Back to resultsA Study to Evaluate the Effect of add-on Pioglitazone or Dapagliflozin in Participants With Type 2 Diabetes Mellitus Inadequately Controlled by DPP-4 Inhibitor and Metformin Therapy (EPIDOTE)
Primary Purpose
Diabetes Mellitus, Type 2
Status
Active
Phase
Phase 4
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Pioglitazone + Alogliptin
Alogliptin
Metformin
Dapagliflozin
Sponsored by
About this trial
This is an interventional treatment trial for Diabetes Mellitus, Type 2 focused on measuring Drug therapy
Eligibility Criteria
Inclusion Criteria:
- The subject is a regular outpatient with an has a historical diagnosis of type 2 diabetes.
The subject has metabolic syndrome as jointly defined by the International Diabetes Federation (IDF); National Heart, Lung, and Blood Institute (NHLBI) / American Heart Association (AHA); and International Association for the Study of Obesity (IASO). If any 3 of the following 5 risk factors are present, metabolic syndrome can be considered:
- High waist circumference: male ≥ 90 cm, female ≥ 85 cm.
- High TGs (drug treatment for high TGs is an alternate indicator): ≥ 150 mg/dL (1.7 mmol/L).
- Low HDL-C (drug treatment for low HDL-C is an alternate indicator): < 40 mg/dL(1.0 mmol/L) in males, < 50 mg/dL (1.3 mmol/L) in females.
- High blood pressure (antihypertensive drug treatment in a subject with a history of hypertension is an alternate indicator): Systolic ≥ 130 mmHg and/or diastolic ≥ 85 mmHg.
- High fasting glucose (drug treatment of high glucose is an alternate indicator): ≥ 100 mg/dL.
- The subject has been receiving a stable dose of DPP-4 inhibitor + metformin therapy with diet and exercise for ≥ 3 months prior to Randomization.
- The subject has a HbA1c value between 7.0 and 11% inclusively within 28 days of Randomization via central laboratory test or after run-in period for 4 weeks via central laboratory test.
Exclusion Criteria:
- The subject has type 1 diabetes, diabetic ketoacidosis, diabetic coma or diabetic precoma.
- The subject has an active bladder cancer or a history of bladder cancer.
- The use of any medications ie, oral or systemically injected glucocorticoids (including intra-articular injection), weight-loss drugs, insulin or other anti-diabetic drugs except DPP-4 inhibitor and metformin, within 3 months prior to randomization. Strong Cytochrome P450 2C8 (CYP2C8) inhibitors (eg, gemfibrozil, montelukast, quercetin, phenelzine) and CYP2C8 inducers (eg, rifampin) that in the opinion of the Investigator or Sponsor require treatment contraindicated during the study. The diuretics, angiotensin receptor blockers (ARBs), angiotensin-converting enzyme (ACE) -inhibitors and nonsteroidal anti-inflammatory drugs (NSAIDs) are to be used per product label with close monitoring under Investigator's supervision.
- Has genetic problems such as galactose intolerance, Lapp lactose dehydrogenase deficiency or glucose-galactose uptake disorder, etc.
- Has a history of alcohol abuse within 2 years prior to randomization.
Sites / Locations
- The Catholic University of Korea, Bucheon, St. Marys Hospital
- Seoul National University Bundang Hospital
- The Catholic University of Korea, ST. Vincents Hospital
- Ajou University Hospital
- Inje University Haeundae Paik Hospital
- Pusan National University Hospital
- YeungNam University Hospital
- Daejeon Eulji Medical Center, Eulji University
- Chosun University Hospital
- Korea University Anam Hospital
- Kangbuk Samsung Hospital
- Yonsei University Health System Severance Hospital
- Kyung Hee University Hospital at Gangdong
- Samsung Medical Center
- Ulsan University Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Pioglitazone + Alogliptin + Metformin (PAM)
Dapagliflozin + Alogliptin + Metformin (DAM)
Arm Description
Pioglitazone 15 milligram (mg) and alogliptin 25 mg in fixed dose combination (FDC) tablet (SYR-322-4833), orally once daily and metformin greater than or equal to (>=) 500 mg, tablet, orally, twice a day for up to 26 weeks. At Week 12, if participants has HbA1c >=7.5%, pioglitazone dose will be titrated up to 30 mg based on investigator's opinion and up-titrated dose will be maintained up to Week 26.
Dapagliflozin 10 mg, tablet, orally, once daily with alogliptin 25 mg, tablet, orally, once daily, and metformin >=500 mg, tablet, orally, twice a day, for up to Week 26.
Outcomes
Primary Outcome Measures
Mean Change from Baseline in HbA1c at Week 26
Secondary Outcome Measures
Mean Change from Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Week 26
HOMA IR measures insulin resistance based on fasting glucose and insulin measurements: HOMA IR equal to (=) fasting insulin (micro unit per milliliter [mcU/mL])*fasting glucose (millimole per milliliter [mmol/mL])/22.5. A higher number indicates a greater insulin resistance.
