primary hypercholesterolemia MedDRA version: 8.1 Level: LLT Classification code 10020604 Term: Hypercholesterolemia
Conditions
Interventions
Trade Name: N/A
Product Code: GW501516
Pharmaceutical Form: Tablet
Current Sponsor code: GW501516
Concentration unit: mg/g milligram(s)/gram
Concentration type: equal
Concentration number: 2.5-10
Phar
Sponsors
GlaxoSmithKline R&D
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female subjects aged 18-70 years (inclusive at the time of Pre- Screening Visit 1) 2. Subjects who are on stable, approved dose of Simvastatin (20, 40 or 80 mg) or Atorvastatin (10, 20, 40 or 80 mg) for a minimum of 8 Weeks prior to the prescreening visit 1. 3. Subjects with stable LDL-C =100 mg/dl (2.59 mmol/L) and =160 mg/dL (4.14 mmol/L) at Visits 1 and 2 4. Females, to be eligible to enter and participate in this study must be: • of non –child bearing potential ( i.e. physiologically incapable of becoming pregnant (tubal ligation, documented hysterectomy), including any female who is post-menopausal [> 1 year without menstrual period and FSH/estradiol concentrations are consistent with postmenopausal state]. Other reasons for amenorrhoea should also be excluded by the Investigator 5. Subject has given full written informed consent prior to any study-related procedures being performed. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Metabolic Disease including: • Diagnosis of Type 1 or Type 2 diabetes mellitus, or FPG >126mg/dL(>7.0mmol/L) • Uncorrected thyroid dysfunction • Significant weight gain or loss within the past 3 months prior to Screening Visit 2. 2. History of recent clinically significant cardiovascular disease at Visit 2 including: • CHD, CHF (NYHA Class II-IV), stroke, peripheral vascular disease. • History or ECG evidence of prior myocardial infarction in the past 6 months. • Current unstable angina or history of unstable angina in the past 6 months. • Coronary revascularization including percutaneous transluminal coronary angioplasty or coronary artery bypass graft surgery • Clinically significant arrhythmia or valve heart disease. • Blood pressure > 160/100 mmHg or resting heart rate > 100 bpm. • Has a QTc interval > 450 msec in males or females, QTcb or QTcf, machine or manual overreads at Screening Visit 2. • Clinically significant ECG abnormalities 3. History of significant co-morbid diseases [e.g., severe Chronic Obstructive Pulmonary disease (COPD), chronic gastrointestinal disease, etc.] 4. TGs in excess of 400mg/dL (4.52 mmol/L) at Visits 1 or 2 (for permitted re-test details see Section 3.1.3) 5. Subjects with cTnI > 0.35ng/ml 6. Serum creatinine at Visit 2 > 1.4 mg/dL (124µmol/L) for females, or > 1.5mg/dL (133µmol/L) for males at Visit 2. 7. Clinically significant anaemia defined by haemoglobin concentration ( 1.5 x ULN at Screening, unless consistent with presumed or diagnosed Gilbert’s disease. 9. History of metabolic acidosis or rhabdomyolysis, or a history of myalgia, myositis or myopathy after taking statins and/or fibrates. 10. Signs or symptoms of myositis and/or CPK =3xULN at Visit 2 11. Any subject who has been withdrawn from therapy due to AEs after taking a PPAR? or a PPARa/? dual agonist 12. Any subject who is taking medications that are contraindicated for use in the atorvastatin and simvastatin label. 13. Any subject currently taking or who has taken any of the following medications as assessed at Screening Visit 2. • Lipid-lowering agents (with exception of simvastatin 20, 40 or 80 mg and atorvastatin 10, 20, 40, or 80 mg) and drugs known to have substantial effect on lipid metabolism including but not limited to fish oil and vitamins within 8 Weeks prior to pre-screening Visit 1 • All oral glucose-lowering agents and insulin • Anti-obesity agents • Warfarin and digoxin • Oral or injectable corticosteroids • Oral anti-coagulant (other than aspirin, clopidogrel and non-steroidal anti-inflammatory drugs [NSAIDs]) within 30 days prior to the pre-screening Visit 1 • Antiretroviral drugs • St. John’s Wort • Use of Thiazolidinedione ( TZDs ) • Any major change in diet, exercise habits or smoking status • Methotrexate, cyclosporine or monoclonal antibodies for rheumatoid arthritis or psoriasis • Atypical antipsychotics medications • Monoamine oxidase inhibitors • Any OTC or herbal medications, including but not limited to vitamins supplements, unless prepared to cease self-me
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate the efficacy and dose response of once daily oral dosing of GW501516 (2.5 mg, 5 mg and 10 mg) versus placebo in percentage change from baseline in LDL-c levels after 12 Weeks of dosing in subjects with primary hypercholesterolemia on background statin therapy. ;Secondary Objective: • Evaluate the effect of once daily oral dosing of GW501516 (2.5 mg, 5 mg and 10 mg) versus placebo on fasting levels of TC, HDL-c, TG, apolipoproteins, ApoB and ApoAI, non-HDL-c, VLDL-c, FFA and an inflammatory marker hs-CRP during 12 weeks of dosing in subjects with primary hypercholesterolemia on background statin therapy. • Evaluate the safety and tolerability of once daily oral dosing of GW501516 (2.5 mg, 5 mg and 10 mg) versus placebo in subjects with primary hypercholesterolemia on background statin therapy. ;Primary end point(s): Primary and Secondary Endpoints: • Lipids: • LDL-C, HDL-C, TC, TG, non-HDL-C (calculated), VLDL-C and FFA • Apolipoproteins: • ApoB and ApoAI • Inflammatory markers • hs-CRP • Safety Analysis • ECGs • Physical Examination • Vital signs • Clinical Laboratory tests • Body weight • AE’s • Exploratory endpoints: • Lipid sub-fractions: (detailed in Section 5.2.3.1) • Inflammatory and metabolic biomarker endpoints including but not limited to novel biomarkers | — |
Countries
Czech Republic, Netherlands
Outcome results
None listed