Trial Outcomes & Findings for 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 (NCT NCT03421730)

NCT ID: NCT03421730

Last Updated: 2019-10-21

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 17 participants
• Primary outcome 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).
• Results posted on: 2019-10-21

Participant Flow

Seventeen subjects were enrolled and randomized to 1 of 12 crossover treatment sequences AB, AC, AD, BA, BC, BD, CA, CB, CD, DA, DB or DC. However, data were analyzed (and presented) by individual treatment only (i.e. A, B, C and D), not per treatment sequence. Fifteen subjects received at least 1 study treatment; 13 subjects completed the trial.

Participant milestones

Measure	AB - VR647 5 Breaths, Then VR647 10 Breaths 5 breaths of VR647 Inhalation Suspension delivered by the VR647 Inhalation System (A) followed by 10 breaths of VR647 Inhalation Suspension delivered by the VR647 Inhalation System (B)	AC - VR647 5 Breaths, Then VR647 20 Breaths 5 breaths of VR647 Inhalation Suspension delivered by the VR647 Inhalation System (A) followed by 20 breaths of VR647 Inhalation Suspension delivered by the VR647 Inhalation System (C)	AD - VR647 5 Breaths, Then Pulmicort 5 breaths of VR647 Inhalation Suspension delivered by the VR647 Inhalation System (A) followed by 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer nebulized to empty (D)	BA - VR647 10 Breaths, Then VR647 5 Breaths 10 breaths of VR647 Inhalation Suspension delivered by the VR647 Inhalation System (B) followed by 5 breaths of VR647 Inhalation Suspension delivered by the VR647 Inhalation System (A)	BC - VR647 10 Breaths, Then VR647 20 Breaths 10 breaths of VR647 Inhalation Suspension delivered by the VR647 Inhalation System (B) followed by 20 breaths of VR647 Inhalation Suspension delivered by the VR647 Inhalation System (C)	BD - VR647 10 Breaths, Then Pulmicort 10 breaths of VR647 Inhalation Suspension delivered by the VR647 Inhalation System (B) followed by 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer nebulized to empty (D)	CA - VR647 20 Breaths, Then VR647 5 Breaths 20 breaths of VR647 Inhalation Suspension delivered by the VR647 Inhalation System (C) followed by 5 breaths of VR647 Inhalation Suspension delivered by the VR647 Inhalation System (A)	CB - VR647 20 Breaths, Then VR647 10 Breaths 20 breaths of VR647 Inhalation Suspension delivered by the VR647 Inhalation System (C) followed by 10 breaths of VR647 Inhalation Suspension delivered by the VR647 Inhalation System (B)	CD - VR647 20 Breaths, Then Pulmicort 20 breaths of VR647 Inhalation Suspension delivered by the VR647 Inhalation System (C) followed by 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer nebulized to empty (D)	DA - Pulmicort, Then VR647 5 Breaths 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer nebulized to empty (D) followed by 5 breaths of VR647 Inhalation Suspension delivered by the VR647 Inhalation System (A)	DB - Pulmicort, Then VR647 10 Breaths 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer nebulized to empty (D) followed by 10 breaths of VR647 Inhalation Suspension delivered by the VR647 Inhalation System (B)	DC - Pulmicort, Then VR647 20 Breaths 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer nebulized to empty (D) followed by 20 breaths of VR647 Inhalation Suspension delivered by the VR647 Inhalation System (C)
First Intervention (Day 1, Visit 2) STARTED	1	3	1	1	3	1	1	1	1	2	1	1
First Intervention (Day 1, Visit 2) COMPLETED	1	1	1	1	3	1	1	1	1	2	1	1
First Intervention (Day 1, Visit 2) NOT COMPLETED	0	2	0	0	0	0	0	0	0	0	0	0
Washout (Days 4 to 10) STARTED	1	1	1	1	3	1	1	1	1	2	1	1
Washout (Days 4 to 10) COMPLETED	1	1	1	1	1	1	1	1	1	2	1	1
Washout (Days 4 to 10) NOT COMPLETED	0	0	0	0	2	0	0	0	0	0	0	0
Second Intervention (Day 8±3, Visit 3) STARTED	1	1	1	1	1	1	1	1	1	2	1	1
Second Intervention (Day 8±3, Visit 3) COMPLETED	1	1	1	1	1	1	1	1	1	2	1	1
Second Intervention (Day 8±3, Visit 3) NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0

