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Healthy SubjectsPhase 2NCT00474864

Study To Evaluate The Effects Of GW856553 On Endothelial Function/Vascular Compliance In Subjects With Dyslipidaemia.

A Phase 2 study testing GW856553 in people with Healthy Subjects and Dyslipidaemias, run by GlaxoSmithKline at 3 sites in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The rationale for this study is to determine whether GW856553 (7.5mg BD for 28 days) has an effect on endothelial function in dyslipidaemic subjects as assessed by venous occlusion plethysmography using brachial artery acetylcholine infusion. Read more about this study

Who is it for?
Ages 18 to 75 yearsHealthy volunteers can take part
Conditions the study is for
Healthy Subjects, Dyslipidaemias, Dyslipidaemia
What is being tested?
GW856553
How many people
66 participants
Where
3 sitesUnited Kingdom
Study dates
Jul 2007to Apr 2008
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 18 to 75 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Healthy adult male and females between 18 and 75 years of age, inclusive.
  • To be eligible, female subjects must have a negative pregnancy test (i.e. Urine or serum β-hCG (for females) and be of:
  • non-childbearing potential (i.e. physiologically incapable of becoming pregnant). This includes any female who is post-menopausal.
  • OR
  • childbearing potential and agree to commit to one of the protocol-approved methods of contraception.
  • Body weight > 50 kg and body mass index (BMI) between 19 and 32kg/m2
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  • Subjects with high LDLc levels, as per NCEP ATPIII criteria:fasting LDLc level > 4.1 mmol/L (160 mg/dL), inclusive. Fasting TG level should be < 4.5mmol/L (400 mg/dL)
  • A signed and dated written informed consent prior to admission to the study
  • The subject is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions.
  • The following criteria must apply only for subjects undergoing FDG-PET/CT and MRI
  • All diabetics will be excluded from the scanning sub-study involving MRI and FDGPET/CT.
  • Subjects will be excluded who have previously participated in a research and/or medical protocol involving nuclear medicine, PET or radiological investigations with significant radiation burden (a significant radiation burden being defined as ICRP category IIb or above: No more than 10 mSv effective radiation dose in addition to natural background radiation, in the previous 3 years including the dose from this study). Given the planned administration of 10 mSv in this study, any subjects who have been exposed to ionizing radiation above background levels, for example as a result of their work with radiation as category A (classified) workers, will be excluded
  • Adult males and females between 50 and 75 years of age, inclusive.
  • Women must be of non-childbearing potential [i.e. either postmenopausal or documented hysterectomy - tubal ligation is not sufficient]. To be eligible, female subjects must have a negative pregnancy test (i.e. serum beta hCG test) and be of non-childbearing potential (i.e. physiologically incapable of becoming pregnant). This includes any female who is post-menopausal. All diabetics will be excluded from the scanning sub-study involving MRI and FDG-PET/CT.
  • Contraindication to MRI scanning (as assessed by local MRI safety questionnaire) which includes but not limited to:
  • Intracranial aneurysm clips (except Sugita) with an appropriate operative conformation,
  • History of intra- orbital metal fragments that have not been removed by an MD,
  • Pacemakers and non-MR compatible heart valves,
  • Inner ear implants,
  • History of claustrophobia in MR.
  • Is unable to lie comfortably on a bed inside a PET camera with their head in the field of view for at least 60 minutes as assessed by physical examination and medical history (e.g. back pain, arthritis).
  • The following criteria apply only for healthy control subjects
  • A subject will be eligible for inclusion in this study only if all of the following criteria apply:
  • Healthy adult male between 18 and 75 years of age, inclusive.
  • Body weight > 50 kg and body mass index (BMI) between 19 and 32kg/m2
  • A signed and dated written informed consent prior to admission to the study
  • The subject is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions.
  • Blood pressure should be <=140 mmHg systolic and/or <=90mmHg diastolic)
  • Subjects with LDLc, < 2.6 mmol/L (100 mg/dL). Fasting TG level should be <1.7mmol/L (150 mg/dL); HDLc > 1.0 mmol/L (40mg/dL)
  • Non-smokers

Who cannot join

  • History of symptomatic coronary artery disease, stroke, or other known atherosclerotic disease.
  • Subjects who are current smokers and require a cigarette within 30 minutes after they wake in the morning, or cannot abstain from smoking for approximately 5 hours.
  • History of chronic viral hepatitis (including presence of hepatitis B surface antigen or hepatitis C antibody), or other chronic hepatic disorders.
  • History of increased liver function tests (ALT, AST) due to acute or chronic liver conditions, above the upper limit of normal in the past 6 months and/or liver function tests (bilirubin, ALT, AST) above the upper limit of normal at Screening.
  • Renal impairment with creatinine clearance of <50 ml/min at screening, or history of kidney transplant or history of contrast nephropathy.
  • Current inadequately controlled hypertension (blood pressure >180 mmHg systolic and/or >100mmHg diastolic) or any subject who has experienced a modified regimen of antihypertensive medication within 6 weeks prior to first dose of study medication, or any subject who is likely to commence treatment of a hypertensive medication
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  • Current poorly controlled diabetes mellitus, defined as HbA1c >10% at Screen.
  • History of heart failure defined as NYHA class II - 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 (e.g., very severe chronic airways disease, HIV positive, life-threatening arrhythmias) that may prevent a subject from completing the study.
  • Alcohol or drug abuse within the past 6 months.
  • Previous exposure to GW856553.
  • Use of an investigational device or investigational drug within 30 days or 5 half-lives (whichever is the longer) preceding the first dose of study medication.
  • Subjects who will commence or who are likely to commence treatment with oral intranasal or topical corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs) (other than aspirin), PPARγ agonists (e.g. rosiglitazone), sulfonylureas, insulin, fibrates, niacin, ACEI, ARBs, nitrates, HRT, etc from screening until study completion.
  • Any non-stable dosing of ongoing medication regimens (as noted above (#14)) throughout the study trial.
  • Any subject that is likely to commence statin treatment from screening until the final follow up visit. Any subjects currently receiving treatment with statins must be able to washout from the statin for 28 days prior to first dose of study medication.
  • The subject has a three month prior history of regular alcohol consumption exceeding an average weekly intake of > 28 units (or an average daily intake of greater than 3 units) for males, or an average weekly intake of > 21 units (or an average daily intake of greater than 2 units) for females or a positive alcohol breath test at the screening visit
  • A positive urine test for drugs of abuse (not related to known medications the subject is taking, ie, codeine for pain management) or alcohol at screening or prior to study medication administration.
  • Any other subject whom the Investigator deems unsuitable for the study (e.g., due to either medical reasons, laboratory abnormalities, expected study medication non-compliance, or subject's unwillingness to comply with all study-related study procedures).
  • Subjects with rheumatoid arthritis, connective tissue disorders and other conditions known to be associated with chronic inflammation (e.g. Inflammatory Bowel Disease).
  • Subjects with chronic infections such as gingivitis, periodontitis, prostatitis, gastritis, and urinary tract infections, or any active diseases, including active tuberculosis or a history of active tuberculosis.
  • Subjects with any acute infection, symptoms suggestive of sinusitis, or significant trauma (burns, fractures).
  • Subjects who have donated more than 500 mL of blood within 56 days prior to the study medication administration.
  • History of myopathy or rhabdomyolysis.
  • QTc interval >450 msec
  • An unwillingness of male subjects to abstain from sexual intercourse with pregnant or lactating women; or an unwillingness of the subject to use contraceptive methods defined in the protocol from the time of the first dose of the study medication until 3 months after administration of last dose of study medication.
  • Pregnant or nursing women

Trial locations and contacts

3 sites in 1 country.

United Kingdom3 sites

  • GSK Investigational Site

    Cambridge, CB2 2GG

  • GSK Investigational Site

    Cardiff, CF144XW

  • GSK Investigational Site

    London, London, EC1M 6BQ

Other trials in United Kingdom

About this study

Official title: A Double-Blind, Placebo-Controlled, Parallel Study To Evaluate The Effects Of GW856553 On Endothelial Function/Vascular Compliance In Subjects With Dyslipidaemia.

The rationale for this study is to determine whether GW856553 (7.5mg BD for 28 days) has an effect on endothelial function in dyslipidaemic subjects as assessed by venous occlusion plethysmography using brachial artery acetylcholine infusion. This will establish consistency with preclinical findings, as well as confirm a physiologic human response at the current safe maximal dose. Safety (specifically serum liver function testing) and tolerability will also be evaluated in this trial.

Being tested
GW856553
Keywords
Endothelial Function,, vascular compliance,, atherosclerosis
Medical subject headings
Dyslipidemias, Atherosclerosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GW856553Drug

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Forearm blood flow ratio measured at baseline and day 28.

    Measured: at baseline and day 28.

Secondary outcomes (4)

  1. Forearm blood flow ratio at (baseline and day28). Augmentation Index(baseline and day28). Pulse wave velocity (baseline and day28). pHSP-27 levels (baseline and day28).

    Measured: baseline and day28

  2. Safety and tolerability parameters (weekly)

    Measured: weekly

  3. Measurement of total and phosphorylated heat shock protein-27 (pHSP-27) levels in sorbitol induced whole blood cells of patients with dyslipidaemia

  4. Safety and tolerability parameters, including physical examination, blood pressure, heart rate, 12-lead electrocardiograms (ECGs), clinical laboratory tests, and adverse events reporting

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 May 2007 (estimated)
  2. Study startJul 2007
  3. Primary completionApr 2008
  4. Study completionApr 2008

Resources

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
Enrolment
66 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00474864
Sponsor's protocol ID
PM1108357
Status last verified
Feb 2011
First submitted
15 May 2007
Last updated
6 Jun 2012
Results posted
No
Data monitoring committee
No

Publications

  • Cheriyan J, Webb AJ, Sarov-Blat L, Elkhawad M, Wallace SM, Maki-Petaja KM, Collier DJ, Morgan J, Fang Z, Willette RN, Lepore JJ, Cockcroft JR, Sprecher DL, Wilkinson IB. Inhibition of p38 mitogen-activated protein kinase improves nitric oxide-mediated vasodilatation and reduces inflammation in hypercholesterolemia. Circulation. 2011 Feb 8;123(5):515-23. doi: 10.1161/CIRCULATIONAHA.110.971986. Epub 2011 Jan 24.

    PubMed 21262998

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing GW856553 in people with Healthy Subjects and Dyslipidaemias, run by GlaxoSmithKline at 3 sites in United Kingdom.

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 30 inclusion and 27 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 6 Jun 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United Kingdom. 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. 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?

Forearm blood flow ratio measured at baseline and day 28. (time frame: at baseline and day 28.). 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 NCT00474864, 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 6 Jun 2012.

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