Acute Lung Injury (ALI) Due to Coronavirus Disease-2019 (COVID-19)
Conditions
Keywords
Acute lung injury, ALI, Coronavirus Disease-2019, COVID-19, Supplemental oxygen
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.
Interventions
DRUGNezulcitinib (TD-0903) Dose A
TD-0903 Dose A
DRUGNezulcitinib (TD-0903) Dose B
TD-0903 Dose B
Sponsors
Theravance Biopharma
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events | Day 1 through 7 following dosing on Day 1 in each of 4 Periods | Number and severity of treatment emergent adverse events |
Countries
United States
Outcome results
None listed