Clinical Drug Experience Knowledgebase

Criteria

Inclusion Criteria:

Type 2 diabetes (as described by the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus24) treated with insulin alone (a stable dose of long and/or intermediate-acting insulin or pre-mixed insulin e.g., "70/30") ≥ 30 units/day for at least 3 months, but poorly controlled on their existing therapy
Or, patients treated with insulin (as above) in combination with non-TZD hypoglycemic agents (e.g., a sulfonylurea, metformin, acrabose, or Byetta for at least 3 months, but poorly controlled on their existing therapy
Or, patients treated with fixed doses of short-acting insulin in combination with intermediate-acting insulin for at least 3 months, but poorly controlled on their existing therapy
Patients in last 2 categories must be willing to discontinue the use of OHA and/or short-acting insulin (or change to pre-mixed insulin) for at least 26 weeks.
Male or female, 18-75 years of age
Provide informed consent and agree to comply with study requirements
Current monotherapy insulin dose regimen ≥ 30 units/day (stable for 8-week Run-in/stabilization Period); or patients who need insulin dose adjustment must have a stabilized dose ≥ 30 units/day. Patients must not have taken TZDs within 5 months of screening
All female patients must be surgically sterile, post-menopausal (at least 40 years of age with no history of menses for at least 2 years) or agree to use adequate contraception(s) that must include a barrier method (other methods may include oral contraceptives, double barrier methods, intra-uterine devices, or abstinence). Depo contraceptives are excluded
Female patients must not be pregnant or lactating
BMI 26-44 kg/m2
Hemoglobin A1c must be ≥7.5%, ≤11.5% at both Screening and Visit 4
Patients must have a FPG ≤ 220 mg/dl
Patients must have liver function tests ≤ 2X the upper limits of normal for AST, ALT, and bilirubin, and ≤ 2.5X the upper limits of normal for ALP and GGT
Patients must have serum creatinine ≤ 1.8 mg/dl for males and ≤ 1.5 mg/dl for females and BUN ≤ 40 mg/dl
Fecal occult blood test must be negative
All other clinical laboratory parameters must be within normal limits or considered not clinically significant for participation in this study, including: hematology, coagulation, other serum chemistry, and other urinalysis parameters
TSH must be ≤ 3x ULN and patient clinically euthyroid in opinion of investigator. If TSH is > ULN but ≤ 3x ULN, and patient is clinically euthyroid, FT4 should be drawn and must be WNL
Electrocardiogram (ECG) must be normal, or considered not clinically significant, for participation in this study
Patients must have a blood pressure ≤ 160/90 mm/hg including hypertensive patients controlled with medication

Exclusion Criteria:

Patients will be excluded from study participation if any of the following applies:

History of diabetes secondary to pancreatitis or pancreatectomy
Requirement for short-acting insulin during the study
Weight loss > 10 pounds in the three months prior to study
History of TZD use (Actos or Avandia) within 5 months of Screening Visit
History of TZD discontinuation due to side effect or lack of efficacy
Prior history of endoscopically or radiographically documented peptic ulcer disease within last 5 years (unless patient had documented H. pylori infection with subsequent treatment and no recurrence)
Prior history of GI bleeding within last 5 years (except for hemorrhoids or perianal disease)
Known infection with the human immunodeficiency virus (HIV) or history of viral hepatitis type B or C
History of congestive heart failure within last 5 years (NYHA Class III-IV)
History of significant pulmonary disease, myocardial infarction, cerebrovascular accident, or nephrotic syndrome within last 1 year
Elevated creatine phosphokinase (> 2X the upper limits of normal)
Malignancy within the last 5 years (except resected basal cell carcinoma)
Ongoing active infection, as evidenced by symptoms such as temperature > 38.5° C and/or clinically significant elevation in WBC count (i.e., not asymptomatic colonization)
Change in treatment with lipid-lowering agent after screening visit
Current or expected requirement for anticoagulant therapy [except for low- dose (≤ 325 mg/d) aspirin]
Current or expected treatment with phenytoin
Current or anticipated treatment with non-steroidal anti-inflammatory drugs (i.e., naproxen, ibuprofen, Vioxx, Celebrex, indomethacin, etc.). However, patients may take aspirin < 325 mg/day for cardiovascular prophylaxis
Known hypersensitivity to NSAIDs
Treatment with any other investigational therapy within the 30 days prior to Screening Visit
History of illicit drug or alcohol abuse within last 1 year
Current or expected treatment with systemic corticosteroids (except topical, ophthalmic, intra-articular, or inhaled at a dose < 1600 μg/day)
Any other condition that compromises the ability of the patient to provide informed consent or to comply with the objectives and procedures of this protocol, as judged by the investigator.