Efficacy of Lapaquistat Acetate Alone and With Ezetimibe in Subjects With Primary Dyslipidemia.

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT00268697
• Date of registration: 20/12/2005
• Prospective Registration: No
• Primary sponsor: Takeda
• Public title: Efficacy of Lapaquistat Acetate Alone and With Ezetimibe in Subjects With Primary Dyslipidemia.
• Scientific title: A Double-Blind, Double-Dummy, Randomized, Parallel Group, Multicenter, Phase 3 Study to Evaluate the Efficacy and Safety of Lapaquistat Acetate 100 mg and Lapaquistat Acetate 100 mg Administered in Combination With Ezetimibe 10 mg vs Ezetimibe 10 mg in Subjects With Primary Dyslipidemia
• Date of first enrolment: October 2005
• Target sample size: 1267
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00268697
• 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

Estonia, Former Serbia and Montenegro, Latvia, Russian Federation, Serbia

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.

- At Randomization, participants must fulfill the above criteria and also have a mean
fasting low density lipoprotein cholesterol levels greater than or equal to 3.36
mmol/L and less than or equal to 5.6 mmol/L and mean triglyceride levels less than or
equal to 4.52 mmol/L.

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

Exclusion Criteria:

- Has active liver disease or jaundice.

- Has a history of cancer, other than basal cell carcinoma, that had been in remission
for less than 5 years prior to the first dose of study drug.

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

- Has a positive hepatitis B surface antigen or hepatitis C virus antibody, as
determined by medical history and/or the subject's verbal report.

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

- Has participated in any other clinical studies with lapaquistat acetate, was
concurrently participating in another investigational study, had 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 half-life.

- Has a known hypersensitivity or history of intolerance to lapaquistat acetate or
ezetimibe.

- 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 and/or
discontinuation of HMG-CoA reductase inhibitors due to myalgia at any time.

- Has uncontrolled hypertension despite medical treatment.

- Has inflammatory bowel or any other malabsorption syndrome or had had gastric bypass
surgery 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 any other serious disease or condition at Visit 1 or Randomization that might
reduce life expectancy, impaired successful management according to the protocol, or
make the participant unsuitable to receive study drug.

- Has a history of coronary heart disease or coronary heart disease-risk factors
comprised of:

- Diabetes mellitus type 1 or 2

- History or presence of myocardial infarction, angina pectoris, unstable angina,
coronary angioplasty, coronary or peripheral arterial surgery (bypass graft),
aortic aneurysm, transient ischemic attacks, or cerebrovascular accident;

- Multiple risk factors that confer a 10-year risk of coronary heart disease
greater than 20% based on the Framingham risk score.



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

Health Condition(s) or Problem(s) studied

Hypercholesterolemia

Intervention(s)

Drug: Ezetimibe

Drug: Lapaquistat acetate

Drug: Lapaquistat acetate and ezetimibe

Primary Outcome(s)

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

Secondary Outcome(s)

Change from Baseline in the ratio of Total Cholesterol/High Density Lipoprotein cholesterol [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]

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]

Change from Baseline in high-sensitivity C-reactive protein [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 apolipoprotein A1/apolipoprotein B [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 non- High Density Lipoprotein cholesterol [Time Frame: Week 24 or Final Visit]

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

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

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

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

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

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

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

Secondary ID(s)

2005-002315-25

U1111-1122-8322

TAK-475/EC303

Source(s) of Monetary Support

Please refer to primary and secondary sponsors