Efficacy of LCQ908 on Cardiovascular Risk (im)

• Myocardial perfusion/coronary flow reserve (Part A and Part B of the study) [ Time Frame: Part A; Baseline, and on day 5 of each of the 2 treatment periods. Part B; Baseline and on treatment day 85 +/- 3 days ] [ Designated as safety issue: No ]
• Time to onset of angina (Part A and Part B) [ Time Frame: Part A; Baseline and on day 5 of each of the two treatment periods. Part B; Baseline and on treatment day 85 +/- 3 days. ] [ Designated as safety issue: No ]
• Time to onset of exercise-induced ischemia(Part A and Part B) [ Time Frame: Part A; Baseline and on day 5 of each of the two treatment periods. Part B; Baseline and on treatment day 85 +/- 3 days. ] [ Designated as safety issue: No ]
• Total exercise duration (Part A and Part B) [ Time Frame: Part A; Baseline and on day 5 of each of the two treatment periods. Part B; Baseline and on treatment day 85 +/- 3 days. ] [ Designated as safety issue: No ]
• Aortic plaque inflammation (Part B) [ Time Frame: Baseline and on treatment day 85 +/- 3 days ] [ Designated as safety issue: No ]

• Myocardial perfusion [ Time Frame: Up to 5 days during each of 2 treatment periods ] [ Designated as safety issue: No ]
  Changes in blood flow to the myocardium (heart muscle) will be determined before and after treatment
• Inflammation and myocardial perfusion [ Time Frame: Up to Day 85 days during treatment period ] [ Designated as safety issue: No ]
  Changes in inflammation as well as changes in blood flow to the myocardium (heart muscle) will be determined before and after treatment

• Postprandial triglycerides in Part A [ Time Frame: Part A: Day 5 of each treatment period ] [ Designated as safety issue: No ]
• Percentage of patients with adverse events (Part A and Part B) [ Time Frame: Part A: approximately 40 days, Part B: Up to 85 days + 30 days follow up ] [ Designated as safety issue: Yes ]
• Pharmacokinetics of LCQ908: Plasma concentration [ Time Frame: Part A: Day 4 and day 5 of each treatment period; Part B: Day 15, 29, 43, 57 and 85. ] [ Designated as safety issue: No ]
• Other related lipid parameters (Part A and Part B) [ Time Frame: Part A: Baseline, day 4 and day 5 of each treatment period. Part B; Baseline, day 15, day 43 and day 85. ] [ Designated as safety issue: No ]
• Interleukin-6 (IL-6) level (Part A and Part B) [ Time Frame: Part A: Baseline, day 4 and day 5, of each treatment period. Part B; Baseline, day 15, day 43 and day 85 ] [ Designated as safety issue: No ]
• Adiponectin level ( Part B) [ Time Frame: Part B; Baseline, day 15, day 43 and day 85 ] [ Designated as safety issue: No ]
• C-reactive protein (CRP) level (Part A and Part B) [ Time Frame: Part A: Baseline, day 4 and day 5, of each treatment period. Part B; Baseline, day 15, day 43 and day 85 ] [ Designated as safety issue: No ]

• Lipids [ Time Frame: Part A: Up to 5 days during each of two treatment periods; Part B: Up to 85 days during the treatment period ] [ Designated as safety issue: No ]
  The levels of lipids and related particles in the blood will be measured
• Biological Markers [ Time Frame: Part A: Up to 5 days during each of two treatment periods; Part B: Up to 85 days during treatment period ] [ Designated as safety issue: No ]
  The level of biological markers of physiologic process in the blood will be measured
• Safety and Tolerability [ Time Frame: Part A:Up to 5 days during each of two treatment periods; Part B: Up to 85 days during treatment period ] [ Designated as safety issue: Yes ]
  Safety and tolerability including percentage of adverse events, laboratory analysis, impact on vital signs (blood pressure and pulse rate) and impact on ECGs will be assessed.
• Levels of the study drug in the blood [ Time Frame: Part A: Up to 5 days during each of two treatment periods - daily; Part B: Up to 85 days during treatment period ] [ Designated as safety issue: No ]
  The level of the study drug in the blood will be measured at set points after the drug has been taken.

This is a study designed to evaluate the potential for the LCQ908 to impact cardiovascular risk.

• Coronary Artery Disease
• Hypertriglyceridemia

• Drug: LCQ908
  In Part A of the study subjects will be randomly assigned to one of two treatment sequences; 1) LCQ908 treatment, followed by washout period, followed by placebo or 2) placebo, followed by a washout period, followed by LCQ908 treatment. In Part B of the study, subjects will be randomly assigned to treatment with LCQ908
• Drug: Placebo
  In Part A of the study subjects will be randomly assigned to one of two treatment sequences; 1) LCQ908 treatment, followed by washout period, followed by placebo or 2) placebo, followed by a washout period, followed by LCQ908 treatment. In Part B of the study subjects will be randomly assigned to receive placebo

• Experimental: LCQ908

  In Part A of the study subjects will receive, in the relevant treatment sequence, an oral loading dose of LCQ908 dose followed by a lower treatment dose

  In Part B of the study, subjects randomized to receive LCQ908 will receive an oral loading dose of LCQ908 followed by a lower treatment dose.

  Intervention: Drug: LCQ908
• Placebo Comparator: Placebo
  In Part A of the study subjects will receive placebo in the relevant treatment sequence. In Part B of the study, subjects will be randomized to receive placebo
  Intervention: Drug: Placebo

Inclusion Criteria:

• History of coronary artery disease
• Elevated triglycerides
• On medication to help lower cholesterol

Exclusion Criteria:

• Poorly controlled diabetic patients and/or change in diabetic medication within 12 weeks of screening
• History of myocardial infarction (heart attack) within 6 months of screening
• History of a procedure to open a blocked coronary artery within 12 months of enrollment
• History of Coronary Artery Bypass Graft (CABG) surgery
• History of congestive heart failure
• History of significant heart valve disease