Effect of Lapaquistat Acetate Combined With Fenofibrate on Blood Cholesterol Levels
A Double-blind, Randomized Study to Evaluate the Efficacy and Safety of TAK-475 or Placebo When Coadministered With Fenofibrate in Subjects With Combined Hyperlipidemia
2 other identifiers
interventional
213
2 countries
36
Brief Summary
The purpose of this study is to compare changes in cholesterol levels in patients with elevated blood cholesterol with administration of lapaquistat acetate, once daily (QD), and fenofibrate.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Feb 2006
Shorter than P25 for phase_2
36 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
February 1, 2006
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2007
CompletedStudy Completion
Last participant's last visit for all outcomes
January 1, 2007
CompletedFirst Submitted
Initial submission to the registry
December 19, 2008
CompletedFirst Posted
Study publicly available on registry
December 23, 2008
CompletedMay 24, 2012
May 1, 2012
11 months
December 19, 2008
May 23, 2012
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Percent change from Baseline in direct fasting plasma low-density lipoprotein cholesterol.
Week 12 or Final Visit.
Secondary Outcomes (11)
Change from baseline in calculated low-density lipoprotein cholesterol.
Week 12 or Final Visit.
Change from baseline in non- high-density lipoprotein cholesterol.
Week 12 or Final Visit.
Change from baseline in total cholesterol.
Week 12 or Final Visit.
Change from baseline in apolipoprotein B.
Week 12 or Final Visit.
Change from baseline in triglycerides.
Week 12 or Final Visit.
- +6 more secondary outcomes
Study Arms (2)
Lapaquistat Acetate 100 mg QD + Fenofibrate 145 mg QD
EXPERIMENTALFenofibrate 145 mg QD
ACTIVE COMPARATORInterventions
Lapaquistat acetate 100 mg, tablets, orally, once daily and fenofibrate 145 mg, tablets, orally, once daily for up to 12 weeks.
Lapaquistat acetate placebo-matching tablets, orally, once daily and fenofibrate 145 mg, tablets, orally, once daily for up to 12 weeks.
Eligibility Criteria
You may qualify if:
- Women of childbearing potential must not be pregnant as determined by a negative serum human chorionic gonadotropin, not lactating, not planning on becoming pregnant between Screening and 30 days following the last dose of study medication, and agreed to use acceptable forms of contraception during the study.
- Prior to Randomization, must have a mean low density lipoprotein cholesterol greater than or equal to 100 mg/dL (2.59 mmol/L) for 2 consecutive samples. The difference between the two individual low density lipoprotein cholesterol values not to exceed 15% of the higher value.
- Prior to Randomization, must have mean triglycerides greater than or equal to 150 and less than or equal to 600 mg/dL (1.70 and 6.78 mmol/L, respectively) for 2 consecutive samples. The upper value for either triglycerides sample must have been less than or equal to 650 mg/dL (7.35 mmol/L).
- Clinical laboratory evaluations (including clinical chemistry \[fasted for at least 10 hours\], hematology and urinalysis) within the reference range for the testing laboratory unless results deemed not clinically significant or considered within normal limits for this subject by the investigator or the sponsor.
- Willing and able to continue to comply with a standardized low cholesterol diet.
You may not qualify if:
- Alanine aminotransferase or aspartate aminotransferase level of greater than 1.5 times the upper limit of normal, active liver disease or jaundice.
- Serum creatinine greater than 1.5 mg/dL (133 μmol/L).
- Creatine phosphokinase greater than 3 times the upper limit of normal.
- Diabetes with a hemoglobin A1c greater than 8 % at Visit 1.
- Previous history of cancer in remission for less than 5 years prior to the first dose of study medication. Does not include those subjects with basal cell or stage I squamous cell carcinoma of the skin.
- An endocrine disorder, such as Cushing's syndrome, hyperthyroidism, or inappropriately treated hypothyroidism, affecting lipid metabolism. Subjects with hypothyroidism on appropriate replacement therapy (defined as stable thyroid hormone replacement therapy at least 3 months prior to Visit 1 and thyrotropin levels less than 1.5 times the upper limit of normal) are eligible for enrollment. If thyrotropin is greater than 1.5 times upper limit of normal, a free thyroxine level is to be determined. If the free thyroxine is within normal limits for that subject, the subject may continue in the study.
- History of myocardial infarction, unstable angina, transient ischemic attacks, cerebrovascular accident, percutaneous coronary intervention, coronary or peripheral arterial surgery (bypass graft surgery) in the 6 months prior to Visit 1.
- Positive hepatitis B surface antigen, or hepatitis C virus antibody, as determined by medical history and/or subject's verbal report.
- Positive human immunodeficiency virus status or is taking anti-retroviral medications, as determined by medical history and/or subject's verbal report.
- Unable or unwilling to discontinue excluded medications or to continue stable doses of "stable dose" medications or required treatment with any excluded medication during the study.
- Exposure to TAK-475 in other studies or currently is 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 halflife.
- Known hypersensitivity or history of adverse reaction to any fibrate.
- History or presence of clinically significant food allergy that would prevent adherence to the therapeutic lifestyle change (or equivalent) diet.
- Known homozygous familial hypercholesterolemia or known Type III hyperlipoproteinemia (familial dysbetalipoproteinemia).
- Active cholecystitis or known cholelithiasis (a fibrate risk factor).
- +8 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Takedalead
Study Sites (36)
Unknown Facility
Huntsville, Alabama, United States
Unknown Facility
Sierra Vista, Arizona, United States
Unknown Facility
Beverly Hills, California, United States
Unknown Facility
Long Beach, California, United States
Unknown Facility
Spring Valley, California, United States
Unknown Facility
Colorado Springs, Colorado, United States
Unknown Facility
Golden, Colorado, United States
Unknown Facility
Waterbury, Connecticut, United States
Unknown Facility
Jacksonville, Florida, United States
Unknown Facility
Kissimmee, Florida, United States
Unknown Facility
Miami, Florida, United States
Unknown Facility
Ocala, Florida, United States
Unknown Facility
Pembroke Pines, Florida, United States
Unknown Facility
Pinellas Park, Florida, United States
Unknown Facility
West Palm Beach, Florida, United States
Unknown Facility
Warner Robins, Georgia, United States
Unknown Facility
Chicago, Illinois, United States
Unknown Facility
Peoria, Illinois, United States
Unknown Facility
Indianapolis, Indiana, United States
Unknown Facility
Wichita, Kansas, United States
Unknown Facility
Edina, Minnesota, United States
Unknown Facility
St Louis, Missouri, United States
Unknown Facility
Raleigh, North Carolina, United States
Unknown Facility
Winston-Salem, North Carolina, United States
Unknown Facility
Cincinnati, Ohio, United States
Unknown Facility
Columbus, Ohio, United States
Unknown Facility
Hillsboro, Oregon, United States
Unknown Facility
Beaver, Pennsylvania, United States
Unknown Facility
Goose Creek, South Carolina, United States
Unknown Facility
Nashville, Tennessee, United States
Unknown Facility
Norfolk, Virginia, United States
Unknown Facility
Richmond, Virginia, United States
Unknown Facility
Coquitlam, British Columbia, Canada
Unknown Facility
Victoria, British Columbia, Canada
Unknown Facility
London, Ontario, Canada
Unknown Facility
Toronto, Ontario, Canada
Related Publications (1)
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.
PMID: 21518985RESULT
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Senior Medical Director
Takeda
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 19, 2008
First Posted
December 23, 2008
Study Start
February 1, 2006
Primary Completion
January 1, 2007
Study Completion
January 1, 2007
Last Updated
May 24, 2012
Record last verified: 2012-05