WheezingPhase 1NCT03421730

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

A Phase 1 study testing VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System and 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer in people with Wheezing and Reactive Airway Disease, run by Vectura Limited at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 4 to 8 years
Conditions the study is for: Wheezing, Reactive Airway Disease, Mild Asthma
What is being tested?: VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System and 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 17 participants
Where: 3 sitesUnited States
Study dates: 18 Dec 2017to 27 Mar 2018
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 4 to 8 years
All sexes
No healthy volunteers
Child

Who may be able to join

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.

Who cannot join

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.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

Vectura Study Site 0003
Colorado Springs, Colorado, 80907
Vectura Study Site 0002
Raleigh, North Carolina, 27607
Vectura Study Site 0001
Tulsa, Oklahoma, 74136

Other trials in United States

About this study

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

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.

Conditions: Wheezing, Reactive Airway Disease, Mild Asthma
Being tested: 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
Keywords: mild asthma, budesonide, nebulizer, pediatric, pharmacokinetics
Medical subject headings: Respiratory Sounds, Pulmonary Disease, Chronic Obstructive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation SystemCombination product
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.
1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizerCombination product
Commercial Pulmicort Respules (budesonide inhalation suspension 1 mg/2 mL) delivered by a conventional jet nebulizer operated to sputtering.

Study groups in NCT03421730
Study group	Role	What they receive
AB - VR647 5 breaths, then VR647 10 breaths	Experimental	5 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System followed by 10 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System Receives: Combination Product: VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System
AC - VR647 5 breaths, then VR647 20 breaths	Experimental	5 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System followed by 20 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System Receives: Combination Product: VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System
AD - VR647 5 breaths, then Pulmicort	Experimental	5 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System followed by 1 mg/2 mL Pulmicort Respules delivered by the conventional jet nebulizer nebulized to empty Receives: Combination Product: VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System; Combination Product: 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer
BA - VR647 10 breaths, then VR647 5 breaths	Experimental	10 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System followed by 5 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System Receives: Combination Product: VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System
BC - VR647 10 breaths, then VR647 20 breaths	Experimental	10 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System followed by 20 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System Receives: Combination Product: VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System
BD - VR647 10 breaths, then Pulmicort	Experimental	10 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System followed by 1 mg/2 mL Pulmicort Respules delivered by the conventional jet nebulizer nebulized to empty Receives: Combination Product: VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System; Combination Product: 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer
CA - VR647 20 breaths, then VR647 5 breaths	Experimental	20 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System followed by 5 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System Receives: Combination Product: VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System
CB - VR647 20 breaths, then VR647 10 breaths	Experimental	20 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System followed by 10 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System Receives: Combination Product: VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System
CD - VR647 20 breaths, then Pulmicort	Experimental	20 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System followed by 1 mg/2 mL Pulmicort Respules delivered by the conventional jet nebulizer nebulized to empty Receives: Combination Product: VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System; Combination Product: 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer
DA - Pulmicort, then VR647 5 breaths	Experimental	1 mg/2 mL Pulmicort Respules delivered by the conventional jet nebulizer nebulized to empty followed by 5 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System Receives: Combination Product: VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System; Combination Product: 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer
DB - Pulmicort, then VR647 10 breaths	Experimental	1 mg/2 mL Pulmicort Respules delivered by the conventional jet nebulizer nebulized to empty followed by 10 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System Receives: Combination Product: VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System; Combination Product: 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer
DC - Pulmicort, then VR647 20 breaths	Experimental	1 mg/2 mL Pulmicort Respules delivered by the conventional jet nebulizer nebulized to empty followed by 20 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System Receives: Combination Product: VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System; Combination Product: 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer

What is being measured

The primary outcome is the main question the study is designed to answer.

