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Type 2 Diabetes Evaluation of Ranolazine in Subjects With Chronic Stable Angina (TERISA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01425359
Recruitment Status : Completed
First Posted : August 30, 2011
Results First Posted : November 4, 2014
Last Update Posted : November 4, 2014
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Angina Pectoris
Coronary Artery Disease
Type 2 Diabetes Mellitus
Interventions Drug: Ranolazine
Drug: Ranolazine placebo
Enrollment 949
Recruitment Details Participants were enrolled at a total of 116 study sites in North America, Europe, and Asia. The first participant was screened on 05 October 2011. The last participant observation occurred on 25 October 2012.
Pre-assignment Details 1142 participants entered the qualifying period.
Arm/Group Title Placebo Ranolazine
Hide Arm/Group Description

Qualifying phase: Participants entered a 2-week washout period if needed to discontinue antianginal drugs (except beta-blockers) followed by placebo to match ranolazine (1 tablet twice daily) during a 4-week run-in period. Participants with at least 85% adherence to documentation requirements (angina frequency and sublingual nitroglycerin use) over the last 21 days of the placebo run-in period were randomized to the treatment period.

Treatment Period: Placebo to match ranolazine (Day 1: 1 tablet in the evening; Days 2-7: 1 tablet twice daily; 2 tablets twice daily thereafter) for up to 8 weeks.

Qualifying phase: Participants entered a 2-week washout period if needed to discontinue antianginal drugs (except beta-blockers) followed by placebo to match ranolazine (1 tablet twice daily) during a 4-week run-in period. Participants with at least 85% adherence to documentation requirements (angina frequency and sublingual nitroglycerin use) over the last 21 days of the placebo run-in period were randomized to the treatment period.

Treatment period: Ranolazine tablets (Day 1: 1 × 500 tablet in the evening; Days 2-7: 1 × 500 mg twice daily; 2 × 500 mg twice daily thereafter) for up to 8 weeks.

Period Title: Overall Study
Started 476 473
Completed 457 451
Not Completed 19 22
Reason Not Completed
Randomized but Not Treated             2             3
Adverse Event             9             8
Revascularization             0             1
Death             0             1
Unsatisfactory Response             1             0
Protocol Violation             1             2
Subject Withdrew Consent             1             2
Investigator’s Discretion             2             0
Did Not Meet Qualifying Criteria             3             5
Arm/Group Title Placebo Ranolazine Total
Hide Arm/Group Description

Qualifying phase: Participants entered a 2-week washout period if needed to discontinue antianginal drugs (except beta-blockers) followed by placebo to match ranolazine (1 tablet twice daily) during a 4-week run-in period. Participants with at least 85% adherence to documentation requirements (angina frequency and sublingual nitroglycerin use) over the last 21 days of the placebo run-in period were randomized to the treatment period.

Treatment Period: Placebo to match ranolazine (Day 1: 1 tablet in the evening; Days 2-7: 1 tablet twice daily; 2 tablets twice daily thereafter) for up to 8 weeks.

Qualifying phase: Participants entered a 2-week washout period if needed to discontinue antianginal drugs (except beta-blockers) followed by placebo to match ranolazine (1 tablet twice daily) during a 4-week run-in period. Participants with at least 85% adherence to documentation requirements (angina frequency and sublingual nitroglycerin use) over the last 21 days of the placebo run-in period were randomized to the treatment period.

Treatment period: Ranolazine tablets (Day 1: 1 × 500 tablet in the evening; Days 2-7: 1 × 500 mg twice daily; 2 × 500 mg twice daily thereafter) for up to 8 weeks.

