Ignite Creation Date:
2024-10-26 @ 3:43 PM
Last Modification Date:
2024-10-26 @ 3:43 PM
Study NCT ID:
NCT06648876
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-10-15
Brief Title:
PK and PD of YG1699 in CKD Patients With Diabetes
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Pharmacokinetic and Pharmacodynamics of YG1699 in Patients With Diabetes and Kidney Dysfunction
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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
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
Detailed Description:
Background
Diabetic kidney disease DKD as one of the most common and serious complications of diabetes has become the leading cause of end-stage renal disease ESRD worldwide A domestic epidemiological survey shows that the prevalence of DKD in community patients was 30-50 from 2009 to 2012 and accounted for about 40 in hospitalized patients in China At present the treatment of DKD is the comprehensive management of blood glucose blood pressure and blood lipid Nevertheless about one-third of patients with type 1 diabetes mellitus T1DM and nearly half of patients with type 2 diabetes mellitus T2DM will progress to ESRD Patients with DKD have higher complication rates and mortality Studies have shown that the mortality rate of patients with diabetes complicated with DKD is 3 to 12 times higher than that of patients with simple diabetes Although blood glucose is actively controlled and angiotensin-converting enzyme inhibitors ACEI or angiotensin II receptor blockers ARB are used to control hypertension in the treatment of diabetes the progression of DKD is still inevitable Much more clinical needs are still present Sodium-glucose co-transporter inhibitors SGLT2i are new hypoglycemic drugs discovered in recent years They play their hypoglycemic roles by inhibiting glucose reabsorption in renal tubules and increasing urinary glucose excretion More clinical studies have found that SGLT2s not only the hypoglycemic effect but also has the effect of delaying the progression of DKD and improving the prognosis of heart failure and is recommended by international authoritative guidelines with class IA evidence for cardiorenal organ protection
Glucose cannot freely pass through the cell membrane and must rely on glucose transporter proteins on the cell membrane Sodium-dependent glucose cotransporters SGLTs are an important family of transporter proteins that regulate glucose absorption and excretion SGLT1 and SGLT2 are the most well studied members of this family and are both major glucose transporter proteins SGLT1 is expressed in various tissues such as the small intestine heart and kidney SGLT2 is mainly expressed in segment S1 of the proximal convoluted tubule of the kidney
In the renal tubules 95 of glucose is reabsorbed through SGLT2 and 5 of glucose is reabsorbed through SGLT1 When SGLT2 is inhibited the glucose reabsorbed through SGLT1 significantly increases to 50 so the hypoglycemic effect of SGLT2 inhibitors may be weakened The dual effects of SGLT1 and SGLT2 inhibitors can bring more potential benefits for treatment including continuing to maintain the effectiveness of SGLT2 selective inhibitors inducing intestinal cells to secrete endogenous glucagon-like peptide-1 GLP-1 and YY peptide PYY reducing the adverse reactions of SGLT2 inhibition such as genitourinary tract infections and constipation blocking or delaying the absorption of glucose by the gastrointestinal tract
Sotagliflozin is a SGLT2i with partial SGLT1 inhibitory activity It was approved by the European Medicines Agency EMA in 2019 for adjuvant treatment of T1DM complicated with obesity Recently the sotagliflozin heart failure protection study was terminated in the middle stage due to the excellent effect of improving the outcome of heart failure And it has a good effect of reducing proteinuria in patients with DKD This suggests that SGLT12 dual-channel blockers may have better hypoglycemic and organ protection effects
YG1699 is an oral SGLT1 and SGLT2 dual-channel blocker belonging to c-aryl glucoside derivatives It can reduce the absorption of glucose into the blood in the gastrointestinal tract by inhibiting SGLT-1 and at the same time inhibit the reabsorption of glucose in the proximal convoluted tubule of the kidney by inhibiting SGLT-2 thereby increasing the excretion of glucose from the kidney and effectively reducing blood glucose levels YG1699 reduces the risk of DKA caused by SGLT2i by increasing SGLT1 inhibitory activity In addition YG1699 shows non-pH-dependent solubility has sufficient solubility in the gastrointestinal tract has a high oral bioavailability in preclinical models and has a low possibility of drug interactions At present including YG1699 there are three SGLT12 dual inhibitor are in the clinical research stage
