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 within the 3 months prior to Screening. Prior treatment in an investigational study of alogliptin. Excluded Medications: Treatment with antidiabetic agents other than a thiazolidinedione alone or in combination with either metformin or a sulfonylurea is not allowed within the 3 months prior to Screening and through the completion of the end-of-treatment/early termination procedures. Treatment with weight-loss drugs, any investigational antidiabetics, or oral or systemically injected glucocorticoids is not allowed from 3 months prior to randomization through the completion of the end-of-treatment/early termination procedures. Inhaled corticosteroids are allowed. Subjects must not take any medications, including over-the-counter products, without first consulting with the investigator.