AUClast of Plasma Budesonide (VR647 Inhalation Suspension Delivered by the VR647 Inhalation System or Pulmicort Respules Delivered by a Conventional Jet Nebulizer).
AUClast is the area under the plasma concentration-time curve, from time 0 to the time of the last measurable concentration (Clast).
Measured: 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).
AUCinf of Plasma Budesonide (VR647 Inhalation Suspension Delivered by the VR647 Inhalation System or Pulmicort Respules Delivered by a Conventional Jet Nebulizer).
AUCinf is the area under the plasma concentration-time curve, from time 0 extrapolated to infinity. AUCinf is calculated as the sum of AUClast plus the ratio of the last measurable plasma concentration (Clast) to the elimination rate constant (λz).
Measured: 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).
Cmax of Plasma Budesonide (VR647 Inhalation Suspension Delivered by the VR647 Inhalation System or Pulmicort Respules Delivered by a Conventional Jet Nebulizer).
Cmax is the maximum observed concentration.
Measured: 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).
Tmax of Plasma Budesonide (VR647 Inhalation Suspension Delivered by the VR647 Inhalation System or Pulmicort Respules Delivered by a Conventional Jet Nebulizer).
Tmax is the time to reach Cmax.
Measured: 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).
Tlast of Plasma Budesonide (VR647 Inhalation Suspension Delivered by the VR647 Inhalation System or Pulmicort Respules Delivered by a Conventional Jet Nebulizer).
Tlast is the time of the last measurable concentration (Clast).
Measured: 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).
T1/2 of Plasma Budesonide (VR647 Inhalation Suspension Delivered by the VR647 Inhalation System or Pulmicort Respules Delivered by a Conventional Jet Nebulizer).
T1/2 is the apparent first-order terminal elimination half-life.
Measured: 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 (10)

Mean Modified Patient Satisfaction and Preference Questionnaire (PASAPQ) Total Score (Q1 to Q8).
The PASAPQ is a validated multi-item measure of satisfaction and preference with inhaler devices. The modified PASAPQ consists of 10 questions. The first 8 questions generate the total score domain. Data from this questionnaire were listed by subject and summarized by treatment. The results from Questions 1 through 8 were added for each subject to generate the Total Score (n = Q1+Q2+Q3+Q4+Q5+Q6+Q7+Q8) and expressed as percentage of maximum total score (i.e., (n/56)*100). Questions 1 to 8 were answered using scores from 1 (i.e., very dissatisfied) to 7 (i.e., very satisfied).
Measured: Following dosing on Day 1 (Visit 2) and Day 8 (Visit 3).
Mean Modified PASAPQ Performance Score
The PASAPQ is a validated multi-item measure of satisfaction and preference with inhaler devices; it was originally a 15-item questionnaire, with performance assessed over 7 items. The modified PASAPQ (mPASAPQ) has 10 questions, including only 4 from the performance domain; the 3 questions not included were dropped from the mPASAPQ as they were not applicable to patient population and device under study. Questions 1, 2, 6, and 7 were assessed, covering satisfaction with nebulizer reliability, ease of inhalation, use and treatment time. Although specified in the protocol, the mPASAPQ performance score was not summarized in the efficacy analysis. The results for each question are presented below, however it was not considered appropriate to analyze the performance domain, as it is not possible to verify the validity of the questionnaire utilising only 4 of the original 7 questions. Questions were answered using scores from 1 (i.e., very dissatisfied) to 7 (i.e., very satisfied).
Measured: Following dosing on Day 1 (Visit 2) and Day 8 (Visit 3).
Mean Modified PASAPQ Satisfaction Score (Q9).
The PASAPQ is a validated multi-item measure of satisfaction and preference with inhaler devices. The modified PASAPQ consists of 10 questions. Question 9 asks for overall satisfaction with the device(s) used in the trial. Question 9 was answered using scores from 1 (i.e., very dissatisfied) to 7 (i.e., very satisfied).
Measured: Following dosing on Day 1 (Visit 2) and Day 8 (Visit 3).
Mean Modified PASAPQ Score Indicating Willingness to Continue With the Device (Q10).
The PASAPQ is a validated multi-item measure of satisfaction and preference with inhaler devices. The modified PASAPQ consists of 10 questions. Question 10 asks about willingness to continue with the device(s) used in the trial. Parents/legal guardians were asked to indicate how willing they would be for their child to use the nebulizer used during the study, providing a number between 0 (unwilling) and 100 (willing).
Measured: Following dosing on Day 1 (Visit 2) and Day 8 (Visit 3).
Changes in Vital Signs (Blood Pressure)
Mean values for blood pressure from pre-dose to 0.5 hours post-dose.
Measured: Baseline to Day 1 0.5 hours post-dose
Changes in Vital Signs (Heart Rate)
Mean values for heart rate from pre-dose to 0.5 hours post-dose.
Measured: Baseline to Day 1 0.5 hours post-dose
Changes in Vital Signs (Respiration Rate)
Mean values for respiratory rate from pre-dose to 0.5 hours post-dose.
Measured: Baseline to Day 1 0.5 hours post-dose
Changes in Vital Signs (Temperature)
Mean values for temperature from pre-dose to 0.5 hours post-dose.
Measured: Baseline to Day 1 0.5 hours post-dose
Changes in Physical Examination
Physical examination data were listed. The number of participants with a change in physical examination status (i.e. from normal to abnormal, or from abnormal to normal) is presented below.
Measured: Visit 1, and Day 8 of Visit 3.
Use of Concomitant Medications
Number of subjects using concomitant medications.
Measured: Visit 1

