HyperlipidemiasPhase 2NCT00813527
Effect of Lapaquistat Acetate Combined With Fenofibrate on Blood Cholesterol Levels
A Phase 2 study testing Lapaquistat acetate and fenofibrate and Fenofibrate in people with Hyperlipidemias, run by Takeda at 36 sites in 2 countries.
Trial summary
The purpose of this study is to compare changes in cholesterol levels in patients with elevated blood cholesterol with administration of lapaquistat acetate, once daily (QD), and fenofibrate. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hyperlipidemias
- What is being tested?
- Lapaquistat acetate and fenofibrate and Fenofibrate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 213 participants
- Where
- 36 sitesin 2 countries
- Study dates
- Feb 2006to Jan 2007
- Phase
- Phase 2
- 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
- Women of childbearing potential must not be pregnant as determined by a negative serum human chorionic gonadotropin, not lactating, not planning on becoming pregnant between Screening and 30 days following the last dose of study medication, and agreed to use acceptable forms of contraception during the study.
- Prior to Randomization, must have a mean low density lipoprotein cholesterol greater than or equal to 100 mg/dL (2.59 mmol/L) for 2 consecutive samples. The difference between the two individual low density lipoprotein cholesterol values not to exceed 15% of the higher value.
- Prior to Randomization, must have mean triglycerides greater than or equal to 150 and less than or equal to 600 mg/dL (1.70 and 6.78 mmol/L, respectively) for 2 consecutive samples. The upper value for either triglycerides sample must have been less than or equal to 650 mg/dL (7.35 mmol/L).
- Clinical laboratory evaluations (including clinical chemistry [fasted for at least 10 hours], hematology and urinalysis) within the reference range for the testing laboratory unless results deemed not clinically significant or considered within normal limits for this subject by the investigator or the sponsor.
- Willing and able to continue to comply with a standardized low cholesterol diet.
Who cannot join
- Alanine aminotransferase or aspartate aminotransferase level of greater than 1.5 times the upper limit of normal, active liver disease or jaundice.
- Serum creatinine greater than 1.5 mg/dL (133 μmol/L).
- Creatine phosphokinase greater than 3 times the upper limit of normal.
- Diabetes with a hemoglobin A1c greater than 8 % at Visit 1.
- Previous history of cancer in remission for less than 5 years prior to the first dose of study medication. Does not include those subjects with basal cell or stage I squamous cell carcinoma of the skin.
- An endocrine disorder, such as Cushing's syndrome, hyperthyroidism, or inappropriately treated hypothyroidism, affecting lipid metabolism. Subjects with hypothyroidism on appropriate replacement therapy (defined as stable thyroid hormone replacement therapy at least 3 months prior to Visit 1 and thyrotropin levels less than 1.5 times the upper limit of normal) are eligible for enrollment. If thyrotropin is greater than 1.5 times upper limit of normal, a free thyroxine level is to be determined. If the free thyroxine is within normal limits for that subject, the subject may continue in the study.
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- History of myocardial infarction, unstable angina, transient ischemic attacks, cerebrovascular accident, percutaneous coronary intervention, coronary or peripheral arterial surgery (bypass graft surgery) in the 6 months prior to Visit 1.
- Positive hepatitis B surface antigen, or hepatitis C virus antibody, as determined by medical history and/or subject's verbal report.
- Positive human immunodeficiency virus status or is taking anti-retroviral medications, as determined by medical history and/or subject's verbal report.
- Unable or unwilling to discontinue excluded medications or to continue stable doses of "stable dose" medications or required treatment with any excluded medication during the study.
- Exposure to TAK-475 in other studies or currently is participating in another investigational study or has 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 halflife.
- Known hypersensitivity or history of adverse reaction to any fibrate.
- History or presence of clinically significant food allergy that would prevent adherence to the therapeutic lifestyle change (or equivalent) diet.
- Known homozygous familial hypercholesterolemia or known Type III hyperlipoproteinemia (familial dysbetalipoproteinemia).
- Active cholecystitis or known cholelithiasis (a fibrate risk factor).
- Severe renal or hepatic dysfunction, including biliary cirrhosis during Run-In or at Randomization (a fibrate risk factor).
- Fibromyalgia, myopathy, rhabdomyolysis or unexplained muscle pain.
- Uncontrolled hypertension (defined as resting diastolic blood pressure greater than100 mm Hg or resting systolic blood pressure greater than 160 mm Hg) at Visit 1.
- Inflammatory bowel disease or any other malabsorption syndrome or has had gastric bypass or any other surgical procedure for weight loss.
- Unwilling or unable, in the opinion of the investigator, to comply with the protocol or scheduled appointments.
- Unable to understand verbal or written English or any other language for which a certified translation of the approved informed consent was available.
- History of drug abuse (defined as illicit drug use) or a history of alcohol abuse (defined as regular or daily consumption of more than 2 alcoholic drinks per day) within the past 2 years.
- Any other serious disease or condition at Screening or at Randomization that might reduce life expectancy, impair successful management according to the protocol, or make the subject an unsuitable candidate to receive study medication.
Trial locations and contacts
36 sites in 2 countries.
36 sites in 2 countries
United States32 sites
Study site
Beaver, Pennsylvania
Study site
Beverly Hills, California
Study site
Chicago, Illinois
Study site
Cincinnati, Ohio
Study site
Colorado Springs, Colorado
Study site
Columbus, Ohio
Study site
Edina, Minnesota
Study site
Golden, Colorado
Study site
Goose Creek, South Carolina
Study site
Hillsboro, Oregon
Study site
Huntsville, Alabama
Study site
Indianapolis, Indiana
Study site
Jacksonville, Florida
Study site
Kissimmee, Florida
Study site
Long Beach, California
Study site
Miami, Florida
Study site
Nashville, Tennessee
Study site
Norfolk, Virginia
Study site
Ocala, Florida
Study site
Pembroke Pines, Florida
Study site
Peoria, Illinois
Study site
Pinellas Park, Florida
Study site
Raleigh, North Carolina
Study site
Richmond, Virginia
Study site
Sierra Vista, Arizona
Study site
Spring Valley, California
Study site
St Louis, Missouri
Study site
Warner Robins, Georgia
Study site
Waterbury, Connecticut
Study site
West Palm Beach, Florida
Study site
Wichita, Kansas
Study site
Winston-Salem, North Carolina
Canada4 sites
Study site
Coquitlam, British Columbia
Study site
London, Ontario
Study site
Toronto, Ontario
Study site
Victoria, British Columbia
About this study
Official title: A Double-blind, Randomized Study to Evaluate the Efficacy and Safety of TAK-475 or Placebo When Coadministered With Fenofibrate in Subjects With Combined Hyperlipidemia
The purpose of this study is to compare changes in cholesterol levels in patients with elevated blood cholesterol with administration of lapaquistat acetate, once daily (QD), and fenofibrate.
Read the detailed description
Elevated plasma cholesterol (hypercholesterolemia) and various other plasma lipid imbalances (dyslipidemias) are major risk factors for coronary heart disease. It has been established that lowering the low-density lipoprotein cholesterol plasma concentration effectively reduces cardiovascular morbidity and mortality. As a result of this finding, the National Cholesterol Education Program Adult Treatment Panel III identifies control of low-density lipoprotein cholesterol as essential in 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 Adult Treatment Panel III-recommended levels of low-density lipoprotein cholesterol reduction, making it necessary to increase the dose or add an additional treatment. This in turn may result in decreased tolerability and potential safety concerns.
At higher doses, statins are associated with various myopathies ranging from rare occurrences of rhabdomyolysis and myositis to more frequent symptoms of muscle weakness, cramps, or pain; these can occur with mild or no increases in creatine kinase. Statin use also is associated with increases in liver transaminase levels. These tolerability and safety concerns may contribute to the high discontinuation rates of statins and their prescription at low, and often ineffective, doses.
TAK-475 (lapaquistat acetate) inhibits the cholesterol synthesis pathway at a different step than statins (acting on squalene synthase rather than 3-hydroxy-3-methylglutaryl coenzyme A); it does not reduce concentrations of isoprenylated intermediates believed to be responsible for the myopathies associated with statin use.
This study was conducted to determine whether lapaquistat acetate with fenofibrate has the potential to be more effective than fenofibrate by itself in lowering low-density lipoprotein cholesterol.