Total of all reporting groups
Overall Number of Baseline Participants 474 470 944
Hide Baseline Analysis Population Description
Safety Analysis Set: randomized participants who received at least one dose of study treatment.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 474 participants 470 participants 944 participants
64  (8.5) 63  (8.6) 64  (8.5)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 474 participants 470 participants 944 participants
< 65 years 249 264 513
65 - 74 years 170 160 330
≥ 75 years 55 46 101
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 474 participants 470 participants 944 participants
Female
182
  38.4%
180
  38.3%
362
  38.3%
Male
292
  61.6%
290
  61.7%
582
  61.7%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 474 participants 470 participants 944 participants
Asian 1 1 2
Black or African American 2 5 7
White 471 464 935
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 474 participants 470 participants 944 participants
Hispanic or Latino 5 4 9
Not Hispanic or Latino 464 462 926
Not Reported 3 3 6
Unknown 2 1 3
Region of Enrollment   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 474 participants 470 participants 944 participants
United States 12 15 27
Belarus 1 0 1
Serbia 3 2 5
Slovenia 0 1 1
Slovakia 12 9 21
Ukraine 53 69 122
Israel 10 14 24
Russian Federation 281 263 544
Czech Republic 3 6 9
Canada 2 1 3
Poland 53 40 93
Bulgaria 9 11 20
Georgia 36 40 76
Germany 1 2 3
[1]
Measure Description: All randomized participants were analyzed for region of enrollment (placebo, n = 476; ranolazine, n = 473).
Body Mass Index  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 474 participants 470 participants 944 participants
31.1  (4.90) 31.3  (5.01) 31.2  (4.96)
Glycosylated hemoglobin (HbA1c)  
Mean (Standard Deviation)
Unit of measure:  Percent HbA1c in blood
Number Analyzed 474 participants 470 participants 944 participants
7.3  (1.53) 7.3  (1.50) 7.3  (1.52)
1.Primary Outcome
Title Average Weekly Angina Frequency Over the Last 6 Weeks of Treatment
Hide Description

Average weekly angina frequency was defined as the total number of angina episodes reported during the last 6 weeks of treatment divided by 6 weeks.

For subjects who terminated with less than 6 weeks of treatment, frequency was calculated as the total number of angina episodes reported during the treatment period divided by the subject’s actual duration of treatment.

Time Frame 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS): randomized participants who received at least 1 dose of randomized study drug with at least 1 postbaseline primary efficacy measurement and did not have any major eligibility violations. Participants were included in the FAS if they did not discontinue study drug prior to Day 14.
Arm/Group Title Placebo Ranolazine
Hide Arm/Group Description:

Qualifying phase: Participants entered a 2-week washout period if needed to discontinue antianginal drugs (except beta-blockers) followed by placebo to match ranolazine (1 tablet twice daily) during a 4-week run-in period. Participants with at least 85% adherence to documentation requirements (angina frequency and sublingual nitroglycerin use) over the last 21 days of the placebo run-in period were randomized to the treatment period.

Treatment Period: Placebo to match ranolazine (Day 1: 1 tablet in the evening; Days 2-7: 1 tablet twice daily; 2 tablets twice daily thereafter) for up to 8 weeks.

Qualifying phase: Participants entered a 2-week washout period if needed to discontinue antianginal drugs (except beta-blockers) followed by placebo to match ranolazine (1 tablet twice daily) during a 4-week run-in period. Participants with at least 85% adherence to documentation requirements (angina frequency and sublingual nitroglycerin use) over the last 21 days of the placebo run-in period were randomized to the treatment period.

Treatment period: Ranolazine tablets (Day 1: 1 × 500 tablet in the evening; Days 2-7: 1 × 500 mg twice daily; 2 × 500 mg twice daily thereafter) for up to 8 weeks.

Overall Number of Participants Analyzed 465 462
Mean (Standard Deviation)
Unit of Measure: angina attacks per week
5.2  (4.73) 4.5  (4.32)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Ranolazine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.008
Comments Angina frequency was compared by fitting a generalized linear model with log link and negative binomial distribution response.
Method Generalized linear model
Comments [Not Specified]
2.Secondary Outcome
Title Average Weekly Frequency of Sublingual Nitroglycerin Use Over the Last 6 Weeks of Treatment
Hide Description Average weekly frequency of sublingual nitroglycerin use was defined as the total number reported during the last 6 weeks of treatment divided by the duration corresponding to the last 6 weeks of treatment.
Time Frame 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Placebo Ranolazine
Hide Arm/Group Description:

Qualifying phase: Participants entered a 2-week washout period if needed to discontinue antianginal drugs (except beta-blockers) followed by placebo to match ranolazine (1 tablet twice daily) during a 4-week run-in period. Participants with at least 85% adherence to documentation requirements (angina frequency and sublingual nitroglycerin use) over the last 21 days of the placebo run-in period were randomized to the treatment period.

