Clinical trial NCT03421730: 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
Official title: A Single-dose, Open-label, Randomized, Incomplete Block Design Trial to Characterize the Pharmacokinetics of VR647 Inhalation Suspension Delivered by the VR647 Inhalation System and Single Doses of Budesonide Delivered by a Conventional Jet Nebulizer in Pediatric Subjects Aged 4 to 8 Years With Wheezing, Reactive Airway Disease or Mild Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Wheezing
Reactive Airway Disease
Mild Asthma
Keywords: mild asthma
budesonide
nebulizer
pediatric
pharmacokinetics
Lead sponsor: Vectura Limited
Sponsor class: INDUSTRY
First posted: 2018-02-05
Enrollment: 17
Sex: ALL
Minimum age (years): 4
Maximum age (years): 8
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
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.
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: AUClast of Plasma Budesonide (VR647 Inhalation Suspension Delivered by the VR647 Inhalation System or Pulmicort Respules Delivered by a Conventional Jet Nebulizer).
timeFrame: Pre-dose, and at 20 minutes, 40 minutes, 1.5, 3, 4, 6 and 8 hours after start of nebulization on Day 1 (Visit 2) and Day 8 (Visit 3).
measure: AUCinf of Plasma Budesonide (VR647 Inhalation Suspension Delivered by the VR647 Inhalation System or Pulmicort Respules Delivered by a Conventional Jet Nebulizer).
timeFrame: Pre-dose, and at 20 minutes, 40 minutes, 1.5, 3, 4, 6 and 8 hours after start of nebulization on Day 1 (Visit 2) and Day 8 (Visit 3).
measure: Cmax of Plasma Budesonide (VR647 Inhalation Suspension Delivered by the VR647 Inhalation System or Pulmicort Respules Delivered by a Conventional Jet Nebulizer).
timeFrame: Pre-dose, and at 20 minutes, 40 minutes, 1.5, 3, 4, 6 and 8 hours after start of nebulization on Day 1 (Visit 2) and Day 8 (Visit 3).
measure: Tmax of Plasma Budesonide (VR647 Inhalation Suspension Delivered by the VR647 Inhalation System or Pulmicort Respules Delivered by a Conventional Jet Nebulizer).
timeFrame: Pre-dose, and at 20 minutes, 40 minutes, 1.5, 3, 4, 6 and 8 hours after start of nebulization on Day 1 (Visit 2) and Day 8 (Visit 3).
measure: Tlast of Plasma Budesonide (VR647 Inhalation Suspension Delivered by the VR647 Inhalation System or Pulmicort Respules Delivered by a Conventional Jet Nebulizer).
timeFrame: Pre-dose, and at 20 minutes, 40 minutes, 1.5, 3, 4, 6 and 8 hours after start of nebulization on Day 1 (Visit 2) and Day 8 (Visit 3).
measure: T1/2 of Plasma Budesonide (VR647 Inhalation Suspension Delivered by the VR647 Inhalation System or Pulmicort Respules Delivered by a Conventional Jet Nebulizer).
timeFrame: Pre-dose, and at 20 minutes, 40 minutes, 1.5, 3, 4, 6 and 8 hours after start of nebulization on Day 1 (Visit 2) and Day 8 (Visit 3).
Secondary outcomes:
measure: Mean Modified Patient Satisfaction and Preference Questionnaire (PASAPQ) Total Score (Q1 to Q8).
timeFrame: Following dosing on Day 1 (Visit 2) and Day 8 (Visit 3).
measure: Mean Modified PASAPQ Performance Score
timeFrame: Following dosing on Day 1 (Visit 2) and Day 8 (Visit 3).
measure: Mean Modified PASAPQ Satisfaction Score (Q9).
timeFrame: Following dosing on Day 1 (Visit 2) and Day 8 (Visit 3).
measure: Mean Modified PASAPQ Score Indicating Willingness to Continue With the Device (Q10).
timeFrame: Following dosing on Day 1 (Visit 2) and Day 8 (Visit 3).
measure: Changes in Vital Signs (Blood Pressure)
timeFrame: Baseline to Day 1 0.5 hours post-dose
measure: Changes in Vital Signs (Heart Rate)
timeFrame: Baseline to Day 1 0.5 hours post-dose
measure: Changes in Vital Signs (Respiration Rate)
timeFrame: Baseline to Day 1 0.5 hours post-dose
measure: Changes in Vital Signs (Temperature)
timeFrame: Baseline to Day 1 0.5 hours post-dose
measure: Changes in Physical Examination
timeFrame: Visit 1, and Day 8 of Visit 3.
measure: Use of Concomitant Medications
timeFrame: Visit 1
Other outcomes:
Locations:
city: Colorado Springs
country: United States
facility: Vectura Study Site 0003
state: Colorado
city: Raleigh
country: United States
facility: Vectura Study Site 0002
state: North Carolina
city: Tulsa
country: United States
facility: Vectura Study Site 0001
state: Oklahoma
Study officials:
affiliation: Vectura Ltd
name: Gary Burgess, MD
role: STUDY_DIRECTOR
References: