AtherosclerosisPhase 2NCT01916720
Study to Determine the Effect of 14 Days Dosing With Darapladib (SB-480848) on Carotid Plague Composition in Patients With Planned Carotid Endarterectomy
A Phase 2 study testing SB-480848 40 mg and SB-480848 80 mg in people with Atherosclerosis, run by GlaxoSmithKline.
Trial summary
The primary objective is to determine Lp-PLA2 activity in atherosclerotic carotid plaques after 14 (+/-4) days treatment with darapladib, compared to placebo. Secondary objectives include determination of the change in Lp-PLA2 activity in blood, Lp-PLA2 mass in blood and plaque, specified biomarkers in blood and… Read more about this study
- Who is it for?
- Ages 35 years and older
- Conditions the study is for
- Atherosclerosis
- What is being tested?
- SB-480848 40 mg and SB-480848 80 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 103 participants
- Where
- No sites listed yet
- Study dates
- Jan 2003to Jul 2003
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 35 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female, >35 years of age
- Females of childbearing potential must be using approved contraceptive measures
- Male patients must be willing to abstain from sexual intercourse or use a form of contraception if engaging in sexual intercourse with a woman who could become pregnant
- Planned carotid endarterectomy within a timeframe compatible with recruitment for the study and able to comply with the requirements of the study, as deemed by the investigator
- Written, informed consent to participate
Who cannot join
- Recent myocardial infarction (within the previous 4 weeks)
- Currently taking corticosteroids, warfarin, digoxin or a potent CYP3A4 inhibitor
- Recent (<3 months) or ongoing acute infection or significant trauma associated with bruising and/or taking antibiotics. Prophylactic antibiotics for surgery are allowed
- Change in dose of lipid-lowering therapy during the previous 4 weeks from randomisation
- History of chronic liver disease (e.g. cirrhosis, hepatitis) OR ALT OR AST ≥1.5 times the upper limit of normal (ULN) at screening
- Diagnosis of systemic lupus erythematosis (SLE) or rheumatoid arthritis (RA)
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- Clinically significant anaemia
- History of severe renal impairment (serum creatinine >1.8mg/dL)
- Unstable angina
- History of asthma , anaphylaxis or anaphylactoid reactions, severe allergic responses
- Abuse of alcohol or drugs within the last 6 months
- Any factor or clinical disease state that, in the investigator's opinion, would preclude completion of a safe surgical procedure and/or completion of the study
- Use of an investigational drugs within 30 days or 5 half-lives of their last dose prior to starting the study, whichever is the longest
About this study
Official title: A Multi-centre, Randomised, Double-blind, Placebo-controlled, Parallel-group Study to Investigate the Effect of the Lp-PLA2 Inhibitor SB-480848 (40, 80mg od) on Carotid Plaque Composition in Patients With Carotid Artery Disease and Planned Carotid Endarterectomy, Stratified for Statin Use and Gender, After 14+/-4 Days Treatment
The primary objective is to determine Lp-PLA2 activity in atherosclerotic carotid plaques after 14 (+/-4) days treatment with darapladib, compared to placebo. Secondary objectives include determination of the change in Lp-PLA2 activity in blood, Lp-PLA2 mass in blood and plaque, specified biomarkers in blood and plaque and their respective correlation's with Lp-PLA2. In addition, the study aims to characterise the PK/PD of repeat oral doses of SB-480848, and safety and tolerability in this population.
- Conditions
- Atherosclerosis
- Being tested
- SB-480848 40 mg, SB-480848 80 mg, Placebo
- Medical subject headings
- Atherosclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SB-480848 40 mgDrug
Study Drug
SB-480848 80 mgDrug
Study Drug
PlaceboDrug
Study Drug
| Study group | Role | What they receive |
|---|---|---|
| SB-480848 40 mg | Experimental | SB-480848 40 milligrams (mg) once a day (od) for 14 +/- 4 days followed by carotid endarterectomy. SB-480848 40 mg was administered as 2 SB-480848 20 mg tablets plus 2 placebo tablets. Receives: Drug: SB-480848 40 mg; Drug: Placebo |
| SB-480848 80 mg | Experimental | SB-480848 80 mg od for 14 +/- 4 days followed by carotid endarterectomy.SB-480848 80 mg was administered as 4 20 mg SB-480848 tablets. Receives: Drug: SB-480848 80 mg |
| Matching Placebo | Placebo comparator | Placebo for 14 +/- 4 days followed by carotid endarterectomy. Placebo was administered as 4 placebo tablets. Placebo tablets were identical in appearance to the SB-480848 20 mg tablets. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Lp-PLA2 activity in the atherosclerotic plaque removed during carotid endarterectomy
Measured: 14 +/- 4 days
Secondary outcomes (4)
Lp-PLA2 mass in plaque removed during the carotid endarterectomy
Measured: 14 +/- 4 days
Lp-PLA2 mass and activity in blood
Measured: 14 +/- days
Lipid and Non-Lipid Biomarkers in Plasma
Lipids: total cholesterol, HDL, LDL, and triglycerides Non-Lipids: hsCRP, CD40L, ICAM-1, E-selectin, PAI-1 antibody, PAI-1 antigen, and MMP-9
Measured: 14 +/- days
Oxidised Lipids and Their Metabolites, and Biomarkers in Plaque
Oxidised Lipids and Their Metabolites: total lyso-PC, total phospholipid, and total phosphatidylcholine Biomarkers: CD68 (macrophages), CD3 (T cells), CD20 or CD22 (B cells), alpha-actin (smooth muscle cells), CD40L, MMP-2, MMP-9, PAI-1, ICAM-1, IL-6, and Lp-PLA2 (mRNA expression)
Measured: 14 +/- 4 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2013 (estimated)
- Study startJan 2003
- Primary completionJul 2003
- Study completionJul 2003
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 103 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
- NCT01916720
- Sponsor's protocol ID
- 480848/010
- Status last verified
- Dec 2016
- First submitted
- 31 Jul 2013
- Last updated
- 5 Dec 2016
- Results posted
- No
- 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
Johnson JL, Shi Y, Snipes R, Janmohamed S, Rolfe TE, Davis B, Postle A, Macphee CH. Effect of darapladib treatment on endarterectomy carotid plaque lipoprotein-associated phospholipase A2 activity: a randomized, controlled trial. PLoS One. 2014 Feb 20;9(2):e89034. doi: 10.1371/journal.pone.0089034. eCollection 2014.
PubMed 24586490
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-centre, Randomised, Double-blind, Placebo-controlled, Parallel-group Study to Investigate the Effect of the Lp-PLA2 Inhibitor SB-480848 (40, 80mg od) on Carotid Plaque Composition in Patients With Carotid Artery Disease and Planned Carotid Endarterectomy, Stratified for Statin Use and Gender, After 14+/-4 Days Treatment
- ClinicalTrials.gov ID
- NCT01916720
- Acronym / sponsor ID
- 480848/010
- Conditions
- Atherosclerosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 103 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- Jan 2003
- Primary completion
- Jul 2003 (actual)
- Study completion
- Jul 2003 (actual)
- First posted
- 6 Aug 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective is to determine Lp-PLA2 activity in atherosclerotic carotid plaques after 14 (+/-4) days treatment with darapladib, compared to placebo. Secondary objectives include determination of the change in Lp-PLA2 activity in blood, Lp-PLA2 mass in blood and plaque, specified biomarkers in blood and plaque and their respective correlation's with Lp-PLA2. In addition, the study aims to characterise the PK/PD of repeat oral doses of SB-480848, and safety and tolerability in this population.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| SB-480848 40 mg | Experimental | Drug: SB-480848 40 mg, Drug: PlaceboSB-480848 40 milligrams (mg) once a day (od) for 14 +/- 4 days followed by carotid endarterectomy. SB-480848 40 mg was administered as 2 SB-480848 20 mg tablets plus 2 placebo tablets. |
| SB-480848 80 mg | Experimental | Drug: SB-480848 80 mgSB-480848 80 mg od for 14 +/- 4 days followed by carotid endarterectomy.SB-480848 80 mg was administered as 4 20 mg SB-480848 tablets. |
| Matching Placebo | Placebo comparator | Drug: PlaceboPlacebo for 14 +/- 4 days followed by carotid endarterectomy. Placebo was administered as 4 placebo tablets. Placebo tablets were identical in appearance to the SB-480848 20 mg tablets. |
Who may qualify
- Ages
- 35 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Male or female, >35 years of age
- Females of childbearing potential must be using approved contraceptive measures
- Male patients must be willing to abstain from sexual intercourse or use a form of contraception if engaging in sexual intercourse with a woman who could become pregnant
- Planned carotid endarterectomy within a timeframe compatible with recruitment for the study and able to comply with the requirements of the study, as deemed by the investigator
- Written, informed consent to participate
Key exclusion criteria (13 listed)
- Recent myocardial infarction (within the previous 4 weeks)
- Currently taking corticosteroids, warfarin, digoxin or a potent CYP3A4 inhibitor
- Recent (<3 months) or ongoing acute infection or significant trauma associated with bruising and/or taking antibiotics. Prophylactic antibiotics for surgery are allowed
- Change in dose of lipid-lowering therapy during the previous 4 weeks from randomisation
- History of chronic liver disease (e.g. cirrhosis, hepatitis) OR ALT OR AST ≥1.5 times the upper limit of normal (ULN) at screening
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-480848 40 mgStudy Drug | Drug | SB-480848 40 mg |
| SB-480848 80 mgStudy Drug | Drug | SB-480848 80 mg |
| PlaceboStudy Drug | Drug | Matching Placebo, SB-480848 40 mg |
Primary outcome
Lp-PLA2 activity in the atherosclerotic plaque removed during carotid endarterectomy
Time frame: 14 +/- 4 days
4 secondary outcomes
Lp-PLA2 mass in plaque removed during the carotid endarterectomy
Time frame: 14 +/- 4 days
Lp-PLA2 mass and activity in blood
Time frame: 14 +/- days
Lipid and Non-Lipid Biomarkers in Plasma
Time frame: 14 +/- days
Oxidised Lipids and Their Metabolites, and Biomarkers in Plaque
Time frame: 14 +/- 4 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2016.
- Derived from this study: PubMed 24586490Johnson JL, Shi Y, Snipes R, Janmohamed S, Rolfe TE, Davis B, Postle A, Macphee CH. Effect of darapladib treatment on endarterectomy carotid plaque lipoprotein-associated phospholipase A2 activity: a randomized, controlled trial. PLoS One. 2014 Feb 20;9(2):e89034. doi: 10.1371/journal.pone.0089034. eCollection 2014.
- 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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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
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing SB-480848 40 mg and SB-480848 80 mg in people with Atherosclerosis, run by GlaxoSmithKline.
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 5 inclusion and 13 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 5 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Lp-PLA2 activity in the atherosclerotic plaque removed during carotid endarterectomy (time frame: 14 +/- 4 days). 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 NCT01916720, 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 5 Dec 2016.