Efficacy of Pioglitazone in Participants With Inadequately Controlled Type 2 Diabetes Mellitus Treated With Stable Triple Oral Therapy

Study Overview
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Brief Summary
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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.

Detailed Description
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The drug being tested in this study is called pioglitazone. Pioglitazone is being tested to treat glycemic control in adults with inadequately controlled type 2 diabetes mellitus. This study will look at glycemic control in people who take triple oral therapy of metformin, sulfonylurea, and pioglitazone 15 mg. The study will enroll approximately 114 patients. All participants will be asked to take one pioglitazone tablet at the same time each day throughout the study as well as continuing their previous dose of metformin and sulfonylurea. This multi-center trial will be conducted in Korea. The overall time to participate in this study is up to 25 weeks. Participants will make 4 visits to the hospital or endocrinologist's office, and will be contacted by telephone 7 days after last dose of study drug for a follow-up assessment.

Official Title
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A 24-Week, Open Label, Phase IV Trial to Evaluate the Efficacy of Pioglitazone 30 mg in Patients With Inadequately Controlled Type 2 Diabetes Mellitus Treated With Stable Triple Oral Therapy of Metformin, Sulfonylurea, and Pioglitazone 15 Mg (ADD Trial)

Conditions
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Type II Diabetes Mellitus

Intervention / Treatment
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* Drug: Pioglitazone
* Drug: Metformin
* Drug: Sulfonylurea


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Participants meeting the following criteria will be considered for inclusion in the study: 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). Participants with a history of clinical diagnosis of established type 2 diabetes mellitus defined by the American Diabetes Association (ADA) criteria 2012. Male or female between 18 and 80 years of age. 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. Participants with glycosylated hemoglobin (HbA1c) ≥7.0% at the screening visit. Participants with C-peptide ≥1.0 ng/mL at the screening visit. 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: Participants with type 1 diabetes mellitus or secondary forms of diabetes. Participants who have been treated with insulin for ≥7 days within 3 months prior to the screening visit. Participants with a history of bladder cancer or participants with active bladder cancer. Participants with a history of acute diabetic complications such as diabetic ketoacidosis. Participants with a history of acute or chronic metabolic acidosis, including diabetic ketoacidosis. Participants with unstable or rapidly progressive diabetic retinopathy, nephropathy (estimated glomerular filtration rate [eGFR] <60mL/min/1.73m2). 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). Participants with cardiac failure or history of cardiac failure (New York Heart Association [NYHA] Stages 3 to 4). Participants with a serum alanine transaminase (ALT) level ≥2.5 times the upper limit of normal (ULN), active liver disease, or jaundice. Participants taking concomitant gemfibrozil or other strong cytochrome P450 (CYP)2C8 inhibitors. Participants with a history of recurrent or severe hypoglycemia. Participants with a history of any hemoglobinopathy (such as hemolytic anemias or sickle cell disease) that may affect determination of HbA1c. Participants with uninvestigated microscopic hematuria Participants with genetic problems such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption, since the study drug contains lactose. Participants with any other condition judged by the Investigator as unsuitable for the study. Participants who have used any investigational or experimental drugs or devices within 60 days of the screening visit. Lactating or pregnant female. A positive pregnancy test before the first administration of investigational medicinal product (IMP) or breastfeeding. Male participants planning to father during clinical trial conduct or within 3 months after the last planned dose of the IMP. Participants were previously enrolled into the current clinical trial. 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. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pioglitazone 15 mg (Double-Blind)<br>Pioglitazone 15 mg tablets, orally, once daily, and metformin and sulfonylurea administered according to the prescribing information of the approved Korean label, for up to 24 weeks. | Drug: Pioglitazone<br>* Pioglitazone tablets<br>* Other names: ACTOS;Drug: Metformin<br>* Metformin as prescribed in clinical practice<br>Drug: Sulfonylurea<br>* Sulfonylurea as prescribed in clinical practice<br>|
| Experimental: Pioglitazone 30 mg (Double-Blind)<br>Pioglitazone 30 mg tablets, orally, once daily, and metformin and sulfonylurea administered according to the prescribing information of the approved Korean label, for up to 24 weeks. | Drug: Pioglitazone<br>* Pioglitazone tablets<br>* Other names: ACTOS;Drug: Metformin<br>* Metformin as prescribed in clinical practice<br>Drug: Sulfonylurea<br>* Sulfonylurea as prescribed in clinical practice<br>|
| Experimental: Pioglitazone 30 mg (Open-Label)<br>Pioglitazone 30 mg tablets, orally, once daily, and metformin and sulfonylurea administered according to the prescribing information of the approved Korean label, for up to 24 weeks. | Drug: Pioglitazone<br>* Pioglitazone tablets<br>* Other names: ACTOS;Drug: Metformin<br>* Metformin as prescribed in clinical practice<br>Drug: Sulfonylurea<br>* Sulfonylurea as prescribed in clinical practice<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24 | The change from baseline in glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) at Week 24. A negative change from baseline indicates improvement. | Baseline and Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Fasting Plasma Glucose at Week 24 | The change between the value of fasting serum glucose collected at Week 24 and fasting serum glucose collected at baseline. A negative change from baseline indicates improvement. | Baseline and Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug therapy