Treatment Period: Placebo to match ranolazine (Day 1: 1 tablet in the evening; Days 2-7: 1 tablet twice daily; 2 tablets twice daily thereafter) for up to 8 weeks.

Qualifying phase: Participants entered a 2-week washout period if needed to discontinue antianginal drugs (except beta-blockers) followed by placebo to match ranolazine (1 tablet twice daily) during a 4-week run-in period. Participants with at least 85% adherence to documentation requirements (angina frequency and sublingual nitroglycerin use) over the last 21 days of the placebo run-in period were randomized to the treatment period.

Treatment period: Ranolazine tablets (Day 1: 1 × 500 tablet in the evening; Days 2-7: 1 × 500 mg twice daily; 2 × 500 mg twice daily thereafter) for up to 8 weeks.

Overall Number of Participants Analyzed 465 462
Mean (Standard Deviation)
Unit of Measure: nitroglycerin uses per week
3.6  (5.35) 2.9  (4.34)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Ranolazine
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments Sublingual nitroglycerin use frequency was compared by fitting a generalized linear model with log link and negative binomial distribution response.
Method Generalized linear model
Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Weeks Participants Achieved at Least a 50% Reduction in Angina Frequency
Hide Description For each participant, the percentage of the last 6 weeks on treatment during which the angina frequency was less than or equal to 50% of the baseline average weekly angina frequency was determined.
Time Frame 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set with available data were analyzed.
Arm/Group Title Placebo Ranolazine
Hide Arm/Group Description:

Qualifying phase: Participants entered a 2-week washout period if needed to discontinue antianginal drugs (except beta-blockers) followed by placebo to match ranolazine (1 tablet twice daily) during a 4-week run-in period. Participants with at least 85% adherence to documentation requirements (angina frequency and sublingual nitroglycerin use) over the last 21 days of the placebo run-in period were randomized to the treatment period.

Treatment Period: Placebo to match ranolazine (Day 1: 1 tablet in the evening; Days 2-7: 1 tablet twice daily; 2 tablets twice daily thereafter) for up to 8 weeks.

Qualifying phase: Participants entered a 2-week washout period if needed to discontinue antianginal drugs (except beta-blockers) followed by placebo to match ranolazine (1 tablet twice daily) during a 4-week run-in period. Participants with at least 85% adherence to documentation requirements (angina frequency and sublingual nitroglycerin use) over the last 21 days of the placebo run-in period were randomized to the treatment period.

Treatment period: Ranolazine tablets (Day 1: 1 × 500 tablet in the evening; Days 2-7: 1 × 500 mg twice daily; 2 × 500 mg twice daily thereafter) for up to 8 weeks.

Overall Number of Participants Analyzed 462 460
Mean (Standard Deviation)
Unit of Measure: percentage of weeks
41  (36) 46  (35)
4.Secondary Outcome
Title Percentage of the Last 6 Weeks on Treatment During Which the Angina Frequency Was ≤ 50% of the Baseline Average Weekly Angina Frequency
Hide Description [Not Specified]
Time Frame 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Placebo Ranolazine
Hide Arm/Group Description:

Qualifying phase: Participants entered a 2-week washout period if needed to discontinue antianginal drugs (except beta-blockers) followed by placebo to match ranolazine (1 tablet twice daily) during a 4-week run-in period. Participants with at least 85% adherence to documentation requirements (angina frequency and sublingual nitroglycerin use) over the last 21 days of the placebo run-in period were randomized to the treatment period.

Treatment Period: Placebo to match ranolazine (Day 1: 1 tablet in the evening; Days 2-7: 1 tablet twice daily; 2 tablets twice daily thereafter) for up to 8 weeks.

Qualifying phase: Participants entered a 2-week washout period if needed to discontinue antianginal drugs (except beta-blockers) followed by placebo to match ranolazine (1 tablet twice daily) during a 4-week run-in period. Participants with at least 85% adherence to documentation requirements (angina frequency and sublingual nitroglycerin use) over the last 21 days of the placebo run-in period were randomized to the treatment period.

Treatment period: Ranolazine tablets (Day 1: 1 × 500 tablet in the evening; Days 2-7: 1 × 500 mg twice daily; 2 × 500 mg twice daily thereafter) for up to 8 weeks.

