Conditions: Asthma
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 86
Healthy volunteers: no

Brief summary:
This is a randomized, double-blind, single-dose, placebo-controlled, 5-period, 5-treatment, crossover, multi-center study to assess the bronchodilatory effect and safety of 2 dose levels of Albuterol Sulfate Pressurized Inhalation Suspension (hereafter referred to as AS MDI), 90 μg and 180 μg, compared with placebo for AS MDI (hereafter referred to as Placebo MDI) and open-label Proventil® hydrofluoroalkane (HFA; hereafter referred to as Proventil) 90 μg and 180 μg in adult and adolescent subjects with mild to moderate asthma. This study design utilizes 10 treatment sequences.

Detailed description:
This is a 5-period crossover study. Each Treatment Period is 1 day. Subjects will receive a single dose of randomized study drug at each of the 5 Treatment Visits (Visits 2, 3, 4, 5, and 6), with a 3- to 7-day Washout Period between Treatment Visits.

Arms:
arm 1: (2 actuations of 45 µg/actuation) arm 2: (2 actuations of 90 µg/actuation) arm 3: (2 actuations) arm 4: (1 actuation of 90 µg/actuation) arm 5: (2 actuations of 90 µg/actuation)

Interventions: intervention 1: AS MDI 90 μg intervention 2: AS MDI 180 µg intervention 3: Placebo MDI intervention 4: Proventil 90 μg intervention 5: Proventil 180 μg
Intervention descriptions: intervention 1: AS MDI 90 μg (2 actuations of 45 μg/actuation) intervention 2: AS MDI 180 μg (2 actuations of 90 μg/actuation) intervention 3: Placebo MDI (2 actuations) intervention 4: Proventil 90 μg (1 actuation of 90 μg/actuation) intervention 5: Proventil 180 μg (2 actuations of 90 μg/actuation)

Protocol document:
Prot_000.pdf: 
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Clinical Study Protocol (CSP) - ANGEL 
Version 18.0 
Template Form Doc ID: LDMS_001_00026737 
Parent Doc ID: SOP AZDoc0018580 
 
Clinical Study Protocol  
 
Drug Substance 
PT007 
 
Study Code 
D6930C00001 (PT007001) 
 
Version 
2.0 
 
Date 
12 January 2018 
 
 
A Randomized, Double-blind, Single dose, Placebo-controlled, 5-Period, 5-
Treatment, Crossover, Multi-center, Dose-ranging Study to Compare PT007 
to Placebo MDI and Open-Label Proventil® HFA in Adult and Adolescent 
Subjects With Mild to Moderate Asthma 
 
Sponsor: AstraZeneca AB, 151 85 Södertälje, Sweden 


Clinical Study Protocol 
Drug Substance PT007  
Study Code D6930C00001 (PT007001) 
Version 2.0 
 
 
Date 12 January 2018 
2 (97) 
VERSION HISTORY 
 
Version 2.0, 12 January 2018 
Post-dose spirometry will be collected at 180 and 300 minutes, in addition to the timepoints 
currently outlined in the protocol. The 180 and 300 minute timepoints were inadvertently 
not included. Table 2 and the protocol have been updated accordingly. 
Table 1 was updated to add the superscript “d” to spirometry. This footnote applies to 
spirometry as well as reversibility testing. 
Section 4.1.1 and 4.1.2, Visit 1 activities: clarifies that spirometry assessments should be 
performed only if subjects held their morning doses of asthma medications and SABA for 
≥6 hours, per Table 1 and inclusion criteria 5. The previous text was confusing to sites. 
Section 4.2.2: moved “conducting pre-dose spirometry” from an after randomization 
activity to a before randomization activity. A pre-bronchodilator FEV1 ≥40% percent 
predicted normal value is a randomization criterion. 
Version 1.0, 27 October 2017 
Initial creation. 
 


Clinical Study Protocol 
Drug Substance PT007  
Study Code D6930C00001 (PT007001) 
Version 2.0 
 
 
Date 12 January 2018 
3 (97) 
This clinical study protocol has been subject to a peer review according to the Sponsor’s 
Standard procedures. The clinical study protocol is publicly registered and the results are 
disclosed and/or published according to the Sponsor’s Global Policy on Bioethics and in 
compliance with prevailing laws and regulations. 
 


Clinical Study Protocol
Drug Substance PT007
Study Code D6930C00001 (PT007001)
Version 2.0
Date 12 January 2018
4 (97)
CLINICAL STUDY PROTOCOL SYNOPSIS
A Randomized, Double-blind, Single dose, Placebo-controlled, 5-Period, 5-
Treatment, Crossover, Multi-center, Dose-ranging Study to Compare 
PT007 to Placebo MDI and Open-Label Proventil® HFA in Adult and 
Adolescent Subjects With Mild to Moderate Asthma
Coordinating Investigator
Study site(s) and number of subjects planned
This study will be conducted at approximately 10 sites in the United States. Across these sites, 
it is planned that approximately 70 subjects with mild to moderate asthma will be randomized.
Phase of development
II
Study design
This is a randomized, double-blind, single-dose, placebo-controlled, 5-period, 5-treatment, 
crossover, multi-center study to assess the bronchodilatory effect and safety of 2 dose levels of 
Albuterol Sulfate Pressurized Inhalation Suspension (hereafter referred to as AS MDI), 90 μg 
and 180 μg, compared with placebo for AS MDI (hereafter referred to as Placebo MDI) and 
open-label Proventil® hydrofluoroalkane (HFA; hereafter referred to as Proventil) 90 μg and 
180 μg in adult and adolescent subjects with mild to moderate asthma. This study design 
utilizes 10 treatment sequences.


Clinical Study Protocol 
Drug Substance PT007  
Study Code D6930C00001 (PT007001) 
Version 2.0 
Date 12 January 2018 
5 (97) 
Objectives 
Primary Objective 
Outcome Measures 
To confirm the dose of albuterol delivered 
from AS MDI that is comparable to Proventil 
Primary: Change from baseline in forced expiratory 
volume in 1 second (FEV1) area under the curve from 
0 to 6 hours (AUC0-6) 
Secondary efficacy endpoints: 
x 
Change from baseline in FEV1 AUC from 0 
to 4 hours (AUC0-4) 
x 
Peak change from baseline in FEV1 
Other efficacy endpoints: 
x 
Change from baseline in FEV1 at each post-
dose timepoint 
x 
Time to peak FEV1  
x 
Percentage of subjects achieving 12% 
improvement in FEV1 from baseline within 
30 minutes of dose  
x 
Percentage of subjects achieving 15% 
improvement in FEV1 from baseline within 
30 minutes of dose 
x 
Time to onset of response 
x 
Duration of response 
 
Secondary Objective 
Outcome Measures 
To assess the dose response of AS MDI versus 
Placebo MDI 
Primary: Change from baseline in FEV1 AUC0-6 
Secondary efficacy endpoints: 
x 
Change from baseline in FEV1 AUC0-4 
x 
Peak change from baseline in FEV1 
Other efficacy endpoints: 
x 
Change from baseline in FEV1 at each post-
dose timepoint 
x 
Time to peak FEV1  
x 
Percentage of subjects achieving 12% 
improvement in FEV1 from baseline within 
30 minutes of dose  
x 
Percentage of subjects achieving 15% 
improvement in FEV1 from baseline within 
30 minutes of dose 
x 
Time to onset of response 
x 
Duration of response 
 


Clinical Study Protocol 
Drug Substance PT007  
Study Code D6930C00001 (PT007001) 
Version 2.0 
Date 12 January 2018 
6 (97) 
Safety Objective 
Outcome Measures 
To evaluate the safety and tolerability of 
AS MDI relative to Placebo MDI and 
Proventil. 
Adverse events (AEs)/serious adverse events (SAEs) 
Vital signs 
Clinical laboratory parameters 
Electrocardiograms 
 
Target subject population 
Adult and adolescent subjects (≥12 to ≤65 years old) with stable mild to moderate asthma 
(pre-bronchodilator FEV1 of ≥40 to <90% predicted normal value), with demonstrated FEV1 
reversibility to Ventolin® HFA (hereafter referred to as Ventolin). 
Subjects must be on either a short-acting β-agonist (SABA) as needed as their only asthma 
therapy or a low to medium inhaled corticosteroid (ICS) dose (either alone or in combination 
with a long-acting β2-agonist [LABA]) for at least 30 days as a consistent regimen before 
screening. 
Duration of treatment 
This is a 5-period crossover study. Each Treatment Period is 1 day. Subjects will receive a 
single dose of randomized study drug at each of the 5 Treatment Visits (Visits 2, 3, 4, 5, and 
6), with a 3- to 7-day Washout Period between Treatment Visits. 
All subjects in this study will discontinue their current asthma medications at Visit 1 and 
initiate Sponsor-provided asthma medication to be used during the Screening Period and 
throughout the duration of the study. Subjects who were using only SABA as needed before 
Visit 1 will discontinue their SABA and initiate Sponsor-provided Ventolin, to be used as 
needed throughout the study, up until 6 hours before each study visit. For these subjects, the 
minimum Screening Period will be 3 days. Subjects who were receiving regularly scheduled 
ICS or ICS/LABA before Visit 1 will discontinue their ICS or ICS/LABA and initiate 
Pulmicort Flexhaler™ 180 μg or 360 μg twice a day, in addition to the Sponsor-provided 
Ventolin as described above. For these subjects, the minimum Run-in Period will be 14 days. 
For all subjects, the maximum Screening/Run-in Period will be 28 days. 
Each subject will participate for a minimum of 23 days and up to a maximum of 68 days, 
including the 3- to 28-day Screening Period described above and a telephone call 3 to 7 days 
after the final dose of study drug. 
Investigational product, dosage, and mode of administration 
Test product: AS MDI; 45 μg albuterol base (equal to 54 μg albuterol sulfate) or 90 μg 
albuterol base (equal to 108 μg albuterol sulfate) per actuation 
Active comparator: Proventil; 90 μg albuterol base (equal to 108 μg albuterol sulfate) per 
actuation 


Clinical Study Protocol 
Drug Substance PT007  
Study Code D6930C00001 (PT007001) 
Version 2.0 
Date 12 January 2018 
7 (97) 
Placebo: Placebo MDI manufactured in the image of AS MDI 
Each product is taken as follows during 1 of 5 Treatment Visits 
x AS MDI 90 μg (2 actuations of 45 μg/actuation) 
x AS MDI 180 μg (2 actuations of 90 μg/actuation) 
x Placebo MDI (2 actuations) 
x Proventil 90 μg (1 actuation of 90 μg/actuation) 
x Proventil 180 μg (2 actuations of 90 μg/actuation) 
Statistical methods 
All efficacy assessments will be compared with Placebo MDI and Proventil, and where 
appropriate, the AS MDI dose levels will be compared. Efficacy analyses will be performed 
for the Modified Intent-to-Treat analysis set (defined as subjects who received treatment and 
have post-treatment efficacy data from at least 2 Treatment Periods). As a sensitivity analysis, 
the Intent-to-Treat analysis set (defined as subjects who are randomized to treatment and 
receive at least 1 dose of the study treatment) will also be applied to the primary endpoint, 
change from baseline in FEV1 AUC0-6. 
The FEV1 AUC0-6 will be analyzed using a linear mixed model with a random subject effect. 
The fixed effects in the model will include treatment, treatment sequence, baseline FEV1, and 
period. 
Superiority comparisons of AS MDI relative to Placebo MDI and Proventil versus Placebo 
MDI will be conducted first using a dose-ordered approach. A 2-sided alpha level of 0.05 will 
be employed. Estimated treatment differences and 95% confidence intervals will be provided 
for the superiority comparisons. 
The secondary endpoints will be analyzed using a similar approach as that of the primary 
endpoint. 
Adverse events will be tabulated by treatment. No hypothesis tests will be performed. 
Sample size 
Power calculations were based on the properties of the primary endpoint, the change from 
baseline in FEV1 AUC0-6. Randomization of 70 subjects in order to achieve at least 
64 subjects completing the study will provide >95% overall probability to demonstrate 
superiority of each treatment relative to Placebo MDI assuming a minimum detectable 
difference (active – Placebo MDI) of 100 mL, within-subject standard deviation of 115 mL, 
and two-sided 5% level test. 


Clinical Study Protocol 
Drug Substance PT007  
Study Code D6930C00001 (PT007001) 
Version 2.0 
Date 12 January 2018 
8 (97) 
TABLE OF CONTENTS 
PAGE 
TITLE PAGE ........................................................................................................... 1 
VERSION HISTORY .............................................................................................. 2 
CLINICAL STUDY PROTOCOL SYNOPSIS ....................................................... 4 
TABLE OF CONTENTS ......................................................................................... 8 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS .......................... 13 
1. 
INTRODUCTION ................................................................................................. 15 
1.1 
Background and rationale for conducting this study ............................................. 15 
1.2 
Rationale for study design, doses and control groups ............................................ 15 
1.3 
Benefit/risk and ethical assessment........................................................................ 16 
1.4 
Study design ........................................................................................................... 17 
1.5 
Study governance and oversight ............................................................................ 20 
2. 
STUDY OBJECTIVES .......................................................................................... 20 
2.1 
Primary objective ................................................................................................... 20 
2.2 
Secondary objectives ............................................................................................. 21 
2.3 
Safety objectives .................................................................................................... 21 
2.4 
Exploratory objectives – not applicable ................................................................. 21 
3. 
SUBJECT SELECTION, ENROLLMENT, RANDOMIZATION, 
RESTRICTIONS, DISCONTINUATION AND WITHDRAWAL ...................... 21 
3.1 
Inclusion criteria .................................................................................................... 21 
3.2 
Exclusion criteria ................................................................................................... 23 
3.3 
Subject enrollment and randomization .................................................................. 25 
3.3.1 
Randomization criteria ........................................................................................... 25 
3.3.2 
Subject identification ............................................................................................. 25 
3.3.3 
Screen failures ........................................................................................................ 26 
3.4 
Procedures for handling incorrectly enrolled or randomized subjects ................... 26 
3.5 
Methods for assigning treatment groups ................................................................ 26 
3.6 
Methods for ensuring blinding ............................................................................... 27 
3.7 
Methods for unblinding .......................................................................................... 27 
3.8 
Restrictions ............................................................................................................ 28 
3.8.1 
Illicit drugs ............................................................................................................. 28 
3.8.2 
Dietary restrictions ................................................................................................. 28 


Clinical Study Protocol
Drug Substance PT007
Study Code D6930C00001 (PT007001)
Version 2.0
Date 12 January 2018
9 (97)
3.9 
Discontinuation of study drug................................................................................28 
3.10 
Discontinuation of the study ..................................................................................29 
4. 
STUDY PLAN AND TIMING OF PROCEDURES.............................................30 
4.1 
Screening period (Visit 1, and Visits 1a/1b if applicable) .....................................34 
4.1.1 
Visit 1.....................................................................................................................34 
4.1.2 
Visit 1a...................................................................................................................35 
4.1.3 
Visit 1b...................................................................................................................35 
4.2 
Treatment periods ..................................................................................................36 
4.2.1 
General guidance for Treatment Visits 2 through 6 (Treatment Periods 1 
through 5)...............................................................................................................36 
4.2.2 
Visit 2 (Randomization Visit, Treatment Period 1)...............................................37 
4.2.3 
Visits 3, 4, and 5 (Treatment Periods 2, 3, and 4)..................................................38 
4.2.4 
Visit 6 (Treatment Period 5) ..................................................................................39 
4.2.5 
Premature Study Withdrawal Visit ........................................................................40 
4.3 
Follow-up period....................................................................................................40 
4.3.1 
Follow-up telephone call........................................................................................40 
4.3.2 
Premature withdrawal from the study....................................................................41 
5. 
STUDY ASSESSMENTS .....................................................................................41 
5.1 
Efficacy assessments..............................................................................................41 
5.1.1 
Standardization of spirometry collections .............................................................41 
5.1.2 
Assessment of FEV1 ..............................................................................................42 
5.1.3 
Characterization of reversibility.............................................................................42 
 
 
5.2 
Safety assessments.................................................................................................43 
5.2.1 
Medical/surgical history and physical examination...............................................43 
5.2.2 
Vital signs ..............................................................................................................43 
5.2.3 
Clinical laboratory safety assessments...................................................................44 
5.2.4 
12-lead ECG...........................................................................................................45 
5.3 
Other assessments – not applicable........................................................................46 
5.4 
Pharmacokinetics – not applicable.........................................................................46 
5.5 
Pharmacodynamics – not applicable......................................................................46 
5.6 
Genetics – not applicable.......................................................................................46 
5.7 
Biomarker analysis - not applicable.......................................................................46 
6. 
SAFETY REPORTING AND MEDICAL MANAGEMENT ..............................46 
6.1 
Definition of AEs...................................................................................................46 
6.2 
Definitions of SAE.................................................................................................47 
6.3 
Recording of AEs...................................................................................................48 
6.3.1 
Performing AE assessments...................................................................................48 


Clinical Study Protocol 
Drug Substance PT007  
Study Code D6930C00001 (PT007001) 
Version 2.0 
Date 12 January 2018 
10 (97) 
6.3.2 
Pre-randomization AEs .......................................................................................... 48 
6.3.3 
AEs based on signs and symptoms ........................................................................ 48 
6.3.4 
AEs based on examinations and tests .................................................................... 48 
6.3.5 
Disease under study ............................................................................................... 49 
6.3.6 
Severity .................................................................................................................. 49 
6.3.7 
Relationship to study drug ..................................................................................... 50 
6.4 
Reporting of SAEs ................................................................................................. 50 
6.4.1 
Supplemental investigations of SAEs .................................................................... 50 
6.4.2 
Post-study follow-up of AEs .................................................................................. 51 
6.4.3 
Notification of post-treatment SAEs ...................................................................... 51 
6.4.4 
IRB notification of SAEs ....................................................................................... 51 
6.4.5 
Health Authority Safety Reports ............................................................................ 51 
6.5 
Overdose ................................................................................................................ 51 
6.6 
Pregnancy ............................................................................................................... 52 
6.6.1 
Maternal exposure .................................................................................................. 52 
6.6.2 
Paternal exposure ................................................................................................... 52 
6.7 
Medication Error .................................................................................................... 52 
6.8 
Management of study drug-related toxicities – not applicable .............................. 54 
7. 
INVESTIGATIONAL PRODUCT AND OTHER TREATMENTS .................... 54 
7.1 
Identity of investigational products........................................................................ 54 
7.2 
Dose and treatment regimens ................................................................................. 55 
7.2.1 
Randomized study drug ......................................................................................... 55 
7.2.2 
Sponsor-provided background asthma therapies ................................................... 56 
7.3 
Labeling ................................................................................................................. 57 
7.3.1 
Primary packaging and labeling ............................................................................. 57 
7.3.2 
Secondary packaging and labeling information (box) ........................................... 57 
7.4 
Storage ................................................................................................................... 58 
7.5 
Compliance ............................................................................................................ 58 
7.6 
Accountability ........................................................................................................ 58 
7.7 
Concomitant and other treatments ......................................................................... 59 
7.7.1 
Prior medications ................................................................................................... 59 
7.7.2 
Concomitant medications ....................................................................................... 60 
7.7.2.1 
Required concomitant medications ........................................................................ 60 
7.7.2.2 
Allowed allergy medications ................................................................................. 61 
7.7.3 
Prohibited medications ........................................................................................... 61 
7.7.3.1 
Prohibited asthma and allergy medications and washout periods.......................... 61 
7.7.3.2 
Prohibited non-asthma and non-respiratory medications ...................................... 62 
7.7.4 
Other concomitant treatment .................................................................................. 63 
8. 
STATISTICAL ANALYSES ................................................................................ 64 


Clinical Study Protocol 
Drug Substance PT007  
Study Code D6930C00001 (PT007001) 
Version 2.0 
Date 12 January 2018 
11 (97) 
8.1 
Statistical considerations ........................................................................................ 64 
8.2 
Sample size estimate .............................................................................................. 64 
8.3 
Definitions of analysis sets .................................................................................... 64 
8.4 
Outcome measures for analyses ............................................................................. 65 
8.5 
Methods for statistical analyses ............................................................................. 65 
8.5.1 
Primary efficacy analysis ....................................................................................... 65 
8.5.2 
Secondary efficacy analysis ................................................................................... 66 
8.5.3 
Other efficacy analysis ........................................................................................... 66 
8.5.4 
Type 1 error control ............................................................................................... 67 
8.5.5 
Data validation and transformation ........................................................................ 67 
8.5.6 
Safety analyses ....................................................................................................... 67 
8.5.6.1 
AEs ......................................................................................................................... 67 
8.5.6.2 
Vital signs .............................................................................................................. 68 
8.5.6.3 
Clinical laboratory measurements .......................................................................... 68 
8.5.6.4 
12-Lead ECGs ........................................................................................................ 68 
8.5.7 
Handling of missing data ....................................................................................... 68 
8.5.8 
Statistical software ................................................................................................. 68 
9. 
STUDY AND DATA MANAGMENT BY THE SPONSOR ............................... 68 
9.1 
Training of study site staff ..................................................................................... 68 
9.2 
Monitoring of the study ......................................................................................... 69 
9.2.1 
Source data ............................................................................................................. 69 
9.2.2 
Study agreements ................................................................................................... 69 
9.2.3 
Archiving of study documents ............................................................................... 69 
9.3 
Study timetable and end of study ........................................................................... 69 
9.4 
Data management ................................................................................................... 70 
10. 
ETHICAL AND REGULATORY REQUIREMENTS ......................................... 70 
10.1 
Ethical conduct of the study ................................................................................... 70 
10.2 
Subject data protection ........................................................................................... 70 
10.3 
Ethics and regulatory review.................................................................................. 70 
10.4 
Informed consent ................................................................................................... 71 
10.5 
Changes to the clinical study protocol and ICF/assent form ................................. 71 
10.6 
Audits and inspections ........................................................................................... 72 
11. 
LIST OF REFERENCES ....................................................................................... 73 
 


Clinical Study Protocol 
Drug Substance PT007  
Study Code D6930C00001 (PT007001) 
Version 2.0 
Date 12 January 2018 
12 (97) 
LIST OF TABLES 
Table 1 
Schedule of Events ................................................................................... 31 
Table 2 
Timed Assessments at Visits 2, 3, 4 and 5 ............................................... 33 
Table 3. 
Timed Assessments at Visit 6 ................................................................... 33 
Table 4. 
List of Laboratory Tests ........................................................................... 45 
Table 5. 
Randomized Study Drugs ......................................................................... 54 
Table 6. 
Other Sponsor-provided Study Medications ............................................ 55 
Table 7 
Dose of Sponsor-provided Pulmicort Flexhaler to be Assigned 
Based on Pre-study ICS or ICS/LABA Dose ........................................... 60 
Table 8  
Allowed Allergy Medications .................................................................. 61 
Table 9  
Prohibited Asthma and Allergy Medications That Must be 
Discontinued at Visit 1 and Required Washout Period Prior to 
Visit 1a ...................................................................................................... 62 
Table 10 
Prohibited Non-Asthma and Non-Respiratory Medications .................... 63 
Table A1-1. 
Recommended Minimal Scale Factors for Time, Volume and Flow 
on Graphical Output ................................................................................. 77 
Table A1-2. 
Summary of Equipment Quality Control ................................................. 78 
Table A1-3. 
Range and Accuracy Recommendations Specified for Forced 
Expiratory Maneuvers .............................................................................. 80 
 
LIST OF FIGURES 
Figure 1 
Study Design Flow Chart ......................................................................... 19 
 
LIST OF APPENDICES 
Appendix A 
Spirometry Assessment Criteria ............................................................... 74 
Appendix B 
Spirometry Performance Recommendations ............................................ 76 
Appendix C 
Additional Safety Information .................................................................. 82 
Appendix D 
Instructions for Use of Inhaled Medications ............................................ 84 
Appendix E 
Sponsor Signatory .................................................................................... 96 
Appendix F 
Investigator’s Agreement and Signature Page.......................................... 97 


Clinical Study Protocol 
Drug Substance PT007  
Study Code D6930C00001 (PT007001) 
Version 2.0 
Date 12 January 2018 
13 (97) 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
The following abbreviations and special terms are used in this study clinical study protocol. 
Abbreviation 
or special term 
Explanation 
AE 
Adverse event 
AS MDI 
Albuterol Sulfate Pressurized Inhalation Suspension 
ATS 
American Thoracic Society 
AUC 
Area under the curve 
AUC0-6 
Area under the curve from 0 to 6 hours 
AUC0-4 
Area under the curve from 0 to 4 hours 
β-hCG 
β-human chorionic gonadotropin 
BID 
Twice a day 
CFR 
Code of Federal Regulations 
CI 
Confidence interval 
DBP 
Diastolic blood pressure 
ECG 
Electrocardiogram 
eCRF 
Case Report Form (electronic/paper) 
ERS 
European Respiratory Society 
FEV1 
Forced expiratory volume in 1 second 
GCP 
Good Clinical Practice 
GMP 
Good Manufacturing Practice 
HFA 
Hydrofluoroalkane 
HR 
Heart rate 
ICF 
Informed consent form 
ICH 
International Conference for Harmonisation 
ICS 
Inhaled corticosteroid 
ID 
Identification 
IRB 
Institutional Review Board 
ITT 
Intent-to-Treat 
IWRS 
Interactive Web Response System 
LABA 
Long-acting β2-agonist 
MedDRA 
Medical Dictionary for Regulatory Activities 
MDI 
Metered dose inhaler 


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Study Code D6930C00001 (PT007001) 
Version 2.0 
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Abbreviation 
or special term 
Explanation 
mITT 
Modified Intent-to-Treat 
PIN 
Personal ID number 
PFT 
Pulmonary function testing 
QTcF 
Fridericia-corrected QT interval 
SABA 
Short-acting β-agonist 
SAE 
Serious adverse event  
SAP 
Statistical Analysis Plan 
SBP 
Systolic blood pressure 
 


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Study Code D6930C00001 (PT007001) 
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1. 
INTRODUCTION 
1.1 
Background and rationale for conducting this study 
Asthma is a heterogeneous disease that is characterized by chronic airway inflammation and 
bronchial hyperreactivity. It is defined by a history of respiratory symptoms such as wheeze, 
shortness of breath, chest tightness, and cough that vary over time and in intensity, together 
with variable expiratory airflow obstruction. Worsening asthma symptoms/airway obstruction 
can be mild to severe (Global Initiative for Asthma 2017). Albuterol sulfate is a short-acting 
β-agonist (SABA) that has been used world-wide in the management of asthma symptoms 
across all severities of asthma for over 40 years (Global Initiative for Asthma 2017). 
The test formulation to be evaluated in this study is a metered dose inhaler (MDI) containing 
albuterol sulfate (Albuterol Sulfate Pressurized Inhalation Suspension; hereafter referred to as 
AS MDI). This study is designed to support the selection of the albuterol dose by comparing 
the bronchodilatory effect and safety of 2 dose levels of AS MDI (90 μg and 180 μg) with 
placebo for AS MDI (hereafter referred to as Placebo MDI) and open-label Proventil® 
hydrofluoroalkane (HFA; hereafter referred to as Proventil; 90 μg and 180 μg) as the reference 
product in adult and adolescent subjects with mild to moderate asthma. 
The drug product in clinical development is an MDI formulated as a suspension with a 
micronized active pharmaceutical ingredient and Co-Suspension™ Delivery Technology, 
which consists of spray-dried porous particles comprised of the phospholipid, 1,2-distearoyl-
sn-glycero-3-phosphocholine and calcium chloride suspended in a HFA propellant. When 
used in MDI products, these particles form strong non-specific associations with the active 
pharmaceutical ingredient, providing reproducible drug delivery and long-term stability. 
All references to doses of AS MDI and Proventil refer to the albuterol base (ie, 90 μg 
albuterol base, which equals 108 μg albuterol sulfate). 
1.2 
Rationale for study design, doses and control groups 
The primary goal of this study is to confirm the bronchodilatory effect of 2 dose levels of 
AS MDI relative to Placebo MDI and the active control, Proventil, in subjects with mild to 
moderate asthma. The study is based on a 5-period Williams (Williams 1949) crossover 
design to allow the comparison of 2 doses of AS MDI against Placebo MDI and Proventil. 
The crossover design was selected to ensure acceptable power with a limited subject exposure 
through within-subject treatment comparisons. 
The dose levels of AS MDI to be tested (90 μg and 180 μg) were selected based on over 
40 years of clinical experience with inhaled albuterol in asthma patients, and are likely to be 
efficacious doses with acceptable safety profiles. It is anticipated that the dose of albuterol 
delivered with AS MDI will be close to the approved dose in Proventil. The doses will allow 
evaluation of the bronchodilation effect of AS MDI relative to Placebo MDI and Proventil 
administered at 90 μg and 180 μg. The recommended dose of Proventil for the treatment or 
prevention of bronchospasm in adults and children aged 4 years and older is 2 actuations of 


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90 μg every 4 to 6 hours; for some patients, 1 actuation may be sufficient (PROVENTIL HFA 
package insert). 
In this double-blind, placebo-controlled study, AS MDI and Placebo MDI will be blinded to 
all subjects, study site staff, endpoint assessors, and Sponsor personnel. Proventil is open-
label. However, to reduce bias, dosing will be performed under the supervision of study staff, 
and spirometry assessments will be performed by different study personnel who will only 
enter the room after dosing is completed; thus, the study personnel conducting the spirometry 
assessments will be blinded to the identity of the study drug. 
Subjects enrolled in this study are selected to represent the intended patient population for an 
albuterol product to be used as needed for symptoms, ie, adults and adolescents 12 years of 
age or older currently treated and well controlled with appropriate background standard of 
care for their asthma severity. 
All subjects will use only Sponsor-provided medication for rescue as needed during the study. 
At Visit 1 (Screening), subjects will discontinue their SABA and initiate Sponsor-provided 
Ventolin, to be used as needed up until 6 hours before each study visit. 
Subjects who were previously on a low to medium dose of an inhaled corticosteroid (ICS) 
with or without a long-acting β2-agonist (LABA) before study entry will be required to 
discontinue their previous therapy and initiate Sponsor-supplied Pulmicort Flexhaler™ for at 
least 14 days to standardize therapy and to confirm asthma is adequately treated prior to 
randomization; these subjects will also use Sponsor-provided Ventolin as needed for 
symptoms as described above. 
Each dose of AS MDI will be compared with Placebo MDI and Proventil on the primary 
efficacy endpoint, change from baseline in forced expiratory volume in 1 second (FEV1) area 
under the curve (AUC) from 0 to 6 hours (AUC0-6), a commonly accepted endpoint for the 
assessment of bronchodilation. The duration of 6 hours was selected to capture the expected 
duration of the effect of albuterol. 
1.3 
Benefit/risk and ethical assessment 
This study has been designed to support the dose selection for a new formulation of albuterol 
in subjects with mild to moderate asthma. The product being tested in this study, AS MDI, is 
being compared with an approved inhaled albuterol product to confirm a pharmacologically 
appropriate dose. The subjects in this study will not gain any therapeutic benefit from the 
study as it is comprised of only 5 single-dose treatments. 
All subjects in this study will be switched at Visit 1 from their current asthma medication to 
Sponsor-provided asthma medication to be used during the Screening Period and throughout 
the duration of the study, as described in Section 1.2. Subjects requiring medications other 
than those specified in Section 1.2 to control or treat their asthma symptoms before Visit 1 
will be excluded from participation in this study. In addition, to be eligible for randomization, 
subjects must not have used more than 8 actuations per day (ie, 4 doses of 2 actuations per 


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Study Code D6930C00001 (PT007001) 
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Date 12 January 2018 
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day) of Sponsor-provided Ventolin for rescue on more than any 3 days during the previous 7 
days before randomization. 
Based on the well-established safety profile of inhaled albuterol, no new or specific risks 
beyond what is described in the PROVENTIL HFA package insert are anticipated with the 
doses and the dose regimens being used in this study. Investigators will ensure adequate 
medical care of the study participants at all times throughout the course of the study, including 
up to the follow-up telephone call 3 to 7 days after the last dose of study drug. 
1.4 
Study design 
This is a randomized, double-blind, single-dose, placebo-controlled, 5-period, 5-treatment, 
crossover, multi-center study to assess the bronchodilatory effect and safety of 2 dose levels of 
AS MDI (90 μg and 180 μg) compared with Placebo MDI and open-label Proventil (90 μg and 
180 μg) in adult and adolescent subjects with mild to moderate asthma (Figure 1). 
This study will be conducted at approximately 10 sites in the US, contributing approximately 
7 subjects per site. Across these sites, it is planned that approximately 70 subjects with mild to 
moderate asthma will be randomized to provide approximately 64 subjects to complete the 
study. Each subject will participate for a minimum of 23 days and up to a maximum of 
68 days, including a 3- to 28-day Screening Period and a telephone call 3 to 7 days after the 
final dose of study drug. The study is anticipated to run for approximately 4 months, including 
the recruitment period. 
This study consists of a Screening Period, which includes a Run-in Period for those subjects 
who will be switched from ICS and ICS/LABA to Sponsor-provided Pulmicort Flexhaler, a 
Treatment Phase, which includes 5 randomized Treatment Periods, and a follow-up telephone 
call. Each Treatment Period will be 1 day, with a Washout Period of 3 to 7 days between 
Treatment Periods. 
The Screening Period begins at Visit 1. At Visit 1, subjects will sign an informed consent 
form (ICF). If the subject is a minor, the parent or guardian will sign an ICF and the subject 
will sign an assent form. Inclusion/exclusion criteria will be assessed. To be eligible, subjects 
must be on either a SABA as needed as their only asthma therapy or a low to medium ICS 
dose (either alone or in combination with a LABA) for at least 30 days as a consistent regimen 
before screening. Subjects must have a pre-bronchodilator FEV1 between ≥40 and <90% 
predicted normal value. 
All subjects must demonstrate FEV1 reversibility to Ventolin (defined as improvement in 
FEV1 of ≥15% post Ventolin dosing) during the Screening Period; historical reversibility is 
not acceptable. For subjects who did not administer their morning asthma maintenance 
medications, as applicable, and/or SABA, reversibility will be measured at Visit 1. For 
subjects who received their morning asthma maintenance medications, as applicable, and/or 
SABA, reversibility will be measured at Visit 1a, which will occur within 10 days of Visit 1 
and after these medications have been held for the appropriate time period (Table 9). Subjects 
who do not meet reversibility criteria at Visit 1 or Visit 1a may be retested at a subsequent 


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Study Code D6930C00001 (PT007001) 
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Screening Visit (1a or 1b). Only 2 reversibility testing attempts are allowed. Subjects not 
meeting reversibility criteria after 2 attempts must be screen failed. 
Subjects meeting eligibility criteria at Visit 1 will continue in the Screening Period. All 
subjects in this study will discontinue their current asthma medications at Visit 1 and initiate 
Sponsor-provided asthma medication to be used during the Screening Period and throughout 
the duration of the study, as described in Section 1.2. For subjects who were using only SABA 
as needed before study entry, the minimum Screening Period will be 3 days. For subjects who 
were receiving regularly scheduled ICS or ICS/LABA before study entry, the minimum Run-
in Period (on Pulmicort Flexhaler) will be 14 days. For all subjects, the maximum 
Screening/Run-in Period will be 28 days. 
Randomization will take place at Visit 2. At Visit 2, before randomization, subjects must 
demonstrate a pre-bronchodilator FEV1 ≥40% predicted normal value (average of 2 pre-
bronchodilator assessments). Subjects who do not meet this randomization criterion will be 
screen failed. Randomization will be centralized through the use of an Interactive Web 
Response System (IWRS). Eligible subjects will be randomized to 1 of 10 pre-defined 
treatment sequences. Each sequence will contain AS MDI 90 μg, AS MDI 180 μg, Placebo 
MDI, Proventil 90 μg, and Proventil 180 μg, in a randomized order. Randomization is planned 
to be stratified by pre-study background asthma maintenance therapy, with approximately 
50% of subjects on an ICS and approximately 50% of subjects who are not on an ICS 
(receiving only a SABA as needed). 
Subjects will receive single doses of randomized study drug at each of the 5 Treatment Visits 
(Visits 2, 3, 4, 5, and 6), with a 3- to 7-day Washout Period between Treatment Visits. At each 
Treatment Visit, bronchodilation activity of the study drug will be assessed through 
pulmonary function testing (PFT). Subjects will be required to remain at the clinic until 
completion of all protocol-defined assessments up to and including the 6-hour post-dose 
timepoint (Table 1). Safety will be assessed by evaluation of adverse events (AEs), clinical 
laboratory tests, vital signs, and electrocardiograms (ECGs). 
Subjects who prematurely discontinue study drug for any reason before completing all study 
visits will undergo a Premature Discontinuation Visit. After the last Treatment Period or 
following a Premature Discontinuation Visit, subjects will be scheduled for a follow-up 
telephone call to occur 3 to 7 days from the date of the last study drug dose. 
The end of study is defined as the last subject’s follow-up telephone call. 
 


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Study Code D6930C00001 (PT007001) 
Version 2.0 
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Figure 1 
Study Design Flow Chart 
 
*Subjects on ICS or ICS/LABA prior to Visit 1 will be run-in on Pulmicort Flexhaler 180 or 360 μg BID for a minimum of 
14 days. 
Abbreviations: BID = twice a day; V=visit; R=randomization; Rx=treatment. 


