Trial Outcomes & Findings for Effect of Ranolazine on Myocardial Perfusion Assessed by Serial Quantitative Exercise SPECT Imaging (NCT NCT01221272)
NCT ID: NCT01221272
Last Updated: 2014-09-03
Results Overview
PDS is the amount (percent) of the myocardium with decreased blood flow. A lower percentage means more of the myocardium is receiving blood flow. Measurements were obtained by gated single photon emission computed tomography (SPECT) imaging following exercise at the end of the ranolazine and placebo treatment periods.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
81 participants
Primary outcome timeframe
Up to 33 days
Results posted on
2014-09-03
Participant Flow
Participants were enrolled in a total of 27 study sites in the United States, Canada, Czech Republic, and Israel. The first participant was screened on 29 September 2010. The last participant observation was on 27 September 2012.
Number screened: 222; randomized and treated (RAT; Safety Analysis Set): 81 Efficacy Analysis Set: 61 RAT participants with data for both end-of-period (EOP) scans, completed ≥ 7 consecutive days treatment in each period, took the morning dose before each EOP scan, and had baseline perfusion defect size ≥ 5% as measured by QPS imaging software.
Participant milestones
| Measure |
Ranolazine/Placebo
Period 1: Participants received ranolazine 1 × 500 mg tablet administered once in the evening on Day 1, 1 × 500 mg tablet twice daily on Days 2-3, and 2 × 500 tablets twice daily from Day 4 to the end of the period (Day 15 ± 2 days), followed by an exercise gated single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) study.
Period 2: Participants received placebo to match ranolazine from Day 1 to the end of the period (Day 15 ± 2 days), followed by an exercise SPECT MPI study.
|
Placebo/Ranolazine
Period 1: Participants received placebo to match ranolazine from Day 1 to the end of the period (Day 15 ± 2 days), followed by an exercise SPECT MPI study.
Period 2: Participants received ranolazine 1 × 500 mg tablet administered once in the evening on Day 1, 1 × 500 mg tablet twice daily on Days 2-3, and 2 × 500 tablets twice daily from Day 4 to the end of the period (Day 15 ± 2 days), followed by an exercise SPECT MPI study.
|
|---|---|---|
|
Period 1
STARTED
|
41
|
40
|
|
Period 1
COMPLETED
|
39
|
38
|
|
Period 1
NOT COMPLETED
|
2
|
2
|
|
Period 2
STARTED
|
39
|
39
|
|
Period 2
COMPLETED
|
39
|
37
|
|
Period 2
NOT COMPLETED
|
0
|
2
|
Reasons for withdrawal
| Measure |
Ranolazine/Placebo
Period 1: Participants received ranolazine 1 × 500 mg tablet administered once in the evening on Day 1, 1 × 500 mg tablet twice daily on Days 2-3, and 2 × 500 tablets twice daily from Day 4 to the end of the period (Day 15 ± 2 days), followed by an exercise gated single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) study.
Period 2: Participants received placebo to match ranolazine from Day 1 to the end of the period (Day 15 ± 2 days), followed by an exercise SPECT MPI study.
|
Placebo/Ranolazine
Period 1: Participants received placebo to match ranolazine from Day 1 to the end of the period (Day 15 ± 2 days), followed by an exercise SPECT MPI study.
Period 2: Participants received ranolazine 1 × 500 mg tablet administered once in the evening on Day 1, 1 × 500 mg tablet twice daily on Days 2-3, and 2 × 500 tablets twice daily from Day 4 to the end of the period (Day 15 ± 2 days), followed by an exercise SPECT MPI study.
|
|---|---|---|
|
Period 1
Adverse Event
|
2
|
0
|
|
Period 1
Consent Withdrawal
|
0
|
1
|
|
Period 1
Significant Dosing Noncompliance
|
0
|
1
|
|
Period 2
Adverse Event
|
0
|
2
|
Baseline Characteristics
Effect of Ranolazine on Myocardial Perfusion Assessed by Serial Quantitative Exercise SPECT Imaging
Baseline characteristics by cohort
| Measure |
All Participants
n=81 Participants
Baseline characteristics were analyzed as a single group (Safety Analysis Set). All participants were assigned to complete the same treatment periods in the same manner.
Ranolazine Treatment Period: Participants received ranolazine 1 × 500 mg tablet administered once in the evening on Day 1, 1 × 500 mg tablet twice daily on Days 2-3, and 2 × 500 tablets twice daily from Day 4 to the end of the period (Day 15 ± 2 days), followed by an exercise SPECT MPI study.
