A Study to Evaluate Safety, Tolerability and Pharmacokinetics of RSN0402 in Healthy Volunteers

Last updated: July 4, 2024
Sponsor: Shenzhen Resproly Biopharmaceutical Co., Ltd
Overall Status: Active - Recruiting

Phase

1

Condition

Cystic Fibrosis

Lung Injury

Idiopathic Pulmonary Fibrosis

Treatment

Placebo

RSN0402 Part 1

RSN0402 Part 2

Clinical Study ID

NCT06482190
RES-RSN0402-P1
  • Ages 18-60
  • All Genders
  • Accepts Healthy Volunteers

Study Summary

This is a phase 1, randomized, First in Human (FIH), double-blinded, placebo-controlled study to assess the safety, tolerability, and PK of RSN0402 in healthy volunteers. A total of about 72 participants are expected to be enrolled.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Participant is overtly healthy or has no clinically significant condition asdetermined by PI/Sub-Investigator including medical history, vital signs, ECG,laboratory tests, and physical examination at Screening and admission (Day -2 andDay -1).

  2. Participant has normal lung function assessment with FEV1 of at least 80% of thepredicted value and FEV1/FVC ratio of > 0.7 measured at Screening.

  3. Availability to participate voluntarily for the entire study duration and willing toadhere to all protocol requirements.

  4. Participant must be 18 to 60 years of age inclusive, at the time of signing theinformed consent.

  5. Male participant with body weight of ≥ 50.0 kg, female participant with body weight ≥ 45.0 kg; males or females with body mass index (BMI) of ≥ 18 to < 30.0 kg/m² atscreening.

  6. Female participants of childbearing potential must have a negative serum pregnancytest result at Screening and a negative pregnancy test result at Baseline and agreeto use acceptable methods of contraception as per protocol.

  7. Male participants agree to use acceptable methods of contraception if the maleparticipant's partner could become pregnant from the time of signing the informedconsent until 3 months after EOS/ET.

Exclusion

Exclusion Criteria:

  1. Vulnerable participants (ie, people under any administrative or legal supervision).

  2. Clinical laboratory evidence or clinical diagnosis of human immunodeficiency virus (HIV) infection, hepatitis C virus (HCV) infection, or chronic hepatitis B virus (HBV) infection (as shown by hepatitis B surface antigen [HbsAg] positivity).

  3. Evidence of a clinically significant cardiovascular, renal, hepatic, hematological,gastrointestinal (GI), pulmonary, metabolic-endocrine, neurological, or psychiatricdisease or psychiatric disease within the previous 2 years; or evidence of activeairway infection.

  4. Known hypersensitivity to the active substance(s) of the drug or its excipient (lactose monohydrate, which contains small amounts of milk protein) and/orintolerance with lactose.

  5. History of vasovagal syncope in past 5 years.

  6. History of anaphylactic/anaphylactoid reactions.

  7. History of seizures including febrile seizures.

  8. History of bleeding disorders or currently being treated with anticoagulants orregular using aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs).

  9. History of thrombotic event (including stroke and transient ischemic attack) within 6 months prior to Screening.

  10. History of pulmonary arterial hypertension.

  11. Cardiovascular diseases, any of the following: Severe hypertension (uncontrolledunder treatment ≥ 160/100 mmHg at multiple occasions) within 3 months prior toScreening; history of myocardial infarction; history of unstable cardiac angina

  12. Surgery of the GI tract (except appendectomy or simple hernia repair).

  13. Any condition requiring regular concomitant treatment (including vitamins,recreational drugs, and dietary or herbal products) or likely to need anyconcomitant treatment during the study. As an exception, paracetamol and ibuprofenfor occasional pain will be allowed.

  14. Intake of any medication that could affect the outcome of the study. As anexception, contraceptives and hormone replacement therapy are allowed. The use ofmedicines that are potential CYP3A4 inducers or inhibitors will be restricted for atleast 2 weeks prior to the first dose of the IP and during the study.

  15. Use of any prescription drugs or the medication leading to prolong the QT/QTcinterval within 14 days or 7 half-lives (whichever is longer) prior to dosing; overthe-counter (OTC) medication, supplements, or vitamins within 7 days or 7 half lives (whichever is longer) prior to the first dose of the IP.

