Efficacy of Alogliptin and Pioglitazone in Subjects With Type 2 Diabetes Mellitus
Condition: Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Alogliptin; Pioglitazone; Metformin; Placebo
Intervention description: Alogliptin tablets.; Pioglitazone tablets.; Metformin HCl tablets (immediate-release, commercially available formulation) ≥1500 mg or maximum tolerated dose.; Matching placebo tablets.
Intervention MeSH terms: Metformin; Pioglitazone; Alogliptin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 803.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Glucose Metabolism Disorder; Dysmetabolic Syndrome; Type II Diabetes; Diabetes Mellitus, Lipoatrophic; Dyslipidemia; Hyperglycemia; Drug Therapy

Summary:

      The purpose of the study is to compare the effect of adding alogliptin, once daily (QD), to
      the ongoing treatment regimen of pioglitazone HCl and metformin in patients with inadequate
      glycemic control.
    

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.