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A Study to Evaluate the Effect of add-on Pioglitazone or Dapagliflozin in Participants With Type 2 Diabetes Mellitus Inadequately Controlled by Alogliptin and Metformin Therapy (EPIDOTE)

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ClinicalTrials.gov Identifier: NCT03499704
Recruitment Status : Recruiting
First Posted : April 17, 2018
Last Update Posted : March 5, 2020
Sponsor:
Information provided by (Responsible Party):
Takeda

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 52.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 2 Drug: Pioglitazone + Alogliptin Drug: Alogliptin Drug: Metformin Drug: Dapagliflozin Phase 4

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 232 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 55 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 232 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Alogliptin and Metformin Therapy
Actual Study Start Date : February 11, 2020
Estimated Primary Completion Date : January 29, 2022
Estimated Study Completion Date : February 12, 2022


Arm Intervention/treatment
Experimental: Pioglitazone + Alogliptin + Metformin (PAM)
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 52 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 52.
Drug: Pioglitazone + Alogliptin
Pioglitazone and Alogliptin FDC tablets
Other Name: SYR-322-4833

Drug: Metformin
Metformin tablets.

Active Comparator: Dapagliflozin + Alogliptin + Metformin (DAM)
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 52.
Drug: Alogliptin
Alogliptin tablets.

Drug: Metformin
Metformin tablets.

Drug: Dapagliflozin
Dapagliflozin tablets.




Primary Outcome Measures :
  1. Mean Change from Baseline in HbA1c at Week 52 [ Time Frame: Baseline and Week 52 ]

Secondary Outcome Measures :
  1. Mean Change from Baseline in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at Week 52 [ Time Frame: Baseline and Week 52 ]
    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.

  2. Mean Change from Baseline in Serum Lipids at Week 52 [ Time Frame: Baseline and Week 52 ]
    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.

  3. Number of Participants who Achieved an HbA1c Goal Target of Less than (<) 6.5 Percent (%) at Week 52 [ Time Frame: Week 52 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   19 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Is a regular outpatient with an historical diagnosis of type 2 diabetes.
  2. 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 centimeter (cm), female >=85 cm.
    • High TGs (drug treatment for high TGs is an alternate indicator): >=150 mg/dL (1.7 millimole per liter [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 participant with a history of hypertension is an alternate indicator): Systolic >=130 millimeter of mercury (mmHg) and/or diastolic >=85 mmHg.
    • High fasting glucose (drug treatment of high glucose is an alternate indicator): >= 100 mg/dL.
  3. Has been receiving a stable dose of alogliptin + metformin therapy with diet and exercise for >=3 months prior to randomization.
  4. Has a HbA1c value between 7.0 to 11% inclusively within 7 days of randomization via central laboratory test.

Exclusion Criteria:

  1. Has received thiazolidinedione (TZD) or sodium-glucose co-transporter-2 (SGLT-2) inhibitor within 6 months prior to randomization.
  2. Has type 1 diabetes, diabetic ketoacidosis, diabetic coma or diabetic pre-coma.
  3. The use of any medications that is, oral or systemically injected glucocorticoids (including intra-articular injection), weight-loss drugs, insulin or other anti-diabetic drugs except alogliptin and metformin, within 3 months prior to randomization. Strong Cytochrome P450 2C8 (CYP2C8) inhibitors (example, gemfibrozil, montelukast, quercetin, phenelzine) and CYP2C8 inducers (example, 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.
  4. Has genetic problems such as galactose intolerance, Lapp lactose dehydrogenase deficiency or glucose-galactose uptake disorder, etc.
  5. Has a history of alcohol abuse within 2 years prior to randomization.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03499704


Contacts
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Contact: Takeda Study Registration Call Center +1-877-825-3327 medicalinformation@tpna.com

Locations
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Korea, Republic of
The Catholic University of Korea, Bucheon, St. Marys Hospital Not yet recruiting
Bucheon-si, Gyeonggi-do, Korea, Republic of, 14647
Inje University Ilsan Paik Hospital Recruiting
Goyang-si, Gyeonggi-do, Korea, Republic of, 10380
Seoul National University Bundang Hospital Recruiting
Seongnam-si, Gyeonggi-do, Korea, Republic of, 13620
The Catholic University of Korea, ST. Vincents Hospital Not yet recruiting
Suwon-si, Gyeonggi-do, Korea, Republic of, 16247
Ajou University Hospital Not yet recruiting
Suwon, Gyeonggi-do, Korea, Republic of, 16499
Pusan National University Hospital Not yet recruiting
Busan, Korea, Republic of, 49241
YeungNam University Hospital Recruiting
Daegu, Korea, Republic of, 42415
Daejeon Eulji Medical Center, Eulji University Recruiting
Daejeon, Korea, Republic of, 35233
Chosun University Hospital Not yet recruiting
Gwangju, Korea, Republic of, 61453
Korea University Anam Hospital Not yet recruiting
Seoul, Korea, Republic of, 02841
Kangbuk Samsung Hospital Recruiting
Seoul, Korea, Republic of, 03181
Yonsei University Health System Severance Hospital Recruiting
Seoul, Korea, Republic of, 03722
Kyung Hee University Hospital at Gangdong Recruiting
Seoul, Korea, Republic of, 05278
Samsung Medical Center Recruiting
Seoul, Korea, Republic of, 06351
Ulsan University Hospital Recruiting
Ulsan, Korea, Republic of, 44033
Sponsors and Collaborators
Takeda
Investigators
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Study Director: Medical Director Takeda

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Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT03499704    
Other Study ID Numbers: Alogliptin-Pio-4001
U1111-1207-8037 ( Other Identifier: World Health Organization )
First Posted: April 17, 2018    Key Record Dates
Last Update Posted: March 5, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Takeda 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), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). 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.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Takeda:
Drug therapy
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Metformin
Pioglitazone
2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol
Alogliptin
Hypoglycemic Agents
Physiological Effects of Drugs
Sodium-Glucose Transporter 2 Inhibitors
Molecular Mechanisms of Pharmacological Action
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors