An Imaging Study in Patients With Atherosclerosis Taking Rilapladib or Placebo for 12 Weeks
Phase 2
Completed
- Conditions
- Atherosclerosis
- Interventions
- Registration Number
- NCT00695305
- Lead Sponsor
- GlaxoSmithKline
- 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, 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 83
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description rilapladib 18F Fluorodeoxylucose (FDG)-PET 250 mg/day placebo placebo placebo to match rilapladib rilapladib 250 mg/day
- Primary Outcome Measures
Name Time Method 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
Name Time Method 24 hour ambulatory blood pressure monitoring 12 weeks 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 PAF levels in human plasma as feasible 12 weeks
Trial Locations
- Locations (1)
GSK Investigational Site
🇺🇸Warwick, Rhode Island, United States