A Study to Evaluate the Efficacy and Safety of Gemigliptin in Type 2 Diabetes Who Have Inadequate GlycemIc Control With Dapagliflozin and Metformin (SOLUTION Study)

Study Overview
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Brief Summary
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The objective of this study is to evaluate the efficacy and safety of gemigliptin 50 mg orally administered once daily for 24 weeks compared with placebo in patients with type 2 diabetes mellitus who have inadequate glycemic control with dapagliflozin and metformin

Official Title
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A Multicenter, Randomized, Placebo-controlled, Parallel Group, Double-blind, Phase III Study to Evaluate the Efficacy and Safety of Gemigliptin 50mg in Patients With Type 2 Diabetes Who Have Inadequate glycemIc Control With Dapagliflozin and Metformin (SOLUTION Study)

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Gemigliptin 50mg
* Drug: Gemigliptin Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with type 2 diabetes mellitus of upper 19 years old at the time of Visit 1 (Screening) Visit 1 (Screening) Patients who had taken Dapagliflozin 10mg/day and Metformin(≥1000mg/day) more than 8 weeks and who have inadequate blood glucose control at Visit 1 (Screening) Patients who have signed an informed consent themselves after receiving explanation about the objectives, methods, effects, etc. of the clinical study Patients who are applicable to one of the three in the following. 1) Surgically infertile patients 2) Postmenopausal female patients of ≥45 years of age for whom ≥2 years elapsed since their last menstruation 3) Premenopausal fertile female patients or surgically non-infertile male patients who have agreed to use at least 2 kinds of contraceptive measures (certainly including one of the barrier methods) to avoid pregnancy until 14 days after the last dose of the investigational product Barrier methods: Condom, Diaphragm, Cervical cap(Pessary), Spermicide Hormonal methods: Pills, Injection(Depot), Skin patch, Hormonal implant(Implanon), Vaginal ring Intrauterine Devices(IUDs): Cooper IUD(Loop), Hormonal IUD(Mirena) Natural methods: Basic body temperature, Ovulation period, Coitus interruptus, Abstinence Exclusion Criteria: Patients with type 1 diabetes mellitus, Diabetic ketoacidosis, Metabolic acidosis Diabetic coma, Diabetic pre-coma Patients with Gestational diabetes, or secondary diabetes Patients with Body Mass Index(BMI) >40 kg/m2 at the time of Visit 1(Screening) Patients with a history of the following Patients with NYHA Class II IV congestive heart failure or arrhythmia requiring treatment at the time of Visit 1(Screening) Patients whose TSH level is out of the normal range and who have thyroidal dysfunction requiring drug therapy at the time of Visit 1(Screening) (However, those who have been taking thyroid hormone at a fixed dose since previous 4 weeks prior to Visit 1(Screening) and whose TSH level is within the normal range can participate in the study.) Patients with a glomerular filtration rate (eGFR) less than 45 mL/min /1.73 m2, moderate of severe stage renal disease, end-stage renal disease, dialysis at the time of Visit 1(Screening) Patients who are receiving intravenous iodine contrast agents within 48 hours prior to Visit 1(Screening) or planned during the clinical trial period (eg, intravenous urography, venous cholangiography, angiography, computed tomography using contrast media, etc.). Patients with pulmonary embolism, severe pulmonary dysfunction, or who are susceptible to be accompanied by hypoxemia at the time of Visit 1(Screening) Patients on dehydration, diarrhea, and vomiting at the time of Visit 1(Screening) Patients with pituitary insufficiency or adrenal insufficiency at the time of Visit 1(Screening) Patients with a history of myocardial infarction, unstable angina, and Cerebrovascular disease within 12 weeks prior to Visit 1(Screening) Patients who had had a surgical operation within 4 weeks prior to Visit 1(Screening) (excluding minor surgeries without restriction on food and fluid intake) or who are scheduled to have a significant surgery during the study period Patients with a history of alcoholism or drug addiction within 1 years prior to Visit 1(Screening) Patients with a history of malignant tumors within 5 years prior to Visit 1(Screening). However, patients with basal cell or squamous cell skin cancer, or in situ cervical cancer treated properly can participate in the study. Patients with the outcomes of the laboratory tests performed at Visit 1(Screening) applicable to the criteria below Bilirubin >2 × upper limit of normal(ULN) AST/ALT >3 × ULN Patients with a history of hypersensitivity reactions to the drugs below Dipeptidyl-peptidase4(DPP4) inhibitors Sodium/glucose co transport-2(SGLT-2) inhibitor Biguanides Patients who were administered the drugs below Patients who had been administered anti-obesity drugs within 12 weeks prior to Visit 1(Screening) Patients who had been administered insulin or GLP-1 analogues within 8 weeks prior to Visit 1(Screening) Patients who had been being administered glucocorticoids, Strong CYP3A4 inducers continuously within 2 weeks prior to Visit 1(Screening) or who are required to take glucocorticoids continuously in the future Patients with positive Serologic results of HBsAg, HCV Ab, HIV Ab test within 4 weeks prior to Visit 1 (Screening) or at Visit 1 (Screening) Patients who have undergone bariatric surgery within the 1 year prior to Visit 1 (Screening) or are scheduled during the trial Patients with a genetic problems such as Galactose intolerance, Lapp lactose deficiency, Glucose-galactose malabsorption) Female patients who are pregnant or lactating Patients who have an experience of participation in another clinical study within 12 weeks prior to Visit1(screening) Patients who are otherwise considered to be ineligible for this study on investigators' judgment

Ages Eligible for Study
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Minimum Age: 19 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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Gemigliptin 50mg<br> | Drug: Gemigliptin 50mg<br>* The subjects should visit a study site 9 times during the treatment period for about 52 weeks in total. Background therapy should be administered at the same time every day, keeping the same dosage administered before the study, according to the following criteria: Dapagliflozin 10 mg / day Metformin ≥ 1,000 mg / day<br>|
| Placebo Comparator: Gemigliptin Placebo<br> | Drug: Gemigliptin Placebo<br>* The subjects should visit a study site 9 times during the treatment period for about 52 weeks in total. - The subjects should visit a study site 9 times during the treatment period for about 52 weeks in total. Background therapy should be administered at the same time every day, keeping the same dosage administered before the study, according to the following criteria: Dapagliflozin 10 mg / day Metformin ≥ 1,000 mg / day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from baseline HbA1c at week 24 |  | Baseline (week 0) and week 24 |