Effect of Lapaquistat Acetate Combined With Fenofibrate on Blood Cholesterol Levels

Inclusion Criteria:

• Women of childbearing potential must not be pregnant as determined by a negative serum human chorionic gonadotropin, not lactating, not planning on becoming pregnant between Screening and 30 days following the last dose of study medication, and agreed to use acceptable forms of contraception during the study.
• Prior to Randomization, must have a mean low density lipoprotein cholesterol greater than or equal to 100 mg/dL (2.59 mmol/L) for 2 consecutive samples. The difference between the two individual low density lipoprotein cholesterol values not to exceed 15% of the higher value.
• Prior to Randomization, must have mean triglycerides greater than or equal to 150 and less than or equal to 600 mg/dL (1.70 and 6.78 mmol/L, respectively) for 2 consecutive samples. The upper value for either triglycerides sample must have been less than or equal to 650 mg/dL (7.35 mmol/L).
• Clinical laboratory evaluations (including clinical chemistry [fasted for at least 10 hours], hematology and urinalysis) within the reference range for the testing laboratory unless results deemed not clinically significant or considered within normal limits for this subject by the investigator or the sponsor.
• Willing and able to continue to comply with a standardized low cholesterol diet.

Exclusion Criteria:

• Alanine aminotransferase or aspartate aminotransferase level of greater than 1.5 times the upper limit of normal, active liver disease or jaundice.
• Serum creatinine greater than 1.5 mg/dL (133 μmol/L).
• Creatine phosphokinase greater than 3 times the upper limit of normal.
• Diabetes with a hemoglobin A1c greater than 8 % at Visit 1.
• Previous history of cancer in remission for less than 5 years prior to the first dose of study medication. Does not include those subjects with basal cell or stage I squamous cell carcinoma of the skin.
• An endocrine disorder, such as Cushing's syndrome, hyperthyroidism, or inappropriately treated hypothyroidism, affecting lipid metabolism. Subjects with hypothyroidism on appropriate replacement therapy (defined as stable thyroid hormone replacement therapy at least 3 months prior to Visit 1 and thyrotropin levels less than 1.5 times the upper limit of normal) are eligible for enrollment. If thyrotropin is greater than 1.5 times upper limit of normal, a free thyroxine level is to be determined. If the free thyroxine is within normal limits for that subject, the subject may continue in the study.
• History of myocardial infarction, unstable angina, transient ischemic attacks, cerebrovascular accident, percutaneous coronary intervention, coronary or peripheral arterial surgery (bypass graft surgery) in the 6 months prior to Visit 1.
• Positive hepatitis B surface antigen, or hepatitis C virus antibody, as determined by medical history and/or subject's verbal report.
• Positive human immunodeficiency virus status or is taking anti-retroviral medications, as determined by medical history and/or subject's verbal report.
• Unable or unwilling to discontinue excluded medications or to continue stable doses of "stable dose" medications or required treatment with any excluded medication during the study.
• Exposure to TAK-475 in other studies or currently is participating in another investigational study or has participated in an investigational study within the past 30 days or, for drugs with a long half-life, within a period of less than 5 times the drug's halflife.
• Known hypersensitivity or history of adverse reaction to any fibrate.
• History or presence of clinically significant food allergy that would prevent adherence to the therapeutic lifestyle change (or equivalent) diet.
• Known homozygous familial hypercholesterolemia or known Type III hyperlipoproteinemia (familial dysbetalipoproteinemia).
• Active cholecystitis or known cholelithiasis (a fibrate risk factor).
• Severe renal or hepatic dysfunction, including biliary cirrhosis during Run-In or at Randomization (a fibrate risk factor).
• Fibromyalgia, myopathy, rhabdomyolysis or unexplained muscle pain.
• Uncontrolled hypertension (defined as resting diastolic blood pressure greater than100 mm Hg or resting systolic blood pressure greater than 160 mm Hg) at Visit 1.
• Inflammatory bowel disease or any other malabsorption syndrome or has had gastric bypass or any other surgical procedure for weight loss.
• Unwilling or unable, in the opinion of the investigator, to comply with the protocol or scheduled appointments.
• Unable to understand verbal or written English or any other language for which a certified translation of the approved informed consent was available.
• History of drug abuse (defined as illicit drug use) or a history of alcohol abuse (defined as regular or daily consumption of more than 2 alcoholic drinks per day) within the past 2 years.
• Any other serious disease or condition at Screening or at Randomization that might reduce life expectancy, impair successful management according to the protocol, or make the subject an unsuitable candidate to receive study medication.