Efficacy of Lapaquistat Acetate in Subjects Currently Treated With Lipid-Lowering Therapy.

NCT ID: NCT00251680

Last Updated: 2012-05-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 400 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-10-31
• Study Completion Date: 2007-05-31

Brief Summary

The purpose of the study is to determine the efficacy of lapaquistat acetate, once daily (QD), taken with established lipid-lowering therapy in subjects with type 2 diabetes mellitus.

Detailed Description

Diabetes mellitus is a recognized cause of secondary dyslipidemia, and is also independently considered to be a major cardiovascular risk factor requiring aggressive lipid-lowering treatment. Type 2 diabetes accounts for 85% to 90% of diabetes worldwide. It affects about 2% of the Caucasian population in most Westernized countries, and the prevalence rises with age to 10% in those over 70 years of age. Five percent or more of young- and middle-aged adults in some Asian or Afro-Caribbean groups in the United Kingdom have this condition. Approximately 12 million Americans have type 2 diabetes, and an estimated 20 million more have some degree of glucose intolerance. The greatest cause of mortality in type 2 diabetes is atherosclerotic vascular disease and its sequelae between 75% and 80% of adult subjects with diabetes die of macrovascular complications.

Lapaquistat acetate is a squalene synthase inhibitor currently under development at Takeda for the treatment of dyslipidemia. This study will evaluate the efficacy and safety of lapaquistat acetate co-administered with an established lipid-lowering therapy including atorvastatin, simvastatin, rosuvastatin, or fenofibrate in subjects with type 2 diabetes mellitus.

Conditions

Type 2 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Lapaquistat Acetate 50 mg QD

(and stable lipid-lowering therapy)

Group Type: EXPERIMENTAL

Lapaquistat acetate and lipid-lowering therapy

Intervention Type: DRUG

Lapaquistat acetate 50 mg, tablets, orally, once daily and stable lipid-lowering therapy for up to 24 weeks.

Stable Lipid-lowering therapy

Group Type: ACTIVE_COMPARATOR

Lipid-lowering therapy

Intervention Type: DRUG

Lapaquistat acetate placebo-matching tablets, tablets, orally, once daily and stable lipid-lowering therapy for up to 24 weeks.

Interventions

Lapaquistat acetate and lipid-lowering therapy

Lapaquistat acetate 50 mg, tablets, orally, once daily and stable lipid-lowering therapy for up to 24 weeks.

Intervention Type: DRUG

Lipid-lowering therapy

Lapaquistat acetate placebo-matching tablets, tablets, orally, once daily and stable lipid-lowering therapy for up to 24 weeks.

Intervention Type: DRUG

Other Intervention Names

TAK-475; Lipitor; Zocor; Crestor; Tricor; Lipitor; Zocor; Crestor; Tricor

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.
• Has a documented history of dyslipidemia with or without cardiovascular risk factors but without type 1 or 2 diabetes.
• Is on a stable antidiabetic regimen, which may have included oral antidiabetic medication and/or insulin, for at least 3 months 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, 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.
• Subject had a history of photoallergic or phototoxic reaction during treatment with a fibrate or ketoprofen.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Takeda

Locations

Tucson, Arizona, United States

Artesia, California, United States

Jacksonville, Florida, United States

Dunwoody, Georgia, United States

Idaho Falls, Idaho, United States

Aurora, Illinois, United States

Chicago, Illinois, United States

Melrose Park, Illinois, United States

Naperville, Illinois, United States

Overland Park, Kansas, United States

Livonia, Michigan, United States

Chesterfield, Missouri, United States

Margate City, New Jersey, United States

Trenton, New Jersey, United States

Cincinnati, Ohio, United States

Bristol, Tennessee, United States

San Antonio, Texas, United States

Richmond, Virginia, United States

Benešov, , Czechia

Holice V Cechach, , Czechia

Kladno, , Czechia

Mladá Boleslav, , Czechia

Olomouc, , Czechia

Prague, , Czechia

Trutnov, , Czechia

Ústí nad Orlicí, , Czechia

Zlín, , Czechia

Pärnu, , Estonia

Tallinn, , Estonia

Tartu, , Estonia

Helsinki, , Finland

Hyvinkää, , Finland

Tampere, , Finland

Turku, , Finland

Berlin, , Germany

Bochum, , Germany

Chemnitz, , Germany

Dresden, , Germany

Frankfurt, , Germany

Görlitz, , Germany

Leipzig, , Germany

Nuremberg, , Germany

Krakow, , Poland

Leszno, , Poland

Lublin, , Poland

Niemodlin, , Poland

Ostrowiec Świętokrzyski, , Poland

Skierniewice, , Poland

Sroda Wlkp, , Poland

Starachowice, , Poland

Warsaw, , Poland

Zakopane, , Poland

Banská Bystrica, , Slovakia

Bojnice, , Slovakia

Bratislava, , Slovakia

Lučenec, , Slovakia

Prešov, , Slovakia

Šamorín, , Slovakia

Žilina, , Slovakia

Bloemfontein, , South Africa

Cape Town, , South Africa

Durban, , South Africa

Lyttleton, , South Africa

Pretoria, , South Africa

Randburg, , South Africa

Bath, , United Kingdom

Birmingham, , United Kingdom

Blackpool, , United Kingdom

Blantyre, , United Kingdom

Chippenham, , United Kingdom

Edinburgh, , United Kingdom

Glasgow, , United Kingdom

Harrow, , United Kingdom

Hinckley, , United Kingdom

Newport, , United Kingdom

Nottingham, , United Kingdom

Woolpit, , United Kingdom

Countries

United States; Czechia; Estonia; Finland; Germany; Poland; Slovakia; South Africa; United Kingdom

References

Stein EA, Bays H, O'Brien D, Pedicano J, Piper E, Spezzi A. Lapaquistat acetate: development of a squalene synthase inhibitor for the treatment of hypercholesterolemia. Circulation. 2011 May 10;123(18):1974-85. doi: 10.1161/CIRCULATIONAHA.110.975284. Epub 2011 Apr 25.

Reference Type: RESULT

PMID: 21518985 (View on PubMed)

Other Identifiers

2005-002316-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1122-8281

Identifier Type: REGISTRY

Identifier Source: secondary_id

TAK-475/EC304

Identifier Type: -

Identifier Source: org_study_id