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NCT00268996

Integrated Biomarker And Imaging Study - 2

Completed Phase 2 Results posted Last updated 20 March 2018
What this trial tests

Phase 2 trial testing SB-480848 in Atherosclerosis in 336 participants. Completed in 28 August 2007.

Timeline
10 November 2005
Primary endpoint
28 August 2007
28 August 2007

Quick facts

Lead sponsorGlaxoSmithKline
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment336
Start date10 November 2005
Primary completion28 August 2007
Estimated completion28 August 2007
Sites26 locations across France, Denmark, Netherlands, Belgium, Austria, Germany, Poland, Norway

Drugs / interventions tested

Conditions studied

Sponsor

GlaxoSmithKline — full company profile →

Who can join

Adults 18 to 80, any sex, with Atherosclerosis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Mean Circulating High Sensitivity C- Reactive Protein (Hs-CRP) Levels at Week 52. Primary · Week 52

hs-CRP is a pentameric protein that is rapidly upregulated in response to inflammation and tissue damage and assessed as circulating biomarkers associated with atherosclerosis and cardiovascular risk. Last Observation Carried Forward (LOCF) data was reported. Only data from 3 months onwards was carried forward. hs-CRP has a skewed distribution and values were log transformed before analysis. The statistics was calculated on the log transformed data and back transformed. The adjusted geometric means of hs-CRP levels at Week 52 were reported. The levels were analyzed using analysis of co-varianc

GroupValue95% CI
Placebo1.0340.854 – 1.251
Darapladib 160 mg EC Tablet0.9130.765 – 1.090
Change From Baseline in the Density of Rotterdam Classification (ROC) Grade III/IV Strain Spots/10 Millimeter (mm) Within the Region of Interest (ROI) on IVUS Grey Scale Based Palpography at the End of Week 52. Primary · Baseline and Week 52

The ROC grade III/IV strain spots per 10 millimetre (mm) within the ROI on intravascular ultrasound (IVUS) grey scale based palpography were assessed and change from Baseline at end of 52 was reported. Change from Baseline was calculated as the density of spots at the end of study minus the density of spots recorded at Baseline. If either value was considered missing then the change from Baseline value was missing for the participant. Between treatment group comparisons of change from Baseline were analyzed using ANCOVA adjusting for ACS status, pooled country, Baseline value, matched segment

GroupValue95% CI
Placebo0.003± 0.048
Darapladib 160 mg EC Tablet-0.079± 0.045
Circulating Hs-CRP at the End of Week 26. Secondary · Week 26

hs-CRP is a pentameric protein that is rapidly upregulated in response to inflammation and tissue damage and assessed as circulating biomarkers associated with atherosclerosis and cardiovascular risk. LOCF data was reported. Only data from 3 months onwards was carried forward. hs-CRP has a skewed distribution and values were log transformed before analysis. The statistics was calculated on the log transformed data and back transformed. The adjusted geometric means of hs-CRP levels at Week 26 were reported. The levels were analyzed using ANCOVA, with ACS status, pooled country and treatment inc

GroupValue95% CI
Placebo0.9240.774 – 1.102
Darapladib 160 mg EC Tablet0.9600.815 – 1.131
Mean Lipoprotein Phospholipase A2 (Lp-PLA2) Activity at the End of Week 26 and Week 52 Secondary · Week 26 and Week 52

Lp-PLA2 is a calcium-independent phospholipase A2 enzyme associated with low density lipoprotein (LDL) in plasma. Blood samples were collected at baseline and at Week 4, 13, 26, and 52 and Lp-PLA2 activity was determined. Percentage inhibition of Lp-PLA2 activity relative to baseline was calculated as, percent inhibition = (\[baseline value - post baseline value\] x 100) / baseline value. The baseline value for each participant was defined as the last value prior to the first dose of study drug.

Week 26 LOCF
GroupValue95% CI
Placebo151.412143.592 – 159.657
Darapladib 160 mg EC Tablet59.44956.591 – 62.452
Week 52 LOCF
GroupValue95% CI
Placebo152.061144.109 – 160.452
Darapladib 160 mg EC Tablet61.85058.838 – 65.015
Change From Baseline in Plaque Volume as IVUS-Grey Scale Assessments at Week 52 Secondary · Baseline and Week 52

Change from Baseline was calculated for each IVUS grey scale assessment recorded at the end of study. The Baseline value for each participant was defined as the last value prior to the first dose of study drug. Change from Baseline was calculated as plaque volume at Week 52 minus Baseline value. The data was analyzed using ANCOVA, with ACS status, pooled country, Baseline value, matched segment length and treatment included as covariates.

GroupValue95% CI
Placebo-5.126± 2.715
Darapladib 160 mg EC Tablet-4.873± 2.464
Change From Baseline in Percent Obstruction Volume as IVUS-Grey Scale Assessments at Week 52 Secondary · Baseline and Week 52

Change from Baseline in percent obstruction volume was calculated for each IVUS grey scale assessment recorded. Percent obstruction volume was calculated as (Plaque volume/ Vessel volume \*100). The Baseline value for each participant was defined as the last value prior to the first dose of study drug. Change from Baseline was calculated as plaque volume at Week 52 minus Baseline value. The data was analyzed using ANCOVA, with ACS status, pooled country, baseline value, matched segment length and treatment included as covariates.

GroupValue95% CI
Placebo0.007± 0.354
Darapladib 160 mg EC Tablet-0.054± 0.321
Change From Baseline in Necrotic Core Volume as Intravenous Ultrasound-Virtual Histology (IVUS-VH) Assessments at Week 52 Secondary · Baseline and Week 52

Change from Baseline was calculated for each IVUS-VH assessment recorded at the end of study. The necrotic core volume was calculated as mean necrotic area multiplied by mean of Baseline and follow-up length. Change from Baseline was calculated as plaque volume at Week 52 minus Baseline value. The data was analyzed using ANCOVA, with ACS status, pooled country, Baseline value, matched segment length and treatment included as covariates. The Baseline value for each participant was defined as the last value prior to the first dose of study drug. Change from Baseline in necrotic core volume as IV

GroupValue95% CI
Placebo4.633± 1.491
Darapladib 160 mg EC Tablet-0.531± 1.376
Change From Baseline in Necrotic Core as a Percent of IVUS-VH Plaque at the End of Week 52. Secondary · Baseline and Week 52

Change from baseline was calculated for each IVUS-VH assessment recorded at the end of study. The baseline value for each participant was defined as the last value prior to the first dose of study drug. Change from baseline in percent necrotic core was calculated as percent necrotic core at Week 52 minus baseline value. The data was analyzed using ANCOVA, with ACS status, pooled country, baseline value, matched segment length and treatment included as covariates. Change from Baseline in necrotic core as a percent of IVUS-VH plaque at the end of week 52 was reported.

GroupValue95% CI
Placebo2.502± 0.722
Darapladib 160 mg EC Tablet0.535± 0.666
Mean Interlukin 6 (IL-6) Levels as Circulating Biomarkers Associated With Inflammatory Burden at Week 26 and Week 52 Secondary · Week 26 and Week 52

Blood was collected at baseline, Week 4, 13, 26 and 52 for evaluation of biomarkers. Mean IL-6 levels as circulating biomarkers associated with inflammatory burden at Week 26 and Week 52 were assessed and reported. LOCF data was reported. Only data from 3 months onwards was carried forward. IL-6 had a skewed distribution and values were log transformed before analysis. The statistics was calculated on the log transformed data and back transformed. The adjusted geometric means of IL-6 levels at Week 26 and 52 were reported. The levels were analyzed using ANCOVA, with ACS status, pooled country

Week 26 LOCF
GroupValue95% CI
Placebo1.8511.609 – 2.128
Darapladib 160 mg EC Tablet1.9791.741 – 2.250
Week 52 LOCF
GroupValue95% CI
Placebo2.0191.749 – 2.331
Darapladib 160 mg EC Tablet2.2671.985 – 2.588
Mean Intercellular Adhesion Molecule-1 (ICAM-1) Levels as Circulating Biomarkers Associated With Inflammatory Burden at Week 26 and Week 52 Secondary · Week 26 and Week 52

Blood was collected at baseline, Week 4, 13, 26 and 52 for evaluation of biomarkers. Mean ICAM-1 levels as circulating biomarkers associated with inflammatory burden at Week 26 and Week 52 were assessed and reported. LOCF data was reported. Only data from 3 months onwards was carried forward. ICAM-1 had a skewed distribution and values were log transformed before analysis. The statistics was calculated on the log transformed data and back transformed. The adjusted geometric means of ICAM-1 levels at Week 26 and 52 were reported. The levels were analyzed using ANCOVA, with ACS status, pooled co

Week 26 (LOCF)
GroupValue95% CI
Placebo269.444258.932 – 280.383
Darapladib 160 mg EC Tablet266.447256.744 – 276.516
Week 52 (LOCF)
GroupValue95% CI
Placebo277.947265.822 – 290.624
Darapladib 160 mg EC Tablet268.950257.998 – 280.367
Mean Myeloperoxidase (MPO) Levels as Circulating Biomarkers Associated With Inflammatory Burden at Week 26 and Week 52 Secondary · Week 26 and Week 52

