NCT03421730

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
17

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Dec 2017

Shorter than P25 for phase_1

Geographic Reach
1 country

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 18, 2017

Completed
25 days until next milestone

First Submitted

Initial submission to the registry

January 12, 2018

Completed
24 days until next milestone

First Posted

Study publicly available on registry

February 5, 2018

Completed
1 month until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 21, 2018

Completed
6 days until next milestone

Study Completion

Last participant's last visit for all outcomes

March 27, 2018

Completed
1.6 years until next milestone

Results Posted

Study results publicly available

October 21, 2019

Completed
Last Updated

October 21, 2019

Status Verified

October 1, 2019

Enrollment Period

3 months

First QC Date

January 12, 2018

Results QC Date

January 29, 2019

Last Update Submit

October 17, 2019

Conditions

Keywords

mild asthmabudesonidenebulizerpediatricpharmacokinetics

Outcome Measures

Primary Outcomes (6)

  • 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).

    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).

    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.

    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.

    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).

    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.

    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).

    Following dosing on Day 1 (Visit 2) and Day 8 (Visit 3).

  • Mean Modified PASAPQ Performance Score

    Following dosing on Day 1 (Visit 2) and Day 8 (Visit 3).

  • Mean Modified PASAPQ Satisfaction Score (Q9).

    Following dosing on Day 1 (Visit 2) and Day 8 (Visit 3).

  • Mean Modified PASAPQ Score Indicating Willingness to Continue With the Device (Q10).

    Following dosing on Day 1 (Visit 2) and Day 8 (Visit 3).

  • Changes in Vital Signs (Blood Pressure)

    Baseline to Day 1 0.5 hours post-dose

  • +5 more secondary outcomes

Study Arms (12)

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

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

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

Combination Product: VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation SystemCombination 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

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

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

Combination Product: VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation SystemCombination 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

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

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

Combination Product: VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation SystemCombination 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

Combination Product: VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation SystemCombination 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

Combination Product: VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation SystemCombination 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

Combination Product: VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation SystemCombination Product: 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer

Interventions

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.

AB - VR647 5 breaths, then VR647 10 breathsAC - VR647 5 breaths, then VR647 20 breathsAD - VR647 5 breaths, then PulmicortBA - VR647 10 breaths, then VR647 5 breathsBC - VR647 10 breaths, then VR647 20 breathsBD - VR647 10 breaths, then PulmicortCA - VR647 20 breaths, then VR647 5 breathsCB - VR647 20 breaths, then VR647 10 breathsCD - VR647 20 breaths, then PulmicortDA - Pulmicort, then VR647 5 breathsDB - Pulmicort, then VR647 10 breathsDC - Pulmicort, then VR647 20 breaths

Commercial Pulmicort Respules (budesonide inhalation suspension 1 mg/2 mL) delivered by a conventional jet nebulizer operated to sputtering.

AD - VR647 5 breaths, then PulmicortBD - VR647 10 breaths, then PulmicortCD - VR647 20 breaths, then PulmicortDA - Pulmicort, then VR647 5 breathsDB - Pulmicort, then VR647 10 breathsDC - Pulmicort, then VR647 20 breaths

Eligibility Criteria

Age4 Years - 8 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Vectura Study Site 0003

Colorado Springs, Colorado, 80907, United States

Location

Vectura Study Site 0002

Raleigh, North Carolina, 27607, United States

Location

Vectura Study Site 0001

Tulsa, Oklahoma, 74136, United States

Location

MeSH Terms

Conditions

Respiratory SoundsPulmonary Disease, Chronic Obstructive

Interventions

Budesonide

Condition Hierarchy (Ancestors)

Signs and Symptoms, RespiratorySigns and SymptomsPathological Conditions, Signs and SymptomsLung Diseases, ObstructiveLung DiseasesRespiratory Tract DiseasesChronic DiseaseDisease AttributesPathologic Processes

Intervention Hierarchy (Ancestors)

PregnenedionesPregnenesPregnanesSteroidsFused-Ring CompoundsPolycyclic Compounds

Results Point of Contact

Title
Gary Burgess, MD
Organization
Vectura Limited

Study Officials

  • Gary Burgess, MD

    Vectura Ltd

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Masking Details
This is an open label trial.
Purpose
TREATMENT
Intervention Model
CROSSOVER
Model Details: 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.
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 12, 2018

First Posted

February 5, 2018

Study Start

December 18, 2017

Primary Completion

March 21, 2018

Study Completion

March 27, 2018

Last Updated

October 21, 2019

Results First Posted

October 21, 2019

Record last verified: 2019-10

Locations