Single Ascending Dose and Multiple Ascending Dose Study of Voriconazole Inhalation Powder in Healthy Adult Subjects

NCT04872231 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: TFF-V1-001
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1 (healthy adult volunteers), 2-part, double-blind, randomized, placebo controlled trial to evaluate the safety and pharmacokinetic (PK) profiles of escalating single doses of Voriconazole Inhalation Powder versus placebo (SAD part) and escalating multiple doses of Voriconazole Inhalation Powder versus placebo (MAD part). SAD part will be initiated first and includes a sentinel design. MAD part will not utilize a sentinel design and will be initiated once the lowest doses from SAD part are deemed safe.

Conditions

Healthy

Keywords

voriconazole; inhaled; VFEND; aspergillosis; IPA; fungal infection; pulmonary aspergillosis

Outcome Measures

Primary Outcomes (18)

• Number of participants who experience Adverse Events (AEs), Serious Adverse Events (SAEs) and withdrawals due to AEs

  Number of AEs, SAEs, and discontinuations due to AEs

  Through study completion, an average of 14 days

• Number of participants who experience vital sign abnormalities

  Number of participants with potentially clinically significant vital sign values

  Baseline through study completion, an average of 14 days

• Number of participants who experience pulse oximetry abnormalities

  Number of participants with potentially clinically significant pulse oximetry values

  Baseline through study completion, an average of 14 days

• Mean change from baseline in forced expiratory volume (FEV1)

  Spirometry used to measure FEV1 lung function

  Baseline through study completion, an average of 14 days

• Mean change from baseline in forced vital capacity (FVC)

  Spirometry used to measure FVC lung function

  Baseline through study completion, an average of 14 days

• Mean change from baseline in FEV1/FVC ratio

  Spirometry used to measure FEV1 and FVC lung function

  Baseline through study completion, an average of 14 days

• Mean change from baseline in QTcF changes via ECG

  Number of participants with potentially clinically significant ECG values

  Baseline through study completion, an average of 14 days

• Number of participants who experience physical examination abnormalities

  Number of participants with potentially clinically significant physical examination findings

  Baseline through study completion, an average of 14 days

• Number of participants who experience laboratory test abnormalities

  Number of participants with potentially clinically significant laboratory test results

  Baseline through study completion, an average of 14 days

• PK of VIP in plasma: Area under the plasma-concentration time curve (AUC)

  Blood samples will be collected for plasma analysis

  Predose Day 1 and through 12 hours post last dose (day 6)

• PK of VIP in plasma: Area under the concentration time curve, from time 0 to the last observed non-zero concentration (AUC0-tlast)

  Blood samples will be collected for analysis

  Predose Day 1 and through 12 hours post last dose (day 6)

• PK of VIP in plasma: Maximum observed concentration (Cmax)

  Blood samples will be collected for analysis

  Predose Day 1 and through 12 hours post last dose (day 6)

• PK of VIP in plasma: Time to maximal observed concentration (tmax)

  Blood samples will be collected for analysis

  Predose Day 1 and through 12 hours post last dose (day 6)

• PK of VIP in plasma: Area under the plasma-concentration time curve over the first 12 hours after dosing (AUC0-12)

  Blood samples will be collected for analysis

  Predose Day 1 and through 12 hours post last dose (day 6)

• PK of VIP in plasma: Area under the concentration time curve from time 0 extrapolated to infinity (AUC∞)

  Blood samples will be collected for analysis

  Predose Day 1 and through 12 hours post last dose (day 6)

• PK of VIP in plasma: Termination elimination half-life (t½)

  Blood samples will be collected for analysis

  Predose Day 1 and through 12 hours post last dose (day 6)

• PK of VIP in plasma: Apparent total body clearance (CL/F)

  Blood samples will be collected for analysis

  Predose Day 1 and through 12 hours post last dose (day 6)

• PK of VIP in plasma: Apparent volume of distribution during the terminal elimination phase (Vz/F)

  Blood samples will be collected for analysis

  Predose Day 1 and through 12 hours post last dose (day 6)

Study Arms (2)

Voriconazole Inhalation Powder

EXPERIMENTAL

Investigational drug will be supplied as capsules, each capsule contains 10 mg of Voriconazole Inhalation Powder. The capsules will be administered with the provided breath actuated Plastiape RS00 Model 8 Dry Powder Inhaler device.

Drug: Voriconazole Inhalation Powder

Placebo

PLACEBO COMPARATOR

Placebo will be supplied as capsules, each capsule will contain no active ingredient. The capsules will be administered with the provided breath actuated Plastiape RS00 Model 8 Dry Powder Inhaler device.