- Conditions
- Hyperlipidemias
- Being tested
- Lapaquistat acetate and fenofibrate, Fenofibrate
- Keywords
- Drug Therapy, Lipid Metabolism Disorders, Hyperlipidemias, Hypercholesterolemia, Hypertriglyceridemia
- Medical subject headings
- Hyperlipidemias, Lipid Metabolism Disorders, Hypercholesterolemia, Hypertriglyceridemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lapaquistat acetate and fenofibrateDrug
Also called Lapaquistat, TAK-475
Lapaquistat acetate 100 mg, tablets, orally, once daily and fenofibrate 145 mg, tablets, orally, once daily for up to 12 weeks.
FenofibrateDrug
Also called Tricor, Trilipix
Lapaquistat acetate placebo-matching tablets, orally, once daily and fenofibrate 145 mg, tablets, orally, once daily for up to 12 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Lapaquistat Acetate 100 mg QD + Fenofibrate 145 mg QD | Experimental | Not described Receives: Drug: Lapaquistat acetate and fenofibrate |
| Fenofibrate 145 mg QD | Active comparator | Not described Receives: Drug: Fenofibrate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent change from Baseline in direct fasting plasma low-density lipoprotein cholesterol.
Measured: Week 12 or Final Visit.
Secondary outcomes (11)
Change from baseline in calculated low-density lipoprotein cholesterol.
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 total cholesterol.
Measured: Week 12 or Final Visit.
Change from baseline in apolipoprotein B.
Measured: Week 12 or Final Visit.
Change from baseline in triglycerides.
Measured: Week 12 or Final Visit.
Change from baseline in high-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 very-low-density lipoprotein cholesterol.
Measured: Week 12 or Final Visit.
Change from baseline in derived ratios including total cholesterol/high-density lipoprotein cholesterol, low-density lipoprotein cholesterol/high-density lipoprotein cholesterol, and apolipoprotein B/ apolipoprotein Al.
Measured: Week 12 or Final Visit.
Change from baseline in high-sensitivity C-reactive protein.
Measured: Week 12 or Final Visit.
Percentage of Subjects Achieving Target Direct low-density lipoprotein cholesterol Levels.
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 posted23 Dec 2008 (estimated)
- Study startFeb 2006
- Primary completionJan 2007
- Study completionJan 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 HyperlipidemiasStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 213 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Senior Medical Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00813527
- Sponsor's protocol ID
- 01-05-TL-475-031
- Other IDs
- U1111-1122-8178
- Status last verified
- May 2012
- First submitted
- 19 Dec 2008
- 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 Study to Evaluate the Efficacy and Safety of TAK-475 or Placebo When Coadministered With Fenofibrate in Subjects With Combined Hyperlipidemia
- ClinicalTrials.gov ID
- NCT00813527
- Acronym / sponsor ID
- 01-05-TL-475-031
- Conditions
- Hyperlipidemias
- Keywords
- Drug Therapy, Lipid Metabolism Disorders, Hyperlipidemias, Hypercholesterolemia, Hypertriglyceridemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 213 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Study start
- Feb 2006
- Primary completion
- Jan 2007 (actual)
- Study completion
- Jan 2007 (actual)
- First posted
- 23 Dec 2008 (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 compare changes in cholesterol levels in patients with elevated blood cholesterol with administration of lapaquistat acetate, once daily (QD), and fenofibrate.
Detailed description
Elevated plasma cholesterol (hypercholesterolemia) and various other plasma lipid imbalances (dyslipidemias) are major risk factors for coronary heart disease. It has been established that lowering the low-density lipoprotein cholesterol plasma concentration effectively reduces cardiovascular morbidity and mortality. As a result of this finding, the National Cholesterol Education Program Adult Treatment Panel III identifies control of low-density lipoprotein cholesterol as essential in 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 Adult Treatment Panel III-recommended levels of low-density lipoprotein cholesterol reduction, making it necessary to increase the dose or add an additional treatment. This in turn may result in decreased tolerability and potential safety concerns.
At higher doses, statins are associated with various myopathies ranging from rare occurrences of rhabdomyolysis and myositis to more frequent symptoms of muscle weakness, cramps, or pain; these can occur with mild or no increases in creatine kinase. Statin use also is associated with increases in liver transaminase levels. These tolerability and safety concerns may contribute to the high discontinuation rates of statins and their prescription at low, and often ineffective, doses.
TAK-475 (lapaquistat acetate) inhibits the cholesterol synthesis pathway at a different step than statins (acting on squalene synthase rather than 3-hydroxy-3-methylglutaryl coenzyme A); it does not reduce concentrations of isoprenylated intermediates believed to be responsible for the myopathies associated with statin use.
This study was conducted to determine whether lapaquistat acetate with fenofibrate has the potential to be more effective than fenofibrate by itself in lowering low-density lipoprotein cholesterol.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lapaquistat Acetate 100 mg QD + Fenofibrate 145 mg QD | Experimental | Drug: Lapaquistat acetate and fenofibrate |
| Fenofibrate 145 mg QD | Active comparator | Drug: Fenofibrate |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Women of childbearing potential must not be pregnant as determined by a negative serum human chorionic gonadotropin, not lactating, not planning on becoming pregnant between Screening and 30 days following the last dose of study medication, and agreed to use acceptable forms of contraception during the study.
- Prior to Randomization, must have a mean low density lipoprotein cholesterol greater than or equal to 100 mg/dL (2.59 mmol/L) for 2 consecutive samples. The difference between the two individual low density lipoprotein cholesterol values not to exceed 15% of the higher value.
- Prior to Randomization, must have mean triglycerides greater than or equal to 150 and less than or equal to 600 mg/dL (1.70 and 6.78 mmol/L, respectively) for 2 consecutive samples. The upper value for either triglycerides sample must have been less than or equal to 650 mg/dL (7.35 mmol/L).
- Clinical laboratory evaluations (including clinical chemistry [fasted for at least 10 hours], hematology and urinalysis) within the reference range for the testing laboratory unless results deemed not clinically significant or considered within normal limits for this subject by the investigator or the sponsor.
- Willing and able to continue to comply with a standardized low cholesterol diet.
Key exclusion criteria (23 listed)
- Alanine aminotransferase or aspartate aminotransferase level of greater than 1.5 times the upper limit of normal, active liver disease or jaundice.
- Serum creatinine greater than 1.5 mg/dL (133 μmol/L).
- Creatine phosphokinase greater than 3 times the upper limit of normal.
- Diabetes with a hemoglobin A1c greater than 8 % at Visit 1.
- Previous history of cancer in remission for less than 5 years prior to the first dose of study medication. Does not include those subjects with basal cell or stage I squamous cell carcinoma of the skin.
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 fenofibrateAlso: Lapaquistat, TAK-475Lapaquistat acetate 100 mg, tablets, orally, once daily and fenofibrate 145 mg, tablets, orally, once daily for up to 12 weeks. | Drug | Lapaquistat Acetate 100 mg QD + Fenofibrate 145 mg QD |
| FenofibrateAlso: Tricor, TrilipixLapaquistat acetate placebo-matching tablets, orally, once daily and fenofibrate 145 mg, tablets, orally, once daily for up to 12 weeks. | Drug | Fenofibrate 145 mg QD |
Primary outcome
Percent change from Baseline in direct fasting plasma low-density lipoprotein cholesterol.
Time frame: Week 12 or Final Visit.
11 secondary outcomes
Change from baseline in calculated low-density lipoprotein cholesterol.
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 total cholesterol.
Time frame: Week 12 or Final Visit.
Change from baseline in apolipoprotein B.
Time frame: Week 12 or Final Visit.
Change from baseline in triglycerides.
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 apolipoprotein A1.
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 derived ratios including total cholesterol/high-density lipoprotein cholesterol, low-density lipoprotein cholesterol/high-density lipoprotein cholesterol, and apolipoprotein B/ apolipoprotein Al.
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 Achieving Target Direct low-density lipoprotein cholesterol Levels.
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.
Senior Medical Director study director
Takeda
36 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lapaquistat acetate and fenofibrate and Fenofibrate in people with Hyperlipidemias, run by Takeda at 36 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 5 inclusion and 23 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 36 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Percent change from Baseline in direct fasting plasma 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 NCT00813527, 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.