Efficacy and Safety of Lapaquistat Acetate Coadministered With Atorvastatin in Subjects With Hypercholesterolemia

NCT00864643 | Completed Phase 2

• 2 other identifiers: 01-04-TL-475-011U1111-1122-7848
• Study Type: interventional
• Target: 172
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Hypercholesterolemia

Keywords

Hyperlipidemia; Drug Therapy; Dyslipidemia

Outcome Measures

Primary Outcomes (1)

• Percent change from Baseline in Low Density Lipoprotein Cholesterol

  Week 6

Secondary Outcomes (6)

• Percent change from Baseline in Total Cholesterol

  Week 6

• Percent change from Baseline in High-Density Lipoprotein Cholesterol

  Week 6

• Percent change from Baseline in Triglycerides

  Week 6

• Percent change from Baseline in Apolipoprotein B

  Week 6

• Percent change from Baseline in Apolipoprotein A1

  Week 6

Study Arms (2)

Lapaquistat Acetate 100 mg QD + Atorvastatin QD

EXPERIMENTAL

Drug: Lapaquistat acetate and atorvastatin

Atorvastatin QD

ACTIVE COMPARATOR

Drug: Atorvastatin

Interventions

Lapaquistat acetate and atorvastatin DRUG

Lapaquistat acetate 100 mg, tablets, orally, once daily and atorvastatin 10 mg or 20 mg, tablets, orally, once daily for up to 6 weeks.

Also known as: Lapaquistat acetate, Lipitor, TAK-475

Lapaquistat Acetate 100 mg QD + Atorvastatin QD

Atorvastatin DRUG

Lapaquistat acetate placebo-matching tablets, orally, once daily and atorvastatin 10 mg or 20 mg, tablets, orally, once daily for up to 6 weeks.

Also known as: Lipitor, TAK-475

Atorvastatin QD

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).
• 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

Sponsors & Collaborators

• Takeda: lead

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: 21518985 RESULT

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; Atorvastatin

Condition Hierarchy (Ancestors)

Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids

Study Officials

• VP, Clinical Science Strategy

  Takeda

  STUDY DIRECTOR

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: March 18, 2009
• First Posted: March 19, 2009
• Study Start: September 1, 2004
• Primary Completion: February 1, 2005
• Study Completion: February 1, 2005
• Last Updated: May 24, 2012

Record last verified: 2012-05