Mean Change from Baseline in Serum Lipids at Week 26
The change from baseline in serum lipids (Total Cholesterol [TC], Low-density Lipoprotein Cholesterol [LDL-C], High-density Lipoprotein Cholesterol [HDL-C], Triglycerides [TGs]) will be analyzed using mixed model repeated measures (MMRM) model.
Number of Participants who Achieved an HbA1c Goal Target of Less than (<) 6.5 Percent (%) at Week 26
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03499704
Brief Title
A Study to Evaluate the Effect of add-on Pioglitazone or Dapagliflozin in Participants With Type 2 Diabetes Mellitus Inadequately Controlled by DPP-4 Inhibitor and Metformin Therapy
Acronym
EPIDOTE
Official Title
A Multicenter, Randomized, Open-label, Two-arm, Phase 4 Study to Evaluate the Effect of Add-on Pioglitazone or Dapagliflozin in Subjects With Type 2 Diabetes Mellitus Inadequately Controlled by Dipeptidyl Peptidase-4 Inhibitor and Metformin Therapy
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 11, 2020 (Actual)
Primary Completion Date
January 31, 2024 (Anticipated)
Study Completion Date
June 30, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Celltrion Pharm, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to assess the pioglitazone plus alogliptin plus metformin is non-inferior to dapagliflozin plus alogliptin plus metformin on glycosylated haemoglobin (HbA1c) change from baseline at Week 26.
Detailed Description
The drug being tested in this study is Alogliptin Benzoate and Pioglitazone Hydrochloride FDC. This study will assess the efficacy of pioglitazone or dapagliflozin in participants with type 2 diabetes mellitus.
The study will enroll approximately 156 participants. Participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups.
Pioglitazone 15 mg + Alogliptin 25 mg + Metformin >=500 mg
Dapagliflozin 10 mg + Alogliptin 25 mg + Metformin >=500 mg
Based on investigators opinion at Week 12, if participant has HbA1c >=7.5%, dose of pioglitazone can be titrated up to 30 mg.
This multi-center trial will be conducted in Republic of Korea. The overall time to participate in this study is up to 36 weeks. Participants will make multiple visits to the clinic, and will be contacted by telephone 14 days after their last dose of drug for a follow-up assessment.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 2
Keywords
Drug therapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
133 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Pioglitazone + Alogliptin + Metformin (PAM)
Arm Type
Experimental
Arm Description
Pioglitazone 15 milligram (mg) and alogliptin 25 mg in fixed dose combination (FDC) tablet (SYR-322-4833), orally once daily and metformin greater than or equal to (>=) 500 mg, tablet, orally, twice a day for up to 26 weeks. At Week 12, if participants has HbA1c >=7.5%, pioglitazone dose will be titrated up to 30 mg based on investigator's opinion and up-titrated dose will be maintained up to Week 26.
Arm Title
Dapagliflozin + Alogliptin + Metformin (DAM)
Arm Type
Active Comparator
Arm Description
Dapagliflozin 10 mg, tablet, orally, once daily with alogliptin 25 mg, tablet, orally, once daily, and metformin >=500 mg, tablet, orally, twice a day, for up to Week 26.
Intervention Type
Drug
Intervention Name(s)
Pioglitazone + Alogliptin
Other Intervention Name(s)
SYR-322-4833
Intervention Description
Pioglitazone and Alogliptin FDC tablets
Intervention Type
Drug
Intervention Name(s)
Alogliptin
Intervention Description
Alogliptin tablets.
Intervention Type
Drug
Intervention Name(s)
Metformin
Intervention Description
Metformin tablets.
Intervention Type
Drug
Intervention Name(s)
Dapagliflozin
Intervention Description
Dapagliflozin tablets.
Primary Outcome Measure Information:
Title
Mean Change from Baseline in HbA1c at Week 26
Time Frame
Baseline and Week 26
Secondary Outcome Measure Information:
Title
Mean Change from Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Week 26
Description
HOMA IR measures insulin resistance based on fasting glucose and insulin measurements: HOMA IR equal to (=) fasting insulin (micro unit per milliliter [mcU/mL])*fasting glucose (millimole per milliliter [mmol/mL])/22.5. A higher number indicates a greater insulin resistance.
Time Frame
Baseline and Week 26
Title
Mean Change from Baseline in Serum Lipids at Week 26
Description
The change from baseline in serum lipids (Total Cholesterol [TC], Low-density Lipoprotein Cholesterol [LDL-C], High-density Lipoprotein Cholesterol [HDL-C], Triglycerides [TGs]) will be analyzed using mixed model repeated measures (MMRM) model.
Time Frame
Baseline and Week 26
Title
Number of Participants who Achieved an HbA1c Goal Target of Less than (<) 6.5 Percent (%) at Week 26
Time Frame
Week 26
10. Eligibility
Sex
All
Minimum Age & Unit of Time
19 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
The subject is a regular outpatient with an has a historical diagnosis of type 2 diabetes.