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Study Code D6930C00001 (PT007001) 
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1.5 
Study governance and oversight 
No study governance or oversight committees will be used in this study. 
2. 
STUDY OBJECTIVES 
2.1 
Primary objective 
Primary Objective 
Outcome Measures 
To confirm the dose of albuterol delivered 
from AS MDI that is comparable to Proventil 
Primary: Change from baseline in FEV1 AUC0-6 
Secondary efficacy endpoints: 
x 
Change from baseline in FEV1 AUC from 0 
to 4 hours (AUC0-4) 
x 
Peak change from baseline in FEV1 
Other efficacy endpoints: 
x 
Change from baseline in FEV1 at each post-
dose timepoint 
x 
Time to peak FEV1  
x 
Percentage of subjects achieving 12% 
improvement in FEV1 from baseline within 
30 minutes of dose  
x 
Percentage of subjects achieving 15% 
improvement in FEV1 from baseline within 
30 minutes of dose 
x 
Time to onset of response 
x 
Duration of response 


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Study Code D6930C00001 (PT007001) 
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2.2 
Secondary objectives 
Secondary Objective 
Outcome Measures 
To assess the dose response of AS MDI versus 
Placebo MDI 
Primary: Change from baseline in FEV1 AUC0-6 
Secondary efficacy endpoints: 
x 
Change from baseline in FEV1 AUC0-4 
x 
Peak change from baseline in FEV1 
Other efficacy endpoints: 
x 
Change from baseline in FEV1 at each post-
dose timepoint 
x 
Time to peak FEV1 
x 
Percentage of subjects achieving 12% 
improvement in FEV1 from baseline within 
30 minutes of dose 
x 
Percentage of subjects achieving 15% 
improvement in FEV1 from baseline within 
30 minutes of dose 
x 
Time to onset of response 
x 
Duration of response 
2.3 
Safety objectives 
Safety Objective 
Outcome Measures 
To evaluate the safety and tolerability of 
AS MDI relative to Placebo MDI and Proventil 
AEs/serious adverse events (SAEs) 
Vital signs 
Clinical laboratory parameters 
ECGs 
 
2.4 
Exploratory objectives – not applicable 
3. 
SUBJECT SELECTION, ENROLLMENT, RANDOMIZATION, 
RESTRICTIONS, DISCONTINUATION AND WITHDRAWAL 
Each subject must meet all of the inclusion criteria and none of the exclusion criteria for this 
study. Under no circumstances will there be exceptions to this rule. 
3.1 
Inclusion criteria 
Each subject must meet the following criteria in relationship to Visit 1, unless otherwise 
noted, to be enrolled in this study: 
1. 
Give their signed written informed consent to participate (and assent, as applicable) 


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2. 
Are at least 12 years of age and no older than 65 years 
3. 
Have stable (for 6 months) physician-diagnosed asthma with historical 
documentation of the diagnosis 
4. 
Must be receiving 1 of the following required inhaled asthma therapies listed below 
for at least the last 30 days: 
x Only SABA, which is used as needed for rescue 
x Low to medium doses of ICS (alone or in combination with LABA), used 
regularly as maintenance asthma therapy, with the ICS doses allowed in 
Table 7, with a stable regimen 
5. 
Pre-bronchodilator FEV1 of ≥40 to <90% predicted normal value after withholding 
SABA for ≥6 hours (and/or Visit 1a and/or Visit 1b, if applicable) 
6. 
Confirmed FEV1 reversibility to Ventolin, defined as a post-Ventolin increase in 
FEV1 of ≥15% at either Visit 1, Visit 1a, or Visit 1b; only 2 reversibility testing 
attempts are allowed 
7. 
Demonstrate acceptable spirometry performance (ie, meet American Thoracic 
Society [ATS]/European Respiratory Society [ERS] acceptability/repeatability 
criteria; Appendix A) 
8. 
Willing and, in the opinion of the Investigator, able to adjust current asthma 
therapy, as required by the protocol 
9. 
Demonstrate acceptable MDI administration technique 
Note: Use of a spacer device during the Screening and randomized Treatment 
Periods is not permitted. 
10. 
Body mass index <40 kg/m2 
11. 
If a female of childbearing potential, have a negative serum pregnancy test 
12. 
Women of childbearing potential must agree to 1 of the following to prevent 
pregnancy: 
Note: Women are considered to be of non-childbearing potential if they are 
physiologically incapable of becoming pregnant, including any female who is 2 
years post-menopausal, or surgically sterile, defined as having a bilateral 
oophorectomy, hysterectomy, or tubal ligation. For purposes of this protocol, 
menopausal women are defined as women ≥50 years old who are amenorrheic for 
12 consecutive months or more following cessation of all exogenous hormonal 
treatment. 
x Practice abstinence 


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x If a female of childbearing potential and sexually active, agrees to prevent 
pregnancy by using 1 of the following methods of birth control from the 
date the ICF is signed until 2 weeks after the final dose of study drug is 
taken: 
o Hormonal contraception (eg, oral contraceptive, contraceptive 
implant, or injectable hormonal contraceptive) 
o Double-barrier birth control (eg, condom plus intrauterine device, 
diaphragm plus spermicide, condom plus spermicide) 
o Maintenance of a monogamous sexual relationship with a male 
partner who has been surgically sterilized by vasectomy 
13. 
Male subjects who are sexually active must be surgically sterile or agree to use a 
double-barrier method of contraception (condom with spermicide) from the first 
dose of randomized study drug until 2 weeks after their last dose, and must not 
donate sperm during their study participation period 
14. 
Compliance: must be willing to remain at the study site as required per protocol to 
complete all visit assessments 
3.2 
Exclusion criteria 
Subjects who meet any of the following criteria in relationship to Visit 1, unless otherwise 
stated, will be excluded from the study. 
1. 
Chronic obstructive pulmonary disease or other significant lung disease (eg, chronic 
bronchitis, emphysema, bronchiectasis with the need of treatment, cystic fibrosis, or 
bronchopulmonary dysplasia) 
2. 
Oral corticosteroid use (any dose) within 6 weeks 
3. 
Received any marketed (eg, omalizumab, mepolizumab, reslizumab) or 
investigational biologic within 3 months or 5 half-lives, whichever is longer, or any 
other medication specifically prohibited by the protocol within the indicated 
exclusionary time periods (Table 9 and Table 10) 
4. 
Received tiotropium within 2 weeks 
5. 
Current smokers, former smokers with >10 pack-years history, or former smokers 
who stopped smoking <6 months (including all forms of tobacco, e-cigarettes 
[vaping], and marijuana) 
6. 
Life-threatening asthma as defined as any history of significant asthma episode(s) 
requiring intubation associated with hypercapnia, respiratory arrest, hypoxic 
seizures, or asthma-related syncopal episode(s) 


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7. 
Completed treatment for lower respiratory infection or asthma exacerbation within 
6 weeks 
8. 
Upper respiratory infection not resolved within 7 days 
9. 
Hospitalizations for asthma within 6 months 
10. 
Clinically significant laboratory abnormalities or ECG abnormalities, in the opinion 
of the Investigator 
Note: If laboratory tests have to be repeated, the results should be available for 
review before Visit 2 (Randomization). 
11. 
Historical or current evidence of a clinically significant disease including, but not 
limited to: cardiovascular (eg, congestive heart failure, known aortic aneurysm, 
clinically significant cardiac arrhythmia, coronary heart disease), hepatic, renal, 
hematological, neuropsychological, endocrine (eg, uncontrolled diabetes mellitus, 
uncontrolled thyroid disorder, Addison’s disease, Cushing’s syndrome), or 
gastrointestinal (eg, poorly controlled peptic ulcer, gastroesophageal reflux disease). 
Significant is defined as any disease that, in the opinion of the Investigator, would 
put the safety of the subject at risk through study participation, or that could affect 
the efficacy or safety analysis if the disease/condition exacerbated during the study. 
12. 
Cancer not in complete remission for at least 5 years 
Note: Subjects with squamous cell carcinoma of the skin, basal cell carcinoma of 
the skin, in situ carcinoma of the cervix, or localized prostate cancer are eligible, if 
in the opinion of the Investigator, the condition has been adequately worked up and 
clinically controlled and the subject’s participation in the study would not represent 
a safety concern. 
13. 
Hospitalized for psychiatric disorder or attempted suicide within 1 year 
14. 
History of psychiatric disease, intellectual deficiency, poor motivation, or other 
conditions limiting informed consent validity 
15. 
Significant, in the opinion of the Investigator, abuse of alcohol or drugs 
16. 
Hypersensitivity to β2-agonists or any component of the investigational MDI or any 
component of Proventil or Ventolin (or Pulmicort Flexhaler, if applicable) 
17. 
Unable to abstain from protocol-defined prohibited medications during the study 
18. 
Using any herbal products by inhalation or nebulizer within 2 weeks and does not 
agree to stop during the study duration 
19. 
Received a live attenuated vaccination within 7 days 
20. 
Currently pregnant or nursing 


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21. 
Study investigators, sub-investigators, coordinators, and their employees or 
immediate family members, or employees of the Sponsor 
22. 
Treatment with investigational study drug (or device) in another clinical study 
within the last 30 days or 5 half-lives, whichever is longer 
23. 
Randomized in any PT007 study 
3.3 
Subject enrollment and randomization 
3.3.1 
Randomization criteria 
Each subject must meet the following criteria on the morning of Visit 2 to be randomized: 
1. 
Subjects of childbearing potential must have a negative urine pregnancy test 
2. 
Received no asthma medication other than Sponsor-provided Pulmicort Flexhaler 
180 μg or 360 μg BID as assigned and/or Sponsor-provided Ventolin from Visit 1 
to Visit 2, except for allowable allergy medications defined in Table 8 
3. 
The last dose of Pulmicort Flexhaler (if applicable) was the previous night (ie, 
morning dose of Pulmicort Flexhaler was not administered), and the last dose of 
Sponsor-provided Ventolin was no later than 6 hours before the study visit (if 
Ventolin is needed in the morning, the visit must be rescheduled) 
4. 
Pre-bronchodilator FEV1 ≥40% percent predicted normal value 
5. 
Has not used >8 actuations per day (ie, 4 doses of 2 actuations per day) of Sponsor-
provided Ventolin for rescue on more than any 3 days during the previous 7 days 
6. 
No upper respiratory infection, lower respiratory infection, or asthma exacerbation 
during the Screening Period 
7. 
Demonstrate acceptable MDI administration technique 
8. 
Able to comply with all study procedures 
For procedures for withdrawal of incorrectly randomized subjects see Section 3.4. 
3.3.2 
Subject identification 
All subjects who undergo screening will be assigned a unique screening identification number 
(ID) at Visit 1. Only subjects continuing to meet all inclusion criteria and none of the 
exclusion criteria at Visit 2 and who meet randomization criteria at Visit 2 will be assigned a 
unique subject randomization number. 


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3.3.3 
Screen failures 
Screening failures are subjects who do not fulfil the eligibility criteria for the study and 
therefore must not be randomized. 
3.4 
Procedures for handling incorrectly enrolled or randomized 
subjects 
Subjects who fail to meet the eligibility criteria should not, under any circumstances, be 
enrolled into the Screening Period or receive study drug. There can be no exceptions to this 
rule. Subjects who are enrolled into the Screening Period but subsequently found not to meet 
all the eligibility criteria must not be randomized or initiated on study drug. 
If a subject does not meet all the eligibility criteria and is randomized in error or is incorrectly 
started on study drug, the Investigator should inform the Sponsor immediately, and the 
Sponsor and the Investigator should discuss whether to continue or discontinue the subject 
from study drug and withdraw the subject from the study. The Sponsor must ensure all 
decisions are appropriately documented. 
3.5 
Methods for assigning treatment groups 
The randomization scheme will be generated by the Sponsor or designee using computer 
software incorporating a random number generator. Subjects will be randomly assigned to 1 
of 10 treatment sequences based on a Williams design (Williams 1949) using an IWRS. Each 
sequence will comprise all 5 of the treatments included in this study in a randomized order. 
All sequences will contain AS MDI 90 μg, AS MDI 180 μg, Placebo MDI, Proventil 90 μg, 
and Proventil 180 μg. 
The 10 treatment sequences are shown below. 


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Sequence 
Period 1 
Period 2 
Period 3 
Period 4 
Period 5 
1 
A 
B 
E 
C 
D 
2 
B 
C 
A 
D 
E 
3 
C 
D 
B 
E 
A 
4 
D 
E 
C 
A 
B 
5 
E 
A 
D 
B 
C 
6 
D 
C 
E 
B 
A 
7 
E 
D 
A 
C 
B 
8 
A 
E 
B 
D 
C 
9 
B 
A 
C 
E 
D 
10 
C 
B 
D 
A 
E 
Note: A=Placebo; B=AS MDI 90 μg; C=AS MDI 180 μg; D= Proventil 90 μg; E= Proventil 180 μg. 
 
Randomization will be centralized and stratified by pre-study background therapy consisting 
of either ICS or non-ICS (subjects not previously treated with ICS). 
3.6 
Methods for ensuring blinding 
AS MDI and Placebo MDI will be blinded to all subjects, study site staff, endpoint assessors, 
and Sponsor personnel. Placebo MDI is designed to mimic the appearance, smell, and taste of 
AS MDI. No double-dummy will be used. Packaging and labeling of AS MDI and Placebo 
MDI will be designed to ensure blinding. 
Randomized Proventil is open-label. However, to reduce bias, dosing will be performed under 
the supervision of study staff, and spirometry assessments will be performed by different 
study personnel who will only enter the room after dosing is completed; thus, the study 
personnel conducting the spirometry assessments will be blinded to the identity of the study 
drug. 
3.7 
Methods for unblinding 
Individual treatment codes, indicating the treatment randomization for each randomized 
subject, will be available to the Investigator(s) or pharmacists from the IWRS. Routines for 
this will be described in the IWRS user manual that will be provided to each study site. 
The IWRS should be used in order to unblind subjects and to unmask drug identity. The 
Sponsor will not provide a disclosure envelope with the clinical supplies. The Investigator or 
treating Physician may unblind a subject’s treatment assignment only in the case of an 
emergency, when knowledge of the study drug treatment is essential for the appropriate 


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clinical management or welfare of the subject. Whenever possible, the Investigator must first 
discuss options with the Sponsor Medical Monitor or appropriate study personnel before 
unblinding the subject’s treatment assignment. If this is impractical, the Investigator must 
notify the Sponsor as soon as possible, but without revealing the treatment assignment of the 
unblinded subject, unless that information is important for the safety of subjects currently in 
the study. The date and reason for the unblinding must be recorded in the appropriate data 
collection tool. 
The Sponsor retains the right to break the code for SAEs that are unexpected and are 
suspected to be causally related to a study drug and that potentially require expedited 
reporting to regulatory authorities. Treatment codes will not be broken for the planned 
analyses of data until all decisions on the evaluability of the data from each individual subject 
have been made and documented. 
3.8 
Restrictions 
Prohibited concomitant medications are described in Section 7.7.3. 
3.8.1 
Illicit drugs 
Illicit drugs or drugs of abuse will not be allowed from Visit 1 to the end of the follow-up 
telephone call or to whenever the subject discontinues from the study drug and withdraws 
from the study. If any illicit drugs or drugs of abuse are used by the subject during the study, 
the dates of use and the amount will be documented and the subject will be discontinued from 
study drug and withdrawn from the study at the discretion of the Investigator. Medical 
marijuana (edibles and tinctures only; inhaled marijuana is excluded) is not an exclusionary 
drug if used for medical purposes and the dose or frequency of consumption does not change 
during the Screening Period or throughout the study. 
3.8.2 
Dietary restrictions 
Subjects must not ingest xanthine and/or xanthine analogue (caffeine)-containing foods or 
beverages or caffeine-containing medications for at least 6 hours before each study visit and 
throughout the duration of each study visit. Examples of such products include coffee, tea, 
chocolate, and cola. Decaffeinated beverages are acceptable. 
3.9 
Discontinuation of study drug 
All subjects who discontinue study drug will be withdrawn from the study. 
Subjects may be withdrawn from the study at their own request at any time for any reason. 
Subjects experiencing any of the changes of concern listed below should be discontinued from 
randomized study drug and withdrawn from the study. 
x 
Asthma worsening requiring change in asthma treatment, other than 
Sponsor-provided Pulmicort Flexhaler, if assigned, and as needed Sponsor-
provided Ventolin 


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Note: Subjects experiencing an asthma exacerbation during the study will 
be evaluated by the Investigator and treated with medications for asthma 
deemed medically necessary and will be discontinued from study drug and 
withdrawn from the study.
x
x
Requirement for any of the prohibited medications listed in Section 7.7.3
x
Any safety reason as judged by the Investigator and/or Sponsor
x
Pregnancy
x
The subject’s treatment code is prematurely broken by the Investigator.
Subjects who discontinue study drug and withdraw from the study should be encouraged to 
complete the Premature Discontinuation Visit (see Section 4.2.5).
Withdrawal of the informed consent
Subjects are free to withdraw from the study at any time without prejudice to further 
treatment.
A subject who withdraws consent will always be asked about the reason(s) and the presence of 
any AE. The Investigator will follow up AEs outside of the clinical study.
If a subject withdraws from participation in the study, then his/her enrollment and/or 
randomization code(s) cannot be reused. Withdrawn subjects will not be replaced.
3.10
Discontinuation of the study
The study may be stopped if, in the judgment of the Sponsor, study subjects are placed at 
undue risk because of clinically significant findings that:
x
meet individual stopping criteria or are otherwise considered significant
x
are assessed as causally related to study drug
x
are not considered to be consistent with continuation of the study
The Sponsor reserves the right to terminate the study at any time for clinical or administrative 
reasons. Such a termination must be implemented by the Investigator, if instructed to do so by 
the Sponsor, in a time frame that is compatible with the subjects’ well-being.
Regardless of the reason for termination, all data available for the subject at the time of 
discontinuation must be recorded in the electronic case report form (eCRF). All reasons for 
discontinuation of study drug must be documented.


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In terminating the study, the Sponsor will ensure that adequate consideration is given to the 
protection of the subjects’ interests. 
4. 
STUDY PLAN AND TIMING OF PROCEDURES 
Note: Before conducting any study-related procedures, subjects are required to provide their 
written informed consent using the Institutional Review Board (IRB)-approved ICF, and 
assent as appropriate. If the subject is a minor, the parent or guardian will sign an ICF and the 
subject will sign an assent form. The ICF and assent form should be signed during Visit 1. 
A time and events schedule is provided in Table 1. Detailed schedules are provided for timed 
assessments at Visits 1 through 5 (Table 2) and Visit 6 (Table 3). 
When data collection timepoints are concurrent, variables will be collected in the following 
order: vital signs, ECG, clinical laboratory assessments, and spirometry. 
 


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Table 1
Schedule of Events
Procedures
Screeninga
Treatment Phaseb
Follow-up
For details 
see Section
Visit 1
Visit 
1a/b
Visit 2
Rand.
(TP 1)
Day 1
Visit 3
(TP 2)
Visit 4
(TP 3)
Visit 5
(TP 4)
Visit 6
(TP 5)
PDV (if 
applicable)c
TC
3 to 7 days 
after final 
dose
Day -28 to Day -1
Informed consent (and 
assent, as appropriate)
X
Section 10.4
Eligibility criteria
X
Section 3
Verify randomization 
criteria
X
Section 3.3.1
Verified continued 
eligibility
X
X
X
X
X
Section 3
MDI 
demonstration/training
X
X
X
X
X
X
Section 4.1
Ventolin reversibility testd
X
X
Section 5.1.3
Medical/surgical history
X
Section 5.2.1
Demographics
X
Section 4.1
Concomitant medicationse
X
X
X
X
X
X
X
X
Section 7.7
Spirometryd
X
X
X
X
X
X
X
Section 5.1.2
Physical examinationf
X
X
X
Section 5.2.1
Vital signs
X
X
X
X
X
X
X
Section 5.2.2
12-lead ECG
X
X
X
Section 5.2.4
Pregnancy testg
X
X
Section 5.2.3


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Table 1 
Schedule of Events 
Procedures 
Screeninga 
Treatment Phaseb 
Follow-up 
For details 
see Section 
Visit 1 
Visit 
1a/b 
Visit 2 
Rand. 
(TP 1) 
Day 1 
Visit 3 
(TP 2) 
Visit 4 
(TP 3) 
Visit 5 
(TP 4) 
Visit 6 
(TP 5) 
PDV (if 
applicable)c 
TC 
3 to 7 days 
after final 
dose 
Day -28 to Day -1 
Clinical laboratory testing 
X 
 
 
 
 
 
X 
X 
 
Section 5.2.3 
Adjust asthma medications 
per protocolh 
X 
X 
 
 
 
 
X 
X 
 
Section 7.2.2 
Randomization  
 
 
X 
 
 
 
 
 
 
Section 3.5 
Randomized study drug 
administered 
 
 
X 
X 
X 
X 
X 
 
 
Section 7.2.1 
AEs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Section 6.3 
Telephone contact 
 
 
 
 
 
 
 
 
X 
Section 4.3.1 
Abbreviations: AE=adverse event; β-hCG= β-human chorionic gonadotropin; ECG=electrocardiogram; FEV1=forced expiratory volume in 1 second; ICS=inhaled 
corticosteroid; LABA= long-acting β2-agonist; MDI=metered dose inhaler; PDV=Premature Discontinuation Visit; Rand.=randomization; SABA= short-acting 
β-agonist; TC=telephone call; TP=Treatment Period. 
Note: When data collection timepoints are concurrent, variables will be collected in the following order: vital signs, ECG, clinical laboratory assessments, and spirometry. 
a 
Screening Period will be 3 to 28 days for subjects on SABA only before study entry, and 14 to 28 days for subjects on ICS or ICS/LABA before study entry.  
b 
Subjects to return to clinic within 3 to 7 days following Visits 2, 3, 4, and 5. 
c 
Subjects who prematurely withdraw from the study will undergo a Premature Discontinuation Visit (see Section 4.2.5). 
d 
For subjects who received their regularly inhaled asthma medications and/or SABA on the morning of the visit, spirometry and reversibility will be measured at Visit 1a, 
which will occur within 10 days of Visit 1. For subjects who do not meet reversibility criteria at Visit 1a, Visit 1b will be scheduled for a second reversibility test, to 
occur within 7 days. Subjects who do not meet reversibility criteria after the second attempt will be screen failed. 
e 
At all visits beyond Visit 1, note time of the last dose of asthma medications. The visit must be rescheduled if the last dose of Ventolin was <6 hours before the visit. 
f 
Includes evaluation of height and weight at Visit 1. 
g 
A serum pregnancy test (β-hCG) will be performed at Visit 1; urine β-hCG test will be performed before randomization at Visit 2 (for women of child-bearing potential 
only). 
h 
At Visit 1, prohibited asthma medications are to be stopped and asthma medications changed as specified in Section 7.2.2. At the end of Visit 6 (or upon premature 
discontinuation or screen failure, if applicable), subjects will return to pre-study or other appropriate maintenance asthma medications. 


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Table 2 
Timed Assessments at Visits 2, 3, 4 and 5 
 
Pre-Dose 
(minutes) 
Post-Dose (minutes) 
Before 
leaving 
clinic 
For details see 
Section 
-60  
-30  
5  
15  
30  
45  
60  
120  
180 
240  
300 
360 
Vital signs 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
Section 5.2.2 
Spirometry 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Section 5.1.2 
AEs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Section 6.3 
Abbreviations: AE=adverse event. 
 
 
Table 3. 
Timed Assessments at Visit 6 
 
Pre-Dose 
(minutes) 
Post-Dose (minutes) 
Before 
leaving 
clinic 
For details see 
Section 
-60  
-30  
5  
15  
30  
45  
60  
120  
180 
240  
300 
360 
Vital signs 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
Section 5.2.2 
12-lead ECG 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Section 5.2.4 
Spirometry 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Section 5.1.2 
Physical 
examination 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Section 5.2.1 
Clinical 
laboratory 
testing 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Section 5.2.3 
AEs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Section 6.3 
Abbreviations: AE=adverse event; ECG=electrocardiogram. 
 


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4.1 
Screening period (Visit 1, and Visits 1a/1b if applicable) 
For subjects who were receiving only SABA as needed before study entry, the minimum and 
maximum Screening Period will be 3 and 28 days, respectively. For subjects who were 
receiving regularly scheduled ICS or ICS/LABA before study entry, the minimum and 
maximum Run-in Period will be 14 and 28 days, respectively. The Screening Period should be 
as short as possible; however, the duration will be determined by the Investigator. 
4.1.1 
Visit 1 
The following activities will be performed at Visit 1: 
x 
Obtain informed consent 
x 
Register subject in IWRS to obtain subject screening number 
x 
Obtain demographic data, including age, race, smoking history, 
medical/surgical history, and age of onset of asthma 
x 
Obtain medication history, including prior and concomitant medications (see 
Section 7.7) 
x 
Obtain vital signs (see Section 5.2.2) 
x 
Conduct a complete physical examination (see Section 5.2.1) 
x 
Confirm acceptable MDI device technique and provide training as necessary 
x 
Confirm the subject satisfies inclusion/exclusion criteria (see Section 3.1 
and Section 3.2) 
x 
Obtain a 12-lead ECG (see Section 5.2.4) 
x 
Obtain clinical laboratory blood samples, including blood sample for serum 
β-hCG for all women of child-bearing potential (see Section 5.2.3) 
x 
Discontinue the subject’s baseline asthma medications and change to 
protocol-specified asthma medications as follows for both the Screening and 
randomized Treatment Periods (see Section 7.7.2.1): 
o For subjects receiving only SABA as needed: switch to Sponsor-
provided Ventolin as needed for symptoms 
o For subjects receiving regularly scheduled ICS or ICS/LABA: switch 
to Sponsor-provided Pulmicort Flexhaler (either 180 μg or 360 μg 
BID, based on the subject’s previous therapy; see Table 7). These 


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subjects will also receive Sponsor-provided Ventolin as needed for 
symptoms.
x
Record AEs (if any)
Note: AEs must be recorded during the Screening Period, that is, from the 
time of signing the ICF (and assent form, as appropriate) to the start of 
randomized study drug. Adverse events that occur during the Screening 
Period will be recorded as medical history and not as study AEs unless they 
meet the definition of an SAE (see definition in Section 6.2).
For subjects who have not taken their regular morning doses of asthma maintenance 
medications and/or SABA within the previous 6 hours, the following activity will also be 
performed at Visit 1:
x
Conduct spirometry assessments (FEV1) (see Section 
x
Perform Ventolin reversibility test (described in Section 5.1.3).
Note: For subjects who complete this reversibility test at Visit 1 and do not meet Ventolin
reversibility criteria, Visit 1a will be scheduled for a second reversibility test.
For subjects who have taken their regular morning doses of inhaled asthma maintenance 
medications and/or SABA within the previous 6 hours before Visit 1 or any of the medications 
listed in Table 9 within the washout periods listed in Table 9, Visit 1a will be scheduled to 
allow for washout of asthma medications before spirometry and reversibility testing.
4.1.2
Visit 1a
The following activities will be performed at Visit 1a for subjects who did not complete 
spirometry at Visit 1 or do not have a reversibility test at Visit 1 or who fail to meet 
reversibility criteria at Visit 1. Visit 1a will be scheduled to occur within 10 days of Visit 1.
x
Review clinical laboratory results from Visit 1
x
Review concomitant medications (see Section 7.7)
x
Confirm the subject satisfies inclusion/exclusion criteria (see Section 3.1
and Section 3.2)
x
Perform Ventolin reversibility test (described in Section 5.1.3)
x
Record AEs (if any)
4.1.3
Visit 1b
Visit 1b may only be scheduled for subjects who did not perform Ventolin reversibility testing 
at Visit 1 and who did not meet Ventolin reversibility criteria at Visit 1a.


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For subjects who do not meet reversibility criteria at Visit 1a, Visit 1b will be scheduled to 
occur within 7 days of Visit 1a for a second reversibility test. Only 2 reversibility attempts 
will be allowed. Subjects who do not meet reversibility criteria after the second attempt will 
be screen failed.
The following activities will be performed at Visit 1b for subjects who do not meet 
reversibility criteria at Visit 1a:
x
Review concomitant medications (see Section 7.7)
x
Confirm the subject satisfies inclusion/exclusion criteria (see Section 3.1
and Section 3.2)
x
Perform Ventolin reversibility test (described in Section 5.1.3)
x
Record AEs (if any)
4.2
Treatment periods
4.2.1
General guidance for Treatment Visits 2 through 6 (Treatment Periods 1 
through 5)
x
At the start of each Treatment Visit, before any study procedures are
performed, site personnel must confirm the subject has withheld all asthma 
medications. The last Pulmicort Flexhaler dose should be no later than the 
previous night. The last dose of Ventolin should be no later than 6 hours 
before the visit. Confirm the last time of dosing.
Note: Subjects who did not withhold their Ventolin as described above 
before the start of study procedures must have their visit rescheduled as 
soon as is practical, but within the specified visit window (±2 days).
 
x
At Visit 2, the first dose of study drug will be administered before 10 am. At 
all subsequent Treatment Visits, the first dose of study drug will be 
administered before 10 am and within 1 hour of the time administered at 
Visit 2.
x
Sites should call the subject on the day before a scheduled visit to remind 
the subject of the following:

Pulmicort Flexhaler and Ventolin should be held for the time periods described 
above

Bring their Sponsor-provided Ventolin and Pulmicort Flexhaler, if assigned, 
with them to the clinic


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 
Refrain from ingesting xanthine-containing foods and beverages and 
caffeine-containing medications for at least 6 hours before each study visit and 
for the duration of each study visit (see Section 3.8.2) 
x 
Study drug should be dispensed as follows: 
 
At 15 to 30 minutes before dosing, the seal around the study day treatment box 
should be opened and the instructions for administration of study drug on the 
inner flap of the study day treatment box should be followed 
 
Refer to Section 7.2.1 for detailed instructions for preparation of treatments for 
administration. These instructions are to be adhered to and are relevant to all 
study treatment visits 
 
Subject will administer the dose of assigned study drug at the clinic 
x 
For doses consisting of 2 inhalations, the in-clinic dosing time will be 
recorded as the time of administration of the second actuation of study drug 
x 
Site personnel will instruct subjects not to take any non-study asthma 
medications without site personnel permission during a visit, until all study 
procedures have been completed and the subject is discharged. Site 
personnel should take every precaution to prevent use of non-study asthma 
medications during the test day. Site personnel may request the subject to 
surrender all non-study asthma medications at the start of the visit before 
performing any study procedures and return them to the subject at the end of 
the visit when all study procedures are completed. 
x 
If a subject is experiencing severe symptoms and requires Ventolin for relief 
of asthma symptoms at any time during a study visit, site personnel must 
note the time and justification for use in the subject’s chart and all 
spirometry assessments should be stopped during the current Treatment 
Visit. Safety assessments should be continued at the discretion of the 
Investigator. 
4.2.2 
Visit 2 (Randomization Visit, Treatment Period 1) 
The following activities should be performed before randomization: 
x 
Perform a urine pregnancy test 
x 
Confirm randomization criteria (see Section 3.3.1), including pre-dose 
spirometry assessments (see Section 5.1.2) 
x 
Review concomitant medications 
x 
Review clinical laboratory results from Visit 1 


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x 
Record AEs (if any) 
Note: Pre-randomization AEs are to be recorded as part of the medical 
history unless the event meets the definition of an SAE (see definition in 
Section 6.2). 
x 
Confirm acceptable MDI device technique 
x 
Register subject in IWRS to obtain subject randomization number. The 
subject is to be considered randomized after receiving a randomization 
number from the IWRS. 
The following activities are to be performed after randomization: 
x 
Perform all pre-dose vital signs assessments (see Section 5.2.2) 
x 
Dispense study drug (see Section 4.2.1) based on subject treatment 
assignment information from IWRS  
x 
Perform post-dose spirometry assessments (see Section 5.1.2) 
The following will be performed after the final (6-hour post-dose) spirometry test: 
x 
Record AEs (if any) 
x 
Schedule Visit 3, allowing for a Washout Period of 3 to 7 days 
x 
Assure that the subject has enough Sponsor-provided asthma medication to 
last until the next Treatment Visit (rescue Ventolin for all subjects, 
Pulmicort Flexhaler 180 μg or 360 μg for those subjects who were on ICS or 
ICS/LABA before study entry) 
x 
Perform post-dose vital signs assessments (see Section 5.2.2) before the 
subject leaves the clinic 
4.2.3 
Visits 3, 4, and 5 (Treatment Periods 2, 3, and 4) 
The following should be performed before any other activities: 
x 
Confirm eligibility criteria (see Section 3.1 and Section 3.2) 
x 
Review concomitant medications 
x 
Confirm acceptable MDI device technique 
Then the following activities are to be performed: 


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x
Perform pre-dose vital signs assessments (see Section 5.2.2)
x
Perform pre-dose spirometry assessments (see Section 5.1.2), 
 
x
Dispense study drug (see Section 4.2.1) based on subject treatment 
assignment information from IWRS
x
Perform post-dose spirometry assessments (see Section 5.1.2)
The following will be performed after the final (6-hour post-dose) spirometry test:
x
Record AEs (if any)
x
Schedule the next Treatment Visit, allowing for a Washout Period of 3 to
7 days.
x
Assure that the subject has enough Sponsor-provided asthma medication to 
last until the next Treatment Visit (rescue Ventolin for all subjects, 
Pulmicort Flexhaler 180 μg or 360 μg for those subjects who were on ICS or 
ICS/LABA before study entry)
x
Perform post-dose vital signs assessments (see Section 5.2.2) before the 
subject leaves the clinic
4.2.4
Visit 6 (Treatment Period 5)
x
Confirm eligibility criteria (see Section 3.1 and Section 3.2)
x
Review concomitant medications
x
Confirm acceptable MDI device technique
x
Perform pre-dose vital signs assessments (see Section 5.2.2)
x
Perform pre-dose spirometry assessments (see Section 
)
x
Dispense study drug (see Section 4.2.1) based on subject treatment 
assignment information from IWRS
x
Perform post-dose spirometry assessments (see Section 5.1.2)
The following will be performed after the final (6-hour post-dose) spirometry test:
x
Conduct a complete physical examination (see Section 5.2.1)


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x 
Obtain a 12-lead ECG (see Section 5.2.4) 
x 
Obtain clinical laboratory blood samples (see Section 5.2.3) 
x 
Record AEs (if any) 
x 
Collect all unused Sponsor-provided asthma medication (Sponsor-provided 
Ventolin and Pulmicort Flexhaler, if applicable) 
x 
Schedule the follow-up telephone call (see Section 4.3.1) 
x 
Perform post-dose vital signs assessments (see Section 5.2.2) before the 
subject leaves the clinic 
x 
Return subjects to their pre-study asthma maintenance medication regimen 
or other appropriate asthma medications 
4.2.5 
Premature Study Withdrawal Visit 
See Section 4.3.2. The following activities should occur at the Premature Discontinuation 
Visit: 
x 
Review concomitant medications 
x 
Perform vital signs assessments (see Section 5.2.2) 
x 
Conduct a complete physical examination (see Section 5.2.1) 
x 
Obtain clinical laboratory blood samples (see Section 5.2.3) 
x 
Obtain a 12-lead ECG (see Section 5.2.4) 
x 
Record AEs (if any) 
x 
Collect all unused Sponsor-provided asthma medication (Sponsor-provided 
Ventolin and Pulmicort Flexhaler, if applicable) 
x 
Return subjects to their pre-study asthma maintenance medication regimen 
or other appropriate asthma medications  
x 
Schedule the follow-up telephone call (see Section 4.3.1) 
4.3 
Follow-up period 
4.3.1 
Follow-up telephone call 
Subjects will be contacted by study personnel through a telephone call 3 to 7 days after the 
last dose of study drug to assess AEs and SAEs, if any. 


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Study Code D6930C00001 (PT007001)
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4.3.2
Premature withdrawal from the study
Complete the end of treatment form of the eCRF and record the reason for premature study 
withdrawal. The following categories should be used to describe these events in the eCRF:
x
Subject discretion (document reason)
x
Investigator considers it to be in the best interest of the subject
x
AEs
x
Administrative reasons (eg, early termination of the study)
x
Subject lost to follow-up
x
Major protocol deviation
x
Death
x
Protocol-specified criteria such as use of prohibited medications (refer to 
Section 7.7.3).
5.
STUDY ASSESSMENTS
The iDatafax system will be used for data collection and query handling. The Investigator will 
ensure that data are recorded on the eCRFs as specified in the clinical study protocol and in 
accordance with the instructions provided.
The Investigator ensures the accuracy, completeness, and timeliness of the data recorded and 
of the provision of answers to data queries according to the clinical study agreement. The 
Investigator will sign the completed eCRFs. A copy of the completed eCRFs will be archived 
at the study site.
5.1
Efficacy assessments
Efficacy will be assessed by PFTs. Forced expiratory spirometry for derivation of FEV1 as 
defined in ATS/ERS guidelines will be performed in accordance with ATS criteria 
(Appendix A) using a spirometer that meets or exceeds minimum performance 
recommendations of the ATS (Appendix B).
5.1.1
Standardization of spirometry collections
To standardize spirometry, all sites will be provided with identical spirometry systems
 with customized, study-specific 
software. Every effort will be made to provide all sites with standardized spirometry 
equipment. The volume accuracy of the spirometer is to be checked daily with appropriate 
documentation in a calibration log prior to the conduct of PFTs on each test day.


Clinical Study Protocol
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Study Code D6930C00001 (PT007001)
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The volume accuracy of the spirometer is checked using a 3 L syringe across 3 flow ranges 
(ie, low, medium, and high flows), with temperature and barometric pressure correction. The 
calibration syringe must meet ATS specifications and not be used beyond the expiry date. 
Required accuracy is ±3% (ie, 3.09 L to 2.91 L; ATS/ERS). The results will be printed and 
maintained in a calibration log, which will be monitored for compliance during the monitoring 
visits (Appendix B).
All study staff responsible for performing PFTs will receive standardized training at an
Investigator meeting. All technicians are required to demonstrate proficiency in the use of the 
equipment and the ability to perform technically acceptable PFTs (ATS criteria) prior to 
performing PFTs on study subjects (Miller et al 2005). After each test is performed, the 
spirometry software will provide immediate feedback to the technician indicating whether the 
effort meets ATS acceptability and repeatability standards (Appendix B). All PFT testing will 
be stored electronically. After completion of testing, the study staff will electronically transmit 
the spirometric measurements for centralized quality assurance review 
 
. Feedback on the quality of the measurements will be provided to the 
investigational site and to the Sponsor or designee for central data management.
5.1.2
Assessment of FEV1
Spirometry will be conducted at all visits except the Premature Discontinuation Visit (when 
applicable).
Spirometry at Visits 1, 1a and/or 1b, and 2 will be used to satisfy enrollment and 
randomization criteria. Multiple forced expiratory efforts (at least 3 but no more than 8) will 
be performed and the 2 best efforts that meet the ATS/ERS acceptability and reproducibility 
criteria will be recorded. The best efforts will be based on the highest FEV1. The average of 
these 2 assessments will be used to calculate the screening FEV1.
At all Treatment Visits (Visits 2, 3, 4, 5, and 6), spirometry will 
be conducted 60 minutes and 30 minutes before study drug administration. The average of 
these 2 assessments will be used to calculate morning pre-dose FEV1.
Following study drug administration at each visit, spirometry will be obtained at 5, 15, 30, 45, 
60, 120, 180, 240, 300, and 360 minutes post-dose. Three tests will be performed at each
timepoint. The highest value at each timepoint will be used for these post-dose assessments.
5.1.3
Characterization of reversibility
Reversibility to Ventolin will be evaluated at Visit 1, 1a, and/or 1b. Subjects must demonstrate 
reversibility to Ventolin to be randomized in the study; no more than 2 reversibility test 
attempts are allowed. Reversibility testing is performed as follows:
1.
Determine if morning doses of all maintenance asthma ICS/LABA, if applicable,
were withheld and that short-acting bronchodilators were not administered within 
6 hours of testing


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2.
Perform pre-bronchodilator PFTs at 30 minutes before administration of Ventolin
3.
Administer 2 actuations of Ventolin (90 μg per actuation; total 180 μg)
4.
Perform post-bronchodilator PFTs 30 minutes after the administration of Ventolin.
Reversibility will be a comparison of the best FEV1 effort obtained at 30 minutes pre-
bronchodilator to the best FEV1 effort obtained at 30 minutes post-bronchodilator following 
administration of Ventolin. A subject is considered reversible to Ventolin if the improvement 
in FEV1 at 30 minutes post-Ventolin is ≥15%.
5.2
Safety assessments
Safety will be assessed by vital signs, ECGs, and clinical laboratory tests, in addition to
recording AEs.
5.2.1
Medical/surgical history and physical examination
Medical and surgical history will be collected at Visit 1. A complete physical examination will 
be performed at Visits 1 and 6 or the Premature Discontinuation Visit, as applicable.
A complete physical examination will include the following: general appearance, skin, head, 
eyes, ears, nose, throat, neck (including thyroid), lymph nodes, chest, heart, abdomen, 
extremities, and nervous system. Additionally, weight, assessed in ordinary indoor clothing 
with shoes off, and height will be recorded at Visit 1 only (Table 1).
5.2.2
Vital signs
At all study visits (Visits 1 to 6 and the Premature Discontinuation Visit, if applicable), heart 
rate (HR), systolic blood pressure (SBP), and diastolic blood pressure (DBP) will be assessed.
At all Treatment Visits, vital signs will be assessed pre-dose and post-dose before the subject 


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leaves the clinic. Heart rate, SBP and DBP will be assessed after the subject is supine or 
seated for 5 minutes. If, in the opinion of the Investigator, a clinically significant vital sign 
change occurs, then the measurement should be repeated at medically appropriate intervals 
until the value returns to within an acceptable range. If the value does not return to baseline, 
the Investigator should determine if this is an AE (see Section 6.1). 
5.2.3 
Clinical laboratory safety assessments 
Blood will be collected for clinical laboratory testing at Visit 1, Visit 6 (post-dose), and during 
the Premature Discontinuation Visit, if applicable. 
Subjects will be in a seated or supine position during blood collection. Clinical laboratory tests 
for this study are listed in Table 4. 
Approximately 10 mL of blood will be collected per subject during the study. The exact blood 
volume collected may vary depending on laboratory procedures. However, it will not exceed 
15 mL per subject during the study. 
Clinical safety laboratory tests will be analyzed by a central laboratory according to 
standardized, validated assays. The laboratory will supply detailed procedures for the 
preparation and collection of blood samples along with all containers needed for their 
collection. Blood sample volumes will meet the laboratory’s specification. Sites must evaluate 
clinical laboratory data before the subject is randomized. 


