Type 2 Diabetes Mellitus MedDRA version: 7.1 Level: LLT Classification code 10045242
Conditions
Interventions
Product Code: GW823093
Pharmaceutical Form: Capsule*
Current Sponsor code: GW823093
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5-
Current Sponsor code: GW823
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subjects with T2DM as defined by the criteria of the American Diabetes Association and recognized by WHO, Expert Committee on the Diagnosis and Classification of Diabetes Mellitus [American Diabetes Association, 2004a] at least 3 months preceding screening (see Section 15.8, Appendix 8, “Diagnosis and Classification of Diabetes Mellitus"). Eligible subjects must demonstrate endogenous insulin production as manifested by a fasting C-peptide level of >/= 0.8 ng/mL at screening. 2. Concurrent T2DM therapy: •Must be diet and exercise treated OR •Not taking more than 1 oral anti-diabetic agent, and willing to stop treatment at Screening (Visit 2) •Previous diabetes monotherapy will be limited to: sulfonylureas, glitinides, biguanides, or alpha-glucosidase inhibitors such as acarbose. A thiazolidinedione (TZD) is only acceptable if stopped 3 or more months prior to screening. Monotherapy with a fixed-dose combination drug is not allowed. Subjects must not have been taking any oral anti-diabetic combination therapy (including with a fixed dose combination drug) for at least 3 months prior to the screen visit. 3. Glycemic parameters: •HbA1c level at Pre-screening (Visit 1) •For subjects treated with oral monotherapy: = 7.0% and 1 year without menstrual period]); or, •If of child-bearing potential, has a negative pregnancy test at Screening (Visit 2) (serum) and at Week 0 (Visit 5) (urine and serum) 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 spermicide) and IUDs are acceptable, or •Uses hormonal contraceptives (oral, depots, patches etc) with double-barrier 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. 8. Informed Consent: a signed and dated written consent obtained from the subject before 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
Exclusion criteria: 1. Metabolic Disease including but not limited to: •Diagnosis of Type 1 diabetes mellitus •Uncorrected thyroid dysfunction. (NOTE: subjects with hypothyroidism on a stable dose of thyroid replacement therapy for at least 3 months prior to Screening (Visit 2), and who have a screening thyroid stimulating hormone (TSH) within the limits of normal may participate). •Significant weight gain or loss (as defined as > 5% of total body weight) within the past 3 months prior to Screening (Visit 2). 2. Previous use of insulin: •Within 3 months of screening; •For > 2 weeks when used for acute illness in the last 12 months prior to Screening (Visit 2); •Used for more than 1 year when associated with gestational DM. 3. History of clinically significant cardiovascular disease including: •Documented myocardial infarction in the past year •Coronary revascularization including percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass graft (CABG) surgery in the previous year. •Unstable angina •Clinically significant arrhythmia or valvular heart disease •Congestive heart failure (CHF) classified as New York Heart Association (NYHA) Class II, III or IV heart failure (see Section 15.9, Appendix 9), New York Heart Association Functional Classification)] •Blood pressure > 150/100mmHg or HR > 100 beats/minute. Subjects using antihypertensives must be on stable doses during the 3 months prior to Screening and during the trial. •A QTc interval = 440msec in males and = 450msec in females at Screening (Visit 2). •Other clinically significant ECG abnormalities which, in the opinion of the Investigator, may affect the interpretation of safety and/or efficacy data, or which otherwise, contraindicates participation in a clinical trial with a new chemical entity. 4. Fasting serum triglycerides =400mg/dL (4.5mmol/L) at Screening (Visit 2). If a subject is receiving lipid-lowering therapy, then they must have been on the same dose of therapy for the past 3 months. 5. Is currently lactating, pregnant or actively trying to become pregnant. 6. Has a significant renal impairment as defined by serum creatinine > 2mg/dL (>176umol/L). 7. History of significant co-morbid diseases active within the last 6 months (e.g., gastrointestinal disease, etc.). 8. History of pancreatitis 9. Has a documented history of chronic or advanced hepato-biliary disease including a history of, or positive laboratory results for hepatitis at Screening (Visit 2), and/or clinically significant hepatic enzyme elevation including: •Any one of the following enzymes greater than 2.5 times the upper limit of the reference range (ULRR) value at Screening (Visit 2) •alanine transaminase (ALT) •aspartate transaminase (AST) •alkaline phosphatase (ALP) •Has a total bilirubin level that is > 1.5 times the ULRR at Screening (Visit 2). 10. Has a history of alcohol or substance abuse within the past year, as determined by the Investigator or a positive urine drug screen (UDS) at Screening (Visit 2) or during treatment: •Unwilling to refrain from the use of excessive alcohol or illicit drugs and adhere to other protocol-stated 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 daily intake of greater than 2 units (females). One unit is equivalent to a half-pint of beer or
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the dose response and efficacy of GW823093 (2.5mg, 7.5mg, 15mg, 30mg and 45mg), versus placebo on the change in HbA1c after 12 weeks of dosing in subjects with T2DM.;Secondary Objective: • To investigate the safety and tolerability of a range of doses of GW823093 versus placebo over 12 weeks of dosing in subjects with T2DM. • To evaluate the effect of a range of doses of GW823093, versus placebo, on glycemic parameters (HbA1c, fasting plasma glucose (FPG), fasting fructosamine), fasting insulin and serum lipid profile during 12 weeks of dosing in subjects with T2DM. • To characterize the pharmacokinetics of GW823093 in type 2 diabetic subjects after chronic administration using a combined sparse and serial sampling scheme, and to investigate pharmacokinetic/pharmacodynamic relationships (e.g. safety and efficacy endpoints). • To evaluate the effect of a range of doses of GW823093 on DPP-IV inhibition as part of population PK assessment;Primary end point(s): •Change from baseline (Week 0) in HbA1c at Week 12. | — |
Countries
Czech Republic, Finland, Germany, Latvia, Sweden
Outcome results
None listed