A Multicenter, Randomized, Double-Blind, Double-Dummy, Parallel-Group, Placebo-Controlled, Study To Evaluate Efficacy, Safety And Tolerability Of Oral GW677954 Capsules (2.5, 5, 10, 15 And 20 Mg Once A Day) As A Monotherapy (Diet and/orexercise treated) Or As An Add-On To Metformin For 16 Weeks Duration In Subjects With Type 2 Diabetes Mellitus

• Conditions: Subjects between the ages of 18 and 70 years with T2DM who are diet and/or exercise treated or receiving stable metformin monotherapy will be recruited; MedDRA version: 7.1Level: LLTClassification code 10052066

• Registration Number: EUCTR2006-001275-38-CZ
• Lead Sponsor: GlaxoSmithKline R&D

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-07-13
• Last Update Posted: 10 July 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1. Subjects with T2DM as defined by the criteria of the ADA and/or recognized by
WHO Expert Committee on the Diagnosis and Classification of Diabetes Mellitus
(American Diabetes Association, 2004), for at least 3 months preceding screening
(see Section 15.3, Appendix 3:, Diagnosis and Classification of Diabetes Mellitus).
2. To be eligible for Randomization into the trial, a subject must satisfy all of the
following glycemic criteria:
• HbA1c level via central laboratory at the pre-screening visit
• If HbA1c = 8.0% but = 10.0%: subject may proceed to Randomization;
• If HbA1c = 7.8% but < 8.0%, subject not eligible to proceed, but may be retested
once to establish eligibility (or lack thereof). If HbA1c level = 8.0% upon retest,
subject is eligible to proceed; otherwise they should be withdrawn.
If HbA1c < 7.8%, subject not eligible to proceed (no retest allowed).
• FPG level via central laboratory at the pre-screening visit must be < 270 mg/dL (15.0 mmol/L). FPG may be retested within a week to confirm eligibility (or lack thereof).
3. Concurrent T2DM therapy:
• Diet and/or exercise treated: Must not have taken antidiabetic medication for at
least 2 months prior to the pre-screening visit,
OR
• Metformin monotherapy: Subjects entering the study on metformin must be on
the same dose, formulation and regimen of metformin for at least 2 months prior
to the pre-screening visit,
AND
• TZDs and insulin are excluded in the 3 months prior to the Screening visit for all
subjects.
4. Males and females who are 18 to 70 years of age inclusive at the time of Screening.
5. If female, eligible to enter and participate in this study:
• If 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,
• If of child-bearing potential, has a negative pregnancy test at Screening (serum),
at Randomization (urine) and:
? Has 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
? Uses double-barrier methods of contraception; condoms with the use of
caps (with spermicide) and IUDs are acceptable, or
? Uses hormonal contraceptives (oral, depots, patches etc) with doublebarrier
methods of contraception as outlined above, or
? Abstains from sexual intercourse, or
? Is with a same sex partner and does not participate in bisexual activities
where there is any risk of pregnancy.
6. Body Mass Index (BMI): = 25 and = 40 kg/m2 and weigh at least 50 kg at Screening.
7. If subject is a smoker, must be able to abstain while in clinic at each visit.
8. Subject has given full written informed consent prior to any study related procedures are 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

1. Metabolic Disease including:
• Diagnosis of Type 1 diabetes mellitus
• Uncorrected thyroid dysfunction.
• Significant weight gain or loss within the 3 months prior to Screening.
2. Previous use of insulin for treatment of hyperglycemia within 3 months of screening.
3. History of recent clinically significant cardiovascular disease including:
• History or ECG evidence of prior myocardial infarction within 6 months prior to
Screening.
• Current unstable angina or history of unstable angina in past 6 months.
• 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 (CHF) with New York Heart Association (NYHA) Class
II-IV symptoms (see Section 15.4, Appendix 4).
• Blood pressure > 160/100 mmHg or resting heart rate > 100 bpm.
• Has a QTc interval (Bazett’s) > 440 msec in males and > 450 msec in females at
Screening.
• Clinically significant ECG abnormalities which, in the opinion of the Investigator,
may affect the interpretation of safety data, or which otherwise, contraindicates
participation in a clinical trial with a new chemical entity.
4. History of chronic pancreatitis.
5. Familial hypercholesterolemia.
6. TGs = 800 mg/dL (8.96 mmol/L) at Screening.
7. Serum creatinine at screening > 1.4 mg/dL (124 µmol/L) for women, or > 1.5 mg/dL
(133 µmol/L) for men.
8. Clinically significant anemia defined by hemoglobin concentrations <12.0 g/dL or <
120.0 g/L for males and < 11.0 g/dL or < 110.0 g/L for females.
9. History of significant co-morbid diseases
10. Documented history of hepato-biliary disease including a history of, or positive
laboratory results for hepatitis at Screening, and/or clinically significant hepatic
enzyme elevation including:
• Any one of the following enzymes greater than 2.5 times the upper limit of normal (ULN) value at Screening
11. History of metabolic acidosis, rhabdomyolysis, myalgia, myositis or myopathy after
taking statins or fibrates.
12. Any subject who has withdrawn therapy due to AEs after taking a PPAR? or a
PPARa/? dual agonist, either marketed (e.g., troglitazone, rosiglitazone or
pioglitazone) or under current or previous clinical investigation.
13. Signs or symptoms of myositis at Screening (or upon 1 repeat test), and/or creatinine phosphokinase (CPK) = 3.0 times ULN
14. Is currently taking or has taken any of the following medications in the 3 months
prior to the pre-screening visit:
• Anti-obesity agents (including fat absorption blocking agents)
• St. John’s Wort
• Warfarin and other oral anticoagulants (excluding aspirin and non-steroidal antiinflammatory
drugs)
• Digoxin
• Oral or injectable corticosteroids (inhaled and intranasal steroids are acceptable)
• Use of antidiabetic agents (other than metformin) in the 2 months prior to the prescreening visit.
• Use of TZDs in the 3 months prior to the pre-screening visit.
• Methotrexate, cyclosporine or monoclonal antibodies (e.g., alemtuzumab,
gemtuzumab ozogamicin, rituximab, trastuzumab, ibritumomab, tioxetan) for
rheumatoid arthritis or psoriasis.
• Atypical antipsychotic medications
• Antiretroviral drugs
• Use of lipid lowering agents within 3 months prior to the pre-screening visit. This
includes statins, fibrates, ezetimibe (Zetia), niacin and bile acid sequestrants.
• Monoamine oxidase inhibitors

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified