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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

Primary Purpose

Wheezing, Reactive Airway Disease, Mild Asthma

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

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

About this trial

This is an interventional treatment trial for Wheezing focused on measuring mild asthma, budesonide, nebulizer, pediatric, pharmacokinetics

Eligibility Criteria

4 Years - 8 Years (Child)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Vectura Study Site 0003
Vectura Study Site 0002
Vectura Study Site 0001

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm Type

Experimental

Arm Label

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

Arm Description

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

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

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

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

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

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

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

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

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

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

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

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

Outcomes

Primary Outcome Measures

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).

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).

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.

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.

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).

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.

Secondary Outcome Measures

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).

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).

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).

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).

Changes in Vital Signs (Blood Pressure)

Mean values for blood pressure from pre-dose to 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.

Changes in Vital Signs (Respiration Rate)

Mean values for respiratory rate from pre-dose to 0.5 hours post-dose.

Changes in Vital Signs (Temperature)

Mean values for temperature from pre-dose to 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.

Use of Concomitant Medications

Number of subjects using concomitant medications.

Full Information

NCT ID

NCT03421730

First Posted

January 12, 2018

Last Updated

October 17, 2019

Sponsor

Vectura Limited

1. Study Identification

Unique Protocol Identification Number

NCT03421730

Brief Title

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

2. Study Status

Record Verification Date

October 2019

Overall Recruitment Status

Completed

Study Start Date

December 18, 2017 (Actual)

Primary Completion Date

March 21, 2018 (Actual)

Study Completion Date

March 27, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Vectura Limited

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Wheezing, Reactive Airway Disease, Mild Asthma

Keywords

mild asthma, budesonide, nebulizer, pediatric, pharmacokinetics

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

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.

Allocation

Randomized

Enrollment

17 (Actual)

8. Arms, Groups, and Interventions

Arm Title

AB - VR647 5 breaths, then VR647 10 breaths

Arm Type

Experimental

Arm Description

Arm Title

AC - VR647 5 breaths, then VR647 20 breaths

Arm Type

Experimental

Arm Description

Arm Title

AD - VR647 5 breaths, then Pulmicort

Arm Type

Experimental

Arm Description

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

Arm Title

BA - VR647 10 breaths, then VR647 5 breaths

Arm Type

Experimental

Arm Description

Arm Title

BC - VR647 10 breaths, then VR647 20 breaths

Arm Type

Experimental

Arm Description

Arm Title

BD - VR647 10 breaths, then Pulmicort

Arm Type

Experimental

Arm Description

Arm Title

CA - VR647 20 breaths, then VR647 5 breaths

Arm Type

Experimental

Arm Description

Arm Title

CB - VR647 20 breaths, then VR647 10 breaths

Arm Type

Experimental

Arm Description

Arm Title

CD - VR647 20 breaths, then Pulmicort

Arm Type

Experimental

Arm Description

Arm Title

DA - Pulmicort, then VR647 5 breaths

Arm Type

Experimental

Arm Description

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

Arm Title

DB - Pulmicort, then VR647 10 breaths

Arm Type

Experimental

Arm Description

Arm Title

DC - Pulmicort, then VR647 20 breaths

Arm Type

Experimental

Arm Description

Intervention Type

Combination Product

Intervention Name(s)

VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System

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.

Intervention Type

Combination Product

Intervention Name(s)

1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Description

AUClast is the area under the plasma concentration-time curve, from time 0 to the time of the last measurable concentration (Clast).

Time Frame