Trial Outcomes & Findings for Efficacy of LCQ908 on Cardiovascular Risk (NCT NCT01474434)

Last Updated: 2016-04-14

Results Overview

MPRi (myocardial perfusion reserve index) is a measure of coronary microvascular function. Myocardial perfusion scans using 0.05 mmol/kg of gadolinium contrast were acquired at rest and under stress (pharmacological stress induced with adenosine 140 μg/kg/min for three minutes). An independent central reader performed the cardiac image analysis of all time points including the calculation of the myocardial perfusion reserve index from the ratio of the global stress myocardial blood flow divided by the resting blood flow values. Higher/increased index indicates improved flow/better outcome. This primary endpoint was only for Part A, Cohort 1 patients.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

41 participants

Primary outcome timeframe

Baseline, and on day 5 of each of the two treatment periods

Results posted on

2016-04-14

Participant Flow

Study was terminated upon Part A interim analysis. Total 41 patients randomized to Part A i.e.17 patients in cohort 1 and 24 patients in Cohort 2.

Participant milestones

Participant milestones
Measure	Part A, Cohort 1: Pradigastat (LCQ908) Followed by Placebo Cohort 1 consisted of patients with evidence of stable symptomatic or obstructive coronary artery disease and mild to moderate hypertriglyceridemia. All patients who randomized to this sequence received pradigastat 80 mg (4 x 20-mg tablets) loading dose daily for three days followed by pradigastat 20 mg (2 x 10-mg tablets) daily for two days followed by a 30-day washout period in between followed by 5-day placebo treatment	Part A, Cohort 1: Placebo Followed by Pradigastat (LCQ908) Cohort 1 consisted of patients with evidence of stable symptomatic or obstructive coronary artery disease and mild to moderate hypertriglyceridemia. All patients who randomized to this sequence received Placebo (5-day treatment period) followed by a 30-day washout period followed by pradigastat 80 mg (4 x 20-mg tablets) loading dose daily for three days followed by 20 mg (2 x 10-mg tablets) daily for two days	Part A, Cohort 2: Pradigastat (LCQ908) Followed by Placebo Cohort 2 consisted of patients with stable asymptomatic non-obstructive coronary artery disease or coronary heart disease risk equivalents and mild to moderate hypertriglyceridemia.. All patients who randomized to this sequence received pradigastat 80 mg (4 x 20-mg tablets) loading dose daily for three days followed by pradigastat 20 mg (2 x 10-mg tablets) daily for two days followed by a 30-day washout period in between followed by 5-day placebo treatment	Part A, Cohort 2: Placebo Followed by Pradigastat (LCQ908) Cohort 2 consisted of patients with stable asymptomatic non-obstructive coronary artery disease or coronary heart disease risk equivalents and mild to moderate hypertriglyceridemia. All patients who randomized to this sequence received Placebo (5-day treatment period) followed by a 30-day washout period followed by pradigastat 80 mg (4 x 20-mg tablets) loading dose daily for three days followed by 20 mg (2 x 10-mg tablets) daily for two days
Treatment Period 1 (5 Days [Day 1 - 5]) STARTED	8	9	11	13
Treatment Period 1 (5 Days [Day 1 - 5]) COMPLETED	7	9	10	11
Treatment Period 1 (5 Days [Day 1 - 5]) NOT COMPLETED	1	0	1	2
Treatment Period 2(5 Days[Day 36 - 40]) STARTED	7	9	10	11
Treatment Period 2(5 Days[Day 36 - 40]) COMPLETED	7	9	10	11
Treatment Period 2(5 Days[Day 36 - 40]) NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Part A, Cohort 1: Pradigastat (LCQ908) Followed by Placebo Cohort 1 consisted of patients with evidence of stable symptomatic or obstructive coronary artery disease and mild to moderate hypertriglyceridemia. All patients who randomized to this sequence received pradigastat 80 mg (4 x 20-mg tablets) loading dose daily for three days followed by pradigastat 20 mg (2 x 10-mg tablets) daily for two days followed by a 30-day washout period in between followed by 5-day placebo treatment	Part A, Cohort 2: Pradigastat (LCQ908) Followed by Placebo Cohort 2 consisted of patients with stable asymptomatic non-obstructive coronary artery disease or coronary heart disease risk equivalents and mild to moderate hypertriglyceridemia.. All patients who randomized to this sequence received pradigastat 80 mg (4 x 20-mg tablets) loading dose daily for three days followed by pradigastat 20 mg (2 x 10-mg tablets) daily for two days followed by a 30-day washout period in between followed by 5-day placebo treatment	Part A, Cohort 2: Placebo Followed by Pradigastat (LCQ908) Cohort 2 consisted of patients with stable asymptomatic non-obstructive coronary artery disease or coronary heart disease risk equivalents and mild to moderate hypertriglyceridemia. All patients who randomized to this sequence received Placebo (5-day treatment period) followed by a 30-day washout period followed by pradigastat 80 mg (4 x 20-mg tablets) loading dose daily for three days followed by 20 mg (2 x 10-mg tablets) daily for two days
Treatment Period 1 (5 Days [Day 1 - 5]) Adverse Event	0	1	1
Treatment Period 1 (5 Days [Day 1 - 5]) Withdrawal by Subject	0	0	1
Treatment Period 1 (5 Days [Day 1 - 5]) Protocol deviation	1	0	0

