A Clinical Trial to Evaluate the Bone Metabolism and the Blood Sugar of Evogliptin and Dapagliflozin

Study Overview
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Brief Summary
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This multi-center, randomized and exploratory clinical trial is designed to evaluate the effect of bone metabolism and blood sugar of evogliptin and dapagliflozin in the menopause female patients with osteopenia and type 2 diabetes. The trial will evaluate bone metabolism (bone markers and bone density) and blood sugar (AGE and glucose variability) after 12 weeks and 48 weeks. This clinical trial conducts in two arms, and each arm recruits 60 subjects.

Detailed Description
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This clinical trial is to evaluate the effect of bone metabolism and blood sugar of evogliptin and dapagliflozin in the menopause female patients with osteopenia and type 2 diabetes. Bone metabolism (bone markers and bone density) and blood sugar (AGE and glucose variability) after 12 weeks and 48 weeks will be evaluated. This clinical trial conducts in two arms, and each arm recruits 60 subjects. If a subject voluntarily agrees to participate and meets the inclusion and exclusion criteria for the clinical trial, the subject will be randomly assigned to one of the two arms. The total period after the subject enrollment is 48 weeks, and a total of six visits are made with screening, baseline, 12 weeks, 24 weeks, 36 weeks, and 48 weeks. Efficacy evaluation will be carried out changes on blood sugar, bone markers and density and after 12 and 48 weeks. The results of this study are intended to be a reference to future clinical trials.

Official Title
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A Multicenter Randomized Exploratory Clinical Trial to Evaluate the Effect of Bone Metabolism and the Efficacy of Evogliptin and Dapagliflozin for Blood Sugar in the Menopause Female Patients With Osteopenia and Type 2 Diabetes

Conditions
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Bone Diseases, Metabolic, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Evogliptin
* Drug: Dapagliflozin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Postmenopausal women between 40 and 70 years of age with type 2 diabetes patients who are not taking diabetes drugs or who are not controlled by blood sugar at 7.0≤HbA1c≤9.0 while taking metformin ※ Menopause corresponds when one or more of the following three conditions are satisfied. (1) 12 months of amenorrhea (2) In the case of FSH≥40 mIL(milli-international unit)/mL in women over 50 years who have undergone a hysterectomy or 6 months of amenorrhea (3) Patients 6 weeks after ovariectomy Lumbar, neck of femur and total femur bone density measurements were -2.4≤T-score≤-1.0 Obtained written informed consent from a patient Patients who can participate during clinical trials and perform all planned trial procedures and visits. Exclusion Criteria: A person who has taken a diabetes medications other than metformin within 12 weeks, or who is hypersensitivity to DPP4(dipeptidyl peptidase-4) inhibitors or SGLT2 inhibitors. AST(ASpartate Transaminase) or ALT(ALanine Transaminase) exceeds 2 times the upper limit of the normal range in laboratory tests Patients with moderate or severe renal impairment, end-stage renal disease (ESRD) or dialysis Patients whose eGFR(epidermal growth factor receptor) calculated using MDRD formula within 4 weeks before screening or at screening is less than 60 mL/minute/1.73 m2 In the case of osteoporosis medication dosage as follows: Patients who have ever used bisphosphonate formulations Patients who have used female hormones, SERM(Selective Estrogen Receptor Modulator), denosumab, and parathyroid hormone preparations within 12 months Have bone or mineral metabolic diseases or have received treatment that affects them (1) Steroid; - Oral steroid 2.5mg or more has been continuously taken for more than 3 months from the date of consent - Continuous use of systemic or inhaled steroids for more than 3 months from the date of consent (2) Taking diuretics (3) Patients at risk for secondary osteoporosis Patients who have participated in other clinical trials within 3 months Patients with a history of malignant tumors within 5 years Those who have a history of hypersensitivity to the main ingredients and additives of the trial drugs Patients with type 1 diabetes or diabetic ketoacidosis Patients with genetic problems such as galactose intolerance, Lapp deficiency, or glucose-galactose malabsorption Any other patient that the investigator has determined is unsuitable for this clinical trial

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

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
Interventional Model Description: If a subject voluntarily agrees to participate and meets the inclusion and exclusion criteria for the clinical trial, the subject will be randomly assigned to one of the two arms. Arm 1: evogliptin 5mg + metformin, oral administration once a day for 48 weeks Arm 2: dapagliflozin 10mg + metformin, oral administration once a day for 48 weeks
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: evogliptin<br>evogliptin 5 mg + metformin, oral administration once a day for 48 weeks | Drug: Evogliptin<br>* evogliptin 5mg + metformin, oral administration once a day for 48 weeks<br>|
| Active Comparator: dapagliflozin<br>dapagliflozin 10mg + metformin, oral administration once a day for 48 weeks | Drug: Dapagliflozin<br>* dapagliflozin 10mg + metformin, oral administration once a day for 48 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of bone density | Change from screening bone density of lumbar spine 1-4, neck of femur and whole femur at 48 weeks | Screening, 48 weeks | 
| Change of CTX(C-terminal telopeptide of type I collagen) | Change from baseline bone marker CTX(C-terminal telopeptide of type I collagen) at 12 weeks and 48 weeks. | Baseline, 12 weeks, 48 weeks | 
| Change of P1NP(Procollagen type 1 Aminoterminal Propeptide) | Change from baseline bone marker P1NP(Procollagen type 1 Aminoterminal Propeptide) at 12 weeks and 48 weeks | Baseline, 12 weeks, 48 weeks | 
| Change of 25OHD(25 Hydroxyvitamin D) | Change from baseline bone metabolism indicator 25OHD(25 Hydroxyvitamin D) at 12 weeks and 48 weeks | Baseline, 12 weeks, 48 weeks | 
| Change of PTH(Parathyroid Hormone) Intact | Change from baseline bone metabolism indicator PTH(Parathyroid Hormone) Intact at 12 weeks and 48 weeks | Baseline, 12 weeks, 48 weeks | 
| Change of FGF23 (Fibroblast growth factor 23) | Change from baseline bone metabolism indicator FGF23(Fibroblast growth factor 23) at 12 weeks and 48 weeks | Baseline, 12 weeks, 48 weeks | 
| Change of 24 hour urine calcium | Change from baseline bone metabolism indicator 24 hour urine calcium at 12 weeks and 48 weeks | Baseline, 12 weeks, 48 weeks | 
| Change of 24 hour urine phosphate | Change from baseline bone metabolism indicator 24 hour urine phosphate at 12 weeks and 48 weeks | Baseline, 12 weeks, 48 weeks | 
| Change of 24 hour urine creatinine | Change from baseline bone metabolism indicator 24 hour urine creatinine at 12 weeks and 48 weeks | Baseline, 12 weeks, 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of HbA1C | Change from baseline HbA1C at 12 weeks and 48 weeks | Baseline, 12 weeks, 48 weeks | 
| Change of FBS(Fasting Blood Sugar) | Change from baseline FBS(Fasting Blood Sugar) at 12 weeks and 48 weeks | Baseline, 12 weeks, 48 weeks | 
| Change of insulin | Change from baseline insulin at 12 weeks and 48 weeks | Baseline, 12 weeks, 48 weeks | 
| Change of c-peptide | Change from baseline c-peptide at 12 weeks and 48 weeks | Baseline, 12 weeks, 48 weeks | 
| Change of AGE(Advanced Glycation End Products) | Change from baseline AGE(Advanced Glycation End Products) at 12 weeks and 48 weeks | Baseline, 12 weeks, 48 weeks | 
| Change of CGM(Continuous Glucose Monitoring) | Change from baseline CGM(Continuous Glucose Monitoring) at 12 weeks and 48 weeks | Baseline, 12 weeks, 48 weeks | 
| Adverse events | Adverse events | 12 weeks, 24 weeks, 36 weeks, 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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osteopenia