Reasons for withdrawal

Measure	AB - VR647 5 Breaths, Then VR647 10 Breaths 5 breaths of VR647 Inhalation Suspension delivered by the VR647 Inhalation System (A) followed by 10 breaths of VR647 Inhalation Suspension delivered by the VR647 Inhalation System (B)	AC - VR647 5 Breaths, Then VR647 20 Breaths 5 breaths of VR647 Inhalation Suspension delivered by the VR647 Inhalation System (A) followed by 20 breaths of VR647 Inhalation Suspension delivered by the VR647 Inhalation System (C)	AD - VR647 5 Breaths, Then Pulmicort 5 breaths of VR647 Inhalation Suspension delivered by the VR647 Inhalation System (A) followed by 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer nebulized to empty (D)	BA - VR647 10 Breaths, Then VR647 5 Breaths 10 breaths of VR647 Inhalation Suspension delivered by the VR647 Inhalation System (B) followed by 5 breaths of VR647 Inhalation Suspension delivered by the VR647 Inhalation System (A)	BC - VR647 10 Breaths, Then VR647 20 Breaths 10 breaths of VR647 Inhalation Suspension delivered by the VR647 Inhalation System (B) followed by 20 breaths of VR647 Inhalation Suspension delivered by the VR647 Inhalation System (C)	BD - VR647 10 Breaths, Then Pulmicort 10 breaths of VR647 Inhalation Suspension delivered by the VR647 Inhalation System (B) followed by 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer nebulized to empty (D)	CA - VR647 20 Breaths, Then VR647 5 Breaths 20 breaths of VR647 Inhalation Suspension delivered by the VR647 Inhalation System (C) followed by 5 breaths of VR647 Inhalation Suspension delivered by the VR647 Inhalation System (A)	CB - VR647 20 Breaths, Then VR647 10 Breaths 20 breaths of VR647 Inhalation Suspension delivered by the VR647 Inhalation System (C) followed by 10 breaths of VR647 Inhalation Suspension delivered by the VR647 Inhalation System (B)	CD - VR647 20 Breaths, Then Pulmicort 20 breaths of VR647 Inhalation Suspension delivered by the VR647 Inhalation System (C) followed by 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer nebulized to empty (D)	DA - Pulmicort, Then VR647 5 Breaths 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer nebulized to empty (D) followed by 5 breaths of VR647 Inhalation Suspension delivered by the VR647 Inhalation System (A)	DB - Pulmicort, Then VR647 10 Breaths 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer nebulized to empty (D) followed by 10 breaths of VR647 Inhalation Suspension delivered by the VR647 Inhalation System (B)	DC - Pulmicort, Then VR647 20 Breaths 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer nebulized to empty (D) followed by 20 breaths of VR647 Inhalation Suspension delivered by the VR647 Inhalation System (C)
First Intervention (Day 1, Visit 2) Withdrawal by subject or legal guardian	0	2	0	0	0	0	0	0	0	0	0	0
Washout (Days 4 to 10) Withdrawal by subject or legal guardian	0	0	0	0	2	0	0	0	0	0	0	0

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Overall Treatment n=15 Participants Baseline measures were not analysed by arm or comparison group, so they are presented for the total number of subjects enrolled in the study who received at least one dose of treatment.
Age, Continuous	82.6 months STANDARD_DEVIATION 14.05 • n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	15 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	9 Participants n=5 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

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).

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

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

Outcome measures

Measure	A - 5 Breaths VR647 n=6 Participants 5 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	B - 10 Breaths VR647 n=7 Participants 10 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	C - 20 Breaths VR647 n=6 Participants 20 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	D - Pulmicort n=5 Participants 1 mg/2 mL Pulmicort Respules delivered by the conventional jet nebulizer nebulized to empty 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer: Commercial Pulmicort Respules (budesonide inhalation suspension 1 mg/2 mL) delivered by a conventional jet nebulizer operated to sputtering.
AUClast of Plasma Budesonide (VR647 Inhalation Suspension Delivered by the VR647 Inhalation System or Pulmicort Respules Delivered by a Conventional Jet Nebulizer).	120.7 pg*hr/mL Standard Deviation 20.498	327.5 pg*hr/mL Standard Deviation 119.49	759.5 pg*hr/mL Standard Deviation 311.79	1357 pg*hr/mL Standard Deviation 564.06

PRIMARY outcome

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).

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

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).

Outcome measures

Measure	A - 5 Breaths VR647 n=4 Participants 5 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	B - 10 Breaths VR647 n=6 Participants 10 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	C - 20 Breaths VR647 n=5 Participants 20 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	D - Pulmicort n=4 Participants 1 mg/2 mL Pulmicort Respules delivered by the conventional jet nebulizer nebulized to empty 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer: Commercial Pulmicort Respules (budesonide inhalation suspension 1 mg/2 mL) delivered by a conventional jet nebulizer operated to sputtering.
AUCinf of Plasma Budesonide (VR647 Inhalation Suspension Delivered by the VR647 Inhalation System or Pulmicort Respules Delivered by a Conventional Jet Nebulizer).	138.3 pg*hr/mL Standard Deviation 25.189	326.2 pg*hr/mL Standard Deviation 116.09	737.1 pg*hr/mL Standard Deviation 313.27	1492 pg*hr/mL Standard Deviation 707.99

PRIMARY outcome

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).

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

Cmax is the maximum observed concentration.

Outcome measures

Measure	A - 5 Breaths VR647 n=6 Participants 5 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	B - 10 Breaths VR647 n=7 Participants 10 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	C - 20 Breaths VR647 n=6 Participants 20 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	D - Pulmicort n=5 Participants 1 mg/2 mL Pulmicort Respules delivered by the conventional jet nebulizer nebulized to empty 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer: Commercial Pulmicort Respules (budesonide inhalation suspension 1 mg/2 mL) delivered by a conventional jet nebulizer operated to sputtering.
Cmax of Plasma Budesonide (VR647 Inhalation Suspension Delivered by the VR647 Inhalation System or Pulmicort Respules Delivered by a Conventional Jet Nebulizer).	71.25 pg/mL Standard Deviation 9.5776	179.7 pg/mL Standard Deviation 79.442	390.3 pg/mL Standard Deviation 178.07	601.8 pg/mL Standard Deviation 405.32

PRIMARY outcome

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).

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

Tmax is the time to reach Cmax.

Outcome measures

Measure	A - 5 Breaths VR647 n=6 Participants 5 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	B - 10 Breaths VR647 n=7 Participants 10 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	C - 20 Breaths VR647 n=6 Participants 20 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	D - Pulmicort n=5 Participants 1 mg/2 mL Pulmicort Respules delivered by the conventional jet nebulizer nebulized to empty 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer: Commercial Pulmicort Respules (budesonide inhalation suspension 1 mg/2 mL) delivered by a conventional jet nebulizer operated to sputtering.
Tmax of Plasma Budesonide (VR647 Inhalation Suspension Delivered by the VR647 Inhalation System or Pulmicort Respules Delivered by a Conventional Jet Nebulizer).	0.3330 hours Interval 0.317 to 0.367	0.3330 hours Interval 0.317 to 0.35	0.3500 hours Interval 0.3 to 0.7	0.3330 hours Interval 0.333 to 0.367

PRIMARY outcome

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).

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

Tlast is the time of the last measurable concentration (Clast).