Baseline Characteristics

Efficacy of LCQ908 on Cardiovascular Risk

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part A, Cohort 1: Pradigastat (LCQ908) Followed by Placebo n=8 Participants Cohort 1 consisted of patients with evidence of stable symptomatic or obstructive coronary artery disease and mild to moderate hypertriglyceridemia. All patients who randomized to this sequence received pradigastat 80 mg (4 x 20-mg tablets) loading dose daily for three days followed by pradigastat 20 mg (2 x 10-mg tablets) daily for two days followed by a 30-day washout period in between followed by 5-day placebo treatment	Part A, Cohort 1: Placebo Followed by Pradigastat (LCQ908) n=9 Participants Cohort 1 consisted of patients with evidence of stable symptomatic or obstructive coronary artery disease and mild to moderate hypertriglyceridemia. All patients who randomized to this sequence received Placebo (5-day treatment period) followed by a 30-day washout period followed by pradigastat 80 mg (4 x 20-mg tablets) loading dose daily for three days followed by 20 mg (2 x 10-mg tablets) daily for two days	Part A, Cohort 2: Pradigastat (LCQ908) Followed by Placebo n=11 Participants Cohort 2 consisted of patients with stable asymptomatic non-obstructive coronary artery disease or coronary heart disease risk equivalents and mild to moderate hypertriglyceridemia.. All patients who randomized to this sequence received pradigastat 80 mg (4 x 20-mg tablets) loading dose daily for three days followed by pradigastat 20 mg (2 x 10-mg tablets) daily for two days followed by a 30-day washout period in between followed by 5-day placebo treatment	Part A, Cohort 2: Placebo Followed by Pradigastat (LCQ908) n=13 Participants Cohort 2 consisted of patients with stable asymptomatic non-obstructive coronary artery disease or coronary heart disease risk equivalents and mild to moderate hypertriglyceridemia. All patients who randomized to this sequence received Placebo (5-day treatment period) followed by a 30-day washout period followed by pradigastat 80 mg (4 x 20-mg tablets) loading dose daily for three days followed by 20 mg (2 x 10-mg tablets) daily for two days	Total n=41 Participants Total of all reporting groups
Age, Continuous	59.6 years STANDARD_DEVIATION 6.67 • n=5 Participants	58.4 years STANDARD_DEVIATION 8.79 • n=7 Participants	56.7 years STANDARD_DEVIATION 9.79 • n=5 Participants	56.1 years STANDARD_DEVIATION 8.85 • n=4 Participants	57.5 years STANDARD_DEVIATION 8.5 • n=21 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	6 Participants n=4 Participants	16 Participants n=21 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants	7 Participants n=4 Participants	25 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline, and on day 5 of each of the two treatment periods

Population: Efficacy analysis set - Patients who took \> 80% of study drug as assessed by drug accountability, had no major protocol deviations, and had a valid assessment of MPRi at both baseline and post-treatment visits. Patients who had no baseline or post-treatment MPRi data in 1 of 2 periods were excluded from the analysis.

Outcome measures

Outcome measures
Measure	Part A, Cohort 1: Pradigastat (LCQ908) n=13 Participants Cohort 1 consisted of patients with evidence of stable symptomatic or obstructive coronary artery disease and mild to moderate hypertriglyceridemia. All randomized patients who received pradigastat in either of 2 treatment period.	Part A, Cohort 1: Placebo n=12 Participants Cohort 1 consisted of patients with evidence of stable symptomatic or obstructive coronary artery disease and mild to moderate hypertriglyceridemia. All randomized patients who received matching placebo in either of 2 treatment period	Part A, Cohort 2: Pradigastat (LCQ908) Cohort 2 consisted of patients with stable asymptomatic non-obstructive coronary artery disease or coronary heart disease risk equivalents and mild to moderate hypertriglyceridemia.. All randomized patients who recieved pradigastat in either of 2 treatment period.	Part A, Cohort 2: Placebo Cohort 2 consisted of patients with stable asymptomatic non-obstructive coronary artery disease or coronary heart disease risk equivalents and mild to moderate hypertriglyceridemia. All randomized patients who received matching placebo in either of 2 treatment period
Change From Baseline in Myocardial Perfusion Reserve Index (MPRi) Overall Mean (Part A, Cohort 1)	-0.22 myocardial perfusion reserve index Standard Error 0.24	0.32 myocardial perfusion reserve index Standard Error 0.24	—	—

PRIMARY outcome

Timeframe: Baseline and on day 5 of each of the two treatment periods

Population: Efficacy analysis set- Patients who took \> 80% of study drug as assessed by drug accountability, had no major protocol deviations, and had a valid assessment of total exercise duration at both baseline and post-treatment visits. Patients who had no baseline or post-treatment exercise duration data in 1 of 2 periods were excluded from the analysis.

Total exercise duration was the elapsed time between the start of exercise and termination of exercise for severe angina, dyspnea or extreme fatigue. This primary endpoint was only for Part A, Cohort 1 patients.

Outcome measures

Outcome measures
Measure	Part A, Cohort 1: Pradigastat (LCQ908) n=11 Participants Cohort 1 consisted of patients with evidence of stable symptomatic or obstructive coronary artery disease and mild to moderate hypertriglyceridemia. All randomized patients who received pradigastat in either of 2 treatment period.	Part A, Cohort 1: Placebo n=14 Participants Cohort 1 consisted of patients with evidence of stable symptomatic or obstructive coronary artery disease and mild to moderate hypertriglyceridemia. All randomized patients who received matching placebo in either of 2 treatment period	Part A, Cohort 2: Pradigastat (LCQ908) Cohort 2 consisted of patients with stable asymptomatic non-obstructive coronary artery disease or coronary heart disease risk equivalents and mild to moderate hypertriglyceridemia.. All randomized patients who recieved pradigastat in either of 2 treatment period.	Part A, Cohort 2: Placebo Cohort 2 consisted of patients with stable asymptomatic non-obstructive coronary artery disease or coronary heart disease risk equivalents and mild to moderate hypertriglyceridemia. All randomized patients who received matching placebo in either of 2 treatment period
Change From Baseline in Total Exercise Duration (Part A, Cohort 1)	-1.52 minute Standard Error 0.46	-1.00 minute Standard Error 0.40	—	—

PRIMARY outcome

Timeframe: Baseline and on day 5 of each of the two treatment periods

Population: The study was terminated based on the interim analysis after patients completed Part A. This outcome measure was not part of interim analysis; hence it is not done. .

Time to onset of angina was defined as the elapsed time between the start of exercise and the onset of anginal chest pain as reported by the patient and recorded by the performing investigator.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Baseline and on day 5 of each of the two treatment periods

Population: The study was terminated based on the interim analysis after patients completed Part A. This outcome measure was not part of interim analysis; hence it is not done. .

