AtherosclerosisPhase 2NCT00268996
Integrated Biomarker And Imaging Study - 2
A Phase 2 study testing SB-480848 in people with Atherosclerosis, run by GlaxoSmithKline at 26 sites in 11 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Atherosclerosis
- What is being tested?
- SB-480848
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 336 participants
- Where
- 26 sitesin 11 countries
- Study dates
- 10 Nov 2005to 28 Aug 2007
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Successful PCI (Percutaneous Coronary Intervention) or uncomplicated diagnostic catheterization
- Suitable non-intervened coronary artery with IVUS
- Antiplatelet therapy
Who cannot join
- Clinical instability
- Previous CABG (Coronary Artery By-pass Graft) surgery
- Planned major surgery
- Recent stroke
- Abnormal QTc
- Renal or hepatic impairment
Show all 10Show fewer
- Uncontrolled hypertension
- Use of corticosteroids
- Class III or IV heart failure
- Asthma
Trial locations and contacts
26 sites in 11 countries.
26 sites in 11 countries
Germany7 sites
GSK Investigational Site
Bad Nauheim, Hesse, 61231
GSK Investigational Site
Bad Segeberg, Schleswig-Holstein, 23795
GSK Investigational Site
Essen, North Rhine-Westphalia, 45122
GSK Investigational Site
Hamburg, 22527
GSK Investigational Site
Heidelberg, Baden-Wurttemberg, 69120
GSK Investigational Site
Munich, Bavaria, 80336
GSK Investigational Site
Ulm, Baden-Wurttemberg, 89081
Netherlands5 sites
GSK Investigational Site
Eindhoven, 5623 EJ
GSK Investigational Site
Enschede, 7511JX
GSK Investigational Site
Leeuwarden, 8934 AD
GSK Investigational Site
Rotterdam, 3015 GD
GSK Investigational Site
Rotterdam, 3075 EA
Belgium3 sites
GSK Investigational Site
Aalst, 9300
GSK Investigational Site
Antwerp, 2020
GSK Investigational Site
Liège, 4000
France2 sites
GSK Investigational Site
Besançon, 25000
GSK Investigational Site
Brest, 29609
Poland2 sites
GSK Investigational Site
Katowice, 40-635
GSK Investigational Site
Krakow, 31-501
Spain2 sites
GSK Investigational Site
Marid, 28040
GSK Investigational Site
Santander, 38008
About this study
Official title: An International, Multicenter, Randomized, Placebo-controlled, Parallel-group, 1 Year Treatment, Integrated Biomarkers and Imaging Study in Subjects With Angiographically Documented Coronary Heart Disease (CHD) to Examine the Effects of the Novel Lipoprotein-associated Phospholipase A2 (Lp-PLA2) Inhibitor SB-480848 on Intermediate Cardiovascular Endpoints, Patient Safety and Tolerability
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.
Read the detailed description
Integrated Biomarker and Imaging Study -2 (IBIS-2): An International, Multicenter, Randomized, Placebo-controlled, Parallel-group, 1 Year Treatment, Integrated Biomarkers and Imaging Study in Subjects with Angiographically Documented Coronary Heart Disease (CHD) to Examine the Effects of the Novel Lipoprotein-associated Phospholipase A2 (Lp-PLA2) inhibitor SB-480848 on Intermediate Cardiovascular Endpoints, Patient Safety and Tolerability.
