study of alogliptin combined with pioglitazone in subjects with type 2 diabetes mellitus

Conditions: Diabetes Mellitus

Summary: the purpose of this study is to evaluate the efficacy and safety of alogliptin, once daily (qd), combined with pioglitazone in adults with type 2 diabetes mellitus

there are approximately 19 million people in the united states who have been diagnosed with diabetes mellitus, of which 90% to 95% are type 2. the prevalence of type 2 diabetes varies among racial and ethnic populations and has been shown to correlate with age, obesity, family history, history of gestational diabetes, and physical inactivity. over the next decade, a marked increase in the number of adults with diabetes mellitus is expected. takeda is developing syr-322 (alogliptin) for the improvement of glycemic control in patients with type 2 diabetes mellitus. alogliptin is an inhibitor of the dipeptidyl peptidase iv enzyme. dipeptidyl peptidase iv is thought to be primarily responsible for the degradation of 2 peptide hormones released in response to nutrient ingestion. it is expected that inhibition of dipeptidyl peptidase iv will improve glycemic (glucose) control in patients with type 2 diabetes. the aim of the current study is to evaluate the efficacy of alogliptin in combination with pioglitazone in subjects who are inadequately controlled on a thiazolidinedione (pioglitazone or rosiglitazone) alone or in combination with metformin or a sulfonylurea. individuals who participate in this study will be required to commit to a screening visit and up to 14 additional visits at the study center. study participation is anticipated to be about 34 weeks (or 8.5 months).

Eligibility criteria:
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.

Keywords: glucose metabolism disorder dysmetabolic syndrome type ii diabetes diabetes mellitus lipoatrophic dyslipidemia drug therapy