TD-0903 Pharmacokinetics Study in Healthy Participants With Supplemental Oxygenation

Study Overview
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Brief Summary
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This is a Phase 1 pharmacokinetic (PK) study in healthy participants to assess the plasma pharmacokinetics, safety, and tolerability of a single inhaled dose of nezulcitinib (TD-0903) with supplemental oxygenation.

Detailed Description
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A Phase 1, open-label, fixed-sequence, 4-period study to evaluate the plasma PK, safety and tolerability of single inhaled doses of nezulcitinib (TD-0903) administered under different supplemental oxygenation scenarios in healthy participants. Approximately 14 healthy adult male and female participants will receive a single inhaled dose of nezulcitinib using a nebulizer device on Day 1 of each administration period, under different supplementary oxygenations conditions. Administration A: Dose A nezulcitinib delivered by nasal inhalation via the Aerogen Solo with a high-flow nasal cannula circuit delivering supplemental oxygen, Administration B: Dose A nezulcitinib delivered by oral inhalation via the Aerogen Solo together with the Aerogen Ultra handheld device with a low-flow nasal cannula delivering supplemental oxygen, Administration C: Dose A nezulcitinib delivered by oral inhalation via the Aerogen Solo together with the Aerogen Ultra handheld device with a high-flow nasal cannula delivering supplemental oxygen, Administration D: Nezulcitinib delivered by inhalation. Route to be determined based on data from administration A-C.

Official Title
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Phase 1, Open-label Study to Assess the Pharmacokinetics and Safety of Inhaled Nezulcitinib (TD-0903) Administered in the Setting of Supplemental Oxygenation Scenarios in Healthy Participants

Conditions
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Acute Lung Injury (ALI) Due to Coronavirus Disease-2019 (COVID-19)

Intervention / Treatment
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* Drug: Nezulcitinib (TD-0903) Dose A
* Drug: Nezulcitinib (TD-0903) Dose B


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index (BMI) ≥ 18.0 and ≤ 35.0 kg/m2 and weighs at least 50 kg at screening Medically healthy with no clinically significant medical history, physical examination, spirometry, laboratory profiles, vital signs or ECGs Forced expiratory volume of 1 second (FEV1) ≥80% predicted at screening and prior to dosing No clinically significant abnormalities in the results of laboratory Female subjects must be either of non-childbearing potential or if of childbearing potential, subject must not be pregnant or breastfeeding, and must agree to use a highly effective birth control method Male subjects must agree to use condoms to prevent potential fetal or partner exposure through seminal fluid, in addition to the use of highly effective pregnancy prevention measures with female partners of childbearing potential Able to understand the correct technique for the use of the nebulizer device Other inclusion criteria apply Exclusion Criteria: History or presence of clinically significant medical or psychiatric condition Abnormal ECG measurements at screening Any signs of respiratory tract infection within 6 weeks of screening Has a current bacterial, parasitic, fungal, or viral infection; any infection requiring hospitalization or intravenous antibiotics within 6 months prior to screening Has any condition of the oro-laryngeal or respiratory tract History or presence of alcoholism or drug abuse Positive urine drugs of abuse test Positive urine or breath alcohol results Uses or has used tobacco or nicotine-containing products (e.g., cigarettes, cigars, chewing tobacco, snuff, patches etc.) within 6 months prior to screening Tests positive for active COVID-19 Additional exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Administration Scenario A<br>Single dose of TD-0903 at Dose A on Day 1, Period 1 delivered by nasal inhalation via nebulizer device with a high-flow nasal cannula delivering supplemental oxygen | Drug: Nezulcitinib (TD-0903) Dose A<br>* TD-0903 Dose A<br>|
| Experimental: Administration Scenario B<br>Single dose of TD-0903 at Dose A on Day 1, Period 2 delivered by oral inhalation via nebulizer device with supplemental oxygen delivery via low-flow nasal cannula | Drug: Nezulcitinib (TD-0903) Dose A<br>* TD-0903 Dose A<br>|
| Experimental: Administration Scenario C<br>Single dose of TD-0903 at Dose A on Day 1, Period 3 delivered by oral inhalation via nebulizer device with supplemental oxygen delivery via high-flow nasal cannula | Drug: Nezulcitinib (TD-0903) Dose A<br>* TD-0903 Dose A<br>|
| Experimental: Administration Scenario D<br>Single dose of TD-0903 at Dose B on Day 1, Period 4 delivered by a route to-be-determined based on data from Scenarios A, B and C. | Drug: Nezulcitinib (TD-0903) Dose B<br>* TD-0903 Dose B<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-inf | The area under the concentration time curve from time 0 extrapolated to infinity (AUC0-inf) of TD-0903 | Predose and at prespecified time points up to 48 hours after dosing on Day 1 of each period | 
| AUC0-t | The area under the concentration time curve, from time 0 to the last observed non-zero concentration (AUC0-t) of TD-0903 | Predose and at prespecified time points up to 48 hours after dosing on Day 1 of each period | 
| Cmax | Maximum observed concentration (Cmax) of TD-0903 in plasma | Predose and at prespecified time points up to 48 hours after dosing on Day 1 of each period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | Number and severity of treatment emergent adverse events | Day 1 through 7 following dosing on Day 1 in each of 4 Periods | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Coronavirus Disease-2019, ALI, COVID-19, Supplemental oxygen, Acute lung injury