A RANDOMISED, DOUBLE-BLIND, PARALLEL GROUP, PLACEBO-CONTROLLED, MULTICENTRE STUDY TO EVALUATE THE SAFETY, TOLERABILITY AND EFFICACY OF ORAL GW677954 CAPSULES 2.5mg, 5mg, 10mg AND 20mg A DAY FOR 24 WEEKS IN OVERWEIGHT DYSLIPIDAEMIC SUBJECTS
- Conditions
- Overweight Dyslipidaemic SubjectsMedDRA version: 7,1Level: LLTClassification code 10052066
- Registration Number
- EUCTR2005-001558-26-LV
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 290
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.
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
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 adh
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method