Status:

COMPLETED

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

Lead Sponsor:

GlaxoSmithKline

Conditions:

Atherosclerosis

Eligibility:

All Genders

50-80 years

Phase:

PHASE2

Brief Summary

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

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, ...

Eligibility Criteria

Inclusion

  • 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

  • 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

Key Trial Info

Start Date :

November 1 2008

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

May 1 2010

Estimated Enrollment :

83 Patients enrolled

Trial Details

Trial ID

NCT00695305

Start Date

November 1 2008

End Date

May 1 2010

Last Update

December 1 2016

Active Locations (10)

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Page 1 of 3 (10 locations)

1

GSK Investigational Site

Boston, Massachusetts, United States, 02114

2

GSK Investigational Site

Brockton, Massachusetts, United States, 02301

3

GSK Investigational Site

Haverhill, Massachusetts, United States, 01830

4

GSK Investigational Site

Linden, New Jersey, United States, 07036