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
Banglore, India
1.3 miles (2.1 km) away from your location
Status
Terminated/Withdrawn
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.
Additional information about the trial
Participate in clinical trial
Additional information
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
Click hereAccess to clinical trial data by researchers
Visit website