Trial Outcomes & Findings for Type 2 Diabetes Evaluation of Ranolazine in Subjects With Chronic Stable Angina (NCT NCT01425359)

Last Updated: 2014-11-04

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

949 participants

Primary outcome timeframe

6 weeks

Results posted on

2014-11-04

Participant Flow

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.

1142 participants entered the qualifying period.

Participant milestones

Participant milestones
Measure	Placebo 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.	Ranolazine 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 Study STARTED	476	473
Overall Study COMPLETED	457	451
Overall Study NOT COMPLETED	19	22

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo 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.	Ranolazine 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 Study Randomized but Not Treated	2	3
Overall Study Adverse Event	9	8
Overall Study Revascularization	0	1
Overall Study Death	0	1
Overall Study Unsatisfactory Response	1	0
Overall Study Protocol Violation	1	2
Overall Study Subject Withdrew Consent	1	2
Overall Study Investigator's Discretion	2	0
Overall Study Did Not Meet Qualifying Criteria	3	5

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=474 Participants 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.	Ranolazine n=470 Participants 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 n=944 Participants Total of all reporting groups
Age, Continuous	64 years STANDARD_DEVIATION 8.5 • n=99 Participants	63 years STANDARD_DEVIATION 8.6 • n=107 Participants	64 years STANDARD_DEVIATION 8.5 • n=206 Participants
Age, Customized < 65 years	249 participants n=99 Participants	264 participants n=107 Participants	513 participants n=206 Participants
Age, Customized 65 - 74 years	170 participants n=99 Participants	160 participants n=107 Participants	330 participants n=206 Participants
Age, Customized ≥ 75 years	55 participants n=99 Participants	46 participants n=107 Participants	101 participants n=206 Participants
Sex: Female, Male Female	182 Participants n=99 Participants	180 Participants n=107 Participants	362 Participants n=206 Participants
Sex: Female, Male Male	292 Participants n=99 Participants	290 Participants n=107 Participants	582 Participants n=206 Participants
Race/Ethnicity, Customized Asian	1 participants n=99 Participants	1 participants n=107 Participants	2 participants n=206 Participants
Race/Ethnicity, Customized Black or African American	2 participants n=99 Participants	5 participants n=107 Participants	7 participants n=206 Participants
Race/Ethnicity, Customized White	471 participants n=99 Participants	464 participants n=107 Participants	935 participants n=206 Participants
Race/Ethnicity, Customized Hispanic or Latino	5 participants n=99 Participants	4 participants n=107 Participants	9 participants n=206 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	464 participants n=99 Participants	462 participants n=107 Participants	926 participants n=206 Participants
Race/Ethnicity, Customized Not Reported	3 participants n=99 Participants	3 participants n=107 Participants	6 participants n=206 Participants
Race/Ethnicity, Customized Unknown	2 participants n=99 Participants	1 participants n=107 Participants	3 participants n=206 Participants
Region of Enrollment United States	12 participants n=99 Participants	15 participants n=107 Participants	27 participants n=206 Participants
Region of Enrollment Belarus	1 participants n=99 Participants	0 participants n=107 Participants	1 participants n=206 Participants
Region of Enrollment Serbia	3 participants n=99 Participants	2 participants n=107 Participants	5 participants n=206 Participants
Region of Enrollment Slovenia	0 participants n=99 Participants	1 participants n=107 Participants	1 participants n=206 Participants
Region of Enrollment Slovakia	12 participants n=99 Participants	9 participants n=107 Participants	21 participants n=206 Participants
Region of Enrollment Ukraine	53 participants n=99 Participants	69 participants n=107 Participants	122 participants n=206 Participants
Region of Enrollment Israel	10 participants n=99 Participants	14 participants n=107 Participants	24 participants n=206 Participants
Region of Enrollment Russian Federation	281 participants n=99 Participants	263 participants n=107 Participants	544 participants n=206 Participants
Region of Enrollment Czech Republic	3 participants n=99 Participants	6 participants n=107 Participants	9 participants n=206 Participants
Region of Enrollment Canada	2 participants n=99 Participants	1 participants n=107 Participants	3 participants n=206 Participants
Region of Enrollment Poland	53 participants n=99 Participants	40 participants n=107 Participants	93 participants n=206 Participants
Region of Enrollment Bulgaria	9 participants n=99 Participants	11 participants n=107 Participants	20 participants n=206 Participants
Region of Enrollment Georgia	36 participants n=99 Participants	40 participants n=107 Participants	76 participants n=206 Participants
Region of Enrollment Germany	1 participants n=99 Participants	2 participants n=107 Participants	3 participants n=206 Participants
Body Mass Index	31.1 kg/m^2 STANDARD_DEVIATION 4.90 • n=99 Participants	31.3 kg/m^2 STANDARD_DEVIATION 5.01 • n=107 Participants	31.2 kg/m^2 STANDARD_DEVIATION 4.96 • n=206 Participants
Glycosylated hemoglobin (HbA1c)	7.3 percent HbA1c in blood STANDARD_DEVIATION 1.53 • n=99 Participants	7.3 percent HbA1c in blood STANDARD_DEVIATION 1.50 • n=107 Participants	7.3 percent HbA1c in blood STANDARD_DEVIATION 1.52 • n=206 Participants

PRIMARY outcome

Timeframe: 6 weeks

Population: 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.

