PK and PD of YG1699 in CKD Patients With Diabetes

NCT06648876 | Not Yet Recruiting Phase 1

• 1 other identifier: IIT-2024-0232
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn PK and PD of YG1699 in patients with diabetes and renal dysfuction. Participants will: Take YG1699 or a placebo every day for 8 days. Visit the clinic 7 times for checkups and tests. Keep a diary of their symptoms. Estimate PK data from a single dose of YG1699. Estimate PD data at baseline and the last day.

Conditions

Diabetes; Renal Insufficiency, Chronic; Hemodialysis

Keywords

PK; PD; SGLT1/2 inhibitor; CKD; Diabetes

Outcome Measures

Primary Outcomes (1)

• YG1699 concentration in plasma at different time

  single-dose pharmacokinetic

  0 hour (h), 0.5h, 1h, 2h, 4h, 8h and 12h after the first dose of YG1699 (Day1); 24 hours after the first dose of YG1699 (Day2 morning)

Secondary Outcomes (7)

• Metabolite 1 concentration in plasma at different time

  0 hour (h), 0.5h, 1h, 2h, 4h, 8h and 12h after the first dose of YG1699 (Day1); 24 hours after the first dose of YG1699 (Day2 morning)

• YG1699 steady-state concentration in plasma

  Day 9 morning（the first day after discontinuation of the drug）

• Metabolite 1 steady-state concentration in plasma

  Day 9 morning（the first day after discontinuation of the drug）

• Hemodialysis clearance of YG1699

  immediately before and immediately after the hemodialysis treatment on Day9

• Hemodialysis clearance of Metabolite 1

  immediately before and immediately after the hemodialysis treatment on Day 9

Other Outcomes (18)

• Red blood cell count

  Day9 morning（the first day after discontinuation of the drug）

• White blood cell count

  Day 9 morning（the first day after discontinuation of the drug）

• Platelet count

  Day 9 morning（the first day after discontinuation of the drug）

Study Arms (4)

eGFR≥30+YG1699

EXPERIMENTAL

patients with eGFR ≥30ml/min/1.73M2 will be treated with YG1699 10mg QD for 8 days.

Drug: YG1699

Hemodialysis+YG1699

EXPERIMENTAL

patients on hemodialysis will be treated with YG1699 10mg QD for 8 days.

Drug: YG1699

eGFR<20+YG1699

EXPERIMENTAL

patients with eGFR \<20ml/min/1.73M2 will be treated with YG1699 10mg QD for 8 days.

Drug: YG1699

eGFR<20+placebo

PLACEBO COMPARATOR

patients with eGFR \<20ml/min/1.73M2 will be treated with placebo 10mg QD for 8 days.

Drug: Placebo

Interventions

YG1699 DRUG

10mg qd for 8 days

Hemodialysis+YG1699; eGFR<20+YG1699; eGFR≥30+YG1699

Placebo DRUG

10mg qd for 8 days

eGFR<20+placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to provide informed consent
• Male or female patients ,age between 18 and 70 at screening
• Meet the diagnostic criteria for diabetic nephropathy, including patients with type 1 or type 2 diabetes;
• Fasting blood glucose \<11.1 mmol/L, stable on baseline anti-diabetic medication
• No history of SGLT2i use within the past month
• Hemodialysis patients must have maintenance hemodialysis for more than 3 months, with 3 sessions per week (limited to HD or HDF treatment), and spKt/V\>1.2 within 6 months
• The patient has not used glucocorticoids, calcineurin inhibitors (cyclosporine, tacrolimus), etc. that affect blood sugar within the past month before signing the informed consent form
• The baseline diabetes management medication regimen has been stable within the past 2 weeks.

You may not qualify if:

• Hypoglycemia occurs more than 2 times in one month
• History of ketoacidosis
• Patients who are being treated with swiram and digoxin
• Patients with acute kidney injury (serum creatinine increased by ≥ 50% within 1 week)
• Abnormal liver function (ALT \> 3 times the upper limit of normal value)
• Hemoglobin \< 80g/L or \> 150g/L
• The blood pressure of patients with recent symptomatic hypotension is lower than 90/60 mmHg
• There is acute myocardial infarction stroke infection in the past month
• There is systemic active infection or uncured tumor
• The dialysis regimen of HD patients included HP treatment
• Participating in other interventional clinical studies
• Pregnant or lactating women
• Other situations that the researcher thinks are not suitable for joining the study

Sponsors & Collaborators

• RenJi Hospital: lead

Study Sites (1)

Department of nephrology , Renji Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200127, China

Location

Related Publications (11)

• Wright EM, Loo DD, Hirayama BA. Biology of human sodium glucose transporters. Physiol Rev. 2011 Apr;91(2):733-94. doi: 10.1152/physrev.00055.2009.

