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

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. Blood samples will be collected on eight occasions from pre-dose up to 8 hours
post-dose at each dosing visit. Treatment allocation at Visits 2 and 3 is determined by a
balanced incomplete block design.

The screening period (including Visit 1) is between 2 and 30 days duration; there is a
washout period of 4 to 10 days between each dose (Visits 2 and 3) and the follow-up safety
assessment (Visit 4) will occur 5 to 9 days after Visit 3. Subjects and their parent(s)/legal
guardian(s) have the option of an overnight stay the day before dosing (Day -1, Visit 2 and
Day 7, Visit 3).

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.