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

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Completed

CT.gov ID

NCT00695305

Collaborator

(none)

Enrollment

Locations

Arms

17.9

Duration (Months)

8.3

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Atherosclerosis	Drug: rilapladib Drug: placebo Other: 18F Fluorodeoxylucose (FDG)-PET	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

83 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Nov 1, 2008

Actual Primary Completion Date :

May 1, 2010

Actual Study Completion Date :

May 1, 2010

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years to 80 Years

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
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
5	GSK Investigational Site	New York	New York	United States	10001
6	GSK Investigational Site	New York	New York	United States	10029
7	GSK Investigational Site	New York	New York	United States	10035
8	GSK Investigational Site	New York	New York	United States	10065
9	GSK Investigational Site	North Massapequa	New York	United States	11758
10	GSK Investigational Site	Warwick	Rhode Island	United States	02886