Last updated: 11/07/2018 17:29:53
An imaging study in patients with atherosclerosis taking rilapladib or placebo for 12 weeks
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
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
Trial description: A study in patients with atherosclerosis to assess safety, effect and PK of rilapladib vs. placebo over 12 weeks of dosing.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation:
Randomized
Primary outcomes:
Number of participants with any adverse events (AEs) and any serious adverse event (SAE)
Timeframe: Up to follow-up ( Weeks 14)
Number of participants with clinical laboratory values of Potential Clinical Importance at any time on treatment
Timeframe: Up to 12 weeks
Number of participants with abnormal Electrocardiogram (ECG) values
Timeframe: Up to 12 weeks
Number of participants with vital signs of Potential Clinical Importance
Timeframe: Up to 12 weeks
Number of participants with Lamellar Bodies Present in Peripheral Blood Lymphocytes
Timeframe: Baseline (PT, Day 1), Week 12 (EOT) and 14 (Follow-up)
Number of participants with abnormal slit lamp eye exam data
Timeframe: Baseline (PT, Day 1) and Week 12 (EOT)
Percent inhibition in Plasma Lipoprotein-associated phospholipase A2 (Lp-PLA2) activity relative to baseline
Timeframe: Baseline (PT, Day 1), Week 4, 6, 8, 10, and early withdrawal
Changes in mean standard values of fluorodeoxyglucose (18FDG) uptake, expressed as tissue to background ratio (TBR) of qualifying segment
Timeframe: Baseline (PT, Day 1) and Week 12
Secondary outcomes:
Rilapladib plasma concentration causing 50% inhibition of plasma Lp-PLA2 activity [IC50]
Timeframe: Up to Week 12
Baseline plasma Lp-PLA2 activity (E0)
Timeframe: Baseline (PT, Day 1)
Change from Baseline in active segment mean of max TBR from qualifying segment at Week 12
Timeframe: Baseline (PT, Day 1) and Week 12 (EOT)
Mean length of active segments
Timeframe: Baseline (PT, Day 1) and Week 12 (EOT)
Categorized slice max TBR data from qualifying segment
Timeframe: Baseline (PT, Day 1) and Week 12 (EOT)
Change from Baseline in imaging data by region: mean of mean TBR, mean of max TBR, and mean of max TBR MDS in each segment (left or right carotid or ascending aorta)
Timeframe: Baseline (PT, Day 1) and Week 12
Change from Baseline in mean of mean TBR in qualifying segment
Timeframe: Baseline (PT, Day 1) and Week 12
Mean categorized slice max TBR by region
Timeframe: Baseline (PT, Day 1), Week 12 (EOT)
Change from Baseline in platelet activating factor (PAF)C16 and PAFC18
Timeframe: Baseline (PT, Day 1) and Week 12
Apparent volume of distribution and apparent volumes of distribution of rilapladib
Timeframe: Baseline (PT, Day 1), Pre-dose (0.0 hour) and 0.5 to 5 hour on Week 4 and Week 8, 5 to 9 hour on Week 10, 9 to 22 hour on Week 6
Interventions:
Drug: rilapladib
Drug: placebo
Other: 18F Fluorodeoxylucose (FDG)-PET
Enrollment:
83
Observational study model:
Not applicable
Primary completion date:
2010-18-05
Time perspective:
Not applicable
Clinical publications:
A Tawakol, P Singh, JHF Rudd, J Soffer, G Cai, E Vucic, SP Brannan, EA Tarka, BC Shaddinger, L Sarov-Blat, P Matthews, S Subramanian, M Farkouh, ZA Fayad.Effect of Treatment for 12 Weeks With Rilapladib, a Lipoprotein-Associated Phospholipase A2 Inhibitor, on Arterial Inflammation as Assessed With 18F-Fluorodeoxyglucose-Positron Emission Tomography Imaging.J Am Coll Cardiol.2014;63(1):86-88
Medical condition
Atherosclerosis
Product
rilapladib
Collaborators
Not applicable
Study date(s)
November 2008 to May 2010
Type
Interventional
Phase
2
Participation criteria
Sex
Female & Male
Age
50 - 80 years
Accepts healthy volunteers
No
- 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.
- 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
Inclusion and exclusion 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
Trial location(s)
Location
GSK Investigational Site
New York, New York, United States, 10001
Status
Study Complete
Location
GSK Investigational Site
Brockton, Massachusetts, United States, 02301
Status
Study Complete
Location
GSK Investigational Site
New York, New York, United States, 10035
Status
Study Complete
Location
GSK Investigational Site
New York, New York, United States, 10065
Status
Study Complete
Location
GSK Investigational Site
Boston, Massachusetts, United States, 02114
Status
Study Complete
Location
GSK Investigational Site
New York, New York, United States, 10029
Status
Study Complete
Location
GSK Investigational Site
Warwick, Rhode Island, United States, 02886
Status
Study Complete
Location
GSK Investigational Site
North Massapequa, New York, United States, 11758
Status
Study Complete
Location
GSK Investigational Site
Haverhill, Massachusetts, United States, 01830
Status
Study Complete
Location
GSK Investigational Site
Linden, New Jersey, United States, 07036
Status
Study Complete
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Completed
Actual primary completion date
2010-18-05
Actual study completion date
2010-18-05
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
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