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

18 Dec 201727 Mar 2018

First posted5 Feb 2018
Study start18 Dec 2017
Primary completion21 Mar 2018
Study completion27 Mar 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for WheezingStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
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)
Enrolment: 17 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03421730
Sponsor's protocol ID: VR647/1/002
Status last verified: Oct 2019
First submitted: 12 Jan 2018
Last updated: 21 Oct 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 21 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT03421730
Acronym / sponsor ID: VR647/1/002
Conditions: Wheezing, Reactive Airway Disease, Mild Asthma
Keywords: mild asthma, budesonide, nebulizer, pediatric, pharmacokinetics
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 17 participants (actual)
Lead sponsor: Vectura LimitedIndustry (pharma, biotech, devices)
Study start: 18 Dec 2017 (actual)
Primary completion: 21 Mar 2018 (actual)
Study completion: 27 Mar 2018 (actual)
First posted: 5 Feb 2018 (actual)
Results: Posted 21 Oct 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 12
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.

Arm	Type	Receives
AB - VR647 5 breaths, then VR647 10 breaths	Experimental	Combination Product: VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System5 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System followed by 10 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System
AC - VR647 5 breaths, then VR647 20 breaths	Experimental	Combination Product: VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System5 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System followed by 20 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System
AD - VR647 5 breaths, then Pulmicort	Experimental	Combination Product: VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System, Combination Product: 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer5 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System followed by 1 mg/2 mL Pulmicort Respules delivered by the conventional jet nebulizer nebulized to empty
BA - VR647 10 breaths, then VR647 5 breaths	Experimental	Combination Product: VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System10 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System followed by 5 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System
BC - VR647 10 breaths, then VR647 20 breaths	Experimental	Combination Product: VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System10 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System followed by 20 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System
BD - VR647 10 breaths, then Pulmicort	Experimental	Combination Product: VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System, Combination Product: 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer10 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System followed by 1 mg/2 mL Pulmicort Respules delivered by the conventional jet nebulizer nebulized to empty
CA - VR647 20 breaths, then VR647 5 breaths	Experimental	Combination Product: VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System20 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System followed by 5 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System
CB - VR647 20 breaths, then VR647 10 breaths	Experimental	Combination Product: VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System20 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System followed by 10 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System
CD - VR647 20 breaths, then Pulmicort	Experimental	Combination Product: VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System, Combination Product: 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer20 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System followed by 1 mg/2 mL Pulmicort Respules delivered by the conventional jet nebulizer nebulized to empty
DA - Pulmicort, then VR647 5 breaths	Experimental	Combination Product: VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System, Combination Product: 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer1 mg/2 mL Pulmicort Respules delivered by the conventional jet nebulizer nebulized to empty followed by 5 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System
DB - Pulmicort, then VR647 10 breaths	Experimental	Combination Product: VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System, Combination Product: 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer1 mg/2 mL Pulmicort Respules delivered by the conventional jet nebulizer nebulized to empty followed by 10 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System
DC - Pulmicort, then VR647 20 breaths	Experimental	Combination Product: VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System, Combination Product: 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer1 mg/2 mL Pulmicort Respules delivered by the conventional jet nebulizer nebulized to empty followed by 20 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System

Who may qualify

Ages: 4 to 8 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (6 listed)

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.

Key exclusion criteria (4 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation SystemThe 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.	Combination product	AB - VR647 5 breaths, then VR647 10 breaths, AC - VR647 5 breaths, then VR647 20 breaths, AD - VR647 5 breaths, then Pulmicort, BA - VR647 10 breaths, then VR647 5 breaths, BC - VR647 10 breaths, then VR647 20 breaths, BD - VR647 10 breaths, then Pulmicort, CA - VR647 20 breaths, then VR647 5 breaths, CB - VR647 20 breaths, then VR647 10 breaths, CD - VR647 20 breaths, then Pulmicort, DA - Pulmicort, then VR647 5 breaths, DB - Pulmicort, then VR647 10 breaths, DC - Pulmicort, then VR647 20 breaths
1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizerCommercial Pulmicort Respules (budesonide inhalation suspension 1 mg/2 mL) delivered by a conventional jet nebulizer operated to sputtering.	Combination product	AD - VR647 5 breaths, then Pulmicort, BD - VR647 10 breaths, then Pulmicort, CD - VR647 20 breaths, then Pulmicort, DA - Pulmicort, then VR647 5 breaths, DB - Pulmicort, then VR647 10 breaths, DC - Pulmicort, then VR647 20 breaths

