Clinical trial NCT00432276 (phase 3, status: completed)
Conditions: diabetes mellitus
ICD codes: P70.2, O24.92, Z83.3, E10.65, E10.9, E11.65, E11.9
Drugs: alogliptin, pioglitazone, metformin, placebo
SMILES: CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O, N[C@@H](CCCNC(N)=N)C(O)=O, CSCC[C@H](N)C(O)=O, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

        Inclusion Criteria:

          -  Has a historical diagnosis of type 2 diabetes mellitus.

          -  Meets one of the following:

               -  Has been inadequately controlled (HbA1c between 7% and 10%, inclusive) on a
                  stable dose of greater than or equal to 1500 mg (or maximum tolerated dose) of
                  metformin and 30 mg of pioglitazone

               -  Has been inadequately controlled (as defined by an HbA1c ≥7.5%) on a combination
                  therapy including metformin and another oral antidiabetic agent (ie,
                  sulfonylureas, rosiglitazone maleate, or pioglitazone 15 mg, etc). Subjects on a
                  combination therapy that included a DPP-4 inhibitor were excluded.

          -  No treatment with antidiabetic agents other than metformin and pioglitazone.

          -  Body mass index greater than or equal to 23 kg/m^2 and less than or equal to 45
             kg/m^2.

          -  Fasting plasma C-peptide concentration greater than or equal to 0.8 ng/mL.

          -  Systolic blood pressure less than 160 mmHg and diastolic pressure less than 100 mmHg.

          -  Hemoglobin greater than or equal to 12 g/dL for males and greater than or equal to 10
             g/dL for females.

          -  Alanine aminotransferase less than or equal to 2.5 x upper limit of normal.

          -  Serum creatinine less than 1.5 mg/dL for males and less than 1.4 mg/dL for females.

          -  Thyroid-stimulating hormone level less than or equal to the upper limit of normal
             range and the patient is clinically euthyroid.

          -  Females of childbearing potential who are sexually active must agree to use adequate
             contraception, and can neither be pregnant nor lactating from Screening throughout the
             duration of 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 patient
             from completing the study.

        Exclusion Criteria:

          -  Urine albumin/creatinine ratio of greater than 1000 μg/mg.

          -  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.

          -  History of bladder cancer.

          -  History of laser treatment for proliferative diabetic retinopathy within the 6 months
             prior to Screening.

          -  Patients with unexplained microscopic hematuria of greater than +1, confirmed by
             repeat testing.

          -  History of treated diabetic gastroparesis.

          -  History of gastric bypass surgery.

          -  New York Heart Association Class I-IV heart failure regardless of therapy.

          -  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 patient'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 abuse 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.

          -  Hypersensitive to pioglitazone HCl, metformin, alogliptin or other excipients.

          -  The patient has donated more than 400 mL of blood within the 90 days prior to
             Screening and Pre-Screening, if applicable.