TD-0903 Pharmacokinetics Study in Healthy Participants With Supplemental Oxygenation

Sponsor

Theravance Biopharma (Industry)

Overall Status

Completed

CT.gov ID

NCT05091723

Collaborator

(none)

Enrollment

Location

Arms

1.4

Actual Duration (Months)

10.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Lung Injury (ALI) Due to Coronavirus Disease-2019 (COVID-19)	Drug: Nezulcitinib (TD-0903) Dose A Drug: Nezulcitinib (TD-0903) Dose B	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

14 participants

Allocation:

Non-Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Oct 13, 2021

Actual Primary Completion Date :

Nov 24, 2021

Actual Study Completion Date :

Nov 24, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

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
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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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