HypercholesterolemiaPhase 2NCT00865228
Efficacy of Lapaquistat Acetate in Subjects With Hypercholesterolemia
A Phase 2 study testing Lapaquistat acetate in people with Hypercholesterolemia, run by Takeda at 22 sites in United States.
Trial summary
The purpose of this study is to determine the role of time of dosing on the lipid-lowering effects of lapaquistat acetate, once daily (QD) or twice daily (BID), in subjects with hypercholesterolemia. 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
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 224 participants
- Where
- 22 sitesUnited States
- Study dates
- Jul 2007to Nov 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
- Females of childbearing potential who are sexually active must agree to use a medically accepted means of contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study.
- Has prior to Randomization a mean low-density lipoprotein cholesterol greater than or equal to 130 mg/dL and less than or equal to 220 mg/dL for 2 consecutive samples.
- Has prior to Randomization mean triglycerides less than 400 mg/dL for 2 consecutive samples.
- Is willing and able to comply with a standardized, therapeutic lifestyle change diet or equivalent.
Who cannot join
- Has an alanine aminotransferase or aspartate aminotransferase level greater than 2 times the upper limit of normal during the screening period.
- Has a serum creatinine greater than133 mmol/L during the screening period.
- Has a creatine phosphokinase greater than 3 times the upper limit of normal, identified during the screening period.
- Has active liver disease or jaundice.
- Has a 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 syndrome, hyperthyroidism, or inappropriately treated hypothyroidism, affecting lipid metabolism.
Show all 47Show fewer
- Has a history of myocardial infarction, angina pectoris, unstable angina, transient ischemic attacks, cerebrovascular accident, peripheral vascular disease, abdomin al aorticaneurysm, coronary angioplasty, coronary or peripheral arterial surgery or multiple risk factors that confer a 10-year risk for cardiovascular 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 is taking antiretroviral medications, as determined by medical history and/or subject's verbal report.
- Has received any investigational compound within 30 days prior to screening Visit 1, or is currently participating in another 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.
- Has fibromyalgia, myopathy, rhabdomyolysis, or unexplained muscle pain.
- Has uncontrolled hypertension despite treatment at Screening Visit 1.
- Has had inflammatory bowel 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 alcohol abuse within the past 2 years.
- Has stage I squamous cell carcinoma of the skin.
- Has type 1 or type 2 diabetes mellitus.
- Is required to take or intends to continue taking any disallowed medication, any prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication, including:
- Fluvastatin
- Lovastatin
- bile acid sequestrants (eg, cholestyramine)
- intestinal cholesterol uptake inhibitors (eg, ezetimibe)
- Fibrates (eg, fenofibrate, gemfibrozil)
- Niacin
- Cholestin
- red yeast rice
- fish oils
- plant sterols and stanols
- orlistat
- sibutramine
- isotretinoin
- tacrolimus
- Probucol
- Systemic corticosteroids and androgens
- Potent CYP3A4 inhibitors
- Cyclosporine
- Erythromycin
- Clarithromycin
- Telithromycin
- human immunodeficiency virus protease inhibitors
- amiodarone
- diltiazem
- verapamil
- nefazodone
- grapefruit juice
Trial locations and contacts
22 sites in 1 country.
22 sites in 1 country
United States22 sites
Study site
Bristol, Tennessee
Study site
Charlotte, North Carolina
Study site
Chicago, Illinois
Study site
Hollywood, Florida
Study site
Jacksonville, Florida
Study site
Long Beach, California
Study site
Louisville, Kentucky
Study site
Madison, Wisconsin
Study site
Margate City, New Jersey
Study site
Medford, Oregon
Study site
New Port Richey, Florida
Study site
Norfolk, Virginia
Study site
Perkasie, Pennsylvania
Study site
Raleigh, North Carolina
Study site
Richmond, Virginia
Study site
Sacramento, California
Study site
San Diego, California
Study site
Sellerville, Pennsylvania
Study site
Statesville, North Carolina
Study site
Wichita, Kansas
Study site
Wilmington, North Carolina
Study site
Winston-Salem, North Carolina
About this study
Official title: A Double-blind, Randomized Study to Evaluate the Efficacy and Safety of Lapaquistat Acetate 100 mg in the Morning vs Lapaquistat Acetate 100 mg in the Evening vs Lapaquistat Acetate 50 mg Twice Daily vs Placebo in Subjects With Hypercholesterolemia
The purpose of this study is to determine the role of time of dosing on the lipid-lowering effects of lapaquistat acetate, once daily (QD) or twice daily (BID), in subjects with hypercholesterolemia.
Read the detailed description
Dyslipidemias are a group of metabolic disorders produced by raised concentrations of lipoproteins, especially low-density lipoprotein cholesterol the lipoprotein that transports endogenous cholesterol from the liver to the peripheral tissues. Increased cholesterol and triglyceride levels lead to an increased risk of arteriosclerosis, the underlying cause of heart attack, strokes and peripheral vascular disease. Despite changes in lifestyle and the availability of potent lipid-lowering agents, cardiovascular disease continues to be the major cause of death in Western Europe and North America.
