HypercholesterolemiaPhase 3NCT00868127
Safety of Lapaquistat Acetate in Subjects With Hypercholesterolemia
A Phase 3 study testing Lapaquistat acetate and Lapaquistat acetate and additional lipid-lowering therapy in people with Hypercholesterolemia, run by Takeda.
Trial summary
The purpose of this study is to determine the long-term safety of lapaquistat acetate, once daily (QD), as monotherapy or in combination with other lipid-lowering agents 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 and Lapaquistat acetate and additional lipid-lowering therapy
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 574 participants
- Where
- No sites listed yet
- Study dates
- Dec 2005to Jul 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
- Has completed the 01-04-TL-475-008 or 01-04-TL-475-009 study.
- 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 clinical laboratory evaluations within reference range for the testing laboratory at the previous visit in study 01-04-TL-475-008 or 01-04-TL-475-009 unless the results were deemed not clinically significant by the investigator or sponsor.
- Is willing and able to comply with a standardized low cholesterol diet.
- Is willing to continue taking the protocol-specified companion lipid-altering medication from the previous study (if applicable) for at least the first 4 weeks.
Who cannot join
- Has an alanine aminotransferase or aspartate aminotransferase level greater than or equal to 3 times the upper limit of normal at the previous visit in the prior study, active liver disease, or jaundice.
- Has serum creatinine greater than or equal to 133 μmol/l at the previous visit in the prior study.
- Has a creatine kinase greater than or equal to 10 times the upper limit of normal at the previous visit in the prior study.
- Has a previous history of cancer that had been in remission for less than 5 years prior to the first dose of study medication. This criterion did not include those subjects with basal cell or Stage 1 squamous cell carcinoma of the skin.
- Has an endocrine disorder, such as Cushing's syndrome, hyperthyroidism, or inappropriately treated hypothyroidism, affecting lipid metabolism.
- Has a positive hepatitis B surface antigen, or hepatitis C virus antibody, as determined by medical history and/or participant's verbal report.
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- Has a positive human immunodeficiency virus status or was taking antiretroviral medications, as determined by medical history and/or subject's verbal report.
- Has a known hypersensitivity to lapaquistat acetate.
- Has a history or presence of clinically significant food allergy that prevented them from maintaining Therapeutic Lifestyle Change (or equivalent) diet.
- Has a known homozygous familial hypercholesterolemia or known Type III hyperlipoproteinemia.
- Has fibromyalgia, myopathy, rhabdomyolysis, or unexplained muscle pain.
- Has uncontrolled hypertension at Visit 1.
- Has inflammatory bowel disease or any other malabsorption syndrome or had gastric bypass or any other surgical procedure for weight loss.
- Has a history of drug abuse or a history of alcohol abuse within the past 2 years.
- Has any other serious disease or condition at Visit 1 that may reduce life expectancy, impair successful management according to the protocol, or make the participant unsuitable to receive study medication.
- 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:
- Orlistat
- Sibutramine
- Isotretinoin
- Tacrolimus
- Probucol
- Systemic corticosteroids and androgens
- Potent cytochrome P-450 3A4 inhibitors
- Azole antifungal agents
- Cyclosporine
- Erythromycin
- Clarithromycin
- Human Immunodeficiency Virus protease inhibitors
- Amiodarone
- Verapamil
- Diltiazem
- Nefazodone
- Large quantities of grapefruit juice
- Warfarin
- Digoxin
About this study
Official title: An Open-Label Extension Study to Evaluate the Safety and Tolerability of Lapaquistat Acetate in Subjects With Hypercholesterolemia
The purpose of this study is to determine the long-term safety of lapaquistat acetate, once daily (QD), as monotherapy or in combination with other lipid-lowering agents in Subjects with Hypercholesterolemia.
Read the detailed description
Elevated plasma cholesterol (hypercholesterolemia) and various other plasma lipid imbalances (dyslipidemias) are major risk factors for coronary heart disease. Normally, the balance among cholesterol synthesis, dietary intake, and degradation is adequate to maintain healthy cholesterol plasma levels. However, in patients with hypercholesterolemia, elevation in low-density lipoprotein cholesterol leads to atherosclerotic deposition of cholesterol in the arterial walls. Consequently, 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. Additional lipid risk factors designated by Adult Treatment Panel III include elevated triglycerides, elevated non-high density lipoprotein cholesterol, and low levels of high-density lipoprotein cholesterol. Lipoproteins rich in triglycerides, such as very low-density lipoprotein cholesterol, appear to contribute to atherosclerosis, whereas the apparent protective effect of high-density lipoprotein cholesterol may be limited at low density lipoprotein concentrations.
Lapaquistat acetate is a squalene synthase inhibitor currently under development at Takeda for the treatment of dyslipidemia.
