Safety of Lapaquistat Acetate in Subjects With Hypercholesterolemia

NCT00868127 | Completed Phase 3

• 2 other identifiers: 01-04-TL-475-010U1111-1122-8368
• Study Type: interventional
• Target: 574
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Hypercholesterolemia

Keywords

Hyperlipidemia; Drug Therapy; Dyslipidemia

Outcome Measures

Primary Outcomes (10)

• Adverse Events

  Weeks 2, 4, 8, 12, 24, 36 and 48

• Vital Signs

  Weeks 2, 4, 8, 12, 24, 36 and 48

• Clinical Laboratory Blood Sample for Lipid Panel

  Weeks 2, 4, 8, 12, 24, 36 and 48

• Clinical Laboratory Serum Chemistries

  Weeks 2, 4, 8, 12, 24, 36 and 48

• Clinical Laboratory Hematology

  Weeks 2, 4, 8, 12, 24, 36 and 48

• Clinical Laboratory Serum Human Chorionic Gonadotropin

  Weeks 2, 4, 8, 12, 24, 36 and 48

• Clinical Laboratory Urinalysis

  Weeks 2, 4, 8, 12, 24, 36 and 48

• Physical Examination

  Week 48

• 12-lead Electrocardiogram

  Week 48

• Best Corrected Visual Acuity

  Week 48

Secondary Outcomes (6)

• Percent change from Baseline in calculated Low Density Lipoprotein Cholesterol

  Week 48

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

  Week 48

• Percent change from Baseline in calculated Total Cholesterol

  Week 48

• Percent change from Baseline in calculated Triglycerides

  Week 48

• Percent change from Baseline in calculated High Density Lipoprotein Cholesterol

  Week 48

Study Arms (2)

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

Interventions

Lapaquistat acetate DRUG

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

Also known as: TAK-475

Lapaquistat Acetate 100 mg QD

Lapaquistat acetate and additional lipid-lowering therapy DRUG

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.

Also known as: TAK-475

Lapaquistat Acetate 100 mg QD + Added Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Takeda: lead

MeSH Terms

Conditions

Hypercholesterolemia; Hyperlipidemias; Dyslipidemias

Interventions

1-((1-(3-acetoxy-2,2-dimethylpropyl)-7-chloro-5-(2,3-dimethoxyphenyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl)acetyl)piperidine-4-acetic acid

Condition Hierarchy (Ancestors)

Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Medical Director

  Takeda

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2009
• First Posted: March 24, 2009
• Study Start: December 1, 2005
• Primary Completion: July 1, 2007
• Study Completion: July 1, 2007
• Last Updated: May 24, 2012

Record last verified: 2012-05