Safety and Efficacy of Lapaquistat Acetate Taken Alone and With Atorvastatin in Subjects With Primary Dyslipidemia

NCT00487994 | Completed Phase 3 DMC

• 3 other identifiers: 01-04-TL-475-0022004-000775-34U1111-1122-7619
• Study Type: interventional
• Target: 2,130
• Locations: 17 countries
• Sites: 128

Brief Summary

The purpose of this study is to evaluate the overall safety of Lapaquistat Acetate, once daily (QD), by itself or in combination with atorvastatin in subjects with primary dyslipidemia.

Conditions

Dyslipidemia

Keywords

Hypercholesterolemia; Hyperlipidemia; Drug Therapy

Outcome Measures

Primary Outcomes (7)

• Lens Opacity Classification System findings

  Weeks 24, 48, 72, and 96 or Final Visit

• Best corrected visual acuity

  Weeks 24, 48, 72, and 96 or Final Visit

• Adverse Events

  Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96 or Final Visit

• Clinical Laboratory Tests

  Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96 or Final Visit

• Vital signs (blood pressure and pulse rate) and weight

  Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, 96 or Final Visit

• 12-lead Electrocardiogram

  Weeks 48 and 96 or Final Visit

• Physical Examination

  Weeks 48 and 96 or Final Visit

Secondary Outcomes (7)

• Change from Baseline in Low Density Lipoprotein cholesterol

  Week 96 or Final Visit

• Change from Baseline in High Density Lipoprotein cholesterol

  Week 96 or Final Visit

• Change from Baseline in Total Cholesterol

  Week 96 or Final Visit

• Change from Baseline in Triglycerides

  Week 96 or Final Visit

• Change from Baseline in Very Low Density Lipoprotein cholesterol

  Week 96 or Final Visit

Study Arms (3)

Lapaquistat Acetate 100 mg QD

EXPERIMENTAL

Drug: Lapaquistat acetate

Lapaquistat Acetate 100 mg QD + Atorvastatin 10 mg QD

EXPERIMENTAL

Drug: Lapaquistat acetate and atorvastatin

Atorvastatin 10 mg QD

ACTIVE COMPARATOR

Drug: Atorvastatin

Interventions

Lapaquistat acetate DRUG

Lapaquistat acetate 100 mg, tablets, orally, once daily and Atorvastatin placebo-matching capsules, orally, once daily for up to 96 weeks.

Also known as: TAK-475

Lapaquistat Acetate 100 mg QD

Lapaquistat acetate and atorvastatin DRUG

Lapaquistat acetate 100 mg, tablets, orally, once daily and Atorvastatin 10 mg, capsules, orally, once daily for up to 96 weeks.

Also known as: TAK-475, Lipitor

Lapaquistat Acetate 100 mg QD + Atorvastatin 10 mg QD

Atorvastatin DRUG

Lapaquistat acetate placebo-matching tablets, orally, once daily and Atorvastatin 10 mg, capsules, orally, once daily for up to 96 weeks.

Also known as: Lipitor

Atorvastatin 10 mg QD

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has a confirmatory central laboratory result with low density lipoprotein cholesterol greater than or equal to 3.37 mmol/L and less than 5.69 mmol/L, and triglyceride less than 4.52 mmol/L.
• Females of child-bearing age must have undergone surgical sterilization, hysterectomy, tubal ligation, or bilateral oophorectomy; other female subjects must have been postmenopausal.
• Must be in good physical and mental health as determined by a physician on the basis of medical history, physical examination, and laboratory results.
• Has a fasting low density lipoprotein cholesterol level greater than or equal to 3.37 mmol/L and less than 4.92 mmol/L, and a triglyceride value less than 4.52 mmol/L.

You may not qualify if:

• 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.
• A body mass index less than 15 or greater than 35.
• A history or presence of:
• Drug abuse or a history of alcohol abuse within the 2 years previous to screening.
• Uncontrolled hypertension despite medical treatment
• Thyroid disease, particularly hyperthyroidism or subjects whose thyroid replacement therapy was initiated within the previous 3 months.
• Human immunodeficiency virus-positive status, or hepatitis B or C infection.
• Malignancy, except subjects whose malignancy had been diagnosed as stage I basal or squamous cell carcinoma.
• Heterozygous or homozygous familial hypercholesterolemia or known type III hyperlipoproteinemia.
• Fibromyalgia, myopathy, rhabdomyolysis, or unexplained muscle pain and/or discontinuation of statins due to myalgia.
• Trauma to the eye or eye irradiation; glaucoma; iritis; uveitis; prior intraocular surgery, laser surgery to the iris, retinal photocoagulation, or laser trabeculoplasty; corneal opacification or other medial opacities; or had undergone LASIK refractive surgery within 6 months prior to screening.
• A clinically significant food allergy that would prevent adherence to the specialized diet.
• Any other serious disease or condition that might have affected life expectancy or made it difficult to successfully manage and monitor the subject according to the protocol.

