Effect of Tofogliflozin on UACR Compared to Metformin Hydrochloride in Diabetic Kidney Disease (TRUTH-DKD)

Sponsor
Shinshu University (Other)
Overall Status
Recruiting
CT.gov ID
NCT05469659
Collaborator
Kowa Company, Ltd. (Industry)
120
1
2
61.2
2

Study Details

Study Description

Brief Summary

This multicenter, randomized, open-label, controlled study will assess the efficacy of the SGLT2 inhibitor tofogliflozin on Urine Albumin-to-Creatinine Ratio (UACR) compared to metformin in patients with type 2 diabetes with chronic kidney disease (CKD).

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

Eligible participants will be randomly assigned (1:1) to tofogliflozin or metformin with stratification based on UACR (<300 mg/gCr,≧300mg/gCr), an estimated glomerular filtration rate (eGFR) (<60mL/min/1.73m2, ≧60 mL/min/1.73m2), and age (<65 years old, ≧65 years old). The primary end point is change in urine albumin-to-creatinine ratio (UACR) from baseline after 52 weeks treatment. Changes in eGFR, HbA1c, body weight, systolic blood pressure, diastolic blood pressure, total serum proteins, serum albumin, uric acid, hematocrit, hemoglobin, red blood cell count, pulse rate, triglyceride, low-density lipoprotein, high-density lipoprotein and albuminuria class transition rate will also be evaluated.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
120 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Effect of Tofogliflozin on Urine Albumin-to-Creatinine Ratio Compared to Metformin Hydrochloride in Diabetic Kidney Disease
Actual Study Start Date :
Sep 22, 2021
Anticipated Primary Completion Date :
Oct 30, 2025
Anticipated Study Completion Date :
Oct 30, 2026

Arms and Interventions

Arm Intervention/Treatment
Experimental: Tofogliflozin

Drug: Tofogliflozin
Tofogliflozin 20 mg is orally administered once daily for 104 weeks before or after breakfast.

Active Comparator: Metformin

Drug: Metformin
Metformin is started at 500 mg daily and orally administered in 2 to 3 divided doses immediately before or after meals. The dose during the maintenance period is determined by observing the effect, but is usually 750 to 1,500 mg daily. Metformin is orally administered for 104 weeks throughout post-start period. The dose may be adjusted according to the patient's condition, but the maximum daily dose should be 2,250 mg.

Outcome Measures

Primary Outcome Measures

  1. Urine albumin-to-creatinine ratio (UACR) [Up to 52 weeks]

    Change from baseline in urine albumin-to-creatinine ratio (UACR) after 52 weeks treatment.

Secondary Outcome Measures

  1. Urine albumin-to-creatinine ratio (UACR) [Up to 26 and 104 weeks]

    Change from baseline in urine albumin-to-creatinine ratio (UACR) after 26 and 104 weeks treatment.

  2. Urine albumin-to-creatinine ratio (UACR) [Up to 26, 52 and 104 weeks]

    Change rates from baseline in urine albumin-to-creatinine ratio (UACR) after 26, 52 and 104weeks treatment.

  3. Change slope in eGFR [Up to 52 and 104 weeks]

    Change slope in eGFR

  4. HbA1c [Up to 52 and 104 weeks]

    Change in HbA1c

  5. Body weight [Up to 52 and 104 weeks]

    Changes in body weight

  6. Systolic / diastolic blood pressure [Up to 52 and 104 weeks]

    Changes in systolic / diastolic blood pressure

  7. Total serum proteins [Up to 52 and 104 weeks]

    Changes in total serum proteins

  8. Serum albumin [Up to 52 and 104 weeks]

    Changes in serum albumin

  9. Uric acid [Up to 52 and 104 weeks]

    Changes in uric acid

  10. Hematocrit [Up to 52 and 104 weeks]

    Changes in hematocrit

  11. Hemoglobin [Up to 52 and 104 weeks]

    Changes in hemoglobin

  12. Red blood cell count [Up to 52 and 104 weeks]

    Changes in red blood cell count

  13. Pulse rate [Up to 52 and 104 weeks]

    Changes in pulse rate

  14. Triglyceride [Up to 52 and 104 weeks]

    Changes in triglyceride

  15. Low-density lipoprotein [Up to 52 and 104 weeks]

    Changes in low-density lipoprotein

  16. High-density lipoprotein [Up to 52 and 104 weeks]

    Changes in high-density lipoprotein

  17. Albuminuria class [Up to 104 weeks]

    Transition of albuminuria class

Eligibility Criteria

Criteria

Ages Eligible for Study:
20 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • Type 2 diabetic patients

  • Patients aged 20 years or older at the time of obtaining consent

  • Patients with HbA1c 6.5 or more and 9.0% or less within 13 weeks before obtaining consent (evaluated by test values after 4 weeks or more without taking SGLT2 inhibitor / metformin)

  • Patients who have been judged by their doctor to need a diabetic drug when they are first seen, or who have already taken a diabetic drug and have decided that it is necessary to add one diabetic drug.

  • Patients who have been receiving RAS inhibitors (ARB, ARNI, ACE inhibitors, direct renin inhibitors) for 4 weeks or longer

  • Patients with eGFR of 30 or more (mL / min / 1.73m2) within 13 weeks before obtaining consent (evaluated by test values after 4 weeks or more without taking SGLT2 inhibitor / metformin)

  • Patients with urinary albumin / creatinine ratio (UACR) of 30 or more and less than 2000 (mg / gCr) (4 weeks or more without taking SGLT2 inhibitor / metformin) within 13 weeks before obtaining consent Evaluate by inspection value)

  • Patients for whom written consent was obtained based on the patient's free will after receiving sufficient explanation for participation in this study

Exclusion Criteria:
  • Patients receiving treatment with SGLT2 inhibitor or metformin within 13 weeks before obtaining consent

  • Dialysis patient

  • Patients with a history of severe hypoglycemia

  • Patients with hypersensitivity to SGLT2 inhibitor or metformin

  • Pregnant women, lactating patients, and patients who wish to raise children

  • Patients with BMI of 35 kg / m2 or more based on the latest measured values within 13 weeks before obtaining consent

  • Patients who are contraindicated for the study drug

  • Other patients who the attending physician deems inappropriate as a subject

Contacts and Locations

Locations

Site City State Country Postal Code
1 Shinshu University Matsumoto Nagano Japan 390-8621

Sponsors and Collaborators

  • Shinshu University
  • Kowa Company, Ltd.

Investigators

  • Study Chair: Koichiro Kuwahara, MD, PhD, Shinshu University School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Koichiro Kuwahara, MD, PhD, Professor, Shinshu University
ClinicalTrials.gov Identifier:
NCT05469659
Other Study ID Numbers:
  • 21-02
  • jRCTs031210339
First Posted:
Jul 22, 2022
Last Update Posted:
Jul 22, 2022
Last Verified:
Jul 1, 2022
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jul 22, 2022