NCT00263081

Brief Summary

The purpose of the study is to determine the efficacy of lapaquistat acetate, once daily (QD), to lower cholesterol in subjects with homozygous familial hypercholesterolemia undergoing lipid-lowering treatment.

Trial Health

63
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
44

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Nov 2005

Shorter than P25 for phase_3

Geographic Reach
6 countries

10 active sites

Status
terminated

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

November 1, 2005

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

December 6, 2005

Completed
1 day until next milestone

First Posted

Study publicly available on registry

December 7, 2005

Completed
1.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2007

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2007

Completed
Last Updated

May 24, 2012

Status Verified

May 1, 2012

Enrollment Period

1.3 years

First QC Date

December 6, 2005

Last Update Submit

May 23, 2012

Conditions

Hypercholesterolemia

Keywords

HyperlipidemiaDyslipidemiaDrug Therapy

Outcome Measures

Primary Outcomes (1)

  • Change from Baseline in Low Density Lipoprotein cholesterol

    Week 12 or Final Visit

Secondary Outcomes (12)

  • 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 Triglycerides

    Week 12 or Final Visit

  • Change from Baseline in Total Cholesterol

    Week 12 or Final Visit

  • Change from Baseline in High Density Lipoprotein cholesterol

    Week 12 or Final Visit

  • +7 more secondary outcomes

Study Arms (2)

Lapaquistat Acetate QD

EXPERIMENTAL

(and current lipid-lowering treatment)

Drug: Lapaquistat acetate and current lipid-lowering treatment

Current lipid-lowering treatment

PLACEBO COMPARATOR
Drug: Current lipid-lowering treatment

Interventions

Lapaquistat acetate and current lipid-lowering treatmentDRUG

Cohort 1: Weight is less than 50 kg: Lapaquistat acetate 50 mg, tablets, orally, once daily and current lipid-lowering treatment for up to 12 weeks. Cohort 2: Weight is more than 50 kg: Lapaquistat acetate 100 mg, tablets, orally, once daily and current lipid-lowering treatment for up to 12 weeks.

Also known as: Lapaquistat, TAK-475
Lapaquistat Acetate QD
Current lipid-lowering treatmentDRUG

Lapaquistat acetate placebo-matching tablets, orally, once daily and current lipid-lowering treatment for up to 12 weeks.

Current lipid-lowering treatment

Eligibility Criteria

Age8 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Must be at least 8 years of age (12 years of age in Poland) and weigh greater than or equal to 30 kg.
  • Must have homozygous FH, as documented by genetic testing that confirmed 2 mutated alleles at the LDL-receptor locus, or by the following clinical criteria:
  • documented history of untreated fasting serum LDL-C \>460 mg/dL (11.91 mmol/L).
  • tendinous or cutaneous xanthomas and/or corneal arcus before age 10 and/or premature coronary heart disease before age 20.
  • Must be taking a stable, approved lipid-lowering drug regimen for a minimum of 8 weeks prior to Screening Visit 1 and were to continue that treatment for the duration of the study.
  • Female participants can not be pregnant, not lactating, not planning on becoming pregnant and agree to use adequate contraception throughout the course of the study.

You may not qualify if:

  • Has alanine aminotransferase or aspartate aminotransferase levels greater than 2 times the upper limit of normal, active liver disease, jaundice, or serum creatinine \>135 μmol/L (1.5 mg/dL) at screening.
  • Has a creatine kinase greater than 3 times the upper limit of normal
  • Has a positive hepatitis B surface antigen, or hepatitis C virus antibody, as determined by medical history.
  • Has a positive human immunodeficiency virus status or was taking antiretroviral medications, as determined by medical history and/or subject's verbal report.
  • Is unable or unwilling to discontinue excluded medications or to continue stable doses of 'stable dose' medications or would require treatment with any excluded medication during the study.
  • Is currently participating in another investigational study or had 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 a previous history of cancer that had been in remission for less than 5 years prior to the first dose of study drug. This criterion was not to include those subjects with basal cell or Stage 1 squamous cell carcinoma of the skin.
  • Has known hypersensitivity or history of adverse reaction to lapaquistat acetate.
  • Has a history of fibromyalgia, myopathy, rhabdomyolysis, or unexplained muscle pain.
  • Has an endocrine disorder, such as Cushing Syndrome, hyperthyroidism, or inappropriately treated hypothyroidism, affecting lipid metabolism. Subjects with hypothyroidism on appropriate replacement therapy.
  • Has uncontrolled hypertension despite medical treatment.
  • 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 screening or at randomization that might have reduced life expectancy, impaired successful management according to the protocol, or made the subject an unsuitable candidate to receive study drug.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (10)

Unknown Facility

Cincinnati, Ohio, United States

Location

Unknown Facility

Columbus, Ohio, United States

Location

Unknown Facility

Québec, Canada

Location

Unknown Facility

Paris, France

Location

Unknown Facility

Strasbourg, France

Location

Unknown Facility

Jerusalem, Israel

Location

Unknown Facility

Bialystok, Poland

Location

Unknown Facility

Warsaw, Poland

Location

Unknown Facility

Zabrze, Poland

Location

Unknown Facility

Manchester, United Kingdom

Location

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

HypercholesterolemiaHyperlipidemiasDyslipidemias

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 DisordersMetabolic DiseasesNutritional and Metabolic Diseases

Study Officials

  • Medical Director

    Takeda

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 3
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 6, 2005

First Posted

December 7, 2005

Study Start

November 1, 2005

Primary Completion

March 1, 2007

Study Completion

March 1, 2007

Last Updated

May 24, 2012

Record last verified: 2012-05

Locations

IL(1)CA(1)FR(2)GB(1)US(2)PL(3)