Exercise-induced ischemia was defined as the new development of horizontal or down-sloping ST-segment depression (≥ 1mm at 60 milliseconds after the J point) versus baseline tracings.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Baseline and on treatment day 85 +/- 3 days

Population: The study was terminated based on the interim analysis after patients completed Part A. Part B of the study was never started.

This endpoint was palnned for analysis on Part B patients which was never started becasue study got terminated on Part A interim analysis.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: approximately 40 days

Population: The safety analysis set included all patients who received at least one dose of study drug.

Outcome measures

Outcome measures
Measure	Part A, Cohort 1: Pradigastat (LCQ908) n=17 Participants Cohort 1 consisted of patients with evidence of stable symptomatic or obstructive coronary artery disease and mild to moderate hypertriglyceridemia. All randomized patients who received pradigastat in either of 2 treatment period.	Part A, Cohort 1: Placebo n=17 Participants Cohort 1 consisted of patients with evidence of stable symptomatic or obstructive coronary artery disease and mild to moderate hypertriglyceridemia. All randomized patients who received matching placebo in either of 2 treatment period	Part A, Cohort 2: Pradigastat (LCQ908) Cohort 2 consisted of patients with stable asymptomatic non-obstructive coronary artery disease or coronary heart disease risk equivalents and mild to moderate hypertriglyceridemia.. All randomized patients who recieved pradigastat in either of 2 treatment period.	Part A, Cohort 2: Placebo Cohort 2 consisted of patients with stable asymptomatic non-obstructive coronary artery disease or coronary heart disease risk equivalents and mild to moderate hypertriglyceridemia. All randomized patients who received matching placebo in either of 2 treatment period
Number of Participants With Adverse Events (Part A, Cohort 1) Death	0 Participants	0 Participants	—	—
Number of Participants With Adverse Events (Part A, Cohort 1) Any Adverse Events	16 Participants	6 Participants	—	—
Number of Participants With Adverse Events (Part A, Cohort 1) Serious Adverse Events	0 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: approximately 40 days

Population: The safety analysis set included all patients who received at least one dose of study drug.

Outcome measures

Outcome measures
Measure	Part A, Cohort 1: Pradigastat (LCQ908) n=24 Participants Cohort 1 consisted of patients with evidence of stable symptomatic or obstructive coronary artery disease and mild to moderate hypertriglyceridemia. All randomized patients who received pradigastat in either of 2 treatment period.	Part A, Cohort 1: Placebo n=24 Participants Cohort 1 consisted of patients with evidence of stable symptomatic or obstructive coronary artery disease and mild to moderate hypertriglyceridemia. All randomized patients who received matching placebo in either of 2 treatment period	Part A, Cohort 2: Pradigastat (LCQ908) Cohort 2 consisted of patients with stable asymptomatic non-obstructive coronary artery disease or coronary heart disease risk equivalents and mild to moderate hypertriglyceridemia.. All randomized patients who recieved pradigastat in either of 2 treatment period.	Part A, Cohort 2: Placebo Cohort 2 consisted of patients with stable asymptomatic non-obstructive coronary artery disease or coronary heart disease risk equivalents and mild to moderate hypertriglyceridemia. All randomized patients who received matching placebo in either of 2 treatment period
Number of Participants With Adverse Events (Part A, Cohort 2) Any Adverse Events	22 Participants	15 Participants	—	—
Number of Participants With Adverse Events (Part A, Cohort 2) Serious Adverse Events	0 Participants	1 Participants	—	—
Number of Participants With Adverse Events (Part A, Cohort 2) Death	0 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: 0 hour (before breakfast), 2 and 4 hours post high-fat breakfast on day 5

Population: The efficacy analysis set included all patients who took more than 80% of study medication as assessed by drug accountability, had no major protocol deviations, and had a valid assessment of the primary efficacy variables at both baseline and post treatment visits.

