Clinical trial NCT03202563: Trial to Evaluate the Efficacy on Glycemic Variability and Safety of Gemigliptin Compared With Dapagliflozin Added on Metformin Alone or Diabetes Medication Naïve Patient in Type 2 Diabetes Mellitus (Stable II Study)
Official title: A Multicenter, Randomized, Active-controlled, Parallel Group, Open-label, Phase 4 Trial to Evaluate the Efficacy on Glycemic Variability and Safety of Gemigliptin 50mg q.d., Versus Dapagliflozin 10mg q.d. Added to Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control on Metformin Alone or Diabetes Medication Naïve Patient
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: LG Chem
Sponsor class: INDUSTRY
First posted: 2017-06-28
Enrollment: 71
Sex: ALL
Minimum age (years): 20
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of this study is to evaluate the efficacy on glycemic variability and safety of gemigliptin 50 mg orally administered once daily for 12 weeks compared with Dapagliflozin 10mg in patients with type 2 diabetes mellitus who have inadequate glycemic control on metformin alone or diabetes medication naïve patient


Eligibility criteria: Inclusion Criteria:

1. Patients with type 2 diabetes mellitus of 20\~70years of age at the time of Visit 1 (Screening)
2. Patients with HbA1c measured in the local lab ranged from 7 to 11%satisfying the following conditions at the time of Visit 1(Screening)

   * Type 2 diabetes mellitus medication naïve patients or patients who had not taken diabetes medication other than metformin within 8 weeks prior to Visit 1(Screening)
   * For patients who have been taking metformin alone within 12 weeks prior to visit 1(Screening) and had taken at least 1000 mg of metformin daily without dose adjustment for 4 weeks prior to Visit 1(Screening)
3. Patients who have signed an informed consent themselves after receiving explanation about the objectives, methods, effects, etc. of the clinical study
4. 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:

1. Patients with type 1 diabetes mellitus\*, Diabetic ketoacidosis, Diabetic coma, Diabetic pre-coma
2. Patients with Gestational diabetes, or secondary diabetes
3. Patients with Body Mass Index(BMI) \>40 kg/m2 at the time of Visit 1(Screening)
4. Patients with a history of the following

   * Patients with NYHA Class III, 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 6 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 60 mL/min /1.73 m2, dnd stage renal disease, dialysis or with renal disease that may result from conditions such as cardiovascular shock, acute myocardial infarction and sepsis, or patients with renal insufficiency at the time of Visit 1(Screening)
   * Patients who are receiving intravenous iodine contrast agents at the time of visit 1(Screening) or planned during the clinical trial period (eg, intravenous urography, venous cholangiography, angiography, computed tomography using contrast media, etc.) ). For patients who have received this test, they can re-evaluate the renal function 48 hours after the test and only participate in clinical trials after they have been found to be normal.
   * 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 drug therapy due to gastrointestinal disturbance including dehydration, diarrhea, and vomiting at the time of Visit 1(Screening) Patients with severe infection or severe trauma at the time of Visit 1(Screening)
   * Patients with malnutrition status, starvation status, weakness status, pituitary insufficiency or adrenal insufficiency at the time of Visit 1(Screening)
   * Patients with a history of diabetic ketoacidosis or hyperosmolar non-ketotic coma within 12 weeks prior to Visit 1(Screening)
   * Patients with a history of myocardial infarction, unstable angina, and coronary artery bypass graft(CABG) 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 12weaks 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.
5. 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
6. Patients with a history of hypersensitivity reactions to the drugs below

   * Gemigliptin or drugs belonging to dipeptidyl-peptidase4(DPP4) inhibitors
   * Dapagliflozin or drugs belonging to Sodium/glucose co transport-2(SGLT-2) inhibitor
   * Metformin or drugs belonging to biguanides
7. Patients who were administered the drugs below

   * Patients who had been administered anti-obesity drugs within 4 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 administered warfarin, dicoumarin, and digoxin within 4 weeks prior to Visit 1(Screening)
   * Patients who are being administered any of the strong CYP3A4 inducers (rifampicin\[rifampin\], dexamethasone, phenytoin, carbamazepine, rifabutin, phenobarbital) at the time of Visit 1(Screening)
   * Patients who had been being administered glucocorticoids continuously within 2 weeks prior to Visit 1(Screening) or who are required to take glucocorticoids continuously in the future
8. Patients with a genetic problems such as Galactose intolerance, Lapp lactose deficiency, Glucose-galactose malabsorption)
9. Female patients who are pregnant or lactating
10. Patients who have an experience of participation in another clinical study within 12 weeks prior to Visit1(screening)
11. Patients who are otherwise considered to be ineligible for this study on investigators' judgment

Primary outcomes:
measure: Changes from baseline MAGE(Mean amplitude of glycemic excursion) at week 12
timeFrame: baseline (visit 2~visit3) and week 12 (visit 5~visit 6)
Secondary outcomes:
measure: Changes from baseline MBG(Mean Blood Glucose) at week 12
timeFrame: baseline (visit 2~visit3) and week 12 (visit 5~visit 6)
measure: Changes from baseline SD(Standard Deviation) at week 12
timeFrame: baseline (visit 2~visit3) and week 12 (visit 5~visit 6)
measure: Changes from baseline CV(Coefficient of variance) at week 12
timeFrame: baseline (visit 2~visit3) and week 12 (visit 5~visit 6)
measure: Changes from baseline hsCRP at week 12
timeFrame: baseline (visit 2) and week 12 (visit 5)
measure: Changes from baseline Nitrotyrosine at week 12
timeFrame: baseline (visit 2) and week 12 (visit 5)
Other outcomes:
measure: Changes of HbA1c at each visit
timeFrame: baseline(visit 2), week 5(visit 4), week 13(visit 5)
measure: Changes of Fasting plasma glucose at each visit
timeFrame: baseline(visit 2), week 5(visit 4), week 13(visit 5)
measure: Changes of Fasting serum insulin at each visit
timeFrame: baseline(visit 2), week 5(visit 4), week 13(visit 5)
measure: Changes of Glycated albumine at each visit
timeFrame: baseline(visit 2), week 5(visit 4), week 13(visit 5)
measure: Changes of baseline HOMA-β at week 13
timeFrame: baseline(visit 2), week 13(visit 5)
measure: Changes of baseline HOMA-IR at week 13
timeFrame: baseline(visit 2), week 13(visit 5)
measure: Changes of baseline LDL-C at week 13
timeFrame: baseline(visit 2), week 13(visit 5)
measure: Changes of baseline HDL-C at week 13
timeFrame: baseline(visit 2), week 13(visit 5)
measure: Changes of baseline Total Cholesterol at week 13
timeFrame: baseline(visit 2), week 13(visit 5)
measure: Changes of baselineTriglyceride at week 13
timeFrame: baseline(visit 2), week 13(visit 5)
measure: Changes of baseline BMI at week 13
timeFrame: baseline(visit 2), week 13(visit 5)
measure: Changes of baseline Body weight at week 13
timeFrame: baseline(visit 2), week 13(visit 5)
Locations:
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
Study officials:
affiliation: Samsung Medical Center
name: Jaehyen Kim
role: PRINCIPAL_INVESTIGATOR
References: