HypercholesterolemiaPhase 3NCT00286481
Efficacy of Lapaquistat Acetate Alone or Combined With Simvastatin in Subjects With Hypercholesterolemia
A Phase 3 study testing Lapaquistat acetate and simvastatin and Simvastatin in people with Hypercholesterolemia, run by Takeda at 67 sites in 2 countries.
Trial summary
The purpose of this study is to evaluate lapaquistat acetate, once daily (QD), taken alone or with simvastatin on cholesterol levels in treating patients with elevated cholesterol. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hypercholesterolemia
- What is being tested?
- Lapaquistat acetate and simvastatin and Simvastatin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,362 participants
- Where
- 67 sitesin 2 countries
- Study dates
- Mar 2006to May 2007
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Woman of childbearing potential can not to be pregnant, lactating, not planning on becoming pregnant, and agree to use acceptable forms of contraception throughout the course of the study.
- Prior to Randomization, has a low-density lipoprotein cholesterol level mean greater than or equal to 3.37 mmol/L and less than or equal to 5.70 mmol/L.
- Prior to Randomization, has a mean triglyceride level less than or equal to 4.52 mmol/L (400 mg/dL).
- Has clinical laboratory evaluations including clinical chemistry, hematology, and urinalysis within the defined reference range.
Who cannot join
- Has an alanine aminotransferase or aspartate aminotransferase level of greater than 1.5 times the upper limit of normal, active liver disease or jaundice.
- Has a serum creatinine of greater than 133 μmol/L.
- Has a creatine kinase greater than 3 times the upper limit of normal.
- Has type 1 or 2 diabetes mellitus.
- Has a previous history of cancer that had been in remission for less than 5 years prior to the first dose of study medication.
- Has an endocrine disorder, such as Cushing syndrome, hyperthyroidism, or inappropriately treated hypothyroidism, affecting lipid metabolism.
Show all 19Show fewer
- Has a history of myocardial infarction, angina pectoris, transient ischemic attacks, cerebrovascular accident, peripheral vascular disease, abdominal aortic aneurysm, coronary revascularization or multiple factors that conferred a 10-year risk for coronary heart disease greater than 20% based on Framingham risk scoring.
- Has a positive hepatitis B surface antigen, or antibody to hepatitis C virus, as determined by medical history and/or subject's verbal report.
- Has a positive human immunodeficiency virus status or was taking antiretroviral medications, as determined by medical history.
- Has exposure to lapaquistat acetate in other studies, was 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 known hypersensitivity or history of adverse reaction to simvastatin.
- Has a known hypersensitivity or history of adverse reaction to simvastatin.
- Has a history or presence of clinically significant food allergy that would prevent adherence to the recommended 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 inflammatory bowel disease, any other malabsorption syndrome, or had gastric bypass or any other surgical procedure for weight loss.
- Is unwilling or unable, in the opinion of the investigator, to comply with the protocol or scheduled appointments.
- Has a history of drug abuse or a history of alcohol abuse within the past 2 years.
- Has any other serious disease or condition that might reduced life expectancy, impaired successful management according to the protocol, or make the participant an unsuitable candidate to receive study medication.
Trial locations and contacts
67 sites in 2 countries.
67 sites in 2 countries
United States50 sites
Study site
Arlington Heights, Illinois
Study site
Bartlesville, Oklahoma
Study site
Beaver, Pennsylvania
Study site
Beverly Hills, California
Study site
Chandler, Arizona
Study site
Chicago, Illinois
Study site
Cincinnati, Ohio
Study site
Colorado Springs, Colorado
Study site
Columbus, Ohio
Study site
Downingtown, Pennsylvania
Study site
Edina, Minnesota
Study site
Goose Creek, South Carolina
Study site
Hialeah, Florida
Study site
Hollywood, Florida
Study site
Huntsville, Alabama
Study site
Indianapolis, Indiana
Study site
Jackson, Tennessee
Study site
Jacksonville, Florida
Study site
Jupiter, Florida
Study site
Kettering, Ohio
Study site
Kissimmee, Florida
Study site
Lakewood, Washington
Study site
Las Vegas, Nevada
Study site
Long Beach, California
Study site
Louisville, Kentucky
Study site
Margate City, New Jersey
Study site
Miami, Florida
Study site
Nashville, Tennessee
Study site
Norfolk, Virginia
Study site
Ocala, Florida
Study site
Overland Park, Kansas
Study site
Pembroke Pines, Florida
Study site
Peoria, Illinois
Study site
Pinellas Park, Florida
Study site
Portland, Oregon
Study site
Raleigh, North Carolina
Study site
Richmond, Virginia
Study site
Sacramento, California
Study site
San Antonio, Texas
Study site
Scottsdale, Arizona
Study site
Sierra Vista, Arizona
Study site
Spring Valley, California
Study site
St Louis, Missouri
Study site
Statesville, North Carolina
Study site
Stuart, Florida
Study site
Tipton, Pennsylvania
Study site
Tucson, Arizona
Study site
West Palm Beach, Florida
Study site
Wichita, Kansas
Study site
Winston-Salem, North Carolina
Canada17 sites
Study site
Abbotsford British Columbia, British Columbia
Study site
Coquitlam, British Columbia
Study site
Cornwall, Ontario
Study site
Cornwall, Prince Edward Island
Study site
London, Ontario
Study site
Mirabel, Quebec
Study site
Mount Pearl, Newfoundland and Labrador
Study site
Oakville, Ontario
Study site
Oshawa, Ontario
Study site
Saint-Lambert, Quebec
Study site
Sherbrooke, Quebec
Study site
St. John's, Newfoundland and Labrador
Study site
Ste-Foy, Quebec
Study site
Thornhill, Ontario
Study site
Toronto, Ontario
Study site
Victoria, British Columbia
Study site
Winnipeg, Manitoba
About this study
Official title: A Double-Blind, Randomized, Placebo-Controlled Factorial Study to Evaluate the Efficacy and Safety of Lapaquistat and Simvastatin Alone and in Combination in Subjects With Hypercholesterolemia
The purpose of this study is to evaluate lapaquistat acetate, once daily (QD), taken alone or with simvastatin on cholesterol levels in treating patients with elevated cholesterol.
Read the detailed description
Elevated plasma cholesterol (hypercholesterolemia) and various other plasma lipid imbalances (dyslipidemias) are major risk factors for coronary heart disease. Patients with hypercholesterolemia have elevated low-density lipoprotein cholesterol, which leads to atherosclerotic deposition of cholesterol in the arterial walls. As identified by the National Cholesterol Education Program Adult Treatment Panel III, lowering the low-density lipoprotein cholesterol plasma concentration effectively reduces cardiovascular morbidity and mortality and is essential for the prevention and management of coronary heart disease.
Currently, 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) are the first-line monotherapies prescribed to reduce low-density lipoprotein cholesterol, after diet and therapeutic lifestyle change. However, low doses of statins often fail to produce the ATP III-recommended levels of low-density lipoprotein cholesterol reduction, making it necessary to increase the dose or add an additional treatment. Dose increases of statins in turn may result in decreased tolerability and potential safety concerns which contribute to the high discontinuation rates of statins and their prescription at low, and often ineffective, doses.
The purpose of this study is to determine whether administration of lapaquistat acetate co-administered with simvastatin will be more efficacious in lowering low-density lipoprotein cholesterol, compared to lapaquistat or simvastatin alone. Total participation time in this study is anticipated to be 19 weeks.
- Conditions
- Hypercholesterolemia
- Being tested
- Lapaquistat acetate and simvastatin, Simvastatin
- Keywords
- Hyperlipidemia, Drug Therapy
- Medical subject headings
- Hypercholesterolemia, Hyperlipidemias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lapaquistat acetate and simvastatinDrug
Also called TAK-475, Zocor
Lapaquistat acetate 50 mg, tablets, orally, once daily and stable dose of simvastatin for up to 12 weeks.
Lapaquistat acetate and simvastatinDrug
Also called TAK-475, Zocor
Lapaquistat acetate 100 mg, tablets, orally, once daily and stable dose of simvastatin for up to 12 weeks.