For both each treatment period, postprandial triglycerides were measured on Day 5 i.e. on 0 hour(before breakfast), two hours and four hours post high-fat breakfast. Results are from an ANCOVA model on change from baseline in the log domain with log(baseline), treatment, sequence and period as fixed effects. Baseline is the Day -1 value within period. The data reported is ratio of geometric mean between post-treatment and baseline data.

Outcome measures

Outcome measures
Measure	Part A, Cohort 1: Pradigastat (LCQ908) n=16 Participants Cohort 1 consisted of patients with evidence of stable symptomatic or obstructive coronary artery disease and mild to moderate hypertriglyceridemia. All randomized patients who received pradigastat in either of 2 treatment period.	Part A, Cohort 1: Placebo n=16 Participants Cohort 1 consisted of patients with evidence of stable symptomatic or obstructive coronary artery disease and mild to moderate hypertriglyceridemia. All randomized patients who received matching placebo in either of 2 treatment period	Part A, Cohort 2: Pradigastat (LCQ908) Cohort 2 consisted of patients with stable asymptomatic non-obstructive coronary artery disease or coronary heart disease risk equivalents and mild to moderate hypertriglyceridemia.. All randomized patients who recieved pradigastat in either of 2 treatment period.	Part A, Cohort 2: Placebo Cohort 2 consisted of patients with stable asymptomatic non-obstructive coronary artery disease or coronary heart disease risk equivalents and mild to moderate hypertriglyceridemia. All randomized patients who received matching placebo in either of 2 treatment period
Postprandial Triglycerides (Part A, Cohort 1) Day 5 Hr 0	1.15 ratio Standard Error 1.08	0.97 ratio Standard Error 1.08	—	—
Postprandial Triglycerides (Part A, Cohort 1) Day 5 Hr 2	1.21 ratio Standard Error 1.08	1.40 ratio Standard Error 1.07	—	—
Postprandial Triglycerides (Part A, Cohort 1) Day 5 Hr 4	1.29 ratio Standard Error 1.09	1.71 ratio Standard Error 1.08	—	—

SECONDARY outcome

Timeframe: 0 hour (before breakfast), 2 and 4 hours post high-fat breakfast on day 5

For both each treatment period, postprandial triglycerides were measured on Day 5 i.e. on 0 hour (before breakfast), two hours and four hours post high-fat breakfast. Results are from an ANCOVA model on change from baseline in the log domain with log(baseline), treatment, sequence and period as fixed effects. Baseline is the Day -1 value within period. The data reported is ratio of geometric mean between post-treatment and baseline data.

Outcome measures

Outcome measures
Measure	Part A, Cohort 1: Pradigastat (LCQ908) n=19 Participants Cohort 1 consisted of patients with evidence of stable symptomatic or obstructive coronary artery disease and mild to moderate hypertriglyceridemia. All randomized patients who received pradigastat in either of 2 treatment period.	Part A, Cohort 1: Placebo n=19 Participants Cohort 1 consisted of patients with evidence of stable symptomatic or obstructive coronary artery disease and mild to moderate hypertriglyceridemia. All randomized patients who received matching placebo in either of 2 treatment period	Part A, Cohort 2: Pradigastat (LCQ908) Cohort 2 consisted of patients with stable asymptomatic non-obstructive coronary artery disease or coronary heart disease risk equivalents and mild to moderate hypertriglyceridemia.. All randomized patients who recieved pradigastat in either of 2 treatment period.	Part A, Cohort 2: Placebo Cohort 2 consisted of patients with stable asymptomatic non-obstructive coronary artery disease or coronary heart disease risk equivalents and mild to moderate hypertriglyceridemia. All randomized patients who received matching placebo in either of 2 treatment period
Postprandial Triglycerides (Part A, Cohort 2) Day 5 Hr 0	1.16 ratio Standard Error 1.08	1.09 ratio Standard Error 1.08	—	—
Postprandial Triglycerides (Part A, Cohort 2) Day 5 Hr 2	1.15 ratio Standard Error 1.07	1.38 ratio Standard Error 1.07	—	—
Postprandial Triglycerides (Part A, Cohort 2) Day 5 Hr 4	1.14 ratio Standard Error 1.08	1.56 ratio Standard Error 1.08	—	—

SECONDARY outcome

Timeframe: Part A: Day 4 and day 5 of each treatment period

Population: The study was terminated based on the interim analysis on Part A, Cohort 1 after patients completed Part A. The analysis of this assessment was not part of interim analysis; hence it is not done.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, day 4 and day 5 of each treatment period

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, day 4 and day 5, of each treatment period

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, day 4 and day 5, of each treatment period

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Part B; Baseline, day 15, day 43 and day 85

Population: The study was terminated based on the interim analysis on Part A, cohort 1 after patients completed Part A. Part B of the study was not commenced.

