TD-0903 Pharmacokinetics Study in Healthy Participants With Supplemental Oxygenation

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

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.

Study Overview

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

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 Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Cypress, California, United States, 90630
      • Theravance Biopharma Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Administration Scenario 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	Drug: Nezulcitinib (TD-0903) Dose A; TD-0903 Dose A
Experimental: Administration Scenario B; 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; TD-0903 Dose A
Experimental: Administration Scenario C; 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; TD-0903 Dose A
Experimental: Administration Scenario D; 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; TD-0903 Dose B

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Theravance Biopharma

Study record dates

Study Major Dates

• Study Start (Actual): October 13, 2021
• Primary Completion (Actual): November 24, 2021
• Study Completion (Actual): November 24, 2021

Study Registration Dates

• First Submitted: October 12, 2021
• First Submitted That Met QC Criteria: October 12, 2021
• First Posted (Actual): October 25, 2021

Study Record Updates

• Last Update Posted (Actual): December 10, 2021
• Last Update Submitted That Met QC Criteria: December 8, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: COVID-19; ALI; Acute lung injury; Supplemental oxygen; Coronavirus Disease-2019
• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Wounds and Injuries; Thoracic Injuries; COVID-19; Coronavirus Infections; Acute Lung Injury; Lung Injury
• Other Study ID Numbers: 0196

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Theravance Biopharma, Inc. will not be sharing individual de-identified participant data or other relevant study documents.

Drug and device information, study documents

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