Placebo Treatment Period: Participants received placebo to match ranolazine from Day 1 to the end of the period (Day 15 ± 2 days), followed by an exercise SPECT MPI study.
|
|---|---|
|
Age, Continuous
|
66 years
STANDARD_DEVIATION 9.0 • n=5 Participants
|
|
Age, Customized
18 to 39 years
|
0 participants
n=5 Participants
|
|
Age, Customized
40 to 64 years
|
29 participants
n=5 Participants
|
|
Age, Customized
65 to 74 years
|
39 participants
n=5 Participants
|
|
Age, Customized
≥ 75 years
|
13 participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
75 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
72 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
African-American
|
5 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
4 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic Or Latino
|
9 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic Or Latino
|
62 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Not Reported
|
5 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Unknown
|
5 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
38 participants
n=5 Participants
|
|
Region of Enrollment
Czech Republic
|
2 participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
27 participants
n=5 Participants
|
|
Region of Enrollment
Israel
|
14 participants
n=5 Participants
|
|
Body mass index
|
29.6 kg/m^2
STANDARD_DEVIATION 3.8 • n=5 Participants
|
|
Weight
|
88.6 kg
STANDARD_DEVIATION 14.2 • n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 33 daysPopulation: Efficacy Analysis Set: 61 randomized and treated participants with data for both end-of-period (EOP) scans, completed ≥ 7 consecutive days treatment in each period, took the morning dose before each EOP scan, and had baseline perfusion defect size ≥ 5% as measured by QPS imaging software
PDS is the amount (percent) of the myocardium with decreased blood flow. A lower percentage means more of the myocardium is receiving blood flow. Measurements were obtained by gated single photon emission computed tomography (SPECT) imaging following exercise at the end of the ranolazine and placebo treatment periods.
Outcome measures
| Measure |
Ranolazine
n=61 Participants
Ranolazine treatment period: Participants received ranolazine 1 × 500 mg tablet administered once in the evening on Day 1, 1 × 500 mg tablet twice daily on Days 2-3, and 2 × 500 tablets twice daily from Day 4 to the end of the period (Day 15 ± 2 days), followed by an exercise SPECT MPI study.
|
Placebo
n=61 Participants
Placebo treatment period: Participants received placebo to match ranolazine from Day 1 to the end of the period (Day 15 ± 2 days), followed by an exercise SPECT MPI study.
|
|---|---|---|
|
Exercise-induced Perfusion Defect Size (PDS) Following Ranolazine and Placebo Treatment
|
21.54 percentage of myocardium
Standard Error 1.51
|
20.87 percentage of myocardium
Standard Error 1.51
|
PRIMARY outcome
Timeframe: Up to 33 daysPopulation: Efficacy Analysis Set
TPD is a score that measures the overall impact of a region of decreased myocardial blood flow, incorporating both the amount and severity of the decreased flow. TPD is measured on a scale of 0-100, with higher scores being worse and lower scores being better. Measurements were obtained by SPECT imaging following exercise at the end of the ranolazine and placebo treatment periods.
Outcome measures
| Measure |
Ranolazine
n=61 Participants
Ranolazine treatment period: Participants received ranolazine 1 × 500 mg tablet administered once in the evening on Day 1, 1 × 500 mg tablet twice daily on Days 2-3, and 2 × 500 tablets twice daily from Day 4 to the end of the period (Day 15 ± 2 days), followed by an exercise SPECT MPI study.
|
Placebo
n=61 Participants
Placebo treatment period: Participants received placebo to match ranolazine from Day 1 to the end of the period (Day 15 ± 2 days), followed by an exercise SPECT MPI study.
|
|---|---|---|
|
Exercise-induced Total Perfusion Deficit (TPD) Following Ranolazine and Placebo Treatment
|
17.23 units on a scale
Standard Error 1.26
|
16.57 units on a scale
Standard Error 1.26
|
SECONDARY outcome
Timeframe: Up to 33 daysPopulation: Efficacy Analysis Set
Perfusion defect severity was assessed for each participant as the percentage of the 17 myocardium segments with a relative perfusion defect score of 3 or 4 on a 0-4 scale. Segment scores are: 0 = normal perfusion; 1 = mild reduction in counts-not definitely abnormal; 2 = moderate reduction in counts-definitely abnormal; 3 = severe reduction in counts; 4 = absent uptake (lower scores correspond to less severity and higher scores correspond to increased severity). A lower percentage means fewer segments have severely reduced blood flow. Measurements were obtained by SPECT imaging following exercise at baseline and at the end of Periods 1 and 2.
