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

• Status: Completed
• Trial end date: 2010-05-01
• Target enrollment: 0
• Participant gender: All

Summary

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

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: GlaxoSmithKline

Criteria

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