- Conditions
- Atherosclerosis
- Being tested
- SB-480848, SB-480848 matching placebo
- Keywords
- Coronary artery disease, Lipoprotein-associated Phospholipase A2, palpography, hs-CRP, endothelial function, intravascular ultrasound
- Medical subject headings
- Atherosclerosis, Coronary Artery Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SB-480848Drug
SB-480848 is available as enteric-coated, free-base micronized tablet
SB-480848 matching placeboDrug
Placebo is available as enteric-coated, free-base micronized tablet
| Study group | Role | What they receive |
|---|---|---|
| Subjects with ACS and evidence of MN:SB-480848 | Experimental | Enrolled subjects (subjects with ACS and evidence of myocardial necrosis) will receive 160mg of SB-480848 once daily with food for 52 weeks Receives: Drug: SB-480848 |
| Subjects with ACS and evidence of MN: placebo | Placebo comparator | Enrolled subjects (subjects with ACS and evidence of myocardial necrosis) will receive SB-480848 matching placebo once daily with food for 52 weeks Receives: Drug: SB-480848 matching placebo |
| Non-ACS and ACS subjects without evidence of MN: SB-480848 | Experimental | Enrolled subjects (non-ACS subjects and those ACS subjects without evidence of myocardial necrosis) will receive 160mg of SB-480848 once daily with food for 52 weeks Receives: Drug: SB-480848 |
| Non-ACS and those ACS subjects without evidence of MN: placebo | Placebo comparator | Enrolled subjects (non-ACS subjects and those ACS subjects without evidence of myocardial necrosis) will receive SB-480848 matching placebo once daily with food for 52 weeks Receives: Drug: SB-480848 matching placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Circulating High Sensitivity C- Reactive Protein (Hs-CRP) Levels at 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-variance (ANCOVA), with Acute Coronary Syndrome (ACS) status, pooled country and treatment included as covariates.
Measured: Week 52
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.
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 length and treatment. Adjusted means and associated standard errors for each treatment group were presented. The baseline value for each participant was defined as the last value prior to the first dose of study drug.
Measured: Baseline and Week 52
Secondary outcomes (17)
Circulating Hs-CRP at the End of 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 included as covariates.
Measured: Week 26
Mean Lipoprotein Phospholipase A2 (Lp-PLA2) Activity at the End of 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.
Measured: Week 26 and Week 52
Change From Baseline in Plaque Volume as IVUS-Grey Scale Assessments at 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.
Measured: Baseline and Week 52
Change From Baseline in Percent Obstruction Volume as IVUS-Grey Scale Assessments at 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.
Measured: Baseline and Week 52
Change From Baseline in Necrotic Core Volume as Intravenous Ultrasound-Virtual Histology (IVUS-VH) Assessments at 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 IVUS-VH assessments at Week 52 was reported.
Measured: Baseline and Week 52
Change From Baseline in Necrotic Core as a Percent of IVUS-VH Plaque at the End of 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.
Measured: Baseline and Week 52
Mean Interlukin 6 (IL-6) Levels as Circulating Biomarkers Associated With Inflammatory Burden at 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 and treatment included as covariates.
Measured: Week 26 and Week 52
Mean Intercellular Adhesion Molecule-1 (ICAM-1) Levels as Circulating Biomarkers Associated With Inflammatory Burden at 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 country and treatment included as covariates.
Measured: Week 26 and Week 52
Mean Myeloperoxidase (MPO) Levels as Circulating Biomarkers Associated With Inflammatory Burden at 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 treatment included as covariates.
Measured: Week 26 and Week 52
Mean sCD40L Levels as Circulating Biomarkers Associated With Inflammatory Burden at 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.
Measured: Week 26 and Week 52
Mean Matrix Metaloproteinases-9 (MMP-9) Levels as Circulating Biomarkers Associated With Plaque Instability at Week 26 and Week 52.
Blood was collected at baseline, Week 4, 13, 26 and 52 for evaluation of biomarkers. Mean MMP-9 levels as circulating biomarkers associated with plaque instability at Week 26 and Week 52 were assessed and reported. LOCF data was reported. Only data from 3 months onwards was carried forward MMP-9 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 MMP-9 levels at Week 26 and 52 were reported. The levels were analyzed using ANCOVA, with ACS status, pooled country and treatment included as covariates.
Measured: Week 26 and Week 52
Mean Levels of Oxidised Phospholipids/ Apolipoprotein B100 (oxPL/apoB) Ratio as Target Circulating Biomarkers at the End of Week 26 and Week 52.
Blood was collected at baseline, Week 4, 13, 26 and 52 for evaluation of biomarkers. Mean OXPL/LAPO B levels as circulating biomarkers associated with Lp-PLA2 target-related biomarkers at Week 26 and Week 52 were assessed and reported. LOCF data was reported. Only data from 3 months onwards was carried forward. OXPL/LAPO B 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 OXPL/LAPO B levels at Week 26 and 52 were reported. The levels were analyzed using ANCOVA, with ACS status, pooled country and treatment included as covariates.
