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

• ClinicalTrials.gov Identifier: NCT00734032
• Recruitment Status: Completed
• First Posted: August 13, 2008
• Results First Posted: January 12, 2018
• Last Update Posted: January 12, 2018
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Atherosclerosis	Drug: SB480848 40mg EC Tablet; Drug: SB480848 80mg EC Tablet; Drug: SB480848 160mg EC Tablet; Drug: SB480848 Placebo Tablet	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 107 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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 -
• Actual Study Start Date: August 26, 2008
• Actual Primary Completion Date: January 16, 2009
• Actual Study Completion Date: January 16, 2009

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo Group; Matched Placebo	Drug: SB480848 Placebo Tablet; 1 tablet once a day
Experimental: SB480848 40mg Group; SB480848 40mg/day	Drug: SB480848 40mg EC Tablet; 1 tablet once a day; Other Name: Darapladib
Experimental: SB480848 80mg Group; SB480848 80mg/day	Drug: SB480848 80mg EC Tablet; 1 tablet once a day
Experimental: SB480848 160mg Group; SB480848 160mg/day	Drug: SB480848 160mg EC Tablet; 1 tablet once a day

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline to Week 4 in Plasma Lipoprotein-associated Phospholipase A2 (Lp-PLA2) Activity [ Time Frame: Baseline (Week 0, Visit 2) and Week 4 ]
   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).

Secondary Outcome Measures :

1. Percent Inhibition of Lp-PLA2 Activity in Plasma Over Time [ Time Frame: Baseline (Week 0, Visit 2) up to Follow-up (up to Week 7) ]
   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]).
2. Change From Baseline in Lp-PLA2 Activity at Week 1, 2 and Follow-up [ Time Frame: Baseline (Week 0, Visit 2), Week 1, Week 2 and Follow-up ( Week 7) ]
   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).

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

1. 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

2. Planned CABG or planned PCI or planned major non-cardiac surgery within study period
3. No measurable Lp-PLA2 activity in plasma (<10 nmol/min/mL) at screening
4. Change in a lipid-lowering medication, regimen or dosage during the 4 week prior to randomization
5. Poorly controlled dyslipidemia (LDL-c >=160 mg/dL) at screening

Contacts and Locations

Locations

Japan

GSK Investigational Site

Fukuoka, Japan, 812-0025

GSK Investigational Site

Fukuoka, Japan, 818-0036

GSK Investigational Site

Fukuoka, Japan, 819-1102

GSK Investigational Site

Tokyo, Japan, 105-0004

GSK Investigational Site

Tokyo, Japan, 154-0024

GSK Investigational Site

Tokyo, Japan, 160-0017

GSK Investigational Site

Tokyo, Japan, 174-0051

Sponsors and Collaborators

GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

More Information

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. 

Study Data/Documents: Informed Consent Form 

Identifier: LPL110118
For additional information about this study please refer to the GSK Clinical Study Register

Annotated Case Report Form 

Identifier: LPL110118
For additional information about this study please refer to the GSK Clinical Study Register

Clinical Study Report 

Identifier: LPL110118
For additional information about this study please refer to the GSK Clinical Study Register

Dataset Specification 

Identifier: LPL110118
For additional information about this study please refer to the GSK Clinical Study Register

Individual Participant Data Set 

Identifier: LPL110118
For additional information about this study please refer to the GSK Clinical Study Register

Statistical Analysis Plan 

Identifier: LPL110118
For additional information about this study please refer to the GSK Clinical Study Register

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00734032
• Other Study ID Numbers: LPL110118
• First Posted: August 13, 2008
• Results First Posted: January 12, 2018
• Last Update Posted: January 12, 2018
• Last Verified: January 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Keywords provided by GlaxoSmithKline:

SB-480848; Dyslipidaemia

Additional relevant MeSH terms:

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Darapladib; Phospholipase A2 Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action