A Study of the Pharmacokinetics, Safety and Tolerability of Single Doses of VR647 Inhalation Suspension Administered Using the VR647 Inhalation System in Children With Wheezing, Reactive Airway Disease or Mild Asthma
Condition: Wheezing; Reactive Airway Disease; Mild Asthma
MeSH terms: Asthma; Respiratory Aspiration; Bronchial Hyperreactivity; Respiratory Sounds
Intervention: VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System; 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer
Intervention description: The VR647 Inhalation System consists of the VR647 Inhalation System 1 control unit, a VR647 nebulizer handset, a mouthpiece and VR647 Smart Cards designed specifically for this trial.; Commercial Pulmicort Respules (budesonide inhalation suspension 1 mg/2 mL) delivered by a conventional jet nebulizer operated to sputtering.
Intervention MeSH terms: Budesonide
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: This is an open label, randomized, balanced, incomplete block design trial. Eligible subjects will be randomized to 1 of 12 treatment sequences (A,B), (A,C), (A,D), (B,A), (B,C), (B,D), (C,A), (C,B), (C,D), (D,A), (D,B) or (D,C), corresponding to the following treatment regimens:
(A) 5 breaths of VR647 Inhalation Suspension delivered by the VR647 Inhalation System
(B) 10 breaths of VR647 Inhalation Suspension delivered by the VR647 Inhalation System
(C) 20 breaths of VR647 Inhalation Suspension delivered by the VR647 Inhalation System
(D) 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer nebulized to empty
The treatment period comprises 2 dosing visits. Each subject will receive their first treatment regimen during Visit 2 and their second treatment regimen during Visit 3.
Masking: None (Open Label)
Masking description: This is an open label trial.
Enrollment: 17.0
Sex: All
Minimum age: 4 Years
Maximum age: 8 Years
Healthy volunteers: No
Keywords: mild asthma; budesonide; nebulizer; pediatric; pharmacokinetics

Summary:

      The primary objective of this study is to evaluate budesonide levels in the blood following
      inhalation of single doses of VR647 Inhalation Suspension in children with wheezing, reactive
      airway disease or mild asthma using a nebulizer, the VR647 Inhalation System. Secondary
      objectives include the evaluation of the safety and tolerability of VR647 Inhalation
      Suspension administered using the VR647 Inhalation System.

      The study consists of four visits; a screening visit (Visit 1), two dosing days (Visits 2 and
      3) and a follow-up visit (Visit 4). On each dosing day a single dose of treatment will be
      administered. Treatment allocation at Visits 2 and 3 is determined by a balanced incomplete
      block design.
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Male or pre-menarchal female subjects.

          -  Aged 4 to 8 years, inclusive.

          -  Diagnosis of wheezing, reactive airway disease or mild asthma confirmed by a physician
             at least 3 months prior to screening.

          -  Wheezing, reactive airway disease or mild asthma controlled by intermittent or regular
             non-steroidal medications commonly used for asthma, such as short-acting β2-agonists
             (SABAs) or leukotriene receptor antagonists (LTRAs), for a minimum of 28 days prior to
             the Screening Visit.

          -  Body weight ≥15 kg.

          -  Subject is able to demonstrate the ability to use the VR647 Inhalation System and the
             conventional jet nebulizer effectively during training.

        Key Exclusion Criteria:

          -  Clinically relevant abnormality or medical condition (other than wheezing, reactive
             airway disease or mild asthma) identified at the screening assessment that, in the
             opinion of the investigator, could interfere with the objectives of the trial or the
             safety of the subject. The sponsor's medical officer should be consulted in case of
             any doubt.

          -  Life-threatening asthma, defined as a history of asthma episode(s) requiring
             intubation, and/or associated with hypercapnia, respiratory arrest, hypoxic seizures,
             or asthma-related syncopal episodes.

          -  Subjects currently using long-acting β2-agonists.

          -  Use of the following prescription medications within 28 days prior to the first
             treatment day: corticosteroids by any route and drugs that inhibit cytochrome P450
             3A4.