Pharmacokinetic Profile of Voriconazole Inhalation Powder in Adult Subjects With Asthma
Condition: Asthma
MeSH terms: Asthma
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): Voriconazole Inhalation Powder; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 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).; 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).
Other intervention name(s): VIP; Vehicle
Intervention MeSH terms: Voriconazole
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: 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
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: voriconazole; asthmatic; inhaled; VFEND; aspergillosis; IPA; fungal infection; pulmonary aspergillosis