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

NCT00695305 | Completed Phase 2

• 1 other identifier: LP2105521
• Study Type: interventional
• Target: 83
• Locations: 1 country
• Sites: 10

Brief Summary

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

Conditions

Atherosclerosis

Keywords

rilapladib,; Lp-PLA2,; atherosclerosis; SB-659032,; FDG-PET,

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (4)

• 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

Study Arms (2)

placebo

PLACEBO COMPARATOR

placebo to match

Drug: placebo

rilapladib

ACTIVE COMPARATOR

250 mg/day

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

Interventions

rilapladib DRUG

250 mg oral dose once daily

Also known as: SB-659032

rilapladib

placebo DRUG

placebo

placebo

18F Fluorodeoxylucose (FDG)-PET OTHER

FDG-PET

Also known as: FDG marker

rilapladib

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (10)

GSK Investigational Site

Boston, Massachusetts, 02114, United States

Location

GSK Investigational Site

Brockton, Massachusetts, 02301, United States

Location

GSK Investigational Site

Haverhill, Massachusetts, 01830, United States

Location

GSK Investigational Site

Linden, New Jersey, 07036, United States

Location

GSK Investigational Site

New York, New York, 10001, United States

Location

GSK Investigational Site

New York, New York, 10029, United States

Location

GSK Investigational Site

New York, New York, 10035, United States

Location

GSK Investigational Site

New York, New York, 10065, United States

Location

GSK Investigational Site

North Massapequa, New York, 11758, United States

Location

GSK Investigational Site

Warwick, Rhode Island, 02886, United States

Location

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Atherosclerosis

Interventions

rilapladib

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2008
• First Posted: June 11, 2008
• Study Start: November 1, 2008
• Primary Completion: May 1, 2010
• Study Completion: May 1, 2010
• Last Updated: December 1, 2016

Record last verified: 2016-11

Data Sharing

• IPD Sharing: Will share

Locations

US (10)