  16. Administration of another investigational drug within the past 30 days prior to thefirst dose of IP.

  17. Any clinically significant abnormal laboratory value or physical finding (includingvital signs) that may interfere with the interpretation of study results orconstitute a health risk for the participant if he/she takes part in the study, asjudged by the PI/Sub-Investigator. More specifically, respiratory rate < 12 or > 22rpm, heart rate (HR) < 45 or > 100 bpm, or systolic blood pressure (BP) ≥ 140 or < 90 or diastolic BP ≥ 90 or < 60 mmHg, or oxygen saturation < 95% after a 5-minuterest. Repeat tests are permitted at Investigator's discretion.

  18. Abnormal ECG findings (eg, QTcF > 450 msec [male] or > 470 msec [female]) atScreening and admission (Day -2 and Day -1). Repeat tests are permitted atInvestigator's discretion

  19. Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) > 1.5 x upperlimit of normal (ULN) or total Bilirubin > 1.5 x ULN.

  20. Pregnant or lactating females.

  21. Women of childbearing potential (WOCBP) who are sexually active with the oppositesex not using acceptable effective methods of contraception (mechanical and/orhormonal contraception, intrauterine device, intrauterine hormonal releasing systemor surgical sterilization, vasectomized partner etc.).

  22. Participants with a positive result of drug abuse test or with a history of drugabuse at Screening.

  23. Participants with a history of alcohol abuse within 1 month prior to Screening (average consuming 14 units or more of alcohol per week: 1 unit = 285 mL of beer, or 25 mL of spirits, or 125 mL of wine) or with a positive result of alcohol breathtest at Screening.

  24. Use of tobacco- or nicotine-containing products (eg, nicotine patches or vaporizingdevices) within 3 months prior to Screening or a positive result of urine cotininetest at Screening.

  25. Participants who consume food or beverage containing grapefruit/pomelo oralcohol/caffeine (eg, coffee, chocolate, cola, tea, etc.) within 48 hours prior toconfinement and during the confinement.

  26. Blood donation or loss of significant amount (≥ 200 mL) of blood within 30 daysprior to the first dose of IP administration.

  27. Unsuitable veins for repeated venipuncture or for cannulation.

  28. Inability to learn the correct inhalation technique.

  29. Predictable poor compliance.

  30. Judged to be not eligible by the Investigator/Sponsor for any other reason

Study Design

Total Participants: 72
Treatment Group(s): 3
Primary Treatment: Placebo
Phase: 1
Study Start date:
July 11, 2024
Estimated Completion Date:
February 10, 2025

Study Description

This study consists of 3 parts. SAD Part: The participants in the SAD cohorts of the study (Cohort 1 to Cohort 5) will receive a single dose of RSN0402 at 2, 4, 8, 12, or 16 mg dose or placebo via inhalation using a dry powder inhalant. Participants from Cohort 2 will receive a single dose of 150 mg nintedanib soft capsule after 7-day washout period. After completion of Cohort 3, SRC will decide whether to enrol Cohort 4 sequentially or to skip Cohort 4 and enrol Cohort 5 directly based on the safety and PK data collected from the Cohort 1 to Cohort 3. If there are no safety concerns, Cohort 5 will be enrolled after Cohort 3.

MAD Part: The MAD Part consists of 4 cohorts with 8 participants in each cohort. Participants will be randomly assigned to receive RSN0402 (4, 8, 12, or 16 mg) or placebo for 7 days at a ratio of 3:1. In MAD study, the IP will be administered once daily from Day 1 to Day 7. The doses in MAD Part of the study could be adjusted at the discretion of the SRC based on the review of data from the SAD cohorts. The dose regimen in MAD Part may also be adjusted to twice daily or another regimen if there is any concern after SRC review of the available data from SAD cohorts. The adjusted dose and dose regimen cannot exceed the maximum safety daily dose confirmed in the SAD Part.

Connect with a study center

  • Nucleus Network Pty Ltd

    Geelong, Victoria 3220
    Australia

    Active - Recruiting

  • Nucleus Network

    Melbourne, Victoria 3004
    Australia

    Active - Recruiting

  • Nucleus Network Pty Ltd

    Melbourne, 3004
    Australia

    Active - Recruiting

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