Effect of Ranolazine on Myocardial Perfusion Assessed by Serial Quantitative Exercise SPECT Imaging

• Sponsor: Gilead Sciences (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01221272
• Collaborator: (none)
• Enrollment: 81
• Locations: 43
• Arms: 2
• Duration (Months): 24
• Patients Per Site: 1.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study enrolled participants with documented exercise-induced myocardial ischemia in order to evaluate whether ranolazine, when taken prior to exercise, can improve blood flow to the heart (myocardial perfusion), as assessed by exercise-induced myocardial perfusion defect size (PDS) and total perfusion deficit (TPD), using gated single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI).

This was a 2-period crossover study. The last dose of each period must have been taken 3-4 hours prior to conduct of the exercise SPECT MPI. After the research exercise SPECT MPI was performed at the end of Period 1, participants discontinued the treatment they were randomized to for that period and began the other treatment in Period 2.

Condition or Disease	Intervention/Treatment	Phase
Myocardial Perfusion Imaging; Myocardial Ischemia	Drug: Ranolazine; Drug: Placebo to match ranolazine; Procedure: SPECT MPI; Behavioral: Exercise	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 81 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 4, Randomized, Double-Blind, Placebo-Controlled, Cross-over Trial to Evaluate the Effects of Ranolazine on Myocardial Perfusion Assessed by Serial Quantitative Exercise SPECT Imaging
• Study Start Date: Sep 1, 2010
• Actual Primary Completion Date: Sep 1, 2012
• Actual Study Completion Date: Sep 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ranolazine/Placebo Participants received ranolazine from Day 1 through Day 15 (± 2 days) of Period 1, followed by an exercise SPECT MPI study, then received placebo to match ranolazine from Day 1 through Day 15 (± 2 days) of Period 2, followed by an exercise SPECT MPI study.	Drug: Ranolazine; One 500 mg tablet in the evening on Day 1 of the period One 500 mg tablet, twice daily on Days 2-3 of the period Two 500 mg tablets (1000 mg total), twice daily from Day 4 to the end of the period (Day 15 ± 2 days); Other Names: Ranexa® ; Drug: Placebo to match ranolazine; Placebo to match ranolazine administered in the same form and frequency as the active drug.; Procedure: SPECT MPI; Gated single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) to confirm the presence of reversible exercise-induced left ventricular perfusion defect size (PDS) performed within 12 weeks prior to baseline or at the baseline visit, and at the end-of-period 1 and end-of-period 2 visits.; Behavioral: Exercise; Treadmill stress test
Experimental: Placebo/Ranolazine Participants received placebo to match ranolazine from Day 1 through Day 15 (± 2 days) of Period 1, followed by an exercise SPECT MPI study, then received ranolazine from Day 1 through Day 15 (± 2 days) of Period 2, followed by an exercise SPECT MPI study.	Drug: Ranolazine; One 500 mg tablet in the evening on Day 1 of the period One 500 mg tablet, twice daily on Days 2-3 of the period Two 500 mg tablets (1000 mg total), twice daily from Day 4 to the end of the period (Day 15 ± 2 days); Other Names: Ranexa® ; Drug: Placebo to match ranolazine; Placebo to match ranolazine administered in the same form and frequency as the active drug.; Procedure: SPECT MPI; Gated single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) to confirm the presence of reversible exercise-induced left ventricular perfusion defect size (PDS) performed within 12 weeks prior to baseline or at the baseline visit, and at the end-of-period 1 and end-of-period 2 visits.; Behavioral: Exercise; Treadmill stress test

Outcome Measures

Primary Outcome Measures

1. Exercise-induced Perfusion Defect Size (PDS) Following Ranolazine and Placebo Treatment [Up to 33 days]

   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.

2. Exercise-induced Total Perfusion Deficit (TPD) Following Ranolazine and Placebo Treatment [Up to 33 days]

   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.

Secondary Outcome Measures

1. Perfusion Defect Severity at Baseline, End of Period 1, and End of Period 2 [Up to 33 days]

   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.

