Single Ascending Dose and Multiple Ascending Dose Study of Voriconazole Inhalation Powder in Healthy Adult Subjects
Condition: Healthy
MeSH terms: Respiratory Aspiration
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a Phase 1 (healthy adult volunteers), 2-part, double-blind, randomized, placebo
      controlled trial to evaluate the safety and pharmacokinetic (PK) profiles of escalating
      single doses of Voriconazole Inhalation Powder versus placebo (SAD part) and escalating
      multiple doses of Voriconazole Inhalation Powder versus placebo (MAD part). SAD part will be
      initiated first and includes a sentinel design. MAD part will not utilize a sentinel design
      and will be initiated once the lowest doses from SAD part are deemed safe.
    

Detailed description: 
      This is a Phase 1, randomized, 2 part double-blind, placebo-controlled trial to evaluate the
      safety and PK profiles of Voriconazole Inhalation Powder (VIP) in a SAD/MAD study design.

      Part A is a double-blinded, placebo-controlled, randomized, dose- ranging single dose study
      evaluating four different dose levels.

      On Day 1 of each group, two selected subjects (sentinel subjects) will receive either
      Voriconazole Inhalation Powder or a matching placebo. Blood and sputum samples and safety
      measurements including Adverse Events (AEs) will be collected over 24 hour period following
      the drug administration. The safety results to be evaluated include AEs, concomitant
      medications, out of specification clinical laboratory results, vital signs,
      Electrocardiograms (ECGs), visual examinations, pulmonary function tests, pulse oximetry
      results and any new findings on physical examinations. If the administration is safe as
      deemed by Principal Investigator & Medical Monitor, the remaining six subjects will be dosed,
      with identical safety and PK procedures performed after minimum of 3 days interval. A minimum
      of 3 days will separate each dose escalation, with the remaining dose groups dosed in a
      sentinel fashion.

      Part B is a double-blinded, placebo-controlled, randomized, dose- ranging multi-dose study
      evaluating four different dose levels. Dose level 1 of Part B can begin in parallel once
      safety assessments of Part A dose level 2 are complete and indicate safety is present.
      Voriconazole Inhalation Powder will be administered twice daily (BID) × 13 doses. Blood
      samples for safety and PK will be collected over 12 hours after the first dose and 24 hours
      after the last dose. A minimum of 1 week will separate the start of each dose escalation,
      with the remaining dose groups.
    

Intervention name(s): Voriconazole Inhalation Powder; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): PART A (SAD): Voriconazole Inhalation Powder (VIP) will be supplied as one to eight 10 mg capsules. Each capsule contains 10 mg of VIP and will be administered with a Plastiape RS00 Dry Powder inhaler. Doses may require multiple inhalations. All inhalations must be conducted within a 10-minute period.
SAD subjects will receive a single dose of study medication. Subjects in Cohort 1 will receive 10 mg, Cohort 2: 20 mg, Cohort 3: 40 mg, Cohort 4: 80 mg.
PART B (MAD): Voriconazole Inhalation Powder (VIP) and will be administered with a will be supplied as one to eight 10 mg capsules. Each capsule contains 10 mg of VIP and will be administered with a Plastiape RS00 Dry Powder inhaler. Doses may require multiple inhalations. All inhalations must be conducted within a 10-minute period.
MAD subjects will receive VIP BID for a total of 13 doses. Subjects in Cohort 1 will receive 10 mg BID, Cohort 2: 20 mg BID, Cohort 3: 40 mg BID, Cohort 4: 80 mg BID.; PART A (SAD): Placebo capsules will be supplied as one to eight capsules. Each capsule contains placebo inhalation powder. The capsules will be matched for use within the provided Plastiape RS00 Dry Powder inhaler device (Model 8). Doses may require multiple inhalations through the inhaler device. All inhalations must be conducted within a maximum of 10-minute period.
Subjects in PART A will receive a single dose of placebo.
PART B (MAD): Placebo will be supplied as one to eight capsules. Each capsule contains placebo inhalation powder. The capsules will be matched for use within the provided Plastiape RS00 Dry Powder inhaler device (Model 8). Doses may require multiple inhalations through the inhaler device. All inhalations must be conducted within a maximum of 10-minute period.
Subjects in PART B will receive Placebo BID for a total of 13 doses.
Other intervention name(s): VIP; Vehicle
Intervention MeSH terms: Voriconazole
Allocation: Randomized
Intervention model: Sequential Assignment
Intervention model description: Part A: Eight (8) subjects will participate in each of the 4 dose escalations. Subjects will be randomized to receive either Voriconazole Inhalation Powder or placebo by inhalation (6 active, 2 placebo per group of 8).
Part B: Eight (8) subjects will participate in each of the 4 dose escalations. Subjects will be randomized to receive either Voriconazole Inhalation Powder or placebo by inhalation (6 active, 2 placebo per group of 8).
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: voriconazole; inhaled; VFEND; aspergillosis; IPA; fungal infection; pulmonary aspergillosis