Overall Number of Participants Analyzed 465 462
Mean (Standard Error)
Unit of Measure: percentage of weeks
50  (1.4) 54  (1.3)
5.Secondary Outcome
Title Change From Baseline in the Short-Form 36® (SF-36) Mental and Physical Component Scores
Hide Description The range of each health domain score is 0-100, with 0 indicating a poorer health state and 100 indicating a better health state. An increase in score indicates an improvement in health state. Participants were asked to complete the survey at randomization (prior to receiving treatment), and at end of treatment visit (Week 8) or early study drug discontinuation or early termination visit. The survey asked participants for responses specific to the preceding 4 weeks prior to completing the survey.
Time Frame Up to 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set with available data were analyzed.
Arm/Group Title Placebo Qualifying Phase: Participants Entered a 2-week Washout Period
Hide Arm/Group Description:

Qualifying phase: Participants entered a 2-week washout period if needed to discontinue antianginal drugs (except beta-blockers) followed by placebo to match ranolazine (1 tablet twice daily) during a 4-week run-in period. Participants with at least 85% adherence to documentation requirements (angina frequency and sublingual nitroglycerin use) over the last 21 days of the placebo run-in period were randomized to the treatment period.

Treatment Period: Placebo to match ranolazine (Day 1: 1 tablet in the evening; Days 2-7: 1 tablet twice daily; 2 tablets twice daily thereafter) for up to 8 weeks.

Qualifying phase: Participants entered a 2-week washout period if needed to discontinue antianginal drugs (except beta-blockers) followed by placebo to match ranolazine (1 tablet twice daily) during a 4-week run-in period. Participants with at least 85% adherence to documentation requirements (angina frequency and sublingual nitroglycerin use) over the last 21 days of the placebo run-in period were randomized to the treatment period.

Treatment period: Ranolazine tablets (Day 1: 1 × 500 tablet in the evening; Days 2-7: 1 × 500 mg twice daily; 2 × 500 mg twice daily thereafter) for up to 8 weeks.

Overall Number of Participants Analyzed 460 456
Mean (Standard Error)
Unit of Measure: units on a scale
Mental Component Score 1.2  (0.37) 1.0  (0.39)
Physical Component Score 1.9  (0.25) 2.8  (0.26)
6.Secondary Outcome
Title Patient's Global Impression of Change (PGIC) Scale Score
Hide Description The PGIC was completed at the end of treatment/last visit.The PGIC scale measures the change in the participant's overall status since the beginning of the study on a scale ranging from 1 (no change or worse) to 7 (very much improved).
Time Frame 8 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in the Full Analysis Set with available data were analyzed.
Arm/Group Title Placebo Ranolazine
Hide Arm/Group Description:

Qualifying phase: Participants entered a 2-week washout period if needed to discontinue antianginal drugs (except beta-blockers) followed by placebo to match ranolazine (1 tablet twice daily) during a 4-week run-in period. Participants with at least 85% adherence to documentation requirements (angina frequency and sublingual nitroglycerin use) over the last 21 days of the placebo run-in period were randomized to the treatment period.

Treatment Period: Placebo to match ranolazine (Day 1: 1 tablet in the evening; Days 2-7: 1 tablet twice daily; 2 tablets twice daily thereafter) for up to 8 weeks.

Qualifying phase: Participants entered a 2-week washout period if needed to discontinue antianginal drugs (except beta-blockers) followed by placebo to match ranolazine (1 tablet twice daily) during a 4-week run-in period. Participants with at least 85% adherence to documentation requirements (angina frequency and sublingual nitroglycerin use) over the last 21 days of the placebo run-in period were randomized to the treatment period.

Treatment period: Ranolazine tablets (Day 1: 1 × 500 tablet in the evening; Days 2-7: 1 × 500 mg twice daily; 2 × 500 mg twice daily thereafter) for up to 8 weeks.

Overall Number of Participants Analyzed 461 457
Mean (Standard Error)
Unit of Measure: units on a scale
3.9  (0.07) 4.0  (0.07)
Time Frame Baseline to Day 56 plus 30 days
Adverse Event Reporting Description Safety Analysis Set: randomized participants who received at least one dose of study treatment.
 
