HypercholesterolemiaPhase 2NCT00864643
Efficacy and Safety of Lapaquistat Acetate Coadministered With Atorvastatin in Subjects With Hypercholesterolemia
A Phase 2 study testing Lapaquistat acetate and atorvastatin and Atorvastatin in people with Hypercholesterolemia, run by Takeda.
Trial summary
The purpose of this study is to determine the efficacy of lapaquistat acetate, once daily (QD), coadministered with a statin to lower lipid levels in Subjects with Hypercholesterolemia. Read more about this study
- Who is it for?
- Ages 18 to 79 years
- Conditions the study is for
- Hypercholesterolemia
- What is being tested?
- Lapaquistat acetate and atorvastatin and Atorvastatin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 172 participants
- Where
- No sites listed yet
- Study dates
- Sep 2004to Feb 2005
- 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 to 79 years
- 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.
- Prior to Screening, participant is not taking any lipid lowering agents and has an low-density lipoprotein cholesterol greater than 145 mg/dL and triglycerides less than 400 mg/dL, or is taking atorvastatin (10 mg or 20 mg) and has an low-density lipoprotein cholesterol greater than 100 mg/dL and triglycerides less than 400 mg/dL.
- Prior to Randomization, participant has taken at least 80% of open-label atorvastatin (10 mg or 20 mg) doses during Run-in, and has a mean low-density lipoprotein cholesterol greater than or equal to 100 mg/dL for 2 consecutive samples within 15% of each other.
Who cannot join
- Has been in remission for at least 5 years prior to the first dose of study drug. This criterion did not include those subjects with basal cell or Stage 1 squamous cell carcinoma of the skin.
- Has an alanine aminotransferase and aspartate aminotransferase level of greater than 1.5x the upper limit of normal, creatine phosphokinase greater than 3 times the upper limit of normal, active liver disease, jaundice, or serum creatinine greater than 2.0 mg/dL (men) or 1.8 mg/dL (women) at Screening.
- Has diabetes or a history of liver disease or had a positive hepatitis B surface antigen, or hepatitis C virus antibody, as determined by medical history and/or subject's verbal report.
- Has fibromyalgia, myopathy, rhabdomyolysis, or unexplained muscle pain and/or discontinuation of statin due to myalgia.
- Has a positive human immunodeficiency virus status or had been taking retroviral medications, as determined by medical history and/or subject's verbal report.
- Has a body mass index of less than 15 or greater than 35 (weight/height2).
Show all 13Show fewer
- Has a history of drug abuse or a history of alcohol abuse.
- Is currently 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 half-life.
- Has any other serious disease or condition at Screening or at Randomization that might affect life expectancy or make it difficult to successfully manage and follow the subject according to the protocol.
- Has a known hypersensitivity or history of adverse reaction to lapaquistat acetate, atorvastatin or other statins, or multiple intolerances or allergies to other medications.
- 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:
- Lipid-lowering agents (including cholesterol absorption inhibitors, ethylicosapentate, plant sterols, niacin, and fibrates).
- Any statin, other than atorvastatin
About this study
Official title: A Double-Blind, Randomized Study to Evaluate the Efficacy and Safety of TAK-475 (100 mg) Vs Placebo When Coadministered With Atorvastatin (10 or 20 mg) in Subjects With Primary Hypercholesterolemia
The purpose of this study is to determine the efficacy of lapaquistat acetate, once daily (QD), coadministered with a statin to lower lipid levels 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.
TAK-475 (lapaquistat acetate) is a squalene synthase inhibitor currently under development at Takeda for the treatment of dyslipidemia.
- Conditions
- Hypercholesterolemia
- Being tested
- Lapaquistat acetate and atorvastatin, Atorvastatin
- 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 acetate and atorvastatinDrug
Also called Lapaquistat acetate, Lipitor, TAK-475
Lapaquistat acetate 100 mg, tablets, orally, once daily and atorvastatin 10 mg or 20 mg, tablets, orally, once daily for up to 6 weeks.