Sponsors & Collaborators

• Takeda: lead

Study Sites (128)

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Birmingham, Alabama, United States

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Mobile, Alabama, United States

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Northport, Alabama, United States

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Chandler, Arizona, United States

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Phoenix, Arizona, United States

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Sierra Vista, Arizona, United States

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Jonesboro, Arkansas, United States

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Little Rock, Arkansas, United States

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Anaheim, California, United States

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Rancho Cucamonga, California, United States

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Santa Rosa, California, United States

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Golden, Colorado, United States

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Coral Gables, Florida, United States

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Fort Myers, Florida, United States

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Jacksonville, Florida, United States

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Sarasota, Florida, United States

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West Palm Beach, Florida, United States

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Dunwoody, Georgia, United States

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Boise, Idaho, United States

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Idaho Falls, Idaho, United States

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Arlington Heights, Illinois, United States

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Chicago, Illinois, United States

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Elk Grove Village, Illinois, United States

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Evansville, Indiana, United States

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Indianapolis, Indiana, United States

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Waterloo, Iowa, United States

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Kansas City, Kansas, United States

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Overland Park, Kansas, United States

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Louisville, Kentucky, United States

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New Orleans, Louisiana, United States

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Flint, Michigan, United States

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Edina, Minnesota, United States

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St Louis, Missouri, United States

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Omaha, Nebraska, United States

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Ship Bottom, New Jersey, United States

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Rochester, New York, United States

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Syracuse, New York, United States

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Charlotte, North Carolina, United States

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Statesville, North Carolina, United States

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Wilmington, North Carolina, United States

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Winston-Salem, North Carolina, United States

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Cincinnati, Ohio, United States

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Tulsa, Oklahoma, United States

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Philadelphia, Pennsylvania, United States

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Tipton, Pennsylvania, United States

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Anderson, South Carolina, United States

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Mt. Pleasant, South Carolina, United States

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Simpsonville, South Carolina, United States

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Cordova, Tennessee, United States

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Morristown, Tennessee, United States

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Corpus Christi, Texas, United States

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Dallas, Texas, United States

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Fort Worth, Texas, United States

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Houston, Texas, United States

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Plano, Texas, United States

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San Antonio, Texas, United States

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Temple, Texas, United States

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Texarkana, Texas, United States

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Norfolk, Virginia, United States

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Richmond, Virginia, United States

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Lakewood, Washington, United States

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Buenos Aires, Argentina

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Córdoba, Argentina

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La Plata, Argentina

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Morón, Argentina

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Pilar, Argentina

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Rosario, Argentina

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Salta, Argentina

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Santa Fe, Argentina

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Santiago, Chile

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Brno, Czechia

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Olomouc, Czechia

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Prague, Czechia

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Tartu, Estonia

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Berlin, Germany

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Freiburg im Breisgau, Germany

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Görlitz, Germany

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Hamburg, Germany

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Mannheim, Germany

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Mönchengladbach, Germany

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Munich, Germany

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Schwerin, Germany

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Budapest, Hungary

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Debrecen, Hungary

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Esztergom, Hungary

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Győr, Hungary

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Gyula, Hungary

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Kecskemét, Hungary

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Warszawa, Hungary

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Riga, Latvia

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Kaunas, Lithuania

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Vilnius, Lithuania

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Vilnius-21, Lithuania

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Distrito Federal, Mexico

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Guadalajara, Mexico

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Jalisco, Mexico

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Mexico City, Mexico

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San Luis Potosí City, Mexico

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Zapopan, Mexico

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Es Velp, Netherlands

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Groningen, Netherlands

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Leiden, Netherlands

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Rotterdam, Netherlands

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Zoetermeer, Netherlands

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Lima, Peru

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Bialystok, Poland

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Bydgoszcz, Poland

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Gdansk, Poland

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Gorzów Wielkopolski, Poland

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Grudziądz, Poland

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Płońsk, Poland

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Torun, Poland

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Wroclaw, Poland

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Włocławek, Poland

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Moscow, Russia

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Saint Petersburg, Russia

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Saratov, Russia

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Komárno, Slovakia

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Košice, Slovakia

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Levice, Slovakia

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Cape Town, South Africa

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Johannesburg, South Africa

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Parow, South Africa

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Western Cape, South Africa

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Truro, Cornwall, United Kingdom

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Blackpool, Lancashire, United Kingdom

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Bolton, Lancashire, United Kingdom

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Guildford, Surrey, United Kingdom

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Related Publications (1)

• 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.

  PMID: 21518985 RESULT

MeSH Terms

Conditions

Dyslipidemias; Hypercholesterolemia; Hyperlipidemias

Interventions

1-((1-(3-acetoxy-2,2-dimethylpropyl)-7-chloro-5-(2,3-dimethoxyphenyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl)acetyl)piperidine-4-acetic acid; Atorvastatin

Condition Hierarchy (Ancestors)

Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids

Study Officials

• Medical Director

  Takeda

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2007
• First Posted: June 19, 2007
• Study Start: November 1, 2004
• Primary Completion: May 1, 2007
• Study Completion: May 1, 2007
• Last Updated: May 24, 2012

Record last verified: 2012-05

Locations

GB (4); SL (3); HU (7); DE (8); AR (8); CZ (3); ES (1); PE (1); LA (1); ME (6); US (61); CL (1); NL (5); RU (3); LI (3); PL (9); ZA (4)