Safety, Tolerability,PK/PD, Food Effect of Single and Multiple Ascending Doses of HSK31858 in Healthy Volunteers

NCT05663593 | Completed Phase 1

• 1 other identifier: HSK31858-102
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase I, randomised, double-blind placebo-controlled, 2-part study to assess the safety, tolerability, pharmacokinetics, pharmacodynamics and food effect of single and multiple oral doses of HSK31858 in healthy volunteers

Conditions

Healthy Volunteers

Keywords

HSK31858; NCFBE; phase I

Outcome Measures

Primary Outcomes (2)

• The number and severity of treatment emergent adverse events (TEAEs)

  To assess the safety and tolerability of single oral dose of HSK31858 in healthy volunteers

  7 days after single dose

• The number and severity of treatment emergent adverse events (TEAEs)

  To assess the safety and tolerability of multiple oral dose of HSK31858 in healthy volunteers

  56 days after multiple dose

Secondary Outcomes (5)

• Cmax

  within 30 minutes before administration until 72 hours after administration

• Tmax

  within 30 minutes before administration until 72 hours after administration

• AUC0-last

  within 30 minutes before administration until until 72 hours after administration

• t½

  within 30 minutes before administration until 72 hours after administration

• Absolute neutrophil count (ANC) normalized relative neutrophil elastase (NE) Activity

  within 30 minutes before administration until until 56 days after administration

Study Arms (2)

HSK31858

EXPERIMENTAL

Single or multiple oral doses of HSK31858 Tablet, orally once daily

Drug: HSK31858, tablet

Placebo

PLACEBO COMPARATOR

Matching placebo Tablet, orally once daily

Drug: Placebo, tablet

Interventions

HSK31858, tablet DRUG

Starting dose in single ascending dose: 5 mg

HSK31858

Placebo, tablet DRUG

Matching placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Must have given written informed consent before any study-related activities are carried out and must be able to understand the full nature and purpose of the trial, including possible risks and adverse effects.
• Adult males and females, 18 to 45 years of age (inclusive) at Screening.
• Body mass index ≥ 18.0 and ≤ 28.0 kg/m2, with a body weight ≥ 45 kg at Screening.
• Be nonsmokers (including tobacco, e-cigarettes, and marijuana) for at least 1 month prior to first study drug administration.
• Medically healthy without clinically significant abnormalities at Screening and predose on Day 1.
• Conventional 12-lead ECG recording in triplicate (the mean of triplicate measurements will be used to determine eligibility at Screening and predose on Day 1) consistent with normal cardiac conduction and function.

You may not qualify if:

• History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic or neurological disease, including any acute illness or surgery within the past 3 months determined by the PI to be clinically relevant.
• Subjects has increased risk of infection:
• History and/or presence of tuberculosis (TB).
• Body temperature of \> 37.7℃.
• Blood neutrophil count \<1.5 × 109/L, or white blood cell count \<3.5×109/L (Screening and Day -1).
• Is in high risk-group (i.e., men who have had unprotected sex with men, women who have had sex without a condom with men who have sex with men, people who have had sex without a condom with a person who has lived or travelled in Africa, people who inject drugs, people who have had sex without a condom with somebody who has injected drugs, people who have caught another sexually transmitted infection, people who have received a blood transfusion while in Africa, eastern Europe, the countries of the former Soviet Union, Asia or central and southern America) for human immunodeficiency virus (HIV) infection within the last 6 months.
• Other latent or chronic infections (e.g., recurrent sinusitis, genital or ocular herpes, urinary tract infection) or at risk of infection (surgery, trauma, or significant infection) within 3 months of Screening, or history of skin abscesses within 3 months of Screening.
• Clinically significant lower respiratory tract infection not resolved within 4weeks prior to Screening, as determined by the PI.
• Volunteers with active malignancy or neoplastic disease in the previous 5 years other than superficial basal cell carcinoma.
• Disease history suggesting abnormal immune function or use of or plans to use systemic immunosuppressive (e.g., corticosteroids, methotrexate, azathioprine, cyclosporine) or immunomodulating medications (e.g., interferon) during the study or within 4 months prior to the first study drug administration.
• Some subjects lacking functional Dipeptidyl peptidase 1 (DPP1) enzyme have been described to have periodontitis and palmoplantar hyperkeratosis:
• Subjects with signs of current gingivitis/periodontitis. Gingival evaluation (by inspection) will be performed by a dental hygienist or trained study physician.
• Subjects with a history of hyperkeratosis or erythema in palms or soles.
• Liver function test results (i.e., aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\], and gamma glutamyl transferase \[GGT\]) and total bilirubin elevated more than 1.5 fold above the ULN.
• Hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCVAb), syphilis antibody and human immunodeficiency virus (HIV) antibody test are positive at screening.

Sponsors & Collaborators

• Haisco Pharmaceutical Group Co., Ltd.: lead

Study Sites (1)

PKUCare Luzhong Hospital

Zibo, Shang Dong, 255400, China

Location

Related Publications (1)

• Wang Y, Yu C, Hu M, Wang L, Chen M, Liu H, Wu N, Hou J. Safety, tolerability, pharmacokinetics and pharmacodynamics of HSK31858, a novel oral dipeptidyl peptidase-1 inhibitor, in healthy volunteers: An integrated phase 1, randomized, double-blind, placebo-controlled, single- and multiple-ascending dose study. Br J Clin Pharmacol. 2025 Aug;91(8):2262-2272. doi: 10.1002/bcp.70027. Epub 2025 Apr 2.

  PMID: 40170587 DERIVED

MeSH Terms

Interventions

Tablets

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Study Officials

• Jie Hou

  Peking University Care Luzhong Hospital

  PRINCIPAL INVESTIGATOR

• Hong Wang

  Peking University Care Luzhong Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2022
• First Posted: December 23, 2022
• Study Start: February 23, 2022
• Primary Completion: August 15, 2022
• Study Completion: November 30, 2022
• Last Updated: December 23, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)