Phase 1 Study in Healthy Participants and Participants With Kidney Dysfunction

A Randomized, Double-blind, Placebo-controlled, Dose-escalation Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetic Characteristics, and the Impact of Food on Pharmacokinetics of HS-10398 in Healthy Participants, and a Clinical Trial to Assess the Pharmacokinetic Characteristics of HS-10398 in Participants With Kidney Dysfunction

A randomized, double-blind, placebo-controlled, dose-escalation clinical trial to evaluate the safety, tolerability, pharmacokinetic characteristics, and the impact of food on pharmacokinetics of oral HS-10398 in Chinese healthy participants, and a clinical trial to assess the pharmacokinetic characteristics of oral HS-10398 in Chinese participants with kidney dysfunction

Study Overview

• Status: Not yet recruiting
• Conditions: Healthy
• Intervention / Treatment: Drug: HS-10398; Drug: HS-10398 Placebo

Detailed Description

This is a phase 1, first-in-human, randomized, double-blind, placebo-controlled, dose-escalation clinical trial. The primary objective is to evaluate the safety, tolerability, and pharmacokinetic characteristics of single and multiple oral doses of HS-10398 in Chinese healthy participants. The secondary objective is to assess the impact of food on the pharmacokinetics of single oral doses of HS-10398 in Chinese healthy participants, as well as to evaluate the pharmacokinetic characteristics of oral HS-10398 in Chinese participants with kidney dysfunction.

• Study Type: Interventional
• Enrollment (Estimated): 116
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Yu Cao, PhD; Phone Number: +86 18661809090; Email: caoyu1767@126.com

Study Locations

• China
  • Qingdao, China
    • The affiliated hospital of Qingdao university
    • Contact: Xiaolei Zhang; Phone Number: 0532-82912611; Email: qingyilunli@126.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Healthy participants aged from 18 to 64 years
• Subjects need to fully understand the research content and process, as well as possible adverse reactions, and voluntarily signed Informed Consent Form
• Males' weight should be ≥ 50kg, and females' weight should be ≥ 45kg. Body mass index (BMI), calculated as weight/height^2 (kg/m^2), should be controlled within the range of 19 to 28, including the critical value
• Vaccination against Neisseria meningitidis and Streptococcus pneumoniae infection is required prior to the start of study treatment. If the patient has not been previously vaccinated, or if a booster is required, vaccine should be given according to local regulations at least 2 weeks prior to first study drug administration
• Participants with Kidney Dysfunction must have met the following additional criteria to be enrolled in this study：Patients with chronic kidney disease (defined as the presence of any markers of kidney damage or an estimated glomerular filtration rate (eGFR) persistently less than 90 mL/min/1.73m² for more than 3 months), and with an estimated glomerular filtration rate (eGFR) at screening and baseline assessments (with a minimum interval of 3 days between screening and baseline assessments) meeting the criteria of 60≤eGFR<90 mL/min/1.73m².

Exclusion Criteria:

• Has a history of chronic or serious disease from neuropsychiatric system, cardiovascular system, urinary system, digestive system, respiratory system, skeletal muscle system, metabolic endocrine system, skin disease, blood system, immune system or tumor
• Has taken any drugs, including prescription drugs, over-the-counter drugs, herbal preparations, some health products or inhibitor/inducer of CYP3A4/5 or CYP2C8 or any medications that inhibit P-glycoprotein transporters., within 2 weeks (or 5 half-lives) before screening and throughout the study period
• Has clinically significant ECG abnormalities, such as QT interval corrected according to Fridericia formula(QTcF), >450 ms (males), >470 ms (females)
• Has participated in another clinical trial involving drugs or medical devices within the month prior to screening and received investigational drugs or used medical devices, or within 5 half-lives of the investigational drugs from another trial at the time of screening, whichever is longer
• Unable to abstain from smoking and alcohol.
• History of drug dependence or substance abuse

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort1：HS-10398; SAD： HS-10398 capsule	Drug: HS-10398; SAD：HS-10398 capsule (5 predefined dose cohorts ) will be administered orally once on Day 1 MAD：HS-10398 capsule (5 predefined dose cohorts ) will be administered orally once or twice from Day 1 to Day 14 IRF：HS-10398 capsule will be administered orally once on Day 1 in Participants With Kidney Dysfunction
Placebo Comparator: Cohort2：HS-10398 Placebo; SAD：HS-10398 capsule placebo	Drug: HS-10398 Placebo; SAD：HS-10398 capsule placebo (5 predefined dose cohorts ) will be administered orally once on Day 1 MAD：HS-10398 capsule placebo (5 predefined dose cohorts ) will be administered orally once or twice from Day 1 to Day 14
Experimental: Cohort3：HS-10398; MAD： HS-10398 capsule	Drug: HS-10398; SAD：HS-10398 capsule (5 predefined dose cohorts ) will be administered orally once on Day 1 MAD：HS-10398 capsule (5 predefined dose cohorts ) will be administered orally once or twice from Day 1 to Day 14 IRF：HS-10398 capsule will be administered orally once on Day 1 in Participants With Kidney Dysfunction
Placebo Comparator: Cohort4：HS-10398 Placebo; MAD：HS-10398 capsule placebo	Drug: HS-10398 Placebo; SAD：HS-10398 capsule placebo (5 predefined dose cohorts ) will be administered orally once on Day 1 MAD：HS-10398 capsule placebo (5 predefined dose cohorts ) will be administered orally once or twice from Day 1 to Day 14
Experimental: Cohort5：HS-10398; HS-10398 capsule will be administered orally once on Day 1 in Participants With Kidney Dysfunction	Drug: HS-10398; SAD：HS-10398 capsule (5 predefined dose cohorts ) will be administered orally once on Day 1 MAD：HS-10398 capsule (5 predefined dose cohorts ) will be administered orally once or twice from Day 1 to Day 14 IRF：HS-10398 capsule will be administered orally once on Day 1 in Participants With Kidney Dysfunction

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of adverse events (AEs)	The definition of adverse event [AE] is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.	From screening to day 15
Serious adverse events (SAEs)	The definition of serious adverse event [SAE] is any untoward medical occurrence at any dose that results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; results in congenital anomaly/birth defect.	From screening to day 15

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Observed maximum plasma concentration (Cmax)	Cmax will be obtained following administration of a single oral dose of HS-10398	up to 216 hours after dosing
Time to reach maximum plasma concentration (Tmax)	Tmax will be obtained following administration of a single oral dose of HS-10398	up to 216 hours after dosing
Elimination Halflife (T1/2)	Elimination Halflife (T1/2) is the time measured for the concentration to decrease by one half which will be obtained following administration of a single oral dose of HS-10398	up to 216 hours after dosing
Apparent clearance（CL/F）	CL/F will be obtained following administration of a single oral dose of HS-10398	up to 216 hours after dosing
Apparent Volume of Distribution（Vd/F）	Vd/F will be obtained following administration of a single oral dose of HS-10398	up to 216 hours after dosing

Collaborators and Investigators

• Sponsor: Jiangsu Hansoh Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): May 31, 2024
• Primary Completion (Estimated): January 31, 2025
• Study Completion (Estimated): January 31, 2025

Study Registration Dates

• First Submitted: June 20, 2023
• First Submitted That Met QC Criteria: April 22, 2024
• First Posted (Actual): April 25, 2024

Study Record Updates

• Last Update Posted (Actual): April 25, 2024
• Last Update Submitted That Met QC Criteria: April 22, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Healthy; Phase 1; HS-10398
• Other Study ID Numbers: HS-10398-101

Drug and device information, study documents

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