SimvastatinDrug
Also called Zocor
Lapaquistat acetate placebo-matching tablets, orally, once daily and stable dose of simvastatin for up to 12 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Lapaquistat Acetate 50 mg QD + Simvastatin | Experimental | Not described Receives: Drug: Lapaquistat acetate and simvastatin |
| Lapaquistat Acetate 100 mg QD + Simvastatin | Experimental | Not described Receives: Drug: Lapaquistat acetate and simvastatin |
| Simvastatin | Active comparator | Not described Receives: Drug: Simvastatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from Baseline in Low Density Lipoprotein cholesterol
Measured: Week 12 or Final Visit
Secondary outcomes (20)
Adverse Events
Measured: Weeks: 2, 4, 8, and 12 or Final Visit
Physical Examination
Measured: Week 12 or Final Visit
Safety Laboratory Tests
Measured: Weeks: 2, 4, 8, and 12 or Final Visit
12- lead Electrocardiogram assessments
Measured: Week 12 or Final Visit
Best Corrected Visual Acuity results
Measured: Week 12 or Final Visit
Vital Signs
Measured: Weeks: 2, 4, 8, and 12 or Final Visit
Change from Baseline in Triglycerides
Measured: Week 12 or Final Visit
Change from Baseline in Total Cholesterol
Measured: Week 12 or Final Visit
Change from Baseline in High Density Lipoprotein cholesterol
Measured: Week 12 or Final Visit
Change from Baseline in Very Low Density Lipoprotein cholesterol
Measured: Week 12 or Final Visit
Change from Baseline in apolipoprotein A1
Measured: Week 12 or Final Visit
Change from Baseline in apolipoprotein B
Measured: Week 12 or Final Visit
Change from Baseline in non- High Density Lipoprotein cholesterol
Measured: Week 12 or Final Visit
Change from Baseline in the ratio of Low Density Lipoprotein cholesterol/High Density
Measured: Week 12 or Final Visit
Change from Baseline in the ratio of Total Cholesterol/High Density Lipoprotein cholesterol
Measured: Week 12 or Final Visit
Change from Baseline in the ratio of apolipoprotein A1/apolipoprotein B
Measured: Week 12 or Final Visit
Change from Baseline in high-sensitivity C-reactive protein
Measured: Week 12 or Final Visit
Percentage of subjects who achieve Low Density Lipoprotein cholesterol concentrations less than 2.59 mmol/L (100 mg/dL)
Measured: Week 12 or Final Visit
Percentage of subjects who achieve Low Density Lipoprotein cholesterol concentrations less than 3.37 mmol/L (130 mg/dL)
Measured: Week 12 or Final Visit
Percentage of subjects who achieve Low Density Lipoprotein cholesterol concentrations less than 4.14 mmol/L (160 mg/dL)
Measured: Week 12 or Final Visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2006 (estimated)
- Study startMar 2006
- Primary completionMay 2007
- Study completionMay 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HypercholesterolemiaStudies of the same condition, open and under way.
- More trials run by TakedaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,362 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00286481
- Sponsor's protocol ID
- 01-05-TL-475-020
- Other IDs
- U1111-1122-7978
- Status last verified
- May 2012
- First submitted
- 1 Feb 2006
- Last updated
- 24 May 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 21518985
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-Blind, Randomized, Placebo-Controlled Factorial Study to Evaluate the Efficacy and Safety of Lapaquistat and Simvastatin Alone and in Combination in Subjects With Hypercholesterolemia
- ClinicalTrials.gov ID
- NCT00286481
- Acronym / sponsor ID
- 01-05-TL-475-020
- Conditions
- Hypercholesterolemia
- Keywords
- Hyperlipidemia, Drug Therapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,362 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Study start
- Mar 2006
- Primary completion
- May 2007 (actual)
- Study completion
- May 2007 (actual)
- First posted
- 3 Feb 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate lapaquistat acetate, once daily (QD), taken alone or with simvastatin on cholesterol levels in treating patients with elevated cholesterol.
Detailed description
Elevated plasma cholesterol (hypercholesterolemia) and various other plasma lipid imbalances (dyslipidemias) are major risk factors for coronary heart disease. Patients with hypercholesterolemia have elevated low-density lipoprotein cholesterol, which leads to atherosclerotic deposition of cholesterol in the arterial walls. As identified by the National Cholesterol Education Program Adult Treatment Panel III, lowering the low-density lipoprotein cholesterol plasma concentration effectively reduces cardiovascular morbidity and mortality and is essential for the prevention and management of coronary heart disease.