Outcome measures

Measure	A - 5 Breaths VR647 n=6 Participants 5 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	B - 10 Breaths VR647 n=7 Participants 10 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	C - 20 Breaths VR647 n=6 Participants 20 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	D - Pulmicort n=5 Participants 1 mg/2 mL Pulmicort Respules delivered by the conventional jet nebulizer nebulized to empty 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer: Commercial Pulmicort Respules (budesonide inhalation suspension 1 mg/2 mL) delivered by a conventional jet nebulizer operated to sputtering.
Tlast of Plasma Budesonide (VR647 Inhalation Suspension Delivered by the VR647 Inhalation System or Pulmicort Respules Delivered by a Conventional Jet Nebulizer).	5.325 hours Standard Deviation 1.6331	7.386 hours Standard Deviation 0.9539	7.620 hours Standard Deviation 0.7962	7.937 hours Standard Deviation 0.0447

PRIMARY outcome

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).

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

T1/2 is the apparent first-order terminal elimination half-life.

Outcome measures

Measure	A - 5 Breaths VR647 n=4 Participants 5 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	B - 10 Breaths VR647 n=6 Participants 10 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	C - 20 Breaths VR647 n=5 Participants 20 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	D - Pulmicort n=4 Participants 1 mg/2 mL Pulmicort Respules delivered by the conventional jet nebulizer nebulized to empty 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer: Commercial Pulmicort Respules (budesonide inhalation suspension 1 mg/2 mL) delivered by a conventional jet nebulizer operated to sputtering.
T1/2 of Plasma Budesonide (VR647 Inhalation Suspension Delivered by the VR647 Inhalation System or Pulmicort Respules Delivered by a Conventional Jet Nebulizer).	1.703 hours Standard Deviation 0.7005	1.991 hours Standard Deviation 0.3587	2.059 hours Standard Deviation 0.5895	2.200 hours Standard Deviation 0.3300

SECONDARY outcome

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

Population: Safety set included 15 (88%) subjects who received at least one dose of study treatment.

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).

Outcome measures

Measure	A - 5 Breaths VR647 n=7 Participants 5 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	B - 10 Breaths VR647 n=8 Participants 10 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	C - 20 Breaths VR647 n=6 Participants 20 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	D - Pulmicort n=7 Participants 1 mg/2 mL Pulmicort Respules delivered by the conventional jet nebulizer nebulized to empty 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer: Commercial Pulmicort Respules (budesonide inhalation suspension 1 mg/2 mL) delivered by a conventional jet nebulizer operated to sputtering.
Mean Modified Patient Satisfaction and Preference Questionnaire (PASAPQ) Total Score (Q1 to Q8).	97.7 percentage of maximum total score Standard Deviation 3.95	95.8 percentage of maximum total score Standard Deviation 7.23	97.5 percentage of maximum total score Standard Deviation 3.56	88.6 percentage of maximum total score Standard Deviation 8.28

SECONDARY outcome

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

Population: Although specified in the protocol, mPASAPQ performance score wasn't summarized in the efficacy analysis as 3 questions were dropped from the PASAPQ that were not applicable. This change from the protocol-planned analysis was described in the SAP, finalized before DB lock. Individual scores for the 4 remaining performance questions are presented.

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).

Outcome measures

Measure	A - 5 Breaths VR647 n=7 Participants 5 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	B - 10 Breaths VR647 n=8 Participants 10 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	C - 20 Breaths VR647 n=6 Participants 20 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	D - Pulmicort n=7 Participants 1 mg/2 mL Pulmicort Respules delivered by the conventional jet nebulizer nebulized to empty 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer: Commercial Pulmicort Respules (budesonide inhalation suspension 1 mg/2 mL) delivered by a conventional jet nebulizer operated to sputtering.
Mean Modified PASAPQ Performance Score Question 1	6.9 scores on a scale Standard Deviation 0.38	6.6 scores on a scale Standard Deviation 0.52	6.3 scores on a scale Standard Deviation 0.82	6.4 scores on a scale Standard Deviation 0.53
Mean Modified PASAPQ Performance Score Question 2	6.9 scores on a scale Standard Deviation 0.38	6.5 scores on a scale Standard Deviation 0.76	7.0 scores on a scale Standard Deviation 0.00	6.0 scores on a scale Standard Deviation 1.15
Mean Modified PASAPQ Performance Score Question 6	6.7 scores on a scale Standard Deviation 0.49	6.6 scores on a scale Standard Deviation 0.52	6.8 scores on a scale Standard Deviation 0.41	6.1 scores on a scale Standard Deviation 1.07
Mean Modified PASAPQ Performance Score Question 7	7.0 scores on a scale Standard Deviation 0.00	6.8 scores on a scale Standard Deviation 0.71	7.0 scores on a scale Standard Deviation 0.00	5.3 scores on a scale Standard Deviation 1.60

