Phase I PK and Safety Study of Ondansetron Inhalation Powder

NCT07498751 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: LPI-1503-901LOO-P3-703
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Postoperative Nausea and Vomiting

Outcome Measures

Primary Outcomes (14)

• 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 Outcomes (3)

• Cmax/D

  pre-dose to 48 hours post-dose

• AUC(0-t)/D

  pre-dose to 48 hours post-dose

• AUC(0-inf)/D

  pre-dose to 48 hours post-dose

Study Arms (7)

4mg LPI-1503 in Period 1, 8mg Oral Ondansetron in Period 2

EXPERIMENTAL

LPI-1503 = Ondansetron Inhalation Powder, 4mg is nominal dose. 8mg oral Ondansetron is an active comparator. Washout between Periods \>= 7 days.

Drug: LPI-1503; Drug: Oral Ondansetron

4mg LPI-1503 in Period 1, 4mg IV Ondansetron in Period 2

EXPERIMENTAL

LPI-1503 = Ondansetron Inhalation Powder, 4mg is nominal dose. 4mg IV Ondansetron is an active comparator. Washout between Periods \>= 7 days.

Drug: LPI-1503; Drug: IV Ondansetron

8mg LPI-1503 in Period 1, 8mg Oral Ondansetron in Period 2

EXPERIMENTAL

LPI-1503 = Ondansetron Inhalation Powder, 8mg is nominal dose. 8mg oral Ondansetron is an active comparator. Washout between Periods \>= 7 days.

Drug: LPI-1503; Drug: Oral Ondansetron

8mg LPI-1503 in Period 1, 4mg IV Ondansetron in Period 2

EXPERIMENTAL

LPI-1503 = Ondansetron Inhalation Powder, 8mg is nominal dose. 4mg IV Ondansetron is an active comparator. Washout between Periods \>= 7 days.

Drug: LPI-1503; Drug: IV Ondansetron

12mg LPI-1503 in Period 1, 8mg Oral Ondansetron in Period 2

EXPERIMENTAL

LPI-1503 = Ondansetron Inhalation Powder, 12mg is nominal dose. 8mg oral Ondansetron is an active comparator. Washout between Periods \>=7 days.

Drug: LPI-1503; Drug: Oral Ondansetron

12mg LPI-1503 in Period 1, 4mg IV Ondansetron in Period 2

EXPERIMENTAL

LPI-1503 = Ondansetron Inhalation Powder, 12mg is nominal dose. 4mg IV Ondansetron is an active comparator. Washout between Periods \>= 7 days.

Drug: LPI-1503; Drug: IV Ondansetron

Matching Placebo in Period 1

PLACEBO COMPARATOR

Matching Placebo of LPI-1503. There is no Period 2 in this Arm.

Drug: Matching Placebo of LPI-1503

Interventions

LPI-1503 DRUG

Micronized ondansetron blended with excipients, to be administrated by inhalation, by using a single-capsule inhaler RS01(R).

Also known as: Ondansetron Inhalation Powder

12mg LPI-1503 in Period 1, 4mg IV Ondansetron in Period 2; 12mg LPI-1503 in Period 1, 8mg Oral Ondansetron in Period 2; 4mg LPI-1503 in Period 1, 4mg IV Ondansetron in Period 2; 4mg LPI-1503 in Period 1, 8mg Oral Ondansetron in Period 2; 8mg LPI-1503 in Period 1, 4mg IV Ondansetron in Period 2; 8mg LPI-1503 in Period 1, 8mg Oral Ondansetron in Period 2

Matching Placebo of LPI-1503 DRUG

Powder that contains only excipient (no API), to be administrated by inhalation, by using a single-capsule inhaler RS01(R).

Also known as: Matching Placebo of Ondansetron Inhalation Powder

Matching Placebo in Period 1

IV Ondansetron DRUG

4mg Ondansetron to be administrated by IV as an active comparator in Period 2.

Also known as: Ondansetron Injection Solution

12mg LPI-1503 in Period 1, 4mg IV Ondansetron in Period 2; 4mg LPI-1503 in Period 1, 4mg IV Ondansetron in Period 2; 8mg LPI-1503 in Period 1, 4mg IV Ondansetron in Period 2

Oral Ondansetron DRUG

8mg ondansetron to be orally administrated as an active comparator in Period 2.

Also known as: Ondansetron Tablet

12mg LPI-1503 in Period 1, 8mg Oral Ondansetron in Period 2; 4mg LPI-1503 in Period 1, 8mg Oral Ondansetron in Period 2; 8mg LPI-1503 in Period 1, 8mg Oral Ondansetron in Period 2

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Luxena Pharmaceuticals, Inc.: lead
• Altasciences Company Inc.: collaborator

Study Sites (1)

Altasciences Clinical Research Unit

Mount Royal, Quebec, H3P 3P1, Canada

Location

MeSH Terms

Conditions

Postoperative Nausea and Vomiting

Interventions

Ondansetron

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Nausea; Signs and Symptoms, Digestive; Signs and Symptoms; Vomiting

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2026
• First Posted: March 27, 2026
• Study Start: March 13, 2025
• Primary Completion: August 23, 2025
• Study Completion: August 23, 2025
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)