Measured: Week 26 and Week 52
Mean Levels of Oxidized Non-esterified Fatty Acids (Ox-NEFA) as Target Circulating Biomarkers at the End of Week 26 and Week 52
Mean ox-NEFA levels as circulating biomarkers associated with Lp-PLA2 target-related biomarkers at Week 26 and Week 52 was planned to be assessed. However, the parameter data were not collected for this endpoint.
Measured: Week 26 and Week 52
Change From Baseline in Vessel Volume and Lumen Volume as IVUS-Grey Scale Assessments at Week 52.
Change from baseline in vessel volume and lumen volume calculated for each IVUS grey scale assessment recorded. Vessel volume (i.e., coronary remodelling) defined by the leading edge of echogenic adventitia/external elastic membrane (EEM) and calculated as, mean vessel area multiplied mean of vessel length at Baseline and Follow-up. Lumen volume was circumscribed by the leading edge of intima/plaque and calculated as mean lumen area multiplied by mean lumen length at Baseline and Follow-up. 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 vessel volume or lumen volume at Week 52 minus baseline value.
Measured: Baseline and Week 52
Change From Baseline in Mean Plaque Area, Mean Vessel Area, and Mean Lumen Area as IVUS-Grey Scale Assessments at Week 52.
Change from baseline in was mean plaque area, mean vessel area, and mean lumen area were derived from IVUS system at each IVUS grey scale assessment recorded. 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 mean area of the parameter (plaque/vessel/lumen) at Week 52 minus baseline value. The data was reported based on observed cases. Data analyzed using ANCOVA, with ACS status, pooled country, baseline value, matched segment length and treatment included as covariates.
Measured: Baseline and Week 52
Change From Baseline in Fibrous Tissue Volume and Fibro-fatty Volume as IVUS-VH Assessments at Week 52
Change from baseline in fibrous tissue volume and fibro-fatty volume were derived from IVUS system at each IVUS grey scale assessment recorded. Fibrous tissue volume was calculated as mean fibro-fatty area multiplied by mean of Baseline and Follow-up length. Fibro-fatty volume was calculated as mean fibrous area multiplied by mean of Baseline and Follow-up length.
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 mean Fibrous tissue volume or Fibro-fatty volume at Week 52 minus baseline value. The data was reported based on observed cases. Data analyzed using ANCOVA, with ACS status, pooled country, baseline value , matched segment length and treatment included as covariates.
Measured: Baseline and Week 52
Change From Baseline in Fibrous Tissue and Fibro-fatty as a Percent of IVUS-VH Plaque as IVUS-VH Assessments at Week 52
Fibro-fatty as percentage of VH plaque and Fibrous tissue as percentage of VH plaque were derived from IVUS-VH system. 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 Fibro-fatty as percentage of VH plaque or Fibrous tissue as percentage of VH plaque at Week 52 minus baseline value. The data was reported based on observed cases. Data analyzed using ANCOVA, with ACS status, pooled country, baseline value , matched segment length and treatment included as covariates.
Measured: Baseline and Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2005 (estimated)
- Study start10 Nov 2005
- Primary completion28 Aug 2007
- Study completion28 Aug 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AtherosclerosisStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 336 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00268996
- Sponsor's protocol ID
- SB-480848/026
- Status last verified
- Aug 2017
- First submitted
- 21 Dec 2005
- Last updated
- 20 Mar 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Publications
Serruys PW, Garcia-Garcia HM, Buszman P, Erne P, Verheye S, Aschermann M, Duckers H, Bleie O, Dudek D, Botker HE, von Birgelen C, D'Amico D, Hutchinson T, Zambanini A, Mastik F, van Es GA, van der Steen AF, Vince DG, Ganz P, Hamm CW, Wijns W, Zalewski A; Integrated Biomarker and Imaging Study-2 Investigators. Effects of the direct lipoprotein-associated phospholipase A(2) inhibitor darapladib on human coronary atherosclerotic plaque. Circulation. 2008 Sep 9;118(11):1172-82. doi: 10.1161/CIRCULATIONAHA.108.771899. Epub 2008 Sep 1.
