Efficacy of Pioglitazone in Participants With Inadequately Controlled Type 2 Diabetes Mellitus Treated With Stable Triple Oral Therapy
Condition: Type II Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Pioglitazone; Metformin; Sulfonylurea
Intervention description: Pioglitazone tablets; Metformin as prescribed in clinical practice; Sulfonylurea as prescribed in clinical practice
Intervention MeSH terms: Metformin; Pioglitazone
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 114.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Drug therapy

Summary:

      The purpose of this study is to evaluate the efficacy of pioglitazone 30 mg on glycemic
      control when used in participants with inadequately controlled type 2 diabetes mellitus
      treated with stable combinations of metformin and sulfonylurea.
    

Eligibility criteria:

        Inclusion Criteria

        Participants meeting the following criteria will be considered for inclusion in the study:

          1. Institutional Review Board (IRB)-approved written informed consent form (ICF) must be
             obtained from the participant or legally authorized representative prior to any trial
             related procedure (including withdrawal of prohibited medication, if applicable).

          2. Participants with a history of clinical diagnosis of established type 2 diabetes
             mellitus defined by the American Diabetes Association (ADA) criteria 2012.

          3. Male or female between 18 and 80 years of age.

          4. Participants with stable triple oral therapy of metformin + sulfonylurea +
             pioglitazone (ACTOS) 15 mg or ACTOSMET(Pioglitazone 15mg/Metformin 850mg) and
             sulfonylurea for at least 12 weeks at the screening visit.

          5. Participants with glycosylated hemoglobin (HbA1c) ≥7.0% at the screening visit.

          6. Participants with C-peptide ≥1.0 ng/mL at the screening visit.

          7. 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, up to 30 days after the last dose of the study medication.

        Exclusion Criteria

        Participants meeting any of the following criteria will be excluded from enrollment:

          1. Participants with type 1 diabetes mellitus or secondary forms of diabetes.

          2. Participants who have been treated with insulin for ≥7 days within 3 months prior to
             the screening visit.

          3. Participants with a history of bladder cancer or participants with active bladder
             cancer.

          4. Participants with a history of acute diabetic complications such as diabetic
             ketoacidosis.

          5. Participants with a history of acute or chronic metabolic acidosis, including diabetic
             ketoacidosis.

          6. Participants with unstable or rapidly progressive diabetic retinopathy, nephropathy
             (estimated glomerular filtration rate [eGFR] <60mL/min/1.73m2).

          7. Participants with cardiac insufficiency (e.g., a myocardial infarction, a coronary
             angioplasty or bypass graft, unstable angina, transient ischemic attacks, or a
             documented cerebrovascular accident within 6 months prior to the screening visit).

          8. Participants with cardiac failure or history of cardiac failure (New York Heart
             Association [NYHA] Stages 3 to 4).

          9. Participants with a serum alanine transaminase (ALT) level ≥2.5 times the upper limit
             of normal (ULN), active liver disease, or jaundice.

         10. Participants taking concomitant gemfibrozil or other strong cytochrome P450 (CYP)2C8
             inhibitors.

         11. Participants with a history of recurrent or severe hypoglycemia.

         12. Participants with a history of any hemoglobinopathy (such as hemolytic anemias or
             sickle cell disease) that may affect determination of HbA1c.

         13. Participants with uninvestigated microscopic hematuria

         14. Participants with genetic problems such as galactose intolerance, Lapp lactase
             deficiency, or glucose-galactose malabsorption, since the study drug contains lactose.

         15. Participants with any other condition judged by the Investigator as unsuitable for the
             study.

         16. Participants who have used any investigational or experimental drugs or devices within
             60 days of the screening visit.

         17. Lactating or pregnant female. A positive pregnancy test before the first
             administration of investigational medicinal product (IMP) or breastfeeding.

         18. Male participants planning to father during clinical trial conduct or within 3 months
             after the last planned dose of the IMP.

         19. Participants were previously enrolled into the current clinical trial.

         20. The participants participated in the active treatment phase of another clinical trial
             where a persisting pharmacodynamic effect of the IMP of that clinical trial cannot be
             excluded.

         21. Participants are considered unable or unwilling to co-operate adequately, i.e., to
             follow clinical trial procedures after Investigator has adequately instructed (e.g.,
             language difficulties, etc.) or participants are anticipated not to be available for
             scheduled clinical trial visits/procedures.