YG1699 has completed three clinical trials named the phase I study YG1699-01 on healthy subjects in the United States and the phase II study YG1699-201 on type 1 diabetes as well as the bridging study YG1699-102 on healthy subjects in China These clinical studies have confirmed that YG1699 has good human PK characteristics and good safety and tolerance In the phase II T1DM study compared head-to-head with DAPA it shows a better effect on reducing postprandial blood glucose All these clinical trials are in patients with eGFRgt30 mlmin173M2
However about 12 million diabetic patients have renal insufficiency and there is still no pharmacokinetic and pharmacodynamic data of YG1699 in patients with renal insufficiency
Key inclusion criteria include
1 Ability to provide informed consent
2 Male or female patients age between 18 and 70 at screening
3 Meet the diagnostic criteria for diabetic nephropathy including patients with type 1 or type 2 diabetes
4 Fasting blood glucose lt111 mmolL stable on baseline anti-diabetic medication
5 No history of SGLT2i use within the past month
6 Hemodialysis patients must have maintenance hemodialysis for more than 3 months with 3 sessions per week limited to HD or HDF treatment and spKtVgt12 within 6 months
7 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
8 The baseline diabetes management medication regimen has been stable within the past 2 weeks
Key exclusion criteria include
1 Hypoglycemia occurs more than 2 times in one month
2 History of ketoacidosis
3 Patients who are being treated with swiram and digoxin
4 Patients with acute kidney injury serum creatinine increased by 50 within 1 week 5 Abnormal liver function ALT 3 times the upper limit of normal value
6 Hemoglobin 80gL or 150gL 7 The blood pressure of patients with recent symptomatic hypotension is lower than 9060 mmHg 8 There is acute myocardial infarction stroke infection in the past month 9 There is systemic active infection or uncured tumor 10 The dialysis regimen of HD patients included HP treatment 11 Participating in other interventional clinical studies 12 Pregnant or lactating women 13 Other situations that the researcher thinks are not suitable for joining the study
Diabetic kidney disease DKD as one of the most common and serious complications of diabetes has become the leading cause of end-stage renal disease ESRD worldwide A domestic epidemiological survey shows that the prevalence of DKD in community patients was 30-50 from 2009 to 2012 and accounted for about 40 in hospitalized patients in China At present the treatment of DKD is the comprehensive management of blood glucose blood pressure and blood lipid Nevertheless about one-third of patients with type 1 diabetes mellitus T1DM and nearly half of patients with type 2 diabetes mellitus T2DM will progress to ESRD Patients with DKD have higher complication rates and mortality Studies have shown that the mortality rate of patients with diabetes complicated with DKD is 3 to 12 times higher than that of patients with simple diabetes Although blood glucose is actively controlled and angiotensin-converting enzyme inhibitors ACEI or angiotensin II receptor blockers ARB are used to control hypertension in the treatment of diabetes the progression of DKD is still inevitable Much more clinical needs are still present Sodium-glucose co-transporter inhibitors SGLT2i are new hypoglycemic drugs discovered in recent years They play their hypoglycemic roles by inhibiting glucose reabsorption in renal tubules and increasing urinary glucose excretion More clinical studies have found that SGLT2s not only the hypoglycemic effect but also has the effect of delaying the progression of DKD and improving the prognosis of heart failure and is recommended by international authoritative guidelines with class IA evidence for cardiorenal organ protection
Glucose cannot freely pass through the cell membrane and must rely on glucose transporter proteins on the cell membrane Sodium-dependent glucose cotransporters SGLTs are an important family of transporter proteins that regulate glucose absorption and excretion SGLT1 and SGLT2 are the most well studied members of this family and are both major glucose transporter proteins SGLT1 is expressed in various tissues such as the small intestine heart and kidney SGLT2 is mainly expressed in segment S1 of the proximal convoluted tubule of the kidney
