Phase I PK and Safety Study of Ondansetron Inhalation Powder

Randomized, Double-Blind, Placebo-Controlled, Single-Dose, 3-Escalating Cohort, 2 Period Crossover Study Investigating the Tolerability, Safety, and Pharmacokinetics of Ondansetron Inhalation Powder

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.

Study Overview

• Status: Completed
• Conditions: Postoperative Nausea and Vomiting
• Intervention / Treatment: Drug: LPI-1503; Drug: Oral Ondansetron; Drug: IV Ondansetron; Drug: Matching Placebo of LPI-1503

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Mount Royal, Quebec, Canada, H3P 3P1
      • Altasciences Clinical Research Unit

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 4mg LPI-1503 in Period 1, 8mg Oral Ondansetron in Period 2; LPI-1503 = Ondansetron Inhalation Powder, 4mg is nominal dose. 8mg oral Ondansetron is an active comparator. Washout between Periods >= 7 days.	Drug: LPI-1503; Micronized ondansetron blended with excipients, to be administrated by inhalation, by using a single-capsule inhaler RS01(R).; Other Names: Ondansetron Inhalation Powder; Drug: Oral Ondansetron; 8mg ondansetron to be orally administrated as an active comparator in Period 2.; Other Names: Ondansetron Tablet
Experimental: 4mg LPI-1503 in Period 1, 4mg IV Ondansetron in Period 2; LPI-1503 = Ondansetron Inhalation Powder, 4mg is nominal dose. 4mg IV Ondansetron is an active comparator. Washout between Periods >= 7 days.	Drug: LPI-1503; Micronized ondansetron blended with excipients, to be administrated by inhalation, by using a single-capsule inhaler RS01(R).; Other Names: Ondansetron Inhalation Powder; Drug: IV Ondansetron; 4mg Ondansetron to be administrated by IV as an active comparator in Period 2.; Other Names: Ondansetron Injection Solution
Experimental: 8mg LPI-1503 in Period 1, 8mg Oral Ondansetron in Period 2; LPI-1503 = Ondansetron Inhalation Powder, 8mg is nominal dose. 8mg oral Ondansetron is an active comparator. Washout between Periods >= 7 days.	Drug: LPI-1503; Micronized ondansetron blended with excipients, to be administrated by inhalation, by using a single-capsule inhaler RS01(R).; Other Names: Ondansetron Inhalation Powder; Drug: Oral Ondansetron; 8mg ondansetron to be orally administrated as an active comparator in Period 2.; Other Names: Ondansetron Tablet
Experimental: 8mg LPI-1503 in Period 1, 4mg IV Ondansetron in Period 2; LPI-1503 = Ondansetron Inhalation Powder, 8mg is nominal dose. 4mg IV Ondansetron is an active comparator. Washout between Periods >= 7 days.	Drug: LPI-1503; Micronized ondansetron blended with excipients, to be administrated by inhalation, by using a single-capsule inhaler RS01(R).; Other Names: Ondansetron Inhalation Powder; Drug: IV Ondansetron; 4mg Ondansetron to be administrated by IV as an active comparator in Period 2.; Other Names: Ondansetron Injection Solution
Experimental: 12mg LPI-1503 in Period 1, 8mg Oral Ondansetron in Period 2; LPI-1503 = Ondansetron Inhalation Powder, 12mg is nominal dose. 8mg oral Ondansetron is an active comparator. Washout between Periods >=7 days.	Drug: LPI-1503; Micronized ondansetron blended with excipients, to be administrated by inhalation, by using a single-capsule inhaler RS01(R).; Other Names: Ondansetron Inhalation Powder; Drug: Oral Ondansetron; 8mg ondansetron to be orally administrated as an active comparator in Period 2.; Other Names: Ondansetron Tablet
Experimental: 12mg LPI-1503 in Period 1, 4mg IV Ondansetron in Period 2; LPI-1503 = Ondansetron Inhalation Powder, 12mg is nominal dose. 4mg IV Ondansetron is an active comparator. Washout between Periods >= 7 days.	Drug: LPI-1503; Micronized ondansetron blended with excipients, to be administrated by inhalation, by using a single-capsule inhaler RS01(R).; Other Names: Ondansetron Inhalation Powder; Drug: IV Ondansetron; 4mg Ondansetron to be administrated by IV as an active comparator in Period 2.; Other Names: Ondansetron Injection Solution
Placebo Comparator: Matching Placebo in Period 1; Matching Placebo of LPI-1503. There is no Period 2 in this Arm.	Drug: Matching Placebo of LPI-1503; Powder that contains only excipient (no API), to be administrated by inhalation, by using a single-capsule inhaler RS01(R).; Other Names: Matching Placebo of Ondansetron Inhalation Powder