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Table 4. 
List of Laboratory Tests 
Hematology 
Hemoglobin  
Platelet count 
Hematocrit  
Mean corpuscular hemoglobin 
White blood cell count with differential  
Mean corpuscular hemoglobin concentration 
Red blood cell count  
Mean corpuscular volume 
Clinical chemistry 
Liver enzyme and other liver function tests Other clinical chemistry 
Alanine aminotransferase 
Albumin 
Aspartate aminotransferase 
Blood urea nitrogen 
Alkaline phosphatase  
Calcium 
Bilirubin, total  
Chloride 
Gamma-glutamyl transferase  
Cholesterol  
 
Bicarbonate 
 
Creatinine 
 
Glucose 
 
Magnesium  
 
Potassium 
 
Phosphate 
 
Protein, total  
 
Sodium 
 
Triglycerides  
 
Urea  
Other tests: 
β-hCG test for pregnancya 
Creatinine clearance will be estimated at Screening only. The CKD-EPI formula will be used for 
subjects >18 years old, and the Schwartz equation will be used for subjects ≤18 years old 
(Schwartz et al 1976). 
Abbreviations: CKD-EPI=Chronic Kidney Disease Epidemiology Collaboration. 
a 
Serum β-hCG will be assessed in all women of childbearing potential at Visit 1. Urine β-hCG test will be 
performed at Visit 2 before randomization. 
 
5.2.4 
12-lead ECG 
A single 12-lead ECG will be obtained at Visit 1, post-study drug dosing at Visit 6, and during 
the Premature Discontinuation Visit, if applicable.   


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To standardize ECG collection, all sites will be provided with identical ECG equipment 
with customized study-specific software on a laptop. All study staff responsible for 
performing ECG collection will receive identical, detailed training at the Investigator meeting 
as well as site-phone training sessions. Each site is required to demonstrate proficiency in the 
use of the equipment and the ability to perform technically acceptable ECGs before 
performing testing on study subjects. After each test is performed, the site will electronically 
transfer the ECG data for centralized quality assurance review 
Feedback on the quality of the ECGs will be provided to the investigational site via a site 
qualification form. Sites must evaluate a subject’s ECG data before the subject is randomized.
The ECG parameters to be assessed include HR, PR interval, QRS axis, QRS interval, and 
QT/Fridericia-corrected QT (QTcF) interval. The QT intervals and calculated QTcF intervals
will be reviewed and checked for gross inaccuracies by the Investigator or designated ECG 
reviewer.
5.3
Other assessments – not applicable
5.4
Pharmacokinetics – not applicable
5.5
Pharmacodynamics – not applicable
5.6
Genetics – not applicable
5.7
Biomarker analysis - not applicable
6.
SAFETY REPORTING AND MEDICAL MANAGEMENT
The Principal Investigator is responsible for ensuring that all staff involved in the study are 
familiar with the content of this section.
6.1
Definition of AEs
The following definitions of terms are guided by the International Conference for
Harmonisation (ICH) and the US Code of Federal Regulations (CFR) (21 CFR 312.32) and 
are included herein.
An AE is any untoward medical occurrence associated with the use of a drug in humans, 
whether or not considered drug related. An AE (also referred to as an adverse experience) can 
be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom, or 
disease temporally associated with the use of a drug, without any judgment about causality. 
An AE can arise from any use of the drug (eg, off label use, use in combination with another 
drug) and from any route of administration, formulation, or dose, including an overdose.
Adverse events include, but are not limited to:


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x 
any symptom or condition not previously reported by the subject (medical 
history) 
x 
an exacerbation of a pre-existing symptom or condition 
x 
a significant increase in frequency or intensity of a pre-existing episodic 
event or condition 
x 
a drug interaction 
x 
a condition first detected or diagnosed after study drug administration even 
though it may have been present prior to the start of the study 
An AE does not include: 
x 
medical or surgical procedures (eg, surgery, endoscopy, tooth extraction, 
blood transfusion); the condition that led to the procedure is an AE (eg, 
bleeding esophageal varices, dental caries) 
x 
overdose of either study drug or concurrent medication without any clinical 
signs or symptoms 
x 
non-clinically significant abnormal laboratory values (if accompanied by 
signs/symptoms, the signs or symptoms are considered an AE) 
6.2 
Definitions of SAE 
An AE is considered “serious” if, in the view of the Investigator or Sponsor, it results in any 
of the following outcomes: 
x 
death 
x 
a life-threatening AE 
x 
inpatient hospitalization or prolongation of existing hospitalization  
x 
a persistent or significant incapacity or substantial disruption of the ability to 
conduct normal life functions 
x 
a congenital anomaly/birth defect 
Important medical events that may not result in death, be life threatening, or require 
hospitalization may be considered an SAE when, based upon appropriate medical judgment, 
they may jeopardize the subject 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 


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dyscrasias or convulsions that do not result in inpatient hospitalization, or the development of 
drug dependency or drug abuse. 
Hospitalization for a pre-existing condition, including an elective procedure, which has not 
worsened, does not constitute an SAE. 
An AE is considered “life-threatening” if, in the view of the Investigator or Sponsor, its 
occurrence places the patient or subject at immediate risk of death. It does not include an 
adverse reaction or suspected adverse reaction that, had it occurred in a more severe form, 
might have caused death. 
For further guidance on the definition of a SAE, see Appendix C. 
6.3 
Recording of AEs 
6.3.1 
Performing AE assessments 
The Investigator is responsible for promptly documenting and reporting all AEs observed 
during the study in the subject’s eCRF and on the AE Reporting Form. If the AE is 
unexpected, the Investigator should report the AE immediately to the Sponsor. In addition, 
certain AEs (as described in Section 6.2) are classified as ‘serious’ and must be reported no 
later than 24 hours after the Investigator recognizes/classifies the event as an SAE to the 
Sponsor or its designee. 
In the case of SAEs, after discussing the details of the event, the Investigator and the Medical 
Monitor may discontinue the subject from randomized study drug. 
6.3.2 
Pre-randomization AEs 
Adverse events occurring from the time the subject signs informed consent until the subject is 
randomized will be summarized as medical history and not as an AE unless the event meets 
the definition of an SAE as defined in Section 6.2. 
6.3.3 
AEs based on signs and symptoms 
When collecting AEs, the recording of diagnoses is preferred (when possible) to recording a 
list of signs and symptoms. However, if a diagnosis is known and there are other signs or 
symptoms that are not generally part of the diagnosis, the diagnosis and each sign or symptom 
will be recorded separately. 
6.3.4 
AEs based on examinations and tests 
Many laboratory abnormalities observed during the course of a study will be included under a 
reported AE describing a clinical syndrome (eg, elevated blood urea nitrogen and creatinine in 
the setting of an AE of renal failure, or decreased hemoglobin in a case of bleeding esophageal 
varices). Isolated laboratory abnormalities should be reported as AEs if they are considered to 
be clinically significant by the Investigator. 


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If deterioration in a laboratory value/vital sign is associated with clinical signs and symptoms, 
the sign or symptom will be reported as an AE and the associated laboratory result/vital sign 
will be considered as additional information. Wherever possible the reporting Investigator 
uses the clinical, rather than the laboratory term (eg, anemia versus low hemoglobin value). In 
the absence of clinical signs or symptoms, clinically relevant deteriorations in non-mandated 
parameters should be reported as AE(s).
Criteria for a “clinically significant” laboratory abnormality are:
x
a laboratory abnormality that leads to study drug dose suspension or 
discontinuation
x
a laboratory abnormality that results in any therapeutic intervention (ie, 
concomitant medication or therapy)
x
Any other laboratory abnormality judged by the Investigator to be of any 
particular clinical concern (eg, significant fall in hemoglobin not requiring 
transfusion)
For laboratory abnormalities that do not meet the above criteria but are outside of the normal 
reference range, the Investigator should indicate whether the value is clinically significant or 
not clinically significant for the subject.
Any new or aggravated clinically relevant abnormal medical finding at a physical examination 
as compared with the baseline assessment will be reported as an AE.
Paradoxical bronchospasm will be monitored 
.
6.3.5
Disease under study 
Symptoms of the disease under study are those which might be expected to occur as a direct 
result of the subject’s asthmatic condition (eg, wheeze, breathlessness, cough). Events that are 
unequivocally due to the disease under study should not be reported as an AE during the study 
unless they meet SAE criteria or lead to discontinuation of study drug.
6.3.6
Severity
The Investigator must categorize the severity of each AE according to the following 
guidelines:
Mild: Associated with no limitation of usual activities or only slight discomfort; generally not 
requiring alteration or cessation of study drug administration; and/or not needing therapeutic 
intervention.
Moderate: Associated with limitation of usual activities or significant discomfort; generally 
requiring alteration or cessation of study drug administration; and/or requiring therapeutic 
intervention.


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Severe: Associated with inability of subject to carry out usual activities or very marked 
discomfort; considered to be life-threatening; resulting in significant disability or incapacity; 
and requiring therapeutic intervention. 
6.3.7 
Relationship to study drug 
The Investigator will assess causal relationship between the study drug and each AE, and 
answer ‘yes’ or ‘no’ to the question ‘Do you consider that there is a reasonable possibility that 
the event may have been caused by the study drug?’ 
For SAEs causal relationship will also be assessed for other medication and study procedures. 
Note that for SAEs that could be associated with any study procedure the causal relationship is 
implied as ‘yes’. 
A guide to the interpretation of the causality question is found in Appendix C. 
6.4 
Reporting of SAEs 
In agreeing to the provisions of this protocol, the Investigator accepts all legal responsibilities 
for AE identification, documentation, grading, assignment of causality, and prompt 
notification of SAEs to the Sponsor or designee. All SAEs must be reported to the Sponsor or 
designee no later than 24 hours after the Investigator recognizes/classifies the event as an 
SAE. All SAEs should be documented and reported using the eCRF. At a minimum, a 
description of the event and the Investigator’s judgment of causality must be provided at the 
time of the initial report using the appropriate form (eg, SAE Report Form). After the initial 
report, as necessary, the Investigator must provide any additional information on an SAE to 
the Sponsor or designee within 2 working days after receiving the information. Follow up 
information will be a detailed written report that may include copies of hospital records, case 
reports, autopsy reports, and other pertinent documents. 
For subjects discontinuing study drug, all AEs/SAEs will be collected through the follow-up 
telephone call. 
Post-treatment SAEs following the last dose of study drug must be reported to the Sponsor as 
described in Section 6.4.3. 
The Investigator is responsible for continuing to report any new or relevant follow-up 
information that s/he learns about the SAE. 
6.4.1 
Supplemental investigations of SAEs 
The Investigator and supporting personnel responsible for subject care should discuss with the 
Sponsor Medical Monitor or designee any need for supplemental investigations of SAEs. If 
additional assessments are conducted, results must be reported to the Sponsor. If a subject dies 
during study participation and if a post mortem examination is performed, a copy of the 
autopsy report should be submitted to the Sponsor. 


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6.4.2 
Post-study follow-up of AEs 
Any AEs that are unresolved at the subject’s last AE assessment in the study are to be 
followed up by the Investigator for as long as medically indicated, but without further 
recording in the eCRF. The Sponsor retains the right to request additional information for any 
subject with ongoing AE(s)/SAE(s) at the end of the study, if judged necessary. 
6.4.3 
Notification of post-treatment SAEs 
Investigators are not obligated to actively follow subjects after completion of the study. 
However, if the Investigator becomes aware of a post-treatment SAE occurring within 3 to 
7 days following the last dose of study drug, the SAE must be reported to the Sponsor, 
whether or not the event is attributable to study drug. All SAEs must be reported to the 
Sponsor no later than 24 hours after the Investigator recognizes/classifies the event as an SAE. 
6.4.4 
IRB notification of SAEs 
The Investigator is responsible for promptly notifying her/his IRB of all SAEs, including any 
follow-up information, occurring at their site and any SAE regulatory report, including any 
follow-up reports, received from the Sponsor. Documentation of IRB submission must be 
retained for each safety report. The Investigator is also responsible for notifying the Sponsor if 
their IRB requires revisions to the ICF or other measures based on its review of an SAE 
Report. 
6.4.5 
Health Authority Safety Reports 
The Sponsor or its representatives will submit a safety report to the appropriate regulatory 
agencies for any suspected adverse reaction that is both serious and unexpected within the 
timeframe specified by each regulatory agency. 
The Sponsor or its representatives will send copies of each submitted safety report to 
Investigators actively participating in the Sponsor’s clinical studies. Safety reports must also 
be submitted to the appropriate IRBs as soon as possible. Documentation of submission to the 
IRB must be retained for each safety report. 
6.5 
Overdose 
An overdose is defined as any dose greater than the highest dose investigated in this study that 
results in clinical signs and symptoms. In the event of a study drug overdose, the Investigator 
should use their best clinical judgment in treating the overdose, and the Sponsor’s Medical 
Monitor should also be contacted. Investigators should refer to the relevant document(s) for 
detailed information regarding warnings, precautions, contraindications, AEs, and other 
significant data pertaining to the study drug(s) being administered. Such document(s) may 
include but are not limited to the Investigator’s Brochure for AS MDI and approved product 
labeling for open-label products. 


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6.6 
Pregnancy 
Any pregnancy that occurs from Visit 1 until study completion must be reported to the 
Sponsor. The pregnancy must be followed up to determine the outcome (including premature 
termination) and status of mother and child. 
6.6.1 
Maternal exposure 
If a subject becomes pregnant during the course of the study, the study drug should be 
discontinued immediately. 
Pregnancy itself is not regarded as an AE unless there is a suspicion that the investigational 
product under study may have interfered with the effectiveness of a contraceptive medication. 
Congenital abnormalities/birth defects and spontaneous miscarriages should be reported and 
handled as SAEs. Elective abortions without complications should not be handled as AEs. The 
outcome of all pregnancies (spontaneous miscarriage, elective termination, ectopic pregnancy, 
normal birth or congenital abnormality) should be followed up and documented even if the 
subject was withdrawn from the study. 
If any pregnancy occurs in the course of the study, then the Investigator or other site personnel 
should inform the appropriate Sponsor representatives immediately but no later than 24 
hours of when he or she becomes aware of it. 
Pregnancy should be recorded on a paper Pregnancy Report Form and reported by the 
Investigator to the Sponsor or designee. Pregnancy follow-up should be recorded on the same 
Pregnancy Report Form and should include possible relationship to the study drug in response 
to the pregnancy outcome. Any SAE experienced during pregnancy must be reported on the 
SAE Report Form. 
The same timelines apply when outcome information is available. 
6.6.2 
Paternal exposure  
Male subjects who are sexually active must agree to use a double barrier method of 
contraception (condom with spermicide) from the first dose of randomized treatment until 
2 weeks after their last dose, and must not donate sperm during their study participation 
period. If a male subject's partner becomes pregnant during the course of the study, it must be 
reported to the Sponsor within 24 hours of the Investigator learning of its occurrence. 
6.7 
Medication Error 
For the purposes of this clinical study a medication error is an unintended failure or mistake in 
the treatment process for a study drug that either causes harm to the subject or has the 
potential to cause harm to the subject.  
A medication error is not lack of efficacy of the drug, but rather a human or process related 
failure while the drug is in control of the study site staff or subject. 


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Medication error includes situations where an error:  
x 
occurred 
x 
was identified and intercepted before the subject received the drug 
x 
did not occur, but circumstances were recognized that could have led to an 
error 
Examples of events to be reported in clinical studies as medication errors: 
x 
drug name confusion 
x 
dispensing error, eg, medication prepared incorrectly, even if it was not 
actually given to the subject 
x 
drug not administered as indicated, for example, wrong route or wrong site 
of administration 
x 
drug not taken as indicated, eg, tablet dissolved in water when it should be 
taken as a solid tablet  
x 
drug not stored as instructed, eg, kept in the refrigerator when it should be at 
room temperature  
x 
wrong subject received the medication (excluding IWRS errors) 
x 
wrong drug administered to subject (excluding IWRS errors) 
Examples of events that do not require reporting as medication errors in clinical studies: 
x 
errors related to or resulting from IWRS, including those which lead to one 
of the above listed events that would otherwise have been a medication error  
x 
subject accidentally missed drug dose(s) (eg, forgot to take medication) 
x 
accidental overdose (will be captured as an overdose) 
x 
subject failed to return unused medication or empty packaging 
x 
errors related to background and rescue medication, or standard of care 
medication in open label studies  
Medication errors are not regarded as AEs but AEs may occur as a consequence of the 
medication error.   


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If a medication error occurs in the course of the study, then the Investigator or other site 
personnel informs the appropriate Sponsor representatives immediately but no later than 
24 hours of when he or she becomes aware of it. 
6.8 
Management of study drug-related toxicities – not applicable 
7. 
INVESTIGATIONAL PRODUCT AND OTHER TREATMENTS 
7.1 
Identity of investigational products 
In this protocol, “study drug” refers to an active ingredient or placebo being tested or used as a 
reference in this study. Study drugs used in this study are summarized in Table 5. Instructions 
for priming and use are provided in Appendix D. 
AS MDI and Placebo MDI are manufactured and supplied by the Sponsor. Placebo MDI is 
manufactured in the image of the active test product. For open-label Proventil (active control), 
MDIs will be provided from commercial supplies. Manufacturer’s instructions for study drug 
administration will be provided.  
Table 5. 
Randomized Study Drugs 
Product Name 
and Dose 
Product Strength 
Manufacturer 
Dosage Form/ 
Fill Count 
Administration 
AS MDI 90 μg 
AS MDI 45 μg/ 
actuationa 
Pearl 
MDI/ 
120 actuations 
Taken as 2 actuations 
AS MDI 180 μg 
AS MDI 90 μg/ 
actuationb 
Pearl 
MDI/ 
120 actuations 
Taken as 2 actuations 
Placebo MDI 
Formulation does 
not contain an 
active ingredient 
Pearl 
MDI/ 
120 actuations 
Taken as 2 actuations 
Proventil 90 μg 
Albuterol 
90 μg/actuationb 
Merck Sharp & 
Dohme Corp. 
MDI/ 
200 actuations 
Taken as 1 actuation 
Proventil 180 μg 
Albuterol 
90 μg/actuationb 
Merck Sharp & 
Dohme Corp. 
MDI/ 
200 actuations 
Taken as 2 actuations 
Note: All study drugs will be administered by oral inhalation. 
a 
Each inhalation contains 54 μg albuterol sulfate corresponding to 45 μg albuterol base per actuation 
b 
Each inhalation contains 108 μg albuterol sulfate corresponding to 90 μg albuterol base per actuation 
 
For the Sponsor-provided background asthma medication (Ventolin and Pulmicort Flexhaler) 
and Ventolin for reversibility testing, commercial dry powder inhalers/MDIs with dose 
counters and manufacturer’s instructions for use will be provided. These medications are 
listed in Table 6. 


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Table 6. 
Other Sponsor-provided Study Medications 
Product 
Name 
Product Strength 
Manufacturer 
Dosage Form/ 
Fill Count 
Administration 
Pulmicort 
Flexhaler 
Budesonide 
180 μg 
AstraZeneca 
DPI/ 
120 actuations 
1 or 2 inhalations BID, as 
directed at Visit 1 
Ventolin 
Albuterol 
90 μg/actuationa 
GlaxoSmithKline 
MDI/ 
200 actuations 
Taken as directed for 
reversibility testing (Visits 
1, 1a, or 1b) and as needed 
for symptoms during the 
Screening and randomized 
Treatment Periods 
Abbreviation: DPI=dry powder inhaler. 
Note: All study drugs will be administered by oral inhalation. 
a 
Each inhalation contains 108 μg albuterol sulfate corresponding to 90 μg albuterol base per actuation. 
 
7.2 
Dose and treatment regimens 
Each of the 5 Treatment Visits will include 1 of the following single-dose treatments, based 
on the subject’s randomized treatment assignment: 
x 
AS MDI 90 μg (2 actuations of 45 μg/actuation) 
x 
AS MDI 180 μg (2 actuations of 90 μg/actuation) 
x 
Placebo MDI (2 actuations) 
x 
Proventil 90 μg (1 actuation of 90 μg/actuation) 
x 
Proventil 180 μg (2 actuations of 90 μg/actuation) 
7.2.1 
Randomized study drug 
AS MDI and Placebo MDI 
Individual AS MDIs and Placebo MDIs will be packaged in a foil pouch and contained in an 
individual visit treatment box. Both the visit treatment box and the foil overwrap will have a 
label with a component ID number. Confirm that the identifier given by IWRS and the ID 
number written on the label are the same. The foil overwrap is labeled with a 2-part label. 
Write the subject number and treatment visit number on each part of the 2-part label. The tear-
off part of the label is to be placed onto the IWRS confirmation report. 
All MDIs must be primed by study personnel before the first use. Priming involves releasing 
4 sprays into the air before the first use of the inhaler. Shaking and priming the inhaler fills a 
chamber inside the canister with the correct dose and mix of medication so that it is ready to 
use.   


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AS MDI must be primed in a separate room from the subject treatment area. Since the MDI is 
primed in a separate room before dosing, there is a possibility that there may be a delay 
between priming and dosing, and therefore to ensure consistency in the administration for all 
subjects, the MDIs are to be gently shaken (5 to 10 seconds) immediately before each 
actuation (inhalation). 
To prime the inhaler, gently shake the inhaler for 5 to 10 seconds and then spray once into the 
air away from yourself and others. Wait approximately 30 seconds and repeat the process 
3 more times.   
Each dose will consist of 2 actuations from the MDI. See Appendix D for instructions on the 
administration of AS MDI and Placebo MDIs. 
Open-label Proventil 
Individual Proventil MDIs will be contained in an individual visit treatment box. The visit 
treatment box will have a 2-part label with a component ID number. Confirm that the 
identifier given by IWRS and the component ID number written on the label are the same. 
Write the subject number and treatment visit number on each part of the 2-part label. The tear-
off part of the label is to be placed onto the IWRS confirmation report. 
Proventil should be primed by study personnel (in a separate room from the subject treatment 
area) per manufacturer’s instructions before administering to subject. Since Proventil is 
primed in a separate room before dosing, there is a possibility that there may be a delay 
between priming and dosing, and therefore to ensure consistency in the administration for all 
subjects, the MDIs are to be gently shaken (5 to 10 seconds) immediately before each 
actuation (inhalation).  
Each dose will consist of 1 or 2 actuations from the MDI. See Appendix D for the 
manufacturer’s instructions on the administration of Proventil. 
7.2.2 
Sponsor-provided background asthma therapies 
Ventolin 
Open-label Ventolin will be provided by the Sponsor and stored in a secured location within 
the clinic or pharmacy facilities. Ventolin should be stored at room temperature by the subject. 
Ventolin should be primed per manufacturer’s instructions before dispensing to subject. See 
Appendix D for the manufacturer’s instructions on the administration of Ventolin. Study 
personnel will record the number on the dose counter at the time of dispensing (following 
priming) and upon return. 
Pulmicort Flexhaler 
Open-label Pulmicort Flexhaler will be provided by the Sponsor and stored in a secured 
location within the clinic or pharmacy facilities. Pulmicort Flexhaler should be stored at room 
temperature by the subject. Pulmicort Flexhaler should be primed per manufacturer’s 


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instructions before dispensing to subject. See Appendix D for the manufacturer’s instructions 
on the administration of Pulmicort Flexhaler. Study personnel will record the number on the 
dose counter at the time of dispensing (following priming) and upon return. 
7.3 
Labeling 
AS MDI and Placebo MDI will be packaged by the Sponsor. Open-label Proventil 
(randomized study drug), Ventolin for rescue and reversibility testing, and Pulmicort 
Flexhaler will be supplied as commercially sourced open-label MDIs. 
7.3.1 
Primary packaging and labeling 
Labels will be prepared in accordance with Good Manufacturing Practice (GMP) and local 
regulatory guidelines. The labels will fulfil GMP Annex 13 requirements for labeling. 
Blinded supplies (AS MDI and Placebo MDI) 
Each MDI will be labeled with a 1-part label. The foil pouch will be labeled with a 1-part 
label. A 2-part label will be affixed to the carton holding the foil. 
Open-label supplies (Proventil) 
Open-label Proventil will be provided as individually labeled MDIs. Each MDI will contain a 
single label.  
Both single and 2-part labels will be printed with black ink and may include the following 
text: 
• Packaging Lot Trace ID # 
• Space for entry of screening # 
• Component ID # 
• Space for entry of randomization # 
• Fill Count & Dosage Form 
• Space for entry of Interval ID (Visit # only) 
• Re-evaluation/Expiration date (if 
applicable) 
• Dosing Instructions 
• Storage Conditions 
• Compound ID - Protocol # 
• Country regulatory requirements 
• Sponsor address (if applicable) 
• Translation Key (if applicable) 
 
7.3.2 
Secondary packaging and labeling information (box) 
AS MDI, Placebo MDI, open-label Proventil, open-label Ventolin, and open-label Pulmicort 
Flexhaler supplies will be provided as 1 MDI per box. Box configuration is subject to change 
due to packaging constraints. 


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Each box will be labeled with a 2-part panel label printed with black ink and may include the 
following text: 
• Packaging Lot ID # 
• Space for entry of screening # 
• Component ID # 
• Space for entry of randomization # 
• Kit Contents (1 MDI) 
• Space for entry of Interval ID 
• Re-evaluation date (if applicable) 
• Dosing Instructions (if applicable) 
• Storage Conditions 
• Compound ID - Protocol # 
• Country regulatory requirements 
• Sponsor address (If applicable) 
• Translation Key (If applicable) 
 
7.4 
Storage 
All study drugs and Sponsor-provided medication should be kept in a secure place under 
appropriate storage conditions. The investigational product label specifies the appropriate 
storage. Commercially sourced medications (Proventil, Ventolin, and Pulmicort Flexhaler) 
should be stored as indicated on the respective product label. 
Note: The clinical supplies storage area at the site must be monitored by the site staff for 
temperature consistency with the acceptable storage temperature range specified in the 
product label. Documentation of temperature monitoring should be maintained. 
7.5 
Compliance 
The time of administration of randomized study drug will be recorded in the appropriate 
sections of the eCRF. 
7.6 
Accountability 
Study personnel will have access to an IWRS to allocate subjects, to assign drug to subjects, 
and to manage the distribution of clinical supplies. Clinical supplies will be packaged 
according to a component schedule generated by the Sponsor or designee. Each person 
accessing the IWRS must be assigned an individual unique personal ID number (PIN). They 
must use only their assigned PIN to access the system and they must not share their assigned 
PIN with anyone. 
The study drug provided for this study will be used only as directed in the clinical study 
protocol. Under no circumstances will the Investigator(s) allow the study drug to be used other 
than as directed by this protocol. 
Investigational clinical supplies must be received by a designated person at the study site, 
handled and stored safely and properly, and kept in a secured location to which only the 
Investigator and designated assistants have access. Storage conditions for the clinical supplies 


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should be observed, monitored, and documented. Clinical supplies are to be dispensed only in 
accordance with the protocol. The Investigator is responsible for keeping accurate records of 
the clinical supplies received from the Sponsor, the amount dispensed to and returned by the 
subjects, and the amount remaining at the conclusion of the study. Study drug should be 
handled in accordance with Good Pharmacy Practices. The Clinical Monitor should be 
contacted with any questions concerning investigational products where special or protective 
handling is indicated. At the end of the study, all clinical supplies including partial and empty 
containers must be returned as directed by the Sponsor. 
Sites should check with the Sponsor representative for appropriate documentation that must be 
completed for drug accountability. 
The Investigator or designated assistant should not open individual clinical supply containers 
until all pre-dose assessments have been completed and the subject is eligible to be 
randomized/continue with the study. Any deviation from this must be discussed with the 
Clinical Monitor. 
For each subject, all used study drug materials will be collected. Used subject supplies will be 
kept at room temperature in a secure and locked cabinet until returned to the Sponsor or 
designee. Note: Used study drug will be stored separately from unused study drug. 
7.7 
Concomitant and other treatments  
7.7.1 
Prior medications 
All prescription and over-the-counter medications, as well as any herbal or vitamin 
supplements, taken by the subject within 30 days of Visit 1 should be recorded on the 
Prior/Concomitant Medications eCRF page; indication, total daily dose, and route and dates of 
drug administration should be captured to the best of the subject’s and site’s ability. 
Some subjects eligible for this study will be on regular inhaled asthma maintenance therapy 
defined as an ICS with or without a LABA with a stable dose for at least 30 days prior to 
Visit 1. The permitted total daily ICS dosage to qualify ICS usage for the 30 days prior to 
Visit 1, along with the assigned dose for Sponsor-provided Pulmicort Flexhaler, is defined in 
Table 7. 


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Table 7 
Dose of Sponsor-provided Pulmicort Flexhaler to be Assigned Based 
on Pre-study ICS or ICS/LABA Dose 
Pre-study Asthma Inhaled 
Corticosteroid 
Total Daily Dose of Pre-
study Inhaled 
Corticosteroid (μg/day) 
Dose of Sponsor-provided 
Pulmicort Flexhaler 
(μg/day) 
Beclomethasone 
100 to ≤200 
360  
Beclomethasone 
>200 to ≤400 
720 
Budesonide 
200 to ≤400 
360 
Budesonide 
>400 to ≤800 
720 
Ciclesonide 
80 to ≤160 
360 
Ciclesonide 
>160 to ≤320 
720 
Fluticasone furoate 
100  
360 
Fluticasone furoate 
200 
720 
Fluticasone propionate 
100 to ≤250 
360 
Fluticasone propionate 
>250 to ≤500 
720 
Mometasone furoate 
110 to ≤220 
360 
Mometasone furoate 
>220 to ≤440 
720 
Triamcinolone acetonide 
400 to ≤1000 
360 
Triamcinolone acetonide 
>1000 to ≤2000 
720 
 
7.7.2 
Concomitant medications 
Any current ongoing medications, including over-the-counter medications and herbal 
supplements, will be allowed provided they are not explicitly prohibited by the protocol 
(Table 9 or Table 10). All concomitant medications taken during the study will be recorded on 
the Concomitant Medications eCRF page with indication, total daily dose, route of 
administration, and dates of drug administration. Any additions, deletions, or changes in the 
dose of these medications while in the study should be entered in the eCRF. Subjects should 
also be instructed to contact the Investigator if they develop any illnesses, especially those 
requiring medicinal intervention. 
7.7.2.1 
Required concomitant medications 
Subjects who were receiving a regularly scheduled ICS or ICS/LABA before study entry will 
be switched to Pulmicort Flexhaler 180 μg or 360 μg BID, and LABA (if applicable) will be 
discontinued (Table 7). These subjects will continue to use Sponsor-provided Pulmicort 
Flexhaler 180 μg or 360 μg BID, as assigned at Visit 1, throughout the Screening Period and 
for the remainder of the study during both the randomized Treatment Periods and Washout 
Periods. 


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No other asthma medications are allowed for the remainder of the study, except for Sponsor-
provided Ventolin to be used as needed for rescue. 
7.7.2.2 
Allowed allergy medications 
Table 8 lists allergy medications that are allowed as long as the subject has been on a stable 
dose for at least 30 days before Visit 1 and remains on a stable dose throughout the study. 
Table 8  
Allowed Allergy Medications 
Non-sedating long-acting antihistaminesa 
Allergen immunotherapy 
Intranasal corticosteroids 
Intranasal antihistamines or combination products of intranasal antihistamines/corticosteroids 
a 
Short-acting antihistamines (eg, diphenhydramine) are also permitted for use as needed, but not regularly. 
 
7.7.3 
Prohibited medications 
7.7.3.1 
Prohibited asthma and allergy medications and washout periods 
Specific prohibited asthma and allergy medications are listed in Table 9. Subjects taking any 
of these prohibited medications are required to stop taking them at Visit 1 and are required to 
attend Visit 1a for reversibility testing. The required washout period for each medication 
before reversibility testing is shown in Table 9. 


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Table 9  
Prohibited Asthma and Allergy Medications That Must be 
Discontinued at Visit 1 and Required Washout Period Prior to 
Visit 1a 
Medication 
Minimum Washout Period Prior to Visit 1a 
Short-acting muscarinic antagonista 
8 hours 
Oral β2-agonists 
2 days 
Theophylline 
2 days 
Cromoglycate 
7 days 
Nedocromil 
7 days 
Ketotifenb 
7 days 
Zileuton 
7 days 
LABAsc 
 
Indacaterol, olodaterol, vilanterol 
7 days 
Salmeterol, formoterol 
48 hours 
Leukotriene receptor antagonist s (eg, Singulair™) 
7 days 
a 
Administered as fixed or loose combinations. 
b 
Ketotifen eye drops are allowed; no washout required. 
c 
In combination with an ICS. 
 
7.7.3.2 
Prohibited non-asthma and non-respiratory medications 
Subjects requiring medications presented in Table 10 are prohibited from participating in this 
study. Subjects who recently discontinued use of these medications may be considered for 
study enrollment provided they have met the minimum cessation period prior to Visit 1. These 
medications are prohibited throughout the course of the study. If subjects require any of the 
prohibited medications listed in Table 10, the Investigator should discuss with the monitor the 
suitability of the subject continuing study drug. 
Note: Use of systemic corticosteroids (eg, oral, parenteral, intraocular, intraarticular) is 
prohibited for the duration of the study, including both the Screening and randomized 
Treatment Periods. If a subject requires a systemic corticosteroid to treat an asthma worsening 
or asthma exacerbation, the subject will be discontinued from study drug and withdrawn from 
the study. 


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Table 10 
Prohibited Non-Asthma and Non-Respiratory Medications 
Class of Medication 
Minimum Cessation Period Prior to Visit 1 
and Prohibited Throughout the Study 
Any drug with potential to significantly prolong 
the QT intervala,b 
14 days or 5 half-lives, whichever is longer 
Other investigational drugs 
30 days or 5 half-lives, whichever is longer 
Non-selective non-ocular β-blocking agents 
7 days 
Cardiac anti-arrhythmics (Class Ia, III) 
7 days, unless amiodarone, then 3 months 
Anticonvulsants for seizure disorderc 
Allowed if stable dose for 12 months and free of 
seizures for 1 year 
Antipsychotic drugsd 
30 days 
Tricyclic antidepressantsd 
14 days 
Monoamine oxidase inhibitors 
14 days 
Antitumor necrosis factor α antibodies (eg, 
infliximab and any other members of this class of 
drugs) 
30 days or 5 half-lives, whichever is longer 
Monoclonal antibodiese 
30 days or 5 half-lives, whichever is longer 
Protease inhibitors (eg, ritonavir) 
30 days 
Note: Benzodiazepines are not exclusionary. Serotonin norepinephrine reuptake inhibitors and selective 
serotonin reuptake inhibitors are not excluded as long as the subject has been on a stable dose for at least 
30 days before Visit 1 and throughout the Screening and Treatment Phase, and the dose does not exceed the 
maximum recommended. 
a 
Subjects who are on medications that have the potential to prolong the QTc interval may be enrolled 
provided the dose has remained stable for at least 3 months before Visit 1, the subject meets all of the ECG 
inclusion criteria and none of the ECG exclusion criteria, and if, in the opinion of the Investigator, there are 
no safety concerns for the subject to participate in the study. Initiation of medications with the potential to 
significantly prolong the QT interval is prohibited throughout the Screening and Treatment Periods. 
b 
Short courses of macrolide and quinolone antibiotics to treat infections are permitted. 
c 
Anticonvulsants for conditions other than seizures may be started and stopped at any time before the study 
and throughout the Screening and Treatment Periods. 
d 
Antipsychotic agents and tricyclic antidepressants used for previously diagnosed underlying medical 
conditions are allowed if, in the opinion of the Investigator, there are no concerns regarding patient safety, 
and if the subject has been on a stable dose for at least 6 weeks. 
e 
Investigators should contact the Medical Monitor to determine the appropriateness and safety of continuing 
study drug on a case-by-case basis (eg, Prolia® [denosumab] for osteoporosis, may be allowed after 
consultation). 
 
7.7.4 
Other concomitant treatment 
Medication other than that described above, which is considered necessary for the subject’s 
safety and wellbeing, may be given at the discretion of the Investigator and recorded in the 
appropriate sections of the eCRF. 


