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Safety of Lapaquistat Acetate in Subjects With Hypercholesterolemia

Primary Purpose

Hypercholesterolemia

Status

Completed

Phase

Phase 3

Locations

Study Type

Interventional

Intervention

Lapaquistat acetate

Lapaquistat acetate and additional lipid-lowering therapy

About this trial

This is an interventional treatment trial for Hypercholesterolemia focused on measuring Hyperlipidemia, Drug Therapy, Dyslipidemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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.
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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Lapaquistat Acetate 100 mg QD

Lapaquistat Acetate 100 mg QD + Added Therapy

Arm Description

Outcomes

Primary Outcome Measures

Adverse Events

Vital Signs

Clinical Laboratory Blood Sample for Lipid Panel

Clinical Laboratory Serum Chemistries

Clinical Laboratory Hematology

Clinical Laboratory Serum Human Chorionic Gonadotropin

Clinical Laboratory Urinalysis

Physical Examination

12-lead Electrocardiogram

Best Corrected Visual Acuity

Secondary Outcome Measures

Percent change from Baseline in calculated Low Density Lipoprotein Cholesterol

Percent change from Baseline in calculated Non-High Density Lipoprotein Cholesterol

Percent change from Baseline in calculated Total Cholesterol

Percent change from Baseline in calculated Triglycerides

Percent change from Baseline in calculated High Density Lipoprotein Cholesterol

Percent change from Baseline in Derived ratios Total Cholesterol / High Density Lipoprotein Cholesterol and Low Density Lipoprotein Cholesterol / High Density Lipoprotein Cholesterol

Full Information

NCT ID

NCT00868127

First Posted

March 18, 2009

Last Updated

May 23, 2012

Sponsor

Takeda

1. Study Identification

Unique Protocol Identification Number

NCT00868127

Brief Title

Safety of Lapaquistat Acetate in Subjects With Hypercholesterolemia

Official Title

An Open-Label Extension Study to Evaluate the Safety and Tolerability of Lapaquistat Acetate in Subjects With Hypercholesterolemia

Study Type

Interventional

2. Study Status

Record Verification Date

May 2012

Overall Recruitment Status

Completed

Study Start Date

December 2005 (undefined)

Primary Completion Date

July 2007 (Actual)

Study Completion Date

July 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Takeda

4. Oversight

Data Monitoring Committee

5. Study Description

Brief 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.

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hypercholesterolemia

Keywords

Hyperlipidemia, Drug Therapy, Dyslipidemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

574 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Lapaquistat Acetate 100 mg QD

Arm Type

Experimental

Arm Title

Lapaquistat Acetate 100 mg QD + Added Therapy

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

Lapaquistat acetate

Other Intervention Name(s)

TAK-475

Intervention Description

Participants from 01-04-TL-475-008 Monotherapy Study: Lapaquistat acetate 100 mg, tablets, orally, once daily for up to 48 weeks.

Intervention Type

Drug

Intervention Name(s)

Lapaquistat acetate and additional lipid-lowering therapy

Other Intervention Name(s)

TAK-475

Intervention Description

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.

Primary Outcome Measure Information:

Title

Adverse Events

Time Frame