischemic ECG changes.
Time in seconds to ischemic ECG changes during ETT. Continuous electrocardiography (ECG) was performed during an exercise treadmill test (modified Bruce protocol) to assess the onset of ST-segment depression after administration of febuxostat or placebo for 6 weeks in participants with a normal ST segment at randomization. . Data at the end of each treatment period was combined for the febuxostat and the placebo arms.
Outcome measures
| Measure |
Placebo
n=4 Participants
Febuxostat placebo-matching capsules, orally, once daily for up to 6 weeks in Period 1 or 2.
|
Febuxostat 80 mg
n=2 Participants
Febuxostat 80 mg, capsules, orally, once daily for up to 6 weeks in Period 1 or 2.
|
|---|---|---|
|
Change in Time to Onset of ≥1 mm ST-Segment Depression During Exercise Treadmill Test (ETT)
|
514 seconds
Standard Deviation 252
|
316 seconds
Standard Deviation 122
|
SECONDARY outcome
Timeframe: Baseline and at the end of each 6 week treatment period (Week 6 and Week 12)Population: Participants from the Full Analysis Set, all randomized participants who received at least one dose of study drug, with ST segment change.
Continuous ECG was performed during an exercise treadmill test (modified Bruce protocol) to assess the maximum ST-segment depression after 6 weeks of febuxostat or placebo treatment in participants with a normal ST segment at randomization. A negative change from Baseline indicates improvement. Data at the end of each treatment period was combined for the febuxostat and the placebo arms.
Outcome measures
| Measure |
Placebo
n=4 Participants
Febuxostat placebo-matching capsules, orally, once daily for up to 6 weeks in Period 1 or 2.
|
Febuxostat 80 mg
n=2 Participants
Febuxostat 80 mg, capsules, orally, once daily for up to 6 weeks in Period 1 or 2.
|
|---|---|---|
|
Change in Maximum ST-segment Depression During Exercise Treadmill Test
|
1.3 mm
Standard Deviation 0.5
|
1.5 mm
Standard Deviation 0.7
|
SECONDARY outcome
Timeframe: At the end of each 6 week treatment period (Week 6 and Week 12)Population: Participants from the Full Analysis Set, all randomized participants who received at least one dose of study drug, with data available.
An exercise treadmill test (modified Bruce protocol) was performed. Data at the end of each treatment period was combined for the febuxostat and the placebo arms.
Outcome measures
| Measure |
Placebo
n=30 Participants
Febuxostat placebo-matching capsules, orally, once daily for up to 6 weeks in Period 1 or 2.
|
Febuxostat 80 mg
n=28 Participants
Febuxostat 80 mg, capsules, orally, once daily for up to 6 weeks in Period 1 or 2.
|
|---|---|---|
|
Percentage of Participants Stopping Exercise Treadmill Test Due to Angina at the End of the Administration of Febuxostat and Placebo
|
0.0 percentage of participants
|
3.6 percentage of participants
|
SECONDARY outcome
Timeframe: At the end of each 6 week treatment period (Week 6 and Week 12)Population: Participants from the Full Analysis Set, all randomized participants who received at least one dose of study drug, with ischemic chest pain.
Time in seconds to ischemic chest pain/ angina during ETT. Data at the end of each period was combined for the febuxostat and the placebo arms
Outcome measures
| Measure |
Placebo
Febuxostat placebo-matching capsules, orally, once daily for up to 6 weeks in Period 1 or 2.
|
Febuxostat 80 mg
n=1 Participants
Febuxostat 80 mg, capsules, orally, once daily for up to 6 weeks in Period 1 or 2.
|
|---|---|---|
|
Time to Onset of Angina During Exercise Treadmill Test at the End of the Administration of Febuxostat and Placebo
|
—
|
330 seconds
Standard Deviation NA
Standard deviation cannot be calculated for 1 participant.
|
SECONDARY outcome
Timeframe: At the end of each 6 week treatment period (Week 6 and Week 12)Population: Participants from the Full Analysis Set, all randomized participants who received at least one dose of study drug, with data available.
Exercise duration is the exercise time in seconds during ETT. Data at the end of each period was combined for the febuxostat and the placebo arms.
Outcome measures
| Measure |
Placebo
n=30 Participants
Febuxostat placebo-matching capsules, orally, once daily for up to 6 weeks in Period 1 or 2.
|
Febuxostat 80 mg
n=28 Participants
Febuxostat 80 mg, capsules, orally, once daily for up to 6 weeks in Period 1 or 2.
|
|---|---|---|
|
Exercise Duration
|
702 seconds
Interval 682.1 to 721.6
|
722 seconds
Interval 700.5 to 742.9
|
Adverse Events
Placebo
Febuxostat 80 mg
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=30 participants at risk
Febuxostat placebo-matching capsules, orally, once daily for up to 6 weeks in Period 1 or 2.
|
Febuxostat 80 mg
n=30 participants at risk
Febuxostat 80 mg, capsules, orally, once daily for up to 6 weeks in Period 1 or 2.
|
|---|---|---|
|
Infections and infestations
Common cold
|
10.0%
3/30 • First dose of study drug to up to 30 days after the last dose of study drug (Up to 16 Weeks)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
3.3%
1/30 • First dose of study drug to up to 30 days after the last dose of study drug (Up to 16 Weeks)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Nervous system disorders
Headache
|
3.3%
1/30 • First dose of study drug to up to 30 days after the last dose of study drug (Up to 16 Weeks)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
6.7%
2/30 • First dose of study drug to up to 30 days after the last dose of study drug (Up to 16 Weeks)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal discomfort
|
3.3%
1/30 • First dose of study drug to up to 30 days after the last dose of study drug (Up to 16 Weeks)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
6.7%
2/30 • First dose of study drug to up to 30 days after the last dose of study drug (Up to 16 Weeks)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Cardiac disorders
Ventricular extrasystoles
|
3.3%
1/30 • First dose of study drug to up to 30 days after the last dose of study drug (Up to 16 Weeks)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
6.7%
2/30 • First dose of study drug to up to 30 days after the last dose of study drug (Up to 16 Weeks)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
6.7%
2/30 • First dose of study drug to up to 30 days after the last dose of study drug (Up to 16 Weeks)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/30 • First dose of study drug to up to 30 days after the last dose of study drug (Up to 16 Weeks)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
General disorders
Fatigue
|
6.7%
2/30 • First dose of study drug to up to 30 days after the last dose of study drug (Up to 16 Weeks)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/30 • First dose of study drug to up to 30 days after the last dose of study drug (Up to 16 Weeks)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
- Publication restrictions are in place
Restriction type: OTHER