Pharmacokinetic Profile of Voriconazole Inhalation Powder in Adult Subjects With Asthma

NCT04576325 | Completed Phase 1 FDA Drug

• 1 other identifier: TFF-V1-002
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1b, randomized, double-blind, placebo-controlled trial to evaluate the safety, tolerability, and pharmacokinetic profiles of voriconazole inhalation powder in adult subjects with well-controlled asthma. This study will involve 2 cohorts.

Conditions

Asthma

Keywords

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

Outcome Measures

Primary Outcomes (10)

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

  Frequency 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 forced expiratory flow over the middle 1/2 of the FVC (FEF25-75%)

  Spirometry used to measure FVC and FEF25-75% 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

Secondary Outcomes (9)

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

  Predose Day 1 and through 12 hours post last dose (day 4)

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

  Predose Day 1 and through 12 hours post last dose (day 4)

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

  Predose Day 1 and through 12 hours post last dose (day 4)

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

  Predose Day 1 and through 12 hours post last dose (day 4)

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

  Predose Day 1 and through 12 hours post last dose (day 4)

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

For each dose, multiple inhalations will be required (4 capsules in Cohort 1 and 8 capsules in Cohort 2). All capsules for a given dose must be inhaled over a maximum 10-minute period. Cohort 1 will receive 40 mg BID and Cohort 2 will receive 80 mg BID. Both Cohorts will administer study drug for 3.5 days (7 days total).

Also known as: VIP

Voriconazole Inhalation Powder

Placebo DRUG

For each dose, multiple inhalations will be required (4 capsules in Cohort 1 and 8 capsules in Cohort 2). All capsules must be inhaled over a maximum 10-minute period. Cohort 1 will receive 4 capsules of inactive BID and Cohort 2 will receive 8 capsules of inactive BID. Both Cohorts will administer placebo capsules for 3.5 days (7 days total).

Also known as: Vehicle

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Provide written informed consent to participate and is willing and able to participate in the study and abide by study restrictions in the judgement of the Investigator.
• Males or non-pregnant, non-lactating females.
• Well-controlled Step 2 or Step 3 asthma defined by the GINA guidelines.
• Body mass index (BMI) ≥ 18.0 and ≤ 35.0 kg/m2 at Screening.
• Normal blood pressure at Screening and Check-In.
• Normal clinical laboratory tests at Screening and Check-In.
• Negative for hepatitis B surface antigen (HBsAg), hepatitis C antibody, human immunodeficiency virus (HIV) I and II antibodies, tuberculosis (TB), or COVID-19 at Screening.
• Able to successfully perform spirometry and use the inhalation device, as demonstrated at Screening and Check-In.

You may not qualify if:

• History or presence of clinically significant medical, ophthalmic, or psychiatric conditions or diseases in the opinion of the Investigator or designee.
• History or current evidence of any chronic upper or lower respiratory conditions other than asthma or allergic (seasonal or perennial), or non-allergic rhinitis. History of mild acute upper or lower respiratory conditions are allowed, provided that it has been at least 3 months since the condition resolved and provided that in the Investigator's judgement, this occurrence poses no additional risk for this subject.
• History of any illness or surgery within 6 months of Screening that, in the opinion of the Investigator, might confound the results of the study or that poses an additional risk to the subject by their participation in the study.
• Current or former smokers, users of e-cigarettes or nicotine replacement products who have more than a 10-pack year history of smoking and who have used these products within the 6 months prior to Screening.
• History or presence of alcoholism or drug abuse within the past 2 years prior to Screening.
• History or presence of hypersensitivity or idiosyncratic reaction to voriconazole or any triazole antifungal.
• Received any marketed or investigational biologic within 4 months or 5 half-lives prior to dosing, whichever is longer.
• Received treatment with investigational study drug (or device) in another clinical study within 30 days or five half-lives of dosing, whichever is longer.
• Subjects who have taken any of the protocol prohibited medications within 30 days of the first dose or who are expected to require these medications during the study.
• ECG with a QTcF interval \>450 msec for males or QTcF interval \> 470 msec for females or ECG findings deemed clinically significantly abnormal by the Investigator prior to the first dose.
• Unable to refrain from or anticipates the use of any vitamin supplements, prescription, over-the-counter (OTC), herbal preparations or medications other than those specified for asthma or allergic rhinitis medications, or topical ophthalmic drops beginning 14 days prior to the first dose and throughout the study.
• Females requiring hormone replacement therapy within 30 days of Screening or during the study.
• Allergy or sensitivity to lactose or milk products.
• Donation of blood or blood products within the last 2 months.
• Loss of 50 to 500 mL whole blood within the past two months.

Sponsors & Collaborators

• TFF Pharmaceuticals, Inc.: lead

Study Sites (1)

Q-Pharm Pty Ltd (Nucleus Networks)

Brisbane, Queensland, 4006, Australia

Location

MeSH Terms

Conditions

Asthma; Respiratory Aspiration; Aspergillosis; Mycoses; Pulmonary Aspergillosis

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Respiration Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Bacterial Infections and Mycoses; Infections; Lung Diseases, Fungal

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: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: In each cohort, 8 eligible subjects will be randomized in a 3:1 ratio (6 on active and 2 on placebo) to receive 7 doses (over 3.5 days) of VIP BID or placebo

Study Record Dates

• First Submitted: September 25, 2020
• First Posted: October 6, 2020
• Study Start: November 15, 2020
• Primary Completion: November 12, 2021
• Study Completion: November 12, 2021
• Last Updated: November 18, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)