The Safety, Tolerability, and Pharmacokinetics of Inhaled TLC19 in Healthy Volunteers

Study Overview
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Brief Summary
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Phase 1 randomized, vehicle-controlled, blinded study to assess the safety, tolerability, and PK of single ascending doses of inhaled TLC19 in healthy volunteer subjects.

Detailed Description
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A Phase 1 randomized, vehicle-controlled, blinded study to assess the safety, tolerability, and PK of single ascending doses of inhaled TLC19 (Hydroxychloroquine Liposome Inhalation Suspension) in healthy volunteer subjects. Three dose levels will be assessed in sequential cohorts, with 2 mL, 4 mL, and 6 mL. Total of approximately 30 subjects will be randomized in the study in 3 cohorts. Subjects will be enrolled and randomized to receiving either TLC19 or TLC 19 Vehicle. Drug Administration: Blinded study medication will be administered through inhalation via a portable vibration mesh nebulizer.

Official Title
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A Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Inhaled TLC19 in Healthy Volunteers

Conditions
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COVID-19

Intervention / Treatment
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* Drug: TLC19
* Drug: TLC19 Vehicle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female 18 to 65 years of age Body mass index (BMI) 18.0 to 30.0 kg/m2. Never-smoker Exclusion Criteria: Body weight <50 kg Donation of blood (450 mL) or blood loss within 3 months prior to study Contraindication, allergy, or hypersensitivity to hydroxychloroquine or chloroquine or other 4 aminoquinolines Use of any prescription or OTC medications or herbal supplements within 2 weeks (or 5half-lives if longer) prior to study Use of any investigational product/medical device within 30 days or 5 half-lives prior to study, or participation in ≥4 investigational drug studies within 1 year prior to study History or presence of any of the following conditions: Autoimmune or rheumatoid inflammatory disease Cardiac disorders Lung disease, prior intubation, or requiring use of an inhaler Liver cirrhosis or Child-Pugh class C Retinopathy or maculopathy Neuromuscular diseases Glucose-6 phosphate dehydrogenase deficiency Hematologic malignancy Chronic kidney disease or renal failure Psoriasis or porphyria Diabetes mellitus Severe allergic or anaphylactic reactions Any other significant condition that would preclude participation History of substance abuse or dependency in the last 12 months, or a history of recreational intravenous drug use over the last 5 years Fever or symptomatic viral or bacterial infection within 2 weeks prior to study Any clinically significant laboratory abnormality

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: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TLC19 (low dose)<br>TLC19 2ml single dose | Drug: TLC19<br>* Hydroxychloroquine Liposome Inhalation Suspension<br>* Other names: TLC19 (Hydroxychloroquine Liposome Inhalation Suspension);|
| Experimental: TLC19 (medium dose)<br>TLC19 4ml single dose | Drug: TLC19<br>* Hydroxychloroquine Liposome Inhalation Suspension<br>* Other names: TLC19 (Hydroxychloroquine Liposome Inhalation Suspension);|
| Experimental: TLC19 (high dose)<br>TLC19 6ml single dose | Drug: TLC19<br>* Hydroxychloroquine Liposome Inhalation Suspension<br>* Other names: TLC19 (Hydroxychloroquine Liposome Inhalation Suspension);|
| Sham Comparator: TLC19 Vehicle (low dose)<br>TLC19 Vehicle 2ml single dose | Drug: TLC19 Vehicle<br>* Liposome Inhalation Suspension (same formulation as TLC19 but without the active ingredient, HCQ)<br>* Other names: TLC19 Vehicle (same formulation as TLC19 but without the active ingredient);|
| Sham Comparator: TLC19 Vehicle (medium dose)<br>TLC19 Vehicle 4ml single dose | Drug: TLC19 Vehicle<br>* Liposome Inhalation Suspension (same formulation as TLC19 but without the active ingredient, HCQ)<br>* Other names: TLC19 Vehicle (same formulation as TLC19 but without the active ingredient);|
| Sham Comparator: TLC19 Vehicle (high dose)<br>TLC19 Vehicle 6ml single dose | Drug: TLC19 Vehicle<br>* Liposome Inhalation Suspension (same formulation as TLC19 but without the active ingredient, HCQ)<br>* Other names: TLC19 Vehicle (same formulation as TLC19 but without the active ingredient);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of AEs | To evaluate the severity, seriousness, outcome, and action taken of AE | 0-28 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum blood concentration | Cmax | 0-168 hours | 
| Time to reach maximum blood concentration | Tmax | 0-168 hours | 
| Area under the blood concentration-time curve | AUC0-last | 0-168 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hydroxychloroquine, Inhalation