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

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

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.

Study Overview

• Status: Unknown
• Conditions: Diabetes Mellitus, Type 2; Bone Diseases, Metabolic
• Intervention / Treatment: Drug: Evogliptin; Drug: Dapagliflozin

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.

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Hoyeon Chung, MD, PhD; Phone Number: +82-2-440-6124; Email: chy1009@hotmail.com

Study Locations

• Korea, Republic of
  • Incheon, Korea, Republic of, 22332
    • Inha University Hospital
    • Contact: Seong Bin Hong, MD, PhD; Phone Number: +82-32-890-3363; Email: sbhongmd@inha.ac.kr
    • Principal Investigator: Seong Bin Hong, MD, PhD
  • Seoul, Korea, Republic of, 05030
    • Konkuk University Medical Center
    • Contact: Kee Ho Song, MD, PhD; Phone Number: +82-2-2030-7533; Email: 20050053@kuh.ac.kr
    • Principal Investigator: Kee Ho Song, MD, PhD
  • Seoul, Korea, Republic of, 02447
    • Kyung Hee University Hospital
    • Contact: So Young Park, MD, PhD; Phone Number: +82-2-958-9431; Email: malcoy@hanmail.net
    • Principal Investigator: So Young Park, MD, PhD
  • Seoul, Korea, Republic of, 05278
    • Kyung Hee University Hospital at Gangdong
    • Contact: Hoyeon Chung, MD, PhD; Phone Number: +82-2-440-6124; Email: chy1009@hotmail.com
    • Principal Investigator: Hoyeon Chung, MD, PhD
  • Seoul, Korea, Republic of, 07345
    • The Catholic University of Korea, Yeouido St. Mary's Hospital
    • Contact: Ki Hyun Baik, MD, PhD; Phone Number: +82-2-3779-1400; Email: drbkh@catholic.ac.kr
    • Principal Investigator: Ki Hyun Baik, MD, PhD
  • Seoul, Korea, Republic of, 04401
    • Soon Chun Hyang University Hospital Seoul
    • Contact: Dong Won Byun, MD,PhD; Phone Number: +82-2-710-4240; Email: byundw@schmc.ac.kr
    • Principal Investigator: Dong Won Byun, MD,PhD
  • Gangwondo
    • Gangneung, Gangwondo, Korea, Republic of, 25440
      • Gangneung Asan Hospital
      • Contact: Ha Young Kim, MD, PhD; Phone Number: +82-33-610-3072; Email: hykimmd@hanmail.net
      • Principal Investigator: Ha Young Kim, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: evogliptin; evogliptin 5 mg + metformin, oral administration once a day for 48 weeks	Drug: Evogliptin; evogliptin 5mg + metformin, oral administration once a day for 48 weeks
ACTIVE_COMPARATOR: dapagliflozin; dapagliflozin 10mg + metformin, oral administration once a day for 48 weeks	Drug: Dapagliflozin; dapagliflozin 10mg + metformin, oral administration once a day for 48 weeks

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Kyung Hee University Hospital at Gangdong
• Collaborators: Dong-A ST Co., Ltd.
• Investigators: Principal Investigator: Hoyeon Chung, MD, PhD, Kyung Hee University Hospital at Gangdong

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): February 1, 2021
• Primary Completion (ANTICIPATED): January 31, 2022
• Study Completion (ANTICIPATED): January 31, 2023

Study Registration Dates

• First Submitted: December 29, 2020
• First Submitted That Met QC Criteria: January 10, 2021
• First Posted (ACTUAL): January 13, 2021

Study Record Updates

• Last Update Posted (ACTUAL): January 13, 2021
• Last Update Submitted That Met QC Criteria: January 10, 2021
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: osteopenia
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Endocrine System Diseases; Diabetes Mellitus; Musculoskeletal Diseases; Diabetes Mellitus, Type 2; Bone Diseases; Bone Diseases, Metabolic; Metabolic Diseases; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Dapagliflozin
• Other Study ID Numbers: EVOMETA-04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No