Participants in this study have primary hypercholesterolemia and have completed either the 12-week monotherapy protocol 01-04-TL-475-008 (NCT00143663) or the 24-week atorvastatin add-on study 01-04-TL-475-009 (NCT00143676).
- Conditions
- Hypercholesterolemia
- Being tested
- Lapaquistat acetate, Lapaquistat acetate and additional lipid-lowering therapy
- Keywords
- Hyperlipidemia, Drug Therapy, Dyslipidemia
- 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
Participants from 01-04-TL-475-008 Monotherapy Study:
Lapaquistat acetate 100 mg, tablets, orally, once daily for up to 48 weeks.
Lapaquistat acetate and additional lipid-lowering therapyDrug
Also called TAK-475
Participants from 01-04-TL-475-009 Atorvastatin Add-on Study:
Lapaquistat acetate 100 mg, tablets, orally, once daily and current Atorvastatin therapy for up to 4 weeks.
Then, Lapaquistat 100 mg, tablets, orally, once daily and dose adjustment of Atorvastatin OR additional companion lipid-lowering therapy as needed for target LDL-C for up to 42 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Lapaquistat Acetate 100 mg QD | Experimental | Not described Receives: Drug: Lapaquistat acetate |
| Lapaquistat Acetate 100 mg QD + Added Therapy | Experimental | Not described Receives: Drug: Lapaquistat acetate and additional lipid-lowering therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Events
Measured: Weeks 2, 4, 8, 12, 24, 36 and 48
Vital Signs
Measured: Weeks 2, 4, 8, 12, 24, 36 and 48
Clinical Laboratory Blood Sample for Lipid Panel
Measured: Weeks 2, 4, 8, 12, 24, 36 and 48
Clinical Laboratory Serum Chemistries
Measured: Weeks 2, 4, 8, 12, 24, 36 and 48
Clinical Laboratory Hematology
Measured: Weeks 2, 4, 8, 12, 24, 36 and 48
Clinical Laboratory Serum Human Chorionic Gonadotropin
Measured: Weeks 2, 4, 8, 12, 24, 36 and 48
Clinical Laboratory Urinalysis
Measured: Weeks 2, 4, 8, 12, 24, 36 and 48
Physical Examination
Measured: Week 48
12-lead Electrocardiogram
Measured: Week 48
Best Corrected Visual Acuity
Measured: Week 48
Secondary outcomes (6)
Percent change from Baseline in calculated Low Density Lipoprotein Cholesterol
Measured: Week 48
Percent change from Baseline in calculated Non-High Density Lipoprotein Cholesterol
Measured: Week 48
Percent change from Baseline in calculated Total Cholesterol
Measured: Week 48
Percent change from Baseline in calculated Triglycerides
Measured: Week 48
Percent change from Baseline in calculated High Density Lipoprotein Cholesterol
Measured: Week 48
Percent change from Baseline in Derived ratios Total Cholesterol / High Density Lipoprotein Cholesterol and Low Density Lipoprotein Cholesterol / High Density Lipoprotein Cholesterol
Measured: Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2009 (estimated)
- Study startDec 2005
- Primary completionJul 2007
- Study completionJul 2007
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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 574 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
- NCT00868127
- Sponsor's protocol ID
- 01-04-TL-475-010
- Other IDs
- U1111-1122-8368
- 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
- An Open-Label Extension Study to Evaluate the Safety and Tolerability of Lapaquistat Acetate in Subjects With Hypercholesterolemia
- ClinicalTrials.gov ID
- NCT00868127
- Acronym / sponsor ID
- 01-04-TL-475-010
- Conditions
- Hypercholesterolemia
- Keywords
- Hyperlipidemia, Drug Therapy, Dyslipidemia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 574 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Study start
- Dec 2005
- Primary completion
- Jul 2007 (actual)
- Study completion
- Jul 2007 (actual)
- First posted
- 24 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 long-term safety of lapaquistat acetate, once daily (QD), as monotherapy or in combination with other lipid-lowering agents in Subjects with Hypercholesterolemia.
Detailed description
Elevated plasma cholesterol (hypercholesterolemia) and various other plasma lipid imbalances (dyslipidemias) are major risk factors for coronary heart disease. Normally, the balance among cholesterol synthesis, dietary intake, and degradation is adequate to maintain healthy cholesterol plasma levels. However, in patients with hypercholesterolemia, elevation in low-density lipoprotein cholesterol leads to atherosclerotic deposition of cholesterol in the arterial walls. Consequently, 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. Additional lipid risk factors designated by Adult Treatment Panel III include elevated triglycerides, elevated non-high density lipoprotein cholesterol, and low levels of high-density lipoprotein cholesterol. Lipoproteins rich in triglycerides, such as very low-density lipoprotein cholesterol, appear to contribute to atherosclerosis, whereas the apparent protective effect of high-density lipoprotein cholesterol may be limited at low density lipoprotein concentrations.
