NCT04576325

Pharmacokinetic Profile of Voriconazole Inhalation Powder in Adult Subjects With Asthma

A Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety, Tolerability, and Pharmacokinetic Profile of Voriconazole Inhalation Powder in Adult Subjects With Asthma

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 17 (actual)
• Sponsor: TFF Pharmaceuticals, Inc. · Industry
• Sex: All
• Age: 18 Years – 55 Years
• Healthy volunteers: Not accepted

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.

Detailed description

This is a Phase 1b, randomized, double-blind, placebo-controlled trial to evaluate the safety, tolerability, and pharmacokinetic (PK) profiles of voriconazole inhalation powder (VIP) in adult subjects with well-controlled Step 2 or Step 3 asthma. This study will involve a minimum of 2 cohorts. The first 2 subjects randomized into each cohort will be sentinel subjects (i.e., one assigned to VIP and one assigned to placebo). If study drug is deemed safe by the PI, the remaining 6 subjects (5 on VIP and 1 on placebo) may be enrolled. * In Cohort 1, 8 eligible subjects will be randomized in a 3:1 ratio (6 on active and 2 on placebo) to receive 7 doses BID (over 3.5 days) of 40mg VIP or inhaled placebo. Following completion of Cohort 1 and after dose escalation has been approved by the SMC, Cohort 2 may begin. * In Cohort 2, 8 eligible subjects will be randomized in a 3:1 ratio to receive 7 doses BID (over 3.5 days) of 80 mg VIP or placebo . Doses will be administered twice daily every 12 (± 1 hours). A third cohort with the same design and number of subjects may be initiated if there are safety or other findings from Cohort 2 that warrant investigation of an intermediary dose (e.g., VIP 60 mg BID). The decision to initiate this potential 3rd cohort will be made by the Sponsor in collaboration with the safety monitoring committee (SMC). A sentinel design will not be required for this cohort. Following a variable length Screening period, all subjects will be domiciled in a clinical research facility from the Check-In Day (Day -1) and will remain domiciled until the morning of Day 5. A follow-up phone call or clinic visit (depending on best practices at the time for Coronavirus Disease 2019 \[COVID-19\] precautions) will be made one week later to assess subject status and record any adverse events (AEs). Safety will be assessed by monitoring AEs, clinical laboratory tests, vital signs, pulse oximetry, spirometry, 12-lead ECGs, and physical examinations. Blood PK will be assessed from serial blood collections following Dose 1 and Dose 7. Study treatment stopping rules for individual subjects will be based on AEs, SAEs, required changes during the treatment period to asthma medications, spirometry measure of forced expiratory volume at 1 second (FEV1), and increases in QTcF values on ECG. The SMC will review the safety information accrued during the study and will be responsible for reviewing Cohort 1 safety information before authorizing dose escalation to Cohort 2.

Conditions

• Asthma

Interventions

Type	Name	Description
DRUG	Voriconazole Inhalation Powder	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).
DRUG	Placebo	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).

Timeline

• Start date: 2020-11-15
• Primary completion: 2021-11-12
• Completion: 2021-11-12
• First posted: 2020-10-06
• Last updated: 2021-11-18

Locations

1 site across 1 country: Australia

Regulatory

• FDA-regulated drug study