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SB-480848 In Subjects With Coronary Heart Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00269048
Recruitment Status : Completed
First Posted : December 23, 2005
Last Update Posted : August 8, 2016
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Tracking Information
First Submitted Date  ICMJE December 21, 2005
First Posted Date  ICMJE December 23, 2005
Last Update Posted Date August 8, 2016
Study Start Date  ICMJE November 2005
Actual Primary Completion Date September 2006   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 14, 2007)
On treatment sustained inhibition of plasma Lp-PLA2 activity. [ Time Frame: 12 Weeks ]
Original Primary Outcome Measures  ICMJE
 (submitted: December 22, 2005)
On treatment sustained inhibition of plasma Lp-PLA2 activity.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 14, 2007)
Difference in dose-dependent effects of SB-480848 on plasma Lp-PLA2 activity, other biomarkers, and safety. [ Time Frame: 12 Weeks ]
Original Secondary Outcome Measures  ICMJE
 (submitted: December 22, 2005)
Difference in dose-dependent effects of SB-480848 on plasma Lp-PLA2 activity, other biomarkers, and safety.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE SB-480848 In Subjects With Coronary Heart Disease
Official Title  ICMJE 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
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
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
Condition  ICMJE Atherosclerosis
Intervention  ICMJE
  • Drug: SB-480848
    SB-480848
  • Drug: placebo
    placebo
Study Arms  ICMJE
  • Experimental: Arm 1
    SB-480848
    Intervention: Drug: SB-480848
  • Placebo Comparator: Arm 2
    placebo
    Intervention: Drug: placebo
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 5, 2016)
969
Original Enrollment  ICMJE
 (submitted: December 22, 2005)
920
Actual Study Completion Date  ICMJE September 2006
Actual Primary Completion Date September 2006   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Bulgaria,   Canada,   Denmark,   Estonia,   France,   Germany,   Hungary,   India,   Netherlands,   New Zealand,   Pakistan,   Romania,   Spain,   United States
Removed Location Countries United Kingdom
 
Administrative Information
NCT Number  ICMJE NCT00269048
Other Study ID Numbers  ICMJE LPL104884
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party GlaxoSmithKline
Study Sponsor  ICMJE GlaxoSmithKline
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: GSK Clinical Trials GlaxoSmithKline
PRS Account GlaxoSmithKline
Verification Date August 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP