SB-480848 In Subjects With Coronary Heart Disease

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00269048
First received: December 21, 2005
Last updated: August 5, 2016
Last verified: August 2016
  Purpose
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 Intervention Phase
Atherosclerosis
Drug: SB-480848
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

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

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

Enrollment: 969
Study Start Date: November 2005
Study Completion Date: September 2006
Primary Completion Date: September 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
SB-480848
Drug: SB-480848
SB-480848
Placebo Comparator: Arm 2
placebo
Drug: placebo
placebo

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
  Eligibility

Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00269048

  Hide Study Locations
Locations
United States, Alabama
GSK Investigational Site
Birmingham, Alabama, United States, 35294
GSK Investigational Site
Northport, Alabama, United States, 35476
United States, Arizona
GSK Investigational Site
Phoenix, Arizona, United States, 85014
GSK Investigational Site
Tucson, Arizona, United States, 85715
United States, California
GSK Investigational Site
Spring Valley, California, United States, 91978
GSK Investigational Site
Torrance, California, United States, 90509
GSK Investigational Site
Walnut Creek, California, United States, 94598
United States, Florida
GSK Investigational Site
Fort Lauderdale, Florida, United States, 33308
GSK Investigational Site
Jacksonville, Florida, United States, 32205
GSK Investigational Site
Pembroke Pines, Florida, United States, 33024
United States, Illinois
GSK Investigational Site
Chicago, Illinois, United States, 60607
GSK Investigational Site
Chicago, Illinois, United States, 60610
United States, Indiana
GSK Investigational Site
Indianapolis, Indiana, United States, 46260
United States, Louisiana
GSK Investigational Site
Lacombe, Louisiana, United States, 70445
GSK Investigational Site
Slidell, Louisiana, United States, 70458
United States, Maine
GSK Investigational Site
Auburn, Maine, United States, 04210
United States, New York
GSK Investigational Site
New York, New York, United States, 10016
United States, North Carolina
GSK Investigational Site
Statesville, North Carolina, United States, 28677
United States, Ohio
GSK Investigational Site
Cincinnati, Ohio, United States, 45219
United States, Oklahoma
GSK Investigational Site
Oklahoma City, Oklahoma, United States, 73132
United States, Pennsylvania
GSK Investigational Site
Camp Hill, Pennsylvania, United States, 17011
GSK Investigational Site
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
GSK Investigational Site
Bryan, Texas, United States, 77802
GSK Investigational Site
Houston, Texas, United States, 77030
GSK Investigational Site
San Antonio, Texas, United States, 78229
United States, Utah
GSK Investigational Site
Salt Lake City, Utah, United States, 84143
United States, Virginia
GSK Investigational Site
Norfolk, Virginia, United States, 23502
GSK Investigational Site
Richmond, Virginia, United States, 23294
Argentina
GSK Investigational Site
Buenos Aires, Argentina, 1425
GSK Investigational Site
Buenos Aires, Argentina, 1704
GSK Investigational Site
Ciudad Autónoma de Buenos Aires, Argentina, C1408INH
Australia, Queensland
GSK Investigational Site
Kippa Ring, Queensland, Australia, 4021
Australia, Victoria
GSK Investigational Site
Caulfield, Victoria, Australia, 3162
GSK Investigational Site
Geelong, Victoria, Australia, 3220
Bulgaria
GSK Investigational Site
Pleven, Bulgaria, 5800
GSK Investigational Site
Sofia, Bulgaria, 1000
GSK Investigational Site
Sofia, Bulgaria, 1309
GSK Investigational Site
Sofia, Bulgaria, 1572
Canada, Ontario
GSK Investigational Site
Oakville, Ontario, Canada, L6H 3P1
GSK Investigational Site
Ottawa, Ontario, Canada, K1Y 4W7
Canada, Quebec
GSK Investigational Site
Sainte-Foy, Quebec, Canada, G1V 4G2
GSK Investigational Site
Sainte-Foy, Quebec, Canada, G1V 4G5
Denmark
GSK Investigational Site
Koebenhavn N, Denmark, 2100
Estonia
GSK Investigational Site
Tallinn, Estonia, 1162
GSK Investigational Site
Tallinn, Estonia, 13419
GSK Investigational Site
Tartu, Estonia, 51014
France
GSK Investigational Site
Anzin, France, 59410