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8. 
STATISTICAL ANALYSES  
This study will be conducted as a 5-period, 5-treatment Williams (Williams 1949) crossover 
design evaluating the following 5 treatments: 
x 
AS MDI 90 μg (2 actuations of 45 μg/actuation) 
x 
AS MDI 180 μg (2 actuations of 90 μg/actuation) 
x 
Placebo MDI (2 actuations) 
x 
Proventil 90 μg (1 actuation of 90 μg/actuation) 
x 
Proventil 180 μg (2 actuations of 90 μg/actuation) 
The primary objective of this study is to determine the dose of albuterol delivered from 
AS MDI that is comparable to Proventil. This design utilizes 10 treatment sequences. 
8.1 
Statistical considerations 
Analyses will be performed by the Sponsor or its representatives. All analyses will be 
specified in a detailed statistical analysis plan (SAP) that will include table and data listing 
shells with mock graphical representations. The SAP will be signed before database lock and 
unblinding. 
8.2 
Sample size estimate 
Power calculations were based on the properties of the primary endpoint, the change from 
baseline in FEV1 AUC0-6. Randomization of 70 subjects in order to achieve at least 
64 subjects completing the study will provide >95% overall probability to demonstrate 
superiority of each treatment relative to Placebo MDI assuming a minimum detectable 
difference (active–Placebo MDI) of 100 mL, within-subject standard deviation of 115 mL, 
and 2-sided 5% level test. The estimate of the within-subject standard deviation was obtained 
from a 5-treatment, 5-period dose-ranging study to evaluate albuterol dry powder inhaler and 
HFA in subjects ages 12 and older with persistent asthma (NCT01058863). 
8.3 
Definitions of analysis sets 
The following analysis sets are defined in this study: 
x 
The Intent-To-Treat (ITT) analysis set is defined as all subjects who are 
randomized to treatment and receive at least 1 dose of the study treatment. 
Subjects will be analyzed in each period according to the treatment they 
were assigned to per the randomization scheme (Note that a subject who 
used a study treatment but took less than 1 full dose of treatment will qualify 
for this analysis set).  


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x 
A Modified ITT (mITT) analysis set is a subset of the ITT analysis set 
including subjects who received treatment and have post-treatment efficacy 
data from at least 2 Treatment Periods. Data judged to be impacted by major 
protocol deviations will be determined prior to unblinding and excluded per 
the statistical protocol deviation plan. Statistical tabulations and analyses 
will be by randomized treatment, but data obtained after subjects receive an 
incorrect treatment will be excluded from the affected periods. 
x 
The Safety analysis set is defined as all subjects who are randomized to 
treatment and receive at least 1 dose of the study treatment. Subjects will be 
analyzed according to treatment received rather than per the randomization 
scheme. 
x 
The Not Randomized analysis set is defined as subjects who did not 
receive a randomization number and therefore did not receive a dose of 
study treatment (eg, subjects who were screen failures or stopped 
participation before being randomized). 
Demographics and baseline characteristics will be summarized for the ITT, mITT, and Safety 
analysis sets. Extent of exposure will be summarized for the Safety analysis set. The Safety 
analysis set will be used to summarize safety. 
Efficacy analyses will be performed for the mITT analysis set. As a sensitivity analysis, the 
primary endpoint, change from baseline in FEV1 AUC0-6, will also be analysed using the ITT 
analysis set. 
8.4 
Outcome measures for analyses 
All efficacy assessments are relative to baseline and will be compared with Placebo MDI and 
Proventil, and where appropriate, the AS MDI dose levels will be compared. Since pre-dose 
values are known to be variable and an isolated timepoint may not accurately reflect the true 
baseline, the following baseline will be used for the statistical analyses of study assessments 
unless otherwise specified: the mean of available pre-dose values on the first day of each 
treatment cycle, ie., the mean of pre-dose values at Visits 2, 3, 4, 5, and 6, where the mean of 
the 60- and 30-minute pre-dose value for each visit is obtained and then the visit means are 
averaged. 
Refer to Section 2 for a complete delineation of efficacy and safety endpoints. 
8.5 
Methods for statistical analyses 
8.5.1 
Primary efficacy analysis  
The FEV1 AUC0-6 is the area under the curve for the change from baseline in FEV1 calculated 
using the trapezoidal rule. All observed data will be utilized with the trapezoidal rule to 
calculate AUC. To aid in interpretation, all AUC values will be normalized by dividing the 
AUC by the time from the first to the last non-missing value (typically 6 hours). 


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The FEV1 AUC0-6 will be analyzed using a linear mixed model with a random subject effect. 
The fixed effects in the model will include treatment, treatment sequence, baseline FEV1, and 
period. Analyses will be conducted on the overall study population, and may also be 
conducted separately within each of the 2 ICS use subgroups (previous ICS use and no 
previous ICS use before Visit 1). 
Superiority comparisons of AS MDI relative to Placebo MDI and Proventil versus Placebo 
MDI will be conducted first using a dose-ordered approach. A 2-sided alpha level of 0.05 will 
be employed. Estimated treatment differences and 95% confidence intervals (CIs) will be 
provided for the superiority comparisons. 
If both AS MDI 180 μg and Proventil 180 μg are statistically superior to Placebo MDI, as an 
exploratory endpoint, the non-inferiority of AS MDI 180 μg versus Proventil 180 μg for FEV1 
AUC0-6 will be assessed using a non-inferiority margin of 100 mL. If both AS MDI 90 μg and 
Proventil 90 μg are statistically superior to Placebo MDI, the non-inferiority of AS MDI 
90 μg versus Proventil 90 μg for FEV1 AUC0-6 will also be tested. 
Comparisons among the dose levels within a product will also be conducted for exploratory 
purposes. Estimated treatment differences and 95% CIs will be provided. 
8.5.2 
Secondary efficacy analysis 
The secondary endpoints will be analyzed using a similar approach as that of the primary 
endpoint. Linear mixed models will be fit with a random subject effect. The fixed effects will 
include baseline FEV1, treatment, treatment sequence, and period. 
The peak change from baseline in FEV1 will be calculated using the largest FEV1 value 
measured during the 6 hours post-dosing. 
The FEV1 AUC0-4 will be calculated in a similar manner as FEV1 AUC0-6; however, the 
trapezoidal rule will only be implemented through the 4-hour nominal timepoint. The AUC 
values will be normalized accordingly. 
8.5.3 
Other efficacy analysis 
Responders will be defined as subjects achieving ≥15% improvement in FEV1 within 
30 minutes after dosing. 
The time to onset of response for each individual subject will be defined as the first timepoint 
for which an increase from baseline FEV1 of at least 15% is observed within the first 
30 minutes post dose. 
The duration of response for each subject will be defined as the time from onset of a 15% or 
greater increase in FEV1 to the offset of the 15% increase in FEV1 relative to baseline. 
Change from baseline in FEV1 at each post-dose timepoint will be presented graphically by 
treatment. 


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The median values for time to peak FEV1, time to onset of response, and duration of response 
will be reported by treatment. The median differences and corresponding Hodges-Lehmann 
CIs will be presented for pairwise comparisons among the treatments. 
The percentages of subjects achieving a 12% and 15% improvement from baseline within 
30 minutes post dose will be tabulated by treatment. The odds of being a responder may also 
be estimated using a generalized mixed effects model. 
8.5.4 
Type 1 error control 
The Type I error rate will be controlled at the 5% level across the superiority comparisons of 
the primary endpoint, FEV1 AUC0-6. In general, the superiority of Proventil relative to Placebo 
MDI will be tested first using a dose-ordered approach. If Proventil 180 μg is superior to 
Placebo MDI, AS MDI 180 μg will be compared to Placebo MDI. If AS MDI 180 μg is 
superior to Placebo MDI, the superiority of the 90-μg dose relative to Placebo MDI will be 
tested. Full details of the procedure will be specified in the statistical analysis plan; however, 
the totality of the data including comparisons among AS MDI dose levels will be used to 
select an appropriate dose for AS MDI. 
8.5.5 
Data validation and transformation 
In general, the distribution of spirometry measures is well approximated by a normal 
distribution. Under some circumstances, however (eg, during an exacerbation unrelated to 
treatment), extreme and atypical values can arise. Such values have high influence on 
estimation of variance parameters and on standard errors of fixed effect estimates. The 
distribution of scaled marginal residuals, and influence statistics will be examined to identify 
such cases. In the event that a single or small number of such outlying values are found to 
exist and found to be highly influential, the effects may be ameliorated by either 
transformation or removal of the outlier. Transformations to be considered may include the 
logarithmic transformation or normal rank transformations. Where outliers are removed, 
sensitivity analyses including those values will be reported. 
Changes in spirometry measures from baseline, and from timepoint to timepoint will be 
examined graphically before database lock, and before unblinding, as part of data quality 
management. 
8.5.6 
Safety analyses 
No formal statistical analysis of safety data is planned. Safety data will be summarized by 
treatment and listed. 
8.5.6.1 
AEs 
Adverse events occurring during each Treatment Period will be summarized by the number of 
subjects experiencing an event and tabulated at the level of the Medical Dictionary for 
Regulatory Activities (MedDRA) system organ class and preferred term. The version of 
MedDRA current at the time of database lock will be used for the final analysis of data. 
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by relationship to study drug. No hypothesis tests will be performed. Tables will show the 
overall incidence of AEs and the incidence for each treatment. 
8.5.6.2 
Vital signs 
Descriptive statistics (mean, median, standard deviation, and range) for change from baseline 
will be tabulated by vital sign parameter and treatment for each scheduled assessment time. 
For vital signs, baseline will be defined as the average of the values prior to dosing on the day 
of randomization. In addition, potentially clinically significant values will be identified and 
summarized. 
8.5.6.3 
Clinical laboratory measurements 
Subjects with out-of-range values will be listed. 
8.5.6.4 
12-Lead ECGs 
Subjects with out-of-range values will be listed. 
8.5.7 
Handling of missing data 
Pre-dose spirometry values will use the average of the non-missing -60 minute and -30 minute 
values. 
For the mITT analyses, FEV1 AUC0-6, FEV1 AUC0-4, and peak FEV1 will be calculated if 
there is at least 1 non-missing data point during the first 2 hours post-dose. 
8.5.8 
Statistical software 
Data processing, statistical screening, descriptive reporting, and analysis of the efficacy and 
safety data will be performed using SAS (SAS Institute, Cary, NC, US; Version 9.3 or 
higher). 
9. 
STUDY AND DATA MANAGMENT BY THE SPONSOR 
9.1 
Training of study site staff 
Before the first subject is entered into the study, a Sponsor representative will review and 
discuss the requirements of the clinical study protocol and related documents with the 
investigational staff and train them in any study specific-procedures and study system(s) used. 
The Principal Investigator will ensure that appropriate training relevant to the study is given to 
all of these staff, and that any new information relevant to the performance of this study is 
forwarded to the staff involved. 
The Principal Investigator will maintain a record of all individuals involved in the study 
(medical, nursing and other staff). 


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9.2 
Monitoring of the study 
During the study, a Sponsor representative will have regular contacts with the study site, 
including visits to: 
x 
provide information and support to the Investigator(s) 
x 
confirm that facilities remain acceptable 
x 
confirm that the Clinical Study Team is adhering to the clinical study 
protocol, that data are being accurately and timely recorded in the eCRFs, 
that biological samples are handled in accordance with the laboratory 
manual, and that study drug accountability checks are being performed 
x 
perform source data verification (a comparison of the data in the eCRFs 
with the subject’s medical records at the hospital or practice, and other 
records relevant to the study) including verification of informed consent of 
participating subjects. This will require direct access to all original records 
for each subject (eg, clinic charts) 
The Sponsor representative will be available between visits if the Investigator(s) or other staff 
at the site needs information and advice about the study conduct. 
9.2.1 
Source data 
Refer to the Clinical Study Agreement for location of source data. 
9.2.2 
Study agreements 
The Principal Investigator at each site should comply with all the terms, conditions, and 
obligations of the Clinical Study Agreement, or equivalent, for this study. In the event of any 
inconsistency between this clinical study protocol and the Clinical Study Agreement, the 
terms of clinical study protocol shall prevail with respect to the conduct of the study and the 
treatment of subjects and in all other respects, not relating to study conduct or treatment of 
subjects, the terms of the Clinical Study Agreement shall prevail. 
Agreements between the Sponsor and the Principal Investigator should be in place before any 
study-related procedures can take place, or subjects are enrolled. 
9.2.3 
Archiving of study documents 
The Investigator should follow the principles outlined in the Clinical Study Agreement. 
9.3 
Study timetable and end of study 
The end of study is defined as the last subject’s follow-up telephone call. 
The study may be terminated at individual study sites if the study procedures are not being 
performed according to Good Clinical Practice (GCP), or if recruitment is slow. 


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9.4 
Data management 
Data management of the study will be performed by the Sponsor or designee, and supervised 
by the Sponsor.  
10. 
ETHICAL AND REGULATORY REQUIREMENTS 
10.1 
Ethical conduct of the study 
The study will be performed in accordance with ethical principles that have their origin in the 
Declaration of Helsinki and are consistent with ICH/GCP, applicable regulatory requirements 
and the Sponsor’s policy on Bioethics and Human Biological Samples. 
10.2 
Subject data protection 
The ICF will incorporate (or, in some cases, be accompanied by a separate document 
incorporating) wording that complies with relevant data protection and privacy legislation. 
10.3 
Ethics and regulatory review 
An IRB should approve the final clinical study protocol, the final version of the ICF, the 
assent form, and any other written information and/or materials to be provided to the subjects. 
The opinion of the IRB should be given in writing.  
The IRB should approve all advertising used to recruit subjects for the study. 
The Sponsor will approve any modifications to the ICF that are needed to meet local 
requirements. 
If required by local regulations, the clinical study protocol should be re-approved by the IRB 
annually. 
Before enrollment of any subject into the study, the final clinical study protocol, including the 
final version of the ICF and assent form, is approved by the national regulatory authority or a 
notification to the national regulatory authority is done, according to local regulations. 
Each Principal Investigator is responsible for providing the IRB with reports of any serious 
and unexpected adverse drug reactions from any other study conducted with the 
investigational product. The Sponsor will provide this information to the Principal 
Investigator so that he/she can meet these reporting requirements. 
The head of the study site should seek the opinion of the IRB with respect to the 
appropriateness of continuing the study at the study site at least once a year when the duration 
of the study exceeds 1 year. The Principal Investigator should submit progress reports to the 
IRB via the head of the study site at the time of the clinical study protocol re-approval. 


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Before enrollment of any subject into the study, the final clinical study protocol, including the 
final version of the ICF, should be approved by the national regulatory authority with 
notification provided, according to local regulations. The Sponsor will handle the distribution 
of any of these documents to the national regulatory authorities. 
The Sponsor will provide regulatory authorities, IRB, the head of the study site, and the 
Principal Investigator with safety updates/reports according to local requirements. 
10.4 
Informed consent 
The Principal Investigator(s) at each study site will: 
x 
ensure each subject is given full and adequate oral and written information 
about the nature, purpose, possible risk and benefit of the study 
x 
ensure each subject is notified that they are free to discontinue from the 
study at any time 
x 
ensure that each subject is given the opportunity to ask questions and 
allowed time to consider the information provided 
x 
ensure each subject provides signed and dated informed consent before 
conducting any procedure specifically for the study. If the subject is a 
minor, the parent or guardian will sign an ICF and the subject will sign an 
assent form. 
x 
ensure the original, signed ICF (and assent form, as appropriate) is/are 
stored in the Investigator’s study file 
x 
ensure a copy of the signed ICF (and assent form, as appropriate) is/are 
given to the subject (and the subject’s parent or guardian if the subject is a 
minor) 
x 
ensure that any incentives for subjects who participate in the study as well as 
any provisions for subjects harmed as a consequence of study participation 
are described in the ICF that is approved by an IRB 
10.5 
Changes to the clinical study protocol and ICF/assent form 
Study procedures will not be changed without the mutual agreement of the Coordinating 
Investigator and the Sponsor. 
If there are any substantial changes to the clinical study protocol, then these changes will be 
documented in a new version of the study protocol. 


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The new version of the clinical study protocol is to be approved by the relevant IRB and if 
applicable, also the national regulatory authority approval, before implementation. Local 
requirements are to be followed for new versions of clinical study protocols. 
The Sponsor will distribute any new versions of the clinical study protocol to each Principal 
Investigator(s). For distribution to the IRBs see Section 10.3. 
If a change to a clinical study protocol requires a change to a site’s ICF and assent form, the 
Sponsor and the site’s IRB are to approve the revised ICF and assent form before the revised 
forms are used. 
10.6 
Audits and inspections 
Authorized representatives of the Sponsor, a regulatory authority, or an IRB may perform 
audits or inspections at the study site, including source data verification. The purpose of an 
audit or inspection is to systematically and independently examine all study-related activities 
and documents, to determine whether these activities were conducted, and data were recorded, 
analysed, and accurately reported according to the clinical study protocol, GCP, guidelines of 
the ICH, and any applicable regulatory requirements. The Investigator will contact the 
Sponsor immediately if contacted by a regulatory agency about an inspection at the site. 


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11. 
LIST OF REFERENCES 
ATS/ERS Task Force 2005 
ATS/ERS Task Force: Standardization of Lung Function Testing: Number 2 in Series. 
European Respiratory Journal. 2005;26(2):319-338. 
EPR-3 2007 
Expert Panel Report 3 (EPR-3): Guidelines for the Diagnosis and Management of Asthma–
Summary Report. J Allergy Clin Immunol. 2007;120(5 suppl):S94-138. 
Global Initiative for Asthma 2017 
Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2017. 
Available from: www.ginasthma.org. Accessed 10 August 2017. 
Miller et al 2005 
Miller MR, Hankinson J, Brusasco V, et al. Standardisation of spirometry. Eur Respir J 
2005;26(2):319-338. 
PROVENTIL HFA package insert 
PROVENTIL HFA (albuterol sulfate) inhalation aerosol [package insert]. Whitehouse Station, NJ: 
Merck Sharp & Dohme Corp.; 2014. 
PULMICORT FLEXHALER package insert 
PULMICORT FLEXHALER (budesonide) Inhalation Powder [package insert]. Wilmington, 
DE: AstraZeneca; 2016. 
Schwartz et al 1976 
Schwartz GJ, Haycock GB, Edelmann CM Jr, Spitzer A. A simple estimate of glomerular 
filtration rate in children derived from body length and plasma creatinine. Pediatrics 
1976;58(2):259-263. 
Williams 1949 
Williams EJ. Experimental designs balanced for the estimation of residual effects of 
treatments. Australian Journal of Scientific Research. 1949;2(3):149-168. 
 
 


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Appendix A 
Spirometry Assessment Criteria 
Spirometry Assessment Criteria 
Acceptable Versus Usable Tests 
Acceptable Tests must meet the following Criteria: 
1. Acceptable start of exhalation with brisk upstroke, no hesitation or false start, and 
EV < 5% of FVC or 0.150 L, whichever is the greater (see example in Figure A2-1) 
2. No cough during the first second 
3. No valsalva maneuver 
4. No leak 
5. No obstruction of mouthpiece 
6. No extra breaths 
7. Plateau achieved, ie., the volume-time curve shows no change in volume (<0.025 L) 
for ≥ 1s, and the subject has tried to exhale for at least 6 seconds 
 
An acceptable test meets all seven criteria listed.  This is to be considered the “gold standard”. 
Usable spirometry tracings are those that only meet criteria 1 and 2.  When this occurs, repeat 
testing up to eight attempts for pre-dose and five attempts for post-dose assessments, in an 
effort to obtain three acceptable spirograms.  If only usable tests are obtained, report results 
based on the three best usable trials with observed limitations. 
Figure A2-1 Example of a Usable Spirogram 
 
EV=back extrapolation volume 
The expanded version of the early part of a subject’s volume-time spirogram, illustrating back 
extrapolation through the steepest part of the curve, where flow is PEFR, to determine the new 
“time zero”.  Forced vital capacity -4.291 L; EV – 0.123 L (2.9% FVC):  back extrapolation 
line through PEF. 


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Between-Maneuver Reproducibility Criteria 
Pre-dose Assessments 
After three acceptable spirograms have been obtained, apply the following tests: 
• The two largest values of FVC must be within 0.150 L of each other 
• The two largest values of FEV1 must be within 0.150 L of each other 
If these criteria are met, the spirometry testing for that timepoint may conclude.  The highest 
FEV1 and the highest FVC obtained at each testing timepoint (even if from different 
reproducible tracings), will be collected. 
If acceptability criteria are not met, continue testing until they are met or the subject cannot/ 
should not continue (maximum of eight attempts). 
Post-dose Assessments 
After two acceptable spirograms have been obtained, apply the following tests: 
• The two largest values of FVC are within 0.150 L of each other and/or 
• The two largest values of FEV1 are within 0.150 L of each other 
If these criteria are met, the spirometry testing for that timepoint may conclude.  The highest 
FEV1 and the highest FVC obtained at each testing timepoint (even if from different 
reproducible tracings), will be collected. 
If acceptability/reproducibility criteria are not met, continue testing until they are met or the 
subject cannot/ should not continue (maximum of five attempts). 
 


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Appendix B 
Spirometry Performance Recommendations 
Spirometry Performance Recommendations 
Spirometry data of the highest quality must be obtained for proper interpretation of the results 
of this protocol. To these ends, a standard spirometer will be used (provided by Pearl 
Therapeutics), central training provided, qualification will be required, and specific operating 
instruction will also be provided. 
Source: ATS/ERS Task Force 2005. 
FEV1, FVC, FEF25-75 MANEUVERS 
Equipment Requirements 
The spirometer must be capable of accumulating volume for >15 s (longer times are 
recommended) and measuring volumes of >8 L (body temperature (ie, 37°C), ambient 
pressure saturated with water vapor, BTPS) with an accuracy of at least ±3% of reading or 
±0.050 L, whichever is greater, with flows between 0 and 14 L-s-1. The total resistance to 
airflow at 14.0 L-s-1 must be <1.5 cmH2O L-1s-1 (0.15 kPa L-1s-1). The total resistance must be 
measured with any tubing, valves, pre-filter, etc. included that may be inserted between the 
subject and the spirometer. Some devices may exhibit changes in resistance due to water 
vapor condensation, and accuracy requirements must be met under BTPS conditions for up to 
8 successive FVC maneuvers performed in a 10-minute period without inspiration from the 
instrument. 
Display 
For optimal quality control, both flow–volume and volume–time displays are useful, and test 
operators should visually inspect the performance of each maneuver for quality assurance 
before proceeding with another maneuver. This inspection requires tracings to meet the 
minimum size and resolution requirements set forth in this standard. Displays of flow versus 
volume provide more detail for the initial portion (first 1 s) of the FVC maneuver. Since this 
portion of the maneuver, particularly the peak expiratory flow rate (PEFR), is correlated with 
the pleural pressure during the maneuver, the flow–volume display is useful to assess the 
magnitude of effort during the initial portions of the maneuver. The ability to overlay a series 
of flow–volume curves registered at the point of maximal inhalation may be helpful in 
evaluating repeatability and detecting sub-maximal efforts. However, if the point of maximal 
inhalation varies between blows, then the interpretation of these results is difficult because the 
flows at identical measured volumes are being achieved at different absolute lung volumes. In 
contrast, display of the FVC maneuver as a volume–time graph provides more detail for the 
latter part of the maneuver. A volume–time tracing of sufficient size also allows independent 
measurement and calculation of parameters from the FVC maneuvers. In a display of multiple 
trials, the sequencing of the blows should be apparent to the user. For the start of test display, 
the volume–time display should include >0.25 s, and preferably 1 s, before exhalation starts 
(zero volume). This time period before there is any change in volume is needed to calculate 
the back extrapolated volume (EV) and to evaluate effort during the initial portion of the 


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maneuver. Time zero, as defined by EV, must be presented as the zero point on the graphical 
output. The last 2 s of the maneuver should be displayed to indicate a satisfactory end of test. 
When a volume–time curve is plotted as hardcopy, the volume scale must be >10 mm L-1 
(BTPS). For a screen display, 5 mm L-1 is satisfactory (Table A1-1).  
Table A1-1. 
Recommended Minimal Scale Factors for Time, Volume and Flow 
on Graphical Output 
Parameter 
Instrument Display 
Hardcopy Graphical 
Output 
 
Resolution Required 
Scale Factor 
Resolution Required 
Volume* 
0.050 L 
5 mm-L-1 
0.050 L 
Flow* 
0.200 L-s-1 
2.5 mm L-1 s-1 
0.200 L-s-1 
Time 
0.2 s 
10 mm-s-1 
0.2 s 
*The correct aspect ratio for flow versus volume display is 2 units of flow per 1 unit of volume 
The time scale should be >20 mm-s-1, and larger time scales are preferred (>30 mm-s-1) when 
manual measurements are made. When the volume–time plot is used in conjunction with a 
flow–volume curve (ie., both display methods are provided for interpretations and no hand 
measurements are performed), the time scale requirement is reduced to 10 mm-s-1 from the 
usually required minimum of 20 mm-s-1 (Table A1-1). The rationale for this exception is that 
the flow–volume curve can provide the means for quality assessment during the initial portion 
of the FVC maneuver. The volume–time curve can be used to evaluate the latter part of the 
FVC maneuver, making the time scale less critical. 
Validation 
It is strongly recommended that spirometry systems should be evaluated using a computer-
driven mechanical syringe or its equivalent, in order to test the range of exhalations that are 
likely to be encountered in the test population. Testing the performance of equipment is not 
part of the usual laboratory procedures. 
Quality Control 
Attention to equipment quality control and calibration is an important part of good laboratory 
practice. At a minimum, the requirements are as follows:  1) a log of calibration results is 
maintained; 2) the documentation of repairs or other alterations which return the equipment to 
acceptable operation; 3) the dates of computer software and hardware updates or changes; and 
4) if equipment is changed or relocated (eg, industrial surveys), calibration checks and quality-
control procedures must be repeated before further testing begins. 


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Key aspects of equipment quality control are summarized in Table A1-2. 
Table A1-2. 
Summary of Equipment Quality Control 
Test 
Minimal 
Interval 
Action 
Volume 
Daily 
Calibration check with a 3 L syringe 
Leak 
Daily 
2 cm H2O (0.3 kPa) constant pressure for 1 minute 
Volume 
Linearity 
Quarterly 
1 L increments with a calibrating syringe measured over 
the entire volume range 
Flow 
Linearity 
Weekly 
Test at least 3 different flow ranges 
Time 
Quarterly 
Mechanical recorder check with stop watch 
Software 
New versions 
Log installation date and perform test using “known” 
subject 
Calibration is the procedure for establishing the relationship between sensor-determined 
values of flow or volume and the actual flow or volume. A calibration check is different from 
calibration and is the procedure used to validate that the device is within calibration limits, eg, 
±3% of true. If a device fails its calibration check then new calibration procedure or 
equipment maintenance is required. Calibration checks must be undertaken daily, or more 
frequently, if specified by the manufacturer. The syringe used to check the volume calibration 
of spirometers must have an accuracy of ±15 mL or ±0.5% of the full scale (15 mL for a 3-L 
syringe), and the manufacturer must provide recommendations concerning appropriate 
intervals between syringe calibration checks. Users should be aware that a syringe with an 
adjustable or variable stop may be out of calibration if the stop is reset or accidentally moved. 
Calibration syringes should be periodically (eg, monthly) leak tested at more than 1 volume up 
to their maximum; this can be done by attempting to empty them with the outlet corked. A 
dropped or damaged syringe should be considered out of calibration until it is checked. 
With regard to time, assessing mechanical recorder time scale accuracy with a stopwatch must 
be performed at least quarterly. An accuracy of within 2% must be achieved. 
Quality Control for Volume-Measuring Devices 
The volume accuracy of the spirometer must be checked at least daily, with a single discharge 
of a 3-L calibrated syringe. Daily calibration checking is highly recommended so that the 
onset of a problem can be determined within 1 day and also to help define day-to-day 
laboratory variability. More frequent checks may be required in special circumstances, such 
as: 1) during industrial surveys or other studies in which a large number of subject maneuvers 


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are carried out, the equipment’s calibration should be checked more frequently than daily; and 
2) when the ambient temperature is changing (eg, field studies), volume accuracy must be 
checked more frequently than daily and the BTPS correction factor appropriately updated.  
The accuracy of the syringe volume must be considered in determining whether the measured 
volume is within acceptable limits. For example, if the syringe has an accuracy of 0.5%, a 
reading of ±3.5% is appropriate. 
The calibration syringe should be stored and used in such a way as to maintain the same 
temperature and humidity of the testing site. This is best accomplished by keeping the syringe 
in close proximity to the spirometer, but out of direct sunlight and away from heat sources. 
Volume-type spirometer systems must be evaluated for leaks every day. The importance of 
undertaking this daily test cannot be overstressed. Leaks can be detected by applying a 
constant positive pressure of >3.0 cmH2O (0.3 kPa) with the spirometer outlet occluded 
(preferably at or including the mouthpiece). Any observed volume loss of .30 mL after 
1 minute indicates a leak and needs to be corrected. 
At least quarterly, volume spirometers must have their calibration checked over their entire 
volume range using a calibrated syringe or an equivalent volume standard. The measured 
volume should be within ±3.5% of the reading or 65 mL, whichever is greater. This limit 
includes the 0.5% accuracy limit for a 3-L syringe. The linearity check procedure provided by 
the manufacturer can be used if it is equivalent to 1 of the following procedures: 1) 
consecutive injections of 1-L volume increments while comparing observed volume with the 
corresponding cumulative measured volume, eg, 0–1,1–2, 2–3,…6–7 and 7–8 L, for an 8-L 
spirometer; and 2) injection of a 3-L volume starting at a minimal spirometer volume, then 
repeating this with a 1-L increment in the start position, eg, 0–3, 1–4, 2–5, 3–6, 4–7 and 5–8 
L, for an 8-L spirometer. The linearity check is considered acceptable if the spirometer meets 
the volume accuracy requirements for all volumes tested. 
Quality Control for Flow-Measuring Devices 
With regards to volume accuracy, calibration checks must be undertaken at least daily, using a 
3-L syringe discharged at least 3 times to give a range of flows varying between 0.5 and 12 L-
s-1 (with 3-L injection times of 6 s and 0.5 s). The volume at each flow should meet the 
accuracy requirement of ±3.5%. For devices using disposable flow sensors, a new sensor from 
the supply used for patient tests should be tested each day. 
For linearity, a volume calibration check should be performed weekly with a 3-L syringe to 
deliver 3 relatively constant flows at a low flow, then 3 at a mid-range flow, and finally 3 at a 
high flow. The volumes achieved at each of these flows should each meet the accuracy 
requirement of ±3.5%. 


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Equipment 
For measurements of VC and IC, the spirometer or flow meter must comply with the 
requirements for FVC (as described previously) and be capable of accumulating volume for 
>30 s. Expiratory maneuvers or, ideally, both inspiratory and expiratory maneuvers should be 
included in the display of VC maneuver. Regardless of whether the inspiratory or expiratory 
maneuver is used for deriving measurements, a display of the entire recorded VC maneuver 
must be provided. The maximal expiratory volume must be assessed to determine whether the 
subject has obtained a plateau in the expiratory effort. For display of the slow VC, the time 
scale may be reduced to 5 mm-s-1. 
Technical Considerations 
Minimal recommendations for spirometry systems 
Accurate results require accurate equipment. Spirometer equipment recommendations apply to 
all spirometers and are minimal requirements. In some circumstances, it may be appropriate to 
exceed these requirements (ie., in some research/surveillance applications). Instrumentation 
recommendations should be followed to provide accurate spirometric data and information 
that is comparable from laboratory to laboratory and from 1 time period to another. The 
accuracy of a spirometry system depends on characteristics of the entire system, from the 
volume or flow transducer and the use of an in-line filter, to the recorder, display or processor. 
Changes in any aspect of the equipment or errors at any step in the process can affect the 
accuracy of the results. For example, if the BTPS correction factor is wrong, an accurately 
measured FVC will be incorrectly reported. Spirometers are not required to measure all of the 
indices in Table A1-3, but must meet the recommendations for those that are measured. 
Accuracy and repeatability recommendations apply over the entire volume range of the 
instrument.  
Table A1-3. 
Range and Accuracy Recommendations Specified for Forced 
Expiratory Maneuvers 
Test 
Range/Accuracy 
(BTPS) 
Flow 
Range 
(L-s-1) 
Time (s) 
Resistance and 
Back Pressure 
Test Signal 
VC 
0.5–8 L, ± 3% of reading 
or ± 0.050 L, whichever 
is greater 
0-14 
30 
 
3-L Calibration 
syringe 
FVC 
0.5–8 L, ± 3% of reading 
or ±0.050 L, whichever is 
greater 
0-14 
15 
<1.5 cm H2O L-1 s-1 
(0.15 kPa L-1s-1) 
24 ATS 
waveforms,  
3-L Cal Syringe 


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Table A1-3. 
Range and Accuracy Recommendations Specified for Forced 
Expiratory Maneuvers 
Test 
Range/Accuracy 
(BTPS) 
Flow 
Range 
(L-s-1) 
Time (s) 
Resistance and 
Back Pressure 
Test Signal 
FEV1 0.5–8 L, ± 3% of reading 
or ± 0.050 L, whichever 
is greater 
0-14 
1 
<1.5 cm H2O L-1 s-1 
(0.15 kPa L-1s-1) 
24 ATS 
waveforms 
Time 
Zero 
The timepoint from 
which all FEVt 
measurements are taken.  
 
 
Back extrapolation 
 
FEVt: forced expiratory volume in t seconds 
 
Body temperature, ambient pressure, saturated with water vapor correction 
All spirometry values should be reported at BTPS by any method (measuring temperature and 
barometric pressure) proven effective by the manufacturer. For volume-type spirometers, the 
temperature inside the spirometer should be measured for each breathing maneuver. 
Regardless of the BTPS correction technique used, the ambient temperature must always be 
recorded with an accuracy of ±1°C. In situations where the ambient air temperature is 
changing rapidly (>3°C in <30 min), continuous temperature corrections may be necessary. 
Spirometer users should be aware of potential problems with testing performed at lower 
ambient temperatures:  17°C is the lower limit for ambient temperature, unless a manufacturer 
states that their spirometer will operate accurately at lower ambient temperatures. If 
barometric pressure is not used in calculating the BTPS correction factor, the range of 
barometric pressures over which the BTPS correction factor is valid must be published.  


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Appendix C 
Additional Safety Information 
Additional Safety Information 
Further Guidance on the Definition of a Serious Adverse Event (SAE) 
Life threatening 
‘Life-threatening’ means that the subject was at immediate risk of death from the AE as it 
occurred or it is suspected that use or continued use of the product would result in the 
subject’s death.  ‘Life-threatening’ does not mean that had an AE occurred in a more severe 
form it might have caused death (eg, hepatitis that resolved without hepatic failure). 
Hospitalization 
Outpatient treatment in an emergency room is not in itself a serious AE, although the reasons 
for it may be (eg, bronchospasm, laryngeal edema). Hospital admissions and/or surgical 
operations planned before or during a study are not considered AEs if the illness or disease 
existed before the subject was enrolled in the study, provided that it did not deteriorate in an 
unexpected way during the study. 
Important medical event or medical intervention 
Medical and scientific judgement should be exercised in deciding whether a case is serious in 
situations where important medical events may not be immediately life threatening or result in 
death, hospitalization, disability or incapacity but may jeopardize the subject or may require 
medical intervention to prevent one or more outcomes listed in the definition of serious.  
These should usually be considered as serious. 
Simply stopping the suspect drug does not mean that it is an important medical event; medical 
judgement must be used. 
x 
Angioedema not severe enough to require intubation but requiring iv hydrocortisone 
treatment 
x 
Hepatotoxicity caused by paracetamol (acetaminophen) overdose requiring treatment 
with N-acetylcysteine 
x 
Intensive treatment in an emergency room or at home for allergic bronchospasm 
x 
Blood dyscrasias (eg, neutropenia or anemia requiring blood transfusion, etc.) or 
convulsions that do not result in hospitalization 
Development of drug dependency or drug abuse 
A Guide to Interpreting the Causality Question 


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When making an assessment of causality consider the following factors when deciding if there 
is a ‘reasonable possibility’ that an AE may have been caused by the drug. 
x 
Time Course.  Exposure to suspect drug.  Has the subject actually received the suspect 
drug?  Did the AE occur in a reasonable temporal relationship to the administration of 
the suspect drug? 
x 
Consistency with known drug profile.  Was the AE consistent with the previous 
knowledge of the suspect drug (pharmacology and toxicology) or drugs of the same 
pharmacological class? Or could the AE be anticipated from its pharmacological 
properties? 
x 
De-challenge experience.  Did the AE resolve or improve on stopping or reducing the 
dose of the suspect drug? 
x 
No alternative cause.  The AE cannot be reasonably explained by another etiology 
such as the underlying disease, other drugs, other host or environmental factors. 
x 
Re-challenge experience.  Did the AE reoccur if the suspected drug was reintroduced 
after having been stopped? The Sponsor would not normally recommend or support a 
re-challenge. 
x 
Laboratory tests.  A specific laboratory investigation (if performed) has confirmed the 
relationship. 
In difficult cases, other factors could be considered such as: 
x 
Is this a recognized feature of overdose of the drug? 
x 
Is there a known mechanism? 
Causality of ‘related’ is made if following a review of the relevant data, there is evidence for a 
‘reasonable possibility’ of a causal relationship for the individual case. The expression 
‘reasonable possibility’ of a causal relationship is meant to convey, in general, that there are 
facts (evidence) or arguments to suggest a causal relationship. 
The causality assessment is performed based on the available data including enough 
information to make an informed judgment. With limited or insufficient information in the 
case, it is likely that the event(s) will be assessed as ‘not related’. 
Causal relationship in cases where the disease under study has deteriorated due to lack of 
effect should be classified as no reasonable possibility. 


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Appendix D 
Instructions for Use of Inhaled Medications 
Instructions for Use of Inhaled Medications 
Instructions for Use of the AS MDI and Placebo for AS MDI 
1. 
How do I store the inhaler? 
x 
The inhaler should be stored between 20°C-25°C (68°-77°F) as directed 
by the label. 
2. 
Preparation of the inhaler 
x 
Take the inhaler out of the pouch. Safely throw away the pouch and the 
desiccant packet that comes inside the pouch. 
x 
Take the cap off the inhaler by gently squeezing the sides of the dust-cap 
and pulling off. 
x 
Inspect the front of the inhaler and make sure there is nothing inside the 
mouthpiece of the inhaler. Make sure the canister is fully and firmly 
inserted into the actuator. 
x 
The inhaler must be primed before first use. Priming involves releasing a 
certain number of sprays (4) into the air before first use of the inhaler.  
Shaking and priming the inhaler fills a chamber inside the canister with 
the correct dose and mix of medication so that the inhaler is ready to use. 
x 
To prime the inhaler, gently shake the inhaler for 5-10 seconds and then 
spray once into the air away from yourself and others. 
NOTE:  an audible “click” may be heard which is advancement of the 
dose counter and considered normal. 
x 
Wait approximately 5-10 seconds and then repeat step #2.2.5, three more 
times.  
3. 
Using the inhaler 
x 
The inhaler should be held upright with the mouthpiece at the bottom and 
the canister at the top as pictured in Figure 1. 
x 
Shake the inhaler for 5 to 10 seconds. 
x 
Breathe out fully through your mouth, expelling as much air from your 
lungs as possible.  Tilt your head back slightly, place the mouthpiece into 
your mouth, holding the inhaler with the mouthpiece down, and closing 


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your lips around it.  To allow the medication to enter your lungs, keep 
your tongue flat on the bottom of your mouth. 
x 
While breathing in deeply and slowly through your mouth, fully depress 
the top of the dose counter with your index finger. Immediately after the 
spray is delivered, release your finger from the canister.  When you have 
breathed in fully, remove the inhaler from your mouth and close your 
mouth. 
x 
Hold your breath as long as possible, up to 10 seconds, and then breathe 
normally. 
x 
If more than one spray is necessary, repeat steps 2.3.2 to 2.3.5 the 
necessary number of times. 
x 
If the device will be used again, place the dust-cap back onto the device. 
 
Figure 1. 
Metered Dose Inhaler Diagram 
 
 
 
 
Actuator 
Dose Counter 
Dust 
C


Clinical Study Protocol Appendix C 
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Version 2.0 
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Instructions for Use of the PROVENTIL HFA 
 
Attention Health Care Professional:  
Detach Patient's Instructions for Use from package insert and dispense with the product 
PROVENTIL® HFA 
(albuterol sulfate) 
Inhalation Aerosol 
FOR ORAL INHALATION ONLY 
Patient's Instructions for Use 
 
Figure 1 
 
 
Figure 2 
Before using your PROVENTIL® HFA (albuterol sulfate) Inhalation Aerosol, read complete 
instructions carefully. Children should use PROVENTIL HFA Inhalation Aerosol under adult 
supervision, as instructed by the patient's doctor 
Please note that indicates that this inhalation aerosol does not contain chlorofluorocarbons (CFCs) 
as the propellant.  
1. SHAKE THE INHALER WELL immediately before each use. Then remove the cap from the 
mouthpiece (see Figure 1). Check mouthpiece for foreign objects prior to use. Make sure the 
canister is fully inserted into the actuator. 
 


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2. As with all aerosol medications, it is recommended to prime the inhaler before using for the 
first time and in cases where the inhaler has not been used for more than 2 weeks. Prime by 
releasing four “test sprays” into the air, away from your face.  
3. BREATHE OUT FULLY THROUGH THE MOUTH, expelling as much air from your lungs as 
possible. Place the mouthpiece fully into the mouth, holding the inhaler in its upright position (see 
Figure 2) and closing the lips around it.  
4. WHILE BREATHING IN DEEPLY AND SLOWLY THROUGH THE MOUTH, FULLY 
DEPRESS THE TOP OF THE METAL CANISTER with your index finger (see Figure 2).  
5. HOLD YOUR BREATH AS LONG AS POSSIBLE, up to 10 seconds. Before breathing out, 
remove the inhaler from your mouth and release your finger from the canister.  
6. If your physician has prescribed additional puffs, wait 1 minute, shake the inhaler again, and 
repeat steps 3 through 5. Replace the cap after use.  
7. KEEPING THE PLASTIC MOUTHPIECE CLEAN IS EXTREMELY IMPORTANT TO 
PREVENT MEDICATION BUILDUP AND BLOCKAGE. THE MOUTHPIECE SHOULD BE 
WASHED, SHAKEN TO REMOVE EXCESS WATER, AND AIR DRIED THOROUGHLY AT 
LEAST ONCE A WEEK. INHALER MAY STOP SPRAYING IF NOT PROPERLY 
CLEANED. Routine cleaning instructions: Step 1. To clean, remove the canister and 
mouthpiece cap. Wash the mouthpiece through the top and bottom with warm running water for 
30 seconds at least once a week (see Figure A). Never immerse the metal canister in water.  
 
Figure A 
Wash mouthpiece under warm running water.  


Clinical Study Protocol Appendix C 
Drug Substance PT007  
Study Code D6930C00001 (PT007001) 
Version 2.0 
Date 12 January 2018 
88 (97) 
Figure B  
Allow mouthpiece to air dry, such as overnight.  
Figure C 
When blocked, little or no medicine comes out. Step 2. To dry, shake off excess water and let the 
mouthpiece air dry thoroughly, such as overnight (see Figure B). When the mouthpiece is dry, 
replace the canister and the mouthpiece cap. Blockage from medication buildup is more likely to 
occur if the mouthpiece is not allowed to air dry thoroughly. IF YOUR INHALER HAS 
BECOME BLOCKED (little or no medication coming out of the mouthpiece, see Figure C), 
wash the mouthpiece as described in Step 1 and air dry thoroughly as described in Step 2. IF 
YOU NEED TO USE YOUR INHALER BEFORE IT IS COMPLETELY DRY, SHAKE 
OFF EXCESS WATER, replace the canister, and test spray twice into the air, away from your 
face, to remove most of the water remaining in the mouthpiece. Then take your dose as prescribed. 
After such use, rewash and air dry thoroughly as described in Steps 1 and 2.  
8. The correct amount of medication in each inhalation cannot be assured after 200 actuations, 
even though the canister is not completely empty. The canister should be  
 


Clinical Study Protocol Appendix C 
Drug Substance PT007  
Study Code D6930C00001 (PT007001) 
Version 2.0 
Date 12 January 2018 
89 (97) 
 
discarded when the labeled number of actuations have been used. Before you reach the specific 
number of actuations, you should consult your physician to determine whether a refill is needed. 
Just as you should not take extra doses without consulting your physician, you also should not 
stop using PROVENTIL HFA Inhalation Aerosol without consulting your physician.  
 
You may notice a slightly different taste or spray force than you are used to with PROVENTIL 
HFA Inhalation Aerosol, compared to other albuterol inhalation aerosol products.  
DOSAGE:  
Use only as directed by your physician.  
WARNINGS:  
The action of PROVENTIL® HFA Inhalation Aerosol should last up to 4 to 6 hours. PROVENTIL 
HFA Inhalation Aerosol should not be used more frequently than recommended. Do not increase 
the number of puffs or frequency of doses of PROVENTIL HFA Inhalation Aerosol without 
consulting your physician. If you find that treatment with PROVENTIL HFA Inhalation Aerosol 
becomes less effective for symptomatic relief, your symptoms become worse, and/or you need to 
use the product more frequently than usual, medical attention should be sought immediately. 
While you are taking PROVENTIL HFA Inhalation Aerosol, other inhaled drugs should be taken 
only as directed by your physician. If you are pregnant or nursing, contact your physician about 
the use of PROVENTIL HFA Inhalation Aerosol.  
Common adverse effects of treatment with PROVENTIL HFA Inhalation Aerosol include 
palpitations, chest pain, rapid heart rate, tremor, or nervousness. Effective and safe use of 
PROVENTIL HFA Inhalation Aerosol includes an understanding of the way that it should be 
administered. Use PROVENTIL HFA Inhalation Aerosol only with the yellow actuator supplied 
with the product. The PROVENTIL HFA Inhalation Aerosol actuator should not be used with 
other aerosol medications.  
For best results, use at room temperature. Avoid exposing product to extreme heat and cold.  
Shake well before use.  
Contents Under Pressure.  
Do not puncture. Do not store near heat or open flame. Exposure to temperatures above 120°F 
may cause bursting. Never throw container into fire or incinerator. Store between 15° - 25°C (59° 
- 77°F). Store the inhaler with the mouthpiece down. Avoid spraying in eyes. Keep out of reach 
of children.  
Further Information: Your PROVENTIL® HFA (albuterol sulfate) Inhalation Aerosol does not 
contain chlorofluorocarbons (CFCs) as the propellant. Instead, the inhaler contains a 
hydrofluoroalkane (HFA-134a) as the propellant.  
Developed and Manufactured by: 3M Health Care Limited  
Loughborough UK or 3M Drug Delivery 
Systems Northridge, CA 91324, USA Rev. 
12/14 Copyright © 1996, 2011, 2012 Merck 
Sharp & Dohme Corp., a subsidiary of 
Merck & Co., Inc.  
All rights reserved.  
653300  
 
 
 


Clinical Study Protocol Appendix C 
Drug Substance PT007  
Study Code D6930C00001 (PT007001) 
Version 2.0 
Date 12 January 2018 
90 (97) 
Instructions for Use of the VENTOLIN HFA
 


Clinical Study Protocol Appendix C 
Drug Substance PT007  
Study Code D6930C00001 (PT007001) 
Version 2.0 
Date 12 January 2018 
91 (97) 
 


Clinical Study Protocol Appendix C 
Drug Substance PT007  
Study Code D6930C00001 (PT007001) 
Version 2.0 
Date 12 January 2018 
92 (97) 
 


Clinical Study Protocol Appendix C 
Drug Substance PT007  
Study Code D6930C00001 (PT007001) 
Version 2.0 
Date 12 January 2018 
93 (97) 
 


Clinical Study Protocol Appendix C 
Drug Substance PT007  
Study Code D6930C00001 (PT007001) 
Version 2.0 
Date 12 January 2018 
94 (97) 
Instructions for Use of PULMICORT FLEXHALER 
 


Clinical Study Protocol Appendix C 
Drug Substance PT007  
Study Code D6930C00001 (PT007001) 
Version 2.0 
Date 12 January 2018 
95 (97) 
 
 




Clinical Study Protocol Appendix C 
Drug Substance PT007  
Study Code D6930C00001 (PT007001) 
Version 2.0 
Date 12 January 2018 
97 (97) 
Appendix F 
Investigator’s Agreement and Signature Page 
Investigator’s Agreement and Signature Page 
Study Title: 
A Randomized, Double-blind, Single dose, Placebo-controlled, 
5-Period, 5-Treatment, Crossover, Multi-center, Dose-ranging 
Study to Compare PT007 to Placebo MDI and Open-Label 
Proventil® HFA in Adult and Adolescent Subjects With Mild to 
Moderate Asthma 
Study Number: 
D6930C00001 (PT007001) 
Final Date: 
12 January 2018 
 
I agree: 
a. 
To assume responsibility for the proper conduct of the study at this site. 
b. 
To conduct the study in compliance with the protocol and with any other study conduct procedures provided 
by Pearl Therapeutics, Inc. (hereafter referred to as Pearl). 
c. 
Not to implement any changes to the protocol without agreement from the Sponsor and prior review and 
written approval from the IRB/IEC, except where necessary to eliminate an immediate hazard to the 
subjects, or for administrative aspects of the study (where permitted by all applicable regulatory 
requirements). 
d. 
That I am aware of, and will fully comply with GCP and all applicable regulatory requirements. 
e. 
That I am thoroughly familiar with the appropriate use of the investigational product(s), and other 
information provided by the Sponsor including, but not limited to, the following: the protocol and the current 
Investigator Brochure (IB). 
f. 
To ensure that all persons assisting me with the study are qualified, adequately informed about the 
investigational product(s) and of their study-related duties and functions. 
g. 
To supply Pearl with any necessary information regarding ownership interest and financial ties; to promptly 
update this information if any relevant changes occur during the course of the study and for 1 year following 
completion of the study; and agree that Pearl may disclose any information it has about such ownership 
interests and financial ties to regulatory authorities. 
h. 
I agree to report all information or data in accordance with the protocol and any other study conduct 
procedures provided by Pearl. 
i. 
That since the information in this protocol and IB is confidential, I understand that its disclosure to any third 
parties, other than those involved in approval, supervision or conduct of the study is prohibited. 
j. 
To accurately transfer all required data from each subject’s source document to the eCRFs. The eCRFs will 
be provided to the Sponsor in a timely manner at the completion of the study, or as otherwise specified by 
the Sponsor. 
k. 
To allow authorized representatives of Pearl or regulatory authority representatives to conduct on-site visits 
to review, audit and copy study documents. I will personally meet with these representatives to answer any 
study-related questions. 
Signature: 
 
Date: 
 
 
 
Name:   
 
 
 
 
 
 
 
 
 
 
 
Site Name: 
 
 
 
 
 
 
 
 
 
 
 

SAP_001.pdf: 
 
Statistical Analysis Plan 
 
Study Code 
D6930C00001(PT007001) 
NCT #  
NCT03364608 
Date 
13 MARCH 2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
A Randomized, Double-blind, Single dose, Placebo-controlled, 5-Period, 5- 
Treatment, Crossover, Multi-center, Dose-ranging Study to Compare PT007 
to Placebo MDI and Open-Label Proventil® HFA in Adult and Adolescent 
Subjects With Mild to Moderate Asthma 
 
 
 
 
 
 


Statistical Analysis Plan
Protocol No. D6930C00001 (PT007001)
Last Revision Date: 13 Mar 2018
(Page 1 of 48)
Confidential and Proprietary 
STATISTICAL ANALYSIS PLAN
Trial Sponsor: 
AstraZeneca
Study Number:
D6930C00001 (PT007001)
Study Phase:
II
Product Name:
Albuterol Sulfate Pressurized Inhalation Suspension (AS MDI);
PT007
PIND Number:
136213
Indication:
Asthma
Dosage Form/Strength
x
AS MDI as
o
2 actuations of 45 μg per actuation (90 μg)
o
2 actuations of 90 μg per actuation (180 μg)
Protocol Title: A Randomized, Double-blind, Single dose, Placebo-controlled, 5-Period, 5-
Treatment, Crossover, Multi-center, Dose-ranging Study to Compare PT007 to Placebo MDI 
and Open-Label Proventil® HFA in Adult and Adolescent Subjects With Mild to Moderate
Asthma 
Date of Issue:
13 Mar 2018
Version
1.0






Statistical Analysis Plan
Protocol No. D6930C00001 (PT007001)
Last Revision Date: 13 Mar 2018
(Page 3 of 48)
Confidential and Proprietary 
TABLE OF CONTENTS 
LIST OF TABLES ................................................................................................................................................ 5 
LIST OF FIGURES .............................................................................................................................................. 5 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS .................................................................... 6 
1.
INTRODUCTION ....................................................................................................................................... 8
2.
STUDY OBJECTIVES ............................................................................................................................... 8
2.1 
PRIMARY OBJECTIVE ........................................................................................................................... 8 
2.2 
SECONDARY OBJECTIVE....................................................................................................................... 8 
2.3 
SAFETY OBJECTIVE.............................................................................................................................. 8 
3.
STUDY ENDPOINTS ................................................................................................................................. 8
3.1 
EFFICACY ASSESSMENTS ..................................................................................................................... 8 
3.2 
PRIMARY EFFICACY ENDPOINT............................................................................................................ 8 
3.3 
SECONDARY EFFICACY ENDPOINTS ..................................................................................................... 9 
3.4 
OTHER EFFICACY ENDPOINTS.............................................................................................................. 9 
3.5 
SAFETY ENDPOINTS ............................................................................................................................. 9 
4.
STUDY DESIGN ......................................................................................................................................... 9
4.1 
STUDY DESIGN AND PLAN ................................................................................................................... 9 
4.2 
RANDOMIZATION ...............................................................................................................................16 
4.3 
HYPOTHESIS TESTING ........................................................................................................................16 
4.4 
INTERIM ANALYSIS ............................................................................................................................17 
4.5 
SAMPLE SIZE......................................................................................................................................17 
5.
DATA AND ANALYTICAL QUALITY ASSURANCE ........................................................................ 18
6.
ANALYSIS SETS ...................................................................................................................................... 18
6.1 
INTENT-TO-TREAT (ITT) ANALYSIS SET............................................................................................18 
6.2 
MODIFIED ITT (MITT) ANALYSIS SET...............................................................................................18 
6.3 
SAFETY ANALYSIS SET ......................................................................................................................19 
6.4 
NOT-RANDOMIZED ANALYSIS SET.....................................................................................................19 
6.5 
ANALYSIS SETS FOR ANALYSES.........................................................................................................19 
7.
STATISTICAL ANALYSIS ..................................................................................................................... 19
7.1.1 
General Data Handling Rules and Definitions ...................................................................19 
7.1.2 
Data Exclusion and Missing Data Imputation ....................................................................20 
7.2 
SUBJECT DISPOSITION........................................................................................................................20 
7.3 
DEMOGRAPHY....................................................................................................................................21 
7.3.1 
Asthma History, Screening/Baseline Spirometry, and Reversibility ..................................21 
7.3.2 
Medical and Surgical History at Screening, Pregnancy Testing at Screening and 
Baseline ..............................................................................................................................22 
7.3.3 
Prior, Concomitant, and Post-Treatment Medications/Treatments .....................................22 
7.3.4 
Extent of Exposure to Study Drug ......................................................................................22 
7.4 
EFFICACY ANALYSES.........................................................................................................................23 
7.4.1 
Primary Efficacy .................................................................................................................23 
7.4.2 
Study Day ...........................................................................................................................23 
7.4.3 
Time Points and Time Intervals for Efficacy Endpoints ....................................................23 
7.4.4 
Primary Efficacy Analysis ..................................................................................................24 


 
Statistical Analysis Plan 
Protocol No. D6930C00001 (PT007001) 
Last Revision Date: 13 Mar 2018 
(Page 4 of 48) 
 
Confidential and Proprietary 
7.4.5 
Secondary Efficacy ............................................................................................................. 26 
7.4.6 
Other Efficacy .................................................................................................................... 26 
7.4.7 
Data Validation and Transformation .................................................................................. 27 
7.5 
SAFETY ANALYSES ............................................................................................................................ 28 
7.5.1 
Adverse Events ................................................................................................................... 28 
7.5.2 
Clinical Laboratory Data .................................................................................................... 30 
7.5.3 
Vital Signs .......................................................................................................................... 32 
7.5.4 
Electrocardiogram (ECG) ................................................................................................... 33 
7.5.5 
Physical Examination ......................................................................................................... 33 
8. 
CHANGES FROM METHODS PLANNED IN THE PROTOCOL .................................................... 33 
9. 
STATISTICAL SOFTWARE .................................................................................................................. 33 
10. REFERENCES .......................................................................................................................................... 34 
APPENDIX 1 DATA HANDLING RULES ..................................................................................................... 35 
APPENDIX 2 ANALYSIS DATASET SPECIFICATIONS ........................................................................... 42 
APPENDIX 3 SAS CODE FOR STATISTICAL ANALYSES ...................................................................... 43 
APPENDIX 4 MOCKUP TABLES, LISTINGS, AND GRAPHS (TLGS) .................................................... 48 
 
 
 


 
Statistical Analysis Plan 
Protocol No. D6930C00001 (PT007001) 
Last Revision Date: 13 Mar 2018 
(Page 5 of 48) 
 
Confidential and Proprietary 
List of Tables 
Table 1 Schedule of Events ................................................................................................................ 12 
Table 2 Timed Assessments at Visits 2, 3, 4, and 5 ............................................................................ 14 
Table 3 Timed Assessments at Visit 6 ................................................................................................ 15 
Table 4 Analysis Study Time Windows for Spirometry Assessments ............................................... 24 
Table 5 Lab Parameters ...................................................................................................................... 30 
Table 6 Potentially Clinically Significant Criteria for Systolic and Diastolic Blood Pressure 
Parameters and Heart Rate ..................................................................................................... 32 
 
List of Figures 
Figure 1 Study Flow Diagram: ............................................................................................................. 11 
 
 
 


 
Statistical Analysis Plan 
Protocol No. D6930C00001 (PT007001) 
Last Revision Date: 13 Mar 2018 
(Page 6 of 48) 
 
Confidential and Proprietary 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
AE 
Adverse event 
ALT 
Alanine aminotransferase 
AS 
Albuterol Sulfate 
AST 
Aspartate aminotransferase 
ATC 
Anatomical Therapeutic Chemical 
ATS 
American Thoracic Society 
AUC0-6 
Area under the curve from time 0 to 6 hours 
AUC0-4 
Area under the curve from time 0 to 4 hours 
β-hCG 
β-human chorionic gonadotropin 
BID 
Bis in die, twice daily 
BMI 
Body mass index 
BMP 
Basic metabolic panel 
BPM 
Beats per minute 
BUN 
Blood urea nitrogen 
CKD-EPI 
Chronic Kidney Disease Epidemiology Collaboration 
CI 
Confidence interval 
CTCAE 
Common Terminology Criteria for Adverse Events 
DBP 
Diastolic blood pressure 
DMP 
Data Management Plan 
CRF 
Case report form 
DMP 
Data management plan 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
eDiary 
Electronic diary 
eGFR 
Estimated glomerular filtration rate 
ERS 
European Respiratory Society 
FEF25-75 
Forced expiratory flow from 25% to 75% of FVC 
FEV1 
Forced expiratory volume in 1 second  
FVC 
Forced vital capacity 
GGT 
Gamma-glutamyl transpeptidase 
H0 
Null hypothesis 
H1 
Alternative hypothesis 
HFA 
Hydrofluoroalkane 
HR 
Heart rate 
ICS 
Inhaled corticosteroid 
ITT 
Intention-to-treat 
IWRS 
Interactive web response system 


 
Statistical Analysis Plan 
Protocol No. D6930C00001 (PT007001) 
Last Revision Date: 13 Mar 2018 
(Page 7 of 48) 
 
Confidential and Proprietary 
LABA 
Long-acting β2-agonist 
MCH 
Mean corpuscular hemoglobin 
MCHC 
Mean corpuscular hemoglobin concentration 
MCV 
Mean corpuscular volume 
MDI 
Metered dose inhaler 
MedDRA 
Medical Dictionary for Regulatory Activities 
mITT 
Modified intent-to-treat 
OTC 
Over-the-counter 
PDV 
Premature discontinuation visit 
PCS  
Potentially clinically significant 
PEFR 
Peak expiratory flow rate 
PFT 
Pulmonary function test 
PR 
Time from electrocardiogram P wave to the end of the R wave 
corresponding to electrical systole 
QA 
Quality assurance 
QC 
Quality control 
QT 
Time from electrocardiogram Q wave to the end of the T wave 
corresponding to electrical systole 
QTcF 
QT corrected using Fridericia’s formula [QT/(RR1/3)] 
RR 
Time from electrocardiogram R wave to the next R wave corresponding to 
electrical systole 
SAE 
Serious adverse event 
SABA 
Short-acting β-agonist 
SAL 
Salmeterol 
SAP 
Statistical analysis plan 
sPDP 
Statistical protocol deviation plan 
SAS 
Statistical Analysis System 
SBP 
Systolic blood pressure 
SD 
Standard deviation 
SI 
International System of Units (Système International d’Unités) 
SOC 
System organ class 
TC 
Telephone call 
TEAE 
Treatment emergent adverse event 
TP 
Treatment period 
ULN 
Upper limit of normal 
US/USA 
United States 
WHO DDE 
World Health Organization Drug Dictionary Enhanced 
WHO HD 
World Health Organization Herbal Dictionary 


Statistical Analysis Plan
Protocol No. D6930C00001 (PT007001)
Last Revision Date: 13 Mar 2018
(Page 8 of 48)
Confidential and Proprietary 
1.
INTRODUCTION 
AstraZeneca is developing a broad range of metered dose inhaler (MDI)-based inhalation 
aerosols using its porous particle technology platform, including Albuterol Sulfate 
Pressurized Inhalation Suspension (AS) MDI.
This Statistical Analysis Plan (SAP) outlines the statistical methods for the display, 
summary, and analysis of data collected within the scope of Clinical Trial Protocol 
D6930C00001 (PT007001), Version 2.0 (Amendment 1), dated January 12, 2018.
All references to doses of AS MDI and Proventil® HFA (hereafter referred to as Proventil) 
refer to the albuterol base (i.e., 90 μg albuterol base, which equals 108 μg albuterol sulfate).
2.
STUDY OBJECTIVES 
2.1
Primary Objective 
x
To confirm the dose of albuterol delivered from AS MDI that is comparable to Proventil  
2.2
Secondary Objective 
x
To assess the dose response of AS MDI versus Placebo for AS MDI (hereafter referred to 
as Placebo MDI) 
2.3
Safety Objective 
x
To evaluate the safety and tolerability of AS MDI relative to Placebo MDI and Proventil 
3.
STUDY ENDPOINTS 
3.1
Efficacy Assessments 
This is a 5-period, 5-treatment Williams design (Williams 1949). Each Treatment Period will 
be 1 day, with a Washout Period of 3 to 7 days between Treatment Periods. The day of 
treatment in each Treatment Period is Day 1.  Baseline forced expiratory volume in 1 second 
(FEV1) will be calculated using the mean of available pre-dose values on the first day of each 
Treatment Period (as defined in Section 7.4.3.1).
3.2
Primary Efficacy Endpoint 
x
Change from baseline in FEV1 area under the curve from 0 to 6 hours (AUC0-6) 


 
Statistical Analysis Plan 
Protocol No. D6930C00001 (PT007001) 
Last Revision Date: 13 Mar 2018 
(Page 9 of 48) 
 
Confidential and Proprietary 
3.3 
Secondary Efficacy Endpoints 
x Change from baseline in FEV1 AUC from 0 to 4 hours (AUC0-4) 
x Peak change from baseline in FEV1 
 
3.4 
Other Efficacy Endpoints 
x Change from baseline in FEV1 at each post-dose timepoint 
x Time to peak FEV1 
x Percentage of subjects achieving 12% improvement in FEV1 from baseline within 30 
minutes of dose 
x Percentage of subjects achieving 15% improvement in FEV1 from baseline within 30 
minutes of dose 
x Time to onset of response 
x Duration of response 
 
3.5 
Safety Endpoints 
The safety endpoints include: 
x Adverse Events (AEs)/serious adverse events (SAEs) 
x Vital signs 
x Clinical laboratory parameters 
x Electrocardiograms (ECGs) 
 
4. 
STUDY DESIGN 
4.1 
Study Design and Plan 
This is a randomized, double-blind, single-dose, placebo-controlled, 5-period, 5-treatment, 
crossover, multi-center study to assess the bronchodilatory effect and safety of 2 dose levels 
of AS MDI (90 μg and 180 μg) compared with Placebo MDI and open-label Proventil (90 μg 
and 180 μg) in adult and adolescent subjects with mild to moderate asthma. 
This study will be conducted at 10 sites in the US, contributing approximately 7 subjects per 
site. Across these sites, it is planned that approximately 70 subjects with mild to moderate 
asthma will be randomized to provide approximately 64 subjects to complete the study.  
The sequence of visits is displayed in the Study Flow Diagram (Figure 1). 
For more details on the study plan please refer to Protocol Section 4. 
 


Statistical Analysis Plan
Protocol No. D6930C00001 (PT007001)
Last Revision Date: 13 Mar 2018
(Page 10 of 48)
Confidential and Proprietary 
Randomization criteria for the study are listed in Section 3.3.1 of Protocol D6930C0001.
Inclusion criteria for the study are listed in Section 3.1 of Protocol D6930C00001.  Subjects 
eligible for enrollment in the study must meet all of the inclusion criteria.  To be eligible, 
must be at least 12 years of age and no older than 65 years with stable physician-diagnosed 
asthma for 6 months. Subjects must be on either a SABA as needed as their only asthma 
therapy or a low to medium ICS dose (either alone or in combination with a LABA) for at 
least 30 days, as a consistent regimen before screening.  Also, subjects must have a pre-
bronchodilator FEV1 between ≥40 and <90% of predicted normal value after withholding 
SABA for ≥6 hours (and/or Visit 1a and/or Visit 1b, as applicable). Additionally, confirmed 
FEV1 reversibility to Ventolin, defined as Post-Ventolin increase in FEV1 of ≥15% at either 
Visit 1, Visit 1a, or Visit 1b.  Exclusion criteria for the study are listed in Section 3.2 of 
Protocol D6930C00001.  Subjects meeting any of the exclusion criteria are to be excluded 
from the study.  Reasons for exclusion from the study include: chronic obstructive pulmonary 
disease or other significant lung disease, receipt of oral corticosteroid use (any dose) within 6 
weeks of their Visit 1 of the study, and hospitalization for asthma within 6 months of Visit 1. 
.
Detailed schedules for pre- and post-dose procedures to be performed at each study visit are 
provided in Section 4 of the protocol.  A time–and-events schedule is provided below in 
Table 1. 
Visit procedures at each treatment visit (Visits 2, 3, 4, and 5) are provided in Table 2 and at 
Visit 6 in Table 3.


6
 
Statistical Analysis Plan 
Protocol No. PT007001 
Last Revision Date: 13 Mar 2018 
(Page 11 of 48) 
Confidential and Proprietary 
Figure 1 
Study Flow Diagram:  
 


6
Statistical Analysis Plan
Protocol No. PT007001
Last Revision Date: 13 Mar 2018
(Page 12 of 48)
Confidential and Proprietary 
Table 1 
Schedule of Events  
Treatment Daya
Screening Perioda
Treatment Phaseb
Follow-up
Visit 1
Visit 1a/b
Visit 2
Rand.
(TP 1)
Day 1
Visit 3
(TP 2)
Visit 4
(TP 3)
Visit 5
(TP 4)
Visit 6
(TP 5)
PDV (if
Applicable)c
TC
3 to 7 days
after final
dose
Day -28 to Day -1
Procedures
Informed consent (and assent, as appropriate)
X
Eligibility Criteria
X
Verify randomization criteria
X
Verify continued eligibility
X
X
X
X
X
MDI demonstration/training
X
X
X
X
X
X
Ventolin reversibility testd
X
X
Medical/surgical history
X
Demographics
X
Concomitant medicationse
X
X
X
X
X
X
X
Xh
Spirometryd
X
X
X
X
X
X
X
X
X
X
X
Physical Examinationf
X
X
X
Vital Signs
X
X
X
X
X
X
X
12-lead ECG
X
X
X
Pregnancy testg
X
X
Clinical laboratory testing
X
X
X
Adjust asthma medications per protocolh
X
X
X
X
Randomization
X
Randomized study drug administered
X
X
X
X
X
AEs
X
X
X
X
X
X
X
X
X
Telephone contact
X
Abbreviations: AE=adverse event; β-hCG= β-human chorionic gonadotropin; ECG=electrocardiogram; FEV1=forced expiratory volume in 1 second; ICS=inhaled corticosteroid; 
LABA= long-acting β2-agonist; MDI=metered dose inhaler; PDV=Premature Discontinuation Visit; Rand.=randomization; SABA= short-acting β-agonist; TC=telephone 
call; TP=Treatment Period. 
Note: When data collection timepoints are concurrent, variables will be collected in the following order: vital signs, ECG, clinical laboratory assessments, and spirometry. 
a.
Screening Period will be 3 to 28 days for subjects on SABA only before study entry, and 14 to 28 days for subjects on ICS or ICS/LABA before study entry. 


6
Statistical Analysis Plan
Protocol No. PT007001
Last Revision Date: 13 Mar 2018
(Page 13 of 48)
Confidential and Proprietary 
b.
Subjects to return to clinic within 3 to 7 days following Visits 2, 3, 4, and 5. 
c.
Subjects who prematurely withdraw from the study will undergo a Premature Discontinuation Visit (see Protocol Section 4.2.5). 
d.
For subjects who received their regularly inhaled asthma medications and/or SABA on the morning of the visit, spirometry and reversibility will be measured at Visit 1a, 
which will occur within 10 days of Visit 1. For subjects who do not meet reversibility criteria at Visit 1a, Visit 1b will be scheduled for a second reversibility test, to occur 
within 7 days. Subjects who do not meet reversibility criteria after the second attempt will be screen failed. 
e.
At all visits beyond Visit 1, note time of the last dose of asthma medications. The visit must be rescheduled if the last dose of Ventolin was <6 hours before the visit. 
f.
Includes evaluation of heig  and weight at Visit 1. 
g.
A serum pregnancy test (β-hCG) will be performed at Visit 1; urine β-hCG test will be performed before randomization at Visit 2 (for women of child-bearing potential only). 
h.
At Visit 1, prohibited asthma medications are to be stopped and asthma medications changed as specified in Section Protocol 7.2.2. At the end of Visit 6 (or upon premature 
discontinuation or screen failure, if applicable), subjects will return to pre-study or other appropriate maintenance asthma medications. 


6
 
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Table 2 
Timed Assessments at Visits 2, 3, 4, and 5 
 
Pre-Dose 
(minutes) 
Post-Dose (minutes) 
Before 
leaving 
clinic 
-60 
-30 
5 
15 
30 
45 
60 
120 
180 
240 
300 
360 
 
Vital signs 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
Spirometry 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
AEs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Abbreviations: AE=adverse event. 
 
 


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Table 3 
Timed Assessments at Visit 6 
 
Pre-Dose 
(minutes) 
Post-Dose (minutes) 
Before 
leaving 
clinic 
-60 
-30 
5 
15 
30 
45 
60 
120 
180 
240 
300 
360 
 
Vital signs 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
12-lead ECGb 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Spirometry 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Physical examination 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Clinical laboratory testing 
 
 
 
 
 
 
 
 
 
 
 
 
X 
AEs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Abbreviations: AE=adverse event; ECG=electrocardiogram. 
 
 


 
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4.2 
Randomization 
Subjects will be randomly assigned to 1 of 10 treatment sequences based on a Williams design 
(Williams 1949) using an interactive web response system (IWRS). Each sequence will comprise 
all 5 of the treatments included in this study in a randomized order.   
 
Randomization will be centralized and stratified by pre-study background therapy consisting of 
either inhaled corticosteroid (ICS) or non-ICS (subjects not previously treated with ICS). 
4.3 
Hypothesis Testing 
Hypothesis testing will be performed within the context of a linear mixed model analysis, 
including all treatments.  For the primary efficacy comparisons for change from baseline in FEV1 
AUC0-6 for the overall population, the primary endpoint, the null hypothesis for each pairwise 
comparison is that the mean test treatment effect is equal to that of Placebo MDI; the alternative 
hypothesis is then that the test treatment effect and that of Placebo MDI are not equal.   However, 
while the hypotheses are written for inequality testing, demonstration of superiority relative to 
placebo is the objective.  P-values will be reported as two-sided.  
The primary null (H0) and alternative (H1) hypotheses with μ representing the mean are: 
x H0: μProventil 180 μg = μplacebo 
H1: μProventil 180 μg ≠ μplacebo 
x H0: μAS MDI 180 μg = μplacebo 
H1: μAS MDI 180 μg ≠ μplacebo 


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x
H0: μProventil 90 μg = μplacebo
H1: μProventil 90 μg ≠ μplacebo
x
H0: μAS MDI 90 μg = μplacebo
H1: μAS MDI 90 μg ≠ μplacebo
The Type I error rate will be controlled at the 5% level (two-sided) across the superiority 
comparisons of the primary endpoint, FEV1 AUC0-6. In general, the superiority of Proventil 
relative to Placebo MDI will be tested first using a dose-ordered approach. If Proventil 180 μg is 
superior to Placebo MDI, AS MDI 180 μg will be compared to Placebo MDI. If AS MDI 180 μg is 
superior to Placebo MDI, the superiority of Proventil 90-μg relative to Placebo MDI will be tested.
If Proventil 90 μg is superior to placebo, then AS MDI 90 μg will be compared to Placebo MDI.
 
 
 
 
: 
  
 
 
  
 
 
 
   
 
 
 
   
 
 
Comparisons among the dose levels within a product will also be conducted for exploratory 
purposes. Estimated treatment differences and 95% CIs will be provided. 
4.4
Interim Analysis 
No interim analyses are planned for this trial. 
4.5
Sample Size 
Power calculations were based on the properties of the primary endpoint, the change from 
baseline in FEV1 AUC0-6. Randomization of 70 subjects in order to achieve at least 64 subjects 
completing the study will provide >95% overall probability to demonstrate superiority of each 
treatment relative to Placebo MDI assuming a minimum detectable difference (active–Placebo 
MDI) of 100 mL, within-subject standard deviation of 115 mL, and two-sided 5% level test. The 
estimate of the within-subject standard deviation was obtained from a 5-treatment, 5-period dose-
ranging study to evaluate albuterol dry powder inhaler and HFA in subjects ages 12 and older 
with persistent asthma (NCT01058863). 


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5.
DATA AND ANALYTICAL QUALITY ASSURANCE 
The overall quality assurance procedures for the study data, statistical programming and analyses 
are described in Standard Operating Procedures (SOPs) 
).  Detailed data management procedures are documented in the study Data 
Management Plan, Data Validation Check Specifications, and Integrated Safety Data Review Plan.  
Detailed statistical and programming quality control and quality assurance procedures are 
documented in the Statistical Analysis and Programming QC/QA Plan. 
Transfer of PFT data from the central PFT laboratory 
 to Everest will 
be defined in the 
 DMP (Data Management Plan), and data handling rules 
related to this data are included in Appendix 1 of this SAP.  The quality of all PFTs obtained at 
each timepoint will be graded independently at iCardiac Technologies by qualified personnel.  
Quality grading assessments will be based on ATS/ERS criteria and will be included in data 
transfers. 
6.
ANALYSIS SETS 
The following analysis sets are defined in this study. 
6.1
Intent-to-Treat (ITT) Analysis Set 
The Intent-To-Treat (ITT) analysis set is defined as all subjects who are randomized to treatment 
and receive at least 1 dose of the study drug.  Subjects will be analyzed in each period according to 
the treatment they were assigned to per the randomization scheme (Note that a subject who used 
study drug but took less than 1 full dose will qualify for this analysis set). 
6.2
Modified ITT (mITT) Analysis Set 
A Modified ITT (mITT) analysis set is a subset of the ITT analysis set including subjects who 
received treatment and have post-treatment efficacy data from at least 2 Treatment Periods. Data 
judged to be impacted by major protocol deviations will be determined prior to unblinding and 
excluded per the statistical protocol deviation plan (sPDP). Statistical tabulations and analyses will 
be by randomized treatment, but data obtained after subjects receive an incorrect treatment will be 
excluded from the affected periods. 
Any evaluability criteria with a potential impact on efficacy results will be defined in an sPDP. 
The evaluability criteria will be programmatically identified in a blinded fashion aided by a review 
of data listings prior to database lock. Major protocol deviations (protocol violations), therefore, 
can result in exclusion of all data from a particular subject from the analysis population or require 
exclusion of data from a specific timepoint or treatment period and/or subsequent timepoints or 
subsequent treatment periods for an endpoint(s). Protocol deviations for exclusion of data from the 
mITT Analysis Set will be agreed by the study team and documented in the blinded data review 
meeting minutes prior to database lock. 


 
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6.3 
Safety Analysis Set 
The Safety analysis set is defined as all subjects who are randomized to treatment and receive at 
least 1 dose of the study drug. Subjects will be analyzed according to treatment received rather 
than per the randomization scheme. 
6.4 
Not-randomized Analysis Set 
The Not Randomized analysis set is defined as subjects who did not receive a randomization 
number and therefore did not receive a dose of study drug (eg, subjects who were screen failures or 
stopped participation before being randomized). 
6.5 
Analysis Sets for Analyses 
Analyses will be performed as follows: 
Demographics and baseline characteristics will be summarized for the ITT, mITT, Safety, and 
Not-randomized analysis sets. Extent of exposure will be listed for the Safety analysis set. The 
Safety analysis set will be used to summarize safety. 
Efficacy analyses will be performed for the mITT analysis set. As a sensitivity analysis, the 
primary endpoint, change from baseline in FEV1 AUC0-6, will also be analyzed using the ITT 
analysis set. 
7. 
STATISTICAL ANALYSIS 
7.1.1 
General Data Handling Rules and Definitions 
All data collected on case report forms will be provided in listings, except data collected only for 
confirmation of study entry criteria and for study administrative purposes.  If any randomized 
subject is found to not have valid documented informed consent, that subject’s data will be 
excluded from the report, except as necessary to document the error. 
Except where specified all continuous variables will be summarized with descriptive statistics (the 
number of non-missing values, mean, standard deviation, median, minimum and maximum) and 
all categorical variables will be summarized with frequency counts and percentages, by treatment. 
Missing data will be maintained as missing in the analysis datasets, unless specified otherwise.  
For variables where missing data are imputed, another analysis dataset will contain a variable with 
the imputed value.  Thus, the original variable value will be maintained as missing in 1 of the 
analysis datasets. 
All efficacy and safety parameters will be summarized by treatment (unless specified otherwise).  
Summary statistics for safety will be provided for the Safety Analysis Set, unless otherwise 
specified. 
 


