Last updated: 11/07/2018 17:30:35
SB-480848 In Subjects With Coronary Heart Disease
Clinicaltrials.gov ID
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
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
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Double (Participant, Care Provider)
Allocation:
Randomized
Primary outcomes:
On treatment sustained inhibition of plasma Lp-PLA2 activity.
Timeframe: 12 Weeks
Secondary outcomes:
Difference in dose-dependent effects of SB-480848 on plasma Lp-PLA2 activity, other biomarkers, and safety.
Timeframe: 12 Weeks
Interventions:
Drug: SB-480848
Drug: placebo
Enrollment:
969
Observational study model:
Not applicable
Primary completion date:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Mohler ER III, Ballantyne CM, Davidson MH, Hanefeld M, Ruilope LM, Johnson JL, Zalewski for the 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. Journal of the American College of Cardiology. 2008;51;1632-1641.
Medical condition
Atherosclerosis
Product
darapladib
Collaborators
Not applicable
Study date(s)
November 2005 to September 2006
Type
Interventional
Phase
2
Participation criteria
Sex
Female & Male
Age
18 - 80 years
Accepts healthy volunteers
No
- Female subjects must be of non-childbearing potential.
- Stable CHD or CHD-risk equivalent.
- Recent cardiovascular event and / or vascular procedure.
- History of difficult to manage dyslipidemia.
Inclusion and exclusion 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).
Trial location(s)
Location
GSK Investigational Site
Rhaunen, Rheinland-Pfalz, Germany, 55624
Status
Study Complete
Location
GSK Investigational Site
Ciudad Autónoma de Buenos Aires, Argentina, C1408INH
Status
Study Complete
Location
GSK Investigational Site
New York, New York, United States, 10016
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Indianapolis, Indiana, United States, 46260
Status
Study Complete
Location
GSK Investigational Site
Phoenix, Arizona, United States, 85014
Status
Study Complete
Location
GSK Investigational Site
Birmingham, Alabama, United States, 35294
Status
Study Complete
Location
GSK Investigational Site
Statesville, North Carolina, United States, 28677
Status
Study Complete
Location
GSK Investigational Site
Richmond, Virginia, United States, 23294
Status
Study Complete
Location
GSK Investigational Site
Norfolk, Virginia, United States, 23502
Status
Study Complete
Location
GSK Investigational Site
Goch, Nordrhein-Westfalen, Germany, 47574
Status
Study Complete
Location
GSK Investigational Site
Kippa Ring, Queensland, Australia, 4021
Status
Study Complete
Location
GSK Investigational Site
Chicago, Illinois, United States, 60607
Status
Study Complete
Location
GSK Investigational Site
Torrance, California, United States, 90509
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Kippenheim, Baden-Wuerttemberg, Germany, 77971
Status
Study Complete
Location
GSK Investigational Site
Witten, Nordrhein-Westfalen, Germany, 58455
Status
Study Complete
Location
GSK Investigational Site
Jacksonville, Florida, United States, 32205
Status
Study Complete
Location
GSK Investigational Site
San Antonio, Texas, United States, 78229
Status
Study Complete
Location
GSK Investigational Site
Northport, Alabama, United States, 35476
Status
Study Complete
Location
GSK Investigational Site
Cincinnati, Ohio, United States, 45219
Status
Study Complete
Location
GSK Investigational Site
Buenos Aires, Buenos Aires, Argentina, 1425
Status
Study Complete
Location
GSK Investigational Site
Buenos Aires, Buenos Aires, Argentina, 1704
Status
Study Complete
Location
GSK Investigational Site
Essen, Nordrhein-Westfalen, Germany, 45359
Status
Study Complete
Location
GSK Investigational Site
Slidell, Louisiana, United States, 70458
Status
Study Complete
Location
GSK Investigational Site
Sta. Coloma de Gramanet/Barcelona, Spain, 08923
Status
Study Complete
Location
GSK Investigational Site
Oklahoma City, Oklahoma, United States, 73132
Status
Study Complete
Location
GSK Investigational Site
Lacombe, Louisiana, United States, 70445
Status
Study Complete
Location
GSK Investigational Site
Camp Hill, Pennsylvania, United States, 17011
Status
Study Complete
Location
GSK Investigational Site
Koeln, Nordrhein-Westfalen, Germany, 51069
Status
Study Complete
Location
GSK Investigational Site
Pembroke Pines, Florida, United States, 33024
Status
Study Complete
Location
GSK Investigational Site
Fort Lauderdale, Florida, United States, 33308
Status
Study Complete
Location
GSK Investigational Site
Philadelphia, Pennsylvania, United States, 19104
Status
Study Complete
Location
GSK Investigational Site
Rednitzhembach, Bayern, Germany, 91126
Status
Study Complete
Location
GSK Investigational Site
Salt Lake City, Utah, United States, 84143
Status
Study Complete
Location
GSK Investigational Site
Schwerin, Mecklenburg-Vorpommern, Germany, 19055
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Santiago de Compostela/La Coruña, Spain, 15706
Status
Study Complete
Location
GSK Investigational Site
Quart de Poblet, Valencia, Spain, 46930
Status
Study Complete
Location
GSK Investigational Site
Walnut Creek, California, United States, 94598
Status
Study Complete
Location
GSK Investigational Site
Bochum, Nordrhein-Westfalen, Germany, 44787
Status
Study Complete
Location
GSK Investigational Site
Spring Valley, California, United States, 91978
Status
Study Complete
Location
GSK Investigational Site
Chicago, Illinois, United States, 60610
Status
Study Complete
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
Completed
Actual primary completion date
Not applicable
Actual study completion date
2006-27-09
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
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