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Treatment-Emergent Adverse Events	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.	pre-dose to 48 hours post-dose or to end of all AEs (if any), whichever is later.
Number of Participants with Serious Adverse Events.	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).	pre-dose to 48 hours post-dose or to end of all AEs (if any), whichever is later.
Number of Participants with Treatment-Related Adverse Events	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).	pre-dose to 48 hours post-dose or to end of all AEs (if any), whichever is later.
Cmax	Cmax (ng/mL): maximum observed concentration of ondansetron in plasma	pre-dose to 48 hours post-dose
Tmax	Tmax (hour): time of maximum observed concentration of ondansetron in plasma	pre-dose to 48 hours post-dose
AUC(0-t)	AUC(0-t) (h*mg/mL): area under the concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration	pre-dose to 48 hours post-dose
AUC(0-inf)	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	pre-dose to 48 hours post-dose
t(1/2)	t(1/2) (hour): terminal elimination half-life, calculated as ln(2)/λz	pre-dose to 48 hours post-dose
CL/F	CL/F (mL/h) (inhalation and oral tablet ondansetron only): apparent clearance of drug, calculated as Dose/AUC(0-inf)	pre-dose to 48 hours post-dose
Vd/F	Vd/F (mL) (inhalation and oral tablet ondansetron only): apparent volume of distribution during the terminal phase, calculated as Dose/(λz × AUC(0-inf))	pre-dose to 48 hours post-dose
CL	CL (mL/h) (IV ondansetron only): total plasma clearance of drug, calculated as Dose/AUC(0-inf)	pre-dose to 48 hours post-dose
Vd	Vd (mL) (IV ondansetron only): volume of distribution during the terminal phase, calculated as Dose/(λz × AUC(0-inf))	pre-dose to 48 hours post-dose
Absolute Bioavailability (F)	Absolute Bioavailability (F) is calculated as: AUC(0-T)/D of inhalation / AUC(0-T)/D of IV	pre-dose to 48 hours post-dose
Relative Bioavailability (F rel)	Relative Bioavailability (F rel) is calculated as: AUC(0-T)/D of inhalation / AUC(0-T)/D of oral tablet	pre-dose to 48 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax/D	Cmax/D (ng/mL/mg): maximum observed concentration of ondansetron in plasma normalized to dose	pre-dose to 48 hours post-dose
AUC(0-t)/D	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	pre-dose to 48 hours post-dose
AUC(0-inf)/D	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	pre-dose to 48 hours post-dose

Collaborators and Investigators

• Sponsor: Luxena Pharmaceuticals, Inc.
• Collaborators: Altasciences Company Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2025
• Primary Completion (Actual): August 23, 2025
• Study Completion (Actual): August 23, 2025

Study Registration Dates

• First Submitted: March 11, 2026
• First Submitted That Met QC Criteria: March 23, 2026
• First Posted (Actual): March 27, 2026

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 23, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Postoperative Complications; Pathologic Processes; Signs and Symptoms, Digestive; Vomiting; Nausea; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Postoperative Nausea and Vomiting; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Azoles; Imidazoles; Indoles; Heterocyclic Compounds, 3-Ring; Carbazoles; Ondansetron
• Other Study ID Numbers: LPI-1503-901; LOO-P3-703 (Other Identifier: Altasciences)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No