  PMID: 21527736 BACKGROUND

• Powell DR, DaCosta CM, Gay J, Ding ZM, Smith M, Greer J, Doree D, Jeter-Jones S, Mseeh F, Rodriguez LA, Harris A, Buhring L, Platt KA, Vogel P, Brommage R, Shadoan MK, Sands AT, Zambrowicz B. Improved glycemic control in mice lacking Sglt1 and Sglt2. Am J Physiol Endocrinol Metab. 2013 Jan 15;304(2):E117-30. doi: 10.1152/ajpendo.00439.2012. Epub 2012 Nov 13.

  PMID: 23149623 BACKGROUND

• Abdul-Ghani MA, DeFronzo RA. Inhibition of renal glucose reabsorption: a novel strategy for achieving glucose control in type 2 diabetes mellitus. Endocr Pract. 2008 Sep;14(6):782-90. doi: 10.4158/EP.14.6.782.

  PMID: 18996802 BACKGROUND

• Rieg T, Masuda T, Gerasimova M, Mayoux E, Platt K, Powell DR, Thomson SC, Koepsell H, Vallon V. Increase in SGLT1-mediated transport explains renal glucose reabsorption during genetic and pharmacological SGLT2 inhibition in euglycemia. Am J Physiol Renal Physiol. 2014 Jan;306(2):F188-93. doi: 10.1152/ajprenal.00518.2013. Epub 2013 Nov 13.

  PMID: 24226519 BACKGROUND

• Jung CH, Jang JE, Park JY. A Novel Therapeutic Agent for Type 2 Diabetes Mellitus: SGLT2 Inhibitor. Diabetes Metab J. 2014 Aug;38(4):261-73. doi: 10.4093/dmj.2014.38.4.261.

  PMID: 25215272 BACKGROUND

• Cariou B, Charbonnel B. Sotagliflozin as a potential treatment for type 2 diabetes mellitus. Expert Opin Investig Drugs. 2015;24(12):1647-56. doi: 10.1517/13543784.2015.1100361. Epub 2015 Nov 7.

  PMID: 26548423 BACKGROUND

• Wang Shanshan, Chen Dong, Chen Mingwei, et al. Analysis of the influence of metabolic syndrome on diabetic nephropathy in patients with type 2 diabetes [J]. Prevention and control of chronic diseases in China, 2011,19 (5):509-511.

  BACKGROUND

• Levin A, Tonelli M, Bonventre J, Coresh J, Donner JA, Fogo AB, Fox CS, Gansevoort RT, Heerspink HJL, Jardine M, Kasiske B, Kottgen A, Kretzler M, Levey AS, Luyckx VA, Mehta R, Moe O, Obrador G, Pannu N, Parikh CR, Perkovic V, Pollock C, Stenvinkel P, Tuttle KR, Wheeler DC, Eckardt KU; ISN Global Kidney Health Summit participants. Global kidney health 2017 and beyond: a roadmap for closing gaps in care, research, and policy. Lancet. 2017 Oct 21;390(10105):1888-1917. doi: 10.1016/S0140-6736(17)30788-2. Epub 2017 Apr 20.

  PMID: 28434650 RESULT

• Bhatt DL, Szarek M, Steg PG, Cannon CP, Leiter LA, McGuire DK, Lewis JB, Riddle MC, Voors AA, Metra M, Lund LH, Komajda M, Testani JM, Wilcox CS, Ponikowski P, Lopes RD, Verma S, Lapuerta P, Pitt B; SOLOIST-WHF Trial Investigators. Sotagliflozin in Patients with Diabetes and Recent Worsening Heart Failure. N Engl J Med. 2021 Jan 14;384(2):117-128. doi: 10.1056/NEJMoa2030183. Epub 2020 Nov 16.

  PMID: 33200892 RESULT

• Cherney DZI, Ferrannini E, Umpierrez GE, Peters AL, Rosenstock J, Powell DR, Davies MJ, Banks P, Agarwal R. Efficacy and safety of sotagliflozin in patients with type 2 diabetes and stage 3 chronic kidney disease. Diabetes Obes Metab. 2023 Jun;25(6):1646-1657. doi: 10.1111/dom.15019. Epub 2023 Feb 28.

  PMID: 36782093 RESULT

• Shanghai Yanjian New Drug R&D Co., Ltd. Handbook for Researchers (Chinese). June 17, 2021

  RESULT

MeSH Terms

Conditions

Diabetes Mellitus; Renal Insufficiency, Chronic

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Leyi Gu

  RenJi Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Leyi Gu

CONTACT

86-21-58752345; guleyi@aliyun.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 15, 2024
• First Posted: October 18, 2024
• Study Start: October 31, 2024
• Primary Completion: August 31, 2025
• Study Completion: October 30, 2025
• Last Updated: October 18, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)