A Study for the Assessment of the Benefits of a Novel Mesh Nebulizer in the Treatment of Patients With Stable COPD
Phase: NA
Conditions: COPD
Sponsor: Philips Respironics

 
 
Version 3.0 1Oct2019 
Page 1 of 40 
Confidential 
SRC-RDD-InnospireGo-2018-10458 
 
 
 
  
 
 
 
 
 
 
 
 
Clinical Protocol 
 
A Study for the Assessment of the Benefits of a Novel Mesh Nebulizer in the 
Treatment of Patients with Stable COPD 
 
Protocol # SRC-RDD-InnospireGo-2018-10458 
 
 
Written By: __________________________________________________ 
Sara Garbin  
 
 
 
 
 
 
 
Date  
Clinical Development Scientist, SRC Clinical Development 
 
Approved By: 
___________________________________________________________ 
Ketah Doty  
 
 
 
 
 
 
 
Date  
Senior Clinical Research Associate, SRC Clinical Operations 
 
Approved By: 
___________________________________________________________ 
Jeff Jasko 
 
 
 
 
 
 
Date  
Senior Data Manager, Q&R Reg. & Clin. Aff. - Biostatistics/DM 
 
 
Sponsored by 
 
 
Respironics, Inc., a Philips Healthcare Company 
1740 Golden Mile Hwy,  
Monroeville, PA 15146 
USA 
 
 
IRB APPROVED 
Allendale IRB 
October 7, 2019 

 
 
Version 3.0 1Oct2019 
Page 2 of 40 
Confidential 
SRC-RDD-InnospireGo-2018-10458 
 
 
 
  
 
Table of Contents 
 
Document Control Page(s) ........................................................................................... 4 
Philips Respironics, Inc. Contact Information ............................................................ 5 
Protocol Approvals ....................................................................................................... 6 
Protocol Revisions ........................................................................................................ 7 
Glossary ......................................................................................................................... 7 
Protocol Synopsis ......................................................................................................... 9 
Background Information ............................................................................................. 14 
Description of the Intervention Studied .................................................................... 15 
Study Design Rationale .............................................................................................. 15 
Study Objectives and Purpose .................................................................................. 15 
Study Design ............................................................................................................... 18 
Schedule of Events .................................................................................................... 20 
Consent for Participation ............................................................................................ 24 
Selection and Withdrawal of Subjects: ..................................................................... 24 
Inclusion Criteria ........................................................................................................ 24 
Exclusion Criteria ....................................................................................................... 25 
Withdrawal ................................................................................................................. 25 
Discontinuation of Study Intervention ......................................................................... 26 
Treatment of Subjects ................................................................................................. 26 
Intended Use .............................................................................................................. 26 
Contraindications ....................................................................................................... 26 
Monitoring .................................................................................................................. 26 
Unscheduled Visits .................................................................................................... 27 
Assessment of Performance ...................................................................................... 27 
Assessment of Safety ................................................................................................. 27 
Adverse Events .......................................................................................................... 27 
Serious Adverse Events ............................................................................................. 27 
Unanticipated Serious Adverse Device Effect ............................................................ 27 
Severity of Event ........................................................................................................ 27 
Relationship to Study Intervention ............................................................................. 28 

 
 
Version 3.0 1Oct2019 
Page 3 of 40 
Confidential 
SRC-RDD-InnospireGo-2018-10458 
 
 
 
  
 
Adverse Event Assessment and Follow-Up ............................................................... 28 
Serious Adverse Event and Unanticipated Adverse Device Effect Reporting ............ 29 
Device Deficiencies ..................................................................................................... 29 
Statistical Methods ...................................................................................................... 29 
Direct Access to Source Data/Documents ................................................................ 30 
Case Report Forms ..................................................................................................... 31 
Quality Control and Quality Assurance ..................................................................... 31 
Ethics ........................................................................................................................... 32 
Data Handling and Recordkeeping ............................................................................ 32 
Financing and Insurance ............................................................................................ 32 
Registration on ClinicalTrials.gov or other applicable registry .............................. 32 
Risk and Benefit Analysis .......................................................................................... 32 
Potential Risks and Discomforts ................................................................................ 32 
Potential Benefits ....................................................................................................... 33 
Compensation for Research-Related Activities .......................................................... 33 
Publication ................................................................................................................... 34 
References ................................................................................................................... 34 
Appendix 1: Chronic Respiratory Disease Questionnaire-Self Report ................... 36 
Appendix 2: Borg Assessment .................................................................................. 37 
Appendix 3: Chronic Respiratory Disease Questionnaire-Self Report (Follow-Up)
 ...................................................................................................................................... 38 
Appendix 4: Nebulizer Satisfaction Assessment ..................................................... 39 
 
 
 

 
 
Version 3.0 1Oct2019 
Page 4 of 40 
Confidential 
SRC-RDD-InnospireGo-2018-10458 
 
 
 
  
 
Document Control Page(s) 
 
Protocol Title: A Study for the Assessment of the Benefits of a Novel Mesh 
Nebulizer in the Treatment of Patients with Stable COPD 
Protocol Number: SRC-RDD-InnospireGo-2018-10458  
 
 
Author(s): Sara Garbin, Chuck Cain, Dirk Von Hollen, Cheryl Nickerson 
 
Study Sponsor: 
Philips Respironics Inc. 
1740 Golden Mile Highway 
Monroeville, PA 15146 
724.387.7500 
 
Site(s): 
Jefferson Associates in Internal Medicine 
575 Coal Valley Road, Suite 511 
Clairton, PA 15025 
Phone: 412-466-6161 
 
 
Principal Investigator: 
Michael I. Mallinger, MD 
575 Coal Valley Road, Suite 511 
Clairton, PA 15025 
Phone: 412-466-6161 
412-606-2924 (24-hour number) 
E-mail: mallmimd01@gmail.com 
 
 
Collaborator(s) 
Consolidated Clinical Trials, Inc. 
4232 Northern Pike, Suite 102 
Pittsburgh, PA 15146 
Phone: 412-273-9100 
 
 
 
 

 
 
Version 3.0 1Oct2019 
Page 5 of 40 
Confidential 
SRC-RDD-InnospireGo-2018-10458 
 
 
 
  
 
Philips Respironics, Inc. Contact Information 
 
Study Monitor(s): 
Ketah Doty, RN, BSN, OCN 
Senior Clinical Research Associate  
1740 Golden Mile Highway 
Monroeville, PA 15146 
Phone: 724-387-7921 
Mobile: 412-738-6281 
Email: ketah.doty@philips.com 
 
 
Reporting of Adverse Events or Adverse Device Effects 
Report the occurrence of a serious adverse event or serious adverse device effect to 
Philips Respironics within 24 hours of the occurrence. 
 
Ketah Doty, RN, BSN, OCN 
Senior Clinical Research Associate  
1740 Golden Mile Highway 
Monroeville, PA 15146 
Phone: 724-387-7921 
Mobile: 412-738-6281 
Email: ketah.doty@philips.com 
 
 
 
 
 
 

 
 
Version 3.0 1Oct2019 
Page 6 of 40 
Confidential 
SRC-RDD-InnospireGo-2018-10458 
 
 
 
  
 
Protocol Approvals 
Investigator Agreement 
As Investigator of the study entitled “A Study for the Assessment of the Benefits of a Novel 
Mesh Nebulizer in the Treatment of Patients with Stable COPD” Protocol # SRC-RDD-
InnospireGo-2018-10458, I agree to:  
 
(i) conduct the Study in accordance with: this Investigator Agreement; the Study’s 
Protocol as approved by the IRB (the “Protocol”); all applicable laws and regulations; 
Good Clinical Practice and the Declaration of Helsinki; and any IRB or FDA conditions of 
approval;   
 
(ii) await IRB approval for the Protocol before obtaining informed consents; 
 
(iii) ensure that all requirements for informed consent are met and not let any subject 
participate in the Study before obtaining that subject’s informed consent;  
 
(iv) not make modifications to the Protocol as supplied to me by Respironics, Inc. (the 
“Sponsor”), without first obtaining the written approval of the Sponsor;  
 
(v) provide the Sponsor with accurate financial information as required by FDA 
regulations; 
 
(vi) supervise all testing of investigational devices that involves any Study subject;  
 
(vii) maintain Study documentation for the period of time as required by FDA regulations;  
 
(viii) will supply to the Sponsor, as part of this Investigator Agreement, my curriculum 
vitae. 
 
