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

Effect of Tofogliflozin on Urine Albumin-to-Creatinine Ratio Compared to Metformin Hydrochloride in Diabetic Kidney Disease

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).

Study Overview

• Status: Recruiting
• Conditions: T2DM (Type 2 Diabetes Mellitus); Metformin; SGLT2-Inhibitors
• Intervention / Treatment: Drug: Tofogliflozin; Drug: Metformin

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 Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Koichiro Kuwahara, MD, PhD; Phone Number: +81-263-37-3191; Email: kkuwah@shinshu-u.ac.jp

Study Locations

• Japan
  • Nagano
    • Matsumoto, Nagano, Japan, 390-8621
      • Recruiting
      • Shinshu University
      • Contact: Koichiro Kuwahara, MD, PhD; Phone Number: +81-263-37-3191; Email: kkuwah@shinshu-u.ac.jp
      • Contact: Masatoshi Minamisawa; Phone Number: +81-263-37-3191; Email: nanchan7131@gmail.com
      • Principal Investigator: Koichiro Kuwahara, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urine albumin-to-creatinine ratio (UACR)	Change from baseline in urine albumin-to-creatinine ratio (UACR) after 52 weeks treatment.	Up to 52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Urine albumin-to-creatinine ratio (UACR)	Change from baseline in urine albumin-to-creatinine ratio (UACR) after 26 and 104 weeks treatment.	Up to 26 and 104 weeks
Urine albumin-to-creatinine ratio (UACR)	Change rates from baseline in urine albumin-to-creatinine ratio (UACR) after 26, 52 and 104weeks treatment.	Up to 26, 52 and 104 weeks
Change slope in eGFR	Change slope in eGFR	Up to 52 and 104 weeks
HbA1c	Change in HbA1c	Up to 52 and 104 weeks
Body weight	Changes in body weight	Up to 52 and 104 weeks
Systolic / diastolic blood pressure	Changes in systolic / diastolic blood pressure	Up to 52 and 104 weeks
Total serum proteins	Changes in total serum proteins	Up to 52 and 104 weeks
Serum albumin	Changes in serum albumin	Up to 52 and 104 weeks
Uric acid	Changes in uric acid	Up to 52 and 104 weeks
Hematocrit	Changes in hematocrit	Up to 52 and 104 weeks
Hemoglobin	Changes in hemoglobin	Up to 52 and 104 weeks
Red blood cell count	Changes in red blood cell count	Up to 52 and 104 weeks
Pulse rate	Changes in pulse rate	Up to 52 and 104 weeks
Triglyceride	Changes in triglyceride	Up to 52 and 104 weeks
Low-density lipoprotein	Changes in low-density lipoprotein	Up to 52 and 104 weeks
High-density lipoprotein	Changes in high-density lipoprotein	Up to 52 and 104 weeks
Albuminuria class	Transition of albuminuria class	Up to 104 weeks

Collaborators and Investigators

• Sponsor: Shinshu University
• Collaborators: Kowa Company, Ltd.
• Investigators: Study Chair: Koichiro Kuwahara, MD, PhD, Shinshu University School of Medicine

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 22, 2021
• Primary Completion (ANTICIPATED): October 30, 2025
• Study Completion (ANTICIPATED): October 30, 2026

Study Registration Dates

• First Submitted: July 15, 2022
• First Submitted That Met QC Criteria: July 21, 2022
• First Posted (ACTUAL): July 22, 2022

Study Record Updates

• Last Update Posted (ACTUAL): July 22, 2022
• Last Update Submitted That Met QC Criteria: July 21, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Urologic Diseases; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Type 2; Kidney Diseases; Diabetic Nephropathies; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Metformin; 6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol
• Other Study ID Numbers: 21-02; jRCTs031210339 (REGISTRY: jRCT)

Drug and device information, study documents

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