SB-480848 In Subjects With Coronary Heart Disease

Atherosclerosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00269048
• Other study ID #: LPL104884
• Status: Completed
• Phase: Phase 2
• First received: December 21, 2005
• Last updated: August 5, 2016
• Start date: November 2005
• Est. completion date: September 2006

Study information

• Verified date: August 2016
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health CanadaUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 969
• Est. completion date: September 2006
• Est. primary completion date: September 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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).

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Atherosclerosis
• Coronary Artery Disease
• Coronary Disease
• Heart Diseases
• Myocardial Ischemia

Intervention

Drug:
• SB-480848
SB-480848
• placebo
placebo

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autónoma de Buenos Aires
Australia	GSK Investigational Site	Caulfield	Victoria
Australia	GSK Investigational Site	Geelong	Victoria
Australia	GSK Investigational Site	Kippa Ring	Queensland
Bulgaria	GSK Investigational Site	Pleven
Bulgaria	GSK Investigational Site	Sofia
Bulgaria	GSK Investigational Site	Sofia
Bulgaria	GSK Investigational Site	Sofia
Canada	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
Denmark	GSK Investigational Site	Koebenhavn N
Estonia	GSK Investigational Site	Tallinn
Estonia	GSK Investigational Site	Tallinn
Estonia	GSK Investigational Site	Tartu
France	GSK Investigational Site	Anzin
France	GSK Investigational Site	Bron Cedex
France	GSK Investigational Site	Créteil
France	GSK Investigational Site	Dommartin-les-Toul
France	GSK Investigational Site	Gières
France	GSK Investigational Site	Montbrison
France	GSK Investigational Site	Montpellier Cedex 5
France	GSK Investigational Site	Pessac cedex
France	GSK Investigational Site	Toulouse
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Bochum	Nordrhein-Westfalen
Germany	GSK Investigational Site	Dresden	Sachsen
Germany	GSK Investigational Site	Essen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Goch	Nordrhein-Westfalen
Germany	GSK Investigational Site	Haag	Bayern
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Kippenheim	Baden-Wuerttemberg
Germany	GSK Investigational Site	Koeln	Nordrhein-Westfalen
Germany	GSK Investigational Site	Kuenzing	Bayern
Germany	GSK Investigational Site	Leipzig	Sachsen
Germany	GSK Investigational Site	Leipzig	Sachsen
Germany	GSK Investigational Site	Muenchen	Bayern
Germany	GSK Investigational Site	Nuernberg	Bayern
Germany	GSK Investigational Site	Rednitzhembach	Bayern
Germany	GSK Investigational Site	Rhaunen	Rheinland-Pfalz
Germany	GSK Investigational Site	Schwerin	Mecklenburg-Vorpommern
Germany	GSK Investigational Site	Witten	Nordrhein-Westfalen
Hungary	GSK Investigational Site	Budapest
Hungary	GSK Investigational Site	Budapest
Hungary	GSK Investigational Site	Debrecen
Hungary	GSK Investigational Site	Szeged
Hungary	GSK Investigational Site	Szolnok
India	GSK Investigational Site	Banglore
India	GSK Investigational Site	Hyderabad
India	GSK Investigational Site	New Delhi
Netherlands	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
New Zealand	GSK Investigational Site	Hamilton
New Zealand	GSK Investigational Site	Takapuna
Pakistan	GSK Investigational Site	Karachi
Pakistan	GSK Investigational Site	Karachi
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Bucuresti
Romania	GSK Investigational Site	Targu-Mures
Spain	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	San Juan De Alicante
Spain	GSK Investigational Site	Santiago de Compostela
Spain	GSK Investigational Site	Santiago de Compostela/La Coruña
Spain	GSK Investigational Site	Sta. Coloma de Gramanet/Barcelona
Spain	GSK Investigational Site	Tarrasa, Barcelona
United States	GSK Investigational Site	Auburn	Maine
United States	GSK Investigational Site	Birmingham	Alabama
United States	GSK Investigational Site	Bryan	Texas
United States	GSK Investigational Site	Camp Hill	Pennsylvania
United States	GSK Investigational Site	Chicago	Illinois
United States	GSK Investigational Site	Chicago	Illinois
United States	GSK Investigational Site	Cincinnati	Ohio
United States	GSK Investigational Site	Fort Lauderdale	Florida
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Indianapolis	Indiana
United States	GSK Investigational Site	Jacksonville	Florida
United States	GSK Investigational Site	Lacombe	Louisiana
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	Norfolk	Virginia
United States	GSK Investigational Site	Northport	Alabama
United States	GSK Investigational Site	Oklahoma City	Oklahoma
United States	GSK Investigational Site	Pembroke Pines	Florida
United States	GSK Investigational Site	Philadelphia	Pennsylvania
United States	GSK Investigational Site	Phoenix	Arizona
United States	GSK Investigational Site	Richmond	Virginia
United States	GSK Investigational Site	Salt Lake City	Utah
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	Slidell	Louisiana
United States	GSK Investigational Site	Spring Valley	California
United States	GSK Investigational Site	Statesville	North Carolina
United States	GSK Investigational Site	Torrance	California
United States	GSK Investigational Site	Tucson	Arizona
United States	GSK Investigational Site	Walnut Creek	California

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	On treatment sustained inhibition of plasma Lp-PLA2 activity.		12 Weeks
Secondary	Difference in dose-dependent effects of SB-480848 on plasma Lp-PLA2 activity, other biomarkers, and safety.		12 Weeks

External Links

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