Outcome measures

Outcome data not reported

Adverse Events

Part A, Cohort 1: Pradigastat (LCQ908)

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Part A, Cohort 1: Placebo

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Part A, Cohort 2: Pradigastat (LCQ908)

Serious events: 0 serious events

Other events: 22 other events

Deaths: 0 deaths

Part A, Cohort 2: Placebo

Serious events: 1 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Part A, Cohort 1: Pradigastat (LCQ908) n=17 participants at risk Cohort 1 consisted of patients with evidence of stable symptomatic or obstructive coronary artery disease and mild to moderate hypertriglyceridemia. All randomized patients who received pradigastat in either of 2 treatment period.	Part A, Cohort 1: Placebo n=17 participants at risk Cohort 1 consisted of patients with evidence of stable symptomatic or obstructive coronary artery disease and mild to moderate hypertriglyceridemia. All randomized patients who received matching placebo in either of 2 treatment period	Part A, Cohort 2: Pradigastat (LCQ908) n=24 participants at risk Cohort 2 consisted of patients with stable asymptomatic non-obstructive coronary artery disease or coronary heart disease risk equivalents and mild to moderate hypertriglyceridemia.. All randomized patients who recieved pradigastat in either of 2 treatment period.	Part A, Cohort 2: Placebo n=24 participants at risk Cohort 2 consisted of patients with stable asymptomatic non-obstructive coronary artery disease or coronary heart disease risk equivalents and mild to moderate hypertriglyceridemia. All randomized patients who received matching placebo in either of 2 treatment period
Cardiac disorders Coronary artery disease	0.00% 0/17 The safety analysis set included all patients who received at least one dose of study drug.	0.00% 0/17 The safety analysis set included all patients who received at least one dose of study drug.	0.00% 0/24 The safety analysis set included all patients who received at least one dose of study drug.	4.2% 1/24 The safety analysis set included all patients who received at least one dose of study drug.

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
Publication restrictions are in place