SECONDARY outcome

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

Population: Safety set included 15 (88%) subjects who received at least one dose of study treatment.

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).

Outcome measures

Measure	A - 5 Breaths VR647 n=7 Participants 5 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	B - 10 Breaths VR647 n=8 Participants 10 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	C - 20 Breaths VR647 n=6 Participants 20 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	D - Pulmicort n=7 Participants 1 mg/2 mL Pulmicort Respules delivered by the conventional jet nebulizer nebulized to empty 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer: Commercial Pulmicort Respules (budesonide inhalation suspension 1 mg/2 mL) delivered by a conventional jet nebulizer operated to sputtering.
Mean Modified PASAPQ Satisfaction Score (Q9).	6.9 scores on a scale Standard Deviation 0.38	6.6 scores on a scale Standard Deviation 0.74	6.8 scores on a scale Standard Deviation 0.41	5.7 scores on a scale Standard Deviation 0.95

SECONDARY outcome

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

Population: Safety set included 15 (88%) subjects who received at least one dose of study treatment.

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).

Outcome measures

Measure	A - 5 Breaths VR647 n=7 Participants 5 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	B - 10 Breaths VR647 n=8 Participants 10 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	C - 20 Breaths VR647 n=6 Participants 20 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	D - Pulmicort n=7 Participants 1 mg/2 mL Pulmicort Respules delivered by the conventional jet nebulizer nebulized to empty 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer: Commercial Pulmicort Respules (budesonide inhalation suspension 1 mg/2 mL) delivered by a conventional jet nebulizer operated to sputtering.
Mean Modified PASAPQ Score Indicating Willingness to Continue With the Device (Q10).	98.6 scores on a scale Standard Deviation 3.78	93.5 scores on a scale Standard Deviation 11.75	98.3 scores on a scale Standard Deviation 4.08	77.3 scores on a scale Standard Deviation 22.10

SECONDARY outcome

Timeframe: Baseline to Day 1 0.5 hours post-dose

Mean values for blood pressure from pre-dose to 0.5 hours post-dose.

Outcome measures

Measure	A - 5 Breaths VR647 n=7 Participants 5 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	B - 10 Breaths VR647 n=8 Participants 10 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	C - 20 Breaths VR647 n=6 Participants 20 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	D - Pulmicort n=7 Participants 1 mg/2 mL Pulmicort Respules delivered by the conventional jet nebulizer nebulized to empty 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer: Commercial Pulmicort Respules (budesonide inhalation suspension 1 mg/2 mL) delivered by a conventional jet nebulizer operated to sputtering.
Changes in Vital Signs (Blood Pressure) Change in systolic blood pressure	-8.4 mm Hg Standard Deviation 8.40	9.0 mm Hg Standard Deviation 5.35	0.8 mm Hg Standard Deviation 4.67	4.4 mm Hg Standard Deviation 5.19
Changes in Vital Signs (Blood Pressure) Change in diastolic blood pressure	-7.4 mm Hg Standard Deviation 13.60	2.1 mm Hg Standard Deviation 7.30	-6.3 mm Hg Standard Deviation 12.93	1.9 mm Hg Standard Deviation 9.51

