Phase I PK and Safety Study of Ondansetron Inhalation Powder

Inclusion criteria

• Provision of signed and dated informed consent form (ICF).
• Subject is, as stated and in the opinion of the investigator, willing and able to comply with the study drug regimen and all other study procedures and requirements, and is available for the duration of the study.
• Healthy adult male or female.
• Subject is willing to comply with the contraceptive requirements as defined in APPENDIX 6.
• Aged at least 18 years but not older than 55 years.
• Body mass index (BMI) within 18.5 kg/m2 to 30.0 kg/m2, inclusively.
• Non-smokers or ex-smokers (an ex-smoker is defined as someone who completely stopped using nicotine products for at least 180 days prior to the first study drug administration).
• Have no clinically significant diseases captured in the medical history or evidence of clinically significant findings on the physical examination, vital signs, and/or ECG, as determined by an investigator.
• Can demonstrate ability to properly use the RS01® inhaler.

Exclusion criteria

• Female who is lactating.
• Female who is pregnant according to the pregnancy test at Screening or prior to the first study drug administration.
• History of significant hypersensitivity to ondansetron or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs.
• Presence or history of significant gastrointestinal, liver or kidney disease, or surgery that may affect drug bioavailability.
• History of significant cardiovascular, metabolic, pulmonary/respiratory (asthma, chronic obstructive pulmonary disease, emphysema, or any other chronic pulmonary condition), hematologic, neurological, psychiatric, endocrine, immunologic, or dermatologic disease, or substance use disorder (excluding caffeine or nicotine).
• Presence of clinically significant ECG abnormalities at the Screening visit, as defined by medical judgment, including QTcF > 440 msec.
• History of asthma or any allergy to common substances (animals, plants).
• Has a forced expiratory volume in the first second (FEV1) < 80% predicted at Screening.
• Immunization with a Coronavirus Disease 2019 (COVID-19) vaccine in the 14 days prior to the first study drug administration.
• Scheduled immunization with a COVID-19 vaccine during the study that, in the opinion of an investigator, could potentially interfere with subject participation, subject safety, study results, or any other reason.
• Any clinically significant illness (including COVID-19 infections) in the 28 days prior to the first study drug administration.
• Use of any prescription drugs in the 28 days prior to the first study drug administration that in the opinion of an investigator would put into question the status of the subject as healthy.
• Use of St. John's wort in the 28 days prior to the first study drug administration.
• Any history of latent or active tuberculosis.
• Positive test result for alcohol and/or drugs of abuse at Screening or prior to the first drug administration.
• Positive Screening results to HIV Ag/Ab combo, hepatitis B surface antigen or hepatitis C virus antibody tests.
• Any other clinically significant abnormalities in laboratory test results at Screening or prior to the first drug administration that would, in the opinion of an investigator, increase the subject's risk of participation, jeopardize complete participation in the study, or compromise interpretation of study data.
• Inclusion in a previous cohort for this clinical study.
• Intake of ondansetron in the 28 days prior to the first study drug administration.
• Intake of an investigational product (IP) in the 28 days prior to the first study drug administration.
• Donation of plasma in the 7 days prior to the first study drug administration.
• Donation of 50 mL or more of blood in the 28 days prior to the first study drug administration.
• Donation of 500 mL or more of blood in the 56 days prior to the first study drug administration.
• Use of nicotine or any products containing nicotine in the 180 days prior to the first study drug administration.
• Use of any enzyme-modifying drugs, including any CYP3A4, CYP2D6, or CYP1A2 inducers or inhibitors, in the 28 days prior to the first study drug administration.
• Estimated glomerular filtration rate < 60 mL/minute/1.73 m2 (as estimated by the Modification of Diet in Renal Disease formula) at Screening or prior to the first study treatment administration.