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

Study Overview
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Brief Summary
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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

Official Title
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A 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
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Healthy Volunteers

Intervention / Treatment
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* Drug: HSK31858, tablet
* Drug: Placebo, tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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. Presence or having sequelae of gastrointestinal, liver, kidney, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs. History of alcohol abuse within 12 months prior to first study drug administration or positive alcohol breath test. Regular alcohol consumption defined as > 21 alcohol units per week (where 1 unit = 284 mL of beer, 25 mL of 40% spirit or a 125 mL glass of wine). Use of any prescription or over-the-counter medication (including herbal products, diet aids, and hormone supplements) within 14 days or 5 half-lives of the medication (whichever is longer) prior to the first study drug administration, except occasional use of paracetamol. Use of any IP or investigational medical device within 30 days prior to Screening, or 5 half-lives of the product (whichever is the longest). Donation of blood or plasma within 30 days prior to first study drug administration, or loss of whole blood of more than 500 mL within 30 days prior to randomization, or receipt of a blood transfusion within 1 year of first study drug administration. Participation in another investigational clinical trial within 60 days prior to the first study drug administration. 19. Pregnant or lactating at Screening or planning to become pregnant (self or partner) at any time during the study, including the Follow-up period.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HSK31858<br>Single or multiple oral doses of HSK31858 Tablet, orally once daily | Drug: HSK31858, tablet<br>* Starting dose in single ascending dose: 5 mg<br>|
| Placebo Comparator: Placebo<br>Matching placebo Tablet, orally once daily | Drug: Placebo, tablet<br>* Matching placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Maximum concentration | within 30 minutes before administration until 72 hours after administration | 
| Tmax | Time to maximum concentration | within 30 minutes before administration until 72 hours after administration | 
| AUC0-last | Area under the drug concentration-time curve, from time 0h to 72h | within 30 minutes before administration until until 72 hours after administration | 
| t½ | Apparent terminal half-life | within 30 minutes before administration until 72 hours after administration | 
| Absolute neutrophil count (ANC) normalized relative neutrophil elastase (NE) Activity | Assessed NE activity changes in multiple doses | within 30 minutes before administration until until 56 days after administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HSK31858, NCFBE, phase I