Lapaquistat acetate is a squalene synthase inhibitor currently under development at Takeda for the treatment of dyslipidemia.
Participants in this study have primary hypercholesterolemia and have completed either the 12-week monotherapy protocol 01-04-TL-475-008 (NCT00143663) or the 24-week atorvastatin add-on study 01-04-TL-475-009 (NCT00143676).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lapaquistat Acetate 100 mg QD | Experimental | Drug: Lapaquistat acetate |
| Lapaquistat Acetate 100 mg QD + Added Therapy | Experimental | Drug: Lapaquistat acetate and additional lipid-lowering therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Has completed the 01-04-TL-475-008 or 01-04-TL-475-009 study.
- 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 clinical laboratory evaluations within reference range for the testing laboratory at the previous visit in study 01-04-TL-475-008 or 01-04-TL-475-009 unless the results were deemed not clinically significant by the investigator or sponsor.
- Is willing and able to comply with a standardized low cholesterol diet.
- Is willing to continue taking the protocol-specified companion lipid-altering medication from the previous study (if applicable) for at least the first 4 weeks.
Key exclusion criteria (35 listed)
- Has an alanine aminotransferase or aspartate aminotransferase level greater than or equal to 3 times the upper limit of normal at the previous visit in the prior study, active liver disease, or jaundice.
- Has serum creatinine greater than or equal to 133 μmol/l at the previous visit in the prior study.
- Has a creatine kinase greater than or equal to 10 times the upper limit of normal at the previous visit in the prior study.
- Has a previous history of cancer that had been in remission for less than 5 years prior to the first dose of study medication. This criterion did not include those subjects with basal cell or Stage 1 squamous cell carcinoma of the skin.
- Has an endocrine disorder, such as Cushing's syndrome, hyperthyroidism, or inappropriately treated hypothyroidism, affecting lipid metabolism.
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-475Participants from 01-04-TL-475-008 Monotherapy Study: Lapaquistat acetate 100 mg, tablets, orally, once daily for up to 48 weeks. | Drug | Lapaquistat Acetate 100 mg QD |
| Lapaquistat acetate and additional lipid-lowering therapyAlso: TAK-475Participants from 01-04-TL-475-009 Atorvastatin Add-on Study: Lapaquistat acetate 100 mg, tablets, orally, once daily and current Atorvastatin therapy for up to 4 weeks. Then, Lapaquistat 100 mg, tablets, orally, once daily and dose adjustment of Atorvastatin OR additional companion lipid-lowering therapy as needed for target LDL-C for up to 42 weeks. | Drug | Lapaquistat Acetate 100 mg QD + Added Therapy |
Primary outcome
Adverse Events
Time frame: Weeks 2, 4, 8, 12, 24, 36 and 48
Vital Signs
Time frame: Weeks 2, 4, 8, 12, 24, 36 and 48
Clinical Laboratory Blood Sample for Lipid Panel
Time frame: Weeks 2, 4, 8, 12, 24, 36 and 48
Clinical Laboratory Serum Chemistries
Time frame: Weeks 2, 4, 8, 12, 24, 36 and 48
Clinical Laboratory Hematology
Time frame: Weeks 2, 4, 8, 12, 24, 36 and 48
Clinical Laboratory Serum Human Chorionic Gonadotropin
Time frame: Weeks 2, 4, 8, 12, 24, 36 and 48
Clinical Laboratory Urinalysis
Time frame: Weeks 2, 4, 8, 12, 24, 36 and 48
Physical Examination
Time frame: Week 48
12-lead Electrocardiogram
Time frame: Week 48
Best Corrected Visual Acuity
Time frame: Week 48
6 secondary outcomes
Percent change from Baseline in calculated Low Density Lipoprotein Cholesterol
Time frame: Week 48
Percent change from Baseline in calculated Non-High Density Lipoprotein Cholesterol
Time frame: Week 48
Percent change from Baseline in calculated Total Cholesterol
Time frame: Week 48
Percent change from Baseline in calculated Triglycerides
Time frame: Week 48
Percent change from Baseline in calculated High Density Lipoprotein Cholesterol
Time frame: Week 48
Percent change from Baseline in Derived ratios Total Cholesterol / High Density Lipoprotein Cholesterol and Low Density Lipoprotein Cholesterol / High Density Lipoprotein Cholesterol
Time frame: Week 48
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.
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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
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Lapaquistat acetate and Lapaquistat acetate and additional lipid-lowering therapy in people with Hypercholesterolemia, run by Takeda.
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 35 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.
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?
Adverse Events (time frame: Weeks 2, 4, 8, 12, 24, 36 and 48). The study lists 10 primary outcomes in all. 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.