Primary outcome

AUClast of Plasma Budesonide (VR647 Inhalation Suspension Delivered by the VR647 Inhalation System or Pulmicort Respules Delivered by a Conventional Jet Nebulizer).
Time frame: 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).
AUClast is the area under the plasma concentration-time curve, from time 0 to the time of the last measurable concentration (Clast).
AUCinf of Plasma Budesonide (VR647 Inhalation Suspension Delivered by the VR647 Inhalation System or Pulmicort Respules Delivered by a Conventional Jet Nebulizer).
Time frame: 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).
AUCinf is the area under the plasma concentration-time curve, from time 0 extrapolated to infinity. AUCinf is calculated as the sum of AUClast plus the ratio of the last measurable plasma concentration (Clast) to the elimination rate constant (λz).
Cmax of Plasma Budesonide (VR647 Inhalation Suspension Delivered by the VR647 Inhalation System or Pulmicort Respules Delivered by a Conventional Jet Nebulizer).
Time frame: 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).
Cmax is the maximum observed concentration.
Tmax of Plasma Budesonide (VR647 Inhalation Suspension Delivered by the VR647 Inhalation System or Pulmicort Respules Delivered by a Conventional Jet Nebulizer).
Time frame: 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).
Tmax is the time to reach Cmax.
Tlast of Plasma Budesonide (VR647 Inhalation Suspension Delivered by the VR647 Inhalation System or Pulmicort Respules Delivered by a Conventional Jet Nebulizer).
Time frame: 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).
Tlast is the time of the last measurable concentration (Clast).
T1/2 of Plasma Budesonide (VR647 Inhalation Suspension Delivered by the VR647 Inhalation System or Pulmicort Respules Delivered by a Conventional Jet Nebulizer).
Time frame: 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).
T1/2 is the apparent first-order terminal elimination half-life.

10 secondary outcomes

Mean Modified Patient Satisfaction and Preference Questionnaire (PASAPQ) Total Score (Q1 to Q8).
Time frame: Following dosing on Day 1 (Visit 2) and Day 8 (Visit 3).
Mean Modified PASAPQ Performance Score
Time frame: Following dosing on Day 1 (Visit 2) and Day 8 (Visit 3).
Mean Modified PASAPQ Satisfaction Score (Q9).
Time frame: Following dosing on Day 1 (Visit 2) and Day 8 (Visit 3).
Mean Modified PASAPQ Score Indicating Willingness to Continue With the Device (Q10).
Time frame: Following dosing on Day 1 (Visit 2) and Day 8 (Visit 3).
Changes in Vital Signs (Blood Pressure)
Time frame: Baseline to Day 1 0.5 hours post-dose
Changes in Vital Signs (Heart Rate)
Time frame: Baseline to Day 1 0.5 hours post-dose
Changes in Vital Signs (Respiration Rate)
Time frame: Baseline to Day 1 0.5 hours post-dose
Changes in Vital Signs (Temperature)
Time frame: Baseline to Day 1 0.5 hours post-dose
Changes in Physical Examination
Time frame: Visit 1, and Day 8 of Visit 3.
Use of Concomitant Medications
Time frame: Visit 1

Results and safety

Results posted to the registry on 21 Oct 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
AB - VR647 5 Breaths, Then VR647 10 Breaths	1	1
AC - VR647 5 Breaths, Then VR647 20 Breaths	3	1
AD - VR647 5 Breaths, Then Pulmicort	1	1
BA - VR647 10 Breaths, Then VR647 5 Breaths	1	1
BC - VR647 10 Breaths, Then VR647 20 Breaths	3	3
BD - VR647 10 Breaths, Then Pulmicort	1	1
CA - VR647 20 Breaths, Then VR647 5 Breaths	1	1
CB - VR647 20 Breaths, Then VR647 10 Breaths	1	1
CD - VR647 20 Breaths, Then Pulmicort	1	1
DA - Pulmicort, Then VR647 5 Breaths	2	2
DB - Pulmicort, Then VR647 10 Breaths	1	1
DC - Pulmicort, Then VR647 20 Breaths	1	1

Primary outcome: AUClast of Plasma Budesonide (VR647 Inhalation Suspension Delivered by the VR647 Inhalation System or Pulmicort Respules Delivered by a Conventional Jet Nebulizer).

