Efficacy of Alogliptin With Pioglitazone (Actos®) in Subjects With Type 2 Diabetes Mellitus
Condition: Diabetes Mellitus
MeSH terms: Diabetes Mellitus
Intervention: Alogliptin; Pioglitazone; Placebo
Intervention description: Alogliptin tablets.; Pioglitazone tablets.; Matching placebo tablets.
Intervention MeSH terms: 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: 655.0
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; Drug Therapy

Summary:

      The purpose of this study is to evaluate the combination of alogliptin, once daily (QD), and
      pioglitazone in patients with type 2 diabetes mellitus who are inadequately controlled with
      diet and exercise alone.
    

Eligibility criteria:

        Inclusion Criteria

          -  Historical diagnosis of type 2 diabetes.

          -  Failed treatment with diet and exercise for at least 2 months prior to Screening.

          -  Is experiencing inadequate glycemic control as defined as glycosylated hemoglobin
             concentration between 7.5-11%, inclusive.

          -  Has received any antidiabetic therapy for less than 7 days within 3 months prior to
             Screening.

          -  Has a body mass index greater than or equal to 23 kg/m2 and less than or equal to45
             kg/m2.

          -  Fasting C-peptide greater than or equal to 0.8 ng per mL.

          -  Regular use of other, non-excluded medications is allowed if participant is on a
             stable dose for at least 4 weeks prior to Screening.

          -  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.

          -  Must be willing and able to monitor their blood concentrations with a home glucose
             monitor.

        Exclusion Criteria

          -  Systolic blood pressure greater than or equal to 160 mmHg and diastolic blood pressure
             greater than or equal to 100 mmHg.

          -  Hemoglobin less than or equal to 12 g per dL for males and less than or equal to 10 g
             per dL for females.

          -  Alanine aminotransferase greater than or equal to 2.5times the upper limit of normal.

          -  Serum creatinine greater than 2.0 mg per dL.

          -  Thyroid stimulating hormone level greater than the upper limit of normal range.

          -  Major illness or debility that in the investigator's opinion prohibits the subject
             from completing the study.

          -  Urine albumin to creatinine ratio of greater than 1000 ug 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

          -  History of laser treatment for proliferative diabetic retinopathy within 6 months
             prior to Screening.

          -  History of gastroparesis.

          -  Has New York Heart Association Class I to IV heart failure regardless of therapy.

          -  History of coronary angioplasty, coronary stent placement, coronary bypass surgery, or
             myocardial infarction within 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 participant's ability to
             participate in the study.

          -  History of angioedema in association with use of angiotensin-converting enzyme
             inhibitors or angiotensin-II receptor inhibitors.

          -  Any alteration in angiotensin-II receptor inhibitors within 2 months prior to
             Randomization, if applicable.

          -  History of alcohol (defined as regular or daily consumption of more than 4 alcoholic
             drinks per day) or substance abuse (defined as illicit drug use) within 2 years prior
             to Screening.

          -  Received any investigational drug within 30 days prior to Screening or a history of
             receipt of an investigational antidiabetic drug within 3 months prior to Screening.

          -  Previously participated in an investigational study of SYR-322.

          -  Glycosylated hemoglobin concentration between 7.5-11%, inclusive, and a fasting plasma
             glucose less than 310 mg per dL.

          -  At least 75% compliant with the single-blind placebo regimen during the
             run-in/stabilization period.