2. Exercise-induced Reversible Perfusion Defect Size (PDS) at Baseline, End of Period 1, and End of Period 2 [Up to 33 days]

   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.

3. Exercise-induced Reversible Total Perfusion Deficit (TPD) at Baseline, End of Period 1, and End of Period 2 [Up to 33 days]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• Exercise SPECT MPI study (stress and rest) showing at least 10% reversible myocardial ischemia (as confirmed by the core nuclear laboratory using Corridor4DM imaging software) performed not more than 12 weeks prior to screening, OR

• Exercise SPECT MPI study (stress and rest) conducted during screening (after consultation with the Medical Monitor and after informed consent was obtained) showing at least 10% reversible myocardial ischemia (as confirmed by the core nuclear laboratory)

• Stable antianginal medical therapy (excluding short-acting nitroglycerin)

Key Exclusion Criteria:

• Left bundle branch block

• Automated implantable defibrillator and/or pacemaker (selected subjects with permanent pacemakers who had an intact sinus mechanism may have been included following consultation with the Medical Monitor)

• Intervening coronary revascularization between the time of qualifying exercise SPECT MPI study and randomization

• Acute myocardial infarction (MI) within 60 days prior to screening or at any time after the qualifying exercise SPECT MPI study, or MI undergoing staged intervention during a subject's participation in the trial

• Unstable angina within 30 days prior to screening, or at any time after the qualifying exercise SPECT MPI study

• Coronary artery bypass graft surgery within 60 days prior to screening or at any time after the qualifying exercise SPECT MPI study, or percutaneous coronary intervention within 30 days prior to screening or at any time after the qualifying exercise SPECT MPI study

• Anticipated coronary revascularization during the trial period

• Cerebrovascular attack or transient ischemic attack within 90 days prior to screening

• History of serious arrhythmias

• Current atrial fibrillation or atrial flutter

• QTc interval > 500 milliseconds

• Diagnosed as having New York Heart Association Class III or IV heart failure

• Inability to exercise or exercise limitation due to other comorbidities that may have interfered with ability to perform required exercise SPECT MPI study

• Body mass index greater than or equal to 38 kg/m^{2 (may have been up to 40 kg/m}2 after consultation with the Medical Monitor)

• Any absolute contraindications to exercise stress testing

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	Imperial Cardiac Center	Imperial	California	United States	92251
3	Clinical Trials Research	Lincoln	California	United States	95648
4	Mission Internal Medical Group	Mission Viejo	California	United States	92691
5	Central Coast Cardiology	Salinas	California	United States	93901
6	Alfieri Cardiology	Newark	Delaware	United States	19713
7	St. Luke's Cardiology Associates	Jacksonville	Florida	United States	32216
8	Cardiovascular Research Center of South Florida	Miami	Florida	United States	33173
9	Research One	Orlando	Florida	United States	32806
10	Cardiology Partners Clinical Research Institute	Wellington	Florida	United States	33449
11	Fox Valley Clinical Research Center, LLC	Aurora	Illinois	United States	60504
12	Research Integrity, LLC	Owensboro	Kentucky	United States	42303
13	Louisiana Heart Center	Covington	Louisiana	United States	70403
14	Louisiana Heart Center	Slidell	Louisiana	United States	70458
15	Androscroggin Cardiology Associates DBA Maine Research Associates	Auburn	Maine	United States	04210
16	Delmarva Heart Research Foundation, Inc	Salisbury	Maryland	United States	21804
17	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
18	Cardiovascular Imaging Technologies	Kansas City	Missouri	United States	64111
19	Dr. Michael Sacher	Massapequa	New York	United States	11758
20	Columbia University Medical Center	New York	New York	United States	10032
21	Duke University Medical Center	Durham	North Carolina	United States	27710
22	Heritage Cardiology	Camp Hill	Pennsylvania	United States	17011
23	University of Pittsburgh Medical Center Cardiovascular Institute	Pittsburgh	Pennsylvania	United States	15213
24	Kore Cardiovascular Research	Jackson	Tennessee	United States	38305
25	East Texas Cardiology PA	Houston	Texas	United States	77002
26	Mercury Medical, LLC	San Antonio	Texas	United States	78229
27	University of Ottawa Heart Institute	Ottawa	Ontario	Canada	K1Y 4W7
28	ECOGENE-21 Clinical Trial Center, Chicoutimi Hospital	Chicoutimi	Quebec	Canada	G7H 7P2
29	Montreal Heart Institute	Montreal	Quebec	Canada	H1T 1C8
30	Chum Hotel Dieu	Montreal	Quebec	Canada	H2W 1T8
31	University Hospital Kralovske Vinohrady	Praha 10		Czech Republic	100 34
32	University Hospital Motol	Praha 5		Czech Republic	150 06
33	Turku University Hospital	Turku		Finland	20520
34	Barzilai Medical Center	Ashkelon		Israel	78278
35	Soroka Medical Center	Beer Sheva		Israel	84101
36	Rambam Health Care Campus	Haifa		Israel	31096
37	Kaplan Medical Center	Rehovot		Israel	76100
38	Assuta MC	Tel Aviv		Israel	69710
39	"Federico II" University	Naples		Italy	80131
40	Federico II University	Naples		Italy	80131
41	National University Health System	Singapore		Singapore	119228
42	National Heart Centre Singapore	Singapore		Singapore	168752
43	Northwick Park Hospital, Watford Road	Middlesex		United Kingdom	HA1 3UJ

