| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | Treatment of dyslipidaemia | |
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial | 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.
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| E.2.2 | Secondary objectives of the trial | 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.
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| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal 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).
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| E.4 | Principal 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
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| E.5 End points |
| E.5.1 | 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. | |
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Information not present in EudraCT |
| E.8.1.3 | Single blind | Information not present in EudraCT |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | Information not present in EudraCT |
| E.8.1.7 | Other | Information not present in EudraCT |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | Information not present in EudraCT |
| E.8.3 | The trial involves single site in the Member State concerned | Information not present in EudraCT |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| E.8.8 | Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial | |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 4 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 4 |
