A Clinical Study to Access the Pharmacokinetics of HMS5552 in Renal Impaired Subjects and Healthy Volunteers

An Open-Label, Paralleled Study of the Pharmacokinetics of HMS5552 Following a Single Oral Dose in Renal Impaired Subjects and Matched Healthy Volunteers

The objectives of this study is to access the pharmacokinetics and safety of HMS5552 in single dose in renal impaired subjects and matched healthy adult subjects.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: HMS5552

Detailed Description

This is an open-label and paralleled study with single oral dose of HMS5552 given to renal impaired subjects and body index matched healthy volunteers.

The primary objective is to access the pharmacokinetic profiles of HMS5552 in 25 mg dose in renal impaired subjects and (gender, age and BMI) matched healthy adult subjects.

The secondary objective is to characterize the safety profiles of HMS5552 in single dose in renal impaired subjects.

The subjects include ESRD subjects without dialysis (P1 group), severe (P2 group), moderate (P3 group), mild (P4 group), and healthy subjects (H Group) matched with renal impairment subjects in gender, age and BMI. The number of subjects in each group was 6-8.

The study is divided into two parts:

• Part 1: ESRD subjects without dialysis and matched healthy subjects (P1 and H groups; n = 8 for each group);
• Part 2: subjects with severe, moderate and mild renal impairment (P2, P3 and P4 groups; n = 6-8 in each group).

The study initiates from Part 1. The data will be evaluated at the end of Part 1 as the medium term. Compared with the matched healthy subjects, if the mean AUC of HMS5552 (either AUClast or AUCinf) increased by ≥ 100% in ESRD subjects without dialysis, which means Part 2 will need to be conducted. The process of Part 2 is the same as that of Part 1

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610000
      • West China Hospital of Sichuan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• For renal impaired subjects:

  1. Male and female subjects between ages of 18 and 65 years, no less than 3 subjects in each gender.
  2. Body weight≥50kg for male and ≥45kg for female； BMI: 18.5~30 kg/m2
  3. eGFR: P1 < 15 mL/min/1.73 m2；P2: 15～29 mL/min/1.73 m2；P3: eGFR 30～59 mL/min/1.73 m2；P4: 60～89 mL/min/1.73 m2，and ACR≥ 3 mg/mmol；
  4. Normal physical conditions, vital signs,12 lead ECG and laboratory recording, blood potassium 3.5~5.5mmol/L;
  5. Left ventricular ejection fraction (LVEF) ≥50%
  6. Willing to sign the informed consent form (ICF) and take reliable contraceptive measures within 6 months after taking the last dose of study drug;
  7. Willing to adhere to the protocol requirement.

• For healthy volunteers:

  1. Male and female subjects between ages of 18 and 65 years, no less than 3 subjects in each gender.
  2. Body weight≥50kg for male and ≥45kg for female； BMI: 18.5~30 kg/m2
  3. MDRD eGFR: ≥90 mL/min/1.73 m2；
  4. Gender, age (±5 years) and BMI (±15%) matched with corresponding subject in P1 group
  5. Normal physical conditions, vital signs,12 lead ECG and laboratory recording
  6. Systolic pressure: 90～140 mmHg，diastolic pressure:50～90 mmHg；
  7. Willing to sign the informed consent form (ICF) and take reliable contraceptive measures within 6 months after taking the last dose of study drug;
  8. Willing to adhere to the protocol requirement.

Exclusion Criteria:

• Subjects with impaired renal function cannot be enrolled if they meet one of the following criteria:

  1. Acute renal failure;
  2. History of allergy;
  3. In addition to renal impaired function, investigators adjudicate subjects have diseases that may affect drug absorption, distribution, metabolism or excretion;
  4. Any other disease may receive treatment or surgery during the study
  5. Abnormal of ECG performance or laboratory recording;
  6. Family history of QT prolongation syndrome;
  7. Have unstable cardiovascular disease, lung disease, gastrointestinal disease, liver disease, blood disease, mental disease, nervous system disease, immune deficiency disease or any malignant tumor;
  8. History of cardiovascular and cerebrovascular disease;
  9. Hear failure (NYHA) class III or IV;
  10. Severe anemia, CHC<6.0g/dl at screening;
  11. Severe infection, trauma, gastrointestinal operation or other surgery within 4 weeks before screening;
  12. History of a) Type 1 diabetes, b) Acute complications of diabetes;
  13. Serious hypoglycemia events within 3 months before screening;
  14. More than 5 cigarettes per day within 3 months before screening;
  15. Alcohol addicts;
  16. History of drug abuse;

• Healthy subjects cannot be enrolled if they meet one of the following criteria:

  1. History of allergy;
  2. Investigators adjudicate subjects have diseases that may affect drug absorption, distribution, metabolism or excretion;
  3. Any other disease may receive treatment or surgery during the study
  4. Abnormal of ECG performance or laboratory recording;
  5. Family history of QT prolongation syndrome;
  6. Have unstable cardiovascular disease, lung disease, gastrointestinal disease, liver disease, blood disease, mental disease, nervous system disease, immune deficiency disease or any malignant tumor; history of cardiovascular and cerebrovascular disease within 6 months before screening; severe infection, trauma, gastrointestinal operation or other surgery within 4 weeks before screening;
  7. Anemia caused by any reason;
  8. History of hypoglycemia (<3.9mmol/L);
  9. More than 5 cigarettes per day within 3 months before screening;
  10. Alcohol addicts;
  11. History of drug abuse;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Undialyzed ESRD subjects (P1); Part 1: Undialyzed end stage renal disease (ESRD) patients to receive a single dose of HMS5552 ( 25mg ) tablets orally .	Drug: HMS5552; single dose of HMS5552 25mg
EXPERIMENTAL: Healthy volunteers (H); Part 1: Matched healthy volunteers to receive a single dose of HMS5552 ( 25mg ) tablets orally Matching principle: H group and P1 group: 1:1 . The matched subjects should be in the same gender, age difference ±5 years, BMI difference ±15%	Drug: HMS5552; single dose of HMS5552 25mg
EXPERIMENTAL: Severe renal impaired subjects (P2); Part 2：Severe renal impaired subjects to receive a single dose of HMS5552 ( 25mg ) tablets orally Matching principle: P2 group and H group: 1:1 . The matched subjects should be in the same gender, age difference ±5 years, BMI difference ±15%	Drug: HMS5552; single dose of HMS5552 25mg
EXPERIMENTAL: Moderate renal impaired subjects (P3); Part 2：Moderate renal impaired subjects to receive a single dose of HMS5552 ( 25mg ) tablets orally Matching principle: P3 group and H group: 1:1 . The matched subjects should be in the same gender, age difference ±5 years, BMI difference ±15%	Drug: HMS5552; single dose of HMS5552 25mg
EXPERIMENTAL: Mild renal impaired subjects (P4); Part 2：Mild renal impaired subjects to receive a single dose of HMS5552 ( 25mg ) tablets orally Matching principle: P4 group and H group: 1:1 . The matched subjects should be in the same gender, age difference ±5 years, BMI difference ±15%	Drug: HMS5552; single dose of HMS5552 25mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of Cmax	Plasma will be collected at predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hour post-dose.	Up to 72 hours post-dose
The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of AUClast	Plasma will be collected at predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hour post-dose.	Up to 72 hours post-dose
The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of AUCinf	Plasma will be collected at predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hour post-dose.	Up to 72 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of Cmax,u (if applicable)	Plasma will be collected at predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hour post-dose. Urine will be collected at predose, 0 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 36, 36 to 48, and 48 to 72 hour post-dose.	Up to 72 hours post-dose
The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of AUClast,u (if applicable)	Plasma will be collected at predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hour post-dose. Urine will be collected at predose, 0 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 36, 36 to 48, and 48 to 72 hour post-dose.	Up to 72 hours post-dose
The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of AUCinf,u (if applicable)	Plasma will be collected at predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hour post-dose. Urine will be collected at predose, 0 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 36, 36 to 48, and 48 to 72 hour post-dose.	Up to 72 hours post-dose
The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of Tmax (if applicable)	Plasma will be collected at predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hour post-dose. Urine will be collected at predose, 0 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 36, 36 to 48, and 48 to 72 hour post-dose.	Up to 72 hours post-dose
The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of T1/2 (if applicable)	Plasma will be collected at predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hour post-dose. Urine will be collected at predose, 0 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 36, 36 to 48, and 48 to 72 hour post-dose.	Up to 72 hours post-dose
The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of CL/F (if applicable)	Plasma will be collected at predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hour post-dose. Urine will be collected at predose, 0 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 36, 36 to 48, and 48 to 72 hour post-dose.	Up to 72 hours post-dose
The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of Vz/F (if applicable)	Plasma will be collected at predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hour post-dose. Urine will be collected at predose, 0 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 36, 36 to 48, and 48 to 72 hour post-dose.	Up to 72 hours post-dose
The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of fu (if applicable)	Plasma will be collected at predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hour post-dose. Urine will be collected at predose, 0 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 36, 36 to 48, and 48 to 72 hour post-dose.	Up to 72 hours post-dose
The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of Ae (if applicable)	Plasma will be collected at predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hour post-dose. Urine will be collected at predose, 0 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 36, 36 to 48, and 48 to 72 hour post-dose.	Up to 72 hours post-dose
The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of CLr (if applicable)	Plasma will be collected at predose, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hour post-dose. Urine will be collected at predose, 0 to 4, 4 to 8, 8 to 12, 12 to 24, 24 to 36, 36 to 48, and 48 to 72 hour post-dose.	Up to 72 hours post-dose

Collaborators and Investigators

• Sponsor: Hua Medicine Limited
• Investigators: Principal Investigator: Ping Fu, MD, West China Hospital

Publications and helpful links

General Publications

• Miao J, Fu P, Ren S, Hu C, Wang Y, Jiao C, Li P, Zhao Y, Tang C, Qian Y, Yang R, Dong Y, Rong J, Wang Y, Jin X, Sun Y, Chen L. Effect of renal impairment on the pharmacokinetics and safety of dorzagliatin, a novel dual-acting glucokinase activator. Clin Transl Sci. 2022 Feb;15(2):548-557. doi: 10.1111/cts.13174. Epub 2021 Nov 11.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 23, 2019
• Primary Completion (ACTUAL): September 30, 2019
• Study Completion (ACTUAL): September 30, 2019

Study Registration Dates

• First Submitted: March 23, 2020
• First Submitted That Met QC Criteria: March 25, 2020
• First Posted (ACTUAL): March 27, 2020

Study Record Updates

• Last Update Posted (ACTUAL): March 27, 2020
• Last Update Submitted That Met QC Criteria: March 25, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: HMM0110

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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