Outcome measures
| Measure |
Ranolazine
n=30 Participants
Ranolazine treatment period: Participants received ranolazine 1 × 500 mg tablet administered once in the evening on Day 1, 1 × 500 mg tablet twice daily on Days 2-3, and 2 × 500 tablets twice daily from Day 4 to the end of the period (Day 15 ± 2 days), followed by an exercise SPECT MPI study.
|
Placebo
n=31 Participants
Placebo treatment period: Participants received placebo to match ranolazine from Day 1 to the end of the period (Day 15 ± 2 days), followed by an exercise SPECT MPI study.
|
|---|---|---|
|
Perfusion Defect Severity at Baseline, End of Period 1, and End of Period 2
Baseline
|
11.4 percentage of segments
Standard Error 2.0
|
8.5 percentage of segments
Standard Error 2.0
|
|
Perfusion Defect Severity at Baseline, End of Period 1, and End of Period 2
End of Period 1
|
11.6 percentage of segments
Standard Error 1.9
|
10.2 percentage of segments
Standard Error 2.1
|
|
Perfusion Defect Severity at Baseline, End of Period 1, and End of Period 2
End of Period 2
|
10.4 percentage of segments
Standard Error 1.9
|
9.5 percentage of segments
Standard Error 2.0
|
SECONDARY outcome
Timeframe: Up to 33 daysPopulation: Efficacy Analysis Set
Exercise-induced reversible PDS was derived as the exercise PDS at baseline and at the end of Periods 1 and 2 minus the resting PDS at baseline. A lower percentage means more of the myocardium is receiving blood flow. Measurements were obtained by SPECT imaging at baseline both at rest and following exercise and following exercise at the end of Periods 1 and 2.
Outcome measures
| Measure |
Ranolazine
n=30 Participants
Ranolazine treatment period: Participants received ranolazine 1 × 500 mg tablet administered once in the evening on Day 1, 1 × 500 mg tablet twice daily on Days 2-3, and 2 × 500 tablets twice daily from Day 4 to the end of the period (Day 15 ± 2 days), followed by an exercise SPECT MPI study.
|
Placebo
n=31 Participants
Placebo treatment period: Participants received placebo to match ranolazine from Day 1 to the end of the period (Day 15 ± 2 days), followed by an exercise SPECT MPI study.
|
|---|---|---|
|
Exercise-induced Reversible Perfusion Defect Size (PDS) at Baseline, End of Period 1, and End of Period 2
Baseline exercise minus baseline resting
|
12.5 percentage of myocardium
Standard Error 1.1
|
13.5 percentage of myocardium
Standard Error 1.3
|
|
Exercise-induced Reversible Perfusion Defect Size (PDS) at Baseline, End of Period 1, and End of Period 2
End of Period 1 exercise minus baseline resting
|
12.7 percentage of myocardium
Standard Error 1.2
|
14.1 percentage of myocardium
Standard Error 1.4
|
|
Exercise-induced Reversible Perfusion Defect Size (PDS) at Baseline, End of Period 1, and End of Period 2
End of Period 2 exercise minus baseline resting
|
12.4 percentage of myocardium
Standard Error 1.0
|
15.2 percentage of myocardium
Standard Error 1.4
|
SECONDARY outcome
Timeframe: Up to 33 daysPopulation: Efficacy Analysis Set
Exercise-induced reversible TPD was derived as the exercise TPD at baseline and at the end of Periods 1 and 2 minus the resting TPD at baseline. TPD is measured on a scale of 0-100, with higher scores being worse and lower scores being better. Measurements were obtained by SPECT imaging at baseline both at rest and following exercise and following exercise at the end of Periods 1 and 2.
Outcome measures
| Measure |
Ranolazine
n=30 Participants
Ranolazine treatment period: Participants received ranolazine 1 × 500 mg tablet administered once in the evening on Day 1, 1 × 500 mg tablet twice daily on Days 2-3, and 2 × 500 tablets twice daily from Day 4 to the end of the period (Day 15 ± 2 days), followed by an exercise SPECT MPI study.
|
Placebo
n=31 Participants
Placebo treatment period: Participants received placebo to match ranolazine from Day 1 to the end of the period (Day 15 ± 2 days), followed by an exercise SPECT MPI study.
|
|---|---|---|
|
Exercise-induced Reversible Total Perfusion Deficit (TPD) at Baseline, End of Period 1, and End of Period 2
End of Period 2 exercise minus baseline resting
|
10.1 units on a scale
Standard Error 0.8
|
11.6 units on a scale
Standard Error 1.1
|
|
Exercise-induced Reversible Total Perfusion Deficit (TPD) at Baseline, End of Period 1, and End of Period 2
Baseline exercise minus baseline resting
|
10.5 units on a scale
Standard Error 0.9
|
10.5 units on a scale
Standard Error 1.0
|
|
Exercise-induced Reversible Total Perfusion Deficit (TPD) at Baseline, End of Period 1, and End of Period 2
End of Period 1 exercise minus baseline resting
|
10.5 units on a scale
Standard Error 0.9
|
10.7 units on a scale
Standard Error 1.0
|
Adverse Events
Onset Following Ranolazine
Serious events: 2 serious events
Other events: 25 other events
Deaths: 0 deaths
Onset Following Placebo
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Onset at Any Time Following Ranolazine
Serious events: 2 serious events
Other events: 28 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Onset Following Ranolazine
n=80 participants at risk
This reporting group includes participants dosed with ranolazine and their events for which the last dosed treatment was ranolazine, ie, events with onset during the ranolazine treatment period or during post-ranolazine treatment period follow-up.
Ranolazine Treatment Period: Participants received ranolazine 1 × 500 mg tablet administered once in the evening on Day 1, 1 × 500 mg tablet twice daily on Days 2-3, and 2 × 500 tablets twice daily from Day 4 to the end of the period (Day 15 ± 2 days), followed by an exercise SPECT MPI study.
Placebo Treatment Period: Participants received placebo to match ranolazine from Day 1 to the end of the period (Day 15 ± 2 days), followed by an exercise SPECT MPI study.
|
Onset Following Placebo
n=79 participants at risk
This reporting group includes participants dosed with placebo and their events for which the last dosed treatment was placebo, ie, events with onset during the placebo treatment period or during post-placebo treatment period follow-up.
Ranolazine Treatment Period: Participants received ranolazine 1 × 500 mg tablet administered once in the evening on Day 1, 1 × 500 mg tablet twice daily on Days 2-3, and 2 × 500 tablets twice daily from Day 4 to the end of the period (Day 15 ± 2 days), followed by an exercise SPECT MPI study.
Placebo Treatment Period: Participants received placebo to match ranolazine from Day 1 to the end of the period (Day 15 ± 2 days), followed by an exercise SPECT MPI study.
|
Onset at Any Time Following Ranolazine
n=80 participants at risk
This reporting group includes participants dosed with ranolazine and their events with onset at any time following ranolazine treatment.
Ranolazine Treatment Period: Participants received ranolazine 1 × 500 mg tablet administered once in the evening on Day 1, 1 × 500 mg tablet twice daily on Days 2-3, and 2 × 500 tablets twice daily from Day 4 to the end of the period (Day 15 ± 2 days), followed by an exercise SPECT MPI study.
Placebo Treatment Period: Participants received placebo to match ranolazine from Day 1 to the end of the period (Day 15 ± 2 days), followed by an exercise SPECT MPI study.
|
|---|---|---|---|
|
Infections and infestations
Bronchitis
|
1.2%
1/80 • Up to 33 days
All participants were assigned to complete the ranolazine and placebo treatment periods during the study, the only difference being which treatment period they started first.
|
0.00%
0/79 • Up to 33 days
All participants were assigned to complete the ranolazine and placebo treatment periods during the study, the only difference being which treatment period they started first.
|
1.2%
1/80 • Up to 33 days
All participants were assigned to complete the ranolazine and placebo treatment periods during the study, the only difference being which treatment period they started first.
|
|
Investigations
Electrocardiogram ST segment elevation
|
1.2%
1/80 • Up to 33 days
All participants were assigned to complete the ranolazine and placebo treatment periods during the study, the only difference being which treatment period they started first.
|
0.00%
0/79 • Up to 33 days
All participants were assigned to complete the ranolazine and placebo treatment periods during the study, the only difference being which treatment period they started first.
|
1.2%
1/80 • Up to 33 days
All participants were assigned to complete the ranolazine and placebo treatment periods during the study, the only difference being which treatment period they started first.
|
Other adverse events
| Measure |
Onset Following Ranolazine
n=80 participants at risk
This reporting group includes participants dosed with ranolazine and their events for which the last dosed treatment was ranolazine, ie, events with onset during the ranolazine treatment period or during post-ranolazine treatment period follow-up.
Ranolazine Treatment Period: Participants received ranolazine 1 × 500 mg tablet administered once in the evening on Day 1, 1 × 500 mg tablet twice daily on Days 2-3, and 2 × 500 tablets twice daily from Day 4 to the end of the period (Day 15 ± 2 days), followed by an exercise SPECT MPI study.
Placebo Treatment Period: Participants received placebo to match ranolazine from Day 1 to the end of the period (Day 15 ± 2 days), followed by an exercise SPECT MPI study.
|
Onset Following Placebo
n=79 participants at risk
This reporting group includes participants dosed with placebo and their events for which the last dosed treatment was placebo, ie, events with onset during the placebo treatment period or during post-placebo treatment period follow-up.
