Study In People With Type 2 Diabetes

• Register: ClinicalTrials.gov
• Last refreshed on: 17 October 2012
• Main ID: NCT00196989
• Date of registration: 13/09/2005
• Primary sponsor: GlaxoSmithKline
• Public title: Study In People With Type 2 Diabetes
• Scientific title: See Detailed Description
• Date of first enrolment: September 2005
• Target sample size: 448
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00196989
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Countries of recruitment

Argentina, Australia, Bulgaria, Canada, Colombia, Costa Rica, Czech Republic, Ecuador, Latvia, Mexico, New Zealand, Peru, Russian Federation, United States

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion criteria

Inclusion criteria:

- 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").

- 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retest, subject is eligible to proceed; otherwise they should be withdrawn.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).

- 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.

- Males and females who are 18 to 70 years of age inclusive at the time of Screening.

- 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 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.

- Body Mass Index (BMI): =25 and =40 kg/m² and weigh at least 50 kg at Screening.

- If subject is a smoker, must be able to abstain while in clinic at each visit.

- Subject has given full written informed consent prior to any study related procedures
are performed.

Exclusion criteria:

Exclusion Criteria:

- Metabolic Disease including:

- Diagnosis of Type 1 diabetes mellitus

- Uncorrected thyroid dysfunction. (NOTE: subjects with hypothyroidism on a
stable dose of thyroid replacement therapy for at least 1 month prior to
Screening, and who have a screening thyroid stimulating hormone (TSH) within the
upper limit of normal may participate).

- Significant weight gain or loss (defined as > 5% of total body weight) within
the 3 months prior to Screening.

- Previous use of insulin for treatment of hyperglycemia within 3 months of Screening.

- 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. Note: subjects
using antihypertensives [e.g., beta blockers, angiotensin converting enzyme
(ACE) inhibitors, angiotensin II antagonists, calcium channel blockers and
diuretics] must be on stable doses during the 30 days prior to Screening and
during the trial.

- 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.

- History of chronic pancreatitis.

- Familial hypercholesterolemia.

- TGs =800 mg/dL (8.96 mmol/L) at Screening.

- Serum creatinine at screening > 1.4 mg/dL (124 µmol/L) for women, or > 1.5 mg/dL (133
µmol/L) for men.

- 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.

- History of significant co-morbid diseases (e.g., cholelithiasis, gastrointestinal
disease, etc.) that would preclude participation in the study.

- Documented history of hepato-biliary disease including a history of, or positive
laboratory results for hepatitis (hepatitis B surface antigen and/or hepatitis C
antibody) 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:

- Alanine aminotransferase (ALT)

- Aspartate aminotransferase (AST)

- Alkaline phosphatase (ALP)

- Total or direct bilirubin > 1.5 times the ULN at Screening, unless consistent
with presumed or diagnosed Gilbert's disease.

- History of metabolic acidosis, rhabdomyolysis, myalgia, myositis or myopathy after
taking statins or fibrates.

- Any subject who has withdrawn therapy due to AEs after taking a


Age minimum: 18 Years
Age maximum: 70 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Diabetes Mellitus, Type 2

Non-Insulin-Dependent Diabetes Mellitus

Intervention(s)

Drug: GW677954

Drug: Pioglitazone

Primary Outcome(s)

Improvement in glucose control over a 16 week period. [Time Frame: 16 weeks]

Secondary Outcome(s)

Change from baseline in 12 lead ECG. Measures include PR, QT and QTc intervals and QRS duration.

Change from baseline in fasting fructosamine at Weeks 2 and 4. Proportion of subjects achieving target HbA1c levels (= 7%) at Weeks 4, 8, 12 and 16.

Change from baseline in vital signs including blood pressure and heart rate measurements in the sitting position. Change from baseline in body weight and waist circumference.

Cholesterol, additional glycemic endpoints, safety endpoints [Time Frame: 16 Weeks]

Clinical laboratory tests including full blood counts, chemistry, urinalysis, exploratory cardiac biomarkers and serum pregnancy tests.

Glycemia Change from baseline in fasting HbA1c levels at Weeks 4, 8 and 12. Change from baseline in fasting FPG at Weeks 1, 2, 4, 6, 8, 12 and 16. Statistical testing will only be performed at Week 16.

Lipids Percentage change from baseline in TC, HDL-C, LDL-C, TGs and FFAs based on log-transformed data at Weeks 2, 4, 8, 12 and 16. Percentage change from baseline in non-HDL-C based on log-transformed data at Week 16.

Ophthalmic assessments. Incidence and severity of hypoglycemia.

Percentage change from baseline in VLDL-C, apo AI, AII and B at Week 16. Change from baseline in Apo B/TC, TC/HDL-C and LDL-C/Apo B ratio at relevant timepoints.

Proportion of subjects achieving a decrease in HbA1c of =0.7% from baseline at Weeks 4, 8, 12 and 16.

Proportion of subjects achieving target FPG (=126 mg/dL [7.0 mmol/L] and=140 mg/dL [7.8 mmol/L]) at Weeks 1, 2, 4, 6, 8, 12 and 16. Proportion of subjects achieving a decrease in FPG of =30 mg/dL [1.66 mmol/L] at Weeks 1, 2, 4, 6, 8, 12 and 16.

Secondary Safety Endpoints Safety and tolerability, assessed by incidence of AEs over the course of the study. Change from baseline in levels of hematocrit and hemoglobin.

Secondary ID(s)

ADG20001

Source(s) of Monetary Support

Please refer to primary and secondary sponsors