Drug: Placebo

Interventions

Voriconazole Inhalation Powder DRUG

PART A (SAD): Voriconazole Inhalation Powder (VIP) will be supplied as one to eight 10 mg capsules. Each capsule contains 10 mg of VIP and will be administered with a Plastiape RS00 Dry Powder inhaler. Doses may require multiple inhalations. All inhalations must be conducted within a 10-minute period. SAD subjects will receive a single dose of study medication. Subjects in Cohort 1 will receive 10 mg, Cohort 2: 20 mg, Cohort 3: 40 mg, Cohort 4: 80 mg. PART B (MAD): Voriconazole Inhalation Powder (VIP) and will be administered with a will be supplied as one to eight 10 mg capsules. Each capsule contains 10 mg of VIP and will be administered with a Plastiape RS00 Dry Powder inhaler. Doses may require multiple inhalations. All inhalations must be conducted within a 10-minute period. MAD subjects will receive VIP BID for a total of 13 doses. Subjects in Cohort 1 will receive 10 mg BID, Cohort 2: 20 mg BID, Cohort 3: 40 mg BID, Cohort 4: 80 mg BID.

Also known as: VIP

Voriconazole Inhalation Powder

Placebo DRUG

PART A (SAD): Placebo capsules will be supplied as one to eight capsules. Each capsule contains placebo inhalation powder. The capsules will be matched for use within the provided Plastiape RS00 Dry Powder inhaler device (Model 8). Doses may require multiple inhalations through the inhaler device. All inhalations must be conducted within a maximum of 10-minute period. Subjects in PART A will receive a single dose of placebo. PART B (MAD): Placebo will be supplied as one to eight capsules. Each capsule contains placebo inhalation powder. The capsules will be matched for use within the provided Plastiape RS00 Dry Powder inhaler device (Model 8). Doses may require multiple inhalations through the inhaler device. All inhalations must be conducted within a maximum of 10-minute period. Subjects in PART B will receive Placebo BID for a total of 13 doses.

Also known as: Vehicle

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Provide written informed consent to participate.
• Healthy, adult males or females (women of non-childbearing potential only).
• Body mass index (BMI) ≥ 18.0 and ≤ 32.0 kg/m2 at Screening.
• Medically healthy with no clinically significant abnormalities in medical history, physical and visual examination, laboratory profiles, vital signs or ECGs, as deemed by the PI or designee.
• Agree to abstain from recreational drug use throughout the study.
• Must be willing and able to comply with the protocol.
• Succeed in training on the use of the device for maximum of 12 inhalations in total, with demonstration of at-least 8 successful inhalations of empty capsules during training.
• Have had a forced expiratory volume in one second (FEV1) ≥80%.

You may not qualify if:

• Is mentally or legally incapacitated or has significant emotional problems in the opinion of the PI.
• History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the PI.
• History of any illness that, in the opinion of the PI, might confound the results of the study or poses an additional risk to the subject by their participation in the study.
• History or presence of alcoholism or drug abuse within the past 2 years.
• History or presence of hypersensitivity or idiosyncratic reaction to voriconazole or any triazole antifungal.
• Has had surgery or any medical condition within 6 months prior to first dosing which may affect the absorption, distribution, metabolism, or elimination of the study drug, in the opinion of the PI or designee.
• Female subjects of childbearing potential.
• Female subjects with a positive pregnancy test or who are lactating.
• Positive urine drug or alcohol results at screening or first check-in.
• Positive cotinine results at screening.
• Diagnosis of asthma.
• Use of albuterol or a similar bronchodilator
• Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV).
• QTcF interval is \>450 msec or has ECG findings deemed abnormal with clinical significance by the PI at screening.
• Seated blood pressure with systolic less than 90 mmHg or diastolic less than 60 mm/Hg or with a systolic greater than 140 mmHg or diastolic greater than 90 mmHg at screening.

Sponsors & Collaborators

• TFF Pharmaceuticals, Inc.: lead

Study Sites (1)

Cliantha Research

Mississauga, Ontario, L4W 1N2, Canada

Location

MeSH Terms

Conditions

Respiratory Aspiration; Aspergillosis; Mycoses; Pulmonary Aspergillosis

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Bacterial Infections and Mycoses; Infections; Lung Diseases, Fungal; Lung Diseases

Study Officials

• Dale Christensen, PhD

  TFF Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The investigators, study coordinators, study subjects and the Sponsor will be blinded to treatment assignment.
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part A: Eight (8) subjects will participate in each of the 4 dose escalations. Subjects will be randomized to receive either Voriconazole Inhalation Powder or placebo by inhalation (6 active, 2 placebo per group of 8). Part B: Eight (8) subjects will participate in each of the 4 dose escalations. Subjects will be randomized to receive either Voriconazole Inhalation Powder or placebo by inhalation (6 active, 2 placebo per group of 8).

Study Record Dates

• First Submitted: April 29, 2021
• First Posted: May 4, 2021
• Study Start: November 22, 2019
• Primary Completion: July 29, 2020
• Study Completion: August 26, 2020
• Last Updated: May 6, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)