 
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7.1.2 
Data Exclusion and Missing Data Imputation 
Pre-dose spirometry values will use the average of the non-missing -60 minute and -30 minute 
values.  A detailed description of the baseline value calculation is in Section 7.4.3.1.   
For the mITT analyses, FEV1 AUC0-6, FEV1 AUC0-4, and peak FEV1 will be calculated if there is 
at least 1 non-missing data point during the first 2 hours post-dose. 
Unless otherwise specified, all lung function assessments analyzed that have at least 1 effort that 
meets ATS/ERS criteria for acceptability will be considered acceptable and contribute to the post-
dose assessments.  If the PFT assessments at a specific timepoint were deemed to be of 
unacceptable quality, i.e., none of the efforts met ATS/ERS criteria for acceptability, the PFT 
assessments obtained at the timepoint will not be included in any efficacy analysis and will be 
considered missing (Miller et al. 2005).  Thus, all observed data will be included in the ITT 
Analysis Set analysis, with the exception of data at a timepoint which had unacceptable quality 
based on ATS/ERS criteria. 
7.2 
Subject Disposition 
A disposition table for all screened subjects will be provided (Table 1.1.1 and Listing 1.2).  This 
tabulation will include the number of subjects in each randomized treatment who received study 
drug, who were withdrawn prematurely, and who completed each treatment.  The number of 
subjects who completed the study will also be provided. The number and percentage of screened 
subjects who were included in the ITT, mITT,  Safety and Not Randomized Analysis Sets will also 
be tabulated (Table 1.1.1). 
A summary of reasons subjects were not randomized, as reported for inclusion/exclusion criteria 
violated, will be provided for all subjects not randomized (Table 1.1.2).  A listing of reasons 
subjects were not randomized will be provided (Listing 1.4).  Subjects discontinued from study 
drug will be withdrawn from the study.  Reasons for Premature discontinuation will be 
summarized for the ITT Analysis Set by randomized treatment (Table 1.2.1).  The number and 
percentage of subjects in the mITT and Safety Analysis Sets withdrawn for each reason for 
withdrawal will be tabulated by treatment actually received (Tables 1.2.2 and 1.2.3).    
 
The number and percentage of randomized subjects who were in each of the analysis sets will be 
tabulated for each treatment – i.e. for the set of subjects who were randomized to receive the 
treatment (Table 1.3). 
 
The reason for exclusion from the mITT Analysis Set will be tabulated by study drug for all ITT 
subjects (Table 1.4). The reasons for exclusion from the ITT and mITT Analysis Sets of a subject 
or of partial data for a subject will be listed for all randomized subjects, in addition to listing 
reasons for any subjects to have been excluded from the Safety Analysis Set (Table 1.1.3). A 
listing of subjects who did not comply with the use of rescue medication and xanthine-containing 
products (protocol deviations requiring removal of data from the mITT Analysis Set analysis) just 
prior to spirometry will be provided in Listing 6.1. Use of Ventolin HFA (hereafter referred to as 
Ventolin) at pre-dose or during the post-dose assessments on each specific test day (yes/no), will 


 
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be provided in Listing 6.4. In addition, the eligibility information (inclusion/exclusion criteria with 
any waivers granted), of all subjects who are randomized will be listed (Listing 2). Subject visits 
where the stability criteria were not met will be listed (Listing 6.2).  
If there are any subjects who took study drug other than what was randomized during the study, 
both the treatment assigned at randomization and actual treatment(s) received during the Treatment 
Period will be listed (Listing 1.3).  All data listings will show the treatment actually received. 
7.3 
Demography 
The demographic variables are age, gender, race, ethnicity, smoking status (current [a disallowed 
category], non-smoker, or former smoker), number of years smoked (for former smokers), average 
number of cigarettes smoked per day (for former smokers), number of pack years smoked (for 
former smokers), and prior asthma treatment regimen (SABA prn use only, ICS, ICS/LABA).  The 
physical characteristics variables are weight, height, and BMI (body mass index).  The data 
handling rules for age, BMI, and number of pack years smoked are described in Appendix 1. 
Subject demographics and smoking status/history will be summarized for the mITT, ITT, and 
Safety Analysis Sets and for Non-Randomized subjects (Tables 1.5.1 through 1.5.4, respectively, 
and Listing 1.2) for all subjects. 
7.3.1 
Asthma History, Screening/Baseline Spirometry, and Reversibility 
The number of months since the date of the diagnosis of asthma as shown on the Screening Visit 1 
eCRF, and determined relative to the first dose of study drug in the study (Appendix 1) will be 
summarized for the mITT and Safety Analysis Sets (Tables 1.6.1 through 1.6.2 respectively, and 
Listing 4.1). The screening and baseline spirometry variables FEV1, FEF25-75, and FVC will be 
summarized separately for Visit 1 and Visit 2 (Tables 1.7.1 and 1.7.2, respectively, for the mITT 
and ITT Analysis Sets, and Listing 6.4). For this purpose, Visit 1 will be Visit 1, 1a, or 1b, 
whichever visit had the highest FEV1 result post-dose. 
Per Protocol Section 4.1, reversibility to Ventolin (SABA) will be evaluated at Visits 1, 1a (if 
needed), or 1b (if needed) and defined as: 
x The comparison of the best FEV1 effort obtained at 30 minutes pre-bronchodilator to the best 
FEV1 effort obtained at 30 minutes post-bronchodilator following administration of Ventolin. 
A subject is considered reversible to Ventolin if the improvement in FEV1 at 30 minutes post-
Ventolin is ≥15%. 
 
See Appendix 1 for data handling rules and the formula for determination of reversibility variables. 
Reversibility to Ventolin at Screening will be summarized for the mITT and ITT Analysis Sets and 
listed (Tables 1.8.1 and 1.8.2, respectively, and Listing 3).  Also included will be a summary of the 
change in FEV1 from pre-bronchodilator to post-bronchodilator.   


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7.3.2
Medical and Surgical History at Screening, Pregnancy Testing at Screening and 
Baseline 
Medical history at Screening will be coded using the version of the Medical Dictionary for 
Regulatory Activities (MedDRA) that is current at the time of data base lock. 
Medical and Surgical History at Screening will be summarized by actual treatment for the Safety 
Analysis Set and listed for all randomized subjects (Table 1.9 and Listing 4.2).   
Pregnancy Testing Results from Screening and Baseline will be listed (Listing 4.3).
7.3.3
Prior, Concomitant, and Post-Treatment Medications/Treatments 
All prescription and over-the-counter (OTC) medications, as well as any herbal or vitamin 
supplements, taken by the subject within 30 days of Visit 1 will be recorded on the Prior and 
Concomitant Medications eCRF page.  All concomitant medications taken during the study will be 
recorded on the Prior and Concomitant Medications eCRF page. 
Coding: Verbatim medication/treatment terms coded by
 
 will be 
assigned a preferred term and an ATC (anatomic therapeutic chemical class) term using the latest 
version of the World Health Organization Drug Dictionary Enhanced and World Health 
Organization Herbal Dictionary (WHO DDE and WHO HD) available (Version: Q3; 2017 or 
later). 
Multiple ATC Assignments: If there are multiple ATC codes assigned to the same concomitant 
medication, the “primary” one based on an AstraZeneca medical evaluation will be used.   
Additional details for the definition of Prior medication/treatment, Concomitant 
medication/treatment, and Post-Treatment medication/treatment are described in Appendix 1.
Concomitant asthma and non-asthma related medications/treatments will be summarized by 
preferred term and actual treatment received for the Safety Analysis Set separately during the 
Treatment and Washout Periods (Tables 1.11.1a, 1.11.1.b, 1.11.2a, and 1.11.2b). Prior, 
concomitant, and post-treatment medications will be displayed in separate listings for Asthma and 
Other medications (Listings 4.4 and 4.5, respectively).  
Reported prior medication for asthma and other indications will be tabulated for all subjects 
(Tables 1.10.1 and 1.10.2) and listed separately (Listings 4.4 and 4.5, respectively). 
Ventolin or Pulmicort dispensing will be listed (Listing 5.1.2). 
7.3.4
Extent of Exposure to Study Drug 
A listing of treatment dosing information will be provided in Listings 5.1.1 and 5.2.  Any 
comments related to study drug or any other study comments will be listed (Listing 9.3).


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7.4
Efficacy Analyses 
Reasons for missed visits (asthma-related or not) for each subject will be listed (Listing 6.3).
Spirometry measurements will be listed (Listing 6.4). 
7.4.1
Primary Efficacy 
7.4.2
Study Day 
Study day is defined relative to the date of the first study drug administration.  Within-period study 
day, or day of assessment/event, is defined relative to the date of study drug within the period.  
Additional definitions are provided in Appendix 1.  Handling of unscheduled visits for efficacy 
endpoints is discussed in Section 7.4.3.3.
7.4.3
Time Points and Time Intervals for Efficacy Endpoints 
The definitions of several terms related to time points and time intervals for efficacy endpoints are 
given in this section. 
7.4.3.1
Baselines for Analysis 
Since pre-dose values are known to be variable and an isolated timepoint may not accurately 
reflect the true baseline, the following baseline will be used for the statistical analyses of study 
assessments unless otherwise specified: the mean of available pre-dose values on the first day of 
each treatment cycle, i.e., the mean of pre-dose values at Visits 2, 3, 4, 5, and 6, where the mean of 
the 60- and 30-minute pre-dose value for each visit is obtained and then the visit means are 
averaged. 
7.4.3.2
Change from Baseline 
Change from baseline denotes the value at a timepoint minus the value at baseline, where baseline 
was defined in the previous subsection. 
7.4.3.3
Handling of Unscheduled Visits: 
Data from unscheduled visits will not be used for efficacy analyses, but will be listed (Listing 6.4). 
7.4.3.4
Time Windows for Spirometry Assessments 
All available data with the actual timepoints (versus nominal timepoints) will be used for AUC 
calculations, determination of peak change from baseline in FEV1, re sponders analyses, onset of 
response, and offset of response. Time windows will apply only to the change from baseline in 
FEV1 by-timepoint analysis. 
  


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7.4.4
Primary Efficacy Analysis 
The primary objective of this study is to confirm the dose of albuterol delivered from AS MDI that 
is comparable to Proventil. 
The FEV1 AUC0-6 is the area under the curve for the change from baseline in FEV1 calculated 
using the trapezoidal rule. All observed data will be utilized with the trapezoidal rule to calculate 


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AUC. For the purpose of AUC calculations, the value of the spirometry parameter at time 0 will be 
the change from baseline in pre-bronchodilator FEV1 at the visit.  To aid in interpretation, all AUC 
values will be normalized by dividing the AUC by the time from the first to the last non-missing 
value (typically 6 hours).  If AUC is based on just one 1 assessment (i.e., a change from baseline 
value), that change from baseline value will be the value of the AUC (the trapezoidal rule and 
normalization will not apply as the area is 0 and the time interval is 0). 
The FEV1 AUC0-6 will be analyzed using a linear mixed model with a random subject effect.  The 
fixed effects in the model will include treatment, treatment sequence, baseline FEV1, and period. 
An ICS use subgroup analysis will be based on a linear mixed model with covariates of treatment, 
treatment sequence, baseline FEV1, period, ICS Use subgroup (ICS use at Screening and Did not 
use ICS at Screening), and treatment-by-subgroup interaction. 
The least squares (LS) mean and the standard error of this mean with the corresponding two-sided 
95% confidence interval will be provided for each treatment based on the overall study population 
and then separately within each of the 2 ICS subgroups.  The estimated treatment differences and 
95% CIs will be provided for all treatment comparisons based on the overall study population, and 
then separately within each of the 2 ICS Use subgroups. 
Superiority comparisons of AS MDI relative to Placebo MDI and Proventil versus Placebo MDI 
will be conducted first using a dose-ordered approach. A two-sided alpha level of 0.05 will be 
employed. Estimated treatment differences and 95% confidence intervals (CIs) will be provided 
for the superiority comparisons.  As described in detail in Section 4.3, the superiority of Proventil 
relative to Placebo MDI will be tested first using this dose-ordered approach. If Proventil 180 μg is 
superior to Placebo MDI, AS MDI 180 μg will be compared to Placebo MDI. If AS MDI 180 μg is 
superior to Placebo MDI, the superiority of the Proventil 90-μg dose relative to Placebo MDI will 
be tested.  If Proventil 90 μg is superior to placebo, then AS MDI 90 μg will be compared to 
Placebo MDI. 
 
 
 
. 
Comparisons among the dose levels within a product and comparisons within the ICS Use
subgroups will  be conducted for exploratory purposes. Estimated treatment differences and 95% 
CIs will be provided. 
The primary analysis will be conducted using the mITT Analysis Set.  Supportive analyses for the 
primary endpoint will be performed using the ITT Analysis Set.  Assumptions underlying the 
primary analysis will be evaluated and additional analyses may be performed (see Section 7.4.7).  


 
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Summary statistics and the results of statistical testing for  the primary endpoint  will be provided 
in Table 2.1.1 by treatment overall and for each subgroup for the mITT Analysis Set and in Table 
2.1.2 for the ITT Analysis Set. 
7.4.5 
Secondary Efficacy 
The secondary endpoints will be analyzed using a similar approach as that of the primary endpoint. 
Linear mixed models will be fit with a random subject effect. The fixed effects in the model will 
include baseline FEV1, treatment, treatment sequence, and period. 
The FEV1 AUC0-4 will be calculated in a similar manner as FEV1 AUC0-6; however, the 
trapezoidal rule will only be implemented through the 4-hour nominal timepoint. The AUC values 
will be normalized accordingly. 
The peak change from baseline in FEV1 will be calculated using the largest FEV1 value measured 
during the 6 hours post-dosing. 
Secondary efficacy endpoints will be analyzed using the mITT Analysis Set. Tables and figures 
will be as follows:  
x Change from baseline in FEV1 AUC0-4: Table 2.2.1 for the mITT Analysis Set.  
x Peak change from baseline in FEV1:  Table 2.2.2 for the mITT Analysis Set. 
 
7.4.6 
Other Efficacy 
Change from baseline in FEV1 at each post-dose timepoint will be presented graphically by 
treatment and will be analyzed using a linear mixed model with a random subject effect.  The fixed 
effects will include treatment, time point, treatment-by-time point interaction, treatment sequence, 
baseline FEV1, and period.  The covariance within subject-periods will be unstructured over the 
time points. Note that the sample sizes (N) at 180- and 300-minutes post-dose will be smaller than 
the remaining timepoints due to adjustment to the spirometry assessment schedule outlined in 
Version 2 of the protocol (See Section 8).   
The median values for time to peak FEV1 will be reported by treatment. The median differences 
and corresponding Hodges-Lehmann 95% CIs will be presented for pairwise comparisons among 
the treatments.   
The percentages of subjects achieving a 12% and 15% improvement from baseline within 30 
minutes post dose will be tabulated by treatment. Responders will be defined as subjects achieving 
≥15% (or  ≥12%) improvement in FEV1 within 30 minutes after dosing. The odds of being a 
responder will also be estimated using a generalized mixed effects model with fixed effects of 
treatment and period, and a random subject effect.  
The time to onset of response for each individual subject will be defined as the first timepoint for 
which an increase from baseline FEV1 of at least 15% (or 12%) is observed within the first 30 
minutes post dose. The median time to onset of response will be reported by treatment. The 


 
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median differences and corresponding Hodges-Lehmann 95% CIs will be presented for pairwise 
comparisons among the treatments (Han L, Paper ST-154). Only subjects who achieved the 15% 
(or 12%) improvement within the first 30 minutes post dose will be included in this analysis. 
The duration of response for each subject will be defined as the time from onset of at least a 15% 
(or 12%) increase in FEV1 to the offset of the 15% (or 12%) increase in FEV1 relative to baseline. 
If offset of response was not achieved during the assessment period, the last available time of 
assessment will be used as the offset. If a subject had a 2nd onset of response subsequent to 
achievement of offset, their data for that period will be excluded from the duration of response 
analysis. Descriptive statistics including the N, arithmetic mean, standard deviation, median, 
minimum, and maximum for duration of response will be reported by treatment. The duration of 
response will be analyzed using a linear mixed effects model similar to that of the primary 
endpoint or a distribution-free method (Hodges-Lehmann) as appropriate to the data. As an 
additional sensitivity analysis to assess potential bias imposed by the limited spirometry sampling 
scheme of protocol Version 1.0, the duration of response analysis will be repeated excluding those 
subjects who are missing the 180- and 300-minute post timepoints. 
The other efficacy endpoints will be analyzed using the mITT Analysis Set. Tables and figures will 
be as follows. 
x Change from Baseline in FEV1 at each post-dose timepoint: Table 2.3.1 and Figures 2.3.1.1 
and 2.3.1.2 for the mITT Analysis Set.  
x Time to peak FEV1: Table 2.3.2 for the mITT Analysis Set.  
x Percentage of subjects achieving 12% improvement in FEV1 from baseline within 30 minutes 
of dose: Table 2.3.3 for the mITT Analysis Set.  
x Percentage of subjects achieving 15% improvement in FEV1 from baseline within 30 minutes 
of dose: Table 2.3.3 for the mITT Analysis Set.  
x Time to onset of response: Table 2.3.4 and Table 2.3.5 for the 12% Improvement in FEV1 and 
the 15% Improvement in FEV1, respectively, for the mITT Analysis Set.  
x Duration of response: Tables 2.3.6, 2.3.7, 2.3.8, and 2.3.9 for the 12% Improvement in FEV1, 
12% Improvement in FEV1 in subjects who have assessments at the 180- and 300-minute post-
dose timepoints, 15% Improvement in FEV1, and 15% Improvement in FEV1, in subjects who 
have assessments at the 180- and 300-minute post-dose timepoints, respectively, for the mITT 
Analysis Set.  
 
7.4.7 
Data Validation and Transformation 
In general, the distribution of spirometry measures is well approximated by a normal distribution. 
Under some circumstances, however (eg, during an exacerbation unrelated to treatment), extreme 
and atypical values can arise. Such values have high influence on estimation of variance 
parameters and on standard errors of fixed effect estimates. The distribution of scaled marginal 
residuals, and influence statistics will be examined to identify such cases. In the event that a single 
or small number of such outlying values are found to exist and found to be highly influential, the 


 
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effects may be ameliorated by either transformation or removal of the outlier. Transformations to 
be considered may include the logarithmic transformation or normal rank transformations. Where 
outliers are removed, sensitivity analyses including those values will be reported. 
The assumption of normality in the primary, secondary, and other efficacy endpoints, Change from 
Baseline in FEV1 AUC0-6, Change from Baseline in FEV1 AUC0-4, Peak change from baseline in 
FEV1, and duration of response will be checked by visually inspecting the distribution of the 
scaled (decorrelated) residuals.  Also, model fit and the assumption of homogeneity of variance 
among treatments will be verified by inspection of scatter plots of predicted vs. residuals, residuals 
vs. treatment, and by box plots of residuals for treatment.  Plots for scaled (marginal) residuals will 
be prepared using option=VCIRY on the model statement and the ODS graphics option.  If the 
assumption of homogeneity does not hold (sample variances appear heterogeneous), then the final 
model will be fit with an UN or CSH covariance structure. (Appendix 3). 
Changes in spirometry measures from baseline, and from timepoint to timepoint will be examined 
graphically before database lock, and before unblinding, as part of data quality management. 
7.5 
Safety Analyses 
All safety analyses are based on Safety Analysis Set.  Hypothesis testing will not be performed for 
any safety analyses.  No formal statistical analysis of safety data is planned. Safety data will be 
summarized by treatment and listed. 
7.5.1 
Adverse Events 
Adverse events will be collected and coded using the latest version (20.1 or later) of the MedDRA 
available.  A glossary of MedDRA preferred terms used for AEs reported in the study along with 
the associated Investigator’s verbatim will be provided in Listing 7.2.  The version of MedDRA 
current at the time of database lock will be used for the final analysis of data. 
Adverse events occurring from the time the subject signs informed consent until the subject is 
randomized will be summarized as medical history and not as an AE unless the event meets the 
definition of an SAE as defined in Protocol Section 6.2. 
An adverse event is considered treatment-emergent if the date of onset is on or after the date of 
first dose of study drug in the study.  An AE would be considered attributable to a treatment 
(corresponding to a treatment period or washout or final follow-up period) if the onset of the AE 
was during a treatment period (or washout period or final follow-up period).  Should there not be 
sufficient information to determine during which period that an AE started, the AE will be counted 
as having occurred in all treatment periods (and washout periods or final follow-up period) prior to 
the end date of the AE if this is reported as long as the subject received study drug during those 
treatment periods.  If both start and end date of an AE are unavailable, the AE will be counted in 
all treatment periods prior to the date of last contact on the End of Treatment eCRF (including the 
treatment taken on the day of the last contact) as long as the subject received study drug during 
those treatment periods.  Any AE with onset after the last treatment in the study will be attributed 
to this last treatment.  Adverse events after the Follow-up Telephone Call scheduled 3-7 days after 


 
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Visit 6 or a discontinuation visit will not be considered treatment-emergent, but will be listed in 
adverse event data listings. 
Counting Rules for Adverse Events with Onset in a Treatment Period or Washout Period (or 
Follow-up Period): 
 A subject with more than 1 different AE in a particular system organ class (SOC) will be 
1.
counted only once in the total of subjects experiencing AEs in that particular SOC. 
 A subject having experienced the same event (AE preferred term) more than once will be 
2.
counted only once in the number of subjects with that event. 
 
Events with Irregular Start Dates: All adverse events will be included in the tabulations 
regardless of the completeness of the onset dates.  
Missing/incomplete (partial) AE start and end dates will not be imputed for data listings. 
Both the treatment and the washout periods include treatment with Pulmicort Flexhaler if subjects 
were previously on an ICS prior to the start of the study. Additionally, the washout periods 
included treatment with Ventolin.  AEs reported as starting during a Washout Period or the final 
follow-up period will be excluded from the main analyses of AEs.  As a supportive analysis, AEs 
will be assigned to the last randomized treatment received including those occurring during the 
Washout Period (Table 3.2.2 for AEs and Table 3.6.2 for SAEs). 
 
All adverse events, whether treatment-emergent or not, will be included in the listings.  Reported 
adverse events by system organ class, preferred term, treatment, center, subject, and onset day will 
be provided (Listing 7.1).  Reported adverse events by treatment, center, subject, and onset date 
will also be provided (Listing 7.3). 
The listing of adverse events will provide the severity, maximum severity, relationship to study 
drug, action taken and outcome for each adverse event. Any SAEs reported will be listed (Table 
3.7.1 for the treatment period analysis not including the washout and follow-up period and Table 
3.7.2 for the analysis including all AEs including those with onset during the washout or follow-up 
period after the treatment period). Suspect drug assessment data associated with an SAE (collected 
on the Suspect Drug Assessment CRF) will be listed by SAE (Listing 4.6). Adverse events leading 
to discontinuation of study drug will be listed (Table 3.5). A listing of any reported deaths during 
the study will be provided (Table 3.10); the study drug taken most recently prior to the death and 
the number of days since the dose of this study drug at the time of the death will be included in the 
listing.  
 
An overview summary table will be prepared.  The table will provide the incidences of subjects, 
for all subjects and for each treatment, with the following: at least 1 treatment-emergent adverse 
event, at least 1 treatment-emergent related adverse event, at least 1 treatment-emergent serious 
adverse event, at least 1 treatment-emergent serious related adverse event, at least 1 treatment-
emergent adverse event leading to study drug discontinuation and premature study withdrawal, and 


 
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a report of death (Table 3.1.1, washout TEAEs excluded).  As a supportive analysis, AEs will be 
assigned to the last randomized treatment received including those occurring during the washout 
period or the final follow-up period (Table 3.1.2). 
The incidence of an adverse event (AE) for a treatment will be defined as the number and percent 
of subjects experiencing an event attributable to that treatment.  For each group, the following will 
be prepared for each treatment and for overall, for each primary system organ class, and for each 
preferred term within a system organ class: 
 The incidence of all treatment-emergent adverse events (Table 3.2.1) 
1.
 The incidence of non-serious treatment-emergent adverse events occurring in ≥5% of subjects 
2.
in a treatment (Table 3.2.4) 
 The incidence of all treatment-related treatment-emergent adverse events (Table 3.3) 
3.
 The incidence of treatment-emergent adverse events leading to study drug discontinuation 
4.
(Table 3.4) 
 The incidence of treatment-emergent serious adverse events (Table 3.6.1) 
5.
 The incidence of treatment-emergent serious related adverse events (Table 3.8) 
6.
 The incidence of all treatment-emergent adverse events by highest severity (Tables 3.9.1-
7.
3.9.5).  There will be a separate table for each treatment. 
 The incidence of treatment-emergent adverse events occurring in at least 2% of subjects in any 
8.
treatment (Table 3.2.3, sorted by descending frequency of events in a preferred term). 
 
7.5.2 
Clinical Laboratory Data 
Clinical safety laboratory tests will be collected at Visit 1, Visit 6 (post-dose) and during a 
Premature Discontinuation Visit, if applicable. Laboratory tests will be analyzed by a central 
laboratory according to standardized, validated assays.  The following clinical laboratory 
parameters that will be assessed are noted in Table 5. 
Table 5 
Lab Parameters 
Hematology 
Hemoglobin  
Mean corpuscular hemoglobin (MCH) 
Hematocrit  
Mean corpuscular hemoglobin concentration (MCHC) 
White Blood Cell count with differential  
Mean corpuscular volume (MCV) 
Red Blood Cell count  
 
Platelet Count  
 
Clinical Blood Chemistry 
Liver Enzyme and Other Function Tests 
Other Clinical Blood Chemistry 
Alanine aminotransferase (ALT)  
Albumin 
Aspartate aminotransferase (AST)  
Blood urea nitrogen (BUN)a 
Alkaline phosphatase  
Calciuma 


 
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Bilirubin, total  
Chloridea 
Gamma-glutamyl transferase  
Cholesterol  
 
Bicarbonate 
 
Creatininea 
 
Glucosea 
  
Magnesium  
 
Potassiuma 
 
Phosphate 
 
Protein, total  
 
Sodiuma 
 
Triglycerides  
 
Urea 
Other Tests: 
Pregnancy test (women of child-bearing potential only): serum (human chorionic gonadotropin [hCG]) at Visit 1, and 
urine HCG before randomization at Visit 2, as detailed in Table 1 
Creatinine clearance will be estimated by the central laboratory at Screening only using eGFR (estimated glomerular 
filtration rate) using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) published formula. 
a 
Parameters included in the Basic Metabolic Panel (BMP). 
 
Clinically Significant Laboratory Abnormalities as identified by the investigator after the start 
of study drug will be recorded as an Adverse Event and tabulated as an AE in the AE analysis.  
Abnormalities occurring prior to the start of treatment will be noted in medical history and 
presented in a data listing.  Per protocol, the criteria for a "clinically significant" laboratory 
abnormality are: 
a. A laboratory abnormality that leads to study drug dose suspension or discontinuation 
b. A laboratory abnormality that results in any therapeutic intervention (i.e., concomitant 
medication or therapy) 
c. Any other laboratory abnormality judged by the Investigator to be of any particular clinical 
concern (eg., significant fall in hemoglobin not requiring transfusion) 
 
For laboratory abnormalities that do not meet the above criteria but are outside of the normal 
reference range, the investigator should indicate whether the value is clinically significant or not 
clinically significant for the subject. 
All laboratory data will be stored in the database with the units in which they are originally 
reported.  Laboratory data in subject data listings will be presented in the International System of 
Units (SI units; Système International d’Unités) where available.  Laboratory data not reported in 
SI units will be converted to SI units before further processing or data analysis. Individual clinical 
laboratory variables for hematology and clinical chemistry, including creatinine clearance (eGFR), 
will be provided in listings (Listing 8.1 for central laboratory hematology, Listing 8.2 for central 


 
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laboratory blood chemistry and kidney function, and Listing 9.3 for pregnancy test results after the 
start of treatment).  Comments for central laboratory testing will be listed (Listing 8.3).  For 
listings, laboratory values will be flagged as Low or High based on the reference ranges provided 
by the central laboratory, Covance.  These flags along with the reference ranges will be provided 
in the laboratory data listings. 
7.5.3 
Vital Signs 
A Clinically Significant Abnormality in vital signs identified by the investigator will be recorded 
as an Adverse Event if it occurs after the start of treatment.  These adverse events will be included 
in the AE summaries; abnormalities prior to the start of treatment will be noted in medical history 
and listed.  
Potentially clinically significant changes in systolic blood pressure (SBP), diastolic blood 
pressure (DBP), and Heart Rate will be defined based on the following criteria provided by 
AstraZeneca: 
Table 6 
Potentially Clinically Significant Criteria for Systolic and Diastolic Blood 
Pressure Parameters and Heart Rate 
Parameter (mmHg) 
Post-Baseline Criteria 
SBP, increase 
≥180 and increase from baseline ≥20  
SBP, decrease 
≤90 and decrease from baseline ≥20 
DBP, increase 
≥105 and increase from baseline ≥ 15 
DBP, decrease 
≤50 and decrease from baseline ≥ 15 
Tachycardia Event 
≥ 110 bpm and increase ≥ 15% from baseline 
Bradycardia Event 
≤ 50 bpm and decrease ≥ 15% from baseline 
 
Vital signs, height, weight, BMI, SBP, DBP, and Heart Rate will be listed (Listing 9.1). 
Baseline is defined as the last pre-dose measurement taken prior to dosing on Day 1 of a treatment 
period. 
 
Change from baseline for a timepoint of a Treatment Period is defined as the vital sign value for 
the timepoint minus the baseline value. 
 
For summaries by timepoint, the latest vital sign value (in the case of multiple values) for a 
scheduled post-baseline timepoint on a scheduled visit for a Treatment Period will be employed.   
Descriptive statistics (mean, median, standard deviation, and range) for change from baseline will 
be tabulated by vital sign parameter and treatment for each scheduled assessment time. 


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Summary statistics (n, mean, median, standard deviation, minimum and maximum) of scheduled 
pre-dose and post-dose values as well as changes from baseline for each vital sign parameter will 
be tabulated by treatment (Table 3.11.1).  Values will not be allocated across Treatment Periods.   
7.5.4
Electrocardiogram (ECG) 
A Clinically Significant Abnormality for a 12-Lead ECG measurement identified by the 
investigator as a clinically significant abnormality will be recorded as an Adverse Event if it 
occurred after the start of study drug.  These adverse events will be included in the AE summaries.
The ECG parameters that will be assessed include heart rate (HR), RR interval, PR interval, QRS 
axis, QRS interval, QT interval, and QTcF (Fridericia’s Formula) interval.  The QTcF (Fridericia 
Corrected QT) is defined as [QT/(RR1/3)]. 
All 12-Lead ECG measurements for the Safety Analysis Set will be listed (Listing 9.2).  
7.5.5
Physical Examination 
Any physical examination abnormality reported after the start of treatment for a subject is to be 
reported as an adverse event and included in the AE summaries. 
8.
CHANGES FROM METHODS PLANNED IN THE PROTOCOL  
The protocol was amended on 12 January 2018 to include spirometry assessments (180 and 300 
minutes post-dose) that were inadvertently omitted from Version 1 of the protocol. Subjects 
randomized after this amendment have spirometry assessments at 180 and 300 minutes in addition 
to the timepoints outlined in Version 1 of the protocol,
. All subjects will be included in the efficacy 
analyses irrespective of their spirometry sampling scheme. 
The protocol specified that the baseline for vital signs analyses would be the average of the vital 
sign values taken prior to dosing on the day of randomization.  Since multiple values were not 
scheduled to be collected at randomization and since each treatment visit had vital signs 
measurements taken prior to dosing (under the condition that restricted asthma medications were 
not to be taken within 6 hours of test day assessments), the baseline for vital signs has been 
updated as follows: Baseline is defined as the last pre-dose measurement taken prior to dosing on 
Day 1 of a treatment period. 
9.
STATISTICAL SOFTWARE 
Data processing, statistical screening, descriptive reporting, and analysis of the efficacy and safety 
data will be performed using SAS (Version 9.4 or higher). 


 
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10. 
REFERENCES 
Miller et al 2005.  Miller MR, Hankinson J, Brusasco V, et al. Standardisation of spirometry. Eur 
Respir J 2005;26(2):319-338. 
Han L, Calculating the point estimate and confidence interval of Hodges-Lehmann's median using 
SAS® software. Southeast SAS® Users Group (SESUG) 2008; Paper ST-154.   
 
 
 


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APPENDIX 1 DATA HANDLING RULES 
Programming of the tables, listings and figures will be performed using SAS Version 9.4 or a more 
recent version.  The following table presents algorithms (not stated elsewhere) to be used in SAS 
to calculate the derived variables, including rules for handling missing data or partial dates, or 
irregular/unexpected data issues. 
Category
Description
Data Handling Rules
Pulmonary 
Function 
Testing Data 
data transferred
x
Only data of rank =1 (best effort) will be 
transferred; data transferred will be grade 1 = 
acceptable, grade 2 = borderline, or grade = 3
(unacceptable).  Only data of grade = 1 or 
grade = 2 will be included in baseline or 
on-treatment spirometry calculations.
x
All data transferred from 
. (grade = 1, 2, or 3) will be 
listed in data listings with the grade.
Age (years) 
Age (years)
Age = integer part of ((Visit 1 date – Birth date + 
1)/365.25)
Smoking 
History 
Number of pack years 
smoked
Number of pack years smoked = (number of 
cigarettes per day/20) x number of years smoked.  
It is zero if the number of years smoked is zero or 
if the subject is a non-smoker.
BMI
Body Mass Index
BMI = (weight(kg))/(height(cm)/100)2
Asthma History
Months Since Diagnosis
Months Since Diagnosis = (Date of First Dose of 
Study Drug in the study – Date Asthma First 
Diagnosed)/30.475.
Missing Date Asthma First 
Diagnosed
Day of Diagnosis will be imputed for all subjects 
as the 1st of the month.  
Missing month of Date 
Asthma First Diagnosed
Missing month of Diagnosis will be imputed as 
June, or the month in which 1st will be the latest
before informed consent date, whichever is 
earliest.
Medical 
History  
Medical History Begin 
Date of Condition
Missing month of Condition will be imputed as 
June, or the month in which 1st will be the latest 
before informed consent date, whichever is 
earliest.  Begin date of Condition will be imputed 
for all subjects as the 1st of the month.


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Category
Description
Data Handling Rules
Medical History End Date 
of Condition
Other than for ‘Ongoing’ conditions, missing 
month of End Date of Condition will be imputed 
as June, or the month in which 1st will be the 
latest before informed consent date, whichever is 
earliest.  End date of Condition will be imputed 
for all subjects as the 1st of the month.
Surgical 
History  
Surgical History Date of 
Surgery
Missing month of Surgery will be imputed as 
June, or the month in which 1st will be the latest 
before informed consent date, whichever is 
earliest.  Begin date of Surgery will be imputed 
for all subjects as the 1st of the month.
Screening 
Reversibility
Screening Percent 
Reversibility
The screening percent reversibility to Ventolin is 
100 x [post-Ventolin FEV1 – pre-Ventolin  
FEV1)]/ [pre-Ventolin FEV1].
For this definition, “post-Ventolin FEV1” and 
“pre-Ventolin FEV1” are the best effort values 
obtained after the dose of Ventolin and before the 
dose of Ventolin, respectively.  
First and Last 
Treatment 
Dates
Date/time of first dose of 
the first study drug taken 
in the study and the 
date/time of the last dose 
of the last study drug taken 
in the study.
The date and time (24 hr. clock) of the dose of 
study drug will be taken from the Study Drug 
Administration eCRF.  The time of the last dose 
of study drug will be the last time of dosing from 
the 
 dataset.
Last Visit Date
Date of Last Visit
Date of last Visit according to the Visit eCRF.
Last Study 
Participation 
Date (STDM 
variable, 
RFPENDTC)
Last Study Participation 
Date (STDM variable, 
RFPENDTC)
Last study participation date is defined as last 
known date of contact which would be the later 
of the following dates: last visit date, date of the 
last dose, date of last contact if lost-to-follow-up,
date of telephone follow-up, or death date.  
Study Day
Definitions 
Study Day for 
assessment/event which 
occurs on or after the date 
of a study drug
Study Day = Date of assessment/event – date of 
the dose of study drug + 1.
Within-Period Study Day 
for an on-treatment 
assessment/event study 
Within-Period Study Day = Date of 
assessment/event – date of dose of study drug
within the respective Treatment Period + 1.


 
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Category 
Description 
Data Handling Rules 
drug 
Study Day for 
assessments/events on 
days prior to the dose of 
the first study drug in the 
study 
Study Day = date of assessment/event - dose date 
of treatment in the study. 
Study Day Post-
Treatment of Assessment 
or event which occurs after 
a study drug 
Study Day = ‘P’ concatenated with the number of 
days post-treatment that the assessment or event 
occurred which is defined as Date of 
assessment/event – date of dose of study drug in 
the last period (i.e. most recent treatment). 
Study Day of 
Randomization 
Study Day of Randomization = date of 
randomization – date of the first dose of study 
drug in the study if date of randomization is 
before date of first dose of study drug.  Study 
Day is 1 if the day of first study drug in the study 
is on the day of randomization. 
First Dose Date 
First Dose Date in the study is defined as the 
date of the first dose of study drug in the study. 
Last Dose Date 
Last Dose Date in the study is defined as the 
date of the last dose of study drug in the study 
(defined as the last date of dosing from the Study 
Drug Administration eCRF). 
Last Study Day  
For subjects who did not receive study drug in 
the study (e.g., Non-Randomized Subjects), 
Last Study Day is defined as (the later of the last 
visit date or the date of last contact for subjects 
lost-to-follow-up from the End of Treatment 
eCRF) – Date of Screening Visit + 1.  
For subjects who received study drug in the 
study, Last Study Day is defined as (the later of 
the last visit date or the date of last contact for 
subjects lost-to-follow-up from the End of 
Treatment eCRF) – first dose date in the study + 
1. 


 
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Category 
Description 
Data Handling Rules 
Days Since Last Dose for 
event (e.g., Death) 
Days Since Last Dose is defined as date of event 
– date of last dose of study drug. 
Treatment Day 
Treatment Day 1 is the study day of the dose of a 
study drug.  
Treatment 
Period 
Treatment Period 
A treatment period for a treatment is the date of 
the dose of the treatment (Treatment Day 1 of a 
treatment) 
Duration of 
Event 
The duration of any event 
(not including duration of 
asthma) 
The duration of any event is defined as (stop date 
– start date + 1). 
Duration of 
Asthma 
Duration of asthma 
(months) 
The duration of asthma = (first dose date of study 
drug – date asthma first diagnosed)/30.475, 
where the day of asthma diagnosed is assumed to 
be the 1st of the month.  
Multiple 
Assessments for 
the Same Visit 
Vital Signs assessments 
x All data will be listed in data listings. 
x The last non-missing assessment of multiple 
valid assessments within a pre-dose or post-
dose study time window will be used for 
summaries 
Spirometry 
Assessments 
Spirometry assessments 
x The last of multiple valid assessments within 
a post-baseline study time window will be 
used for summaries and statistical testing, 
except for AUC parameters, where all post-
baseline assessments in the study time 
window will be used. 
Tine to onset of 
response 
Time to onset of response 
Time to Onset of Response (minutes) = (time of 
first achievement of a ≥ 15% (or 12%) increase in 
FEV1 from baseline, within 30 minutes of dose – 
treatment administration time). 
Time to offset 
of response 
Time to offset of response 
Time to Offset of Response:  For responders 
only:  (time of first assessment  after achievement 
of response for which the increase from baseline 
in FEV1 is < 15% (or 12%) – treatment 
administration time). If offset of  FEV1 < 15% 
(or 12%) is not achieved and the last available 


 
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Category 
Description 
Data Handling Rules 
assessment is ≥ 15% (or 12%), the time to offset 
will be defined as (the time of the last available 
assessment – treatment administration time 
Duration of 
response 
Duration of response 
Duration of Response = time of offset of 
Response – time of onset of Response 
Special Lab 
Value Handling  
Lab values with a prefix 
such as: ‘>’, ‘<’, ‘+’ and 
‘Less than’ etc… 
 
x ‘>’: use the available original value +0.001 in 
the analyses. 
x ‘<’: use the available original value –0.001 in 
the analyses. 
x ‘+’: use the available original value without 
the prefix in the analyses. 
x ‘>=’: use the available original value in the 
analyses. 
x ‘<=’: use the available original value in the 
analyses. 
Prior, 
Concomitant, 
and Post-
treatment 
Medication/ 
Treatment 
Prior, concomitant, and 
post-treatment 
medication/treatment 
1. Prior medication/treatment is any 
medication/treatment taken prior to Visit 1, 
even if this medication continued after Visit 
1.  A medication/treatment will be considered 
prior if: 
a. The start and end date of the 
medication/treatment are missing, or 
b. The start date is missing and the end date 
is on or after Visit 1, or 
c. Either the medication/treatment start date 
or end date or both are before Visit 1.  
2. Concomitant medication/treatment is any 
medication/treatment taken on or after Visit 
1and on or before the date prior to the last 
dose of study drug for the subject.  A 
medication/treatment will be identified as 
concomitant if: 
a. Medication/treatment start date is after 
Visit 1 to the date prior to the last dose of 
study drug, or 
b. The end date is after Visit 1 to the date 
prior to the last dose of study drug for the 
subject, or 


 
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Category 
Description 
Data Handling Rules 
c. ‘Ongoing’ is checked. 
3. A medication with an onset date on or after 
the last dose of study drug for the subject will 
not be considered concomitant, but will be 
considered a Post-Treatment 
medication/treatment. 
4. Any medication/treatment which cannot be 
identified as Prior, Concomitant, or Post-
Treatment will be considered as being in each 
of the categories that are possible from the 
available information. 
Adverse Event 
Missing severity 
For the AE summary by severity, an AE with 
missing severity will be deemed as Severe.  
Imputed values will not be listed in data listings. 
Missing relationship to 
study drug 
For AE summary by relationship, an AE with a 
missing relationship to study drug (yes/no) will 
be deemed as Related.  Imputed values will not 
be listed in data listings.  
Treatment-emergent 
adverse event 
An adverse event is considered treatment-
emergent if the date of onset is on or after the 
date of first dose of study drug.  The study site 
will enter a new onset date when there is an 
increase in severity or intensity for a pre-existing 
event after the start of a study drug. 
If the AE start date is partial/missing, then 
x If AE start date is completely missing, then 
the AE is considered as treatment emergent. 
x If both AE start month and day are missing 
and AE start year is the same or after the first 
dose year, then the AE is considered as 
treatment emergent. 
x If AE start day is missing and AE start year 
and month are the same or after the first dose 
year and month, then the AE is considered as 
treatment emergent. 
Missing/incomplete (partial) AE start and end 


 
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Category 
Description 
Data Handling Rules 
dates will not be imputed for data listings. 
Exposure 
(days) 
Exposure (days) 
(Treatment Duration) 
Exposure is defined as the number of days at 
which doses were administered.   
Hard Coding 
Hard coding for data 
analysis 
Hard Coding is not allowed during data analysis 
unless it is agreed to in writing by AstraZeneca. 
 


 
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APPENDIX 2 ANALYSIS DATASET SPECIFICATIONS  
Analysis datasets will be built to gain efficiency and ensure consistency in data analyses and 
presentation for this trial.  The specifications for each analysis data set will be prepared separately 
and will not be a part of this SAP. 


 
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APPENDIX 3 SAS CODE FOR STATISTICAL ANALYSES 
Test 
Template SAS Code for Modeling (SAS Version 9.4) 
 
Linear Mixed 
Model analysis 
for a continuous 
efficacy 
endpoint, change 
from baseline in 
AUC0-6, change 
from baseline in 
AUC0-4, or Peak 
Change from 
Baseline in 
FEV1.  Use this 
code for the 
analysis of the 
primary and 
secondary 
endpoints.   
PROC MIXED PLOTS (ALL) METHOD=REML; 
   CLASS SUBJECT PERIOD TRT SEQUENCE ; 
   MODEL Y = BASE PERIOD TRT SEQUENCE      
                         /   DDFM=KENWARDROGER SOLUTION VCIRY 
OUTP=OUT; 
   RANDOM SUBJECT; 
   LSMEANS TRT / PDIFF CL ALPHA=0.05  
                       CORR COV; 
   ODS OUTPUT LSMEANS=MEANS; 
  ODS OUTPUT DIFFS=DIFF; 
RUN; 
 
Where BASE is the baseline value of the endpoint and TRT is the 
treatment. 
 
THE PLOTS (ALL) OPTION FOR PROC MIXED WILL BE USED 
TO GET PLOTS TO PERFORM MODEL DIAGNOSTICS (for 
normality and heterogeneity of variance).  Scaled residuals will be used. 
Influence statistics will be requested.  
 
If the assumption of homogeneity does not hold (sample variances 
appear heterogeneous), the following will replace the Random subject 
and ODS statements above.  
  REPEATED TRT / TYPE=UN (or CSH)      
SUBJECT=SUBJECT;   LSMEANS TRT / PDIFF CL ALPHA=0.05 
CORR COV;   
   ODS OUTPUT LSMEANS=MEANS; 
   ODS OUTPUT DIFFS=DIFF; 
 
Linear mixed 
effects model for 
a continuous 
efficacy 
endpoint 
involving 
multiple 
measures per 
period.  Use this 
PROC MIXED PLOTS (ALL) METHOD=REML; 
   CLASS SUBJECT PERIOD TRT SEQUENCE ; 
   MODEL Y = BASE PERIOD TRT TIMEPOINT TRT*TIMEPOINT 
SEQUENCE      
                         /   DDFM=KENWARDROGER SOLUTION VCIRY 
OUTP=OUT; 
   RANDOM SUBJECT; 
   REPEATED TIMEPOINT / TYPE=UN SUBJECT=SUBJECT; 
   LSMEANS TRT*TIMEPOINT  / PDIFF CL ALPHA=0.05  


 
Statistical Analysis Plan 
Protocol No. PT007001 
Last Revision Date: 13 Mar 2018 
(Page 44 of 48) 
 
Confidential and Proprietary 
code for the 
Other Efficacy 
parameter 
Change from 
Baseline in FEV1 
at each post-dose 
timepoint at 5, 
15, 30, 45, 60, 
120, 180, 240, 
300, and 360 
Minutes Post 
Dose.  
                       CORR COV; 
   ODS OUTPUT LSMEANS=MEANS; 
  ODS OUTPUT DIFFS=DIFF; 
RUN; 
 
Where BASE is the baseline value of the endpoint and TRT is the 
treatment. 
 
One model includes all time points. 
Generalized 
mixed effects 
model for an 
other efficacy 
categorical 
endpoint, 
percentages of 
subjects 
achieving a 12% 
and 15% 
improvement 
from baseline 
within 30 
minutes post 
dose.   
PROC GLIMMIX METHOD=QUAD; 
    CLASS TRT(REF=FIRST) PERIOD SUBJECT; 
   MODEL Y=TRT PERIOD / DIST=BIN LINK=LOGIT; 
   RANDOM INT / SUBJECT=SUBJECT; 
   LSMEANS TRT / DIFF OR; 
RUN; 
 
Where TRT is the treatment. 
 
Non-parametric 
descriptive 
statistics and 
CI’s of the 
treatment 
differences for 
Time to Peak 
FEV1, Time to 
onset of 
response, and 
Duration of 
response (as 
appropriate) 
 
The following macro can be used to calculate the point estimate and 
confidence interval of the Hodges-Lehmann's median for paired data 
(Han L, Paper ST-154): 
%macro HL_paired(dsn=, trt1=, trt2=, alpha=); 
***   STEP 1:  Calculate the differences between each pair of treatments  
for each subject and record the sample size as a macro variable for later 
use.  Note that the macro only calculates differences for 2 treatments so 
repeat this macro as needed.  
DATA ONE; SET &DSN; 
CALL SYMPUT('SIZE',TRIM(LEFT(_N_))); 
DIFF=&TRT1-&TRT2; 
RUN; 


 
Statistical Analysis Plan 
Protocol No. PT007001 
Last Revision Date: 13 Mar 2018 
(Page 45 of 48) 
 
Confidential and Proprietary 
 
***  STEP 2:  Use ARRAY to form all possible ordered pairs of 
differences and average values; 
PROC TRANSPOSE DATA=ONE OUT=TWO(DROP=_NAME_); 
VAR DIFF; 
RUN; 
DATA THREE; SET TWO; 
ARRAY X{&SIZE} COL1-COL&SIZE; 
DO I=1 TO &SIZE; 
DO J= I TO &SIZE; 
STAT=(X{I}+X{J})/2; 
OUTPUT; 
END; 
END; 
 
***  STEP 3:  Calculate the point estimate of the Hodges-Lehmann 
median difference; 
PROC SORT DATA=THREE; 
BY STAT; 
RUN; 
PROC MEANS MEDIAN NOPRINT; 
VAR STAT; 
OUTPUT OUT=EST(DROP=_FREQ_ _TYPE_) 
MEDIAN=ESTIMATE; 
RUN; 
 
***  STEP 4:  Calculate the confidence interval of the Hodges-Lehmann 
median difference; 
DATA FOUR; 
LOWORD=1+INT(&SIZE*(&SIZE+1)/4 + PROBIT(&ALPHA/2) 
*SQRT(&SIZE*(&SIZE+1)*(2*&SIZE+1)/24)); 
UPPORD= CEIL(&SIZE*(&SIZE+1)/4 + PROBIT(1-&ALPHA/2) 
*SQRT(&SIZE*(&SIZE+1)*(2*&SIZE+1)/24)); 
RUN; 
DATA FIVE; SET THREE END=LAST; 
IF _N_=1 THEN SET FOUR; 
RETAIN LOWER UPPER; 
IF _N_=LOWORD THEN LOWER=STAT; 
IF _N_=UPPORD THEN UPPER=STAT; 
IF LAST THEN OUTPUT; 
KEEP LOWER UPPER; 
RUN; 
 


 
Statistical Analysis Plan 
Protocol No. PT007001 
Last Revision Date: 13 Mar 2018 
(Page 46 of 48) 
 
Confidential and Proprietary 
***  STEP 5:  Put the point estimate and confidence into one dataset; 
DATA HL_EST; MERGE EST FIVE; 
RUN; 
%MEND HL_PAIRED; 
Linear mixed 
effects model for 
duration of 
response 
parameters when 
a parametric 
analysis is 
appropriate 
(Hodges-
Lehmann code 
below when a 
non-parametric 
analysis is 
appropriate) 
PROC MIXED PLOTS (ALL) METHOD=REML; 
   CLASS SUBJECT PERIOD TRT SEQUENCE ; 
   MODEL Y = BASE PERIOD TRT SEQUENCE      
                         /   DDFM=KENWARDROGER SOLUTION VCIRY 
OUTP=OUT; 
   RANDOM SUBJECT; 
   LSMEANS TRT / PDIFF CL ALPHA=0.05; 
   ODS OUTPUT LSMEANS=MEANS CORR COV; 
  ODS OUTPUT DIFFS=DIFF; 
RUN; 
 
Where BASE is the baseline value of the endpoint and TRT is the 
treatment. 
Descriptive 
statistics for 
Percentage of 
subjects 
achieving 12% 
improvement in 
FEV1 from 
baseline within 
30 minutes of 
dose and 
Percentage of 
subjects 
achieving 15% 
improvement in 
FEV1 from 
baseline within 
30 minutes of 
dose 
PROC FREQ; 
   TABLES Y / OUT=FREQCOUNT SPARSE; 
   BY TRT; 
RUN;   
 
Where TRT is the treatment. 
 
Linear Mixed 
Model analysis 
for a continuous 
efficacy 
endpoint, change 
PROC MIXED PLOTS (ALL) METHOD=REML; 
   CLASS SUBJECT PERIOD TRT SEQUENCE ; 
   MODEL Y = BASE PERIOD TRT SEQUENCE     
                         SUBGROUP TRT*SUBGROUP   
       /   DDFM=KENWARDROGER VCIRY SOLUTION OUTP=OUT; 


 
Statistical Analysis Plan 
Protocol No. PT007001 
Last Revision Date: 13 Mar 2018 
(Page 47 of 48) 
 
Confidential and Proprietary 
 
 
 
from baseline in 
AUC0-6, change 
from baseline in 
AUC0-4, or Peak 
Change from 
Baseline in 
FEV1.  Use this 
code for the 
subgroup 
analysis of the 
primary and 
secondary 
endpoints.   
   RANDOM SUBJECT; 
   LSMEANS TRT|SUBGROUP / PDIFF CL ALPHA=0.05  
      CORR COV; 
   ODS OUTPUT LSMEANS=MEANS; 
   ODS OUTPUT DIFFS=DIFF; 
RUN; 
 
Where BASE is the baseline value of the endpoint, TRT is the 
treatment, and SUBGROUP is 1=ICS Use at Screening and 2=No ICS 
Use at Screening 
 
THE PLOTS (ALL) OPTION FOR PROC MIXED WILL BE USED 
TO GET PLOTS TO PERFORM MODEL DIAGNOSTICS (for 
normality and heterogeneity of variance).  Scaled residuals will be used. 


 
Statistical Analysis Plan 
Protocol No. PT007001 
Last Revision Date: 13 Mar 2018 
(Page 48 of 48) 
 
Confidential and Proprietary 
APPENDIX 4 MOCKUP TABLES, LISTINGS, AND GRAPHS (TLGS) 
Mockup tables, listings, and graphs are presented in a separate document. 


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APPENDIX 4 
SPECIFICATION OF END-OF-TEXT STANDARD OUTPUT 
TABLES, LISTINGS, AND FIGURES (TLFs) 
 
 
 
Protocol Title: A Randomized, Double-blind, Single dose, Placebo-controlled, 5-Period, 5-Treatment, 
Crossover, Multi-center, Dose-ranging Study to Compare PT007 to Placebo MDI and Open-Label 
Proventil® HFA in Adult and Adolescent Subjects With Mild to Moderate Asthma 
 
 
PT007001 
 
Trial Sponsor:  
AstraZeneca AB 
Study Number: 
D6930C00001 (PT007001) 
Study Phase: 
II 
Product Name: 
Albuterol Sulfate Pressurized Inhalation Suspension (AS MDI); PT007 
PIND Number: 
136213 
Indication: 
Asthma 
Dosage Form/Strength 
x AS MDI as 
o 2 actuations of 45 μg per actuation (90 μg) 
o 2 actuations of 90 μg per actuation (180 μg) 
 
Date of Issue: 
13 Mar 2018 
Version 
1.0 
 
 
 


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General Instructions for End-of-Text TFLs 
 
Following are the specifications for end of text standard Tables, listings, and Figures (TFLs). 
 
Header 
 
The following header should appear at the very top of each page of a Table, a listing, or a Figure (TLF): 
Protocol PT007001 
Albuterol Sulfate Pressurized Inhalation Suspension 
 
Footer 
 
The following footer should appear at the bottom of each page of a TLF generated in SAS: 
 
Report generated by program:/sasdir/PGNAME.sas  Version YYYY-mm-dd hh:mm (Page n of N) 
 
where: PGNAME = SAS program name. Version will be replaced by “Draft” or “Final”.  Page number will be right-justified. 
 
Title 
 
At least two (2) lines should be reserved for the whole title. The first line of the title is for the TLF number (i.e., title index #) and 
the actual title (title); a longer title may continue onto subsequent lines. The analysis analysis set descriptor (Analysis Set) will be 
specified on the line following the title line(s). All titles should be centered, as shown in the following example:  
 
Table 1.5.3 
Demographics 
Analysis Set: Safety Analysis Set 
 
Footnotes 
 
x 
In general, a footnote serves as a brief explanation/clarification/definition/concept of a flag symbol or a character, an 
abbreviation, a terminology, etc., that appears in or related directly to the displayed content of a TLF. Detailed/technical 
elaboration of, for example, a mathematical/statistical formula, a statistical term/test, or an algorithm for deriving a 
parameter value, should be addressed in the text of the statistical analysis plan (SAP). 
x 
All footnotes should follow immediately after a horizontal solid line. There should be one and only one space between the 
last footnote and the footer.  
x 
Each line of a complete footnote should end with a period. When a footnote needs more than 1 line, one (1) period is 
needed. 
x 
Large data listings will have footnotes on the first page only. 
 
Row Labels/Column Labels: The mockups will reflect the preferred style of capitalization. 
 
Page Layout  
 
x 
All output should be in landscape orientation. A margin of 1.5, 1, 1, and 1 inch should be on the top, right, left, and bottom, 
respectively.  
x 
All efforts should be made to present all Treatment groups in one page. 
x 
When 3 or more Treatment groups are designed for a study and if it is not possible to fit all of them in one page, the 4th and 
5th treatment groups should be displayed on the 2nd page, etc. The Study Biostatistician will pre-determine the order for the 
display of the treatment groups.  
 
Page Format 
 
x 
There should be a solid line at the top of the Tables and listings just below the title. 
x 
There should be a solid line just below the column headings that runs completely across the width of the Tables and 
listings. 
x 
There should be a solid line at the bottom of the Tables and listings just above the footnote(s) on every page. 
 


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Font 
 
x 
The default font to be used in the actual study Tables/listings should be Courier New 8 point which is approximately 
equivalent to the accepTable font size of Times New Roman 9-10 in accordance with the FDA’s guidance on Electronic 
Common Technical Document Specification.  
x 
The use of Courier New 7 point is optional for some Tables/listings and will be determined at the study level by the Study 
Biostatistician and Study Programmer. However, it is recommended that this option be used primarily for data listings. 
 
Descriptive Statistics 
 
By default, descriptive statistics in this template covers: n, Mean, Median, Standard Deviation (SD), Minimum (Min), and 
Maximum (Max). Unless otherwise specified in the actual Table shells, the mean, standard deviation, standard error of the mean, 
and median should be displayed to one more decimal place than the original data. The standard error of the mean will be 
displayed with at least 2 significant digits for efficacy Tables. 
 
Rounding for Percentage 
 
Unless specified in the actual Table shells for a study, all percentages will be rounded to 1 decimal place in all TLFs.  Percentage 
signs will not be included in the body of the Table (i.e., 99.9 will be displayed, not 99.9%), but may be included in row or column 
headings. 
 
Unless specified in the actual Table shells for a study, p-values will be presented with 4 decimal places. 
 
Alignment of Decimals 
 
x 
It is recommended that all the decimal places be aligned in summary Tables, as shown in the following example: 
 
 
Decimal Align 
n 
xxx 
Mean 
xx.xx 
SD 
xx.xx 
Median 
xx.xx 
Minimum, Maximum 
xx.x, xx.x 
 
x 
When numbers with decimal points are included in brackets (e.g., percentages), have the brackets aligned to the right and 
then padded to allow for all possible percentages and then the left brackets will also be aligned. For example: 
 
Brackets Align 
(99.9) 
(xx.x) 
(  9.9) 
(  x.x) 
 
 
x 
It is recommended that all column entries in a summary Tables and listings are aligned to the center. 
x 
Columns for text fields are all left justified. Columns with whole numbers are all right justified. 
x 
For graphs, the lines are distinguishable and that the symbols for each line are appropriate. Legend is consistent across 
output for Treatment names and abbreviations. 
  
Use of N Versus n 
 
x 
N = total number of subjects in the defined analysis set. 
x 
n = total number of subjects in the specific category. 
x 
If N is specified in the column heading then any reference to the number of subjects in the body should be small n, as 
shown in the following example:  
 


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Demographic Parameter 
Treatment 
Group A 
(N=XXX) 
Treatment  
Group B 
(N=XXX) 
Total 
(N=XXX) 
 
 
 
 
Age (years) 
 
 
 
n 
        xxx 
        xxx 
        xxx 
Mean 
        xx.x 
        xx.x 
        xx.x 
SD 
          x.x 
          x.x 
          x.x 
Median 
        xx.x 
        xx.x 
        xx.x 
Minimum, Maximum   
        xx, xx 
        xx, xx 
        xx, xx 
 
 
A Note for Subject Data Listings 
 
x 
Observed Dates/AE Severity/Relationship to investigational product are used in subject data listings. 
x 
Observed values or raw assessment scores are used in data listings along with their derived values used in analyses, e.g., raw 
assessment scores and derived total scores. 
 
 
 


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Table of Contents 
1. 
SUBJECT DISPOSITION, DEMOGRAPHIC, BASELINE, AND OTHER SUMMARY 
TABLES ........................................................................................................................................... 11 
Table 1.1.1 
Subject Disposition ........................................................................................................ 11 
Analysis Set: All Screened Subjects 
Table 1.1.2 
Reasons for Subjects Not Randomized .......................................................................... 12 
Analysis Set: All Subjects Not Randomized 
Table 1.1.3 
Exclusions From ITT, mITT, and Safety Analysis Sets ................................................. 13 
Analysis Set: All Subjects Randomized 
Table 1.2.1 
Reason for Premature Treatment Discontinuation ......................................................... 14 
Analysis Set: ITT Analysis Set 
Table 1.2.2 
Reason for Premature Treatment Discontinuation ......................................................... 14 
Analysis Set: mITT Analysis Set 
Table 1.2.3 
Reason for Premature Treatment Discontinuation ......................................................... 15 
Analysis Set: Safety Analysis Set 
Table 1.3 
Analysis Sets by Treatment ............................................................................................ 16 
Analysis Set: All Subjects Randomized 
Table 1.4 
Reason for Exclusion From the mITT Analysis Set ....................................................... 17 
Analysis Set: ITT Analysis Set 
Table 1.5.1 
Demographics and Baseline Characteristics .................................................................. 18 
Analysis Set: mITT Analysis Set 
Table 1.5.2 
Demographics and Baseline Characteristics .................................................................. 20 
Analysis Set: ITT Analysis Set 
Table 1.5.3 
Demographics and Baseline Characteristics .................................................................. 20 
Analysis Set: Safety Analysis Set 
Table 1.5.4 
Demographics and Baseline Characteristics .................................................................. 20 
Analysis Set: All Subjects Not Randomized 
Table 1.6.1 
Duration of Asthma ........................................................................................................ 21 
Analysis Set: mITT Analysis Set 
Table 1.6.2 
Duration of Asthma ........................................................................................................ 21 
Analysis Set: Safety Analysis Set 
Table 1.7.1 
Screening Pre- and Post-Bronchodilator and Baseline Spirometry Parameters ............. 22 
Analysis Set: mITT Analysis Set 
Table 1.7.2 
Screening Pre- and Post-Bronchodilator and Baseline Spirometry Parameters ............. 23 
Analysis Set: ITT Analysis Set 
Table 1.8.1 
Reversibility to Ventolin HFA at Screening .................................................................. 24 
Analysis Set: mITT Analysis Set 
Table 1.8.2 
Reversibility to Ventolin HFA at Screening .................................................................. 24 
Analysis Set: ITT Analysis Set 
Table 1.9 
Medical/Surgical History ............................................................................................... 25 
Analysis Set: Safety Analysis Set 


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Table 1.10.1 
Prior Medications – Asthma-Related ............................................................................. 26 
Analysis Set: Safety Analysis Set 
Table 1.10.2 
Prior Medications-Other than Asthma-Related .............................................................. 26 
Analysis Set: Safety Analysis Set 
Table 1.11.1a 
Concomitant Medications During Treatment Period – Asthma-Related ........................ 27 
Analysis Set: Safety Analysis Set 
Table 1.11.1b 
Concomitant Medications During Washout Period – Asthma-Related .......................... 27 
Analysis Set: Safety Analysis Set 
Table 1.11.2.a 
Concomitant MedicationsDuring Treatment Period-Non-Asthma Related .................... 27 
Analysis Set: Safety Analysis Set 
Table 1.11.2b 
Concomitant Medications During Washout Period-Non-Asthma Related ..................... 27 
Analysis Set: Safety Analysis Set 
2. 
EFFICACY SUMMARY TABLES AND FIGURES ...................................................................... 28 
PRIMARY EFFICACY ENDPOINT ......................................................................................................... 28 
Table 2.1.1 
Change from Baseline in FEV1 AUC0-6 (L) Overall and by ICS Use Subgroups .......... 29 
Analysis Set: mITT Analysis Set 
Table 2.1.2 
Change from Baseline in FEV1 AUC0-6 (L) Overall and by ICS Use Subgroups .......... 31 
Analysis Set: ITT Analysis Set 
SECONDARY EFFICACY ENDPOINTS ................................................................................................. 31 
Table 2.2.1 
Change from Baseline in FEV1 AUC0-4 (L) ................................................................... 31 
Analysis Set: mITT Analysis Set 
Table 2.2.2 
Peak Change from Baseline in FEV1 (L) ....................................................................... 31 
Analysis Set: mITT Analysis Set 
OTHER EFFICACY ENDPOINTS ............................................................................................................ 32 
Table 2.3.1 
Change from Baseline in FEV1 (L) by Timepoint .......................................................... 32 
Analysis Set: mITT Analysis Set 
Figure 2.3.1.1 
Change from Baseline in FEV1 (L) ± SE Over Time ..................................................... 34 
Analysis Set: mITT Analysis Set 
Figure 2.3.1.2 
Treatment Differences From Placebo*: Change from Baseline in FEV1 (L) ± 95% 
CI Over Time ................................................................................................................. 35 
Analysis Set: mITT Analysis Set 
Table 2.3.2 
Time to Peak FEV1 ......................................................................................................... 36 
Analysis Set: mITT Analysis Set 
Table 2.3.3 
Percentage of Subjects Achieving a 12% or 15% Improvement in FEV1 from 
Baseline Within 30 Minutes Post-Dose .......................................................................... 37 
Analysis Set: mITT Analysis Set 
Table 2.3.4 
Time to Onset of 12% Improvement in FEV1 ................................................................ 38 
Analysis Set: mITT Analysis Set 
Table 2.3.5 
Time to Onset of 15% Improvement in FEV1 ................................................................ 38 
Analysis Set: mITT Analysis Set 
Table 2.3.6 
Duration of 12% Improvement in FEV1 ......................................................................... 39 
Analysis Set: mITT Analysis Set 


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Table 2.3.7 
Duration of 12% Improvement in FEV1: Subjects who Have Assessments at the 
180- and 300-Minute Post-Dose Timepoints ................................................................. 40 
Analysis Set: mITT Analysis Set 
Table 2.3.8 
Duration of 15% Improvement in FEV1 ......................................................................... 41 
Analysis Set: mITT Analysis Set 
Table 2.3.9 
Duration of 15% Improvement in FEV1: Subjects who Have Assessments at the 
180- and 300-Minute Post-Dose Timepoints ................................................................. 41 
Analysis Set: mITT Analysis Set 
3. 
SAFETY ........................................................................................................................................... 42 
ADVERSE EVENTS .................................................................................................................................. 42 
Table 3.1.1 
Overall Summary of Treatment-Emergent Adverse Events ........................................... 42 
Analysis Set: Safety Analysis Set 
Table 3.1.2 
Overall Summary of Treatment-Emergent Adverse Events Including Adverse 
Events on a Treatment Day or During the Washout or Follow-up Periods .................... 43 
Analysis Set: Safety Analysis Set 
Table 3.2.1 
Treatment-Emergent Adverse Events by MedDRA Primary System Organ Class 
and Preferred Term ........................................................................................................ 44 
Analysis Set: Safety Analysis Set 
Table 3.2.2 
Treatment-Emergent Adverse Events by MedDRA Primary System Organ Class 
and Preferred Term Including Events Occurring During the Washout or Follow-up 
Periods: Sensitivity Analysis .......................................................................................... 44 
Analysis Set: Safety Analysis Set 
Table 3.2.3 
Treatment-Emergent Adverse Events Occurring in >=2% of Subjects in a 
Treatment by Descending Frequency ............................................................................. 44 
Analysis Set: Safety Analysis Set 
Table 3.2.4 
Non-serious Treatment-Emergent Adverse Events Occurring in  >=5% of Subjects 
in a Treatment by MedDRA Primary System Organ Class and Preferred Term ............ 45 
Analysis Set: Safety Analysis Set 
Table 3.3 
Treatment-Related Treatment-Emergent Adverse Events by MedDRA Primary 
System Organ Class and Preferred Term ....................................................................... 46 
Analysis Set: Safety Analysis Set 
Table 3.4 
Treatment-Emergent Adverse Events Leading to Study Drug Discontinuation by 
MedDRA Primary System Organ Class and Preferred Term ......................................... 46 
Analysis Set: Safety Analysis Set 
Table 3.5 
Listing of Adverse Events Leading to Permanent Discontinuation of Study 
Treatment ....................................................................................................................... 47 
Analysis Set: All Subjects Randomized 
Table 3.6.1 
Serious Adverse Events by MedDRA Primary System Organ Class and Preferred 
Term ............................................................................................................................... 48 
Analysis Set: Safety Analysis Set 
Table 3.6.2 
Serious Adverse Events by MedDRA Primary System Organ Class and Preferred 
Term Including Events Occurring During the Washout and Follow-up Period: 
Sensitivity Analysis ........................................................................................................ 48 
Analysis Set: Safety Analysis Set 


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Table 3.7.1 
Listing of Serious Adverse Events (SAEs) .................................................................... 49 
Analysis Set: All Subjects Screened 
Table 3.7.2 
Listing of SAE-Specific Report Information ................................................................. 50 
Analysis Set: Screened 
Table 3.8 
Treatment Related Serious Adverse Events by MedDRA Primary System Organ 
Class and Preferred Term ............................................................................................... 52 
Analysis Set: Safety Analysis Set 
Table 3.9.1 
TEAEs by Primary System Organ Class, Preferred Term, and Highest Severity – 
Placebo ........................................................................................................................... 53 
Analysis Set: Safety Analysis Set 
Table 3.9.2 
TEAEs by Primary System Organ Class, Preferred Term, and Highest Severity – 
AS MDI 90 μg................................................................................................................ 53 
Analysis Set: Safety Analysis Set 
Table 3.9.3 
TEAEs by Primary System Organ Class, Preferred Term, and Highest Severity – 
AS MDI 180 μg.............................................................................................................. 53 
Analysis Set: Safety Analysis Set 
Table 3.9.4 
TEAEs by Primary System Organ Class, Preferred Term, and Highest Severity – 
Proventil 90 μg ............................................................................................................... 53 
Analysis Set: Safety Analysis Set 
Table 3.9.5 
TEAEs by Primary System Organ Class, Preferred Term, and Highest Severity – 
Proventil 180 μg ............................................................................................................. 53 
Analysis Set: Safety Analysis Set 
Table 3.10 
Listing of Deaths ............................................................................................................ 54 
Analysis Set: All Subjects Screened 
VITAL SIGNS ............................................................................................................................................ 55 
Table 3.11.1 
Vital Sign Parameters ..................................................................................................... 55 
Analysis Set: Safety Analysis Set 
4. 
SUBJECT DATA LISTINGS .......................................................................................................... 56 
4.1 
SUBJECT DISCONTINUATIONS/COMPLETIONS .................................................................... 56 
Listing 1.1 
Study Centers ................................................................................................................. 56 
Analysis Set: All Subjects Screened 
Listing 1.2 
Subject Disposition and Demographic Data................................................................... 57 
Analysis Set: All Subjects Screened 
Listing 1.3 
Randomized Treatment, Actual Treatment, and Duration of Treatment ........................ 59 
Analysis Set: All Subjects Randomized 
Listing 1.4 
Reasons Subjects Were Not Randomized ...................................................................... 61 
Analysis Set: All Subjects Not Randomized 
4.2 
PROTOCOL DEVIATIONS ............................................................................................................ 62 
Listing 2 
 Violation of Inclusion/Exclusion Criteria ..................................................................... 62 
Analysis Set: All Subjects Randomized 
4.3 
SCREENING LUNG FUNCTION AND REVERSIBILITY .......................................................... 63 
Listing 3 
 Screening Lung Function and Ventolin HFA Reversibility .......................................... 63 
Analysis Set: All Subjects Randomized 


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4.4 
BASELINE CHARACTERISTICS ................................................................................................. 64 
Listing 4.1 
Asthma Diagnosis .......................................................................................................... 64 
Analysis Set: All Subjects Randomized 
Listing 4.2 
Medical and Surgical History ......................................................................................... 65 
Analysis Set: All Subjects Randomized 
Listing 4.3 
Screening Reproductive Status and Pregnancy Test Results .......................................... 66 
Analysis Set: All Subjects Randomized 
Listing 4.4 
Prior, Concomitant, and Post-Treatment Asthma Medications ...................................... 67 
Analysis Set: All Subjects Randomized 
Listing 4.5 
Prior, Concomitant, and Post-Treatment Non-Asthma-Related Medications ................ 67 
Analysis Set: All Subjects Randomized 
Listing 4.6 
Suspect Drug Assessment for SAEs ............................................................................... 68 
Analysis Set: All Subjects Randomized 
4.5 
DOSING ........................................................................................................................................... 69 
Listing 5.1.1 
Study Drug Administration ............................................................................................ 69 
Analysis Set: All Subjects Randomized 
Listing 5.1.2 
Ventolin HFA and Pulmicort Flexhaler Dispensing ...................................................... 70 
Analysis Set: All Subjects Randomized 
Listing 5.2 
Exposure to Study Treatment ......................................................................................... 71 
Analysis Set: Safety Analysis Set 
4.6 
INDIVIDUAL EFFICACY DATA .................................................................................................. 72 
4.6.1 Efficacy............................................................................................................................................. 72 
Listing 6.1 
Subjects Who Failed Restrictions Prior to Spirometry Assessment ............................... 72 
Analysis Set: All Subjects Randomized 
Listing 6.2 
Failure of Stability Criteria ............................................................................................ 73 
Analysis Set: All Subjects Randomized 
Listing 6.3 
Reason for Missed Visit ................................................................................................. 74 
Analysis Set: All Subjects Randomized 
Listing 6.4 
Spirometry Measurements.............................................................................................. 75 
Analysis Set: All Subjects Randomized 
Listing 6.5 
Spirometry Derived Endpoints ....................................................................................... 76 
Analysis Set: All Subjects Randomized 
4.7 
ADVERSE EVENT LISTINGS ....................................................................................................... 78 
Listing 7.1 
Adverse Events by Primary System Organ Class, Preferred Term, Treatment, 
Country, Center, Subject ID, and Onset Day ................................................................. 78 
Analysis Set: All Subjects Randomized 
Listing 7.2 
Glossary of Adverse Event Preferred Terms vs. Investigator’s Verbatim ..................... 80 
Listing 7.3 
Adverse Events by Treatment, Center, Subject ID, and Onset Day ............................... 81 
Analysis Set: All Subjects Randomized 
4.8 
LABORATORY VALUES .............................................................................................................. 82 
Listing 8.1 
Laboratory Test Results (Hematology Panel) ................................................................ 82 
Analysis Set: All Subjects Randomized 


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Listing 8.2 
Laboratory Test Results (Chemistry Panel and Kidney Function) ................................. 82 
Analysis Set: All Subjects Randomized 
Listing 8.3 
Laboratory Test Comments ............................................................................................ 83 
Analysis Set: All Subjects Randomized 
4.9 
OTHER CLINICAL OBSERVATIONS AND MEASUREMENTS ............................................... 84 
Listing 9.1 
Vital Signs, Weight, and Height ..................................................................................... 84 
Analysis Set: All Subjects Randomized 
Listing 9.2 
12-Lead Electrocardiogram (ECG) ................................................................................ 86 
Analysis Set: All Subjects Randomized 
Listing 9.3 
Comments ...................................................................................................................... 87 
Analysis Set: All Subjects Randomized 


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1. Subject Disposition, Demographic, Baseline, and Other Summary Tables 
 
Table 1.1.1 
Subject Disposition 
Analysis Set: All Screened Subjects 
 
All Subjects 
(N=xxx) 
n (%) 
Not Treated 
xx (xx.x) 
Treated  
xx (xx.x) 
 Treated with AS MDI 90 μg 
xx (xx.x) 
 Treated with AS MDI 180 μg 
xx (xx.x) 
 Treated with Proventil 90 μg 
xx (xx.x) 
 Treated with Proventil 180 μg 
xx (xx.x) 
 Treated with Placebo 
xx (xx.x) 
 
 Length of Subject Participation in the Study  
 
   5 Treatment Periods 
xx (xx.x) 
   4 Treatment Periods 
xx (xx.x) 
   3 Treatment Periods 
xx (xx.x) 
   2 Treatment Periods 
xx (xx.x) 
   1 Treatment Period only 
xx (xx.x) 
   0 Treatment Periods 
xx (xx.x) 
 
Completed Study 
xx (xx.x) 
Premature Discontinuation 
xx (xx.x) 
 
ITT Analysis Set [a] 
xx (xx.x) 
mITT Analysis Set [b] 
xx (xx.x) 
Safety Analysis Set [c] 
xx (xx.x) 
Not Randomized Analysis Set [d] 
xx (xx.x) 
[a] The Intent-To-Treat (ITT) Analysis Set was defined as all subjects who were randomized to treatment and received at least 1 dose 
of the study treatment.  Subjects were analyzed in each period according to the treatment they were assigned to per the randomization 
scheme (Note that a subject who used a study treatment but took less than 1 full dose of treatment qualified for this analysis set). 
[b] The mITT Analysis Set was defined as a subset of the ITT analysis set including subjects who received treatment and had post-
treatment efficacy data from at least 2 Treatment Periods. Data judged to be impacted by major protocol deviations was determined 
prior to unblinding and excluded per the statistical protocol deviation plan. Statistical tabulations and analyses were by randomized 
treatment, but data obtained after subjects received an incorrect treatment were excluded from the affected periods. 
[c] The Safety Analysis Set was defined as all subjects who were randomized to treatment and received at least 1 dose of the study 
treatment. Subjects were analyzed according to treatment received rather than per the randomization scheme. 
[d] The Not Randomized analysis set was defined as subjects who did not receive a randomization number and therefore did not receive a 
dose of study treatment (eg, subjects who were screen failures or stopped participation before being randomized). 
Report generated by program: PT007001/sasdir/programs/statout/t_010101.sas  Version  YYYY-MM-DD xx:xx  (Page n of N)   


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Table 1.1.2 
Reasons for Subjects Not Randomized 
Analysis Set: All Subjects Not Randomized 
 
Reason Not Randomized 
All Subjects Not Randomized 
(N=xxx) 
            n (%) 
Any Inclusion/Exclusion Criterion  
          xxx (xx.x) 
Exclusion Criterion #x: xxxx xxxx xx xxxxx xxxxx xxxx 
          xxx (xx.x) 
Exclusion Criterion #x: xxx xxxxxxxxxxxx xx xxxxx x 
          xxx (xx.x) 
Inclusion Criterion #x: xx x x xxx xxxx xxxx xxxxxxxxxxxx  
          xxx (xx.x) 
Inclusion Criterion #x: xxxx xxxx xx xxxxx xxxxx xxxx 
          xxx (xx.x) 
 
FAny Failure of Randoimzation Criteria 
  Cfiteria #X; XXXXXXXXXXXXXXXXXXXXXXXX 
          xxx (xx.x) 
          xxx (xx.x) 
Note: Reasons of Other are listed by subject in Listing 1.X. 
Report generated by program: PT007001/sasdir/programs/statout/t010102.sas Version  YYYY-MM-DD xx:xx              (Page n of N) 
Notes to Programmer: Order by frequency within each category. Display all protocol-specified criteria shown on the End of Treatment/ CRF that have counts> 0.. 
From Section 3.3.1 of the Protocol, the Randomization Criteria are: 
1. Subjects of childbearing potential must have a negative urine pregnancy test 
2. Received no asthma medication other than Sponsor-provided Pulmicort Flexhaler 
180 μg or 360 μg BID as assigned and/or Sponsor-provided Ventolin from Visit 1 
to Visit 2, except for allowable allergy medications defined in Table 8 of the Protocol. 
3. The last dose of Pulmicort Flexhaler (if applicable) was the previous night (ie, 
morning dose of Pulmicort Flexhaler was not administered), and the last dose of 
Sponsor-provided Ventolin was no later than 6 hours before the study visit (if 
Ventolin is needed in the morning, the visit must be rescheduled) 
4. Pre-bronchodilator FEV1 ≥40% percent predicted normal value 
5. Has not used >8 actuations per day (ie, 4 doses of 2 actuations per day) of Sponsorprovided 
Ventolin for rescue on more than any 3 days during the previous 7 days 
6. No upper respiratory infection, lower respiratory infection, or asthma exacerbation 
during the Screening Period 
7. Demonstrate acceptable MDI administration technique 
8. Able to comply with all study procedures 
 
 


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Table 1.1.3 
Exclusions From ITT, mITT, and Safety Analysis Sets 
Analysis Set: All Subjects Randomized 
 
Subject 
ID 
Treatment 
Sequence 
Analysis 
Set 
Excluded 
Period 
Excluded  
Timepoints 
Excluded 
Variable(s) 
Excluded 
Reason for Exclusion 
 
Study Center # / (Investigator):  ### / (xxxxxxxxxx) 
 
xxxxx 
-/-/-/-/- 
ITT 
All 
All 
All 
Subject did not receive treatment in at least 1 
treatment period.  
mITT 
All 
All 
All 
Subject did not have post-treatment efficacy data from 
at least 2 Treatment Periods. 
Safety 
All 
All 
All 
Did not receive at least one dose of the study treatment 
in the study. 
mITT 
Period 1 
300, 360 
Minutes 
All 
Subject did not have post-treatment efficacy data from 
at least 2 Treatment Periods. 
 