Restriction type: OTHER

Measure	Part A, Cohort 1: Pradigastat (LCQ908) n=17 participants at risk Cohort 1 consisted of patients with evidence of stable symptomatic or obstructive coronary artery disease and mild to moderate hypertriglyceridemia. All randomized patients who received pradigastat in either of 2 treatment period.	Part A, Cohort 1: Placebo n=17 participants at risk Cohort 1 consisted of patients with evidence of stable symptomatic or obstructive coronary artery disease and mild to moderate hypertriglyceridemia. All randomized patients who received matching placebo in either of 2 treatment period	Part A, Cohort 2: Pradigastat (LCQ908) n=24 participants at risk Cohort 2 consisted of patients with stable asymptomatic non-obstructive coronary artery disease or coronary heart disease risk equivalents and mild to moderate hypertriglyceridemia.. All randomized patients who recieved pradigastat in either of 2 treatment period.	Part A, Cohort 2: Placebo n=24 participants at risk Cohort 2 consisted of patients with stable asymptomatic non-obstructive coronary artery disease or coronary heart disease risk equivalents and mild to moderate hypertriglyceridemia. All randomized patients who received matching placebo in either of 2 treatment period
Cardiac disorders Supraventricular extrasystoles	0.00% 0/17 The safety analysis set included all patients who received at least one dose of study drug.	5.9% 1/17 The safety analysis set included all patients who received at least one dose of study drug.	0.00% 0/24 The safety analysis set included all patients who received at least one dose of study drug.	0.00% 0/24 The safety analysis set included all patients who received at least one dose of study drug.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/17 The safety analysis set included all patients who received at least one dose of study drug.	0.00% 0/17 The safety analysis set included all patients who received at least one dose of study drug.	8.3% 2/24 The safety analysis set included all patients who received at least one dose of study drug.	4.2% 1/24 The safety analysis set included all patients who received at least one dose of study drug.
Gastrointestinal disorders Abdominal distension	11.8% 2/17 The safety analysis set included all patients who received at least one dose of study drug.	5.9% 1/17 The safety analysis set included all patients who received at least one dose of study drug.	20.8% 5/24 The safety analysis set included all patients who received at least one dose of study drug.	8.3% 2/24 The safety analysis set included all patients who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain	17.6% 3/17 The safety analysis set included all patients who received at least one dose of study drug.	0.00% 0/17 The safety analysis set included all patients who received at least one dose of study drug.	8.3% 2/24 The safety analysis set included all patients who received at least one dose of study drug.	4.2% 1/24 The safety analysis set included all patients who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain upper	5.9% 1/17 The safety analysis set included all patients who received at least one dose of study drug.	0.00% 0/17 The safety analysis set included all patients who received at least one dose of study drug.	20.8% 5/24 The safety analysis set included all patients who received at least one dose of study drug.	4.2% 1/24 The safety analysis set included all patients who received at least one dose of study drug.
Gastrointestinal disorders Constipation	0.00% 0/17 The safety analysis set included all patients who received at least one dose of study drug.	0.00% 0/17 The safety analysis set included all patients who received at least one dose of study drug.	4.2% 1/24 The safety analysis set included all patients who received at least one dose of study drug.	8.3% 2/24 The safety analysis set included all patients who received at least one dose of study drug.
Gastrointestinal disorders Diarrhoea	88.2% 15/17 The safety analysis set included all patients who received at least one dose of study drug.	5.9% 1/17 The safety analysis set included all patients who received at least one dose of study drug.	87.5% 21/24 The safety analysis set included all patients who received at least one dose of study drug.	33.3% 8/24 The safety analysis set included all patients who received at least one dose of study drug.
Gastrointestinal disorders Nausea	52.9% 9/17 The safety analysis set included all patients who received at least one dose of study drug.	5.9% 1/17 The safety analysis set included all patients who received at least one dose of study drug.	54.2% 13/24 The safety analysis set included all patients who received at least one dose of study drug.	20.8% 5/24 The safety analysis set included all patients who received at least one dose of study drug.
Gastrointestinal disorders Vomiting	35.3% 6/17 The safety analysis set included all patients who received at least one dose of study drug.	0.00% 0/17 The safety analysis set included all patients who received at least one dose of study drug.	25.0% 6/24 The safety analysis set included all patients who received at least one dose of study drug.	0.00% 0/24 The safety analysis set included all patients who received at least one dose of study drug.
General disorders Chest pain	5.9% 1/17 The safety analysis set included all patients who received at least one dose of study drug.	0.00% 0/17 The safety analysis set included all patients who received at least one dose of study drug.	0.00% 0/24 The safety analysis set included all patients who received at least one dose of study drug.	0.00% 0/24 The safety analysis set included all patients who received at least one dose of study drug.
General disorders Chills	5.9% 1/17 The safety analysis set included all patients who received at least one dose of study drug.	0.00% 0/17 The safety analysis set included all patients who received at least one dose of study drug.	0.00% 0/24 The safety analysis set included all patients who received at least one dose of study drug.	0.00% 0/24 The safety analysis set included all patients who received at least one dose of study drug.
