Efficacy of Lapaquistat Acetate and Simvastatin in Subjects With Primary Dyslipidemia.

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT00256178
• Date of registration: 16/11/2005
• Prospective Registration: No
• Primary sponsor: Takeda
• Public title: Efficacy of Lapaquistat Acetate and Simvastatin in Subjects With Primary Dyslipidemia.
• Scientific title: A Placebo-controlled, Double-blind, Randomized Study to Evaluate the Efficacy and Safety of TAK-475 50 mg and 100 mg Versus Placebo, When Co-administered With Simvastatin 20 mg or 40 mg in Subjects With Primary Dyslipidemia.
• Date of first enrolment: October 2005
• Target sample size: 411
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00256178
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
• Phase: Phase 3

Countries of recruitment

Czech Republic, Estonia, Finland, Germany, Poland, South Africa, United Kingdom

Contacts

• Name: Medical Director
• Affiliation: Takeda

Key inclusion & exclusion criteria

Inclusion Criteria:

- Females of childbearing potential who are sexually active must agree to use adequate
contraception from screening throughout the duration of the study and for 30 days
following the last dose.

- Has a documented history of dyslipidemia with or without cardiovascular risk factors
but without type 1 or 2 diabetes.

- Is on a stable dose of simvastatin, either 20 or 40 mg, for at least 4 weeks prior to
Screening.

- Prior to Randomization, the participant has a mean low density lipoprotein
cholesterol level greater than or equal to 100 mg/dL and less than or equal to 190
mg/dL for 2 consecutive samples.

- Prior to Randomization, the subject has mean triglyceride level greater than or equal
to 400 mg/dL for 2 consecutive samples.

- Is willing and able to comply with the recommended, standardized diet.

Exclusion Criteria:

- Has annine aminotransferase or aspartate aminotransferase level greater than 1.5
times the upper limit of normal, identified during screening.

- Has a serum creatinine greater than 133 mmol/L, identified during screening.

- Has a creatine kinase greater than 3 times the upper limit of normal, identified
during screening.

- Has active liver disease or jaundice.

- Has taken any bile acid sequestrants [eg, cholestyramine], and intestinal cholesterol
uptake inhibitors [eg, ezetimibe]) from 30 days before Screening until study
completion or any fibrates for 6 weeks before Visit 1.

- Has a previous history of cancer that has been in remission for less than 5 years
prior to the first dose of study medication.

- Has an endocrine disorder, such as Cushing's syndrome, hyperthyroidism, or
inappropriately treated hypothyroidism affecting lipid metabolism.

- Has a history of myocardial infarction, angina pectoris, unstable angina, transient
ischemic attacks, cerebrovascular accident, peripheral vascular disease, abdominal
aortic aneurysm, coronary angioplasty, coronary or peripheral arterial surgery, or
multiple risk factors that confer a 10-year risk for cardiovascular heart disease
greater than 20% based on Framingham risk scoring.

- Has a positive hepatitis B surface antigen or hepatitis C virus antibody test, as
determined by medical history.

- Has a positive human immunodeficiency virus status or is taking antiretroviral
medications, as determined by medical history and/or subject's verbal report.

- Has received any investigational medication 30 days prior to screening, (for drugs
with a long half-life, within a period of less than 5 times the drug's half-life) or
is participating in an investigational study.

- Has received lapaquistat acetate in a previous clinical study or as a therapeutic
agent.

- Has a history or presence of clinically significant food allergy that would prevent
adherence to the specialized diet.

- Has a known heterozygous or homozygous familial hypercholesterolemia or known type
III hyperlipoproteinemia (familial dysbetalipoproteinemia).

- Has fibromyalgia, myopathy, rhabdomyolysis, or unexplained muscle pain.

- Has uncontrolled hypertension

- Has had inflammatory bowel disease or any other malabsorption syndrome, or has had
gastric bypass or any other surgical procedure for weight loss.

- Has a history of drug abuse or a history of high alcohol intake within the previous 2
years.

- Has type 1 or 2 diabetes mellitus.



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Hypercholesterolemia

Intervention(s)

Drug: Lapaquistat acetate and simvastatin

Drug: Simvastatin

Primary Outcome(s)

Change from Baseline in fasting plasma Low Density Lipoprotein cholesterol [Time Frame: Week 24 or Final Visit]

Secondary Outcome(s)

Adverse Events [Time Frame: Weeks 2, 4, 8, 12, 16, 20, and 24 or Final Visit]

Best corrected visual acuity [Time Frame: Week 24 or Final Visit]

Percentage of subjects who achieve Low Density Lipoprotein cholesterol concentrations less than 1.81 mmol/L (70 mg/dL) [Time Frame: Week 24 or Final Visit]

Change from Baseline in non- High Density Lipoprotein cholesterol [Time Frame: Week 24 or Final Visit]

Change from Baseline in Very Low Density Lipoprotein cholesterol [Time Frame: Week 24 or Final Visit]

Change from Baseline in apolipoprotein A1 [Time Frame: Week 24 or Final Visit]

Change from Baseline in the ratio of Total Cholesterol/High Density Lipoprotein cholesterol [Time Frame: Week 24 or Final Visit]

Change from Baseline in apolipoprotein B [Time Frame: Week 24 or Final Visit]

Change from Baseline in high-sensitivity C-reactive protein [Time Frame: Week 24 or Final Visit]

Clinical Laboratory Tests [Time Frame: Weeks 2, 4, 8, 12, 16, 20, and 24 or Final Visit]

Physical Examination [Time Frame: Week 24 or Final Visit]

Percentage of subjects who achieve Low Density Lipoprotein cholesterol concentrations less than 2.59 mmol/L (100 mg/dL) [Time Frame: Week 24 or Final Visit]

Change from Baseline in the ratio of Low Density Lipoprotein cholesterol/High Density Lipoprotein cholesterol [Time Frame: Week 24 or Final Visit]

Change from Baseline in Triglycerides [Time Frame: Week 24 or Final Visit]

Vital Signs [Time Frame: Weeks 2, 4, 8, 12, 16, 20, and 24 or Final Visit]

12-lead Electrocardiogram [Time Frame: Timeframe: Weeks 12 and 24 or Final Visit]

Change from Baseline in High Density Lipoprotein cholesterol [Time Frame: Week 24 or Final Visit]

Change from Baseline in Total Cholesterol [Time Frame: Week 24 or Final Visit]

Percentage of subjects who achieve Low Density Lipoprotein cholesterol concentrations less than 3.37 mmol/L (130 mg/dL) [Time Frame: Week 24 or Final Visit]

Change from Baseline in the ratio of apolipoprotein A1/apolipoprotein B [Time Frame: Week 24 or Final Visit]

Secondary ID(s)

TAK-475/EC302

2005-002313-21

U1111-1122-8212

Source(s) of Monetary Support

Please refer to primary and secondary sponsors