GSK Investigational Site
Bron Cedex, France, 69677
GSK Investigational Site
Créteil, France, 94000
GSK Investigational Site
Dommartin-les-Toul, France, 54201
GSK Investigational Site
Gières, France, 38610
GSK Investigational Site
Montbrison, France, 42600
GSK Investigational Site
Montpellier Cedex 5, France, 34295
GSK Investigational Site
Pessac cedex, France, 33604
GSK Investigational Site
Toulouse, France, 31300
Germany
GSK Investigational Site
Kippenheim, Baden-Wuerttemberg, Germany, 77971
GSK Investigational Site
Haag, Bayern, Germany, 83527
GSK Investigational Site
Kuenzing, Bayern, Germany, 94550
GSK Investigational Site
Muenchen, Bayern, Germany, 81241
GSK Investigational Site
Nuernberg, Bayern, Germany, 90402
GSK Investigational Site
Rednitzhembach, Bayern, Germany, 91126
GSK Investigational Site
Schwerin, Mecklenburg-Vorpommern, Germany, 19055
GSK Investigational Site
Bochum, Nordrhein-Westfalen, Germany, 44787
GSK Investigational Site
Essen, Nordrhein-Westfalen, Germany, 45359
GSK Investigational Site
Goch, Nordrhein-Westfalen, Germany, 47574
GSK Investigational Site
Koeln, Nordrhein-Westfalen, Germany, 51069
GSK Investigational Site
Witten, Nordrhein-Westfalen, Germany, 58455
GSK Investigational Site
Rhaunen, Rheinland-Pfalz, Germany, 55624
GSK Investigational Site
Dresden, Sachsen, Germany, 01307
GSK Investigational Site
Leipzig, Sachsen, Germany, 04229
GSK Investigational Site
Leipzig, Sachsen, Germany, 04315
GSK Investigational Site
Berlin, Germany, 10249
GSK Investigational Site
Berlin, Germany, 10367
GSK Investigational Site
Berlin, Germany, 12163
GSK Investigational Site
Berlin, Germany, 13125
GSK Investigational Site
Hamburg, Germany, 20249
GSK Investigational Site
Hamburg, Germany, 22041
GSK Investigational Site
Hamburg, Germany, 22143
GSK Investigational Site
Hamburg, Germany, 22335
Hungary
GSK Investigational Site
Budapest, Hungary, 1032
GSK Investigational Site
Budapest, Hungary, 1135
GSK Investigational Site
Debrecen, Hungary, 4004
GSK Investigational Site
Szeged, Hungary, 6720
GSK Investigational Site
Szolnok, Hungary, 5000
India
GSK Investigational Site
Banglore, India
GSK Investigational Site
Hyderabad, India, 500034
GSK Investigational Site
New Delhi, India, 110044
Netherlands
GSK Investigational Site
Den Helder, Netherlands, 1782 GZ
GSK Investigational Site
EDE, Netherlands, 6716 RP
GSK Investigational Site
Enschede, Netherlands, 7511JX
GSK Investigational Site
Haarlem, Netherlands, 2035 RC
GSK Investigational Site
Hoofddorp, Netherlands, 2130 AT
GSK Investigational Site
Rotterdam, Netherlands, 3011 TD
GSK Investigational Site
Sneek, Netherlands, 8601 ZK
GSK Investigational Site
Zeist, Netherlands, 3707 HL
New Zealand
GSK Investigational Site
Hamilton, New Zealand, 2001
GSK Investigational Site
Takapuna, New Zealand
Pakistan
GSK Investigational Site
Karachi, Pakistan, 74800
GSK Investigational Site
Karachi, Pakistan, 75510
Romania
GSK Investigational Site
Bucharest, Romania
GSK Investigational Site
Bucuresti, Romania
GSK Investigational Site
Targu-Mures, Romania
Spain
GSK Investigational Site
Alicante, Spain, 03114
GSK Investigational Site
Barcelona, Spain, 080018
GSK Investigational Site
Barcelona, Spain, 08022
GSK Investigational Site
Cáceres, Spain, 10004
GSK Investigational Site
Madrid, Spain, 28034
GSK Investigational Site
Madrid, Spain, 28035
GSK Investigational Site
Madrid, Spain, 28037
GSK Investigational Site
Madrid, Spain, 28041
GSK Investigational Site
Madrid, Spain, 28046
GSK Investigational Site
Móstoles/Madrid, Spain, 28935
GSK Investigational Site
Oviedo, Spain, 33006
GSK Investigational Site
Palma de Mallorca, Spain, 07014
GSK Investigational Site
Quart de Poblet, Valencia, Spain, 46930
GSK Investigational Site
San Juan De Alicante, Spain, 3550
GSK Investigational Site
Santiago de Compostela/La Coruña, Spain, 15706
GSK Investigational Site
Santiago de Compostela, Spain, 15706
GSK Investigational Site
Sta. Coloma de Gramanet/Barcelona, Spain, 08923
GSK Investigational Site
Tarrasa, Barcelona, Spain, 08221
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Additional Information:
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 
Study First Received: December 21, 2005
Last Updated: August 5, 2016
Health Authority: Canada: Health Canada
United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on August 25, 2016