TD-0903 Pharmacokinetics Study in Healthy Participants With Supplemental Oxygenation

Phase 1

Completed

• Conditions: Acute Lung Injury (ALI) Due to Coronavirus Disease-2019 (COVID-19)
• Interventions: Drug: Nezulcitinib (TD-0903) Dose A; Drug: Nezulcitinib (TD-0903) Dose B

• Registration Number: NCT05091723
• Lead Sponsor: Theravance Biopharma

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2021-10-12
• Study First Submitted QC: 2021-10-12
• Study Start: 2021-10-13
• Study First Posted: 2021-10-25
• Primary Completion: 2021-11-24
• Study Completion: 2021-11-24
• Status Verified: 2021-12
• Last Update Submitted: 2021-12-08
• Last Update Posted: 2021-12-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 14

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Administration Scenario A	Nezulcitinib (TD-0903) Dose A	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
Administration Scenario B	Nezulcitinib (TD-0903) Dose A	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
Administration Scenario C	Nezulcitinib (TD-0903) Dose A	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
Administration Scenario D	Nezulcitinib (TD-0903) Dose B	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Adverse Events	Day 1 through 7 following dosing on Day 1 in each of 4 Periods	Number and severity of treatment emergent adverse events

Trial Locations

Locations (1)

Theravance Biopharma Investigational Site; 🇺🇸 Cypress, California, United States