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

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 2

Conditions: Atherosclerosis

Treatments: Drug: placebo; Drug: rilapladib; Other: 18F Fluorodeoxylucose (FDG)-PET

Study type: Interventional

Funder types: Industry

Identifiers

NCT00695305

LP2105521

Details and patient eligibility

About

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

Full 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.

Enrollment: 83 patients

Sex: All

Ages: 50 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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83 participants in 2 patient groups, including a placebo group

placebo

Placebo Comparator group

Description:

placebo to match

Treatment:

Drug: placebo

rilapladib

Active Comparator group

Description:

250 mg/day

Treatment:

Other: 18F Fluorodeoxylucose (FDG)-PET

Drug: rilapladib