Lapaquistat acetate is being developed by Takeda for the treatment of hypercholesterolemia.
- Conditions
- Hypercholesterolemia
- Being tested
- Lapaquistat acetate, Placebo
- Keywords
- Hyperlipidemia, Dyslipidemia, High Cholesterol, Drug Therapy
- Medical subject headings
- Hypercholesterolemia, Hyperlipidemias, Dyslipidemias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lapaquistat acetateDrug
Also called TAK-475
Lapaquistat acetate 100 mg, tablets, orally, once daily in the morning and Lapaquistat acetate placebo-matching tablets, orally, once daily in the evening for up to six weeks.
Lapaquistat acetateDrug
Also called TAK-475
Lapaquistat acetate placebo-matching tablets, orally, once daily in the morning and Lapaquistat acetate 100 mg, tablets, orally, once daily in the evening for up to six weeks.
Lapaquistat acetateDrug
Also called TAK-475
Lapaquistat acetate 50 mg, tablets, orally, once daily in the morning and Lapaquistat acetate 50 mg, tablets, orally, once daily in the evening for up to six weeks.
PlaceboDrug
Lapaquistat acetate placebo-matching tablets, orally, once daily in the morning and Lapaquistat acetate placebo-matching tablets, orally, once daily in the evening for up to six weeks.
| Study group | Role | What they receive |
|---|---|---|
| Lapaquistat Acetate 100 mg QD (morning) | Experimental | Not described Receives: Drug: Lapaquistat acetate |
| Lapaquistat Acetate 100 mg QD (evening) | Experimental | Not described Receives: Drug: Lapaquistat acetate |
| Lapaquistat Acetate 50 mg BID | Experimental | Not described Receives: Drug: Lapaquistat acetate |
| Placebo BID | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent change from Baseline in the Fasting Plasma Low-Density Lipoprotein Cholesterol concentration
Measured: Week 6
Secondary outcomes (11)
Change from Baseline in Total Cholesterol
Measured: Week 6
Percent change from Baseline in apolipoprotein B
Measured: Week 6
Percent change from Baseline in apolipoprotein A1
Measured: Week 6
Change from Baseline in Triglycerides
Measured: Week 6
Percent change from Baseline in High-Density Lipoprotein Cholesterol
Measured: Week 6
Percent change from Baseline in Very Low-Density Lipoprotein Cholesterol
Measured: Week 6
Percent change from Baseline in non- High-Density Lipoprotein Cholesterol
Measured: Week 6
Percent change from Baseline in derived ratio of Low-Density Lipoprotein Cholesterol / High-Density Lipoprotein Cholesterol
Measured: Week 6
Percent change from Baseline in derived ratio of Total Cholesterol / High-Density Lipoprotein Cholesterol
Measured: Week 6
Percent change from Baseline in derived ratio of apolipoprotein B / apolipoprotein A1
Measured: Week 6
Change from Baseline in high sensitivity C-Reactive Protein.
Measured: Week 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2009 (estimated)
- Study startJul 2007
- Primary completionNov 2007
- Study completionNov 2007
Why it stopped: Overall profile of the compound does not offer significant clinical advantage to patients over currently available lipid lowering agents
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 224 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- VP, Clinical Science, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00865228
- Sponsor's protocol ID
- TAK-475_201
- Other IDs
- U1111-1122-8404
- Status last verified
- May 2012
- First submitted
- 18 Mar 2009
- Last updated
- 24 May 2012
- Results posted
- No
- Data monitoring committee
- No
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 Lapaquistat Acetate 100 mg in the Morning vs Lapaquistat Acetate 100 mg in the Evening vs Lapaquistat Acetate 50 mg Twice Daily vs Placebo in Subjects With Hypercholesterolemia
- ClinicalTrials.gov ID
- NCT00865228
- Acronym / sponsor ID
- TAK-475_201
- Conditions
- Hypercholesterolemia
- Keywords
- Hyperlipidemia, Dyslipidemia, High Cholesterol, Drug Therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Overall profile of the compound does not offer significant clinical advantage to patients over currently available lipid lowering agents
- Enrolment
- 224 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Study start
- Jul 2007
- Primary completion
- Nov 2007 (actual)
- Study completion
- Nov 2007 (actual)
- First posted
- 19 Mar 2009 (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 determine the role of time of dosing on the lipid-lowering effects of lapaquistat acetate, once daily (QD) or twice daily (BID), in subjects with hypercholesterolemia.
