Phase 1 Three Part SAD, MAD & Cross-Over Study of ZP-059 in Healthy and Asthmatic Subjects
Condition: Allergic Bronchopulmonary Aspergillosis
MeSH terms: Aspergillosis; Pulmonary Aspergillosis; Aspergillosis, Allergic Bronchopulmonary
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): Voriconazole inhaled; oral voriconazole
Intervention type(s): Drug; Drug
Intervention description(s): 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).; 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.
Other intervention name(s): ZP-059; Vfend
Intervention MeSH terms: Voriconazole
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Safety, tolerability and PK will be assessed following either single ascending (SAD) or multiple ascending (MAD) dosing of ZP-059; Part 1 and Part 2, respectively. Part 1 will comprise 4 separate cohorts planned to receive single doses of ZP-059; part 2 will comprise 3 separate cohorts planned to receive daily doses of ZP-059 on Day 1 to 10; part 3 is a 2-period, randomised crossover study in subjects with mild to moderate stable asthma to assess the safety, tolerability and PK of single doses of ZP-059 and single doses of oral voriconazole.
Masking: None (Open Label)
Primary purpose: Other
Keywords: ABPA; Asthma; Voriconazole; Allergic Bronchopulmonary Aspergillosis