Infections and infestations Urinary tract infection	0.00% 0/17 The safety analysis set included all patients who received at least one dose of study drug.	5.9% 1/17 The safety analysis set included all patients who received at least one dose of study drug.	0.00% 0/24 The safety analysis set included all patients who received at least one dose of study drug.	4.2% 1/24 The safety analysis set included all patients who received at least one dose of study drug.
Injury, poisoning and procedural complications Fibula fracture	5.9% 1/17 The safety analysis set included all patients who received at least one dose of study drug.	0.00% 0/17 The safety analysis set included all patients who received at least one dose of study drug.	0.00% 0/24 The safety analysis set included all patients who received at least one dose of study drug.	0.00% 0/24 The safety analysis set included all patients who received at least one dose of study drug.
Metabolism and nutrition disorders Decreased appetite	5.9% 1/17 The safety analysis set included all patients who received at least one dose of study drug.	0.00% 0/17 The safety analysis set included all patients who received at least one dose of study drug.	8.3% 2/24 The safety analysis set included all patients who received at least one dose of study drug.	0.00% 0/24 The safety analysis set included all patients who received at least one dose of study drug.
Metabolism and nutrition disorders Dehydration	0.00% 0/17 The safety analysis set included all patients who received at least one dose of study drug.	0.00% 0/17 The safety analysis set included all patients who received at least one dose of study drug.	8.3% 2/24 The safety analysis set included all patients who received at least one dose of study drug.	0.00% 0/24 The safety analysis set included all patients who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	5.9% 1/17 The safety analysis set included all patients who received at least one dose of study drug.	0.00% 0/17 The safety analysis set included all patients who received at least one dose of study drug.	0.00% 0/24 The safety analysis set included all patients who received at least one dose of study drug.	0.00% 0/24 The safety analysis set included all patients who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Fracture pain	5.9% 1/17 The safety analysis set included all patients who received at least one dose of study drug.	0.00% 0/17 The safety analysis set included all patients who received at least one dose of study drug.	0.00% 0/24 The safety analysis set included all patients who received at least one dose of study drug.	0.00% 0/24 The safety analysis set included all patients who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/17 The safety analysis set included all patients who received at least one dose of study drug.	5.9% 1/17 The safety analysis set included all patients who received at least one dose of study drug.	4.2% 1/24 The safety analysis set included all patients who received at least one dose of study drug.	4.2% 1/24 The safety analysis set included all patients who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Neck pain	5.9% 1/17 The safety analysis set included all patients who received at least one dose of study drug.	0.00% 0/17 The safety analysis set included all patients who received at least one dose of study drug.	0.00% 0/24 The safety analysis set included all patients who received at least one dose of study drug.	0.00% 0/24 The safety analysis set included all patients who received at least one dose of study drug.
Nervous system disorders Dizziness	0.00% 0/17 The safety analysis set included all patients who received at least one dose of study drug.	5.9% 1/17 The safety analysis set included all patients who received at least one dose of study drug.	0.00% 0/24 The safety analysis set included all patients who received at least one dose of study drug.	8.3% 2/24 The safety analysis set included all patients who received at least one dose of study drug.
Nervous system disorders Headache	11.8% 2/17 The safety analysis set included all patients who received at least one dose of study drug.	0.00% 0/17 The safety analysis set included all patients who received at least one dose of study drug.	16.7% 4/24 The safety analysis set included all patients who received at least one dose of study drug.	4.2% 1/24 The safety analysis set included all patients who received at least one dose of study drug.
Renal and urinary disorders Polyuria	5.9% 1/17 The safety analysis set included all patients who received at least one dose of study drug.	0.00% 0/17 The safety analysis set included all patients who received at least one dose of study drug.	4.2% 1/24 The safety analysis set included all patients who received at least one dose of study drug.	0.00% 0/24 The safety analysis set included all patients who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Dermatitis contact	0.00% 0/17 The safety analysis set included all patients who received at least one dose of study drug.	5.9% 1/17 The safety analysis set included all patients who received at least one dose of study drug.	4.2% 1/24 The safety analysis set included all patients who received at least one dose of study drug.	0.00% 0/24 The safety analysis set included all patients who received at least one dose of study drug.
Vascular disorders Flushing	5.9% 1/17 The safety analysis set included all patients who received at least one dose of study drug.	0.00% 0/17 The safety analysis set included all patients who received at least one dose of study drug.	0.00% 0/24 The safety analysis set included all patients who received at least one dose of study drug.	0.00% 0/24 The safety analysis set included all patients who received at least one dose of study drug.