Efficacy and Safety of Alogliptin and Metformin Fixed-Dose Combination in Participants With Type 2 Diabetes
Condition: Diabetes Mellitus
MeSH terms: Diabetes Mellitus
Intervention: Alogliptin; Metformin HCl; Alogliptin and Metformin Fixed-Dose Combination (FDC); Alogliptin Placebo; Metformin Placebo; Alogliptin and Metformin FDC Placebo
Intervention description: Alogliptin tablets; Metformin HCl capsules; Alogliptin and metformin FDC tablets; Alogliptin placebo-matching tablets; Metformin placebo-matching capsules; Alogliptin and metformin FDC placebo-matching tablets
Intervention MeSH terms: Metformin; Alogliptin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 647.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Drug therapy

Summary:

      The purpose of this study is to evaluate the efficacy and safety of alogliptin and metformin
      fixed-dose combination (FDC) as compared with alogliptin alone or metformin alone on Type 2
      Diabetes Mellitus (T2DM).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Capable of understanding and complying with protocol requirements.

          2. The participant or, when applicable, the participant's legally acceptable
             representative signs and dates a written, informed consent form and any required
             privacy authorization prior to the initiation of any study procedures.

          3. Has a historical diagnosis of Type 2 diabetes mellitus (T2DM).

          4. Male or female and aged 18 to 75 years, inclusive.

          5. Body mass index (BMI) between 20 and 45 kg/m^2, inclusive.

          6. A female of childbearing potential who is sexually active with a nonsterilized male
             partner agrees to use routinely adequate contraception from signing of informed
             consent throughout the duration of the study.

          7. Is experiencing inadequate glycemic control defined as glycosylated hemoglobin (HbA1c)
             concentration between 7.5% and 10%, inclusive, and has been treated with diet and
             exercise for at least 2 months prior to Screening. (Exception: a participant who has
             received any other diabetic therapy for less than 7 days in total within the 2 months
             prior to the screening, can be included).

          8. If male, has a hemoglobin >12 g/dL (>120 g/L) at Screening or if female, has a
             hemoglobin >10 g/dL (>100 g/L) at Screening.

          9. If male, has a serum creatinine <1.5 mg/dL at Screening or if female, has a serum
             creatinine <1.4 mg/dL at Screening, and estimated glomerular filtration rate (eGFR)
             >60 mL/min/1.73 m^2 based on calculation using the Modification of Diet in Renal
             Disease (MDRD) at Screening.

         10. Willing and able to monitor their own blood glucose concentrations using a home
             glucose monitor and complete a subject diary.

        Exclusion Criteria:

          1. Participated in another clinical study within 90 days prior to Screening.

          2. Received any investigational compound within 30 days prior to Randomization.

          3. Received a dipeptidyl peptidase-4 (DPP-4) inhibitor within 3 months prior to
             screening.

          4. History of laser treatment for proliferative diabetic retinopathy within the 6 months
             prior to Screening.

          5. History of treatment for diabetic gastric paresis, gastric banding, or gastric bypass
             surgery.

          6. History of diabetic ketoacidosis or hyperosmolar non-ketotic coma.

          7. Chronic pancreatitis and/or history of acute pancreatitis.

          8. Systolic blood pressure >180 mm Hg and/or diastolic blood pressure >110 mm Hg at
             Screening.

          9. History of any hemoglobinopathy or diagnosis of chronic anemia.

         10. New York Heart Association Class III or IV heart failure. (Participants who are stable
             at Class I or II and are currently treated, are candidates for the study.)

         11. History of coronary angioplasty, coronary stent placement, coronary bypass surgery, or
             myocardial infarction within 6 months prior to Screening.

         12. History of any cancer, other than squamous cell or basal cell carcinoma of the skin,
             which has not been in full remission for at least 5 years prior to Screening.
             Participants with a history of treated cervical intraepithelial neoplasia [CIN] I or
             CIN II are allowed.

         13. Significant clinical sign or symptom of hepatopathy, acute or chronic hepatitis, human
             immunodeficiency virus or alanine aminotransferase (ALT) is 2.5 times above upper
             limit of normal value.

         14. History of angioedema in association with use of angiotensin-converting enzyme
             inhibitors (ACEI) or angiotensin II receptor blockers (ARB).

         15. History of hypersensitivity or allergies to any DPP-4 inhibitor and/or metformin or
             related compounds.

         16. Has used oral or systemically injected glucocorticoids (including intra-articular
             injection) or has used weight-loss drugs within 2 months prior to Screening. (Inhaled
             or topical corticosteroids were allowed.)

         17. History of alcohol or substance abuse within 2 years prior to Screening.

         18. Has used medicine for weight loss within 60 days prior to Screening (such as Xenical,
             Sibutramine, Phenylpropanolamine or similar nonprescription drugs).

         19. History of organ transplantation.

         20. Is an immediate family member, study site employee, or is in a dependant relationship
             with a study site employee who is involved in conduct of this study (eg, spouse,
             parent, child, sibling) or may consent under duress.

         21. Has, in the judgment of the investigator, any major illness or debility that may
             prohibit the participant from completing the study.

         22. If female, is pregnant or lactating or intending to become pregnant before, during, or
             within 1 month after participating in this study; or intending to donate ova during
             such time period.