NCT00256178

Brief Summary

The purpose of the study is to determine the efficacy of lapaquistat acetate, once daily (QD), taken with simvastatin on cholesterol levels in subjects with primary dyslipidemia

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
411

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Oct 2005

Geographic Reach
7 countries

53 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 1, 2005

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

November 16, 2005

Completed
5 days until next milestone

First Posted

Study publicly available on registry

November 21, 2005

Completed
1.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2007

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2007

Completed
Last Updated

May 24, 2012

Status Verified

May 1, 2012

Enrollment Period

1.4 years

First QC Date

November 16, 2005

Last Update Submit

May 23, 2012

Conditions

Keywords

HyperlipidemiaDrug Therapy

Outcome Measures

Primary Outcomes (1)

  • Change from Baseline in fasting plasma Low Density Lipoprotein cholesterol

    Week 24 or Final Visit

Secondary Outcomes (20)

  • Change from Baseline in Triglycerides

    Week 24 or Final Visit

  • Change from Baseline in Total Cholesterol

    Week 24 or Final Visit

  • Change from Baseline in High Density Lipoprotein cholesterol

    Week 24 or Final Visit

  • Change from Baseline in Very Low Density Lipoprotein cholesterol

    Week 24 or Final Visit

  • Change from Baseline in apolipoprotein A1

    Week 24 or Final Visit

  • +15 more secondary outcomes

Study Arms (3)

Lapaquistat Acetate 50 mg QD + Simvastatin

EXPERIMENTAL
Drug: Lapaquistat acetate and simvastatin

Lapaquistat Acetate 100 mg QD + Simvastatin

EXPERIMENTAL
Drug: Lapaquistat acetate and simvastatin

Simvastatin

ACTIVE COMPARATOR
Drug: Simvastatin

Interventions

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

Also known as: Lapaquistat, Zocor, TAK-475
Lapaquistat Acetate 50 mg QD + Simvastatin

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

Also known as: Zocor
Simvastatin

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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 dose of simvastatin, either 20 or 40 mg, for at least 4 weeks 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.

You may not qualify if:

  • 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, (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.
  • +4 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (53)

Unknown Facility

Benešov, Czechia

Location

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Holice V Čechách, Czechia

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Kladno, Czechia

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Mladá Boleslav, Czechia

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Olomouc, Czechia

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Prague, Czechia

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Trutnov, Czechia

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ĂšstĂ­ nad OrlicĂ­, Czechia

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ZlĂ­n, Czechia

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Pärnu, Estonia

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Tallinn, Estonia

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Tartu, Estonia

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Aura, Finland

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Helsinki, Finland

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Hyvinkää, Finland

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Oulu, Finland

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Tampere, Finland

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Turku, Finland

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Berlin, Germany

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Bochum, Germany

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Chemnitz, Germany

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Dresden, Germany

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Frankfurt, Germany

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Görlitz, Germany

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Leipzig, Germany

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Nuremberg, Germany

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Krakow, Poland

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Lublin, Poland

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Niemodlin, Poland

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Skierniewice, Poland

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Sroda Wlkp., Poland

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Starachowice, Poland

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Swietokrzyski, Poland

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Warsaw, Poland

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Zakopane, Poland

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Bloemfontein, South Africa

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Cape Town, South Africa

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Johannesburg, South Africa

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Pretoria, South Africa

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Randburg, South Africa

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Tongaat, South Africa

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Bath, United Kingdom

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Birmingham, United Kingdom

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Blackpool, United Kingdom

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Blantyre, United Kingdom

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Chippenham, United Kingdom

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Eastwood, United Kingdom

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Glasgow, United Kingdom

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Harrow, United Kingdom

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Hinckley, United Kingdom

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Newport Isle of Wight, United Kingdom

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Nottingham, United Kingdom

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Unknown Facility

Woolpit, United Kingdom

Location

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.

MeSH Terms

Conditions

HypercholesterolemiaHyperlipidemias

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 acidSimvastatin

Condition Hierarchy (Ancestors)

DyslipidemiasLipid Metabolism DisordersMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

LovastatinNaphthalenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPolycyclic Compounds

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

November 16, 2005

First Posted

November 21, 2005

Study Start

October 1, 2005

Primary Completion

March 1, 2007

Study Completion

March 1, 2007

Last Updated

May 24, 2012

Record last verified: 2012-05

Locations