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

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

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.

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Drug: TLC19; Drug: TLC19 Vehicle

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 10449
    • Mackay Memorial Hospital Tamsui Branch

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:

1. Male or female 18 to 65 years of age
2. Body mass index (BMI) 18.0 to 30.0 kg/m2.
3. Never-smoker

Exclusion Criteria:

1. Body weight <50 kg
2. Donation of blood (450 mL) or blood loss within 3 months prior to study
3. Contraindication, allergy, or hypersensitivity to hydroxychloroquine or chloroquine or other 4 aminoquinolines
4. Use of any prescription or OTC medications or herbal supplements within 2 weeks (or 5half-lives if longer) prior to study
5. 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

6. 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
7. History of substance abuse or dependency in the last 12 months, or a history of recreational intravenous drug use over the last 5 years
8. Fever or symptomatic viral or bacterial infection within 2 weeks prior to study
9. Any clinically significant laboratory abnormality

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Taiwan Liposome Company
• Investigators: Study Director: Carl Brown, PhD, Taiwan Liposome Company, Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): October 8, 2020
• Primary Completion (Actual): June 18, 2021
• Study Completion (Actual): June 18, 2021

Study Registration Dates

• First Submitted: January 4, 2021
• First Submitted That Met QC Criteria: January 4, 2021
• First Posted (Actual): January 6, 2021

Study Record Updates

• Last Update Posted (Actual): November 26, 2021
• Last Update Submitted That Met QC Criteria: November 24, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: hydroxychloroquine; Inhalation
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Hydroxychloroquine
• Other Study ID Numbers: TLC19A1001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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