Treatment of dyslipidaemia
Conditions
Interventions
Product Name: GW501516X
Product Code: As above
Pharmaceutical Form: Tablet
Current Sponsor code: GW501516X
Concentration unit: mg milligram(s)
Concentration number: 2.5-
Pharmaceutical form of the pl
Sponsors
GlaxoSmithKine Research & Development Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A subject will be eligible for inclusion in this study only if all of the following criteria apply: 1. Male or female subjects aged 18 to 75 years. 2. Females must be of non-childbearing potential (surgically sterile or post-menopausal [amenorrhoeic] for more than one year). 3. Fasting plasma HDLc concentration less than or equal to 45mg/dL (less than or equal to 1.16mmol/L) 4. Subjects whose plasma LDLc concentration does not require treatment according to the NCEP/ATPIII guidelines: ? Plasma LDLc concentration less than or equal to 190mg/dL (less than or equal to 4.91mmol/L) if no more than one cardiovascular risk factor, or ? Plasma LDLc concentration less than or equal to 160mg/dL (less than or equal to 4.13mmol/L) if two or more cardiovascular risk factors, and a 10-year CHD risk less than or equal to 10% (Framingham Point Scores; see Section 14.8), or ? Plasma LDLc concentration less than or equal to 130mg/dL (less than or equal to 3.36mmol/L) if two or more cardiovascular risk factors, and a 10-year CHD risk >10% and less than or equal to 20% (Framingham Point Scores). 5. Fasting plasma TG concentration less than or equal to 500mg/dL (less than or equal to 5.65mmol/L). 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. A medical history significant for the following: ? CHD, heart failure, stroke, peripheral vascular disease, angina pectoris or previous myocardial infarction) or a 10-year risk for developing CHD >20% (Framingham Point Scores). ? QTc interval >440msec (males) or >450msec (females) at screening. ? Known Type 1 or Type 2 diabetes mellitus or fasting plasma glucose (FPG) at screening AND at Visit 2 both >126mg/dL (>7mmol/L). ? History of renal disease or renal impairment or serum creatinine >1.5mg/dL (135micromol/L) at screening. ? History of metabolic acidosis or rhabdomyolysis, or a history of myalgia, myositis or myopathy after taking statins and/or fibrates, or CPK >3 x ULN at screening. ? Pre-existing gallbladder disease (unless the subject has since undergone a cholescystectomy). ? History of chronic pancreatitis. ? History of familial adenomatous polyposis or colonic polyps. ? History of chronic viral hepatitis (including presence of hepatitis B surface antigen or hepatitis C antibody), or other chronic hepatic disorders; or ALT or AST >2 x ULN, or alkaline phosphatase or total bilirubin >1.5 x ULN of laboratory reference range at screening. ? Inadequately treated thyroid dysfunction or an abnormal thyroid function test at screening. 2. Subjects who are taking or who have taken within eight weeks of screening any of the following drugs: ? Drugs for the treatment for dyslipidaemia ? Drugs known to have a substantial effect on lipid or lipoprotein metabolism, ? Anticoagulants or anti-platelet agents (other than low dose [75mg] aspirin). 3. Any change in concomitant medication that has a moderate effect on lipid or lipoprotein metabolism within eight weeks prior to screening. 4. Any major change in diet, exercise habits or smoking status within eight weeks prior to screening. 5. Use of an investigational drug within 30 days or 5 half-lives (whichever is the longer) preceding the first dose of study medication
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: ? To assess the safety and tolerability of once daily dosing of 2.5mg, 5mg and 10mg GW501516 for 12 weeks in subjects with low HDLc. ? To compare the effect of various doses of GW501516 on plasma concentrations of HDLc with respect to change from baseline relative to placebo. ;Secondary Objective: ? To determine the effect of various doses of GW501516 on plasma concentrations of total cholesterol, low density lipoprotein cholesterol (LDLc), TG and other lipid parameters with respect to change from baseline relative to placebo. ? To determine the optimal doses of GW501516 to take forward into subsequent clinical trials based on safety and efficacy results. ? To characterise the population pharmacokinetics (PK) of GW501516 in subjects with low HDLc. ? To explore the relationship between GW501516 exposure and lipid parameters. ? To explore the effect of GW501516 on apolipoproteins and other metabolic and inflammatory markers. ;Primary end point(s): The primary efficacy endpoint is change from baseline in fasting plasma HDLc concentration at the end of 12 weeks of double-blind treatment. | — |
Countries
Denmark, Finland, Lithuania, Sweden
Outcome results
None listed