NCT00268697

Brief Summary

The purpose of the study is to determine the efficacy of lapaquistat acetate, once daily (QD), taken with ezetimibe on cholesterol levels in subjects with primary dyslipidemia

Trial Health

90
On Track

Trial Health Score

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

Enrollment
1,267

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started Oct 2005

Shorter than P25 for phase_3

Geographic Reach
4 countries

9 active sites

Status
completed

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

October 1, 2005

Completed
3 months until next milestone

First Submitted

Initial submission to the registry

December 20, 2005

Completed
2 days until next milestone

First Posted

Study publicly available on registry

December 22, 2005

Completed
1 year until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2007

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2007

Completed
Last Updated

May 24, 2012

Status Verified

May 1, 2012

Enrollment Period

1.3 years

First QC Date

December 20, 2005

Last Update Submit

May 23, 2012

Conditions

Hypercholesterolemia

Keywords

HyperlipidemiaDrug Therapy

Outcome Measures

Primary Outcomes (1)

  • Change from Baseline in fasting plasma Low Density Lipoprotein cholesterol

    Week 24 or Final Visit

Secondary Outcomes (19)

  • Change from Baseline in Triglycerides

    Week 24 or Final Visit

  • Change from Baseline in Total Cholesterol

    Week 24 or Final Visit

  • Change from Baseline in High Density Lipoprotein cholesterol

    Week 24 or Final Visit

  • Change from Baseline in Very Low Density Lipoprotein cholesterol

    Week 24 or Final Visit

  • Change from Baseline in apolipoprotein A1

    Week 24 or Final Visit

  • +14 more secondary outcomes

Study Arms (3)

Lapaquistat Acetate 100 mg QD

EXPERIMENTAL
Drug: Lapaquistat acetate

Lapaquistat Acetate 100 mg QD + Ezetimibe

EXPERIMENTAL
Drug: Lapaquistat acetate and ezetimibe

Ezetimibe

ACTIVE COMPARATOR
Drug: Ezetimibe

Interventions

Lapaquistat acetateDRUG

Lapaquistat acetate 100 mg, tablets, orally, once daily for up to 24 weeks.

Also known as: TAK-475
Lapaquistat Acetate 100 mg QD
Lapaquistat acetate and ezetimibeDRUG

Lapaquistat acetate 100 mg, tablets, orally, once daily and stable ezetimibe therapy for up to 24 weeks.

Also known as: TAK-475, Zetia
Lapaquistat Acetate 100 mg QD + Ezetimibe
EzetimibeDRUG

Lapaquistat acetate placebo-matching tablets, orally, once daily and stable ezetimibe therapy for up to 24 weeks.

Also known as: Zetia
Ezetimibe

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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 a documented history of dyslipidemia with or without cardiovascular risk factors but without type 1 or 2 diabetes.
  • At Randomization, participants must fulfill the above criteria and also have a mean fasting low density lipoprotein cholesterol levels greater than or equal to 3.36 mmol/L and less than or equal to 5.6 mmol/L and mean triglyceride levels less than or equal to 4.52 mmol/L.
  • Is willing and able to comply with the recommended, standardized diet.

You may not qualify if:

  • Has active liver disease or jaundice.
  • Has a history of cancer, other than basal cell carcinoma, that had been in remission for less than 5 years prior to the first dose of study drug.
  • Has an endocrine disorder, such as Cushing 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 the subject's verbal report.
  • Has a positive human immunodeficiency virus status or was taking antiretroviral medications, as determined by medical history and/or the subject's verbal report. .
  • Has participated in any other clinical studies with lapaquistat acetate, was concurrently participating in another investigational study, 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 known hypersensitivity or history of intolerance to lapaquistat acetate or ezetimibe.
  • 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 and/or discontinuation of HMG-CoA reductase inhibitors due to myalgia at any time.
  • Has uncontrolled hypertension despite medical treatment.
  • Has inflammatory bowel or any other malabsorption syndrome or had had gastric bypass surgery 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 any other serious disease or condition at Visit 1 or Randomization that might reduce life expectancy, impaired successful management according to the protocol, or make the participant unsuitable to receive study drug.
  • Has a history of coronary heart disease or coronary heart disease-risk factors comprised of:
  • +3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (9)

Unknown Facility

Tallinn, Estonia

Location

Unknown Facility

Tartu, Estonia

Location

Unknown Facility

Riga, Latvia

Location

Unknown Facility

Moscow, Russia

Location

Unknown Facility

Saint Petersburg, Russia

Location

Unknown Facility

Saratov, Russia

Location

Unknown Facility

Smolensk, Russia

Location

Unknown Facility

Tyumen, Russia

Location

Unknown Facility

Kragujevac, Serbia

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

HypercholesterolemiaHyperlipidemias

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 acidEzetimibe

Condition Hierarchy (Ancestors)

DyslipidemiasLipid Metabolism DisordersMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

AzetidinesAzetinesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

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 20, 2005

First Posted

December 22, 2005

Study Start

October 1, 2005

Primary Completion

January 1, 2007

Study Completion

January 1, 2007

Last Updated

May 24, 2012

Record last verified: 2012-05

Locations

ES(2)LA(1)SE(1)RU(5)