Sponsors and Collaborators

• Gilead Sciences

Investigators

• Study Director: Patrick Yue, MD, Gilead Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT01221272
• Other Study ID Numbers: GS-US-259-0103
• First Posted: Oct 14, 2010
• Last Update Posted: Sep 3, 2014
• Last Verified: Aug 1, 2014

• Keywords provided by Gilead Sciences: SPECT MPI
• Additional relevant MeSH terms: Myocardial Ischemia; Ischemia; Ranolazine

Study Results

Participant Flow

Recruitment Details	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.
Pre-assignment Detail	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.

Arm/Group Title	Ranolazine/Placebo	Placebo/Ranolazine
Arm/Group Description	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.	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 Title: Period 1
STARTED	41	40
COMPLETED	39	38
NOT COMPLETED	2	2
Period Title: Period 1
STARTED	39	39
COMPLETED	39	37
NOT COMPLETED	0	2

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	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.
Overall Participants	81
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66 (9.0)
Age, Customized (participants) [Number]
18 to 39 years	0 0%
40 to 64 years	29 35.8%
65 to 74 years	39 48.1%
≥ 75 years	13 16%
Sex: Female, Male (Count of Participants)
Female	6 7.4%
Male	75 92.6%
Race/Ethnicity, Customized (participants) [Number]
White	72 88.9%
African-American	5 6.2%
Other	4 4.9%
Race/Ethnicity, Customized (participants) [Number]
Hispanic Or Latino	9 11.1%
Not Hispanic Or Latino	62 76.5%
Not Reported	5 6.2%
Unknown	5 6.2%
Region of Enrollment (participants) [Number]
United States	38 46.9%
Czech Republic	2 2.5%
Canada	27 33.3%
Israel	14 17.3%
Body mass index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	29.6 (3.8)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	88.6 (14.2)

Outcome Measures

1. Primary Outcome

Title	Exercise-induced Perfusion Defect Size (PDS) Following Ranolazine and Placebo Treatment
Description	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.
Time Frame	Up to 33 days

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Ranolazine	Placebo
Arm/Group Description	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.
Measure Participants	61	61
Least Squares Mean (Standard Error) [percentage of myocardium]	21.54 (1.51)	20.87 (1.51)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ranolazine, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.29
	Comments	The null hypothesis that ranolazine treatment had no effect on PDS would be rejected if the PDS and TPD p-values were less than 0.05 or the PDS p-value was less than 0.05/2 = 0.025.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mixed Models Analysis
	Estimated Value	0.67
	Confidence Interval	(2-Sided) 95%; -0.6 to 1.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Exercise-induced Total Perfusion Deficit (TPD) Following Ranolazine and Placebo Treatment
Description	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.
Time Frame	Up to 33 days

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Set

Arm/Group Title	Ranolazine	Placebo
Arm/Group Description	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.
Measure Participants	61	61
Least Squares Mean (Standard Error) [units on a scale]	17.23 (1.26)	16.57 (1.26)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ranolazine, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.22
	Comments	The null hypothesis that ranolazine treatment had no effect on TPD would be rejected if the PDS and TPD p-values were less than 0.05 or the TPD p-value was less than 0.05/2 = 0.025.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mixed Models Analysis
	Estimated Value	0.65
	Confidence Interval	(2-Sided) 95%; -0.4 to 1.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Perfusion Defect Severity at Baseline, End of Period 1, and End of Period 2
Description	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.
Time Frame	Up to 33 days

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Set

Arm/Group Title	Ranolazine/Placebo	Placebo/Ranolazine
Arm/Group Description	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 SPECT 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.	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.
Measure Participants	30	31
Baseline	11.4 (2.0)	8.5 (2.0)
End of Period 1	11.6 (1.9)	10.2 (2.1)
End of Period 2	10.4 (1.9)	9.5 (2.0)

4. Secondary Outcome

Title	Exercise-induced Reversible Perfusion Defect Size (PDS) at Baseline, End of Period 1, and End of Period 2
Description	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.
Time Frame	Up to 33 days

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Set

Arm/Group Title	Ranolazine/Placebo	Placebo/Ranolazine
Arm/Group Description	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 SPECT 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.	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.
Measure Participants	30	31
Baseline exercise minus baseline resting	12.5 (1.1)	13.5 (1.3)
End of Period 1 exercise minus baseline resting	12.7 (1.2)	14.1 (1.4)
End of Period 2 exercise minus baseline resting	12.4 (1.0)	15.2 (1.4)

5. Secondary Outcome

Title	Exercise-induced Reversible Total Perfusion Deficit (TPD) at Baseline, End of Period 1, and End of Period 2
Description	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.
Time Frame	Up to 33 days

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Set

Arm/Group Title	Ranolazine/Placebo	Placebo/Ranolazine
Arm/Group Description	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 SPECT 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.	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.
Measure Participants	30	31
Baseline exercise minus baseline resting	10.5 (0.9)	10.5 (1.0)
End of Period 1 exercise minus baseline resting	10.5 (0.9)	10.7 (1.0)
End of Period 2 exercise minus baseline resting	10.1 (0.8)	11.6 (1.1)

Adverse Events

Time Frame	Up to 33 days
Adverse Event Reporting Description	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.
Arm/Group Title	Onset Following Ranolazine		Onset Following Placebo		Onset at Any Time Following Ranolazine
Arm/Group Description	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.		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.		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.
All Cause Mortality
	Onset Following Ranolazine		Onset Following Placebo		Onset at Any Time Following Ranolazine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Onset Following Ranolazine		Onset Following Placebo		Onset at Any Time Following Ranolazine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/80 (2.5%)		0/79 (0%)		2/80 (2.5%)
Infections and infestations
Bronchitis	1/80 (1.3%)		0/79 (0%)		1/80 (1.3%)
Investigations
Electrocardiogram ST segment elevation	1/80 (1.3%)		0/79 (0%)		1/80 (1.3%)
Other (Not Including Serious) Adverse Events
	Onset Following Ranolazine		Onset Following Placebo		Onset at Any Time Following Ranolazine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/80 (31.3%)		7/79 (8.9%)		28/80 (35%)
Cardiac disorders
Angina pectoris	3/80 (3.8%)		1/79 (1.3%)		4/80 (5%)
Gastrointestinal disorders
Constipation	6/80 (7.5%)		1/79 (1.3%)		6/80 (7.5%)
Nausea	5/80 (6.3%)		2/79 (2.5%)		5/80 (6.3%)
Nervous system disorders
Dizziness	11/80 (13.8%)		0/79 (0%)		11/80 (13.8%)
Headache	3/80 (3.8%)		3/79 (3.8%)		4/80 (5%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	7/80 (8.8%)		2/79 (2.5%)		9/80 (11.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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