SB-480848 In Subjects With Coronary Heart Disease

NCT ID: NCT00269048

Last Updated: 2016-08-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 969 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-11-30
• Study Completion Date: 2006-09-30

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.

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

Conditions

Atherosclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Arm 1

SB-480848

Group Type: EXPERIMENTAL

SB-480848

Intervention Type: DRUG

SB-480848

Arm 2

placebo

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

placebo

Interventions

SB-480848

SB-480848

Intervention Type: DRUG

placebo

placebo

Intervention Type: DRUG

Eligibility 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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Birmingham, Alabama, United States

GSK Investigational Site

Northport, Alabama, United States

GSK Investigational Site

Phoenix, Arizona, United States

GSK Investigational Site

Tucson, Arizona, United States

GSK Investigational Site

Spring Valley, California, United States

GSK Investigational Site

Torrance, California, United States

GSK Investigational Site

Walnut Creek, California, United States

GSK Investigational Site

Fort Lauderdale, Florida, United States

GSK Investigational Site

Jacksonville, Florida, United States

GSK Investigational Site

Pembroke Pines, Florida, United States

GSK Investigational Site

Chicago, Illinois, United States

GSK Investigational Site

Chicago, Illinois, United States

GSK Investigational Site

Indianapolis, Indiana, United States

GSK Investigational Site

Lacombe, Louisiana, United States

GSK Investigational Site

Slidell, Louisiana, United States

GSK Investigational Site

Auburn, Maine, United States

GSK Investigational Site

New York, New York, United States

GSK Investigational Site

Statesville, North Carolina, United States

GSK Investigational Site

Cincinnati, Ohio, United States

GSK Investigational Site

Oklahoma City, Oklahoma, United States

GSK Investigational Site

Camp Hill, Pennsylvania, United States

GSK Investigational Site

Philadelphia, Pennsylvania, United States

GSK Investigational Site

Bryan, Texas, United States

GSK Investigational Site

Houston, Texas, United States

GSK Investigational Site

San Antonio, Texas, United States

GSK Investigational Site

Salt Lake City, Utah, United States

GSK Investigational Site

Norfolk, Virginia, United States

GSK Investigational Site

Richmond, Virginia, United States

GSK Investigational Site

Buenos Aires, Buenos Aires, Argentina

GSK Investigational Site

Buenos Aires, Buenos Aires, Argentina

GSK Investigational Site

Buenos Aires, , Argentina

GSK Investigational Site

Kippa-Ring, Queensland, Australia

GSK Investigational Site

Caulfield, Victoria, Australia

GSK Investigational Site

Geelong, Victoria, Australia

GSK Investigational Site

Pleven, , Bulgaria

GSK Investigational Site

Sofia, , Bulgaria

GSK Investigational Site

Sofia, , Bulgaria

GSK Investigational Site

Sofia, , Bulgaria

GSK Investigational Site

Oakville, Ontario, Canada

GSK Investigational Site

Ottawa, Ontario, Canada

GSK Investigational Site

Sainte-Foy, Quebec, Canada

GSK Investigational Site

Sainte-Foy, Quebec, Canada

GSK Investigational Site

Koebenhavn N, , Denmark

GSK Investigational Site

Tallinn, , Estonia

GSK Investigational Site

Tallinn, , Estonia

GSK Investigational Site

Tartu, , Estonia

GSK Investigational Site

Anzin, , France

GSK Investigational Site

Bron, , France

GSK Investigational Site

Créteil, , France

GSK Investigational Site

Dommartin-lès-Toul, , France

GSK Investigational Site

Gières, , France

GSK Investigational Site

Montbrison, , France

GSK Investigational Site

Montpellier, , France

GSK Investigational Site

Pessac, , France

GSK Investigational Site

Toulouse, , France

GSK Investigational Site

Kippenheim, Baden-Wurttemberg, Germany

GSK Investigational Site

Haag, Bavaria, Germany

GSK Investigational Site

Künzing, Bavaria, Germany

GSK Investigational Site

Munich, Bavaria, Germany

GSK Investigational Site

Nuremberg, Bavaria, Germany

GSK Investigational Site

Rednitzhembach, Bavaria, Germany

GSK Investigational Site

Hamburg, City state of Hamburg, Germany

GSK Investigational Site

Hamburg, City state of Hamburg, Germany

GSK Investigational Site

Hamburg, City state of Hamburg, Germany

GSK Investigational Site

Hamburg, City state of Hamburg, Germany

GSK Investigational Site

Schwerin, Mecklenburg-Vorpommern, Germany

GSK Investigational Site

Bochum, North Rhine-Westphalia, Germany

GSK Investigational Site

Cologne, North Rhine-Westphalia, Germany

GSK Investigational Site

Essen, North Rhine-Westphalia, Germany

GSK Investigational Site

Goch, North Rhine-Westphalia, Germany

GSK Investigational Site

Witten, North Rhine-Westphalia, Germany

GSK Investigational Site

Rhaunen, Rhineland-Palatinate, Germany

GSK Investigational Site

Dresden, Saxony, Germany

GSK Investigational Site

Leipzig, Saxony, Germany

GSK Investigational Site

Leipzig, Saxony, Germany

GSK Investigational Site

Berlin, State of Berlin, Germany

GSK Investigational Site

Berlin, State of Berlin, Germany

GSK Investigational Site

Berlin, State of Berlin, Germany

GSK Investigational Site

Berlin, State of Berlin, Germany

GSK Investigational Site

Budapest, , Hungary

GSK Investigational Site

Budapest, , Hungary

GSK Investigational Site

Debrecen, , Hungary

GSK Investigational Site

Szeged, , Hungary

GSK Investigational Site

Szolnok, , Hungary

GSK Investigational Site

Banglore, , India

GSK Investigational Site

Hyderabad, , India

GSK Investigational Site

New Delhi, , India

GSK Investigational Site

Den Helder, , Netherlands

GSK Investigational Site

Ede, , Netherlands

GSK Investigational Site

Enschede, , Netherlands

GSK Investigational Site

Haarlem, , Netherlands

GSK Investigational Site

Hoofddorp, , Netherlands

GSK Investigational Site

Rotterdam, , Netherlands

GSK Investigational Site

Sneek, , Netherlands

GSK Investigational Site

Zeist, , Netherlands

GSK Investigational Site

Hamilton, , New Zealand

GSK Investigational Site

Takapuna, , New Zealand

GSK Investigational Site

Karachi, , Pakistan

GSK Investigational Site

Karachi, , Pakistan

GSK Investigational Site

Bucharest, , Romania

GSK Investigational Site

Târgu Mureş, , Romania

GSK Investigational Site

Alicante, , Spain

GSK Investigational Site

Barcelona, , Spain

GSK Investigational Site

Barcelona, , Spain

GSK Investigational Site

Cáceres, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Móstoles/Madrid, , Spain

GSK Investigational Site

Oviedo, , Spain

GSK Investigational Site

Palma de Mallorca, , Spain

GSK Investigational Site

Quart de Poblet, Valencia, , Spain

GSK Investigational Site

Sant Joan d'Alacant, , Spain

GSK Investigational Site

Santa Coloma de Gramanet/Barcelona, , Spain

GSK Investigational Site

Santiago de Compostela, , Spain

GSK Investigational Site

Santiago de Compostela/La Coruña, , Spain

GSK Investigational Site

Tarrasa, Barcelona, , Spain

Countries

United States; Argentina; Australia; Bulgaria; Canada; Denmark; Estonia; France; Germany; Hungary; India; Netherlands; New Zealand; Pakistan; Romania; Spain

References

Mohler ER 3rd, Ballantyne CM, Davidson MH, Hanefeld M, Ruilope LM, Johnson JL, Zalewski A; Darapladib Investigators. The effect of darapladib on plasma lipoprotein-associated phospholipase A2 activity and cardiovascular biomarkers in patients with stable coronary heart disease or coronary heart disease risk equivalent: the results of a multicenter, randomized, double-blind, placebo-controlled study. J Am Coll Cardiol. 2008 Apr 29;51(17):1632-41. doi: 10.1016/j.jacc.2007.11.079.

Reference Type: DERIVED

PMID: 18436114 (View on PubMed)

Study Documents

Document Type: Clinical Study Report

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Informed Consent Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Statistical Analysis Plan

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Individual Participant Data Set

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Annotated Case Report Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Study Protocol

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Dataset Specification

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Related Links

https://www.clinicalstudydatarequest.com

Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Other Identifiers

LPL104884

Identifier Type: -

Identifier Source: org_study_id