 
 
 
Investigator Signature: 
 
 
 
 
 
 
Date:  
 
 
Printed Name: 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
Version 3.0 1Oct2019 
Page 7 of 40 
Confidential 
SRC-RDD-InnospireGo-2018-10458 
 
 
 
  
 
Protocol Revisions 
 
Revision 
Level 
 
Changes Made to Protocol 
 
Date 
 
By 
0.0 
Initial release 
15Apr2019 
C. Cain, K. Doty, S. 
Garbin, J. Jasko, C. 
Nickerson, D. Von 
Hollen 
1.0 
Updated inclusion/exclusion criteria, 
added collection of height and 
weight, clarified study procedure 
details 
19Apr2019 
S. Garbin 
2.0 
Revised inclusion criteria to allow 
use of albuterol alone; updated 
study procedures and potential side 
effects to reflect use of albuterol; 
added site contact information 
17Jun2019 
S. Garbin 
3.0 
Updated site information, 
investigator name and contact 
information; revised instruction in 
the nebulizer satisfaction 
assessment 
1Oct2019 
S. Garbin 
Glossary 
6MWT 
6-Minute Walk Test 
ADE 
Adverse Device Effect 
AE 
Adverse Event 
CFR 
Code of Federal Regulations 
COPD 
Chronic Obstructive Pulmonary Disease 
CRQ-SR 
Chronic Respiratory Disease Questionnaire Self-Report 
DPI 
Dry Powder Inhaler 
DSMB 
Data Safety Monitoring Board 
eCRF 
Electronic Case Report Form 
FDA 
Food and Drug Administration 
FEV1 
Forced Expiratory Volume in 1 second 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
ICH 
International Conference on Harmonisation 
IRB 
Institutional Review Board 
mMRC 
Modified Medical Research Council (dyspnea scale) 
PI 
Principal Investigator 
PIF 
Peak Inspiratory Flow 
pMDI 
Pressurized Metered Dose Inhaler 
QC 
Quality Control 
SAE 
Serious Adverse Event 
US 
United States 
USADE 
Unanticipated Serious Adverse Device Effect 

 
 
Version 3.0 1Oct2019 
Page 8 of 40 
Confidential 
SRC-RDD-InnospireGo-2018-10458 
 
 
 
  
 
 
 

 
 
Version 3.0 1Oct2019 
Page 9 of 40 
Confidential 
SRC-RDD-InnospireGo-2018-10458 
 
 
 
  
 
Protocol Synopsis 
Title 
A Study for the Assessment of the Benefits of a Novel Mesh 
Nebulizer in the Treatment of Patients with Stable COPD 
Background 
Chronic obstructive pulmonary disease (COPD) is a slowly 
progressive disease that results in airflow obstruction. Affecting 
more than 5% of adults, COPD is the third leading cause of death 
in the United States.1, 2 Manifestations of COPD may include 
dyspnea, poor exercise tolerance, chronic cough (with or without 
sputum production), wheezing, respiratory failure or cor 
pulmonale.1 
GOLD 
states 
that 
pharmacologic 
treatment 
should 
be 
individualized and guided by the severity of symptoms, risk of 
exacerbations, side effects, comorbidities, drug availability and 
cost, and the patient’s response, preference and ability to use 
various drug delivery devices.3 
Their final point regarding preference and ability to use various 
drug delivery devices may be related, in part, to the issues that 
patients with COPD have in using pressurized metered dose 
inhalers (pMDIs) and dry powder inhalers (DPIs) correctly.4 
Administration of nebulized therapy to patients with COPD avoids 
many of these issues because the aerosol is typically inhaled 
using the patients usual breathing cycle, and inhalation 
maneuver, coordination and moderate to high flows are not 
required for inhalation of the aerosolized drug.5 Use of nebulized 
therapy may therefore be preferred over inhaler therapy in some 
situations.6-8 In the US a nebulized combination of short acting 
beta2-agonists and anti-muscarinic drugs is widely prescribed to 
patients with COPD discharged from hospital after an 
exacerbation.9 
A nebulizer breaks up medical solutions into small droplets 
suspended in air (aerosol) so that they may be delivered to the 
patient’s airways for respiratory therapy. Jet nebulizers have been 
the standard delivery system for aerosolized medications. From 
the perspective of medication delivery to the lungs, jet nebulizers 
are relatively inefficient and require an external pressurized gas 
source to operate. There also is limited control of the dose 
delivered to the patient.10 
A vibrating mesh nebulizer is composed of a liquid reservoir with 
a piezo mesh disk mounted on one side of it, and a piezo mesh 
driver circuit board with batteries. The piezo mesh disk consists 

 
 
Version 3.0 1Oct2019 
Page 10 of 40 
Confidential 
SRC-RDD-InnospireGo-2018-10458 
 
 
 
  
 
of a metallic plate with thousands of precision formed holes 
surrounded by a piezoelectric material. The piezoelectric material 
vibrates at a very high rate of speed. As a result of rapid vibration, 
solution is drawn through the holes in the piezoelectric material to 
form droplets of consistent size that are delivered at a low velocity 
to be inhaled directly into the lungs.11 
Devices that use a vibrating mesh or plate with multiple apertures 
to generate aerosol create aerosols with a high fine particle 
fraction and they have a significantly higher efficiency of delivering 
drugs to the lung than conventional jet or ultrasonic nebulizers. 
The aerosol is generated as a fine mist and no baffling system is 
required. Vibrating mesh devices are portable, battery-operated 
(operation with alternating current is optional in some devices), 
and they efficiently aerosolize solutions and suspensions with 
minimal residual volume (volume of liquid remaining in the 
nebulizer at the end of nebulization).12 
Philips Respironics has developed a new handheld mesh 
nebulizer (InnoSpire Go), which has recently been cleared for use 
by the Food and Drug Administration. 
Study Design 
This will be a randomized open-label cross-over trial to investigate 
the potential benefits to the patient of using the InnoSpire Go over 
one month, compared to one month’s use of their usual jet 
nebulizer. 
Objectives 
Primary Objective: The primary objective of this study is to assess 
device preference in stable ambulatory COPD patients. 
Secondary Objective: The secondary objective of this study is to 
evaluate the treatment effect of InnoSpire Go on quality of life. 
Exploratory Objectives: The exploratory objectives of this study 
are to: 
• Evaluate the treatment effect of InnoSpire Go on physical 
activity 
• Assess effects of InnoSpire Go on symptom scores 
• Assess device satisfaction based on specific elements of 
the device’s operation and handling 
• Evaluate use of the device 
• Evaluate the safety of the InnoSpire Go device 
Endpoints 
Primary Endpoint: 
• Difference in overall device preference after 30 days of device 
use 
o Measure: Nebulizer Satisfaction Questionnaire, question 8 

 
 
Version 3.0 1Oct2019 
Page 11 of 40 
Confidential 
SRC-RDD-InnospireGo-2018-10458 
 
 
 
  
 
Secondary Endpoint:  
• Change in quality of life scores after 30 days of device use 
compared to baseline 
o Measure: Chronic Respiratory disease Questionnaire – 
Self-Report (CRQ-SR) 
Exploratory Endpoints 
• Difference in total distance walked 
o Measure: 6-Minute Walk Test (6MWT) 
• The change  in the modified Borg score following 6MWT, 
where the visit’s post-nebulizer Borg score will be used as 
the baseline for this endpoint) 
o Measure: Borg 
• The change in the modified Borg score following nebulizer 
use, where the visit’s pre-nebulizer Borg score will be used 
as the baseline for this endpoint) 
o Measure: Borg 
• Difference in modified Borg score from pre-nebulizer to post-
6MWT 
o Measure: Borg 
• Difference in device confidence after 30 days of device use 
o Measure: Nebulizer Satisfaction Assessment, question 1 
• Difference in perceived effect of the device after 30 days of 
device use 
o Measure: Nebulizer Satisfaction Assessment, question 2 
• Difference in difficulty of device assembly/disassembly after 
30 days of device use 
o Measure: Nebulizer Satisfaction Assessment, question 3-
1 
• Difference in difficulty of cleaning and regular care after 30 
days of device use 
o Measure: Nebulizer Satisfaction Assessment, question 3-
2 
• Difference in overall ease of handling or usability after 30 
days of device use 
o Measure: Nebulizer Satisfaction Assessment, question 3-
3 
• Difference in overall burden of use after 30 days of device 
use 
o Measure: Nebulizer Satisfaction Assessment, question 3-
4 

 
 
Version 3.0 1Oct2019 
Page 12 of 40 
Confidential 
SRC-RDD-InnospireGo-2018-10458 
 
 
 
  
 
• Difference in medication delivery confidence after 30 days of 
device use 
o Measure: Nebulizer Satisfaction Assessment, question 4 
• Difference in overall satisfaction after 30 days of device use 
o Measure: Nebulizer Satisfaction Assessment, question 5 
• Difference in likelihood of recommendation after 30 days of 
device use 
o Measure: Nebulizer Satisfaction Assessment, question 6 
• Difference in perception of fit with lifestyle needs after 30 
days of device use 
o Measure: Nebulizer Satisfaction Assessment, question 7 
• Difference in average ease of use score after 30 days of 
device use 
o Measure: Nebulizer Preference Questionnaire, average of 
scores from questions 3-1 through 3-4 
• Time in mouth (treatment time = first insert of mouthpiece to 
last removal of mouthpiece) 
o Video recording 
• Time to fill (open disposable nebulizer, dispense ampule, 
close or reassemble) 
o Video recording 
• Amount of fluid nebulized (pre- and post-weight of nebulizer) 
o Nebulizer cup/reservoir weights 
• Time to sputter 
o Video recording 
• Incidence of Unanticipated Serious Adverse Device Effects 
(USADEs) and Serious Adverse Events (SAEs) 
o Measure: Side Effects and Adverse Event Assessment 
Study Population 
Up to 25 stable ambulatory COPD patients who are currently 
prescribed 
jet 
nebulizer 
albuterol 
treatment 
or 
albuterol/ipratropium bromide combination will be included in this 
study. The goal is to have 20 participants complete the study. 
Inclusion Criteria 
1. Patients ≥ 40 years of age. 
2. Diagnosis of COPD. 
3. Currently using only a mouthpiece with their nebulizer system. 
4. FEV1 ≥ 30% predicted (pre- or post-bronchodilator). 
5. mMRC grade ≥ 1. 
6. Use of a jet nebulizer for the administration of albuterol or 
combination albuterol/ipratropium for the past 6 months. 
7. Willing to use the same compressor/nebulizer system 
throughout the study. 

 
 
Version 3.0 1Oct2019 
Page 13 of 40 
Confidential 
SRC-RDD-InnospireGo-2018-10458 
 
 
 
  
 
8. Willing to refrain from using the jet nebulizer system when 
using the InnoSpire Go. 
9. Prescribed nebulizer combination albuterol/ipratropium (single 
or multiple vials) with self-report of at least daily use or 
prescribed nebulizer albuterol with self-report of at least twice 
daily use. 
10. Willing to permit audio and video recording during the visit. 
11. Willing and able to follow instructions and complete all 
activities required by the trial, including phone calls. 
12. Able to read and understand English. 
Exclusion 
Criteria 
1. Unable to complete 6MWT or, if patient is not currently 
prescribed oxygen, persistent oxygen desaturation ≤ 88% on 
the 6MWT. 
2. Exacerbation of COPD requiring hospitalization (defined as 
hospital admission, urgent care visit, or emergency room visit) 
in the last 3 months. 
3. Prescribed non-selective beta blockers. 
4. Prescribed additional ipratropium bromide via nebulizer or 
inhaler or any other nebulized treatments via the subject’s jet 
nebulizer. 
5. Patients currently in assisted living or nursing home. 
6. Diagnosis of asthma, parenchymal lung disease other than 
COPD, bronchiectasis, tuberculosis, cor pulmonale, clinically 
significant 
obstructive 
urinary 
disease, 
narrow-angle 
glaucoma, unstable angina, depression, anxiety, or other 
serious medical condition that, in the opinion of the 
investigator, would interfere with the patient’s participation in 
the trial. 
7. History of thoracotomy. 
8. Myocardial infarction within the last 6 months. 
9. Participation in any other therapeutic clinical trial in the 
previous 4 weeks. 
Phase 
Post-market study 
Sites/Facilities 
Consolidated Clinical Trials, Inc. 
4232 Northern Pike, Suite 102 
Pittsburgh, PA 15146 
Enrolling 
Participants: 
COPD patients 
Description of 
Study 
Intervention: 
General purpose vibrating mesh nebulizer 
Study Duration 
Approximately 6 months 

 
 
Version 3.0 1Oct2019 
Page 14 of 40 
Confidential 
SRC-RDD-InnospireGo-2018-10458 
 
 
 
  
 
Participant 
Duration 
Approximately 60 days 
Background Information 
Chronic obstructive pulmonary disease (COPD) is a slowly progressive disease that 
results in airflow obstruction. Affecting more than 5% of adults, COPD is the third leading 
cause of death in the United States.1, 2 Manifestations of COPD may include dyspnea, 
poor exercise tolerance, chronic cough (with or without sputum production), wheezing, 
respiratory failure or cor pulmonale.1 
GOLD states that pharmacologic treatment should be individualized and guided by the 
severity of symptoms, risk of exacerbations, side effects, comorbidities, drug availability 
and cost, and the patient’s response, preference and ability to use various drug delivery 
devices.3 
Their final point regarding preference and ability to use various drug delivery devices may 
be related, in part, to the issues that patients with COPD have in using pressurized 
metered dose inhalers (pMDIs) and dry powder inhalers (DPIs) correctly.4 Administration 
of nebulized therapy to patients with COPD avoids many of these issues because the 
aerosol is typically inhaled using the patients usual breathing cycle, and inhalation 
maneuver, coordination and moderate to high flows are not required for inhalation of the 
aerosolized drug.5 Use of nebulized therapy may therefore be preferred over inhaler 
therapy in some situations.6-8 In the US a nebulized combination of short acting beta2-
agonists and anti-muscarinic drugs is widely prescribed to patients with COPD discharged 
from hospital after an exacerbation.9 
A nebulizer breaks up medical solutions into small droplets suspended in air (aerosol) so 
that they may be delivered to the patient’s airways for respiratory therapy. Jet nebulizers 
have been the standard delivery system for aerosolized medications. From the 
perspective of medication delivery to the lungs, jet nebulizers are relatively inefficient and 
require an external pressurized gas source to operate. There also is limited control of the 
dose delivered to the patient.10 
A vibrating mesh nebulizer is composed of a liquid reservoir with a piezo mesh disk 
mounted on one side of it, and a piezo mesh driver circuit board with batteries. The piezo 
mesh disk consists of a metallic plate with thousands of precision formed holes 
surrounded by a piezoelectric material. The piezoelectric material vibrates at a very high 
rate of speed. As a result of rapid vibration, solution is drawn through the holes in the 
piezoelectric material to form droplets of consistent size that are delivered at a low velocity 
to be inhaled directly into the lungs.11 
Devices that use a vibrating mesh or plate with multiple apertures to generate aerosol 
create aerosols with a high fine particle fraction and they have a significantly higher 
efficiency of delivering drugs to the lung than conventional jet or ultrasonic nebulizers. 

 
 
Version 3.0 1Oct2019 
Page 15 of 40 
Confidential 
SRC-RDD-InnospireGo-2018-10458 
 
 
 
  
 
The aerosol is generated as a fine mist and no baffling system is required. Vibrating mesh 
devices are portable, battery-operated (operation with alternating current is optional in 
some devices), and they efficiently aerosolize solutions and suspensions with minimal 
residual volume (volume of liquid remaining in the nebulizer at the end of nebulization).12 
Philips Respironics has developed a new handheld mesh nebulizer (InnoSpire Go), which 
has recently been cleared for use by the Food and Drug Administration. 
Description of the Intervention Studied  
The InnoSpire Go (see Figure 1) is a handheld, single patient use, vibrating mesh 
nebulizer system designed to aerosolize liquid medications for respiratory disease. The 
device operates continuously once initiated and automatically switches off once the 
medication has been delivered. The device may be used in pediatric and adult 
populations, as permitted by the prescribed medication, and is suitable for use in home 
environments or hospital/clinic settings. 
 
FIGURE 1 
 
Study Design Rationale  
Study Objectives and Purpose  
 
Primary Objective 
Primary Endpoint 
To assess device preference in stable 
ambulatory COPD patients 
• Difference in overall device preference 
after 30 days of device use 
o Measure: Nebulizer Satisfaction 
Questionnaire, question 8 
Secondary Objective 
Secondary Endpoint 

 
 
Version 3.0 1Oct2019 
Page 16 of 40 
Confidential 
SRC-RDD-InnospireGo-2018-10458 
 
 
 
  
 
To evaluate the treatment effect of 
InnoSpire Go on quality of life 
• Change in quality of life scores after 
30 days of device use compared to 
baseline 
o Measure: Chronic Respiratory 
disease Questionnaire – Self-
Report (CRQ-SR) 
Exploratory Objectives 
Exploratory Endpoints 
To evaluate the treatment effect of 
InnoSpire Go on physical activity 
• Difference in total distance walked 
o Measure: 6-Minute Walk Test 
(6MWT) 
To assess effects of InnoSpire Go on 
symptom scores 
• The change in the modified Borg 
score following 6MWT, where the 
visit’s post-nebulizer Borg score will 
be used as the baseline for this 
endpoint) 
o Measure: Borg 
• The change in the modified Borg 
score following nebulizer use, where 
the visit’s pre-nebulizer Borg score will 
be used as the baseline for this 
endpoint) 
o Measure: Borg 
• Difference in modified Borg score from 
pre-nebulizer to post-6MWT 
o Measure: Borg 
To assess device satisfaction based on 
specific elements of the device’s 
operation and handling 
• Difference in device confidence after 
30 days of device use 
o Measure: Nebulizer Satisfaction 
Assessment, question 1 
• Difference in perceived effect of the 
device after 30 days of device use 
o Measure: Nebulizer Satisfaction 
Assessment, question 2 
• Difference in difficulty of device 
assembly/disassembly after 30 days 
of device use 
o Measure: Nebulizer Satisfaction 
Assessment, question 3-1 
• Difference in difficulty of cleaning and 
regular care after 30 days of device 
use 

 
 
Version 3.0 1Oct2019 
Page 17 of 40 
Confidential 
SRC-RDD-InnospireGo-2018-10458 
 
 
 
  
 
o Measure: Nebulizer Satisfaction 
Assessment, question 3-2 
• Difference in overall ease of handling 
or usability after 30 days of device use 
o Measure: Nebulizer Satisfaction 
Assessment, question 3-3 
• Difference in overall burden of use 
after 30 days of device use 
o Measure: Nebulizer Satisfaction 
Assessment, question 3-4 
• Difference in medication delivery 
confidence after 30 days of device use 
o Measure: Nebulizer Satisfaction 
Assessment, question 4 
• Difference in overall satisfaction after 
30 days of device use 
o Measure: Nebulizer Satisfaction 
Assessment, question 5 
• Difference in likelihood of 
recommendation after 30 days of 
device use 
o Measure: Nebulizer Satisfaction 
Assessment, question 6 
• Difference in perception of fit with 
lifestyle needs after 30 days of device 
use 
o Measure: Nebulizer Satisfaction 
Assessment, question 7 
• Difference in average ease of use 
score after 30 days of device use 
o Measure: Nebulizer Preference 
Questionnaire, average of scores 
from questions 3-1 through 3-4 
To evaluate use of the device 
• Time in mouth (treatment time = first 
insert of mouthpiece to last removal of 
mouthpiece) 
o Video recording 
• Time to fill (open disposable nebulizer, 
dispense 
ampule, 
close 
or 
reassemble) 
o Video recording 

 
 
Version 3.0 1Oct2019 
Page 18 of 40 
Confidential 
SRC-RDD-InnospireGo-2018-10458 
 
 
 
  
 
• Amount of fluid nebulized (pre- and 
post-weight of nebulizer) 
o Nebulizer cup/reservoir weights 
• Time to sputter 
o Video recording 
To evaluate the safety of the InnoSpire 
Go device 
• Incidence of Unanticipated Serious 
Adverse Device Effects (USADEs) and 
Serious Adverse Events (SAEs) 
o Measure: Side Effects and Adverse 
Event Assessment 
Study Design 
This will be a randomized open-label cross-over trial to investigate the potential benefits 
to the patient of using the InnoSpire Go over one month, compared to one month’s use 
of their usual jet nebulizer. 
 
Up to 25 stable ambulatory COPD patients who are currently prescribed jet nebulizer 
albuterol treatment or albuterol/ipratropium bromide combination will be included in this 
study. The goal is to have 20 participants complete the study. 
 
 

 
 
Version 3.0 1Oct2019 
Page 19 of 40 
Confidential 
SRC-RDD-InnospireGo-2018-10458 
 
 
 
  
 
Figure 2 
 
 

 
 
Version 3.0 1Oct2019 
Page 20 of 40 
Confidential 
SRC-RDD-InnospireGo-2018-10458 
 
 
 
  
 
Schedule of Events 
Procedures  
 
 
 
 
 
Pre-Screening 
Visit 1 (Day 1) 
Screening/Baseline 
Visit 2 (15 days ± 3 
days after Visit 1) 
Interim Visit 
Visit 3 
(Day 30 ± 3 days) 
Crossover 
Visit 4 (15 days ± 3 
days after Visit 3) 
Interim Visit 
Visit 5 
(30 days ± 3 days after 
Visit 3) 
Final Visit 
Recruitment 
X 
 
 
 
 
 
Informed Consent 
 
X 
 
 
 
 
Inclusion/Exclusion Criteria Review 
 
X 
 
 
 
 
Demographics 
 
X 
 
 
 
 
Medical History 
 
X 
 
 
 
 
Height and Weight 
 
X 
 
 
 
 
Concomitant Medication 
 
X 
X 
X 
X 
X 
Device Photograph 
 
X 
 
 
 
 
Modified Medical Research Council Dyspnea 
Scale 
 
X 
 
 
 
 
Chronic Respiratory Disease Questionnaire 
Self-Report 
 
X 
X 
X 
X 
X 
Spirometry 
 
X 
 
 
 
 
Peak Inspiratory Flow Assessment 
 
X 
 
X 
 
X 
Vital Signs 
 
X 
 
X 
 
X 
6-Minute Walk Test 
 
X 
 
X 
 
X 
Modified Borg Assessment* 
 
X 
 
X 
 
X 
Device Use Demonstration (Audio/Video) 
 
 
 
X 
 
X 
Nebulizer Weight 
 
 
 
X 
 
X 
Training Session 
 
X† 
 
X§ 
 
 
Side Effects and Adverse Event Assessment 
 
 
X 
X 
X 
X 
Nebulizer Satisfaction Assessment 
 
 
X 
X 
X 
X 
*Borg assessment will be performed up to three times at each designated visit (see visit procedures 
below). 
†For participants randomized to InnoSpire Go in the first treatment arm. 
§For participants randomized to InnoSpire Go in the second treatment arm. 
Screening Procedures: 
Participants will be contacted by designated study site staff. Participants may be pre-
screened through medical records over the phone to assess potential eligibility. 
Participants that are interested will be scheduled for a screening visit at the clinical office. 
Visit 1 – Screening/Baseline: 
Once the participant arrives, the study will be explained in full detail. If the participant 
agrees, he/she will be consented into the study and the participant will be given a copy of 
the informed consent. After the consent is signed, the following procedures will be 
performed: 
Demographics 

 
 
Version 3.0 1Oct2019 
Page 21 of 40 
Confidential 
SRC-RDD-InnospireGo-2018-10458 
 
 
 
  
 
Demographic data will be collected from standard sources. 
Medical History 
Information related to the patient’s medical history, including COPD history. 
Height and Weight 
Participants’ height and weight will be collected. 
Concomitant Medication 
Prescription history will be collected. Participants will be asked to bring all inhaled 
medications to this visit. Their self-reported use of either albuterol or combination 
albuterol/ipratropium will also be documented. 
mMRC 
Dyspnea ratings will be collected using the Modified Medical Research Council (mMRC) 
dyspnea scale. 
CRQ-SR 
The participant will complete the CRQ-SR13, 14 (Appendix 1) to assess disease-related 
quality of life. 
Pulmonary Function Tests 
Spirometry will be performed at Visit 1. Participants must have an FEV1 ≥ 30 to be eligible 
for participation. Site staff will document the number of hours since the participant’s last 
use of bronchodilators. 
Additionally, peak inspiratory flow (PIF) will be measured using In-Check inspiratory flow 
device. The highest of three attempts should be recorded. 
Vital Signs 
Heart rate, blood pressure and SpO2 will be collected before 6MWT is performed. 
6-Minute Walk Test 
A 6MWT will be performed according to international guidelines.15, 16 Parameters 
measured during this test include total distance walked and Borg17-19 dyspnea scale pre- 
and post-test. SpO2 will be continuously measured using a pulse oximeter. 
Modified Borg Assessment 
The modified Borg assessment (Appendix 2) will be performed before and after 6MWT. 
Inclusion/Exclusion Criteria Review 
Site staff will review inclusion/exclusion criteria to determine participant eligibility. Only 
eligible participants will be randomized. 
Device Photograph 
Participants will be asked to bring their current jet nebulizer system to the visit. Study staff 
will take a photograph of the compressor, handset, and associated labels, if available. 

 
 
Version 3.0 1Oct2019 
Page 22 of 40 
Confidential 
SRC-RDD-InnospireGo-2018-10458 
 
 
 
  
 
Randomization 
Participants will be randomly assigned to either their current jet nebulizer or the InnoSpire 
Go device for the first 30 days of treatment. 
Training Session 
Participants randomized to InnoSpire Go in the first treatment arm will be trained on the 
use and cleaning of the device before being sent home. These participants will be asked 
to refrain from using their own jet nebulizer system during this 30-day period. 
 
Visit 2 – Interim Visit: 
Participants will be asked to return to the research center 15 days ± 3 days after Visit 1. 
Side Effects and Adverse Event Assessment 
Participants will be asked about any side effects or adverse events (AEs) since the last 
visit. 
Concomitant Medications 
Participants will be asked about any changes in their medication since the last visit. 
CRQ-SR (Follow-Up) 
Participants will complete the follow-up CRQ-SR (Appendix 3) to assess disease-related 
quality of life since the previous visit. 
Nebulizer Satisfaction Assessment 
Participant satisfaction with the device used in the first treatment arm will be assessed. 
See Appendix 4 for assessment details. 
 
Visit 3 – Cross-over: 
Participants will be asked to return to the research center within 30 days ± 3 days after 
Visit 1. They will be instructed to bring the first assigned study device and their prescribed 
albuterol or combination albuterol/ipratropium medication for the demonstration. 
CRQ-SR (Follow-Up) 
Participants will complete the follow-up CRQ-SR to assess disease-related quality of life 
since the previous visit. 
Concomitant Medications 
Participants will be asked about any changes in their medication since the last visit.  
Device Use Demonstration 
Participants will be asked to assemble their device and administer their next scheduled 
dose in the clinic to demonstrate their use of the device before completing the 6MWT. 
Site staff will verify that the demonstration does not conflict with patient’s prescribed 

 
 
Version 3.0 1Oct2019 
Page 23 of 40 
Confidential 
SRC-RDD-InnospireGo-2018-10458 
 
 
 
  
 
dosage. All demonstrations will be video recorded to provide information on nebulizer use 
in post-study analysis. 
Nebulizer Weight 
The nebulizer cup/reservoir alone will be weighed with the medication before device use 
and after device use to capture residual medication. This process will take place during 
video recording. 
PIF 
Peak inspiratory flow will be measured using the In-Check inspiratory flow device. The 
highest of three attempts should be recorded. 
Vital Signs 
Blood pressure and SpO2 will be collected after nebulizer use but before 6MWT is 
performed. Heart rate will be collected before nebulizer use, after nebulizer use, 
immediately after and approximately 15 minutes after the 6MWT. 
Modified Borg Assessment 
The modified Borg assessment will be performed three times (i.e., before and after 
nebulizer use and after 6MWT). The post-nebulizer Borg assessment should be 
performed at least 15 minutes after the completion of the nebulizer treatment. 
6-Minute Walk Test 
A 6MWT will be performed after nebulizer has been used and all post-nebulizer 
assessments (i.e., vital signs and modified Borg) have been completed. 
Nebulizer Satisfaction Assessment 
Participant satisfaction with the device used in the first treatment arm will be assessed. 
Training Session 
Participants randomized to InnoSpire Go in the second treatment arm will be trained on 
the use and cleaning of the device before being sent home. These participants will be 
asked to refrain from using their own jet nebulizer system during this 30-day period. 
 
Visit 4 – Interim Visit: 
Participants will be asked to return to the research center 15 days ± 3 days after Visit 3. 
Participants will complete procedures outlined in Visit 2. 
 
Visit 5 –Final Visit: 
Participants will return to the clinical facility 30 days (± 3 days) after Visit 3 completion. 
They will be instructed to bring the second assigned study device and their prescribed 
albuterol or combination albuterol/ipratropium medication for the demonstration. 
Participants will complete the procedures outlined in Visit 3. Participants will need to 
return all study equipment at this visit. 

 
 
Version 3.0 1Oct2019 
Page 24 of 40 
Confidential 
SRC-RDD-InnospireGo-2018-10458 
 
 
 
  
 
Participants will be discharged from the study following completion of study procedures. 
Consent for Participation 
Consent forms describing in detail the study intervention, study procedures and risks will 
be given to the participant and written documentation of informed consent is required prior 
to starting intervention/administering study intervention. 
Informed consent is a process that will be initiated prior to the individual’s agreeing to 
participate in the study and continues throughout the individual’s study participation. An 
Independent Review Board will review consent forms. After approval, the participants will 
be asked to read, review and sign the document. The investigator or Investigator’s 
representative will explain the research study to the participant and answer any questions 
that may arise. A verbal explanation will be provided in terms suited to the participant’s 
comprehension of the purposes, procedures, and potential risks of the study and of their 
rights as research participants. Participants will have the opportunity to carefully review 
the written consent form and ask questions prior to signing. The participants should have 
the opportunity to discuss the study with their family and/or friends or think about it prior 
to agreeing to participate. The participant will sign the informed consent document prior 
to any study procedures being done. Participants will be informed that participation is 
voluntary and that they may withdraw from the study at any time, without prejudice. A 
copy of the informed consent document will be given to the participants for their records. 
The informed consent process will be conducted and documented in the source document 
(including the date). The rights and welfare of the participants will be protected by 
emphasizing to them that the quality of their medical care will not be adversely affected if 
they decline to participate in this study. 
Selection and Withdrawal of Subjects: 
Inclusion Criteria 
1. Patients ≥ 40 years of age. 
2. Diagnosis of COPD. 
3. Currently using only a mouthpiece with their nebulizer system. 
4. FEV1 ≥ 30% predicted (pre- or post-bronchodilator). 
5. mMRC grade ≥ 1. 
6. Use of a jet nebulizer for the administration of albuterol or combination 
albuterol/ipratropium for the past 6 months. 
7. Willing to use the same compressor/nebulizer system throughout the study. 
8. Willing to refrain from using the jet nebulizer system when using the InnoSpire Go. 
9. Prescribed nebulizer combination albuterol/ipratropium (single or multiple vials) with 
self-report of at least daily use or prescribed nebulizer albuterol with self-report of at 
least twice daily use. 

 
 
Version 3.0 1Oct2019 
Page 25 of 40 
Confidential 
SRC-RDD-InnospireGo-2018-10458 
 
 
 
  
 
10. Willing to permit audio and video recording during the visit. 
11. Willing and able to follow instructions and complete all activities required by the trial, 
including phone calls. 
12. Able to read and understand English. 
Exclusion Criteria 
1. Unable to complete 6MWT or, if patient is not currently prescribed oxygen, persistent 
oxygen desaturation ≤ 88% on the 6MWT. 
2. Exacerbation of COPD requiring hospitalization (defined as hospital admission, urgent 
care visit, or emergency room visit) in the last 3 months. 
3. Prescribed non-selective beta blockers. 
4. Prescribed additional ipratropium bromide via nebulizer or inhaler or any other 
nebulized treatments via the subject’s jet nebulizer. 
5. Patients currently in assisted living or nursing home. 
6. Diagnosis of asthma, parenchymal lung disease other than COPD, bronchiectasis, 
tuberculosis, cor pulmonale, clinically significant obstructive urinary disease, narrow-
angle glaucoma, unstable angina, depression, anxiety, or other serious medical 
condition that, in the opinion of the investigator, would interfere with the patient’s 
participation in the trial. 
7. History of thoracotomy. 
8. Myocardial infarction within the last 6 months. 
9. Participation in any other therapeutic clinical trial in the previous 4 weeks. 
Withdrawal 
The term “discontinuation” refers to the participant’s premature withdrawal from the study 
prior to completing all procedures. Participants may be discontinued from the study for 
any of the following reasons: 
• If in the investigator’s judgement, continuation in the study may prove harmful to 
the participant. Such a decision may be precipitated by AEs, including fever, 
nausea, rash, changes in vital signs, or the development of a new medical 
condition. The investigator will be solely responsible for making medical/safety 
decisions regarding the participant’s continued participation in the study. 
• Non-compliance with protocol requirements, including concomitant medication 
requirements 
• At the request of the participant 
• Exacerbation resulting in hospitalization 

 
 
Version 3.0 1Oct2019 
Page 26 of 40 
Confidential 
SRC-RDD-InnospireGo-2018-10458 
 
 
 
  
 
The study team will document whether or not each participant completed the study. If 
study treatment or assessments were discontinued for any participant, the reason will be 
recorded. Participants who are discontinued will not be replaced. 
The goal is to have 20 participants successfully complete the study. 
Discontinuation of Study Intervention 
If a participant requests to stop using the device it does not mean discontinuation from 
the study, and remaining study procedures should be completed as indicated by the study 
protocol unless the participant does not wish to return and complete the follow-up visits. 
If a clinically significant side effect is identified (including, but not limited to negative 
changes from baseline) after enrollment, the investigator or qualified designee will 
determine if any change in participant management is needed. Any new any unfavorable 
and unintended sign (including an abnormal laboratory finding), symptom, or disease 
temporally associated with the use of the investigational device, whether or not related to 
the investigational device will be reported as an AE. See Assessment of Safety section 
for additional definitions and AE management. 
Treatment of Subjects 
Intended Use  
InnoSpire Go is intended to be used as a general purpose mesh nebulizer used to 
aerosolize commonly prescribed liquid inhalation drugs for respiratory disease in children 
and adults. It is to be used by, but not limited to, patients with asthma, COPD and cystic 
fibrosis. 
Contraindications 
InnoSpire Go is not be used by patients that are unconscious or not breathing 
spontaneously. 
Monitoring 
Remote monitoring will be conducted for this study. Data that is directly entered into EDC 
will not be verified. 100% of the remaining data will be verified among 10% of the study 
participants’ records. 
This study will be monitored in compliance with Code of Federal Regulations (CFR) for 
clinical research; namely, 21 CFR Parts 50, 54, 56 and 812 and others as applicable. The 
purpose of such monitoring is to ensure that the rights and wellbeing of trial participants 
are protected, that the reported trial data are accurate, complete, and verifiable, and that 
the 
conduct 
of 
the 
trial 
is 
in 
compliance 
with 
the 
currently 
approved 
protocol/amendment(s), with International Conference on Harmonisation (ICH) Good 
Clinical Practice (GCP), and with applicable regulatory requirement(s). Monitoring visits 
will be performed periodically and will be conduct by trained clinical research 

 
 
Version 3.0 1Oct2019 
Page 27 of 40 
Confidential 
SRC-RDD-InnospireGo-2018-10458 
 
 
 
  
 
professionals. The monitoring process includes initial subject qualifications, periodic 
contact with the subject, and a final review once the study is complete. 
It has been determined that this study does not require a Data Safety Monitoring Board 
(DSMB). 
Unscheduled Visits 
Unscheduled calls and/or visits will be documented in the participant study file upon 
occurrence. Participants may be asked to receive additional phone calls in order to 
evaluate a technical or device issue and on an as needed basis. 
Assessment of Performance  
Device performance will be assessed based on the endpoints described in the Study 
Objectives and Purpose section. 
Assessment of Safety  
Adverse Events 
Adverse event means any untoward medical occurrence associated with the use of an 
intervention in humans, whether or not considered intervention-related. 
An adverse device effect (ADE) is an AE related to the use of an investigational medical 
device. 
Serious Adverse Events 
An AE or suspected adverse reaction is considered "serious" if, in the view of either the 
investigator or sponsor, it results in any of the following outcomes: death, a life-
threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a 
persistent or significant incapacity or substantial disruption of the ability to conduct normal 
life functions, or a congenital anomaly/birth defect. Important medical events that may not 
result in death, be life-threatening, or require hospitalization may be considered serious 
when, based upon appropriate medical judgment, they may jeopardize the participant and 
may require medical or surgical intervention to prevent one of the outcomes listed in this 
definition. Examples of such medical events include allergic bronchospasm requiring 
intensive treatment in an emergency room or at home, blood dyscrasias or convulsions 
that do not result in inpatient hospitalization, or the development of drug dependency or 
drug abuse. 
Unanticipated Serious Adverse Device Effect 
A USADE is a serious ADE which by its nature, incidence, severity or outcome has not 
been identified in the current version of the risk analysis report. 
Severity of Event 
The following guidelines will be used to describe AE severity: 

 
 
Version 3.0 1Oct2019 
Page 28 of 40 
Confidential 
SRC-RDD-InnospireGo-2018-10458 
 
 
 
  
 
• Mild – Events require minimal or no treatment and do not interfere with the 
participant’s daily activities. 
• Moderate – Events result in a low level of inconvenience or concern with the 
therapeutic measures. Moderate events may cause some interference with 
functioning. 
• Severe – Events interrupt a participant’s usual daily activity and may require 
systemic drug therapy or other treatment. Severe events are usually potentially 
life-threatening or incapacitating. Of note, the term “severe” does not necessarily 
equate to “serious”. 
Relationship to Study Intervention 
All AEs must have their relationship to study intervention assessed by the clinician who 
examines and evaluates the participant based on temporal relationship and his/her 
clinical judgement. The degree of certainty about causality will be graded using the 
categories below. In a clinical trial, the study product must always be suspect. 
• Related – The AE is known to occur with the study intervention, there is a 
reasonable possibility that the study intervention caused the AE, or there is a 
temporal relationship between the study intervention and event. Reasonable 
possibility means that there is evidence to suggest a causal relationship between 
the study intervention and the AE. 
• Not Related – There is not a reasonable possibility that the administration of the 
study intervention caused the event, there is no temporal relationship between the 
study intervention and event onset, or an alternate etiology has been established. 
Adverse Event Assessment and Follow-Up 
Adverse events will be collected on an ongoing basis following signing of informed 
consent. Detailed information regarding the event will be recorded on the appropriate form 
in the electronic case report form (eCRF), where the Investigator will determine the 
severity of the event, relationship to study product (assessed only by those with the 
training and authority to make a diagnosis), and time of resolution/stabilization of the 
event. Follow-up data to ascertain the existence of residual effects from the event will be 
obtained. Serious adverse events must be reported to the sponsor within 24 hours of 
discovering the occurrence of the SAE. The research staff is required to complete and 
submit the sponsor’s standard SAE form detailing the event. Reports should be directed 
to: 
Ketah Doty, RN, BSN, OCN 
Senior Clinical Research Associate  
1740 Golden Mile Highway 
Monroeville, PA 15146 
Phone: 724-387-7921 
Mobile: 412-738-6281 

 
 
Version 3.0 1Oct2019 
Page 29 of 40 
Confidential 
SRC-RDD-InnospireGo-2018-10458 
 
 
 
  
 
Email: ketah.doty@philips.com 
 
Serious Adverse Event and Unanticipated Adverse Device Effect Reporting 
The study investigator will complete an SAE/Unanticipated Adverse Device Effect Form 
and submit to the study sponsor and to the reviewing IRB as soon as possible, but in no 
event later than 10 working days after the investigator first learns of the effect. The study 
sponsor is responsible for conducting an evaluation of an unanticipated adverse device 
effect and shall report the results of such evaluation to local regulatory authorities and to 
all reviewing IRBs and participating investigators within 10 working days after the sponsor 
first receives notice of the effect. Thereafter, the sponsor shall submit such additional 
reports concerning the effect to local regulatory authorities. 
Device Deficiencies 
All device deficiencies, use or user errors, and equipment failures will be documented. 
Use or User errors will be captured as part of the source documentation. Device 
deficiencies and equipment failures will be kept on a separate log. The serial numbers 
and type of deficiency/failure will be captured. Unanticipated device deficiencies that lead 
to SAE’s will be reviewed with the principal investigator (PI) and reported to the IRB as 
required. 
Statistical Methods 
Determination of Sample Size 
The study plans to randomize up to 25 participants with a goal of having 20 participants 
complete the study. The sample size is based on project timelines and budgetary 
constraints.  
General Considerations 
The primary analysis will be include all randomized participants. Descriptive data tables 
will be provided for all variables of interest.  Continuous data will be presented by mean, 
standard deviation, median, minimum, and maximum observation. Data will be presented 
in the untransformed and transformed format (if applicable) for each continuous variable. 
Categorical data will be presented as frequencies and percentages. All formal statistical 
analyses will be performed using either SAS® or SPSS® software. Significance tests will 
be conducted at a two-sided significance level of p < 0.05. 
There are no statistical criteria for terminating the study. No sensitivity analysis will be 
completed, and any deviations to the original statistical plan will be noted in the analysis 
report. 
Participant Disposition 

 
 
Version 3.0 1Oct2019 
Page 30 of 40 
Confidential 
SRC-RDD-InnospireGo-2018-10458 
 
 
 
  
 
Participant disposition, including the total number of participants enrolled, completed, 
early terminations and withdrawals, will be presented. A listing will be provided with the 
reasons for discontinuation.  
Primary Analysis 
Continuous ratings that are collected at only one interval per device will be examined 
using either a paired t-test or the non-parametric Wilcoxon Singed-Ranks test, depending 
on the distribution of the paired differences. Mixed Models with repeated measures may 
be used for endpoints collected at multiple intervals per device. 
Categorical ratings that are provided for each device will be analyzed using the McNemar 
test; if there are more than two levels for these ratings, they will need to be grouped into 
two levels for this analysis. 
Categorical preference endpoints that are answered at the final visit (e.g., “Which device 
do you prefer?”) will be analyzed with a One-sample Binomial Test that compares the 
observed proportion to a 50/50 split. 
Treatment Compliance and Missing Data 
Any discontinued participants or protocol deviations will be tracked and reported in data 
listings. If a participant discontinues a device after the 15-day assessment, their ratings 
will be carried forward to the 30-day interval for the intent-to-treat analysis. This 
imputation will only be necessary for participants that complete at least the 15-day 
assessment for both devices. If a participant discontinues before providing ratings for both 
devices, they will be excluded from the analysis. 
Safety Analysis 
Safety evaluations will be performed by recording clinical adverse events at the time 
originally reported, and they will be followed at regular intervals until resolution, or until 
the study is completed, whichever comes first. Adverse events will be provided in data 
listings. 
Interim Analysis 
Preliminary results will be assessed after 10 participants complete the study, but the 
sample size will not be adjusted based on these interim outcomes. 
Direct Access to Source Data/Documents  
Only site clinical study staff and approved Philips staff working with the research will know 
the identity of the participants. All information recorded by the study team and provided 
for analysis will be given a study ID number. A unique source record will be created for 
each study participant. 

 
 
Version 3.0 1Oct2019 
Page 31 of 40 
Confidential 
SRC-RDD-InnospireGo-2018-10458 
 
 
 
  
 
Privacy rules and requirements according to federal and state governing regulations will 
be implemented. Except when required by law, participants will not be identified by name, 
social security number, address, telephone number, or any other direct personal identifier 
in study records. For records disclosed outside the Institution conducting this study, 
participants will be assigned a unique code number. The key to the code will be kept by 
the investigators. Data will be managed by study number and analyzed anonymously. 
The study record will include documentation of the informed consent form review process, 
HIPAA completion according to site policies, and applicable medical history. The Sponsor 
will have access to these source records.  
In addition, participants’ records including sensitive information and/or identifying 
information, may be inspected by the IRB, government agencies, and/or competent 
authorities, in the course of carrying out their duties. 
All data will be kept confidential and in a secure location if on paper or on a secure server 
or device. Only approved study personnel will have access to study related documents. 
Approved study personnel are trained on privacy, HIPAA and data protection laws. 
In addition, participant records may be reviewed in order to meet federal and state 
regulations. Reviewers may include representatives from the FDA or similar government 
authorities in other countries where the device is being used, and Philips Respironics for 
the purposes of the following side effects, and to gather additional information related to 
the study, and the IRB. Participant permission for review of confidential information is 
granted by signing the associated informed consent. Philips Respironics will ensure that 
it follows all applicable state and federal data protection regulations. 
Data may be reviewed by any Philips research team, in any location, for purposes as 
outlined above, made available via a secure Philips site. 
Case Report Forms  
Study related eCRFs and source documentation will be collected and maintained by the 
sponsor, will be kept confidential, and stored in a secure location if on paper or on a 
secure server or protected device. Only staff delegated by the PI will have the ability to 
enter in, or make changes to, the eCRFs and source documents.  
Quality Control and Quality Assurance 
Each clinical site will perform internal quality management of study conduct, data 
collection, documentation and completion.  
Quality control (QC) procedures will be implemented beginning with the data entry system 
and data QC checks that will be run on the database will be generated. Any missing data 
or data anomalies will be communicated to the site(s) for clarification/resolution. 
The clinical monitor(s) will verify that the clinical trial is conducted and data are generated, 
tests are completed and documented (recorded), and reported in compliance with the 

 
 
Version 3.0 1Oct2019 
Page 32 of 40 
Confidential 
SRC-RDD-InnospireGo-2018-10458 
 
 
 
  
 
protocol and ICH GCP. Monitoring will be completed in accordance with FDA US CFR 
and ICH-E6 GCP Section 6, as applicable. 
The investigational site will provide direct access to all source data/documents, and 
reports for the purpose of monitoring and auditing by the sponsor, and inspection by local 
and regulatory authorities. 
Ethics 
This study will be submitted and reviewed by an IRB. All participants will be consented 
prior to completing the trial. The Primary Investigator will review all AEs as it relates to 
the study device. 
All the information collected as part of this study will be kept confidential. All information 
collected for this study will be kept in a secured area or stored in a password protected 
computer, if digital. Results of the study-related tests, medical history and information 
obtained from the questionnaires will be reported to the study sponsor (Philips 
Respironics, Inc.). Philips Respironics may use participant study data for research or 
regulatory purposes. Investigators may use participant study data to prepare research 
publications or presentations at meetings. No personally identifiable information will be 
used in any reports, meeting presentations, or publications of this study. 
Data Handling and Recordkeeping  
Hard copies of the study will be kept on site for at least 2 years after study completion. 
The sponsor will maintain study records indefinitely. Records will be stored at Iron 
Mountain, a secure information management services company. 
Financing and Insurance  
If the participant is injured during the course of the trial and as a direct result of this trial, 
they should contact the Principal Investigator. The participant will be directed to seek 
clinically appropriate medical care for that injury. However, we cannot guarantee that the 
medical care and treatment will be provided without charge or that it will be paid for by 
the participants insurance company, and the costs incurred may ultimately be the 
participant’s responsibility. 
Registration on ClinicalTrials.gov or other applicable registry  
This trial will be registered at ClinicalTrials.gov, and results information from this trial will 
be submitted to ClinicalTrials.gov. In addition, every attempt will be made to publish 
results in peer-reviewed journals. 
Risk and Benefit Analysis 
Potential Risks and Discomforts 
Adverse effects of nebulizer use are usually minor and manageable. All AEs encountered, 
will be recorded on data sheets that are part of the eCRF. 

 
 
Version 3.0 1Oct2019 
Page 33 of 40 
Confidential 
SRC-RDD-InnospireGo-2018-10458 
 
 
 
  
 
The risks of using the InnoSpire Go device are minimal. Use of nebulizer devices 
themselves do not have any known side effects. Side effects are generally associated 
with the medication being nebulized. The medications used in this study will be albuterol 
sulfate and combination ipratropium bromide/albuterol sulfate, which is a commonly 
prescribed medication for COPD patients.  
Reported side effects of albuterol sulfate or combination ipratropium bromide/albuterol 
sulfate include tremors, dizziness, nervousness, headache, insomnia, nasal congestion, 
tachycardia, hypertension, bronchospasm, cough, bronchitis, wheezing, chest or body 
pain, diarrhea, dyspepsia, nausea, muscle cramps, bronchitis, lung disease, pharyngitis, 
pneumonia, urinary tract infection, constipation and voice alterations.20, 21 
The use of albuterol sulfate and ipratropium bromide singly or in combination has also 
been associated with precipitation or worsening of narrow-angle glaucoma, acute eye 
pain, blurred vision, mydriasis, exacerbation of COPD symptoms, drowsiness, aching, 
flushing, upper respiratory tract infection, palpitations, taste perversion, sinusitis, back 
pain, urticaria, angioedema, rash, oropharyngeal edema, arrhythmias (including atrial 
fibrillations, supraventricular tachycardia, extrasystoles) and metabolic acidosis.20, 21  
There are minimal risks of using the device and should they occur during the course of 
the study, they will be recorded. Other more serious AEs are distinctly unusual in the 
outpatient setting but will be recorded if they occur. Serious adverse events and device-
related AEs will be reported to the IRB per their policy. Patients may find InnoSpire Go to 
be less comfortable than their previous nebulizer, but this is not a real medical risk. 
Thus, we believe that although there may be discomforts associated with the use of this 
device and study related procedures, the risks are minimal. 
We believe that the risks and discomforts associated with this study are minimal. 
The following measures will be taken to minimize risk to patients 
• Physicians and staff will receive adequate training on the use of the device. 
• Patients will be closely monitored throughout the trial. 
• Reported AEs will be reviewed regularly throughout the study and appropriate 
medical measures will be taken to resolve the AEs. 
Potential Benefits 
Although participation in this trial will not result in any direct benefit to the subject, they 
will be contributing to generalizable data that will help improve device design and function. 
Compensation for Research-Related Activities 
Participants will only be compensated for the activities that they complete. Participants’ 
compensation will be paid according to the following schedule. 
Activity 
Payment Amount 

 
 
Version 3.0 1Oct2019 
Page 34 of 40 
Confidential 
SRC-RDD-InnospireGo-2018-10458 
 
 
 
  
 
Visit 1 
$100 
Visit 2 
$25 
Visit 3 
$50 
Visit 4 
$25 
Visit 5 
$50 
 
Publication  
It is the intent that these data will be used/considered for a submission to peer-reviewed 
publication, white paper or scientific abstract. 
References  
 
1. 
Qaseem, A., et al., Diagnosis and management of stable chronic obstructive 
pulmonary disease: a clinical practice guideline update from the American 
College of Physicians, American College of Chest Physicians, American Thoracic 
Society, and European Respiratory Society. Ann Intern Med, 2011. 155(3): p. 
179-91. 
2. 
Global Health Estimates 2016: Deaths by Cause, Age, Sex, by Country and by 
Region, 2000-2016. 2018, World Health Organization: Geneva. 
3. 
Global Strategy for the Diagnosis, Management and Prevention of Chronic 
Obstructive Pulmonary Disease. 2019, Global Initiative for Chronic Obstructive 
Lung Disease. 
4. 
Taffet, G.E., J.F. Donohue, and P.R. Altman, Considerations for managing 
chronic obstructive pulmonary disease in the elderly. Clin Interv Aging, 2014. 9: 
p. 23-30. 
5. 
Gardenhire, D.S., et al. A Guide To Aerosol Delivery Devices for Respiratory 
Therapists. 2017; 4:[Available from: https://www.aarc.org/wp-
content/uploads/2018/03/aersol-guides-for-rts.pdf. 
6. 
Tashkin, D.P., A review of nebulized drug delivery in COPD. Int J Chron Obstruct 
Pulmon Dis, 2016. 11: p. 2585-2596. 
7. 
Loh, C.H. and J.A. Ohar, Personalization of Device Therapy - Prime Time for 
Peak Inspiratory Flow Rate. Chronic Obstr Pulm Dis, 2017. 4(3): p. 172-176. 
8. 
Tashkin, D.P., et al., Comparing COPD treatment: nebulizer, metered dose 
inhaler, and concomitant therapy. Am J Med, 2007. 120(5): p. 435-41. 
9. 
Pritchard, J.N., Nebulized drug delivery in respiratory medicine: what does the 
future hold? Ther Deliv, 2017. 8(6): p. 391-399. 
10. 
Gowda, A.A., A.D. Cuccia, and G.C. Smaldone, Reliability of Vibrating Mesh 
Technology. Respir Care, 2017. 62(1): p. 65-69. 
11. 
Vecellio, L., The mesh nebuliser: a recent technical innovation for aerosol 
delivery. Breathe, 2006. 2(3): p. 252-260. 
12. 
Dhand, R., Nebulizers that use a vibrating mesh or plate with multiple apertures 
to generate aerosol. Respir Care, 2002. 47(12): p. 1406-16; discussion 1416-8. 

 
 
Version 3.0 1Oct2019 
Page 35 of 40 
Confidential 
SRC-RDD-InnospireGo-2018-10458 
 
 
 
  
 
13. 
Guyatt, G.H., et al., A measure of quality of life for clinical trials in chronic lung 
disease. Thorax, 1987. 42(10): p. 773-8. 
14. 
Puhan, M.A., et al., Relative responsiveness of the Chronic Respiratory 
Questionnaire, St. Georges Respiratory Questionnaire and four other health-
related quality of life instruments for patients with chronic lung disease. Respir 
Med, 2007. 101(2): p. 308-16. 
15. 
Holland, A.E., et al., An official European Respiratory Society/American Thoracic 
Society technical standard: field walking tests in chronic respiratory disease. Eur 
Respir J, 2014. 44(6): p. 1428-46. 
16. 
ATS, ATS Committee on Proficiency Standards for Clinical Pulmonary Function 
Laboratories: guidelines for the six-minute walk test. . Am J Respir Crit Care Med 
2002. 166: p. 111-117. 
17. 
Rating of perceived exertion: Borg scales. 2014  [cited 2019; Available from: 
http://www.heartonline.org.au/media/DRL/Rating_of_perceived_exertion_-
_Borg_scale.pdf. 
18. 
Kendrick, K.R., S.C. Baxi, and R.M. Smith, Usefulness of the modified 0-10 Borg 
scale in assessing the degree of dyspnea in patients with COPD and asthma. J 
Emerg Nurs, 2000. 26(3): p. 216-22. 
19. 
Borg, G. and H. Weight, Perceived exertion (Borg rating of perceived exertion 
scale). National Center for chronic disease prevetion and health promotion, CDC, 
1998. 
20. 
Albuterol Sulfate Solution Product Labeling -Mylan Pharmaceuticals Inc. 2013. 
21. 
DuoNeb® Product Labeling - DEY. 2004. 
 

 
 
Version 3.0 1Oct2019 
Page 36 of 40 
Confidential 
SRC-RDD-InnospireGo-2018-10458 
 
 
 
  
 
Appendix 1: Chronic Respiratory Disease Questionnaire-Self Report 
Document attached. 

 
 
Version 3.0 1Oct2019 
Page 37 of 40 
Confidential 
SRC-RDD-InnospireGo-2018-10458 
 
 
 
  
 
Appendix 2: Borg Assessment 
Document attached. 

 
 
Version 3.0 1Oct2019 
Page 38 of 40 
Confidential 
SRC-RDD-InnospireGo-2018-10458 
 
 
 
  
 
Appendix 3: Chronic Respiratory Disease Questionnaire-Self Report (Follow-Up) 
Document attached. 

 
 
Version 3.0 1Oct2019 
Page 39 of 40 
Confidential 
SRC-RDD-InnospireGo-2018-10458 
 
 
 
  
 
Appendix 4: Nebulizer Satisfaction Assessment 
No. 
Questions (select one) 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
1 
How confident are you in using the device?  
Not at all 
confident 
 
 
 
 
 
Very confident 
2 
How does this device affect your shortness of 
breath?  
Much worse 
 
 
 
 
 
Much better 
3 
Please tell us about any difficulties you 
experienced when using the device 
3-1 
Device assembly and disassembly? 
Very difficult 
 
 
 
 
 
Very easy 
3-2 
Device cleaning and regular care 
Very difficult 
 
 
 
 
 
Very easy 
3-3 
Overall ease of handling or usability for a 
treatment  
Very difficult 
 
 
 
 
 
Very easy 
3-4 
Overall burden (filling, taking treatment and 
cleaning) 
Very difficult 
 
 
 
 
 
Very easy 
4 
How confident are you the device delivered 
all your medication? 
Not at all 
confident 
 
 
 
 
 
Very confident 
5 
Please rate your overall satisfaction with the 
device 
Very 
dissatisfied 
 
 
 
 
 
Very satisfied 
6 
Would you recommend the device to others 
(i.e., family, friends) that are prescribed a 
nebulizer? 
Very unlikely 
 
 
 
 
 
Very likely 

 
 
Version 3.0 1Oct2019 
Page 40 of 40 
Confidential 
SRC-RDD-InnospireGo-2018-10458 
 
 
 
  
 
No. 
Questions (select one) 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
7 
How well does the device fit your lifestyle 
needs? 
Not well at all 
 
 
 
 
 
Very well 
 
 
To be asked at Visit 5 only 
8 
Which nebulizer do you prefer? 
 
Jet/ 
Compressor 
InnoSpire Go