SECONDARY outcome

Timeframe: Baseline to Day 1 0.5 hours post-dose

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

Outcome measures

Measure	A - 5 Breaths VR647 n=7 Participants 5 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	B - 10 Breaths VR647 n=8 Participants 10 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	C - 20 Breaths VR647 n=6 Participants 20 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	D - Pulmicort n=7 Participants 1 mg/2 mL Pulmicort Respules delivered by the conventional jet nebulizer nebulized to empty 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer: Commercial Pulmicort Respules (budesonide inhalation suspension 1 mg/2 mL) delivered by a conventional jet nebulizer operated to sputtering.
Changes in Vital Signs (Heart Rate)	6.6 change in beats per minute Standard Deviation 9.86	2.6 change in beats per minute Standard Deviation 13.18	4.0 change in beats per minute Standard Deviation 11.30	-2.6 change in beats per minute Standard Deviation 17.09

SECONDARY outcome

Timeframe: Baseline to Day 1 0.5 hours post-dose

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

Outcome measures

Measure	A - 5 Breaths VR647 n=7 Participants 5 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	B - 10 Breaths VR647 n=8 Participants 10 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	C - 20 Breaths VR647 n=6 Participants 20 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	D - Pulmicort n=7 Participants 1 mg/2 mL Pulmicort Respules delivered by the conventional jet nebulizer nebulized to empty 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer: Commercial Pulmicort Respules (budesonide inhalation suspension 1 mg/2 mL) delivered by a conventional jet nebulizer operated to sputtering.
Changes in Vital Signs (Respiration Rate)	0.0 Change in breaths per minute Standard Deviation 1.15	0.3 Change in breaths per minute Standard Deviation 0.71	0.3 Change in breaths per minute Standard Deviation 1.51	0.3 Change in breaths per minute Standard Deviation 0.76

SECONDARY outcome

Timeframe: Baseline to Day 1 0.5 hours post-dose

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

Outcome measures

Measure	A - 5 Breaths VR647 n=7 Participants 5 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	B - 10 Breaths VR647 n=8 Participants 10 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	C - 20 Breaths VR647 n=6 Participants 20 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	D - Pulmicort n=7 Participants 1 mg/2 mL Pulmicort Respules delivered by the conventional jet nebulizer nebulized to empty 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer: Commercial Pulmicort Respules (budesonide inhalation suspension 1 mg/2 mL) delivered by a conventional jet nebulizer operated to sputtering.
Changes in Vital Signs (Temperature)	0.27 Change in degrees Celsius Standard Deviation 0.373	0.04 Change in degrees Celsius Standard Deviation 0.320	0.05 Change in degrees Celsius Standard Deviation 0.207	0.14 Change in degrees Celsius Standard Deviation 0.351

SECONDARY outcome

Timeframe: Visit 1, and Day 8 of Visit 3.

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.

Outcome measures

Measure	A - 5 Breaths VR647 n=7 Participants 5 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	B - 10 Breaths VR647 n=8 Participants 10 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	C - 20 Breaths VR647 n=6 Participants 20 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	D - Pulmicort n=7 Participants 1 mg/2 mL Pulmicort Respules delivered by the conventional jet nebulizer nebulized to empty 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer: Commercial Pulmicort Respules (budesonide inhalation suspension 1 mg/2 mL) delivered by a conventional jet nebulizer operated to sputtering.
Changes in Physical Examination	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Visit 1

Number of subjects using concomitant medications.

Outcome measures

Measure	A - 5 Breaths VR647 n=7 Participants 5 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	B - 10 Breaths VR647 n=8 Participants 10 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	C - 20 Breaths VR647 n=6 Participants 20 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	D - Pulmicort n=7 Participants 1 mg/2 mL Pulmicort Respules delivered by the conventional jet nebulizer nebulized to empty 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer: Commercial Pulmicort Respules (budesonide inhalation suspension 1 mg/2 mL) delivered by a conventional jet nebulizer operated to sputtering.
Use of Concomitant Medications	7 Participants	8 Participants	6 Participants	7 Participants

