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SB-480848 In Subjects With Coronary Heart Disease

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ClinicalTrials.gov Identifier: NCT00269048
Recruitment Status : Completed
First Posted : December 23, 2005
Last Update Posted : August 8, 2016
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Description
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
This trial of SB-480848 in approximately 920 subjects with Coronary Heart Disease (CHD) or CHD-risk equivalent will examine whether SB-480848 produces sustained inhibition of plasma Lp-PLA2 activity, explore the effects of SB-480848 on other circulating biomarkers associated with cardiovascular risk, and evaluate the pharmacokinetics, safety and tolerability of SB-480848 over 12 weeks of once-daily oral dosing. Subjects will first be randomized 1:1 to double-blind atorvastatin 20 mg or 80 mg once daily for a minimum of 3 weeks. Subjects will then be randomized 1:1:1:1 to oral doses of SB-480848 40 mg, 80 mg, 160 mg or placebo once daily for 12 weeks. Blood samples will be collected at various timepoints. Vital signs, electrocardiograms, clinical laboratory safety tests and adverse event assessments will be performed to evaluate the safety and tolerability of SB-480848.

Condition or disease Intervention/treatment Phase
Atherosclerosis Drug: SB-480848 Drug: placebo Phase 2

Detailed Description:
A multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study of SB-480848, an oral lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor, in subjects with stable coronary heart disease (CHD) or CHD-risk equivalent to examine chronic inhibition of Lp-PLA2, effects on circulating biomarkers associated with cardiovascular risk, safety and tolerability over 12 weeks

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 969 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Dose-ranging Study of SB-480848, an Oral Lipoprotein-associated Phospholipase A2 (Lp-PLA2) Inhibitor, in Subjects With Stable Coronary Heart Disease (CHD) or CHD-risk Equivalent to Examine Chronic Inhibition of Lp-PLA2 Effects on Circulating Biomarkers Associated With Cardiovascular Risk, Safety and Tolerability Over 12 Weeks
Study Start Date : November 2005
Actual Primary Completion Date : September 2006
Actual Study Completion Date : September 2006

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U.S. FDA Resources

Arms and Interventions
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Arm Intervention/treatment
Experimental: Arm 1
SB-480848
 Drug: SB-480848
SB-480848
Placebo Comparator: Arm 2
placebo
 Drug: placebo
placebo


Outcome Measures
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Primary Outcome Measures :
  1. On treatment sustained inhibition of plasma Lp-PLA2 activity. [ Time Frame: 12 Weeks ]

Secondary Outcome Measures :
  1. Difference in dose-dependent effects of SB-480848 on plasma Lp-PLA2 activity, other biomarkers, and safety. [ Time Frame: 12 Weeks ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Female subjects must be of non-childbearing potential.
  • Stable CHD or CHD-risk equivalent.
  • Must have been on a stable dose of a statin for =4 weeks with LDL <130 mg/dL (3.4 mmol/L) or off statin therapy for =4 weeks with LDL <160 mg/dL (4.1 mmol/L).
  • On a stable dose of at least one oral antiplatelet agent (e.g., aspirin, clopidogrel, or ticlopidine).

Exclusion criteria:

  • Recent cardiovascular event and / or vascular procedure.
  • History of difficult to manage dyslipidemia.
  • Planned cardiac surgery or PCI (percutaneous coronary intervention) or planned major non-cardiac surgery.
  • Inadequately controlled hypertension.
  • Poorly controlled diabetes mellitus.
  • Serum triglycerides >400 mg/dL (4.52 mmol/L).
  • Recent or ongoing acute infection.
  • History of chronic inflammatory disease.
  • Receiving topical, oral, inhaled or injectable corticosteroids.
  • History of chronic viral hepatitis, or other chronic hepatic disorders.
  • History of kidney transplant.
  • History of myopathy or inflammatory muscle disease, or elevated total serum CK (3 x ULN).
  • Severe heart failure (NYHA class III or IV), or severe left ventricular dysfunction (ejection fraction <30%).
  • Asthma manifested by bronchospasm in the past 6 months, or currently taking inhaled bronchodilator on regular basis.
  • History of anaphylaxis, anaphylactoid reactions or severe allergic responses within the past 6 months.
  • Malignancy within the past 2 years, other than non-melanoma skin cancer.
  • Current life-threatening condition other than vascular disease that may prevent a subject from completing the study.
  • QTc interval >440 msec (males) or >450 msec (females).
  • Alcohol or drug abuse within the past 6 months.
  • Previous exposure to SB-480848.
  • Use of an investigational drug within 30 days or 5 half-lives (whichever is the longer) preceding the first dose of study medication (blinded atorvastatin).
Contacts and Locations
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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00269048


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Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
More Information
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.  This link exits the ClinicalTrials.gov site

Study Data/Documents: Clinical Study Report  This link exits the ClinicalTrials.gov site
Identifier: LPL104884
For additional information about this study please refer to the GSK Clinical Study Register
Informed Consent Form  This link exits the ClinicalTrials.gov site
Identifier: LPL104884
For additional information about this study please refer to the GSK Clinical Study Register
Statistical Analysis Plan  This link exits the ClinicalTrials.gov site
Identifier: LPL104884
For additional information about this study please refer to the GSK Clinical Study Register
Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Identifier: LPL104884
For additional information about this study please refer to the GSK Clinical Study Register
Annotated Case Report Form  This link exits the ClinicalTrials.gov site
Identifier: LPL104884
For additional information about this study please refer to the GSK Clinical Study Register
Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: LPL104884
For additional information about this study please refer to the GSK Clinical Study Register
Dataset Specification  This link exits the ClinicalTrials.gov site
Identifier: LPL104884
For additional information about this study please refer to the GSK Clinical Study Register

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00269048     History of Changes
Other Study ID Numbers: LPL104884
First Posted: December 23, 2005    Key Record Dates
Last Update Posted: August 8, 2016
Last Verified: August 2016

Keywords provided by GlaxoSmithKline:
CHD
Lp-PLA2
SB-480848

Additional relevant MeSH terms:
Heart Diseases
Atherosclerosis
Coronary Disease
Coronary Artery Disease
Myocardial Ischemia
 Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases