Study of Alogliptin Combined With Pioglitazone in Subjects With Type 2 Diabetes Mellitus

Inclusion Criteria

• Diagnosis of type 2 diabetes mellitus currently treated with a thiazolidinedione either alone or in combination with metformin or a sulfonylurea but who are experiencing inadequate glycemic control. The subject should have received the thiazolidinedione therapy (rosiglitazone or pioglitazone) either alone or in combination with metformin or a sulfonylurea for at least the 3 months prior to Screening and must have been on a stable dose for all their antidiabetic treatments for at least the month prior to Screening.
• No treatment with antidiabetic agents other than a thiazolidinedione alone or in combination with either metformin or a sulfonylurea within the 3 months prior to Screening. (Exception: if a subject has received other antidiabetic therapy for less than 7 days within the 3 months prior to Screening.)
• Body mass index greater than or equal to 23 kg/m2 and less than or equal to 45 kg/m2
• Fasting C-peptide concentration greater than or equal to 0.8 ng per mL. (If this screening criterion is not met, the subject still qualifies if C-peptide is greater than or equal to 1.5 ng per mL after a challenge test.)
• Glycosylated hemoglobin concentration between 7.0% and 10.0%, inclusive.
• If regular use of other, non-excluded medications, must be on a stable dose for at least the 4 weeks prior to Screening. However, as needed use of prescription or over-the-counter medications is allowed at the discretion of the investigator.
• Systolic blood pressure less than or equal to 180 mm Hg and diastolic pressure less than or equal to 110 mm Hg.
• Hemoglobin greater than or equal to 12 g per dL for males and greater than or equal to10 g per dL for females.
• Alanine aminotransferase less than or equal to 2.5 times the upper limit of normal.
• Serum creatinine less than or equal to 2.0 mg per dL.
• Thyroid-stimulating hormone level less than or equal to the upper limit of the normal range and the subject is clinically euthyroid.
• Neither pregnant nor lactating.
• Female subjects of childbearing potential must be practicing adequate contraception. Adequate contraception must be practiced for the duration of participation in the study.
• Able and willing to monitor their own blood glucose concentrations with a home glucose monitor.
• No major illness or debility that in the investigator's opinion prohibits the subject from completing the study.
• Able and willing to provide written informed consent.

Exclusion Criteria

• Urine albumin to creatinine ratio of greater than 1000 μg per mg at Screening. If elevated, the subject may be rescreened within 1 week.
• History of cancer, other than squamous cell or basal cell carcinoma of the skin, that has not been in full remission for at least 5 years prior to Screening. (A history of treated cervical intraepithelial neoplasia I or cervical intraepithelial neoplasia II is allowed.)
• History of laser treatment for proliferative diabetic retinopathy within the 6 months prior to Screening.
• History of treated diabetic gastric paresis.
• New York Heart Association Class III or IV heart failure regardless of therapy. Currently treated subjects who are stable at Class I or II are candidates for the study.
• History of coronary angioplasty, coronary stent placement, coronary bypass surgery, or myocardial infarction within the 6 months prior to Screening
• History of any hemoglobinopathy that may affect determination of glycosylated hemoglobin.
• History of infection with hepatitis B, hepatitis C, or human immunodeficiency virus.
• History of a psychiatric disorder that will affect the subject's ability to participate in the study.
• History of angioedema in association with use of angiotensin-converting enzyme inhibitors or angiotensin-II receptor inhibitors.
• History of alcohol or substance abuse within the 2 years prior to Screening.
• Receipt of any investigational drug within the 30 days prior to Screening or a history of receipt of an investigational antidiabetic drug wi