Type II Diabetes Mellitus
Conditions
Keywords
Drug therapy
Brief 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.
Detailed description
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.
Interventions
DRUGPioglitazone
Pioglitazone tablets
DRUGMetformin
Metformin as prescribed in clinical practice
DRUGSulfonylurea
Sulfonylurea as prescribed in clinical practice
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24 | Baseline and 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Fasting Plasma Glucose at Week 24 | Baseline and 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. |
Countries
South Korea
Participant flow
Recruitment details
Participants took part in the study at 15 investigative sites in Korea from 16 December 2013 to 17 October 2016.
Pre-assignment details
Participants with a diagnosis of Type 2 Diabetes Mellitus were enrolled equally in one of 2 treatment groups in the Double-Blind study: pioglitazone15 mg + metformin + sulfonylurea or pioglitazone pioglitazone 30 mg plus metformin + sulfonylurea. Participants received pioglitazone 30 mg + metformin + sulfonylurea in the Open Label study.
Participants by arm
| Arm | Count |
|---|---|
| Pioglitazone 15 mg (Double-Blind) 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. | 17 |
| Pioglitazone 30 mg (Double-Blind) 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. | 17 |
| Pioglitazone 30 mg (Open-Label) 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. | 77 |
| Total | 111 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double-Blind | Adverse Event | 1 | 0 | 0 |
| Double-Blind | Rescue Criteria Met | 1 | 0 | 0 |
| Double-Blind | Significant Protocol Deviation | 5 | 8 | 0 |
| Double-Blind | Withdrawal of Consent | 2 | 1 | 0 |
| Open-Label | Significant Protocol Deviation | 0 | 0 | 2 |
| Open-Label | Withdrew Consent | 0 | 0 | 3 |
Baseline characteristics
| Characteristic | Pioglitazone 15 mg (Double-Blind) | Pioglitazone 30 mg (Double-Blind) | Pioglitazone 30 mg (Open-Label) | Total |
|---|---|---|---|---|
| Age, Continuous | 59.6 years FULL_RANGE 8.73 | 57.0 years FULL_RANGE 12 | 59.2 years FULL_RANGE 7.88 | 58.6 years |
| Body Mass Index (BMI) | 26.86 kg/m^2 | 26.46 kg/m^2 | 26.25 kg/m^2 | 26.52 kg/m^2 |
| Height | 161.94 cm FULL_RANGE 8.392 | 163.50 cm FULL_RANGE 9.702 | 163.25 cm FULL_RANGE 9.148 | 162.89 cm |
| Race/Ethnicity, Customized Asian | 17 Participants | 17 Participants | 77 Participants | 111 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 17 Participants | 17 Participants | 77 Participants | 111 Participants |
| Region of Enrollment Korea, Republic Of | 17 Participants | 17 Participants | 77 Participants | 111 Participants |
| Sex: Female, Male Female | 9 Participants | 7 Participants | 35 Participants | 51 Participants |
| Sex: Female, Male Male | 8 Participants | 10 Participants | 42 Participants | 60 Participants |
| Weight | 70.39 kg | 71.20 kg | 70.38 kg | 70.65 kg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 17 | 7 / 17 | 0 / 77 |
| serious Total, serious adverse events | 1 / 17 | 0 / 17 | 3 / 77 |
Outcome results
Primary
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.
Time frame: Baseline and Week 24
Population: Intent-to-treat population was defined as all participants who took at least 1 dose of the study drug. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone 15 mg (Double-Blind) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24 | -0.0003 percentage of glycosylated hemoglobin | Standard Deviation 0.00725 |
| Pioglitazone 30 mg (Double-Blind) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24 | -0.0030 percentage of glycosylated hemoglobin | Standard Deviation 0.00894 |
| Pioglitazone 30 mg (Open-Label) | Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 24 | -0.0275 percentage of glycosylated hemoglobin | Standard Deviation 0.21126 |
Secondary
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.
Time frame: Baseline and Week 24
Population: Intent-to-treat population was defined as all participants who took at least 1 dose of the study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone 15 mg (Double-Blind) | Change From Baseline in Fasting Plasma Glucose at Week 24 | 0.6727 mmol/L | Standard Deviation 1.80662 |
| Pioglitazone 30 mg (Double-Blind) | Change From Baseline in Fasting Plasma Glucose at Week 24 | -0.4278 mmol/L | Standard Deviation 1.88067 |
| Pioglitazone 30 mg (Open-Label) | Change From Baseline in Fasting Plasma Glucose at Week 24 | -0.4412 mmol/L | Standard Deviation 2.30378 |