Clinical trial NCT00291902: A Pharmacokinetic Study Of SB-681323 In Subjects With Coronary Heart Disease Undergoing Percutaneous Intervention
Official title: A 28-day, Randomized, Double-blind, Placebo-controlled Study to Assess the Safety, Tolerability, Anti-inflammatory Effect and Steady-state Pharmacokinetics of SB-681323 (7.5 mg) in Subjects With Coronary Heart Disease (CHD) Undergoing Elective Percutaneous Coronary Interventions (PCI)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Coronary Heart Disease
Keywords: CHD
coronary heart disease
atherosclerosis
inflammation
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2006-02-15
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Study of SB-681323 (a novel p38 MAPkinase inhibitor) in subjects with documented coronary heart disease (CHD) undergoing elective percutaneous coronary intervention (PCI).


Eligibility criteria: Inclusion Criteria:

* Females must be of non-child-bearing potential.
* Female subjects must have a negative pregnancy test.
* Subjects scheduled to undergo elective single vessel PCI to be performed within the 6 weeks of diagnostic coronary angiography.
* Must be on stable dose of statin for = 6 weeks prior to screening, with statin tolerability and LDL \<130 mg/dL (3.4 mmol/L) at Screening visit.
* Must be capable of providing informed consent.
* Have an hsCRP concentration of \>2 mg/L, but \< 10 mg/L at screening.

Exclusion Criteria:

* Women who are pregnant or breast feeding.
* Planned PCI with multi-vessel stenting.
* Planned PCI with additional revascularization procedures staged at different days during the study period.
* Planned PCI other than stenting (e.g., atherectomy, PTCA without stenting, etc).
* Planned PCI of any bypass graft.
* History of CABG surgery.
* Planned cardiac or major non-cardiac surgery within the study period.
* Disabling stroke in the past 6 months.
* History of chronic viral hepatitis or other chronic hepatic disorders.
* History of Gilbert's syndrome or elevated bilirubin concentrations at screening.
* History of increased liver function tests (ALT, AST) due to acute or chronic liver conditions, above the upper limit of normal at screening or in the past 6 months.
* Renal impairment with serum creatinine \>2.0 mg/dl (177umol/L) at Screening, or history of kidney transplant, or a history of contrast nephropathy.
* Current inadequately controlled hypertension (blood pressure \>160 mmHg systolic and/or \>100 mmHg diastolic) on a stable dose of antihypertensive medication.
* Current poorly controlled diabetes mellitus, defined as HbA1c \>10% at Screening.
* History of severe heart failure defined as NYHA class III or IV or those with known severe LV dysfunction (EF\<30%) regardless of symptomatic status.
* History of malignancy within the past 5 years, other than non-melanoma skin cancer.
* Current life-threatening condition other than vascular disease that may prevent a subject from completing the study.
* Alcohol or drug abuse within the past 6 months.

Primary outcomes:
measure: Patient safety Tolerability Anti-inflammatory effect (high sensitivity C-reactive Protein)
timeFrame: 28 days
Secondary outcomes:
measure: Anti-inflammatory effect (biomarkers) Endothelial function (peripheral artery tonometry) Pharmacokinetics
timeFrame: 28 days
Other outcomes:
Locations:
city: Esbjerg
country: Denmark
facility: GSK Investigational Site
city: Haderslev
country: Denmark
facility: GSK Investigational Site
city: Hellerup
country: Denmark
facility: GSK Investigational Site
city: Herning
country: Denmark
facility: GSK Investigational Site
city: Viborg
country: Denmark
facility: GSK Investigational Site
city: Bialystok
country: Poland
facility: GSK Investigational Site
city: Poznan
country: Poland
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Sarov-Blat L, Morgan JM, Fernandez P, James R, Fang Z, Hurle MR, Baidoo C, Willette RN, Lepore JJ, Jensen SE, Sprecher DL. Inhibition of p38 mitogen-activated protein kinase reduces inflammation after coronary vascular injury in humans. Arterioscler Thromb Vasc Biol. 2010 Nov;30(11):2256-63. doi: 10.1161/ATVBAHA.110.209205. Epub 2010 Aug 5.