In the renal tubules 95 of glucose is reabsorbed through SGLT2 and 5 of glucose is reabsorbed through SGLT1 When SGLT2 is inhibited the glucose reabsorbed through SGLT1 significantly increases to 50 so the hypoglycemic effect of SGLT2 inhibitors may be weakened The dual effects of SGLT1 and SGLT2 inhibitors can bring more potential benefits for treatment including continuing to maintain the effectiveness of SGLT2 selective inhibitors inducing intestinal cells to secrete endogenous glucagon-like peptide-1 GLP-1 and YY peptide PYY reducing the adverse reactions of SGLT2 inhibition such as genitourinary tract infections and constipation blocking or delaying the absorption of glucose by the gastrointestinal tract
Sotagliflozin is a SGLT2i with partial SGLT1 inhibitory activity It was approved by the European Medicines Agency EMA in 2019 for adjuvant treatment of T1DM complicated with obesity Recently the sotagliflozin heart failure protection study was terminated in the middle stage due to the excellent effect of improving the outcome of heart failure And it has a good effect of reducing proteinuria in patients with DKD This suggests that SGLT12 dual-channel blockers may have better hypoglycemic and organ protection effects
YG1699 is an oral SGLT1 and SGLT2 dual-channel blocker belonging to c-aryl glucoside derivatives It can reduce the absorption of glucose into the blood in the gastrointestinal tract by inhibiting SGLT-1 and at the same time inhibit the reabsorption of glucose in the proximal convoluted tubule of the kidney by inhibiting SGLT-2 thereby increasing the excretion of glucose from the kidney and effectively reducing blood glucose levels YG1699 reduces the risk of DKA caused by SGLT2i by increasing SGLT1 inhibitory activity In addition YG1699 shows non-pH-dependent solubility has sufficient solubility in the gastrointestinal tract has a high oral bioavailability in preclinical models and has a low possibility of drug interactions At present including YG1699 there are three SGLT12 dual inhibitor are in the clinical research stage
YG1699 has completed three clinical trials named the phase I study YG1699-01 on healthy subjects in the United States and the phase II study YG1699-201 on type 1 diabetes as well as the bridging study YG1699-102 on healthy subjects in China These clinical studies have confirmed that YG1699 has good human PK characteristics and good safety and tolerance In the phase II T1DM study compared head-to-head with DAPA it shows a better effect on reducing postprandial blood glucose All these clinical trials are in patients with eGFRgt30 mlmin173M2
However about 12 million diabetic patients have renal insufficiency and there is still no pharmacokinetic and pharmacodynamic data of YG1699 in patients with renal insufficiency
Key inclusion criteria include
1 Ability to provide informed consent
2 Male or female patients age between 18 and 70 at screening
3 Meet the diagnostic criteria for diabetic nephropathy including patients with type 1 or type 2 diabetes
4 Fasting blood glucose lt111 mmolL stable on baseline anti-diabetic medication
5 No history of SGLT2i use within the past month
6 Hemodialysis patients must have maintenance hemodialysis for more than 3 months with 3 sessions per week limited to HD or HDF treatment and spKtVgt12 within 6 months
7 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
8 The baseline diabetes management medication regimen has been stable within the past 2 weeks
Key exclusion criteria include
1 Hypoglycemia occurs more than 2 times in one month
2 History of ketoacidosis
3 Patients who are being treated with swiram and digoxin
4 Patients with acute kidney injury serum creatinine increased by 50 within 1 week 5 Abnormal liver function ALT 3 times the upper limit of normal value
6 Hemoglobin 80gL or 150gL 7 The blood pressure of patients with recent symptomatic hypotension is lower than 9060 mmHg 8 There is acute myocardial infarction stroke infection in the past month 9 There is systemic active infection or uncured tumor 10 The dialysis regimen of HD patients included HP treatment 11 Participating in other interventional clinical studies 12 Pregnant or lactating women 13 Other situations that the researcher thinks are not suitable for joining the study
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None