Adverse Events

A - 5 Breaths VR647

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

B - 10 Breaths VR647

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

C - 20 Breaths VR647

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

D - Pulmicort

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Overall Treatment

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	A - 5 Breaths VR647 n=7 participants at risk 5 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	B - 10 Breaths VR647 n=8 participants at risk 10 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	C - 20 Breaths VR647 n=6 participants at risk 20 breaths of the VR647 Inhalation Suspension 1 mg/2 mL delivered by the VR647 Inhalation System VR647 Inhalation Suspension (budesonide) 1 mg/2 mL delivered by the VR647 Inhalation System: 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.	D - Pulmicort n=7 participants at risk 1 mg/2 mL Pulmicort Respules delivered by the conventional jet nebulizer nebulized to empty 1 mg/2 mL Pulmicort Respules delivered by a conventional jet nebulizer: Commercial Pulmicort Respules (budesonide inhalation suspension 1 mg/2 mL) delivered by a conventional jet nebulizer operated to sputtering.	Overall Treatment n=15 participants at risk The total number of subjects enrolled in the study who received at least one dose of treatment.
Gastrointestinal disorders Nausea	14.3% 1/7 • Number of events 1 • 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. Any changes from baseline (pre-dose value on Day 1) in vital signs and physical examination findings that were judged to be clinically significant were recorded as AEs.	0.00% 0/8 • 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. Any changes from baseline (pre-dose value on Day 1) in vital signs and physical examination findings that were judged to be clinically significant were recorded as AEs.	0.00% 0/6 • 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. Any changes from baseline (pre-dose value on Day 1) in vital signs and physical examination findings that were judged to be clinically significant were recorded as AEs.	0.00% 0/7 • 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. Any changes from baseline (pre-dose value on Day 1) in vital signs and physical examination findings that were judged to be clinically significant were recorded as AEs.	6.7% 1/15 • Number of events 1 • 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. Any changes from baseline (pre-dose value on Day 1) in vital signs and physical examination findings that were judged to be clinically significant were recorded as AEs.
Gastrointestinal disorders Vomiting	14.3% 1/7 • Number of events 1 • 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. Any changes from baseline (pre-dose value on Day 1) in vital signs and physical examination findings that were judged to be clinically significant were recorded as AEs.	0.00% 0/8 • 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. Any changes from baseline (pre-dose value on Day 1) in vital signs and physical examination findings that were judged to be clinically significant were recorded as AEs.	0.00% 0/6 • 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. Any changes from baseline (pre-dose value on Day 1) in vital signs and physical examination findings that were judged to be clinically significant were recorded as AEs.	0.00% 0/7 • 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. Any changes from baseline (pre-dose value on Day 1) in vital signs and physical examination findings that were judged to be clinically significant were recorded as AEs.	6.7% 1/15 • Number of events 1 • 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. Any changes from baseline (pre-dose value on Day 1) in vital signs and physical examination findings that were judged to be clinically significant were recorded as AEs.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/7 • 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. Any changes from baseline (pre-dose value on Day 1) in vital signs and physical examination findings that were judged to be clinically significant were recorded as AEs.	12.5% 1/8 • Number of events 1 • 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. Any changes from baseline (pre-dose value on Day 1) in vital signs and physical examination findings that were judged to be clinically significant were recorded as AEs.	16.7% 1/6 • Number of events 1 • 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. Any changes from baseline (pre-dose value on Day 1) in vital signs and physical examination findings that were judged to be clinically significant were recorded as AEs.	0.00% 0/7 • 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. Any changes from baseline (pre-dose value on Day 1) in vital signs and physical examination findings that were judged to be clinically significant were recorded as AEs.	6.7% 1/15 • Number of events 1 • 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. Any changes from baseline (pre-dose value on Day 1) in vital signs and physical examination findings that were judged to be clinically significant were recorded as AEs.

Additional Information

Gary Burgess, MD

Vectura Limited

Phone: +44 (0)1249 667700

Email: clinical.enquiries@vectura.com

Results disclosure agreements

• Principal investigator is a sponsor employee Publication can be delayed for 60 days for Sponsor review and revisions/deletions can be required. Furthermore, a 6-month delay to publication can be required by the Sponsor in order to take steps to protect its proprietary information and/or intellectual property rights.
• Publication restrictions are in place

Restriction type: OTHER