Postoperative Nausea and Vomiting
Conditions
Brief summary
The goal of this clinical trial is to learn if LPI-1503 (Ondansetron Inhalation Powder) can deliver ondansetron into blood through inhalation. It will also learn about the safety of LPI-1503. The main questions it aims to answer are: Does ondansetron enter into blood after inhalation of LPI-1503? And if it does, how efficiently? how rapidly? What medical problems do participants have when and after inhaling LPI-1503? Researchers will compare LPI-1503 to a placebo (a look-alike substance that contains no drug), and to orally swallowed and injected administrated ondansetron. Participants will: Visit site and take LPI-1503 or a placebo once by inhalation, followed by checkups and tests; and (if took LPI-1503 in visit 1) After one week, visit site again to take ondansetron by orally swallowing or by injection, followed by checkups and tests.
Interventions
DRUGLPI-1503
Micronized ondansetron blended with excipients, to be administrated by inhalation, by using a single-capsule inhaler RS01(R).
DRUGMatching Placebo of LPI-1503
Powder that contains only excipient (no API), to be administrated by inhalation, by using a single-capsule inhaler RS01(R).
DRUGIV Ondansetron
4mg Ondansetron to be administrated by IV as an active comparator in Period 2.
DRUGOral Ondansetron
8mg ondansetron to be orally administrated as an active comparator in Period 2.
Sponsors
Luxena Pharmaceuticals, Inc.
Altasciences Company Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Provision of signed and dated informed consent form (ICF). 2. 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. 3. Healthy adult male or female. 4. Subject is willing to comply with the contraceptive requirements as defined in APPENDIX 6. 5. Aged at least 18 years but not older than 55 years. 6. Body mass index (BMI) within 18.5 kg/m2 to 30.0 kg/m2, inclusively. 7. 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). 8. 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. 9. Can demonstrate ability to properly use the RS01® inhaler.
Exclusion criteria
1. Female who is lactating. 2. Female who is pregnant according to the pregnancy test at Screening or prior to the first study drug administration. 3. 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. 4. Presence or history of significant gastrointestinal, liver or kidney disease, or surgery that may affect drug bioavailability. 5. 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). 6. Presence of clinically significant ECG abnormalities at the Screening visit, as defined by medical judgment, including QTcF \> 440 msec. 7. History of asthma or any allergy to common substances (animals, plants). 8. Has a forced expiratory volume in the first second (FEV1) \< 80% predicted at Screening. 9. Immunization with a Coronavirus Disease 2019 (COVID-19) vaccine in the 14 days prior to the first study drug administration. 10. 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. 11. Any clinically significant illness (including COVID-19 infections) in the 28 days prior to the first study drug administration. 12. 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. 13. Use of St. John's wort in the 28 days prior to the first study drug administration. 14. Any history of latent or active tuberculosis. 15. Positive test result for alcohol and/or drugs of abuse at Screening or prior to the first drug administration. 16. Positive Screening results to HIV Ag/Ab combo, hepatitis B surface antigen or hepatitis C virus antibody tests. 17. 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. 18. Inclusion in a previous cohort for this clinical study. 19. Intake of ondansetron in the 28 days prior to the first study drug administration. 20. Intake of an investigational product (IP) in the 28 days prior to the first study drug administration. 21. Donation of plasma in the 7 days prior to the first study drug administration. 22. Donation of 50 mL or more of blood in the 28 days prior to the first study drug administration. 23. Donation of 500 mL or more of blood in the 56 days prior to the first study drug administration. 24. Use of nicotine or any products containing nicotine in the 180 days prior to the first study drug administration. 25. 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. 26. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Treatment-Emergent Adverse Events | pre-dose to 48 hours post-dose or to end of all AEs (if any), whichever is later. | An Adverse Event (AE) is defined as any untoward medical occurrence in a subject administered a study drug (including the placebo or the positive comparators), which dose not necessarily have a causal relationship with the treatment. For example (but not limited to), any Clinical Significant Changes/Findings in Clinically Laboratory, Spirometry, Pulse Oximetry, Vitals Signs, Physical Examinations, or Electrocardiogram (ECG) will be reproted as AEs. An Treatment-Emergent Adverse Events (TEAE) is defined as any AE occurred at the time of, or after, administration of the study drug. Number of Participants with TEAE will also summarized by Severity, for which all AEs will be graded per the current FDA Guidance for Industry - Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. |
| Number of Participants with Serious Adverse Events. | pre-dose to 48 hours post-dose or to end of all AEs (if any), whichever is later. | An Serious Adverse Event (SAE) is any AE that: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity (defined as a substantial disruption of a person's ability to conduct normal life functions), is a congenital anomaly or birth defect, or is an important medical event that may jeopardize the subject or may require intervention to prevent one of the other outcomes listed above (according to medical judgment of aninvestigator). |
| Number of Participants with Treatment-Related Adverse Events | pre-dose to 48 hours post-dose or to end of all AEs (if any), whichever is later. | Reasonable Possibility of Treatment-Relatedness: A temporal relationship exists between the AE onset and administration of the IP that cannot be readily explained by the subject's clinical state or concomitant therapies. Furthermore, the AE appears with some degree of certainty to be related, based on the known therapeutic and pharmacologic actions or AE profile of the IP. No Reasonable Possibility of Treatment-Relatedness: Evidence exists that the AE has an etiology other than the IP. For SAEs, an alternative causality must be provided (eg, preexisting condition, underlying disease, intercurrent illness, or concomitant medication). |
| Cmax | pre-dose to 48 hours post-dose | Cmax (ng/mL): maximum observed concentration of ondansetron in plasma |
| Tmax | pre-dose to 48 hours post-dose | Tmax (hour): time of maximum observed concentration of ondansetron in plasma |
| AUC(0-t) | pre-dose to 48 hours post-dose | AUC(0-t) (h\*mg/mL): area under the concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration |
| AUC(0-inf) | pre-dose to 48 hours post-dose | AUC(0-inf) (h\*ng/mL): area under the concentration time curve extrapolated to infinity, calculated as AUC(0-t) + C(last)/λz, where C(last) is the last quantifiable concentration |
| t(1/2) | pre-dose to 48 hours post-dose | t(1/2) (hour): terminal elimination half-life, calculated as ln(2)/λz |
| CL/F | pre-dose to 48 hours post-dose | CL/F (mL/h) (inhalation and oral tablet ondansetron only): apparent clearance of drug, calculated as Dose/AUC(0-inf) |
| Vd/F | pre-dose to 48 hours post-dose | Vd/F (mL) (inhalation and oral tablet ondansetron only): apparent volume of distribution during the terminal phase, calculated as Dose/(λz × AUC(0-inf)) |
| CL | pre-dose to 48 hours post-dose | CL (mL/h) (IV ondansetron only): total plasma clearance of drug, calculated as Dose/AUC(0-inf) |
| Vd | pre-dose to 48 hours post-dose | Vd (mL) (IV ondansetron only): volume of distribution during the terminal phase, calculated as Dose/(λz × AUC(0-inf)) |
| Absolute Bioavailability (F) | pre-dose to 48 hours post-dose | Absolute Bioavailability (F) is calculated as: AUC(0-T)/D of inhalation / AUC(0-T)/D of IV |
| Relative Bioavailability (F rel) | pre-dose to 48 hours post-dose | Relative Bioavailability (F rel) is calculated as: AUC(0-T)/D of inhalation / AUC(0-T)/D of oral tablet |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax/D | pre-dose to 48 hours post-dose | Cmax/D (ng/mL/mg): maximum observed concentration of ondansetron in plasma normalized to dose |
| AUC(0-t)/D | pre-dose to 48 hours post-dose | AUC(0-t)/D (h\*ng/mL/mg): area under the concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration, normalized to dose |
| AUC(0-inf)/D | pre-dose to 48 hours post-dose | AUC(0-inf)/D (h\*ng/mL/mg): area under the concentration time curve extrapolated to infinity, calculated as AUC(0-t) + C(last) / λz, where Clast is the last quantifiable concentration, normalized to dose |
Countries
Canada
Outcome results
None listed