Clinical trial NCT00532558: Efficacy of Lapaquistat Acetate on Blood Cholesterol Levels in Treating Subjects With Hypercholesterolemia
Official title: A Double-Blind, Randomized Study to Evaluate the Efficacy and Safety of Lapaquistat Acetate 50 mg vs Placebo in Subjects With Hypercholesterolemia, With an Optional Open-Label Extension
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Hypercholesterolemia
Keywords: Hyperlipidemia
Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2007-09-20
Enrollment: 657
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to determine the reduction of LDL-cholesterol level after treatment with 50 mg per day of lapaquistat acetate once daily (QD).

Detailed description: This study is being conducted to determine the potential of lapaquistat acetate 50 mg per day to lower LDL-C levels compared with placebo. This study is also being conducted to further evaluate the safety and tolerability of lapaquistat acetate 50 mg over a period of 12 weeks. An optional, 48-week, open-label extension will follow the 12 week, double-blind treatment period to evaluate the long-term safety and tolerability of lapaquistat acetate 50 mg/day.

Eligibility 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.
* Prior to Randomization, the participant has a mean low density lipoprotein cholesterol level greater than or equal to 130 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 an nine 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 fibrates within 42 days of Visit 1 or any lipid-lowering therapy for at least 30 days prior to Screening.
* 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.

Primary outcomes:
measure: Change from Baseline in fasting plasma Low Density Lipoprotein cholesterol
timeFrame: Week 12 or Final Visit
Secondary outcomes:
measure: Change from Baseline in Total Cholesterol
timeFrame: Week 12 or Final Visit
measure: Change from Baseline in High Density Lipoprotein cholesterol
timeFrame: Week 12 or Final Visit
measure: Change from Baseline in Very Low Density Lipoprotein cholesterol
timeFrame: Week 12 or Final Visit
measure: Change from Baseline in apolipoprotein A1 Timeframe: Week 12 or Final Visit
timeFrame: Week 12 or Final Visit
measure: Change from Baseline in apolipoprotein B
timeFrame: Week 12 or Final Visit
measure: Change from Baseline in non- High Density Lipoprotein cholesterol
timeFrame: Week 12 or Final Visit
measure: Change from Baseline in the ratio of Low Density Lipoprotein cholesterol/High Density Lipoprotein cholesterol
timeFrame: Week 12 or Final Visit
measure: Change from Baseline in the ratio of Total Cholesterol/High Density Lipoprotein cholesterol
timeFrame: Week 12 or Final Visit
measure: Change from Baseline in the ratio of apolipoprotein A1/apolipoprotein B
timeFrame: Week 12 or Final Visit
measure: Change from Baseline in Triglycerides
timeFrame: Week 12 or Final Visit
Other outcomes:
Locations:
city: Tallinn
country: Estonia
city: Tartu
country: Estonia
city: Balatonfured
country: Hungary
city: Budapest
country: Hungary
city: Debrecen
country: Hungary
city: Pecs
country: Hungary
city: Szekszárd
country: Hungary
city: Érd
country: Hungary
city: Beer Sheva
country: Israel
city: Hadera
country: Israel
city: Haifa
country: Israel
city: Jerusalem
country: Israel
city: Kfar-Saba
country: Israel
city: Nahariya
country: Israel
city: Safed
country: Israel
city: Tel Aviv
country: Israel
city: Daugavpils
country: Latvia
city: Kuldiga
country: Latvia
city: Riga
country: Latvia
city: Amsterdam
country: Netherlands
city: Breda
country: Netherlands
city: GA Nijmegen
country: Netherlands
city: Groningen
country: Netherlands
city: Hoorn
country: Netherlands
city: Rotterdam
country: Netherlands
city: Utrecht
country: Netherlands
city: Zoetermeer
country: Netherlands
city: Elverum
country: Norway
city: Hamar
country: Norway
city: Kongsberg
country: Norway
city: Oslo
country: Norway
city: Ålesund
country: Norway
city: Moscow
country: Russian Federation
city: Saratov
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Tyumen
country: Russian Federation
city: Volgograd
country: Russian Federation
city: Bratislava
country: Slovakia
city: Dolný Kubín
country: Slovakia
city: Kosice
country: Slovakia
city: Nitra
country: Slovakia
city: Nové Mesto Nad Váhom
country: Slovakia
city: Trebišov
country: Slovakia
city: Cordoba
country: Spain
city: Madrid
country: Spain
city: Pontevedra
country: Spain
city: REUS (Tarragona)
country: Spain
city: Valencia
country: Spain
city: Dnepropetrovsk
country: Ukraine
city: Kharkiv
country: Ukraine
city: Kharkov
country: Ukraine
city: Kiev
country: Ukraine
city: Kyiv
country: Ukraine
city: Lutsk
country: Ukraine
city: Lviv
country: Ukraine
city: Belfast
country: United Kingdom
city: Bolton
country: United Kingdom
city: Glasgow, Scotland
country: United Kingdom
city: Oldham
country: United Kingdom
city: Paignton, Devon
country: United Kingdom
city: Sheffield
country: United Kingdom
Study officials:
affiliation: Takeda
name: Medical Director
role: STUDY_DIRECTOR
References: