A Phase II Clinical Study of SB-480848 in Dyslipidemic Patients

Study Overview
=================
Brief Summary
-----------------
The primary objective of this study is to examine the effects of SB-480848 on plasma lipoprotein associated phospholipase A2 (Lp-PLA2) activity in dyslipidemic patients during a 4-week treatment with SB-480848.

Official Title
-----------------
A Phase II Clinical Study of SB-480848 in Dyslipidemic Patients- A Multicenter, Randomized, Double-blind, Placebo-controlled Study of SB-480848 to Evaluate the Efficacy and Safety -

Conditions
-----------------
Atherosclerosis

Intervention / Treatment
-----------------
* Drug: SB480848 40mg EC Tablet
* Drug: SB480848 80mg EC Tablet
* Drug: SB480848 160mg EC Tablet
* Drug: SB480848 Placebo Tablet


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Dyslipidemic subject who is currently undergoing statin therapy and no change in lipid-lowering therapy or dose during the 4 week prior to randomization Exclusion criteria: Recent (i.e.,<6 months prior to screening) CV event and/or vascular procedure defined as: A)ST-elevation MI or non-ST-elevation MI B)Unstable angina C)Coronary revascularization [(percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG)] D)Stroke of any etiology E)Peripheral arterial disease with critical limb ischemia (resting pain or ischemic skin lesions, either ulcers or gangrene) F)Resuscitated cardiac arrest Planned CABG or planned PCI or planned major non-cardiac surgery within study period No measurable Lp-PLA2 activity in plasma (<10 nmol/min/mL) at screening Change in a lipid-lowering medication, regimen or dosage during the 4 week prior to randomization Poorly controlled dyslipidemia (LDL-c >=160 mg/dL) at screening

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo Group<br>Matched Placebo | Drug: SB480848 Placebo Tablet<br>* 1 tablet once a day<br>|
| Experimental: SB480848 40mg Group<br>SB480848 40mg/day | Drug: SB480848 40mg EC Tablet<br>* 1 tablet once a day<br>* Other names: Darapladib;|
| Experimental: SB480848 80mg Group<br>SB480848 80mg/day | Drug: SB480848 80mg EC Tablet<br>* 1 tablet once a day<br>|
| Experimental: SB480848 160mg Group<br>SB480848 160mg/day | Drug: SB480848 160mg EC Tablet<br>* 1 tablet once a day<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 4 in Plasma Lipoprotein-associated Phospholipase A2 (Lp-PLA2) Activity | Blood sample for Lp-PLA2 activity was collected before administration of study medication on the sampling day. Participants were instructed to visit without meal and study medication in the morning. The study medication was administered with food following test. Baseline value was defined as the assessment done on Week 0 (Visit 2). Change from Baseline was calculated as the post-Baseline (Week 4) assessment value minus the Baseline assessment value. If either value was missing, then the change from Baseline was set to be missing. The natural logarithm (log) was used for transformation in Lp-PLA2 activity. In case of zero values, an offset of 0.0001 was added to the zero values to ensure that the log transformation was successfully applied. The log transformation was conducted on the original value and then taken the change from Baseline on that log original value, calculated as log (post-Baseline value [week 4]) minus log (Baseline value). | Baseline (Week 0, Visit 2) and Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Inhibition of Lp-PLA2 Activity in Plasma Over Time | Blood sample for Lp-PLA2 activity was collected before administration of study medication on the sampling day. Participants were instructed to visit without meal and study medication in the morning. The study medication was administered with food following test. Baseline value was defined as the assessment done on Week 0 (Visit 2). Percentage inhibition of Lp-PLA2 activity relative to a Baseline value was calculated as: 100 multiplied by (post-Baseline values (Week 1, 2, 4 and Follow-up-Baseline value) divided by [Baseline value]). | Baseline (Week 0, Visit 2) up to Follow-up (up to Week 7) | 
| Change From Baseline in Lp-PLA2 Activity at Week 1, 2 and Follow-up | Blood sample for Lp-PLA2 activity was collected before administration of study medication on the sampling day. Participants were instructed to visit without meal and study medication in the morning. The study medication was administered with food following test. Baseline value was defined as the assessment done on Week 0 (Visit 2). Change from Baseline was calculated as the post-Baseline (Week 1, Week 2 and Follow-up) assessment values minus the Baseline assessment value. If either value was missing, then the change from Baseline was set to be missing. The log was used for transformation in Lp-PLA2 activity. In case of zero values, an offset of 0.0001 was added to the zero values to ensure that the log transformation was successfully applied. The log transformation was conducted on the original value and then taken change from Baseline on that log original value, calculated as log (post-Baseline [Week 1, Week 2 and Follow-up] values) minus log (Baseline value). | Baseline (Week 0, Visit 2), Week 1, Week 2 and Follow-up ( Week 7) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
SB-480848, Dyslipidaemia