The subject has metabolic syndrome as jointly defined by the International Diabetes Federation (IDF); National Heart, Lung, and Blood Institute (NHLBI) / American Heart Association (AHA); and International Association for the Study of Obesity (IASO). If any 3 of the following 5 risk factors are present, metabolic syndrome can be considered:
High waist circumference: male ≥ 90 cm, female ≥ 85 cm.
High TGs (drug treatment for high TGs is an alternate indicator): ≥ 150 mg/dL (1.7 mmol/L).
Low HDL-C (drug treatment for low HDL-C is an alternate indicator): < 40 mg/dL(1.0 mmol/L) in males, < 50 mg/dL (1.3 mmol/L) in females.
High blood pressure (antihypertensive drug treatment in a subject with a history of hypertension is an alternate indicator): Systolic ≥ 130 mmHg and/or diastolic ≥ 85 mmHg.
High fasting glucose (drug treatment of high glucose is an alternate indicator): ≥ 100 mg/dL.
The subject has been receiving a stable dose of DPP-4 inhibitor + metformin therapy with diet and exercise for ≥ 3 months prior to Randomization.
The subject has a HbA1c value between 7.0 and 11% inclusively within 28 days of Randomization via central laboratory test or after run-in period for 4 weeks via central laboratory test.
Exclusion Criteria:
The subject has type 1 diabetes, diabetic ketoacidosis, diabetic coma or diabetic precoma.
The subject has an active bladder cancer or a history of bladder cancer.
The use of any medications ie, oral or systemically injected glucocorticoids (including intra-articular injection), weight-loss drugs, insulin or other anti-diabetic drugs except DPP-4 inhibitor and metformin, within 3 months prior to randomization. Strong Cytochrome P450 2C8 (CYP2C8) inhibitors (eg, gemfibrozil, montelukast, quercetin, phenelzine) and CYP2C8 inducers (eg, rifampin) that in the opinion of the Investigator or Sponsor require treatment contraindicated during the study. The diuretics, angiotensin receptor blockers (ARBs), angiotensin-converting enzyme (ACE) -inhibitors and nonsteroidal anti-inflammatory drugs (NSAIDs) are to be used per product label with close monitoring under Investigator's supervision.
Has genetic problems such as galactose intolerance, Lapp lactose dehydrogenase deficiency or glucose-galactose uptake disorder, etc.
Has a history of alcohol abuse within 2 years prior to randomization.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Team
Organizational Affiliation
Celltrionpharm Inc.
Official's Role
Study Director
Facility Information:
Facility Name
The Catholic University of Korea, Bucheon, St. Marys Hospital
City
Bucheon-si
State/Province
Gyeonggi-do
ZIP/Postal Code
14647
Country
Korea, Republic of
Facility Name
Seoul National University Bundang Hospital
City
Seongnam-si
State/Province
Gyeonggi-do
ZIP/Postal Code
13620
Country
Korea, Republic of
Facility Name
The Catholic University of Korea, ST. Vincents Hospital
City
Suwon-si
State/Province
Gyeonggi-do
ZIP/Postal Code
16247
Country
Korea, Republic of
Facility Name
Ajou University Hospital
City
Suwon
State/Province
Gyeonggi-do
ZIP/Postal Code
16499
Country
Korea, Republic of
Facility Name
Inje University Haeundae Paik Hospital
City
Busan
ZIP/Postal Code
48108
Country
Korea, Republic of
Facility Name
Pusan National University Hospital
City
Busan
ZIP/Postal Code
49241
Country
Korea, Republic of
Facility Name
YeungNam University Hospital
City
Daegu
ZIP/Postal Code
42415
Country
Korea, Republic of
Facility Name
Daejeon Eulji Medical Center, Eulji University
City
Daejeon
ZIP/Postal Code
35233
Country
Korea, Republic of
Facility Name
Chosun University Hospital
City
Gwangju
ZIP/Postal Code
61453
Country
Korea, Republic of
Facility Name
Korea University Anam Hospital
City
Seoul
ZIP/Postal Code
02841
Country
Korea, Republic of
Facility Name
Kangbuk Samsung Hospital
City
Seoul
ZIP/Postal Code
03181
Country
Korea, Republic of
Facility Name
Yonsei University Health System Severance Hospital
City
Seoul
ZIP/Postal Code
03722
Country
Korea, Republic of
Facility Name
Kyung Hee University Hospital at Gangdong
City
Seoul
ZIP/Postal Code
05278
Country
Korea, Republic of
Facility Name
Samsung Medical Center
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Name
Ulsan University Hospital
City
Ulsan
ZIP/Postal Code
44033
Country
Korea, Republic of
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Celltrionpharm makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), and an opportunity for the primary publication of the research and final report development has been allowed. To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.
Learn more about this trial
A Study to Evaluate the Effect of add-on Pioglitazone or Dapagliflozin in Participants With Type 2 Diabetes Mellitus Inadequately Controlled by DPP-4 Inhibitor and Metformin Therapy
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