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Efficacy of Lapaquistat Acetate Co-Administered With Statins in Subjects With Hypercholesterolemia

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ClinicalTrials.gov Identifier: NCT00532311
Recruitment Status : Terminated (Overall profile of the compound does not offer significant clinical advantage to patients over currently available lipid lowering agents)
First Posted : September 20, 2007
Last Update Posted : June 22, 2016
Sponsor:
Information provided by (Responsible Party):
Takeda

Tracking Information
First Submitted Date  ICMJE September 18, 2007
First Posted Date  ICMJE September 20, 2007
Last Update Posted Date June 22, 2016
Study Start Date  ICMJE July 2007
Actual Primary Completion Date April 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 14, 2009)
Change from Baseline in fasting plasma Low Density Lipoprotein cholesterol [ Time Frame: Week 12 or Final Visit ]
Original Primary Outcome Measures  ICMJE
 (submitted: September 19, 2007)
  • Double-blind: The primary objective is to evaluate the the reduction in calculated LDL-C. [ Time Frame: 12 weeks ]
  • Open label: Evaluate the long-term safety and lipid variables after open-label treatment. [ Time Frame: 48 weeks ]
Change History Complete list of historical versions of study NCT00532311 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 14, 2009)
  • Change from Baseline in Triglycerides [ Time Frame: Week 12 or Final Visit ]
  • Change from Baseline in Total Cholesterol [ 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 Very Low 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 apolipoprotein B [ 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 the ratio of Low Density Lipoprotein cholesterol/High Density Lipoprotein cholesterol [ Time Frame: Week 12 or Final Visit ]
  • Change from Baseline in the ratio of Total Cholesterol/High Density Lipoprotein cholesterol [ Time Frame: Week 12 or Final Visit ]
  • Change from Baseline in the ratio of apolipoprotein A1/apolipoprotein B [ 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 who achieve Low Density Lipoprotein cholesterol concentrations less than 1.81 mmol/L (70 mg/dL) [ Time Frame: Week 12 or Final Visit ]
  • Percentage of subjects who achieve Low Density Lipoprotein cholesterol concentrations less than 2.59 mmol/L (100 mg/dL) [ Time Frame: Week 12 or Final Visit ]
  • Percentage of subjects who achieve Low Density Lipoprotein cholesterol concentrations less than 3.37 mmol/L (130 mg/dL) [ Time Frame: Week 12 or Final Visit ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy of Lapaquistat Acetate Co-Administered With Statins in Subjects With Hypercholesterolemia
Official Title  ICMJE A Double-Blind, Randomized Study to Evaluate the Efficacy and Safety of Lapaquistat Acetate 50 mg or Placebo When Co-administered With Statins in Subjects With Hypercholesterolemia, With an Optional Open-Label Extension
Brief Summary The purpose of the study is to determine the efficacy of lapaquistat acetate, once daily (QD), taken with statins on cholesterol levels in subjects with hypercholesterolemia
Detailed Description

Dyslipidemias are a group of metabolic disorders produced by raised concentrations of lipoproteins, especially low-density lipoprotein cholesterol, which is the lipoprotein that transports endogenous cholesterol from the liver to the peripheral tissues. Increased cholesterol and triglycerides levels lead to an increased risk of arteriosclerosis, which is 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. Serum cholesterol levels exceeding 5 mmol/L (193 mg/dL) are common in adults in Britain and much of Europe, the United States, Australia and New Zealand.

This study will evaluate the efficacy and safety of lapaquistat acetate taken with either torvastatin, simvastatin, rosuvastatin, pravastatin, fluvastatin or lovastatin (stable statin therapy) in subjects with hypercholesterolemia. Total participation time in this study is expected to be up to 12 weeks, with an optional, 48-week, open-label extension period for participants who qualify.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Hypercholesterolemia
Intervention  ICMJE
  • Drug: Lapaquistat acetate and stable statin therapy
    Lapaquistat acetate 50 mg, tablets, orally, once daily and stable statin therapy for up to 12 weeks.
    Other Names:
    • TAK-475
    • Lipitor
    • Zocor
    • Crestor
    • Pravachol
    • Lescol
    • Mevacor
  • Drug: Stable statin therapy
    Lapaquistat acetate placebo-matching tablets, orally, once daily and stable statin therapy for up to 12 weeks.
    Other Names:
    • Lipitor
    • Zocor
    • Crestor
    • Pravachol
    • Lescol
    • Mevacor
Study Arms  ICMJE
  • Experimental: Lapaquistat Acetate 50 mg QD
    (and stable statin therapy)
    Intervention: Drug: Lapaquistat acetate and stable statin therapy
  • Active Comparator: Stable statin therapy
    Intervention: Drug: Stable statin therapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: January 14, 2009)
411
Original Estimated Enrollment  ICMJE
 (submitted: September 19, 2007)
600
Actual Study Completion Date  ICMJE April 2008
Actual Primary Completion Date April 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Females of childbearing potential who are sexually active must agree to use adequate contraception from screening throughout the duration of the study and for 30 days following the last dose.
  • Has been on a stable dose of statin for at least 3 months prior to Screening. Participants enrolled in Canada, Latin America, and South Africa must be on the maximum approved dose of statin (atorvastatin 80 mg, simvastatin 80 mg, rosuvastatin 40 mg, pravastatin 80 mg, fluvastatin 80 mg, or lovastatin 80 mg).
  • Prior to Randomization, the participant has a mean low density lipoprotein cholesterol level greater than or equal to 100 mg/dL and less than or equal to 190 mg/dL for 2 consecutive samples.
  • Prior to Randomization, the subject has mean triglyceride level greater than or equal to 400 mg/dL for 2 consecutive samples.
  • Is willing and able to comply with the recommended, standardized diet.

Exclusion Criteria:

  • Has an nine aminotransferase or aspartate aminotransferase level greater than 1.5 times the upper limit of normal, identified during screening.
  • Has a serum creatinine greater than 133 mmol/L, identified during screening.
  • Has a creatine kinase greater than 3 times the upper limit of normal, identified during screening.
  • Has active liver disease or jaundice.
  • Has taken any bile acid sequestrants [eg, cholestyramine], and intestinal cholesterol uptake inhibitors [eg, ezetimibe]) from 30 days before Screening until study completion or any fibrates for 6 weeks before Visit 1.
  • Has a previous 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's syndrome, hyperthyroidism, or inappropriately treated hypothyroidism affecting lipid metabolism.
  • Has a history of myocardial infarction, angina pectoris, unstable angina, transient ischemic attacks, cerebrovascular accident, peripheral vascular disease, abdominal aortic aneurysm, coronary angioplasty, coronary or peripheral arterial surgery, or multiple risk factors that confer a 10-year risk for cardiovascular heart disease greater than 20% based on Framingham risk scoring.
  • Has a positive hepatitis B surface antigen or hepatitis C virus antibody test, as determined by medical history.
  • 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 medication 30 days prior to screening, (for drugs with a long half-life, within a period of less than 5 times the drug's half-life) or is participating in an 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 (familial dysbetalipoproteinemia).
  • Has fibromyalgia, myopathy, rhabdomyolysis, or unexplained muscle pain.
  • Has uncontrolled hypertension
  • Has had inflammatory bowel disease 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 a history of high alcohol intake within the previous 2 years.
  • Has type 1 or 2 diabetes mellitus.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00532311
Other Study ID Numbers  ICMJE TAK-475_307
U1111-1122-8479 ( Registry Identifier: WHO )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Takeda
Study Sponsor  ICMJE Takeda
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Takeda
PRS Account Takeda
Verification Date June 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP