A Study to Evaluate the Pharmacokinetics of HSK16149 in Subjects With Renal Impairment

This is an open-label, single-dose study to evaluate the pharmacokinetics and safety of HSK16149 in subjects with mild, moderate and severe renal impairment compared to the matched control subjects with normal renal function.

Study Overview

• Status: Completed
• Conditions: Renal Impairment
• Intervention / Treatment: Drug: HSK16149

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Subjects with renal impairment(RI):

  1. Voluntarily sign the informed consent form, understand the trial procedures, and be willing to comply with all trial procedures and restrictions;
  2. 18 years to 75 years (inclusive), male and female;
  3. Male subjects weight ≥50 kg and female subjects weight ≥45 kg. Body mass index (BMI) : 18-30 kg/m2 (inclusive) (BMI= weight (kg)/height2 (m^2));
  4. Subjects with medically stable RI until study completion corresponding to the classifications of Renal Function based on GFR: mild RI: 60≤GFR<90 mL/min; moderate RI: 30≤GFR<60 mL/min, severe RI:15≤GFR<30 mL/min;
  5. Physical examination, vital sign measurements, 12-lead electrocardiogram (ECG), and clinical laboratory tests results were deemed appropriate by the investigator;
  6. Not in use of any drug within 2 weeks prior to screening, except for the medication necessary for RI/ other comorbidities (last more than four weeks in good compliance);
  7. Subjects (including partners) are willing to voluntarily use effective contraceptives from screening to at least 6 months after the last dose administration.

• Subjects with normal renal function :

  1. Voluntarily sign the informed consent form, understand the trial procedures, and be willing to comply with all trial procedures and restrictions;
  2. 18 years to 75 years (inclusive), male and female, age and sex must be matched with subjects with RI;
  3. Male subjects weight ≥50 kg and female subjects weight ≥45 kg, weight must be matched with subjects with RI. Body mass index (BMI) : 18-30 kg/m^2 (inclusive) (BMI= weight (kg)/height2 (m^2));
  4. 90≤GFR<130 mL/min;
  5. Physical examination, vital sign measurements, 12-lead electrocardiogram (ECG), and clinical laboratory tests results were deemed appropriate by the investigator;
  6. Not in use of any drug within 2 weeks prior to screening, except for the medication necessary for comorbidities (last more than four weeks in good compliance);
  7. Subjects (including partners) are willing to voluntarily use effective contraceptives from screening to at least 6 months after the last dose administration.

Exclusion Criteria:

1. Allergic to any component in HSK16149 capsules;
2. Uncontrolled or unstable cardiovascular, respiratory, liver, gastrointestinal tract, endocrine, blood, mental/nervous, etc.Systemic diseases;
3. Those who have committed suicide or suicidal tendency in the past, or those who have recurrent dizziness, headache, memory and cognitive impairment;
4. According to the researcher's judgment, there are factors that affect the absorption, distribution, metabolism and excretion of drugs, such as diseases, drugs, surgery, etc.; Taking Niaoduqing granules, the stool is irregular or shapeless;
5. Acute renal failure;
6. Smoking more than 5 cigarettes a day on average in the 3 months before screening or unable to stop using any tobacco products during the test period;
7. Drinking more than 14 units per week within 3 months before screening (1 unit = 17.7 mL ethanol, that is, 1 unit =357 mL beer with 5% alcohol content, 43 mL white wine with 40% alcohol content or 147 mL wine with 12% alcohol content), or those who can't ban alcohol during the test, or those who are positive in alcohol breath test;
8. Have a history of drug abuse within 5 years before screening, or have a positive drug abuse screening;
9. Those who have ingested beverages or foods rich in xanthine (coffee, tea, chocolate, etc.) or grapefruit for a long time in the past, or have taken any products rich in xanthine or grapefruit orally within 48 hours before administration;
10. Those who have participated in any clinical trials of drugs or medical devices within 3 months before screening (subject to administration).
11. The amount of blood donation (or blood loss) within 3 months before screening is ≥400 mL, or those who have received blood products to improve anemia;
12. One of ALT and/or AST >2*ULN, total bilirubin > 1.5* ULN and creatine kinase > 2*ULN during screening;
13. Those who are positive for hepatitis B surface antigen, hepatitis C virus antibody, human immunodeficiency virus antibody and treponema pallidum antibody;
14. Female subjects who are pregnant or lactating or whose serum pregnancy results are positive during the screening period or during the trial;
15. Subjects considered by the researcher to have any factors that are not suitable for participating in this trial.

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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mild Renal Impairment	Drug: HSK16149; single oral adminiatration, 20mg
Experimental: Moderate Renal Impairment	Drug: HSK16149; single oral adminiatration, 20mg
Experimental: Severe Renal Impairment	Drug: HSK16149; single oral adminiatration, 20mg
Experimental: Normal Renal function	Drug: HSK16149; single oral adminiatration, 20mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	The maximun plasma concentration of HSK16149	From the start to 72 hours after administration
AUC0-t	Area under the concentration-time curve from time zero to time of last quantifiable concentration	From the start to 72 hours after administration
AUC0-inf	Area under the concentration-time curve from time zero extrapolated to infinite time	From the start to 72 hours after administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tmax	Time of maximum concentration	From the start to 72 hours after administration
Vz	Volume of distribution associated with the terminal phase	From the start to 72 hours after administration
CL	Plasma clearance	From the start to 72 hours after administration
Ae	Cumulative urinary recovery of unchanged drug	From the start to 72 hours after administration
Fe	Cumulative urinary recovery fraction of unchanged drug	From the start to 72 hours after administration
CLr	Renal clearance	From the start to 72 hours after administration
t1/2	half-life	From the start to 72 hours after administration

Collaborators and Investigators

• Sponsor: Haisco Pharmaceutical Group Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2022
• Primary Completion (Actual): February 27, 2023
• Study Completion (Actual): April 26, 2023

Study Registration Dates

• First Submitted: June 14, 2023
• First Submitted That Met QC Criteria: June 14, 2023
• First Posted (Actual): June 23, 2023

Study Record Updates

• Last Update Posted (Actual): June 23, 2023
• Last Update Submitted That Met QC Criteria: June 14, 2023
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Renal Insufficiency
• Other Study ID Numbers: HSK16149-104

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No