Phase I Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetic Characteristics, and Primary Efficacy of HSK39004 Suspension for Inhalation

Phase I Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetic and Pharmacodynamics Characteristics of HSK39004 Suspension for Inhalation.

To evaluate the safety, tolerability and pharmacokinetic characteristics of HSK39004 suspension for inhalation in single/multiple administration(s) in healthy subjects; to evaluate the safety,tolerability and efficacy of HSK39004 suspension for inhalation in multiple administrations in patients with Chronic Obstructive Pulmonary Disease（COPD）.

Study Overview

• Status: Completed
• Conditions: Healthy Donors
• Intervention / Treatment: Drug: HSK39004 in healthy; Drug: HSK39004; Drug: HSK39004 in COPD

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610044
      • West China Hospital of Sichuan University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• For healthy volenteers:

  1. Voluntarily sign the informed consent form, understand the trialprocedures, and be willing to comply with all trial procedures andrestrictions;
  2. 18 years to 45 years (inclusive), male and female;
  3. Male subjects weight ≥50 kg and female subjects weight ≥45 kg. Body mass index (BMI) : 18-26 kg/m2 (inclusive) ;
  4. Ability to perform acceptable and reproducible spirometry;
  5. Normal lung function during the screening period, no airway obstruction, FEV1 and forced vital capacity(FVC) are at least 80% of the predicted values;
  6. Subjects are willing to voluntarily use effectivecontraceptives from screening to at least 3 months after the last dose administration.

• For COPD patients:

  1. Voluntarily sign the informed consent form, understand the trialprocedures, and be willing to comply with all trial procedures andrestrictions;
  2. Age ≥ 40 years , male and female;
  3. According to the diagnostic criteria of 2024 Practical Edition of Guidelines , the patient was diagnosed with COPD; The patient has chronic respiratory symptoms such as shortness of breath, chronic cough or expectoration, and/or a history of exposure to risk factors, and the results of pulmonary function tests show that post-bronchodilator spirometry demonstrate FEV1/FVC ratio of ≤0.70 ;
  4. At screening: post-bronchodilator spirometry demonstrate FEV1/FVC ratio of ≤0.70 and FEV1 must be ≥40 % to ≤80% of predicted normal and FEV1 increased by ≥100ml compared with pre-bronchiectasis;
  5. No regular treatment of COPD was performed before joining the study. COPD agents (except SABA and/or SAMA) that are contraindicated in the protocol may be discontinued during the screening and treatment;
  6. Subjects are willing to voluntarily use effectivecontraceptives from screening to at least 3 months after the last dose administration.

Exclusion Criteria:

• For healthy volenteers:

  1. Have a history of severe and uncontrolled diseases, such ascardiovascular, respiratory, liver, gastrointestinal, endocrine,hematologic, mental/nervous systems diseases within 3 months prior to screening;
  2. Have a history of any malignant tumors;
  3. Normal or abnormal vital signs, physical examination, laboratory examination, electrocardiogram, and imageological examination have no clinical significance (only for healthy subjects);
  4. Previous or current gastrointestinal, liver, kidney, or other disease known to interfere with drug absorption, distribution, metabolism, or excretion;
  5. Acute respiratory infections occurred within 6 weeks before screening and/or before randomization;
  6. Have a history of high consumption of grapefruit juice, methylxanthinerich food or beverage (such as coffee, tea, cola, chocolate, energydrinks) ,consumption of grapefruit juice, methylxanthine-rich food within 48 hours before the administration;
  7. Smoking more than 5 cigarettes per day within 3 months prior toscreening or smoking during the study (only for healthy subjects);
  8. Average alcohol intake is more than 14 unit per week (1unit=10g alcohol , 1 unit=285 mL 4.9% alcohol beer, or 30 mL 40% alcohol spirit, or 100mL 12% alcohol wine) within the 3 months prior to screening;
  9. Have a history of drug abuse prior to screening, or positive urine drug screen at screening (If COPD patients were false positives due to other medications, they can be retested after the medication is washed);
  10. Blood donation (or blood loss) ≥400 mL within 3 months prior to the screening;
  11. Subjects who have a allergic to any component of HSK39004 or allergic history to opiates;
  12. Intolerance to this product or the same target drug;
  13. Subjects who use any live vaccine within 30 days prior to screening;
  14. Have participated in any clinical investigator within 3 months prior to screening;
  15. A pregnant/lactating woman, or has a positive pregnancy test at screening or during the trial;
  16. Not suitable for this study as judged by the investigator.

• For COPD patients, in addition to meeting the above exclusion criteria, they should also:

  1. Present with any of the following diseases: Alpha-1 antitrypsin deficiency, asthma, active pulmonary tuberculosis, lung cancer, pulmonary edema, cystic fibrosis, bronchiolitis obliterans, sarcoidosis (sarcoidosis), bronchiectasis, unstable sleep apnea, Or clinically significant pulmonary fibrosis, pulmonary hypertension, or interstitial lung disease determined by the study physician to be a safety risk to the patient and/or to affect the analysis of the study results;
  2. Previous or current history of serious cardiovascular disease;
  3. Have type 1 diabetes or poorly controlled type 2 diabetes (fasting blood glucose ≥10 mmol/L at screening);
  4. During the screening period, the investigators determined that the patient's laboratory tests had clinically significant abnormalities that could pose a safety risk to the patient;
  5. Patients who were hospitalized for COPD or infectious pneumonia within 8 weeks prior to screening and/or had acute exacerbations of COPD or infectious pneumonia between the screening period and prior to randomization, indicating the presence of an active infection;
  6. Patients with acute exacerbations of moderate to severe COPD ≥2 times/year within 1 year before screening;
  7. Acute exacerbations of COPD requiring treatment with oral or parenteral corticosteroids occurred within 8 weeks prior to screening;
  8. Had lung volume reduction surgery within 1 year prior to lung resection or screening;
  9. Patients who use oxygen therapy for long-trem and more than 12 hours per day;
  10. Not suitable for this study as judged by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: HSK39004; Placebo
Experimental: HSK39004 in healthy volenteers; Single or multiple inhaled HSK39004	Drug: HSK39004 in healthy; 1.5-12mg
Experimental: HSK39004 in COPD patients; multiple inhaled HSK39004	Drug: HSK39004 in COPD; 1.5-6mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
adverse events	The Incidence of adverse events as assessed by CTCAE v5.0	From the enrollment of the subjects to 72 hours after the last administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC	area under the concentration-time curve	from 0 to 72 hours after administration
Cmax	maximum plasma concentration	from 0 to 72 hours after administration
t1/2	half-life	from 0 to 72 hours after administration
Vz/F	apparent volume of distribution	from 0 to 72 hours after administration
CL/F	apparent clearance	from 0 to 72 hours after administration
Forced Expiratory Volume in the first second (FEV1) for patients with COPD	Mean Change From Baseline in Peak FEV1, Mean Change From Baseline FEV1 to Morning Trough FEV1	From 0 before first administration to 24 hours after last administration

Collaborators and Investigators

• Sponsor: Haisco Pharmaceutical Group Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): September 2, 2024
• Primary Completion (Actual): January 13, 2025
• Study Completion (Actual): March 20, 2025

Study Registration Dates

• First Submitted: December 31, 2024
• First Submitted That Met QC Criteria: March 24, 2025
• First Posted (Actual): April 2, 2025

Study Record Updates

• Last Update Posted (Actual): April 2, 2025
• Last Update Submitted That Met QC Criteria: March 24, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Respiratory Aspiration
• Other Study ID Numbers: HSK39004-101

Drug and device information, study documents

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