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

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

The objectives of this study is to access the pharmacokinetics and safety of HMS5552 in single dose in mild and moderate hepatic 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 hepatic impaired subjects and matched healthy volunteers.

The primary objective is to access the pharmacokinetic profiles of HMS5552 in 25 mg dose in hepatic 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 hepatic impaired subjects.

The subjects include mild hepatic impaired subjects (A group), moderate hepatic impaired subjects (B group), and healthy subjects (C Group) matched with hepatic impaired subjects in gender, age and BMI. The number of subjects in each group was no less than 8, and no less than 3 subjects in each gender.

• Study Type: Interventional
• Enrollment (Actual): 25
• 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: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• For hepatic 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. ALT>2×normal upper limit (ULN), or TBiL>1.5×ULN, or diagnosed cirrhosis. The related clinical manifestations have been stable for 4-12 weeks, and Child-Pugh score is in grade A or B:

     A= mild liver damage (Group A): Child-Pugh 5-6; B= moderate liver damage (Group B): Child-Pugh 7-9;

  4. Willing to sign the informed consent form (ICF) and take reliable contraceptive measures within 6 months after taking the last dose of study drug;
  5. 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. Gender, age (±5 years) and BMI (±15%) matched with corresponding subject in hepatic impaired group;
  4. Normal physical conditions, vital signs,12 lead ECG and laboratory recording;
  5. Willing to sign the informed consent form (ICF) and take reliable contraceptive measures within 6 months after taking the last dose of study drug;
  6. Willing to adhere to the protocol requirement.

Exclusion Criteria:

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

  1. Liver cancer, liver transplantation, liver failure, autoimmune liver disease, biliary cirrhosis, or drug-induced liver damage;
  2. History of allergy;
  3. Investigators adjudicate subjects have surgery that may affect drug absorption, distribution, metabolism or excretion;
  4. In addition to diseases and complications of impaired hepatic function, investigator adjudicate subjects have clinically meaningful or unstable diseases or complications of central nervous system, cardiovascular system, digestive system, endocrine system, respiratory system, urinary system, blood system, mental disease, or malignant tumor, etc;
  5. Abnormal of ECG performance or laboratory recording during screening;
  6. Family history of QT prolongation syndrome;
  7. History of hepatic encephalopathy or hepatic coma within 6 months before screening;
  8. More than 5 cigarettes per day within 3 months before screening;
  9. Alcohol addicts;
  10. 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 surgery that may affect drug absorption, distribution, metabolism or excretion;
  3. Investigator adjudicate subjects have clinically meaningful or unstable diseases or complications of central nervous system, cardiovascular system, digestive system, endocrine system, respiratory system, urinary system, blood system, mental disease, or malignant tumor, etc;
  4. Abnormal of ECG performance or laboratory recording during screening;
  5. Family history of QT prolongation syndrome;
  6. Severe infection, severe trauma or major surgery judged by investigator within 3 months before screening;
  7. More than 5 cigarettes per day within 3 months before screening;
  8. Alcohol addicts;
  9. History of drug abuse

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mild hepatic impaired subjects (A); Mild hepatic impaired subjects: to receive a single dose of HMS5552 ( 25mg ) tablet orally	Drug: HMS5552; single dose of HMS5552 25mg
Experimental: Moderate hepatic impaired subjects (B); Moderate hepatic impaired subjects: to receive a single dose of HMS5552 ( 25mg ) tablet orally	Drug: HMS5552; single dose of HMS5552 25mg
Experimental: Healthy volunteers (C); Matched healthy volunteers: to receive a single dose of HMS5552 ( 25mg ) tablet orally	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	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,u	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,u	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 Tmax ;	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 T1/2;	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 CL/F;	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 Vz/F;	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 fu;	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

Collaborators and Investigators

• Sponsor: Hua Medicine Limited

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2019
• Primary Completion (Actual): July 3, 2020
• Study Completion (Actual): July 3, 2020

Study Registration Dates

• First Submitted: June 8, 2020
• First Submitted That Met QC Criteria: June 8, 2020
• First Posted (Actual): June 11, 2020

Study Record Updates

• Last Update Posted (Actual): November 29, 2022
• Last Update Submitted That Met QC Criteria: November 28, 2022
• Last Verified: June 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: HMM0109

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