AtorvastatinDrug
Also called Lipitor, TAK-475
Lapaquistat acetate placebo-matching tablets, orally, once daily and atorvastatin 10 mg or 20 mg, tablets, orally, once daily for up to 6 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Lapaquistat Acetate 100 mg QD + Atorvastatin QD | Experimental | Not described Receives: Drug: Lapaquistat acetate and atorvastatin |
| Atorvastatin QD | Active comparator | Not described Receives: Drug: Atorvastatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent change from Baseline in Low Density Lipoprotein Cholesterol
Measured: Week 6
Secondary outcomes (6)
Percent change from Baseline in Total Cholesterol
Measured: Week 6
Percent change from Baseline in High-Density Lipoprotein Cholesterol
Measured: Week 6
Percent change from Baseline in Triglycerides
Measured: Week 6
Percent change from Baseline in Apolipoprotein B
Measured: Week 6
Percent change from Baseline in Apolipoprotein A1
Measured: Week 6
Percent change from Baseline in Very-Low Density Lipoprotein Cholesterol
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 startSep 2004
- Primary completionFeb 2005
- Study completionFeb 2005
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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 172 participants (actual)
Sponsor and investigators
- Lead sponsor
- Takeda
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- VP, Clinical Science Strategy, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00864643
- Sponsor's protocol ID
- 01-04-TL-475-011
- Other IDs
- U1111-1122-7848
- Status last verified
- May 2012
- First submitted
- 18 Mar 2009
- 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 (100 mg) Vs Placebo When Coadministered With Atorvastatin (10 or 20 mg) in Subjects With Primary Hypercholesterolemia
- ClinicalTrials.gov ID
- NCT00864643
- Acronym / sponsor ID
- 01-04-TL-475-011
- Conditions
- Hypercholesterolemia
- Keywords
- Hyperlipidemia, Drug Therapy, Dyslipidemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 172 participants (actual)
- Lead sponsor
- TakedaIndustry (pharma, biotech, devices)
- Study start
- Sep 2004
- Primary completion
- Feb 2005 (actual)
- Study completion
- Feb 2005 (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 efficacy of lapaquistat acetate, once daily (QD), coadministered with a statin to lower lipid levels 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.
TAK-475 (lapaquistat acetate) is a squalene synthase inhibitor currently under development at Takeda for the treatment of dyslipidemia.
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 + Atorvastatin QD | Experimental | Drug: Lapaquistat acetate and atorvastatin |
| Atorvastatin QD | Active comparator | Drug: Atorvastatin |
Who may qualify
- Ages
- 18 to 79 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 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.
- Prior to Screening, participant is not taking any lipid lowering agents and has an low-density lipoprotein cholesterol greater than 145 mg/dL and triglycerides less than 400 mg/dL, or is taking atorvastatin (10 mg or 20 mg) and has an low-density lipoprotein cholesterol greater than 100 mg/dL and triglycerides less than 400 mg/dL.
- Prior to Randomization, participant has taken at least 80% of open-label atorvastatin (10 mg or 20 mg) doses during Run-in, and has a mean low-density lipoprotein cholesterol greater than or equal to 100 mg/dL for 2 consecutive samples within 15% of each other.
Key exclusion criteria (13 listed)
- Has been in remission for at least 5 years prior to the first dose of study drug. This criterion did not include those subjects with basal cell or Stage 1 squamous cell carcinoma of the skin.
- Has an alanine aminotransferase and aspartate aminotransferase level of greater than 1.5x the upper limit of normal, creatine phosphokinase greater than 3 times the upper limit of normal, active liver disease, jaundice, or serum creatinine greater than 2.0 mg/dL (men) or 1.8 mg/dL (women) at Screening.
- Has diabetes or a history of liver disease or had a positive hepatitis B surface antigen, or hepatitis C virus antibody, as determined by medical history and/or subject's verbal report.
- Has fibromyalgia, myopathy, rhabdomyolysis, or unexplained muscle pain and/or discontinuation of statin due to myalgia.
- Has a positive human immunodeficiency virus status or had been taking retroviral medications, as determined by medical history and/or subject's verbal report.
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 atorvastatinAlso: Lapaquistat acetate, Lipitor, TAK-475Lapaquistat acetate 100 mg, tablets, orally, once daily and atorvastatin 10 mg or 20 mg, tablets, orally, once daily for up to 6 weeks. | Drug | Lapaquistat Acetate 100 mg QD + Atorvastatin QD |
| AtorvastatinAlso: Lipitor, TAK-475Lapaquistat acetate placebo-matching tablets, orally, once daily and atorvastatin 10 mg or 20 mg, tablets, orally, once daily for up to 6 weeks. | Drug | Atorvastatin QD |
Primary outcome
Percent change from Baseline in Low Density Lipoprotein Cholesterol
Time frame: Week 6
6 secondary outcomes
Percent change from Baseline in Total Cholesterol
Time frame: Week 6
Percent change from Baseline in High-Density Lipoprotein Cholesterol
Time frame: Week 6
Percent change from Baseline in Triglycerides
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
Percent change from Baseline in Very-Low Density Lipoprotein Cholesterol
Time frame: Week 6
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.
VP, Clinical Science Strategy study director
Takeda
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lapaquistat acetate and atorvastatin and Atorvastatin 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 3 inclusion and 13 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 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 Low Density Lipoprotein Cholesterol (time frame: Week 6). 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 NCT00864643, 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.