Arm/Group Title Placebo Ranolazine
Hide Arm/Group Description

Qualifying phase: Participants entered a 2-week washout period if needed to discontinue antianginal drugs (except beta-blockers) followed by placebo to match ranolazine (1 tablet twice daily) during a 4-week run-in period. Participants with at least 85% adherence to documentation requirements (angina frequency and sublingual nitroglycerin use) over the last 21 days of the placebo run-in period were randomized to the treatment period.

Treatment Period: Placebo to match ranolazine (Day 1: 1 tablet in the evening; Days 2-7: 1 tablet twice daily; 2 tablets twice daily thereafter) for up to 8 weeks.

Qualifying phase: Participants entered a 2-week washout period if needed to discontinue antianginal drugs (except beta-blockers) followed by placebo to match ranolazine (1 tablet twice daily) during a 4-week run-in period. Participants with at least 85% adherence to documentation requirements (angina frequency and sublingual nitroglycerin use) over the last 21 days of the placebo run-in period were randomized to the treatment period.

Treatment period: Ranolazine tablets (Day 1: 1 × 500 tablet in the evening; Days 2-7: 1 × 500 mg twice daily; 2 × 500 mg twice daily thereafter) for up to 8 weeks.

All-Cause Mortality
Placebo Ranolazine
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Ranolazine
Affected / at Risk (%) Affected / at Risk (%)
Total   20/474 (4.22%)   16/470 (3.40%) 
Blood and lymphatic system disorders     
Anaemia  1  1/474 (0.21%)  0/470 (0.00%) 
Cardiac disorders     
Acute myocardial infarction  1  3/474 (0.63%)  2/470 (0.43%) 
Angina unstable  1  1/474 (0.21%)  3/470 (0.64%) 
Angina pectoris  1  1/474 (0.21%)  1/470 (0.21%) 
Acute coronary syndrome  1  1/474 (0.21%)  0/470 (0.00%) 
Cardiac failure acute  1  2/474 (0.42%)  0/470 (0.00%) 
Cardiac failure chronic  1  0/474 (0.00%)  1/470 (0.21%) 
Cardiogenic shock  1  0/474 (0.00%)  1/470 (0.21%) 
Atrial fibrillation  1  3/474 (0.63%)  0/470 (0.00%) 
Coronary artery disease  1  1/474 (0.21%)  0/470 (0.00%) 
Ventricular tachycardia  1  0/474 (0.00%)  1/470 (0.21%) 
General disorders     
Chest pain  1  1/474 (0.21%)  2/470 (0.43%) 
Sudden cardiac death  1  0/474 (0.00%)  1/470 (0.21%) 
Thrombosis in device  1  1/474 (0.21%)  0/470 (0.00%) 
Injury, poisoning and procedural complications     
Hip fracture  1  0/474 (0.00%)  1/470 (0.21%) 
Metabolism and nutrition disorders     
Hyperglycaemia  1  0/474 (0.00%)  1/470 (0.21%) 
Nervous system disorders     
Ischaemic stroke  1  3/474 (0.63%)  1/470 (0.21%) 
Cervical myelopathy  1  1/474 (0.21%)  0/470 (0.00%) 
Syncope  1  0/474 (0.00%)  1/470 (0.21%) 
Transient ischaemic attack  1  1/474 (0.21%)  0/470 (0.00%) 
Renal and urinary disorders     
Calculus ureteric  1  1/474 (0.21%)  0/470 (0.00%) 
Calculus urinary  1  1/474 (0.21%)  0/470 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Pulmonary embolism  1  1/474 (0.21%)  0/470 (0.00%) 
Vascular disorders     
Circulatory collapse  1  0/474 (0.00%)  1/470 (0.21%) 
Hypertension  1  1/474 (0.21%)  0/470 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (15.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Ranolazine
Affected / at Risk (%) Affected / at Risk (%)
Total   0/474 (0.00%)   0/470 (0.00%) 
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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
Results Point of Contact
Name/Title: Clinical Trial Disclosures
Organization: Gilead Sciences, Inc.
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01425359     History of Changes
Other Study ID Numbers: GS-US-259-0133
First Submitted: August 24, 2011
First Posted: August 30, 2011
Results First Submitted: October 20, 2014
Results First Posted: November 4, 2014
Last Update Posted: November 4, 2014