An Imaging Study in Patients With Atherosclerosis Taking Rilapladib or Placebo for 12 Weeks

A Multicenter, Randomized, 12 Week, Double-blind, Placebo-controlled, Parallel-group, Phase IIa Study Using 18F Fluorodeoxyglucose (FDG)-PET to Measure the Effects of Rilapladib on Macrophage Activity in Subjects With Atherosclerosis

A study in patients with atherosclerosis to assess safety, effect and PK of rilapladib vs. placebo over 12 weeks of dosing.

Study Overview

• Status: Completed
• Conditions: Atherosclerosis
• Intervention / Treatment: Drug: placebo; Drug: rilapladib; Other: 18F Fluorodeoxylucose (FDG)-PET

Detailed Description

Study LP2105521 is a randomized, double-blind, placebo-controlled, parallel-group study to examine the safety, tolerability, and effects of rilapladib on plasma Lp-PLA2 activity, plaque inflammation, and PAF (if feasible). Subjects will receive placebo or rilapladib once daily for 12 weeks. The study will be conducted in subjects with established atherosclerosis.

• Study Type: Interventional
• Enrollment (Actual): 83
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • GSK Investigational Site
    • Brockton, Massachusetts, United States, 02301
      • GSK Investigational Site
    • Haverhill, Massachusetts, United States, 01830
      • GSK Investigational Site
  • New Jersey
    • Linden, New Jersey, United States, 07036
      • GSK Investigational Site
  • New York
    • New York, New York, United States, 10065
      • GSK Investigational Site
    • New York, New York, United States, 10029
      • GSK Investigational Site
    • New York, New York, United States, 10001
      • GSK Investigational Site
    • New York, New York, United States, 10035
      • GSK Investigational Site
    • North Massapequa, New York, United States, 11758
      • GSK Investigational Site
  • Rhode Island
    • Warwick, Rhode Island, United States, 02886
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Capable of giving written informed consent and able to understand and comply with protocol requirements, instructions and protocol-stated restrictions.
• Male or female, aged 50 to 80 years inclusive, at screening.
• Females must be of non-childbearing potential
• Body weight ≥ 50 kg and BMI within the range 19-35 kg/m2
• Documented atherosclerotic vascular disease (e.g. prior MI, prior revascularization, peripheral arterial disease, carotid disease, or cerebrovascular disease) and clinically stable for at least 6 months
• If diabetic, have well controlled diabetes, defined for the purpose of this study as HbA1c ≤8% or FPG ≤200 mg/dL
• Evidence of plaque inflammation [carotid artery or ascending aorta plaque inflammation defined as a tissue to background ratio (TBR) ≥ 1.6]
• On a stable dose of a statin for 3 months prior to screening with no evidence of statin intolerance

Exclusion Criteria:

• Recent (i.e., <6 months from Screening Visit) CV event defined as ST-elevation MI or non-ST-elevation MI, confirmed by cardiac enzyme elevation and ECG changes, coronary revascularization (PCI or CABG), stroke of any etiology, resuscitated sudden death, prior carotid surgery or stenting procedure
• Evidence of clinical instability or abnormal clinical laboratory findings prior to randomization that, in the opinion of the Investigator, makes the subject unsuitable for the study.
• Exposure to substantial radiation within the past 12 months
• Planned cardiac surgery (e.g., CABG, valve repair or replacement, or aneurysmectomy), PCI or major non-cardiac surgery within the study period
• Current inadequately controlled hypertension (blood pressure ≥160 mmHg systolic or ≥100 mmHg diastolic) on a stable dose of anti-hypertensive medication
• Diabetics taking injectable insulin at screening
• Serum triglycerides >400 mg/dL, LDLc >130 mg/dL
• Recent (<1 month) or ongoing acute infection.
• History of chronic inflammatory disease
• Recently received (<1 month) or currently receiving oral or injectable corticosteroids, or regular use of nasal, inhaled or topical corticosteroids.
• Subjects who will commence, or who are likely to commence regular treatment with oral, non-steroidal anti-inflammatory drugs (NSAIDs) from screening until study completion
• Currently receiving oral or injectable potent CYP3A4 inhibitor(s)
• History of chronic viral hepatitis or other chronic hepatic disorders; or ALT or AST >1.5 x ULN, or alkaline phosphatase or total bilirubin >1.5 x ULN of laboratory reference range at Screen
• Renal impairment with serum creatinine >2.0 mg/dl or history of kidney transplant or status post nephrectomy.
• History of myopathy or inflammatory muscle disease, or elevated total CPK at screening
• History of severe heart failure defined as NYHA class III or IV or those with known severe left ventricular dysfunction (ejection fraction<30%) regardless of symptomatic status
• History of adult asthma (or reactive airway disease) manifested by bronchospasm in the past 6 months, or currently taking regular anti-asthmatic medication(s)
• History of anaphylaxis, anaphylactoid (resembling anaphylaxis) reactions or severe allergic responses
• History of malignancy within the past 2 years.
• A history of glaucoma or any other findings in the baseline eye exam
• Current life-threatening condition other than vascular disease that may prevent a subject from completing the study
• QTc interval ≥450msec at screening or ≥480 msec for subjects with bundle branch block
• History of drug abuse within the past 6 months
• Previous exposure to rilapladib.
• Contraindication to MRI scanning
• Use of an investigational drug within 30 days or 5 half-lives (whichever is the longer) preceding the first dose of study medication
• Any other subject the Investigator deems unsuitable for the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo; placebo to match	Drug: placebo; placebo
Active Comparator: rilapladib; 250 mg/day	Drug: rilapladib; 250 mg oral dose once daily; Other Names: SB-659032; Other: 18F Fluorodeoxylucose (FDG)-PET; FDG-PET; Other Names: FDG marker

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety from AE reporting, vital signs, clinical labs, ECGs, slit lamp eye exams and electron microscopy of peripheral blood lymphocytes.	12 weeks
LP-PLA2 activity;	12 weeks
changes in mean standard values of 18 FDG uptake as assessed by PET and MRI imaging	12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Estimation of PK parameters (such as: apparent volume of distribution, apparent clearance, etc.) of rilapladib and their associated variability, appropriate to the final model	12 weeks
Estimation of PK/PD parameters (such as: IC50, Eo) and their associated variability, appropriate to the final model	12 weeks
24 hour ambulatory blood pressure monitoring	12 weeks
PAF levels in human plasma as feasible	12 weeks

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: November 1, 2008
• Primary Completion (Actual): May 1, 2010
• Study Completion (Actual): May 1, 2010

Study Registration Dates

• First Submitted: June 9, 2008
• First Submitted That Met QC Criteria: June 9, 2008
• First Posted (Estimate): June 11, 2008

Study Record Updates

• Last Update Posted (Estimate): December 1, 2016
• Last Update Submitted That Met QC Criteria: November 30, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: atherosclerosis; rilapladib,; Lp-PLA2,; SB-659032,; FDG-PET,
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis
• Other Study ID Numbers: LP2105521

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. Dataset Specification
   Information identifier: LP2105521
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Clinical Study Report
   Information identifier: LP2105521
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Statistical Analysis Plan
   Information identifier: LP2105521
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Annotated Case Report Form
   Information identifier: LP2105521
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Individual Participant Data Set
   Information identifier: LP2105521
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Study Protocol
   Information identifier: LP2105521
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Informed Consent Form
   Information identifier: LP2105521
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register