PubMed 18765397
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An International, Multicenter, Randomized, Placebo-controlled, Parallel-group, 1 Year Treatment, Integrated Biomarkers and Imaging Study in Subjects With Angiographically Documented Coronary Heart Disease (CHD) to Examine the Effects of the Novel Lipoprotein-associated Phospholipase A2 (Lp-PLA2) Inhibitor SB-480848 on Intermediate Cardiovascular Endpoints, Patient Safety and Tolerability
- ClinicalTrials.gov ID
- NCT00268996
- Acronym / sponsor ID
- SB-480848/026
- Conditions
- Atherosclerosis
- Keywords
- Coronary artery disease, Lipoprotein-associated Phospholipase A2, palpography, hs-CRP, endothelial function, intravascular ultrasound
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 336 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 10 Nov 2005 (actual)
- Primary completion
- 28 Aug 2007 (actual)
- Study completion
- 28 Aug 2007 (actual)
- First posted
- 23 Dec 2005 (estimated)
- Results
- Posted 19 Feb 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Integrated Biomarker and Imaging Study -2 (IBIS-2): An International, Multicenter, Randomized, Placebo-controlled, Parallel-group, 1 Year Treatment, Integrated Biomarkers and Imaging Study in Subjects with Angiographically Documented Coronary Heart Disease (CHD) to Examine the Effects of the Novel Lipoprotein-associated Phospholipase A2 (Lp-PLA2) inhibitor SB-480848 on Intermediate Cardiovascular Endpoints, Patient Safety and Tolerability.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Subjects with ACS and evidence of MN:SB-480848 | Experimental | Drug: SB-480848Enrolled subjects (subjects with ACS and evidence of myocardial necrosis) will receive 160mg of SB-480848 once daily with food for 52 weeks |
| Subjects with ACS and evidence of MN: placebo | Placebo comparator | Drug: SB-480848 matching placeboEnrolled subjects (subjects with ACS and evidence of myocardial necrosis) will receive SB-480848 matching placebo once daily with food for 52 weeks |
| Non-ACS and ACS subjects without evidence of MN: SB-480848 | Experimental | Drug: SB-480848Enrolled subjects (non-ACS subjects and those ACS subjects without evidence of myocardial necrosis) will receive 160mg of SB-480848 once daily with food for 52 weeks |
| Non-ACS and those ACS subjects without evidence of MN: placebo | Placebo comparator | Drug: SB-480848 matching placeboEnrolled subjects (non-ACS subjects and those ACS subjects without evidence of myocardial necrosis) will receive SB-480848 matching placebo once daily with food for 52 weeks |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Successful PCI (Percutaneous Coronary Intervention) or uncomplicated diagnostic catheterization
- Suitable non-intervened coronary artery with IVUS
- Antiplatelet therapy
Key exclusion criteria (10 listed)
- Clinical instability
- Previous CABG (Coronary Artery By-pass Graft) surgery
- Planned major surgery
- Recent stroke
- Abnormal QTc
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SB-480848SB-480848 is available as enteric-coated, free-base micronized tablet | Drug | Non-ACS and ACS subjects without evidence of MN: SB-480848, Subjects with ACS and evidence of MN:SB-480848 |
| SB-480848 matching placeboPlacebo is available as enteric-coated, free-base micronized tablet | Drug | Non-ACS and those ACS subjects without evidence of MN: placebo, Subjects with ACS and evidence of MN: placebo |
Primary outcome
Mean Circulating High Sensitivity C- Reactive Protein (Hs-CRP) Levels at Week 52.
Time frame: 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-variance (ANCOVA), with Acute Coronary Syndrome (ACS) status, pooled country and treatment included as covariates.
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.
Time frame: 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 length and treatment. Adjusted means and associated standard errors for each treatment group were presented. The baseline value for each participant was defined as the last value prior to the first dose of study drug.
17 secondary outcomes
Circulating Hs-CRP at the End of Week 26.