Outcome measures

Outcome measures
Measure	Placebo n=465 Participants 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.	Ranolazine n=462 Participants 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.
Average Weekly Angina Frequency Over the Last 6 Weeks of Treatment	5.2 angina attacks per week Standard Deviation 4.73	4.5 angina attacks per week Standard Deviation 4.32

SECONDARY outcome

Timeframe: 6 weeks

Population: Full Analysis Set

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.

Outcome measures

Outcome measures
Measure	Placebo n=465 Participants 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.	Ranolazine n=462 Participants 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.
Average Weekly Frequency of Sublingual Nitroglycerin Use Over the Last 6 Weeks of Treatment	3.6 nitroglycerin uses per week Standard Deviation 5.35	2.9 nitroglycerin uses per week Standard Deviation 4.34

SECONDARY outcome

Timeframe: 6 weeks

Population: Participants in the Full Analysis Set with available data were analyzed.

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.

Outcome measures

Outcome measures
Measure	Placebo n=462 Participants 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.	Ranolazine n=460 Participants 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.
Percentage of Weeks Participants Achieved at Least a 50% Reduction in Angina Frequency	41 percentage of weeks Standard Deviation 36	46 percentage of weeks Standard Deviation 35

SECONDARY outcome

Timeframe: 6 weeks

Population: Full Analysis Set

Outcome measures

Outcome measures
Measure	Placebo n=465 Participants 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.	Ranolazine n=462 Participants 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.
Percentage of the Last 6 Weeks on Treatment During Which the Angina Frequency Was ≤ 50% of the Baseline Average Weekly Angina Frequency	50 percentage of weeks Standard Error 1.4	54 percentage of weeks Standard Error 1.3

SECONDARY outcome

Timeframe: Up to 8 weeks

Population: Participants in the Full Analysis Set with available data were analyzed.

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.

Outcome measures

Outcome measures
Measure	Placebo n=460 Participants 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.	Ranolazine n=456 Participants 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.
Change From Baseline in the Short-Form 36® (SF-36) Mental and Physical Component Scores Mental Component Score	1.2 units on a scale Standard Error 0.37	1.0 units on a scale Standard Error 0.39
Change From Baseline in the Short-Form 36® (SF-36) Mental and Physical Component Scores Physical Component Score	1.9 units on a scale Standard Error 0.25	2.8 units on a scale Standard Error 0.26

SECONDARY outcome

Timeframe: 8 weeks

Population: Participants in the Full Analysis Set with available data were analyzed.

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).

Outcome measures

Outcome measures
Measure	Placebo n=461 Participants 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.	Ranolazine n=457 Participants 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.
Patient's Global Impression of Change (PGIC) Scale Score	3.9 units on a scale Standard Error 0.07	4.0 units on a scale Standard Error 0.07

Adverse Events

Placebo

Serious events: 20 serious events

Other events: 0 other events

Deaths: 0 deaths

Ranolazine

Serious events: 16 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Adverse event data not reported

Additional Information

Clinical Trial Disclosures

Gilead Sciences, Inc.

Email: [email protected]

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

Measure	Placebo n=474 participants at risk 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.	Ranolazine n=470 participants at risk 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.
Blood and lymphatic system disorders Anaemia	0.21% 1/474 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.	0.00% 0/470 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.
Cardiac disorders Acute myocardial infarction	0.63% 3/474 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.	0.43% 2/470 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.
Cardiac disorders Angina unstable	0.21% 1/474 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.	0.64% 3/470 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.
Cardiac disorders Angina pectoris	0.21% 1/474 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.	0.21% 1/470 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.
Cardiac disorders Acute coronary syndrome	0.21% 1/474 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.	0.00% 0/470 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.
Cardiac disorders Cardiac failure acute	0.42% 2/474 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.	0.00% 0/470 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.
Cardiac disorders Cardiac failure chronic	0.00% 0/474 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.	0.21% 1/470 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.
Cardiac disorders Cardiogenic shock	0.00% 0/474 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.	0.21% 1/470 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.
Cardiac disorders Atrial fibrillation	0.63% 3/474 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.	0.00% 0/470 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.
Cardiac disorders Coronary artery disease	0.21% 1/474 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.	0.00% 0/470 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.
Cardiac disorders Ventricular tachycardia	0.00% 0/474 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.	0.21% 1/470 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.
General disorders Chest pain	0.21% 1/474 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.	0.43% 2/470 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.
General disorders Sudden cardiac death	0.00% 0/474 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.	0.21% 1/470 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.
General disorders Thrombosis in device	0.21% 1/474 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.	0.00% 0/470 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.
Injury, poisoning and procedural complications Hip fracture	0.00% 0/474 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.	0.21% 1/470 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/474 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.	0.21% 1/470 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.
Nervous system disorders Ischaemic stroke	0.63% 3/474 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.	0.21% 1/470 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.
Nervous system disorders Cervical myelopathy	0.21% 1/474 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.	0.00% 0/470 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.
Nervous system disorders Syncope	0.00% 0/474 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.	0.21% 1/470 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.
Nervous system disorders Transient ischaemic attack	0.21% 1/474 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.	0.00% 0/470 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.
Renal and urinary disorders Calculus ureteric	0.21% 1/474 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.	0.00% 0/470 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.
Renal and urinary disorders Calculus urinary	0.21% 1/474 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.	0.00% 0/470 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.21% 1/474 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.	0.00% 0/470 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.
Vascular disorders Circulatory collapse	0.00% 0/474 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.	0.21% 1/470 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.
Vascular disorders Hypertension	0.21% 1/474 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.	0.00% 0/470 • Baseline to Day 56 plus 30 days Safety Analysis Set: randomized participants who received at least one dose of study treatment.