Clinical trial NCT04706637: A Clinical Trial to Evaluate the Bone Metabolism and the Blood Sugar of Evogliptin and Dapagliflozin
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Bone Diseases, Metabolic
Diabetes Mellitus, Type 2
Keywords: osteopenia
Lead sponsor: Kyung Hee University Hospital at Gangdong
Sponsor class: OTHER
Collaborators: name: Dong-A ST Co., Ltd.
First posted: 2021-01-13
Enrollment: 120
Sex: FEMALE
Minimum age (years): 40
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.

1. Arm 1: evogliptin 5mg + metformin, oral administration once a day for 48 weeks
2. Arm 2: dapagliflozin 10mg + metformin, oral administration once a day for 48 weeks
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. 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
2. Lumbar, neck of femur and total femur bone density measurements were -2.4≤T-score≤-1.0
3. Obtained written informed consent from a patient
4. Patients who can participate during clinical trials and perform all planned trial procedures and visits.

Exclusion Criteria:

1. 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.
2. AST(ASpartate Transaminase) or ALT(ALanine Transaminase) exceeds 2 times the upper limit of the normal range in laboratory tests
3. Patients with moderate or severe renal impairment, end-stage renal disease (ESRD) or dialysis
4. 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
5. 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
6. 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
7. Patients who have participated in other clinical trials within 3 months
8. Patients with a history of malignant tumors within 5 years
9. Those who have a history of hypersensitivity to the main ingredients and additives of the trial drugs
10. Patients with type 1 diabetes or diabetic ketoacidosis
11. Patients with genetic problems such as galactose intolerance, Lapp deficiency, or glucose-galactose malabsorption
12. Any other patient that the investigator has determined is unsuitable for this clinical trial

Primary outcomes:
measure: Change of bone density
timeFrame: Screening, 48 weeks
measure: Change of CTX(C-terminal telopeptide of type I collagen)
timeFrame: Baseline, 12 weeks, 48 weeks
measure: Change of P1NP(Procollagen type 1 Aminoterminal Propeptide)
timeFrame: Baseline, 12 weeks, 48 weeks
measure: Change of 25OHD(25 Hydroxyvitamin D)
timeFrame: Baseline, 12 weeks, 48 weeks
measure: Change of PTH(Parathyroid Hormone) Intact
timeFrame: Baseline, 12 weeks, 48 weeks
measure: Change of FGF23 (Fibroblast growth factor 23)
timeFrame: Baseline, 12 weeks, 48 weeks
measure: Change of 24 hour urine calcium
timeFrame: Baseline, 12 weeks, 48 weeks
measure: Change of 24 hour urine phosphate
timeFrame: Baseline, 12 weeks, 48 weeks
measure: Change of 24 hour urine creatinine
timeFrame: Baseline, 12 weeks, 48 weeks
Secondary outcomes:
measure: Change of HbA1C
timeFrame: Baseline, 12 weeks, 48 weeks
measure: Change of FBS(Fasting Blood Sugar)
timeFrame: Baseline, 12 weeks, 48 weeks
measure: Change of insulin
timeFrame: Baseline, 12 weeks, 48 weeks
measure: Change of c-peptide
timeFrame: Baseline, 12 weeks, 48 weeks
measure: Change of AGE(Advanced Glycation End Products)
timeFrame: Baseline, 12 weeks, 48 weeks
measure: Change of CGM(Continuous Glucose Monitoring)
timeFrame: Baseline, 12 weeks, 48 weeks
measure: Adverse events
timeFrame: 12 weeks, 24 weeks, 36 weeks, 48 weeks
Other outcomes:
Locations:
city: Gangneung
country: Korea, Republic of
facility: GangNeung Asan Hospital
state: Gangwondo
city: Incheon
country: Korea, Republic of
facility: Inha University Hospital
city: Seoul
country: Korea, Republic of
facility: Kyung Hee University Hospital
city: Seoul
country: Korea, Republic of
facility: Soon Chun Hyang University Hospital Seoul
city: Seoul
country: Korea, Republic of
facility: Konkuk University Medical Center
city: Seoul
country: Korea, Republic of
facility: Kyung Hee University Hospital at Gangdong
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Yeouido St. Mary's Hospital
Study officials:
affiliation: Kyung Hee University Hospital at Gangdong
name: Hoyeon Chung, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: