SB-480848 In Subjects With Coronary Heart Disease

NCT00269048 | Completed Phase 2

• 1 other identifier: LPL104884
• Study Type: interventional
• Target: 969
• Locations: 15 countries
• Sites: 116

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.

Conditions

Atherosclerosis

Keywords

CHD; Lp-PLA2; SB-480848

Outcome Measures

Primary Outcomes (1)

• On treatment sustained inhibition of plasma Lp-PLA2 activity.

  12 Weeks

Secondary Outcomes (1)

• Difference in dose-dependent effects of SB-480848 on plasma Lp-PLA2 activity, other biomarkers, and safety.

  12 Weeks

Study Arms (2)

Arm 1

EXPERIMENTAL

SB-480848

Drug: SB-480848

Arm 2

PLACEBO COMPARATOR

placebo

Drug: placebo

Interventions

SB-480848 DRUG

SB-480848

Arm 1

placebo DRUG

placebo

Arm 2

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (119)

GSK Investigational Site

Birmingham, Alabama, 35294, United States

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GSK Investigational Site

Northport, Alabama, 35476, United States

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Phoenix, Arizona, 85014, United States

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GSK Investigational Site

Tucson, Arizona, 85715, United States

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Spring Valley, California, 91978, United States

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GSK Investigational Site

Torrance, California, 90509, United States

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GSK Investigational Site

Walnut Creek, California, 94598, United States

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Fort Lauderdale, Florida, 33308, United States

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Jacksonville, Florida, 32205, United States

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GSK Investigational Site

Pembroke Pines, Florida, 33024, United States

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Chicago, Illinois, 60607, United States

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Chicago, Illinois, 60610, United States

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Indianapolis, Indiana, 46260, United States

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Lacombe, Louisiana, 70445, United States

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Slidell, Louisiana, 70458, United States

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Auburn, Maine, 04210, United States

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New York, New York, 10016, United States

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Statesville, North Carolina, 28677, United States

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Cincinnati, Ohio, 45219, United States

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Oklahoma City, Oklahoma, 73132, United States

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Camp Hill, Pennsylvania, 17011, United States

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Philadelphia, Pennsylvania, 19104, United States

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Bryan, Texas, 77802, United States

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Houston, Texas, 77030, United States

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San Antonio, Texas, 78229, United States

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Salt Lake City, Utah, 84143, United States

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Norfolk, Virginia, 23502, United States

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Richmond, Virginia, 23294, United States

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Buenos Aires, Buenos Aires, 1425, Argentina

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Buenos Aires, Buenos Aires, 1704, Argentina

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Buenos Aires, C1408INH, Argentina

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Kippa-Ring, Queensland, 4021, Australia

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Caulfield, Victoria, 3162, Australia

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Geelong, Victoria, 3220, Australia

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Pleven, 5800, Bulgaria

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Sofia, 1000, Bulgaria

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Sofia, 1309, Bulgaria

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Sofia, 1572, Bulgaria

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Oakville, Ontario, L6H 3P1, Canada

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Ottawa, Ontario, K1Y 4W7, Canada

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Sainte-Foy, Quebec, G1V 4G2, Canada

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Sainte-Foy, Quebec, G1V 4G5, Canada

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GSK Investigational Site

Koebenhavn N, 2100, Denmark

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Tallinn, 1162, Estonia

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Tallinn, 13419, Estonia

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Tartu, 51014, Estonia

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Anzin, 59410, France

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Bron, 69677, France

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Créteil, 94000, France

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Dommartin-lès-Toul, 54201, France

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Gières, 38610, France

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Montbrison, 42600, France

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Montpellier, 34295, France

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Pessac, 33604, France

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Toulouse, 31300, France

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Kippenheim, Baden-Wurttemberg, 77971, Germany

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Haag, Bavaria, 83527, Germany

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Künzing, Bavaria, 94550, Germany

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Munich, Bavaria, 81241, Germany

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Nuremberg, Bavaria, 90402, Germany

