NCT04229303

Phase 1 Three Part SAD, MAD & Cross-Over Study of ZP-059 in Healthy and Asthmatic Subjects

To Assess Safety, PK of Inhaled Voriconazole (ZP-059) Single Doses in Healthy Subjects (Part 1), ZP-059 Multiple Doses in Stable Asthma (Part 2) and in a Crossover Trial of ZP-059 and Oral Voriconazole Single Doses in Stable Asthma (Part 3)

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 58 (actual)
• Sponsor: Zambon SpA · Industry
• Sex: All
• Age: 18 Years – 60 Years
• Healthy volunteers: Accepted

Summary

The primary safety objectives were: * Part 1: To determine the safety and tolerability of single doses of ZP-059 in healthy subjects * Part 2: To determine the safety and tolerability of multiple doses of ZP-059 in subjects with mild stable asthma * Part 3: To determine the safety and tolerability of single doses of ZP-059 in subjects with mild to moderate stable asthma. The primary PK objectives were: * Part 1: To characterize systemic PK of voriconazole and N-oxide voriconazole after single doses of ZP-059 in healthy subjects * Part 2: To characterize systemic PK of voriconazole and N-oxide voriconazole after multiple doses of ZP-059 in subjects with mild stable asthma * Part 3: To characterize systemic PK of voriconazole and N-oxide voriconazole after single doses of ZP-059 and single doses of oral voriconazole in subjects with mild to moderate stable asthma.

Detailed description

This was an integrated Phase 1, single centre, multi-part, open-label study in both healthy subjects (Part 1), subjects with mild stable asthma (Part 2) and subjects with mild to moderate stable asthma (Part 3). In all three parts of the study every effort was made to include as close as possible an equal balance between male and female subjects. This study assessed safety, tolerability and PK of single and multiple ascending doses of ZP-059 capsules administered as dry powder for inhalation in Part 1 to healthy volunteers (single ascending dose; SAD) and in Part 2 to subjects with mild asthma (multiple ascending dose; MAD), respectively. In Part 3, the bioavailability of ZP-059 in subjects with mild to moderate stable asthma were compared to that of oral voriconazole. Part 3 started only after review of safety data from cohorts 1 to 4 of Part 1 (SAD) have been completed. Parts 2 and 3 of the study also explored voriconazole concentrations in induced sputum samples in asthmatic subjects. As part of the safety and tolerability assessment, this study investigated the effects of ZP-059 on airway function in both mild and mild to moderate stable asthma subjects.

Conditions

• Allergic Bronchopulmonary Aspergillosis

Interventions

Type	Name	Description
DRUG	Voriconazole inhaled	Part 1 (SAD): eligible subjects received a single ascending inhaled dose (5 mg, 10 mg, 20 mg, and 40 mg) of ZP-059 5mg capsules administered via dry powder inhaler (DPI) on the morning of Day 1. Part 2 (MAD): eligible subjects received 2 (10mg twice daily \[BID\]) or 4 \[20mg BID\]) inhaled doses of ZP-059 5mg capsules administered via DPI BID for 9 days and once in the morning of Day 10, or 8 inhaled doses of ZP-059 5 mg capsules (40mg once daily \[QD\]) for 10 days. For QD dosing, subjects received QD doses of ZP-059 (at hour 0) on Days 1 to 10. Part 3 (2-period crossover): eligible subjects received a 4 \[20mg BID\] inhaled doses of ZP-059 5mg capsules administered via DPI on the morning of Day 1 according to the crossover scheme of the study. ZP-059 (inhaled voriconazole) was provided in clear, colorless size 3 hydroxypropylmethylcellulose hard capsules, which were individually and manually triggered by a breath actuated inhalation device (RS01 monodose inhaler).
DRUG	oral voriconazole	Part 3 (2-period crossover): eligible subjects received a single dose of oral voriconazole (200mg oral film-coated tablet, Vfend) on the morning of Day 1 according to the crossover scheme of the study.

Timeline

• Start date: 2020-02-11
• Primary completion: 2020-08-31
• Completion: 2020-08-31
• First posted: 2020-01-18
• Last updated: 2021-11-15
• Results posted: 2021-11-15

Locations

1 site across 1 country: United Kingdom