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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00695305
First received: June 9, 2008
Last updated: November 15, 2012
Last verified: November 2012
  Purpose

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


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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Safety from AE reporting, vital signs, clinical labs, ECGs, slit lamp eye exams and electron microscopy of peripheral blood lymphocytes. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • LP-PLA2 activity; [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • changes in mean standard values of 18 FDG uptake as assessed by PET and MRI imaging [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

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 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Estimation of PK/PD parameters (such as: IC50, Eo) and their associated variability, appropriate to the final model [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • 24 hour ambulatory blood pressure monitoring [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • PAF levels in human plasma as feasible [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Enrollment: 83
Study Start Date: November 2008
Study Completion Date: May 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: placebo
placebo to match
Drug: placebo
placebo
Other Name: placebo
Active Comparator: rilapladib
250 mg/day
Drug: rilapladib
250 mg oral dose once daily
Other Name: SB-659032
Other: 18F Fluorodeoxylucose (FDG)-PET
FDG-PET
Other Name: FDG marker

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.

  Eligibility

Ages Eligible for Study:   50 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00695305

Locations
United States, Massachusetts
GSK Investigational Site
Boston, Massachusetts, United States, 02114
GSK Investigational Site
Brockton, Massachusetts, United States, 02301
GSK Investigational Site
Haverhill, Massachusetts, United States, 01830
United States, New Jersey
GSK Investigational Site
Linden, New Jersey, United States, 07036
United States, New York
GSK Investigational Site
New York, New York, United States, 10001
GSK Investigational Site
New York, New York, United States, 10065
GSK Investigational Site
New York, New York, United States, 10029
GSK Investigational Site
New York, New York, United States, 10035
GSK Investigational Site
North Massapequa, New York, United States, 11758
United States, Rhode Island
GSK Investigational Site
Warwick, Rhode Island, United States, 02886
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00695305     History of Changes
Other Study ID Numbers: LP2105521
Study First Received: June 9, 2008
Last Updated: November 15, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
rilapladib,
Lp-PLA2,
atherosclerosis
SB-659032,
FDG-PET,

Additional relevant MeSH terms:
Atherosclerosis
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on October 16, 2014