Efficacy of Lapaquistat Acetate Co-Administered With Current Lipid-Lowering Treatment on Blood Cholesterol Levels in Subjects With Homozygous Familial Hypercholesterolemia

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT00263081
• Date of registration: 06/12/2005
• Prospective Registration: No
• Primary sponsor: Takeda
• Public title: Efficacy of Lapaquistat Acetate Co-Administered With Current Lipid-Lowering Treatment on Blood Cholesterol Levels in Subjects With Homozygous Familial Hypercholesterolemia
• Scientific title: A Double-blind, Placebo-controlled, Randomized Study to Evaluate the Efficacy and Safety of TAK-475 or Placebo When Co-administered With Current Lipid-lowering Therapy in Subjects With Homozygous Familial Hypercholesterolemia.
• Date of first enrolment: November 2005
• Target sample size: 44
• Recruitment status: Terminated
• URL: http://clinicaltrials.gov/show/NCT00263081
• 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

Canada, France, Israel, Poland, United Kingdom, United States

Contacts

• Name: Medical Director
• Affiliation: Takeda

Key inclusion & exclusion criteria

Inclusion Criteria:

- Must be at least 8 years of age (12 years of age in Poland) and weigh greater than or
equal to 30 kg.

- Must have homozygous FH, as documented by genetic testing that confirmed 2 mutated
alleles at the LDL-receptor locus, or by the following clinical criteria:

- documented history of untreated fasting serum LDL-C >460 mg/dL (11.91 mmol/L).

- tendinous or cutaneous xanthomas and/or corneal arcus before age 10 and/or
premature coronary heart disease before age 20.

- Must be taking a stable, approved lipid-lowering drug regimen for a minimum of 8
weeks prior to Screening Visit 1 and were to continue that treatment for the duration
of the study.

- Female participants can not be pregnant, not lactating, not planning on becoming
pregnant and agree to use adequate contraception throughout the course of the study.

Exclusion Criteria:

- Has alanine aminotransferase or aspartate aminotransferase levels greater than 2
times the upper limit of normal, active liver disease, jaundice, or serum creatinine
>135 µmol/L (1.5 mg/dL) at screening.

- Has a creatine kinase greater than 3 times the upper limit of normal

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

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

- Is unable or unwilling to discontinue excluded medications or to continue stable
doses of 'stable dose' medications or would require treatment with any excluded
medication during the study.

- Is currently participating in another investigational study or 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 previous history of cancer that had been in remission for less than 5 years
prior to the first dose of study drug. This criterion was not to include those
subjects with basal cell or Stage 1 squamous cell carcinoma of the skin.

- Has known hypersensitivity or history of adverse reaction to lapaquistat acetate.

- Has a history of fibromyalgia, myopathy, rhabdomyolysis, or unexplained muscle pain.

- Has an endocrine disorder, such as Cushing Syndrome, hyperthyroidism, or
inappropriately treated hypothyroidism, affecting lipid metabolism. Subjects with
hypothyroidism on appropriate replacement therapy.

- Has uncontrolled hypertension despite medical treatment.

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

- Has a history of drug abuse or a history of alcohol abuse within the past 2 years.

- Has any other serious disease or condition at screening or at randomization that
might have reduced life expectancy, impaired successful management according to the
protocol, or made the subject an unsuitable candidate to receive study drug.



Age minimum: 8 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Hypercholesterolemia

Intervention(s)

Drug: Current lipid-lowering treatment

Drug: Lapaquistat acetate and current lipid-lowering treatment

Primary Outcome(s)

Change from Baseline in Low Density Lipoprotein cholesterol [Time Frame: Week 12 or Final Visit]

Secondary Outcome(s)

Change from Baseline in Very Low Density Lipoprotein cholesterol [Time Frame: Week 12 or Final Visit]

Change from Baseline in non- High Density Lipoprotein cholesterol [Time Frame: Week 12 or Final Visit]

Change from Baseline in apolipoprotein B [Time Frame: Week 12 or Final Visit]

Change from Baseline in the ratio of apolipoprotein A1/apolipoprotein B [Time Frame: Week 12 or Final Visit]

Change from Baseline in calculated Low Density Lipoprotein cholesterol [Time Frame: Week 12 or Final Visit]

Change from Baseline in High Density Lipoprotein cholesterol [Time Frame: Week 12 or Final Visit]

Change from Baseline in the ratio of Total Cholesterol/High Density Lipoprotein cholesterol [Time Frame: Week 12 or Final Visit]

Change from Baseline in Triglycerides [Time Frame: Week 12 or Final Visit]

Change from Baseline in high-sensitivity C-reactive protein [Time Frame: Week 12 or Final Visit]

Lipoprotein cholesterol/High Density Lipoprotein cholesterol [Time Frame: Week 12 or Final Visit]

Change from Baseline in apolipoprotein A1 [Time Frame: Week 12 or Final Visit]

Change from Baseline in Total Cholesterol [Time Frame: Week 12 or Final Visit]

Secondary ID(s)

01-05-TL-475-016

U1111-1122-7919

2005-003626-26

Source(s) of Monetary Support

Please refer to primary and secondary sponsors