SB-480848 In Subjects With Coronary Heart Disease

August 5, 2016 updated by: GlaxoSmithKline

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

969

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Buenos Aires, Argentina, 1425
        • GSK Investigational Site
      • Buenos Aires, Argentina, 1704
        • GSK Investigational Site
      • Ciudad Autónoma de Buenos Aires, Argentina, C1408INH
        • GSK Investigational Site
  • Australia
    • Queensland
      • Kippa Ring, Queensland, Australia, 4021
        • GSK Investigational Site
    • Victoria
      • Caulfield, Victoria, Australia, 3162
        • GSK Investigational Site
      • Geelong, Victoria, Australia, 3220
        • GSK Investigational Site
  • Bulgaria
      • Pleven, Bulgaria, 5800
        • GSK Investigational Site
      • Sofia, Bulgaria, 1000
        • GSK Investigational Site
      • Sofia, Bulgaria, 1309
        • GSK Investigational Site
      • Sofia, Bulgaria, 1572
        • GSK Investigational Site
  • Canada
    • Ontario
      • Oakville, Ontario, Canada, L6H 3P1
        • GSK Investigational Site
      • Ottawa, Ontario, Canada, K1Y 4W7
        • GSK Investigational Site
    • Quebec
      • Sainte-Foy, Quebec, Canada, G1V 4G5
        • GSK Investigational Site
      • Sainte-Foy, Quebec, Canada, G1V 4G2
        • GSK Investigational Site
  • Denmark
      • Koebenhavn N, Denmark, 2100
        • GSK Investigational Site
  • Estonia
      • Tallinn, Estonia, 13419
        • GSK Investigational Site
      • Tallinn, Estonia, 1162
        • GSK Investigational Site
      • Tartu, Estonia, 51014
        • GSK Investigational Site
  • France
      • 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
        • GSK Investigational Site
  • Germany
      • Berlin, Germany, 10367
        • GSK Investigational Site
      • Berlin, Germany, 13125
        • GSK Investigational Site
      • Berlin, Germany, 10249
        • GSK Investigational Site
      • Berlin, Germany, 12163
        • GSK Investigational Site
      • Hamburg, Germany, 22143
        • GSK Investigational Site
      • Hamburg, Germany, 20249
        • GSK Investigational Site
      • Hamburg, Germany, 22335
        • GSK Investigational Site
      • Hamburg, Germany, 22041
        • GSK Investigational Site
    • Baden-Wuerttemberg
      • Kippenheim, Baden-Wuerttemberg, Germany, 77971
        • GSK Investigational Site
    • Bayern
      • 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
    • Mecklenburg-Vorpommern
      • Schwerin, Mecklenburg-Vorpommern, Germany, 19055
        • GSK Investigational Site
    • Nordrhein-Westfalen
      • 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
    • Rheinland-Pfalz
      • Rhaunen, Rheinland-Pfalz, Germany, 55624
        • GSK Investigational Site
    • Sachsen
      • Dresden, Sachsen, Germany, 01307
        • GSK Investigational Site
      • Leipzig, Sachsen, Germany, 04229
        • GSK Investigational Site
      • Leipzig, Sachsen, Germany, 04315
        • GSK Investigational Site
  • Hungary
      • 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
        • GSK Investigational Site
  • India
      • Banglore, India
        • GSK Investigational Site
      • Hyderabad, India, 500034
        • GSK Investigational Site
      • New Delhi, India, 110044
        • GSK Investigational Site
  • Netherlands
      • 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
        • GSK Investigational Site
  • New Zealand
      • Hamilton, New Zealand, 2001
        • GSK Investigational Site
      • Takapuna, New Zealand
        • GSK Investigational Site
  • Pakistan
      • Karachi, Pakistan, 74800
        • GSK Investigational Site
      • Karachi, Pakistan, 75510
        • GSK Investigational Site
  • Romania
      • Bucharest, Romania
        • GSK Investigational Site
      • Bucuresti, Romania
        • GSK Investigational Site
      • Targu-Mures, Romania
        • GSK Investigational Site
  • Spain
      • Alicante, Spain, 03114
        • GSK Investigational Site
      • Barcelona, Spain, 08022
        • GSK Investigational Site
      • Barcelona, Spain, 080018
        • GSK Investigational Site
      • Cáceres, Spain, 10004
        • GSK Investigational Site
      • Madrid, Spain, 28041
        • GSK Investigational Site
      • Madrid, Spain, 28046
        • GSK Investigational Site
      • Madrid, Spain, 28034
        • GSK Investigational Site
      • Madrid, Spain, 28035
        • GSK Investigational Site
      • Madrid, Spain, 28037
        • 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, Spain, 15706
        • GSK Investigational Site
      • Santiago de Compostela/La Coruña, Spain, 15706
        • GSK Investigational Site
      • Sta. Coloma de Gramanet/Barcelona, Spain, 08923
        • GSK Investigational Site
      • Tarrasa, Barcelona, Spain, 08221
        • GSK Investigational Site
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • GSK Investigational Site
      • Northport, Alabama, United States, 35476
        • GSK Investigational Site
    • Arizona
      • Phoenix, Arizona, United States, 85014
        • GSK Investigational Site
      • Tucson, Arizona, United States, 85715
        • GSK Investigational Site
    • California
      • Spring Valley, California, United States, 91978
        • GSK Investigational Site
      • Torrance, California, United States, 90509
        • GSK Investigational Site
      • Walnut Creek, California, United States, 94598
        • GSK Investigational Site
    • Florida
      • Fort Lauderdale, Florida, United States, 33308
        • GSK Investigational Site
      • Jacksonville, Florida, United States, 32205
        • GSK Investigational Site
      • Pembroke Pines, Florida, United States, 33024
        • GSK Investigational Site
    • Illinois
      • Chicago, Illinois, United States, 60610
        • GSK Investigational Site
      • Chicago, Illinois, United States, 60607
        • GSK Investigational Site
    • Indiana
      • Indianapolis, Indiana, United States, 46260
        • GSK Investigational Site
    • Louisiana
      • Lacombe, Louisiana, United States, 70445
        • GSK Investigational Site
      • Slidell, Louisiana, United States, 70458
        • GSK Investigational Site
    • Maine
      • Auburn, Maine, United States, 04210
        • GSK Investigational Site
    • New York
      • New York, New York, United States, 10016
        • GSK Investigational Site
    • North Carolina
      • Statesville, North Carolina, United States, 28677
        • GSK Investigational Site
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • GSK Investigational Site
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73132
        • GSK Investigational Site
    • Pennsylvania
      • Camp Hill, Pennsylvania, United States, 17011
        • GSK Investigational Site
      • Philadelphia, Pennsylvania, United States, 19104
        • GSK Investigational Site
    • Texas
      • Bryan, Texas, United States, 77802
        • GSK Investigational Site
      • Houston, Texas, United States, 77030
        • GSK Investigational Site
      • San Antonio, Texas, United States, 78229
        • GSK Investigational Site
    • Utah
      • Salt Lake City, Utah, United States, 84143
        • GSK Investigational Site
    • Virginia
      • Norfolk, Virginia, United States, 23502
        • GSK Investigational Site
      • Richmond, Virginia, United States, 23294
        • GSK Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Arm 1
SB-480848
Drug: SB-480848
SB-480848
PLACEBO_COMPARATOR: Arm 2
placebo
Drug: placebo
placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
On treatment sustained inhibition of plasma Lp-PLA2 activity.
Time Frame: 12 Weeks
12 Weeks

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

GlaxoSmithKline

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2005

Primary Completion (ACTUAL)

September 1, 2006

Study Completion (ACTUAL)

September 1, 2006

Study Registration Dates

First Submitted

December 21, 2005

First Submitted That Met QC Criteria

December 22, 2005

First Posted (ESTIMATE)

December 23, 2005

Study Record Updates

Last Update Posted (ESTIMATE)

August 8, 2016

Last Update Submitted That Met QC Criteria

August 5, 2016

Last Verified

August 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LPL104884

Plan for Individual participant data (IPD)

Study Data/Documents

  1. Clinical Study Report
    Information identifier: LPL104884
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  2. Informed Consent Form
    Information identifier: LPL104884
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  3. Statistical Analysis Plan
    Information identifier: LPL104884
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  4. Individual Participant Data Set
    Information identifier: LPL104884
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  5. Annotated Case Report Form
    Information identifier: LPL104884
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  6. Study Protocol
    Information identifier: LPL104884
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  7. Dataset Specification
    Information identifier: LPL104884
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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