A Study of the Pharmacokinetics, Pharmacodynamics, and Safety of Rongliflozin in Type 2 Diabetic Subjects With Renal Impairment

Study Overview
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Brief Summary
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To evaluate the pharmacokinetic characteristics of pyroglutamate rongliflozin capsules in type 2 diabetic subjects with normal renal function and mild to moderate renal impairment.

Official Title
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A Phase I Study of the Pharmacokinetics/Pharmacodynamics and Safety of Rongliflozin in Chinese Subjects With Type 2 Diabetes With Normal Renal Function and Mild to Moderate Renal Impairment

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: pyroglutamate rongliflozin capsules


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes patients. The subject is willing to take effective contraceptive measures without a pregnancy plan within 4 weeks after signing the informed consent form to taking the test drug. When screening, 19.0 kg/m2 < or = body mass index (BMI) < or = 35.0 kg/m2. No hypoglycemic drugs have been used in the 4 weeks before the baseline period, or stable doses of hypoglycemic drugs are being used. No medications for other comorbidities or stable medication regimens within 4 weeks before the baseline period. In the screening period, 6.5% < or = glycosylated hemoglobin < or =11.0%, and fasting blood glucose < or = 13.9 mmol/L. Glomerular filtration rate (eGFR) > or = 90 mL/min/1.73m2 estimated according to the modified dietary trial for kidney disease (MDRD) formula (only applicable to patients with type 2 diabetes with normal renal function). Accompanied by mild or moderate renal impairment, the eGFR calculated according to the MDRD formula meets the following criteria: mild renal impairment: 60 89 mL/min/1.73m2, moderate renal impairment: 30 59 mL/min/ 1.73m2 (only for patients with type 2 diabetes with impaired renal function). Accompanied by mild or moderate renal impairment, accompanied by stable disease in the first 3 months of the baseline period (only applicable to patients with type 2 diabetes with renal impairment). Exclusion Criteria: Known allergy to sodium-glucose cotransporter 2 (SGLT2) inhibitor drugs or related excipients. In the 3 months before screening, those who smoked more than 5 cigarettes per day on average or who could not give up smoking from signing informed consent to leaving the group. Have a history of alcoholism. Ingested any food or drink containing caffeine, xanthine, alcohol, grapefruit within 48 hours before taking the test drug. Those who donate blood or lose a lot of blood (>400 mL) within 3 months before taking the test drug, or have a history of blood transfusion within 1 month before screening, or plan to donate blood within 1 month after the end of the trial. Those who have taken the trial drug or such drugs within 1 month before taking the trial drug, or participated in the clinical trial of any drug or medical device within 3 months before screening. Those who have a positive urine drug screen or have a history of drug abuse or drug use in the past 5 years. The subject is breastfeeding or the serum pregnancy test result is positive. Subjects had undergone surgery within 1 month before screening, or major surgery was planned during the study period. Have severe mental illness or language barrier, unwilling or unable to fully understand and cooperate. History or evidence of other diseases, such as history of repeated urinary tract infections, poorly controlled high blood pressure, type I diabetes, urinary incontinence, etc. Abnormal laboratory tests, such as a) Alanine transaminase (ALT)/Aspartate aminotransferase (AST)>2.0×UNL and/or total bilirubin>1.5×UNL; b) hemoglobin <100 g/L; c) hepatitis B surface antigen positive, hepatitis C antibody positive, HIV antibody positive , Syphilis antibody positive. The researcher believes that the subject has any situation that may interfere with the interpretation of the pharmacokinetics, efficacy and safety data of this study. Subjects considered by the researcher to be unsuitable to participate in this trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group A and C (normal kidney function)<br>Each subject will receive a single dose of rongliflozin on Day 1 | Drug: pyroglutamate rongliflozin capsules<br>* Subjects will receive one 50mg capsule orally (by mouth) on Day 1<br>|
| Experimental: Group B (mild renal impairment)<br>Each subject will receive a single dose of rongliflozin on Day 1 | Drug: pyroglutamate rongliflozin capsules<br>* Subjects will receive one 50mg capsule orally (by mouth) on Day 1<br>|
| Experimental: Group D (moderate renal impairment)<br>Each subject will receive a single dose of rongliflozin on Day 1 | Drug: pyroglutamate rongliflozin capsules<br>* Subjects will receive one 50mg capsule orally (by mouth) on Day 1<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentrations of rongliflozin | Plasma concentrations of rongliflizin following the administration of a single dose of rongliflozin, the pharmacokinetic parameters for rongliflozin will be measured in varying degrees of kidney function. | 0 hour（pre-dose） to 96 hours after administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in 24-hour urine glucose excretion in varying degrees of kidney function | Change from baseline in 24-hour urine glucose excretion following the administration of a single dose of rongliflozin will be used to evaluate the pharmacodynamics of rongliflozin (ie, how the drug affects the body) in varying degrees of kidney function. | Day -1 (Baseline) to Day 5 |