Time frame: 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).. Mean (Standard Deviation). Unit: pg*hr/mL

Measure	A - 5 Breaths VR647 n = 6	B - 10 Breaths VR647 n = 7	C - 20 Breaths VR647 n = 6	D - Pulmicort n = 5
Value	120.7 (20.498)	327.5 (119.49)	759.5 (311.79)	1357 (564.06)

A - 5 Breaths VR647 vs D - Pulmicort: Geometric mean ratio (%): 8.69
B - 10 Breaths VR647 vs D - Pulmicort: Geometric mean ratio (%): 28.18
C - 20 Breaths VR647 vs D - Pulmicort: Geometric mean ratio (%): 59.51

Population analysed: Pharmacokinetic set included 13 (76%) subjects.

Primary outcome: AUCinf of Plasma Budesonide (VR647 Inhalation Suspension Delivered by the VR647 Inhalation System or Pulmicort Respules Delivered by a Conventional Jet Nebulizer).

Time frame: 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).. Mean (Standard Deviation). Unit: pg*hr/mL

Measure	A - 5 Breaths VR647 n = 4	B - 10 Breaths VR647 n = 6	C - 20 Breaths VR647 n = 5	D - Pulmicort n = 4
Value	138.3 (25.189)	326.2 (116.09)	737.1 (313.27)	1492 (707.99)

A - 5 Breaths VR647 vs D - Pulmicort: Geometric mean ratio (%): 13.35
B - 10 Breaths VR647 vs D - Pulmicort: Geometric mean ratio (%): 35.97
C - 20 Breaths VR647 vs D - Pulmicort: Geometric mean ratio (%): 76.98

Population analysed: Pharmacokinetic set included 13 (76%) subjects.

Primary outcome: Cmax of Plasma Budesonide (VR647 Inhalation Suspension Delivered by the VR647 Inhalation System or Pulmicort Respules Delivered by a Conventional Jet Nebulizer).

Time frame: 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).. Mean (Standard Deviation). Unit: pg/mL

Measure	A - 5 Breaths VR647 n = 6	B - 10 Breaths VR647 n = 7	C - 20 Breaths VR647 n = 6	D - Pulmicort n = 5
Value	71.25 (9.5776)	179.7 (79.442)	390.3 (178.07)	601.8 (405.32)

A - 5 Breaths VR647 vs D - Pulmicort: Geometric mean ratio (%): 9.55
B - 10 Breaths VR647 vs D - Pulmicort: Geometric mean ratio (%): 32.42
C - 20 Breaths VR647 vs D - Pulmicort: Geometric mean ratio (%): 59.75

Population analysed: Pharmacokinetic set included 13 (76%) subjects.

Primary outcome: Tmax of Plasma Budesonide (VR647 Inhalation Suspension Delivered by the VR647 Inhalation System or Pulmicort Respules Delivered by a Conventional Jet Nebulizer).

Time frame: 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).. Median (Full Range). Unit: hours

Measure	A - 5 Breaths VR647 n = 6	B - 10 Breaths VR647 n = 7	C - 20 Breaths VR647 n = 6	D - Pulmicort n = 5
Value	0.3330 (0.317 to 0.367)	0.3330 (0.317 to 0.350)	0.3500 (0.300 to 0.700)	0.3330 (0.333 to 0.367)

Population analysed: Pharmacokinetic set included 13 (76%) subjects.

10 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events (AEs) and adverse device effects were monitored throughout the trial, until resolution. The total duration of participation for each subject was approximately 47 days, which included a 30-day screening period, two dosing visits with a washout period of 4 to 10 days between each dose, and a follow-up assessment approximately 7 days after last nebulization.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
A - 5 Breaths VR647	0 of 7 (0%)	1 of 7 (14.3%)	0 of 7
B - 10 Breaths VR647	0 of 8 (0%)	1 of 8 (12.5%)	0 of 8
C - 20 Breaths VR647	0 of 6 (0%)	1 of 6 (16.7%)	0 of 6
D - Pulmicort	0 of 7 (0%)	0 of 7 (0%)	0 of 7
Overall Treatment	0 of 15 (0%)	2 of 15 (13.3%)	0 of 15

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Gary Burgess, MD study director

Vectura Ltd

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

AUClast of Plasma Budesonide (VR647 Inhalation Suspension Delivered by the VR647 Inhalation System or Pulmicort Respules Delivered by a Conventional Jet Nebulizer). (time frame: 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).). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03421730.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2019.