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Rednitzhembach, Bavaria, 91126, Germany

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Hamburg, Hamburg, 20249, Germany

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Hamburg, Hamburg, 22041, Germany

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Hamburg, Hamburg, 22143, Germany

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Hamburg, Hamburg, 22335, Germany

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Schwerin, Mecklenburg-Vorpommern, 19055, Germany

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Bochum, North Rhine-Westphalia, 44787, Germany

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Cologne, North Rhine-Westphalia, 51069, Germany

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Essen, North Rhine-Westphalia, 45359, Germany

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Goch, North Rhine-Westphalia, 47574, Germany

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Witten, North Rhine-Westphalia, 58455, Germany

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Rhaunen, Rhineland-Palatinate, 55624, Germany

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Dresden, Saxony, 01307, Germany

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Leipzig, Saxony, 04229, Germany

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Leipzig, Saxony, 04315, Germany

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Berlin, State of Berlin, 10249, Germany

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Berlin, State of Berlin, 10367, Germany

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Berlin, State of Berlin, 12163, Germany

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Berlin, State of Berlin, 13125, Germany

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Budapest, 1032, Hungary

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Budapest, 1135, Hungary

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Debrecen, 4004, Hungary

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Szeged, 6720, Hungary

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Szolnok, 5000, Hungary

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Banglore, India

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Hyderabad, 500034, India

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New Delhi, 110044, India

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Den Helder, 1782 GZ, Netherlands

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GSK Investigational Site

Ede, 6716 RP, Netherlands

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GSK Investigational Site

Enschede, 7511JX, Netherlands

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Haarlem, 2035 RC, Netherlands

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Hoofddorp, 2130 AT, Netherlands

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Rotterdam, 3011 TD, Netherlands

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Sneek, 8601 ZK, Netherlands

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Zeist, 3707 HL, Netherlands

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Hamilton, 2001, New Zealand

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Takapuna, New Zealand

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Karachi, 74800, Pakistan

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GSK Investigational Site

Karachi, 75510, Pakistan

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Bucharest, Romania

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GSK Investigational Site

Târgu Mureş, Romania

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GSK Investigational Site

Alicante, 03114, Spain

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GSK Investigational Site

Barcelona, 080018, Spain

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GSK Investigational Site

Barcelona, 08022, Spain

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GSK Investigational Site

Cáceres, 10004, Spain

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GSK Investigational Site

Madrid, 28034, Spain

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GSK Investigational Site

Madrid, 28035, Spain

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GSK Investigational Site

Madrid, 28037, Spain

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GSK Investigational Site

Madrid, 28041, Spain

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GSK Investigational Site

Madrid, 28046, Spain

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GSK Investigational Site

Móstoles/Madrid, 28935, Spain

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GSK Investigational Site

Oviedo, 33006, Spain

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GSK Investigational Site

Palma de Mallorca, 07014, Spain

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GSK Investigational Site

Quart de Poblet, Valencia, 46930, Spain

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GSK Investigational Site

Sant Joan d'Alacant, 3550, Spain

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GSK Investigational Site

Santa Coloma de Gramanet/Barcelona, 08923, Spain

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GSK Investigational Site

Santiago de Compostela, 15706, Spain

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GSK Investigational Site

Santiago de Compostela/La Coruña, 15706, Spain

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GSK Investigational Site

Tarrasa, Barcelona, 08221, Spain

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Related Publications (1)

• 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.

  PMID: 18436114 DERIVED

Related 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.

MeSH Terms

Conditions

Atherosclerosis

Interventions

darapladib

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2005
• First Posted: December 23, 2005
• Study Start: November 1, 2005
• Primary Completion: September 1, 2006
• Study Completion: September 1, 2006
• Last Updated: August 8, 2016

Record last verified: 2016-08

Locations

US (28); DK (1); BU (4); IN (3); NZ (2); ES (18); CA (4); PA (2); AU (3); RO (2); DE (24); HU (5); FR (9); NL (8); AR (3)