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

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 -

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.

Study Overview

• Status: Completed
• Conditions: Atherosclerosis
• Intervention / Treatment: Drug: SB480848 Placebo Tablet; Drug: SB480848 40mg EC Tablet; Drug: SB480848 80mg EC Tablet; Drug: SB480848 160mg EC Tablet

• Study Type: Interventional
• Enrollment (Actual): 107
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan, 812-0025
    • GSK Investigational Site
  • Fukuoka, Japan, 818-0036
    • GSK Investigational Site
  • Fukuoka, Japan, 819-1102
    • GSK Investigational Site
  • Tokyo, Japan, 160-0017
    • GSK Investigational Site
  • Tokyo, Japan, 154-0024
    • GSK Investigational Site
  • Tokyo, Japan, 105-0004
    • GSK Investigational Site
  • Tokyo, Japan, 174-0051
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / 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 Names: 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

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)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

Helpful Links

• 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 record dates

Study Major Dates

• Study Start (ACTUAL): August 26, 2008
• Primary Completion (ACTUAL): January 16, 2009
• Study Completion (ACTUAL): January 16, 2009

Study Registration Dates

• First Submitted: August 12, 2008
• First Submitted That Met QC Criteria: August 12, 2008
• First Posted (ESTIMATE): August 13, 2008

Study Record Updates

• Last Update Posted (ACTUAL): January 12, 2018
• Last Update Submitted That Met QC Criteria: January 10, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: Dyslipidaemia; SB-480848
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Phospholipase A2 Inhibitors; Darapladib
• Other Study ID Numbers: LPL110118

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.

Study Data/Documents

1. Informed Consent Form
   Information identifier: LPL110118
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Annotated Case Report Form
   Information identifier: LPL110118
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Clinical Study Report
   Information identifier: LPL110118
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Dataset Specification
   Information identifier: LPL110118
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Individual Participant Data Set
   Information identifier: LPL110118
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Statistical Analysis Plan
   Information identifier: LPL110118
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register