| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Dyslipidaemia and overweight |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 7.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10052066 |
|
| 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 compare the effect of GW677954 at doses of 2.5mg, 5mg, 10mg and 20mg with those of placebo on non-HDL-C at 24 weeks in overweight subjects with low HDL-C, high TGs dyslipidaemia.
|
|
| E.2.2 | Secondary objectives of the trial |
• To characterise the safety and tolerability of GW677954 at doses of 2.5mg, 5mg,
10mg and 20mg and compare with that of placebo through assessment of physical
examination, vital signs, clinical laboratory tests, and AE reporting.
• To compare the effect of GW677954 at doses of 2.5mg, 5mg, 10mg and 20mg with
that of placebo on levels of TC, LDL-C, HDL-C, TGs, and other lipid parameters.
• To compare the effect of GW677954 at doses of 2.5mg, 5mg, 10mg and 20mg with
that of placebo on biomarkers for liver and skeletal muscle effects.
• To compare the effect of GW677954 at doses of 2.5mg, 5mg and 20 mg with that of
placebo on change in proportion of subjects with metabolic syndrome who meet
ATP III criteria.
• To compare the effect of GW677954 at doses of 2.5mg, 5mg and 20 mg with that of
placebo on measures of insulin resistance through Homeostasis Model Assessment-insulin sensitivity (HOMA-S). |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
1. Waist circumference ≥102cm (men) or ≥88cm (women) at visit 1
2. Fasting plasma HDL-C ≤40mg/dL (1.03mmol/L) (men) or ≤50mg/dL (1.29mmol/L)
(women) at Screening Visit 1
3. Fasting TGs ≥150mg/dL (1.69mmol/L) and ≤800mg/dL (8.96mmol/L) at Screening
Visit 1
4. Subjects whose plasma LDL-C concentration does not require treatment according to the NCEP ATP III guidelines at Screening Visit 1
• Plasma LDL-C concentration ≤190mg/dL (≤4.91mmol/L) if no more than one
cardiovascular risk factor, or
• Plasma LDL-C concentration ≤160mg/dL (≤4.13mmol/L) if two or more
cardiovascular risk factors, and a 10-year congestive heart failure (CHF) risk
≤10% (Framingham Point Scores), or
• Plasma LDL-C concentration ≤130mg/dL (≤3.36mmol/L) if two or more
cardiovascular risk factors, and a 10-year CHF risk >10% and ≤20%
(Framingham Point Scores).
5. Male and female subjects 18 to 70 years of age (inclusive at the time of Screening) at Visit 2
6. Females, to be eligible to enter and participate in this study must be:
either, of non-childbearing potential (i.e., physiologically incapable of becoming pregnant (tubal ligation), including any female who is post-menopausal [>1 year without menstrual period]); or, of child-bearing potential and have a negative pregnancy test at Screening (serum), and: have a male partner who is sterile prior to the female subject’s entry into the study and is the sole sexual partner for that female subject, or use double-barrier methods of contraception; condoms with the use of caps (with spermicide) and intrauterine devices are acceptable, or use hormonal contraceptives (oral, depots, patches, etc) with double-barrier methods of contraception as outlined above, or abstain from sexual intercourse, or be with a same sex partner and does not participate in bisexual activities where there
is any risk of pregnancy.
7. Subject has given full written informed consent prior to any study-related procedures are performed.
8. If subject is a smoker, must be able to abstain while in clinic at each visit. |
|
| E.4 | Principal exclusion criteria |
1. Metabolic Disease including:
• Diagnosis of Type 1 or Type 2 diabetes mellitus, or FPG at Screening, and at Visit 2 both >126mg/dL (>7.0mmol/L);
• Uncorrected thyroid dysfunction;
• Significant weight gain or loss within the 3 months prior to Screening (Visit 1).
2. History of recent clinically significant cardiovascular disease at Visit 2 including:
• History or ECG evidence of prior myocardial infarction
• Current unstable angina or history of unstable angina
• Coronary revascularization including percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass graft (CABG) surgery that is either planned or occurred in the 6 months prior to Screening.
• Clinically significant arrhythmia or valvular heart disease.
• Congestive heart failure with NYHA Class II-IV symptoms.
• Blood pressure > 160/100 mmHg or resting heart rate > 100 bpm at Visit 2.
• Has a QTc interval > 440 msec in males and > 450 msec in females at Visit 2
• Clinically significant ECG abnormalities
3. History of chronic pancreatitis;
4. Diagnosis of either Familial hypercholesterolaemia or Familial combined hyperlipidaemia
5. History of TGs in excess of 800mg/dL (8.96mmol/L)
6. Serum creatinine at visit 2 > 1.4 mg/dL (124µmol/L) for women, or > 1.5mg/dL
(133µmol/L) for men at visit 2.
7. Clinically significant anaemia defined by haemoglobin concentration <12.0g/dL or
<120.0g/L for males and <11.0g/dL or <110.0g/L for females at Visit 2
8. Documented history of hepato-biliary disease including a history of, or positive
laboratory results for hepatitis (hepatitis B surface antigen, hepatitis B core antigen,
and/or hepatitis C antibody) at Run-in [Visit 2], and/or clinically significant hepatic
enzyme elevation including:
• Any one of the following enzymes greater than 2.5 times the ULN value:
- Alanine aminotransferase
- Aspartate aminotransferase
- Alkaline phosphatase
• Total or direct bilirubin >1.5 x ULN, unless due to diagnosed or presumed 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 CK >3 x ULN at Screening;
11. Is currently taking or has taken any of the following medications in the 3 months
prior to Screening (Visit 1) as assessed at visit 2:
• All lipid-lowering agents and drugs known to have substantial effect on lipid
metabolism
• All oral glucose-lowering agents and insulin
• Anti-obesity agents
• Warfarin and digoxin
• Oral or injectable corticosteroids (other than inhaled, intranasal and topical)
• Oral anti-coagulant (other than aspirin, clopidogrel and non-steroidal
anti-inflammatory drugs [NSAIDs])
• Antiretroviral drugs
• St. John’s Wort
• Use of TZDs in the 3 months prior to the screening
• Methotrexate, cyclosporine or monoclonal antibodies
• Atypical antipsychotics medications
• Monoamine oxidase inhibitors
12. History of cancer
13. Women who are lactating, pregnant, or planning to become pregnant.
14. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to any drug
chemically related to the study drug.
15. Known allergy to any of the capsule excipients, or history of drug or other allergy,
which, in the opinion of the responsible study physician, contradicts participation.
16. Has a history of substance abuse within the past year as determined by the
Investigator at (Visit 2) or during treatment:
• Unwilling to refrain from the use of illicit drugs and adhere to other protocolstated
restrictions while participating in the study.
• History of alcohol abuse defined as an average weekly intake of greater than
21 units or an average daily intake of greater than 3 units (males) or defined as
an average weekly intake of greater than 14 units or an average of daily intake
of greater than 2 units (females).
17. Received treatment with the investigational product during the previous 4 months or any other trial during the previous 3 months, or has participated in a previous study with GW677954.
18. Subjects with ongoing oedema or history of oedema requiring pharmacological
treatment in the 3 months prior to Screening (Visit 1) as assessed at Visit 2
19. Subjects who have a history of adverse events after taking a PPARγ or a PPARαγ
agonist. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Percentage change from baseline in non-HDL-C based on log-transformed data at
week 24.
|
|
| 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 | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| 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 | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| 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 | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| 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 | |
| E.8.9.1 | In the Member State concerned months | 12 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 12 |
Print