Blood was collected at baseline, Week 4, 13, 26 and 52 for evaluation of biomarkers. Mean MPO levels as circulating biomarkers associated with inflammatory burden at Week 26 and Week 52 were assessed and reported. LOCF data was reported. Only data from 3 months onwards was carried forward. MPO had a skewed distribution and values were log transformed before analysis. The statistics was calculated on the log transformed data and back transformed. The adjusted geometric means of MPO levels at Week 26 and 52 were reported. The levels were analyzed using ANCOVA, with ACS status, pooled country and

Week 26 (LOCF)
GroupValue95% CI
Placebo324.534294.535 – 357.589
Darapladib 160 mg EC Tablet378.811346.275 – 414.405
Week 52 (LOCF)
GroupValue95% CI
Placebo370.999331.989 – 414.592
Darapladib 160 mg EC Tablet405.339365.718 – 449.253
Mean sCD40L Levels as Circulating Biomarkers Associated With Inflammatory Burden at Week 26 and Week 52 Secondary · Week 26 and Week 52

Blood was collected at baseline, Week 4, 13, 26 and 52 for evaluation of biomarkers. Mean sCD40L levels as circulating biomarker associated with inflammatory burden at Week 26 and Week 52 were assessed and reported. sCD40L had a skewed distribution and values were log transformed before analysis. The statistics was calculated on the log transformed data and back transformed. The adjusted geometric means of sCD40L levels at Week 26 and 52 were reported. The levels were analyzed using ANCOVA, with ACS status, pooled country and treatment included as covariates.

Week 26
GroupValue95% CI
Placebo178.738152.832 – 209.035
Darapladib 160 mg EC Tablet206.351177.412 – 240.012
Week 52
GroupValue95% CI
Placebo183.449149.887 – 224.526
Darapladib 160 mg EC Tablet254.200208.840 – 309.412

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events (AEs) were recorded from the time a participant consents to participate until completion of follow-up period (10 to 21 days after discontinuation of treatment). On-treatment (up to 52 weeks) serious-AE (SAE) and non-SAE are reported.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo
Serious: 45/151 (30%)
Deaths: 0/151
Darapladib 160 mg EC Tablet
Serious: 46/172 (27%)
Deaths: 0/172

Serious adverse events (62 terms)

ReactionSystemPlaceboDarapladib 160 mg EC Tablet
Coronary artery diseaseCardiac disorders
Angina pectorisCardiac disorders
In-stent coronary artery restenosisCardiac disorders
Acute myocardial infarctionCardiac disorders
Angina unstableCardiac disorders
Coronary artery restenosisCardiac disorders
Non-cardiac chest painGeneral disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
Coronary artery stenosisCardiac disorders
Myocardial infarctionCardiac disorders
BronchitisInfections and infestations
HypotensionVascular disorders
Arteriospasm coronaryCardiac disorders
BradycardiaCardiac disorders
Cardiac asthmaCardiac disorders
Cardiac failure congestiveCardiac disorders
Cardiac pseudoaneurysmCardiac disorders
Coronary artery dissectionCardiac disorders
Mitral valve incompetenceCardiac disorders
TachycardiaCardiac disorders
Ventricular extrasystolesCardiac disorders
Ventricular tachycardiaCardiac disorders
CellulitisInfections and infestations
DiverticulitisInfections and infestations
GastroenteritisInfections and infestations
Other adverse events (8 terms — click to expand)

ReactionSystemPlaceboDarapladib 160 mg EC Tablet
Angina pectorisCardiac disorders
Abnormal faecesGastrointestinal disorders
Urine odour abnormalRenal and urinary disorders
DiarrhoeaGastrointestinal disorders
FatigueGeneral disorders
NasopharyngitisInfections and infestations
Non-cardiac chest painGeneral disorders
Oedema peripheralGeneral disorders

Most-reported serious reactions: Coronary artery disease, Angina pectoris, In-stent coronary artery restenosis, Acute myocardial infarction, Angina unstable, Coronary artery restenosis, Non-cardiac chest pain, Pulmonary embolism.

Data from ClinicalTrials.gov NCT00268996 adverse events section.

Sponsor's own description

IBIS-2 is a study using SB-480848 versus placebo in subjects with angiographically documented coronary heart disease. Endpoints include coronary imaging, endothelial function, biomarkers, safety and tolerability.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.

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Currently open trials in the same condition.

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Trials by the same sponsor.

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