Currently, 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) are the first-line monotherapies prescribed to reduce low-density lipoprotein cholesterol, after diet and therapeutic lifestyle change. However, low doses of statins often fail to produce the ATP III-recommended levels of low-density lipoprotein cholesterol reduction, making it necessary to increase the dose or add an additional treatment. Dose increases of statins in turn may result in decreased tolerability and potential safety concerns which contribute to the high discontinuation rates of statins and their prescription at low, and often ineffective, doses.
The purpose of this study is to determine whether administration of lapaquistat acetate co-administered with simvastatin will be more efficacious in lowering low-density lipoprotein cholesterol, compared to lapaquistat or simvastatin alone. Total participation time in this study is anticipated to be 19 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Woman of childbearing potential can not to be pregnant, lactating, not planning on becoming pregnant, and agree to use acceptable forms of contraception throughout the course of the study.
- Prior to Randomization, has a low-density lipoprotein cholesterol level mean greater than or equal to 3.37 mmol/L and less than or equal to 5.70 mmol/L.
- Prior to Randomization, has a mean triglyceride level less than or equal to 4.52 mmol/L (400 mg/dL).
- Has clinical laboratory evaluations including clinical chemistry, hematology, and urinalysis within the defined reference range.
Key exclusion criteria (19 listed)
- Has an alanine aminotransferase or aspartate aminotransferase level of greater than 1.5 times the upper limit of normal, active liver disease or jaundice.
- Has a serum creatinine of greater than 133 μmol/L.
- Has a creatine kinase greater than 3 times the upper limit of normal.
- Has type 1 or 2 diabetes mellitus.
- Has a previous history of cancer that had been in remission for less than 5 years prior to the first dose of study medication.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lapaquistat acetate and simvastatinAlso: TAK-475, ZocorLapaquistat acetate 50 mg, tablets, orally, once daily and stable dose of simvastatin for up to 12 weeks. | Drug | Lapaquistat Acetate 50 mg QD + Simvastatin |
| Lapaquistat acetate and simvastatinAlso: TAK-475, ZocorLapaquistat acetate 100 mg, tablets, orally, once daily and stable dose of simvastatin for up to 12 weeks. | Drug | Lapaquistat Acetate 100 mg QD + Simvastatin |
| SimvastatinAlso: ZocorLapaquistat acetate placebo-matching tablets, orally, once daily and stable dose of simvastatin for up to 12 weeks. | Drug | Simvastatin |
Primary outcome
Change from Baseline in Low Density Lipoprotein cholesterol
Time frame: Week 12 or Final Visit
20 secondary outcomes
Adverse Events
Time frame: Weeks: 2, 4, 8, and 12 or Final Visit
Physical Examination
Time frame: Week 12 or Final Visit
Safety Laboratory Tests
Time frame: Weeks: 2, 4, 8, and 12 or Final Visit
12- lead Electrocardiogram assessments
Time frame: Week 12 or Final Visit
Best Corrected Visual Acuity results
Time frame: Week 12 or Final Visit
Vital Signs
Time frame: Weeks: 2, 4, 8, and 12 or Final Visit
Change from Baseline in Triglycerides
Time frame: Week 12 or Final Visit
Change from Baseline in Total 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 Very Low 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 apolipoprotein B
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 the ratio of Low Density Lipoprotein cholesterol/High Density
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 the ratio of apolipoprotein A1/apolipoprotein B
Time frame: Week 12 or Final Visit
Change from Baseline in high-sensitivity C-reactive protein
Time frame: Week 12 or Final Visit
Percentage of subjects who achieve Low Density Lipoprotein cholesterol concentrations less than 2.59 mmol/L (100 mg/dL)
Time frame: Week 12 or Final Visit
Percentage of subjects who achieve Low Density Lipoprotein cholesterol concentrations less than 3.37 mmol/L (130 mg/dL)
Time frame: Week 12 or Final Visit
Percentage of subjects who achieve Low Density Lipoprotein cholesterol concentrations less than 4.14 mmol/L (160 mg/dL)
Time frame: Week 12 or Final Visit
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 May 2012.
- Results publication: PubMed 21518985Stein 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Takeda
67 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Lapaquistat acetate and simvastatin and Simvastatin in people with Hypercholesterolemia, run by Takeda at 67 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 May 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 67 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from Baseline in Low Density Lipoprotein cholesterol (time frame: Week 12 or Final Visit). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00286481, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 May 2012.