Detailed description
Dyslipidemias are a group of metabolic disorders produced by raised concentrations of lipoproteins, especially low-density lipoprotein cholesterol the lipoprotein that transports endogenous cholesterol from the liver to the peripheral tissues. Increased cholesterol and triglyceride levels lead to an increased risk of arteriosclerosis, the underlying cause of heart attack, strokes and peripheral vascular disease. Despite changes in lifestyle and the availability of potent lipid-lowering agents, cardiovascular disease continues to be the major cause of death in Western Europe and North America.
Lapaquistat acetate is being developed by Takeda for the treatment of hypercholesterolemia.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Lapaquistat Acetate 100 mg QD (morning) | Experimental | Drug: Lapaquistat acetate |
| Lapaquistat Acetate 100 mg QD (evening) | Experimental | Drug: Lapaquistat acetate |
| Lapaquistat Acetate 50 mg BID | Experimental | Drug: Lapaquistat acetate |
| Placebo BID | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Females of childbearing potential who are sexually active must agree to use a medically accepted means of contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study.
- Has prior to Randomization a mean low-density lipoprotein cholesterol greater than or equal to 130 mg/dL and less than or equal to 220 mg/dL for 2 consecutive samples.
- Has prior to Randomization mean triglycerides less than 400 mg/dL for 2 consecutive samples.
- Is willing and able to comply with a standardized, therapeutic lifestyle change diet or equivalent.
Key exclusion criteria (47 listed)
- Has an alanine aminotransferase or aspartate aminotransferase level greater than 2 times the upper limit of normal during the screening period.
- Has a serum creatinine greater than133 mmol/L during the screening period.
- Has a creatine phosphokinase greater than 3 times the upper limit of normal, identified during the screening period.
- Has active liver disease or jaundice.
- Has a history of cancer that has 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 acetateAlso: TAK-475Lapaquistat acetate 100 mg, tablets, orally, once daily in the morning and Lapaquistat acetate placebo-matching tablets, orally, once daily in the evening for up to six weeks. | Drug | Lapaquistat Acetate 100 mg QD (morning) |
| Lapaquistat acetateAlso: TAK-475Lapaquistat acetate placebo-matching tablets, orally, once daily in the morning and Lapaquistat acetate 100 mg, tablets, orally, once daily in the evening for up to six weeks. | Drug | Lapaquistat Acetate 100 mg QD (evening) |
| Lapaquistat acetateAlso: TAK-475Lapaquistat acetate 50 mg, tablets, orally, once daily in the morning and Lapaquistat acetate 50 mg, tablets, orally, once daily in the evening for up to six weeks. | Drug | Lapaquistat Acetate 50 mg BID |
| PlaceboLapaquistat acetate placebo-matching tablets, orally, once daily in the morning and Lapaquistat acetate placebo-matching tablets, orally, once daily in the evening for up to six weeks. | Drug | Placebo BID |
Primary outcome
Percent change from Baseline in the Fasting Plasma Low-Density Lipoprotein Cholesterol concentration
Time frame: Week 6
11 secondary outcomes
Change from Baseline in Total Cholesterol
Time frame: Week 6
Percent change from Baseline in apolipoprotein B
Time frame: Week 6
Percent change from Baseline in apolipoprotein A1
Time frame: Week 6
Change from Baseline in Triglycerides
Time frame: Week 6
Percent change from Baseline in High-Density Lipoprotein Cholesterol
Time frame: Week 6
Percent change from Baseline in Very Low-Density Lipoprotein Cholesterol
Time frame: Week 6
Percent change from Baseline in non- High-Density Lipoprotein Cholesterol
Time frame: Week 6
Percent change from Baseline in derived ratio of Low-Density Lipoprotein Cholesterol / High-Density Lipoprotein Cholesterol
Time frame: Week 6
Percent change from Baseline in derived ratio of Total Cholesterol / High-Density Lipoprotein Cholesterol
Time frame: Week 6
Percent change from Baseline in derived ratio of apolipoprotein B / apolipoprotein A1
Time frame: Week 6
Change from Baseline in high sensitivity C-Reactive Protein.
Time frame: Week 6
Results and safety
The study was stopped early (reason given: Overall profile of the compound does not offer significant clinical advantage to patients over currently available lipid lowering agents). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 May 2012.
Related trials for Hypercholesterolemia
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A Study of Inclisiran to Prevent Cardiovascular Events in High-risk Primary Prevention Patients.
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Early Detection of Familial Hypercholesterolaemia in Pre-school Children ( CzeCH-IT)
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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.
VP, Clinical Science study director
Takeda
22 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lapaquistat acetate in people with Hypercholesterolemia, run by Takeda at 22 sites in United States.
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 47 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: stopped early, 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 22 sites in United States. 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. Some participants in this study may receive a placebo. 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 was stopped early (reason given: Overall profile of the compound does not offer significant clinical advantage to patients over currently available lipid lowering agents). Results are not available in the source record.
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 the Fasting Plasma Low-Density Lipoprotein Cholesterol concentration (time frame: Week 6). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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.