Foxiga Korea Local Phase 4 Study (BEYOND)

Effects of Dapagliflozin Compared With Glimepiride on Body Composition in Patients With Type 2 Diabetes Inadequately Controlled With Metformin

To evaluate the effect of dapagliflozin on body composition in Korean T2DM subjects.12-month, randomised, open-label, parallel-group, multi-centre phase IV study.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Dapagliflozin; Drug: Glimepiride

Detailed Description

This is a 52 weeks, randomized, open-label, parallel-group, multi-centres phase IV study.

Participants will be randomized 1:1 to receive dapagliflozin 10 mg qd or glimepiride 1~2 mgqd in an open-label manner for 12 months as add-on to metformin 1000 mg.

Parallel group study design was chosen. In order maintain the practicality of the phase IV study, open label design of study drug delivery was chosen. The reading of the DXA scans will be conducted by one expert in blinded manner. Glimepiride is the most frequently used SUs in Korea and therefore this was chosen as comparator.Dapagliflozin treatment will be associated with reduction of total body FM, BW, abdominal VAT and SAT volume compared with glimepiride.

• Study Type: Interventional
• Enrollment (Actual): 125
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Ansan-si, Korea, Republic of, 15355
    • Research Site
  • Changwon-si, Korea, Republic of, 51353
    • Research Site
  • Daegu, Korea, Republic of, 41931
    • Research Site
  • Daejeon-si, Korea, Republic of, 35233
    • Research Site
  • Goyang-si, Korea, Republic of, 10326
    • Research Site
  • Incheon, Korea, Republic of, 21565
    • Research Site
  • Seongnam-si, Korea, Republic of, 13620
    • Research Site
  • Seoul, Korea, Republic of, 06273
    • Research Site
  • Seoul, Korea, Republic of, 04401
    • Research Site
  • Seoul, Korea, Republic of, 05278
    • Research Site
  • Seoul, Korea, Republic of, 01830
    • Research Site
  • Suwon-si, Korea, Republic of, 16499
    • Research Site
  • Uijeongbu-si, Korea, Republic of, 11765
    • Research Site
  • Wonju-si, Korea, Republic of, 220-701
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adults with T2DM (Male or female, ≥ 19 and ≤ 75 yrs)
2. Patients in insufficient glycemic control (HbA1c > 7.5% and < 9.5% in recent 4 weeks)
3. Patients with an unchanged dose of metformin (≥ 1,000 mg/day) for > 8 weeks prior to randomization
4. Written informed consent

5. WOCBP must take precautions to avoid pregnancy throughout the study and for 4 weeks after intake of the last dose.

   • WOCBP must have a negative urine pregnancy test at screening visit WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal.
   • WOCBP must be willing to use a medically accepted method of contraception that is considered reliable in the judgment of the Investigator.

Exclusion Criteria:

1. Type 1 diabetes or history of diabetic ketoacidosis
2. Pregnant or breast-feeding patients
3. eGFR < 60 mL/min/1.73 m2 (MDRD) on visit 1.
4. Indication of active liver disease (AST/ALT/total bilirubin > 3 X upper limits of normal) on visit 1.
5. Acute coronary syndrome, stroke or TIA within 3 months prior to randomization
6. Bariatric surgery within 2 years; treatment of anti-obesity drugs 3 months prior to randomization; any treatment leading to unstable body weight. (Unstable body weight is considered reliable in the judgment of the Investigator.)
7. History of bladder cancer or history of radiation therapy to the lower abdomen or pelvis at any time
8. History of any other malignancy within 5 years (with the exception of successfully treated non-melanoma skin cancers)
9. History of alcohol or drug abuse judged by physician within 3 months prior to randomization
10. Concomitant participation in any other clinical study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dapagliflozin; Dapagliflozin 10mg + Metformin 1000mg	Drug: Dapagliflozin; Subject who will be randomized to the 'Dapagliflozin arm' will be treated with dapagliflozin 10mg + Metformin 1000 mg as Diabetes Treatment
Active Comparator: Glimepiride; Glimepiriide 1-2mg + Metformin 1000mg	Drug: Glimepiride; Subject who will be randomized to the 'Glimepiride arm' will be treated with glimepiride 1-2mg + Metformin 1000 mg as Diabetes Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adjusted Mean Changes From Baseline in Total Body Fat Mass by DXA Scan	Adjusted mean changes in total body fat mass from baseline using DXA scan in 52 weeks after the start of the treatment	From baseline to Week 52
Adjusted Mean Changes From Baseline in Percentage of Total Body Fat Assessed by DXA Scan	Adjusted mean percent changes in total body fat mass from baseline using DXA scan in 52 weeks after the start of the treatment	From baseline to Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adjusted Mean Change in HbA1c at Week 52	Adjusted Mean Change in HbA1c at Week 52	From baseline to Week 52
HbA1c <7.0% at Week 52	HbA1c <7.0% at Week 52	52 weeks
Adjusted Mean Change in Fasting Blood Sugar (FBS) at Week 52	Adjusted Mean Change in Fasting Blood Sugar (FBS) at Week 52	From baseline to Week 52
Adjusted Mean Change in Total Body Weight at Week 52	Adjusted Mean Change in Total Body Weight at Week 52	From baseline to Week 52
Adjusted Mean Change in Waist Circumference at Week 52	Adjusted Mean Change in Waist Circumference at Week 52	From baseline to Week 52
Adjusted Mean Change in Body Mass Index (BMI) at Week 52	Adjusted Mean Change in Body Mass Index (BMI) at Week 52	From baseline to Week 52
Adjusted Mean Change in Systolic Blood Pressure (SBP) at Week 52	Adjusted Mean Change in Systolic Blood Pressure (SBP) at Week 52	From baseline to Week 52
Adjusted Mean Change in Diastolic Blood Pressure (DBP) at Week 52	Adjusted Mean Change in Diastolic Blood Pressure (DBP) at Week 52	From baseline to Week 52
Adjusted Mean Change in Visceral Adipose Tissue (VAT) Area at Week 52	Adjusted Mean Change in Visceral Adipose Tissue (VAT) area at Week 52	From baseline to Week 52
Adjusted Mean Change in Subcutaneous Adipose Tissue (SAT) Area at Week 52	Adjusted Mean Change in Subcutaneous Adipose Tissue (SAT) area at Week 52	From baseline to Week 52
Adjusted Mean Change in Visceral to Subcutaneous Adipose Tissue Ratio at Week 52	Adjusted Mean Change in Visceral to Subcutaneous Adipose Tissue Ratio at Week 52	From baseline to Week 52
Adjusted Mean Change in Lean Body Mass at Week 52	Adjusted Mean Change in Lean Body Mass at Week 52	From baseline to Week 52
Adjusted Mean Change in Adinopectin at Week 52	Adjusted Mean Change in Adinopectin at Week 52	From baseline to Week 52
Adjusted Mean Change in High Sensitivity C-Reactive Protein (hsCRP) at Week 52	Adjusted Mean Change in High Sensitivity C-Reactive Protein (hsCRP) at Week 52	From baseline to Week 52

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

Helpful Links

• D1690l00067_CSP_Redacted
• D1690l00067_SAP_Redacted

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2016
• Primary Completion (Actual): January 15, 2018
• Study Completion (Actual): January 15, 2018

Study Registration Dates

• First Submitted: September 23, 2015
• First Submitted That Met QC Criteria: September 30, 2015
• First Posted (Estimate): October 1, 2015

Study Record Updates

• Last Update Posted (Actual): August 20, 2019
• Last Update Submitted That Met QC Criteria: August 19, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: DM
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Immunosuppressive Agents; Immunologic Factors; Sodium-Glucose Transporter 2 Inhibitors; Dapagliflozin; Glimepiride
• Other Study ID Numbers: D1690L00067