Time frame: Week 26
Mean Lipoprotein Phospholipase A2 (Lp-PLA2) Activity at the End of Week 26 and Week 52
Time frame: Week 26 and Week 52
Change From Baseline in Plaque Volume as IVUS-Grey Scale Assessments at Week 52
Time frame: Baseline and Week 52
Change From Baseline in Percent Obstruction Volume as IVUS-Grey Scale Assessments at Week 52
Time frame: Baseline and Week 52
Change From Baseline in Necrotic Core Volume as Intravenous Ultrasound-Virtual Histology (IVUS-VH) Assessments at Week 52
Time frame: Baseline and Week 52
Change From Baseline in Necrotic Core as a Percent of IVUS-VH Plaque at the End of Week 52.
Time frame: Baseline and Week 52
Mean Interlukin 6 (IL-6) Levels as Circulating Biomarkers Associated With Inflammatory Burden at Week 26 and Week 52
Time frame: Week 26 and Week 52
Mean Intercellular Adhesion Molecule-1 (ICAM-1) Levels as Circulating Biomarkers Associated With Inflammatory Burden at Week 26 and Week 52
Time frame: Week 26 and Week 52
Mean Myeloperoxidase (MPO) Levels as Circulating Biomarkers Associated With Inflammatory Burden at Week 26 and Week 52
Time frame: Week 26 and Week 52
Mean sCD40L Levels as Circulating Biomarkers Associated With Inflammatory Burden at Week 26 and Week 52
Time frame: Week 26 and Week 52
Mean Matrix Metaloproteinases-9 (MMP-9) Levels as Circulating Biomarkers Associated With Plaque Instability at Week 26 and Week 52.
Time frame: Week 26 and Week 52
Mean Levels of Oxidised Phospholipids/ Apolipoprotein B100 (oxPL/apoB) Ratio as Target Circulating Biomarkers at the End of Week 26 and Week 52.
Time frame: Week 26 and Week 52
Mean Levels of Oxidized Non-esterified Fatty Acids (Ox-NEFA) as Target Circulating Biomarkers at the End of Week 26 and Week 52
Time frame: Week 26 and Week 52
Change From Baseline in Vessel Volume and Lumen Volume as IVUS-Grey Scale Assessments at Week 52.
Time frame: Baseline and Week 52
Change From Baseline in Mean Plaque Area, Mean Vessel Area, and Mean Lumen Area as IVUS-Grey Scale Assessments at Week 52.
Time frame: Baseline and Week 52
Change From Baseline in Fibrous Tissue Volume and Fibro-fatty Volume as IVUS-VH Assessments at Week 52
Time frame: Baseline and Week 52
Change From Baseline in Fibrous Tissue and Fibro-fatty as a Percent of IVUS-VH Plaque as IVUS-VH Assessments at Week 52
Time frame: Baseline and Week 52
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 18765397Serruys PW, Garcia-Garcia HM, Buszman P, Erne P, Verheye S, Aschermann M, Duckers H, Bleie O, Dudek D, Botker HE, von Birgelen C, D'Amico D, Hutchinson T, Zambanini A, Mastik F, van Es GA, van der Steen AF, Vince DG, Ganz P, Hamm CW, Wijns W, Zalewski A; Integrated Biomarker and Imaging Study-2 Investigators. Effects of the direct lipoprotein-associated phospholipase A(2) inhibitor darapladib on human coronary atherosclerotic plaque. Circulation. 2008 Sep 9;118(11):1172-82. doi: 10.1161/CIRCULATIONAHA.108.771899. Epub 2008 Sep 1.
- Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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Hypercholesterolemia, Atherosclerosis
Active, not recruitingPhase 4
Comparison of Moderate-Intensity Statin Plus Ezetimibe vs. High-Intensity Statin for Coronary Plaque Stabilization
Coronary Artery Disease, Atherosclerosis of Coronary Artery
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
26 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing SB-480848 in people with Atherosclerosis, run by GlaxoSmithKline at 26 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 26 sites in Germany, Netherlands, Belgium, France, Poland and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Feb 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Circulating High Sensitivity C- Reactive Protein (Hs-CRP) Levels at Week 52. (time frame: Week 52). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00268996, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2018.