Ranolazine Treatment Period: Participants received ranolazine 1 × 500 mg tablet administered once in the evening on Day 1, 1 × 500 mg tablet twice daily on Days 2-3, and 2 × 500 tablets twice daily from Day 4 to the end of the period (Day 15 ± 2 days), followed by an exercise SPECT MPI study.
Placebo Treatment Period: Participants received placebo to match ranolazine from Day 1 to the end of the period (Day 15 ± 2 days), followed by an exercise SPECT MPI study.
|
Onset at Any Time Following Ranolazine
n=80 participants at risk
This reporting group includes participants dosed with ranolazine and their events with onset at any time following ranolazine treatment.
Ranolazine Treatment Period: Participants received ranolazine 1 × 500 mg tablet administered once in the evening on Day 1, 1 × 500 mg tablet twice daily on Days 2-3, and 2 × 500 tablets twice daily from Day 4 to the end of the period (Day 15 ± 2 days), followed by an exercise SPECT MPI study.
Placebo Treatment Period: Participants received placebo to match ranolazine from Day 1 to the end of the period (Day 15 ± 2 days), followed by an exercise SPECT MPI study.
|
|---|---|---|---|
|
Cardiac disorders
Angina pectoris
|
3.8%
3/80 • Up to 33 days
All participants were assigned to complete the ranolazine and placebo treatment periods during the study, the only difference being which treatment period they started first.
|
1.3%
1/79 • Up to 33 days
All participants were assigned to complete the ranolazine and placebo treatment periods during the study, the only difference being which treatment period they started first.
|
5.0%
4/80 • Up to 33 days
All participants were assigned to complete the ranolazine and placebo treatment periods during the study, the only difference being which treatment period they started first.
|
|
Gastrointestinal disorders
Constipation
|
7.5%
6/80 • Up to 33 days
All participants were assigned to complete the ranolazine and placebo treatment periods during the study, the only difference being which treatment period they started first.
|
1.3%
1/79 • Up to 33 days
All participants were assigned to complete the ranolazine and placebo treatment periods during the study, the only difference being which treatment period they started first.
|
7.5%
6/80 • Up to 33 days
All participants were assigned to complete the ranolazine and placebo treatment periods during the study, the only difference being which treatment period they started first.
|
|
Gastrointestinal disorders
Nausea
|
6.2%
5/80 • Up to 33 days
All participants were assigned to complete the ranolazine and placebo treatment periods during the study, the only difference being which treatment period they started first.
|
2.5%
2/79 • Up to 33 days
All participants were assigned to complete the ranolazine and placebo treatment periods during the study, the only difference being which treatment period they started first.
|
6.2%
5/80 • Up to 33 days
All participants were assigned to complete the ranolazine and placebo treatment periods during the study, the only difference being which treatment period they started first.
|
|
Nervous system disorders
Dizziness
|
13.8%
11/80 • Up to 33 days
All participants were assigned to complete the ranolazine and placebo treatment periods during the study, the only difference being which treatment period they started first.
|
0.00%
0/79 • Up to 33 days
All participants were assigned to complete the ranolazine and placebo treatment periods during the study, the only difference being which treatment period they started first.
|
13.8%
11/80 • Up to 33 days
All participants were assigned to complete the ranolazine and placebo treatment periods during the study, the only difference being which treatment period they started first.
|
|
Nervous system disorders
Headache
|
3.8%
3/80 • Up to 33 days
All participants were assigned to complete the ranolazine and placebo treatment periods during the study, the only difference being which treatment period they started first.
|
3.8%
3/79 • Up to 33 days
All participants were assigned to complete the ranolazine and placebo treatment periods during the study, the only difference being which treatment period they started first.
|
5.0%
4/80 • Up to 33 days
All participants were assigned to complete the ranolazine and placebo treatment periods during the study, the only difference being which treatment period they started first.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
8.8%
7/80 • Up to 33 days
All participants were assigned to complete the ranolazine and placebo treatment periods during the study, the only difference being which treatment period they started first.
|
2.5%
2/79 • Up to 33 days
All participants were assigned to complete the ranolazine and placebo treatment periods during the study, the only difference being which treatment period they started first.
|
11.2%
9/80 • Up to 33 days
All participants were assigned to complete the ranolazine and placebo treatment periods during the study, the only difference being which treatment period they started first.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: * The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or * The study has been completed at all study sites for at least 2 years
- Publication restrictions are in place
Restriction type: OTHER