Efficacy and Safety of Alogliptin Combined With Metformin in Participants With Type 2 Diabetes Mellitus
Condition: Diabetes Mellitus
MeSH terms: Diabetes Mellitus
Intervention: Alogliptin and metformin; Alogliptin and metformin; Metformin
Intervention description: Alogliptin 12.5 mg, tablets, orally, once daily and metformin for up to 26 weeks.; Alogliptin 25 mg, tablets, orally, once daily and metformin for up to 26 weeks.; Alogliptin placebo-matching tablets, orally, once daily and metformin for up to 26 weeks.
Intervention MeSH terms: Metformin; 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: 527.0
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 efficacy and safety of alogliptin, once daily
      (QD), combined with metformin in adults with type 2 diabetes mellitus.
    

Eligibility criteria:

        Inclusion Criteria

          -  Diagnosis of type 2 diabetes mellitus currently treated with metformin alone but,
             experiencing inadequate glycemic control. The participant should have received the
             metformin monotherapy for at least the 3 months prior to Screening; and must have a
             stable dose of greater than or equal to 1500 mg metformin for at least 8 weeks prior
             to randomization. Participants with a maximum tolerated dose that is documented to be
             less than 1500 mg of metformin may also be enrolled if this dose has been stable for 8
             weeks prior to randomization.

          -  No treatment with antidiabetic agents other than metformin within the 3 months prior
             to Screening. (Exception: if a participant 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 participant 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 to
             10 g per dL for females

          -  Alanine aminotransferase less than or equal to 3 time the upper limit of normal

          -  Serum creatinine less than1.5 mg per dL for males and less than 1.4 mg per dL for
             females

          -  Thyroid-stimulating hormone level less than or equal to the upper limit of the normal
             range and the participant is clinically euthyroid.

          -  Neither pregnant nor lactating.

          -  Female participants 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
             participant 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 participant 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 participants 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 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

          -  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 study drug or metformin 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.

               -  Participants must be instructed not to take any medications, including
                  over-the-counter products, without first consulting with the investigator.