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

NCT04324424 | Completed Phase 1

• 1 other identifier: HMM0110
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (10)

• The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of Cmax,u (if applicable)

  Up to 72 hours post-dose

• The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of AUClast,u (if applicable)

  Up to 72 hours post-dose

• The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of AUCinf,u (if applicable)

  Up to 72 hours post-dose

• The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of Tmax (if applicable)

  Up to 72 hours post-dose

• The single dose pharmacokinetics of HMS5552 will be described by estimating parameters of T1/2 (if applicable)

  Up to 72 hours post-dose

Study Arms (5)

Undialyzed ESRD subjects (P1)

EXPERIMENTAL

Part 1: Undialyzed end stage renal disease (ESRD) patients to receive a single dose of HMS5552 ( 25mg ) tablets orally .

Drug: HMS5552

Healthy volunteers (H)

EXPERIMENTAL

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

Severe renal impaired subjects (P2)

EXPERIMENTAL

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

Moderate renal impaired subjects (P3)

EXPERIMENTAL

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

Mild renal impaired subjects (P4)

EXPERIMENTAL

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

Interventions

HMS5552 DRUG

single dose of HMS5552 25mg

Healthy volunteers (H); Mild renal impaired subjects (P4); Moderate renal impaired subjects (P3); Severe renal impaired subjects (P2); Undialyzed ESRD subjects (P1)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For renal impaired subjects:
• Male and female subjects between ages of 18 and 65 years, no less than 3 subjects in each gender.
• Body weight≥50kg for male and ≥45kg for female； BMI: 18.5\~30 kg/m2
• 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；
• Normal physical conditions, vital signs,12 lead ECG and laboratory recording, blood potassium 3.5\~5.5mmol/L;
• Left ventricular ejection fraction (LVEF) ≥50%
• Willing to sign the informed consent form (ICF) and take reliable contraceptive measures within 6 months after taking the last dose of study drug;
• Willing to adhere to the protocol requirement.
• For healthy volunteers:
• Male and female subjects between ages of 18 and 65 years, no less than 3 subjects in each gender.
• Body weight≥50kg for male and ≥45kg for female； BMI: 18.5\~30 kg/m2
• MDRD eGFR: ≥90 mL/min/1.73 m2；
• Gender, age (±5 years) and BMI (±15%) matched with corresponding subject in P1 group
• Normal physical conditions, vital signs,12 lead ECG and laboratory recording
• Systolic pressure: 90～140 mmHg，diastolic pressure:50～90 mmHg；

You may not qualify if:

• Subjects with impaired renal function cannot be enrolled if they meet one of the following criteria:
• Acute renal failure;
• History of allergy;
• In addition to renal impaired function, investigators adjudicate subjects have diseases that may affect drug absorption, distribution, metabolism or excretion;
• Any other disease may receive treatment or surgery during the study
• Abnormal of ECG performance or laboratory recording;
• Family history of QT prolongation syndrome;
• 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;
• Hear failure (NYHA) class III or IV;
• Severe anemia, CHC\<6.0g/dl at screening;
• Severe infection, trauma, gastrointestinal operation or other surgery within 4 weeks before screening;
• History of a) Type 1 diabetes, b) Acute complications of diabetes;
• Serious hypoglycemia events within 3 months before screening;
• More than 5 cigarettes per day within 3 months before screening;

Sponsors & Collaborators

• Hua Medicine Limited: lead

Study Sites (1)

West China Hospital of Sichuan University

Chengdu, Sichuan, 610000, China

Location

Related Publications (1)

• 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.

  PMID: 34706161 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Dorzagliatin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Jia Miao, MD

  West China Hospital

  PRINCIPAL INVESTIGATOR

• Ping Fu, MD

  West China Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2020
• First Posted: March 27, 2020
• Study Start: April 23, 2019
• Primary Completion: September 30, 2019
• Study Completion: September 30, 2019
• Last Updated: March 27, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)