 
 
 
 
 
 
xxxxx 
A/B/E/C/D 
Safety 
All 
All 
All 
Subject did not receive treatment in at least 1 
treatment period. 
 
 
 
 
 
 
 
xxxxx 
B/C/-/-/- 
ITT 
All 
All 
All 
Subject did not receive treatment in at least 1 
treatment period. 
 
 
mITT 
All 
All 
All 
Subject did not have post-treatment efficacy data from 
at least 2 Treatment Periods. 
 
 
Safety 
All 
All 
All 
Did not receive at least one dose of the study treatment 
in the study. 
 
 
 
 
 
 
 
xxxxx 
A/E/-/-/- 
mITT 
All 
All 
All 
Subject took incorrect study medication. 
 
 
 
 
 
 
 
xxxxx 
B/A/C/E/- 
mITT 
Period 4 
All  
All  
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx. 
 
 
 
 
 
 
 
Treatment: A = Placebo, B = AS MDI 90 μg, C = AS MDI 180 μg, D = Proventil 90 μg, E = Proventil 180 μg, - = Not Treated. 
Subjects may be included in a analysis set as a whole, but have period or timepoint data excluded. 
 
Report generated by program: PT007001/sasdir/programs/statout/t010103.sas  Version  YYYY-MM-DD xx:xx           (Page n of N) 
 
Notes to Programmer:  
Sort by Study Center, Investigator, and Subject within Study Center. 
List records per subject, analysis set excluded, period excluded, and timepoint excluded.   
Move ‘Study Center/Inv’ row header to the next page whenever there is not enough room on current page to fit at least one row of data underneath this header.   
 
 


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Table 1.2.1 
Reason for Premature Treatment Discontinuation 
Analysis Set: ITT Analysis Set 
 
Placebo 
(N=xxx) 
AS MDI 
90 μg 
(N=xxx) 
AS MDI 
180 μg 
(N=xxx) 
Proventil 
90 μg 
(N=xxx) 
Proventil 
180 μg 
(N=xxx) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
 
 
 
 
 
Premature Treatment Discontinuation 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
Reason for Premature Treatment Discontinuation 
 
 
 
 
 
Administrative Reasons 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Adverse Event 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Lack of Efficacy 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Subject Discretion 
  Withdrawal of Consent 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Asthma 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
  Other 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Investigator or Designee Considers it to be in the Best Interest of 
the Subject 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Subject Lost-to-Follow-up 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Major Protocol Deviation 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Protocol-Specified Discontinuation Criteria 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
FEV1 Stability Criteria Sec 5.1.4 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Requirement of any Prohibited Medications Listed in Sec 7.7.3 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Positive Pregnancy Test 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Asthma Worsening Requiring Change in Asthma Treatment Sec 3.9 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
The Subject’s Treatment Code Prematurely Broken by Investigator 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
Other 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
Note: Reasons of Other are listed by subject in Listing 1.2. 
Report generated by program: PT007001/sasdir/programs/statout/t010201.sas Version  YYYY-MM-DD xx:xx                 (Page n of N) 
 
Notes to Programmer:Sort by descending frequency of major reason category using AS MDI column. Within a major reason category, sort by descending frequency of subcategory 
using AS MDI column. 
 
 
Table 1.2.2 
Reason for Premature Treatment Discontinuation 
Analysis Set: mITT Analysis Set 
 
Footnotes:  
Subjects were included in summaries for a treatment if they received at least one dose of the treatment. 
 


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Table 1.2.3 
Reason for Premature Treatment Discontinuation 
Analysis Set: Safety Analysis Set 
 
Footnotes:  
Subjects were included in summaries for a treatment if they received at least one dose of the treatment. 
 
 


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Table 1.3 
Analysis Sets by Treatment 
Analysis Set: All Subjects Randomized 
 
Placebo 
(N=xxx) 
AS MDI 
90 μg 
(N=xxx) 
AS MDI 
180 μg 
(N=xxx) 
Proventil 90 
μg 
(N=xxx) 
Proventil 180 
μg 
(N=xxx) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
 
 
 
 
 
Intent-to-treat Analysis Set [a] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
mITT Analysis Set [b] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
Safety Analysis Set [c] 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
n = number of subjects in the category, N=# of subjects who were randomized to the treatment, % = 100 x n/N. 
[a] The Intent-To-Treat (ITT) Analysis Set was defined as all subjects who were randomized to treatment and received at least 1 dose 
of the study treatment.  Subjects were analyzed in each period according to the treatment they were assigned to per the randomization 
scheme (Note that a subject who used a study treatment but took less than 1 full dose of treatment qualified for this analysis set). 
[b] The mITT Analysis Set was defined as a subset of the ITT analysis set including subjects who received treatment and had post-
treatment efficacy data from at least 2 Treatment Periods. Data judged to be impacted by major protocol deviations were determined 
prior to unblinding and excluded per the statistical protocol deviation plan. Statistical tabulations and analyses were by randomized 
treatment, but data obtained after subjects received an incorrect treatment was excluded from the affected periods. 
[c] The Safety Analysis Set was defined as all subjects who were randomized to treatment and received at least 1 dose of the study 
treatment. Subjects were analyzed according to treatment received rather than per the randomization scheme. 
Report generated by program: PT007001/sasdir/programs/statout/t0103.sas  Version  YYYY-MM-DD xx:xx             (Page n of N)   
 
 
 


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Table 1.4 
Reason for Exclusion From the mITT Analysis Set 
Analysis Set: ITT Analysis Set 
 
Reason for 
Placebo 
(N=xxx) 
AS MDI 
90 μg 
(N=xxx) 
AS MDI 
180 μg 
(N=xxx) 
Proventil 
90 μg 
(N=xxx) 
Proventil 
180 μg 
(N=xxx) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
 
 
 
 
 
 
Exclusion of a Subject from mITT Analysis Set 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
<Reason 1> 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
<Reason 2> 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
… 
 
 
 
 
 
 
 
 
 
 
 
Exclusion of a Treatment Period from mITT Analysis Set 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
<Reason 1> 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
<Reason 2> 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Subjects may have multiple reasons for exclusion; therefore, counts for individual reasons may not add up to the total 
number of subjects excluded from the analysis set. 
 
Report generated by program: PT007001/sasdir/programs/statout/t0104.sas  Version  YYYY-MM-DD xx:xx               (Page n of 
N) 
 
Note to the Programmer: Subjects are to be included in summaries and N= in the column header for a treatment if they attended a visit designated for a treatment in their 
treatment sequence. 
 
 
 


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Table 1.5.1 
Demographics and Baseline Characteristics 
Analysis Set: mITT Analysis Set 
 
Parameter 
All Subjects 
(N=xxx) 
 
 
Age (Years)[a] 
 
  n 
xxx 
  Mean  
xx.x 
  SD 
xx.x 
  Median 
xx.x 
  Minimum 
xx 
  Maximum 
xx 
 
 
Age Group, n (%) 
 
   Age 12 to < 18 years 
xxx (xx.x) 
   Age 18 to 65 years 
xxx (xx.x) 
   Missing 
  x (xx.x) 
 
 
Gender, n (%) 
 
  Male 
xxx (xx.x) 
  Female 
xxx (xx.x) 
  Missing 
  x (xx.x) 
 
 
Race, n (%) 
 
  Black or African  
  American 
 xx (xx.x) 
  White 
xxx (xx.x) 
  Native Hawaiian or Other Pacific Islander 
 xx (xx.x) 
  American Indian or Alaska Native 
 xx (xx.x) 
  Asian 
 xx (xx.x) 
  Other 
 xx (xx.x) 
  Missing 
 xx (xx.x) 
 
 
Ethnicity, n (%) 
 
   Hispanic 
xxx (xx.x) 
   Not Hispanic or Latino 
xxx (xx.x) 
   Unknown 
xxx (xx.x) 
   Not Reported 
 xx (xx.x) 
 
 
Smoking Status, n (%) [b] 
 
  Former Smoker 
xxx (xx.x) 
  Non Smoker 
xxx (xx.x) 
  Missing 
xxx (xx.x) 
 
 
Number of Years Smoked 
 


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Parameter 
All Subjects 
(N=xxx) 
  n 
xxx 
  Mean  
xx.x 
  SD 
xx.x 
  Median 
xx.x 
  Minimum 
  Maximum 
xx.x 
xx.x 
 
 
Average Number of Cigarettes Smoked Per Day 
 
  n 
xxx 
  Mean  
xx.x 
  SD 
xx.x 
  Median 
xx.x 
  Minimum 
  Maximum 
xx.x 
xx.x 
 
 
Number of Pack Years Smoked [c] 
 
  n 
xxx 
  Mean  
xx.x 
  SD 
xx.x 
  Median 
xx.x 
  Minimum 
  Maximum 
xx.x  
xx.x 
 
Prior Asthma Medication 
 
    SABA prn only, n (%) 
xx.x 
   ICS, n (%) 
xx.x 
   ICS/LABA, n (%) 
xx.x 
 
 
Weight (kg) 
 
  n 
xxx 
  Mean  
xx.x 
  SD 
xx.x 
  Median 
xx.x 
  Minimum 
  Maximum 
xx.x 
xx.x 
 
 
Height (cm) 
 
  n 
xxx 
  Mean  
xxx.x 
  SD 
xxx.x 
  Median 
xxx.x 
  Minimum 
  Maximum 
xxx.x  
xxx.x 
 
 
BMI (kg/m^2) 
 
  n 
xxx 


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Parameter 
All Subjects 
(N=xxx) 
  Mean  
xx.x 
  SD 
xx.x 
  Median 
xx.x 
  Minimum 
  Maximum 
xx.x  
xx.x 
 
 
[a]  Age is age at Visit 1.  The remaining characteristics were based on data from Screening visits 
prior to the start of the study. 
[b]  Former Smoker was defined as those who have stopped smoking for at least 6 months prior to first 
Screening Visit and have no more than 10 pack years history of smoking. 
[c]  Number of pack years smoked = (number of cigarettes per day / 20) x number of years smoked. 
 
Report generated by program: PT007001/sasdir/programs/statout/t010501.sas Version  YYYY-MM-DD xx:xx    
(Page n of N) 
 
Notes to Programmer:  
Repeat titles, column headers, and footnotes on each page. Keep the summary for a parameter in the same page when breaking the Table into multiple pages.  
Sort race by decreasing frequecing. The race/ethnicities of Native Hawaiian or Other Pacific Islander OR American Indian or Alaska Native can be removed from this Table if 
they do not exist in the database.  
Calculate BMI using Height at Visit 1. BMI = weight (kg)/height (m)2.  
Please delete Missing row when there are no missing values. 
 
Table 1.5.2 
Demographics and Baseline Characteristics 
Analysis Set: ITT Analysis Set 
 
 
Table 1.5.3 
Demographics and Baseline Characteristics 
Analysis Set: Safety Analysis Set 
 
Note to Programmer: Remove Table 1.5.3 if Safety Analysis Set is the same as the ITT Analysis Set. 
 
Table 1.5.4 
Demographics and Baseline Characteristics 
Analysis Set: All Subjects Not Randomized 
 
 
 
 


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Table 1.6.1 
Duration of Asthma 
Analysis Set: mITT Analysis Set 
 
 
   
All Subjects 
(N=xxx) 
 
 
Duration of Asthma (months) [a] 
   n 
   Mean 
   SD 
 
xxx 
xx.x 
xx.x 
   25th Percentile  
xx.x 
   Median  
xx.x 
   75th Percentile  
xx.x 
   Minimum 
   Maximum 
xx.x 
xx.x 
 
 
[a]  The duration of asthma is calculated relative to the first dose of study medication. 
 
Report generated by program: PT007001/sasdir/programs/statout/t010601.sas Version  YYYY-MM-DD 
xx:xx            (Page n of N)  
 
Notes to Programmer: Duration of Asthma = (First Dose date of Study Treatment - Date Asthma First Diagnosed)/30.4375, where day of Asthma diagnosed is assumed to be the 
1st of the month.  
 
Table 1.6.2 
Duration of Asthma 
Analysis Set: Safety Analysis Set 
 
 
 


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Table 1.7.1 
Screening Pre- and Post-Bronchodilator and Baseline Spirometry Parameters 
Analysis Set: mITT Analysis Set 
 
 
All Subjects 
(N=xxx) 
 
 
FEV1 (% predicted) 
 
 
Visit 1 [a] 
 
Pre-Ventolin HFA: 
n 
Mean  
SD 
 
xx 
xx.xxx  
xx.xxx 
25th Percentile  
xx.xxx 
Median  
xx.xxx 
75th Percentile  
xx.xxx 
Minimum 
Maximum 
xx.xxx 
xx.xxx 
 
 
Post-Ventolin HFA: 
n 
Mean  
SD 
 
xx 
xx.xxx  
xx.xxx 
25th Percentile  
xx.xxx 
Median  
xx.xxx 
75th Percentile  
xx.xxx 
Minimum 
Maximum 
xx.xxx 
xx.xxx 
 
 
Visit 2 (Pre-dose) 
 
Pre-Ventolin HFA: 
n 
Mean  
SD 
 
xx 
xx.xxx  
xx.xxx 
25th Percentile  
xx.xxx 
Median  
xx.xxx 
75th Percentile  
xx.xxx 
Minimum 
Maximum 
xx.xxx 
xx.xxx 
 
 
Post-Ventolin HFA: 
n 
Mean  
SD 
 
xx 
xx.xxx  
xx.xxx 
25th Percentile  
xx.xxx 
Median  
xx.xxx 


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75th Percentile  
xx.xxx 
Minimum 
Maximum 
xx.xxx 
xx.xxx 
 
 
Repeat the above for these parameters: 
FEV1 (L)  
FVC (% predicted) 
FVC (L) 
FEF 25-75 (% predicted) 
FEF 25-75 (L/sec) 
 
 
 
[a] Visit 1, for this purpose, was Visit 1, 1a, or 1b, whichever visit had the highest FEV1 
result post-dose.  
 
Report generated by program: PT007001/sasdir/programs/statout/t010701.sas Version  YYYY-MM-DD 
xx:xx             (Page n of N)  
 
 
Table 1.7.2 
Screening Pre- and Post-Bronchodilator and Baseline Spirometry Parameters  
Analysis Set: ITT Analysis Set 
 
 
 


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Table 1.8.1 
Reversibility to Ventolin HFA at Screening 
Analysis Set: mITT Analysis Set 
 
 
All Subjects 
(N=xxx) 
 
 
Post-Ventolin HFA FEV1 - Pre-Ventolin HFA FEV1 (mL) 
 n  
 Mean 
 SD 
 Median 
 Minimum 
 Maximum 
xx 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
 
 
Reversibility (%) Post-Ventolin HFA for FEV1 [a] 
 n 
 Mean 
 SD 
 Median 
 Minimum  
 Maximum 
xx 
xx.x 
xx.x 
xx.x 
xx.x 
xx.x 
 
 
 Reversible [b], n (%) 
xx (xx.x) 
 
 
If a subject was missing a Post- or Pre-Ventolin HFA FEV1 value at Screening Visit 1, these values 
were replaced by the Pre- and Post-Ventolin HFA values from Screening Visit 1a.  Similarly, if 
values were missing at Screening Visits 1 and 1a, the values were replaced by those from Screening 
Visit 1b.    
[a]  Reversibility (%) is defined as 100 x (the change from pre-Ventolin HFA to post for FEV1)/pre- 
     Ventolin HFA FEV1. 
[b]  Reversible is defined as Improvement in FEV1 post-Ventolin HFA administration compared to pre-  
     Ventolin HFA of >=15%. 
 
Report generated by program: PT007001/sasdir/programs/statout/t010801.sas  Version  YYYY-MM-DD xx:xx  
(Page n of N)  
 
Table 1.8.2 
Reversibility to Ventolin HFA at Screening  
Analysis Set: ITT Analysis Set 
 
 
 


Albuterol Sulfate Pressurized Inhalation Suspension 
Protocol D6930C00001 (PT007001) 
Version 0.1 
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Page 25 of 87 
 
 
 
Table 1.9 
Medical/Surgical History 
Analysis Set: Safety Analysis Set 
 
 
All Subjects 
(N=xxx) 
n  (%) 
 
 
Subject Had Medical/Surgical History 
 
No 
xxx (xx.x) 
Yes 
xxx (xx.x) 
Cardiovascular 
xxx (xx.x) 
CNS/Neurological 
xxx (xx.x) 
Dermatologic 
xxx (xx.x) 
Drug Allergy 
xxx (xx.x) 
EENT 
xxx (xx.x) 
Endocrine/Metabolic 
xxx (xx.x) 
Gastrointestinal 
xxx (xx.x) 
Genitourinary 
xxx (xx.x) 
Hepatic 
xxx (xx.x) 
Hematologic 
xxx (xx.x) 
Immunological 
xxx (xx.x) 
Malignancy 
xxx (xx.x) 
Musculoskeletal 
xxx (xx.x) 
Psychiatric 
xxx (xx.x) 
Respiratory 
xxx (xx.x) 
Renal 
xxx (xx.x) 
Other 
xxx (xx.x) 
 
 
 
Report generated by program: PT007001/sasdir/programs/statout/t0109.sas Version  YYYY-MM-DD xx:xx       
(Page n of N)         
 
Note to Programmer: Please sort by descending frequency of occurrence in All Subjects. Denominator should be N from the column header for a treatment. 
 
 
 


Albuterol Sulfate Pressurized Inhalation Suspension 
Protocol D6930C00001 (PT007001) 
Version 0.1 
13 Mar 2018 
Page 26 of 87 
 
 
 
 
Table 1.10.1 
Prior Medications – Asthma-Related 
Analysis Set: Safety Analysis Set 
 
Preferred Term 
All Subjects 
(N=xxx) 
n (%) 
 
 
Any Prior Asthma Medication 
xxx (xx.x) 
Medication 1 
xxx (xx.x) 
Medication 2 
xxx (xx.x) 
 
 
Preferred term is according to WHODRUG Qxxxx. 
 
Report generated by program: PT007001/sasdir/programs/statout/t011001.sas Version  YYYY-MM-DD xx:xx      
(Page n of N)  
 
Notes to Programmer: Sort Medications by descending frequency of use in All Subjects. 
 
Table 1.10.2 
Prior Medications-Other than Asthma-Related 
Analysis Set: Safety Analysis Set 
 
Notes to Programmer: Sort Medications by descending frequency of use for All Subjects.  Add a row for “Any Prior Other Medication”. 
 


Albuterol Sulfate Pressurized Inhalation Suspension 
Protocol D6930C00001 (PT007001) 
Version 0.1 
13 Mar 2018 
Page 27 of 87 
 
 
Table 1.11.1a 
Concomitant Medications During Treatment Period – Asthma-Related 
Analysis Set: Safety Analysis Set 
 
Preferred Term 
Placebo 
(N=xxx) 
AS MDI 
90 μg 
(N=xxx) 
AS MDI 
180 μg 
(N=xxx) 
Proventil 90 
μg 
(N=xxx) 
Proventil 180 
μg 
(N=xxx) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
 
 
 
 
 
 
Any Concomitant Asthma Medication 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
Medication 1 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
Medication 2 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
 
 
 
 
 
 
Preferred term is according to WHODRUG Qxxxx. 
All subjects were allowed only sponsor-provided Ventolin HFA and/or Pulmicort Flexhaler for relief of symptoms.  
See Listing 6.4 for the use of Ventolin HFA as rescue medication.  
 
Report generated by program: PT007001/sasdir/programs/statout/t011101a.sas Version  YYYY-MM-DD xx:xx              (Page n of 
N)  
 
Notes to Programmer: Sort Medications by descending frequency of use in All Subjects. 
 
Table 1.11.1b 
Concomitant Medications During Washout Period – Asthma-Related 
Analysis Set: Safety Analysis Set 
 
Concomitant medications are tabulated by the treatment received during the Treatment Period just prior to the washout. 
Preferred term is according to WHODRUG Qxxxx. 
All subjects were allowed only sponsor-provided Ventolin HFA and/or Pulmicort Flexhaler for relief of symptoms.  
See Listing 6.4 for the use of Ventolin HFA as rescue medication.  
 
Report generated by program: PT007001/sasdir/programs/statout/t011101b.sas Version  YYYY-MM-DD xx:xx              (Page n of 
N)  
 
Table 1.11.2.a 
Concomitant MedicationsDuring Treatment Period-Non-Asthma Related 
Analysis Set: Safety Analysis Set 
 
Notes to Programmer: Sort Medications by descending frequency of use in All Subjects.  Add a row for “Any Concomitant Other Medication”. 
 
Table 1.11.2b 
Concomitant Medications During Washout Period-Non-Asthma Related 
Analysis Set: Safety Analysis Set 
 
Notes to Programmer: Sort Medications by descending frequency of use in All Subjects.  Add a row for “Any Concomitant Other Medication 
 
 


Albuterol Sulfate Pressurized Inhalation Suspension 
Protocol D6930C00001 (PT007001) 
Version 0.1 
13 Mar 2018 
Page 28 of 87 
 
 
 
 
2. Efficacy Summary Tables and Figures 
 
Primary Efficacy Endpoint 
   
 


Albuterol Sulfate Pressurized Inhalation Suspension 
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Table 2.1.1 
Change from Baseline in FEV1 AUC0-6 (L) Overall and by ICS Use Subgroups 
Analysis Set: mITT Analysis Set 
 
Treatment 
Baseline FEV1 
Change From 
Baseline  
AUC0-6 
LS Mean Differences Between Treatments  
Placebo 
AS MDI 90 μg 
Proventil 180 μg 
Proventil 90 μg 
 
Combined ICS Use Groups [a] 
 
AS MDI 180 μg 
  N 
xx 
xx 
 
 
 
 
  Mean  
x.xxx 
x.xxx 
 
 
 
 
  SD 
x.xxx 
x.xxx 
 
 
 
 
  Median 
x.xxx 
x.xxx 
 
 
 
 
  Min-Max 
x.xxx-x.xxx 
x.xxx-x.xxx 
 
 
 
 
  LS Mean (SE) 
 
  x.xxx 
(x.xxxx)       
  x.xxx (x.xxxx)      x.xxx (x.xxxx)      x.xxx (x.xxxx)      x.xxx (x.xxxx)   
  95% CI 
 
( x.xxx, 
x.xxx) 
( x.xxx, x.xxx) 
( x.xxx, x.xxx) 
( x.xxx, x.xxx) 
( x.xxx, x.xxx) 
  P-value 
 
 
x.xxxx 
x.xxxx 
x.xxxx 
 
 
 
 
 
 
 
 
AS MDI 90 μg 
  N 
xx 
xx 
 
 
 
 
  Mean  
x.xxx 
x.xxx 
 
 
 
 
  SD 
x.xxx 
x.xxx 
 
 
 
 
  Median 
x.xxx 
x.xxx 
 
 
 
 
  Min-Max 
x.xxx-x.xxx 
x.xxx-x.xxx 
 
 
 
 
  LS Mean (SE) 
 
  x.xxx 
(x.xxxx)       
  x.xxx (x.xxxx)    Not Applicable 
  x.xxx (x.xxxx)      x.xxx (x.xxxx)   
  95% CI 
 
( x.xxx, 
x.xxx) 
( x.xxx, x.xxx) 
 
( x.xxx, x.xxx) 
( x.xxx, x.xxx) 
  P-value 
 
 
x.xxxx 
 
 
x.xxxx 
 
 
 
 
 
 
 
Proventil 180 μg 
  N 
xx 
xx 
 
 
 
 
  Mean  
x.xxx 
x.xxx 
 
 
 
 
  SD 
x.xxx 
x.xxx 
 
 
 
 
  Median 
x.xxx 
x.xxx 
 
 
 
 
  Min-Max 
x.xxx-x.xxx 
x.xxx-x.xxx 
 
 
 
 
  LS Mean (SE) 
 
  x.xxx 
(x.xxxx)       
  x.xxx (x.xxxx)    Shown Above 
Not Applicable 
  x.xxx (x.xxxx)   
  95% CI 
 
( x.xxx, 
x.xxx) 
( x.xxx, x.xxx) 
 
 
( x.xxx, x.xxx) 
  P-value 
 
 
x.xxxx 
 
 
x.xxxx 
 
 
 
 
 
 
 
Proventil 90 μg 
  N 
xx 
 
 
 
 
 


Albuterol Sulfate Pressurized Inhalation Suspension 
Protocol D6930C00001 (PT007001) 
Version 0.1 
13 Mar 2018 
Page 30 of 87 
 
 
Treatment 
Baseline FEV1 
Change From 
Baseline  
AUC0-6 
LS Mean Differences Between Treatments  
Placebo 
AS MDI 90 μg 
Proventil 180 μg 
Proventil 90 μg 
  Mean  
x.xxx 
 
 
 
 
 
  SD 
x.xxx 
 
 
 
 
 
  Median 
x.xxx 
 
 
 
 
 
  Min-Max 
x.xxx-x.xxx 
 
 
 
 
 
  LS Mean (SE) 
 
  x.xxx 
(x.xxxx) 
  x.xxx (x.xxxx)    Shown Above 
Shown Above 
Not Applicable 
  95% CI 
 
( x.xxx, 
x.xxx) 
( x.xxx, x.xxx) 
 
 
 
  P-value 
 
 
x.xxxx 
 
 
 
 
 
 
 
 
 
 
Placebo 
  N 
xx 
 
 
 
 
 
  Mean  
x.xxx 
 
 
 
 
 
  SD 
x.xxx 
 
 
 
 
 
  Median 
x.xxx 
 
 
 
 
 
  Min-Max 
x.xxx-x.xxx 
 
 
 
 
 
  LS Mean (SE) 
 
  x.xxx 
(x.xxxx) 
Not Applicable 
Shown Above 
Shown Above 
Shown Above 
  95% CI 
 
( x.xxx, 
x.xxx) 
 
 
 
 
 
Repeat Above for: 
Subgroup: ICS Use at Screening [b] 
 
Repeat Above for: 
Subgroup: Did Not Use ICS at Screening [b] 
 
Treatment-by-Subgroup Interaction P-value: 0.xxxx 
Baseline is defined as the mean of evaluable 60 and 30 minute pre-dose values across Visits 2, 3, 4, 5, and 6.  
ICS = Inhaled Corticosteroid 
LS Mean = least squares mean from the the linear mixed effects model 
[a] Combined ICS Use Groups Model: 
A linear mixed effect model with a random subject effect for the correlation across periods and fixed effects for treatment, 
treatment sequence, baseline FEV1, and period. 
[b] ICS Use Subgroups Model: 
A linear mixed effect model with a random subject effect and fixed effects for treatment, treatment sequence, baseline FEV1, 
period, ICS Use subgroup, and treatment-by-subgroup interaction. 
The p-value is for the superiority comparison of AS MDI or Proventil to Placebo.  The non-inferiority of AS MDI 180 μg to 
Proventil 180 μg or of AS MDI 90 μg to Proventil 90 μg is concluded when the lower CI limit for the difference between 
treatments is >-100 mL. 
 
Report generated by program: PT007001/sasdir/programs/statout/t020101.sas  Version  YYYY-MM-DD hh:mm             (Page n of N)  
 
Note to Programmer: The baseline summary statistics are based on subjects who had at least one data point post-baseline on Day 1. 


Albuterol Sulfate Pressurized Inhalation Suspension 
Protocol D6930C00001 (PT007001) 
Version 0.1 
13 Mar 2018 
Page 31 of 87 
 
 
Table 2.1.2 
Change from Baseline in FEV1 AUC0-6 (L) Overall and by ICS Use Subgroups 
Analysis Set: ITT Analysis Set 
 
 
 
Secondary Efficacy Endpoints 
 
Table 2.2.1 
Change from Baseline in FEV1 AUC0-4 (L) 
Analysis Set: mITT Analysis Set 
 
Notes to Programmer:  
Follow the format of Table 2.1.1. 
 
Table 2.2.2 
Peak Change from Baseline in FEV1 (L) 
Analysis Set: mITT Analysis Set 
 
Notes to Programmer:  
Follow the format of Table 2.1.1. 
 


Albuterol Sulfate Pressurized Inhalation Suspension 
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Version 0.1 
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Page 32 of 87 
 
 
Other Efficacy Endpoints 
 
Table 2.3.1 
Change from Baseline in FEV1 (L) by Timepoint 
Analysis Set: mITT Analysis Set 
 
Treatment 
Baseline FEV1 
Change From 
Baseline 
LS Mean Differences Between Treatments  
Placebo 
AS MDI 90 μg 
Proventil 180 μg 
Proventil 90 μg 
 
5 Minutes Post-Dose [a] 
 
AS MDI 180 μg 
  N 
xx 
xx 
 
 
 
 
  Mean  
x.xxx 
x.xxx 
 
 
 
 
  SD 
x.xxx 
x.xxx 
 
 
 
 
  Median 
x.xxx 
x.xxx 
 
 
 
 
  Min-Max 
x.xxx-x.xxx 
x.xxx-x.xxx 
 
 
 
 
  LS Mean (SE) 
 
  x.xxx 
(x.xxxx)       
  x.xxx (x.xxxx)      x.xxx (x.xxxx)      x.xxx (x.xxxx)      x.xxx (x.xxxx)   
  95% CI 
 
( x.xxx, 
x.xxx) 
( x.xxx, x.xxx) 
( x.xxx, x.xxx) 
( x.xxx, x.xxx) 
( x.xxx, x.xxx) 
  P-value 
 
 
x.xxxx 
x.xxxx 
x.xxxx 
 
 
 
 
 
 
 
 
AS MDI 90 μg 
  N 
xx 
xx 
 
 
 
 
  Mean  
x.xxx 
x.xxx 
 
 
 
 
  SD 
x.xxx 
x.xxx 
 
 
 
 
  Median 
x.xxx 
x.xxx 
 
 
 
 
  Min-Max 
x.xxx-x.xxx 
x.xxx-x.xxx 
 
 
 
 
  LS Mean (SE) 
 
  x.xxx 
(x.xxxx)       
  x.xxx (x.xxxx)    Not Applicable 
  x.xxx (x.xxxx)      x.xxx (x.xxxx)   
  95% CI 
 
( x.xxx, 
x.xxx) 
( x.xxx, x.xxx) 
 
( x.xxx, x.xxx) 
( x.xxx, x.xxx) 
  P-value 
 
 
x.xxxx 
 
 
x.xxxx 
 
 
 
 
 
 
 
Proventil 180 μg 
  N 
xx 
xx 
 
 
 
 
  Mean  
x.xxx 
x.xxx 
 
 
 
 
  SD 
x.xxx 
x.xxx 
 
 
 
 
  Median 
x.xxx 
x.xxx 
 
 
 
 
  Min-Max 
x.xxx-x.xxx 
x.xxx-x.xxx 
 
 
 
 
  LS Mean (SE) 
 
  x.xxx 
(x.xxxx)       
  x.xxx (x.xxxx)    Shwon Above 
Not Applicable 
  x.xxx (x.xxxx)   
  95% CI 
 
( x.xxx, 
x.xxx) 
( x.xxx, x.xxx) 
 
 
( x.xxx, x.xxx) 
  P-value 
 
 
x.xxxx 
 
 
x.xxxx 


Albuterol Sulfate Pressurized Inhalation Suspension 
Protocol D6930C00001 (PT007001) 
Version 0.1 
13 Mar 2018 
Page 33 of 87 
 
 
Treatment 
Baseline FEV1 
Change From 
Baseline 
LS Mean Differences Between Treatments  
Placebo 
AS MDI 90 μg 
Proventil 180 μg 
Proventil 90 μg 
 
 
 
 
 
 
 
Proventil 90 μg 
  N 
xx 
 
 
 
 
 
  Mean  
x.xxx 
 
 
 
 
 
  SD 
x.xxx 
 
 
 
 
 
  Median 
x.xxx 
 
 
 
 
 
  Min-Max 
x.xxx-x.xxx 
 
 
 
 
 
  LS Mean (SE) 
 
  x.xxx 
(x.xxxx) 
  x.xxx (x.xxxx)    Shown Above 
Shown Above 
Not Applicable 
  95% CI 
 
( x.xxx, 
x.xxx) 
( x.xxx, x.xxx) 
 
 
 
  P-value 
 
 
x.xxxx 
 
 
 
 
 
 
 
 
 
 
Placebo 
  N 
xx 
 
 
 
 
 
  Mean  
x.xxx 
 
 
 
 
 
  SD 
x.xxx 
 
 
 
 
 
  Median 
x.xxx 
 
 
 
 
 
  Min-Max 
x.xxx-x.xxx 
 
 
 
 
 
  LS Mean (SE) 
 
  x.xxx 
(x.xxxx) 
Not Applicable 
Shown Above 
Shown Above 
Shown Above 
  95% CI 
 
( x.xxx, 
x.xxx) 
 
 
 
 
 
Repeat for 30, 45, 60, 120, 180, 240, 300, and 360 minutes. 
 
 
 
 
 


Albuterol Sulfate Pressurized Inhalation Suspension 
Protocol D6930C00001 (PT007001) 
Version 0.1 
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Page 34 of 87 
 
 
 
Figure 2.3.1.1 
Change from Baseline in FEV1 (L) ± SE Over Time 
Analysis Set: mITT Analysis Set 
 
 
 
Source: Table 2.3.1 
 
Report generated by program: PT007001/sasdir/programs/statout/f02030101.sas  Version  YYYY-MM-DD xx:xx     (Page n of N) 
 
Notes to Programmer: Replace Number of Weeks Post-Dose with Number of Minutes Post-Dose. 
Replace the treatment labels with ‘AS MDI 180 μg’, ‘AS MDI 90 μg’, ‘Proventil 180 μg’, ‘Proventil 90 μg’, and ‘Placebo’. 
Replace y-axis label with ‘FEV1 Change From Baseline’. 
 
 


Albuterol Sulfate Pressurized Inhalation Suspension 
Protocol D6930C00001 (PT007001) 
Version 0.1 
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Figure 2.3.1.2 
Treatment Differences From Placebo*: Change from Baseline in FEV1 (L) ± 95% CI Over Time 
Analysis Set: mITT Analysis Set 
 
 
*Differences of active treatments vs. Plabebo. 
 
Source: Table 2.3.1 
 
Report generated by program: PT007001/sasdir/programs/statout/f02030102.sas Version  YYYY-MM-DD xx:xx    (Page n of N) 
 
Notes to Programmer: Replace Number of Weeks Post-Dose with Number of Minutes Post-Dose. 
Replace the treatment labels with ‘AS MDI 180 μg’, ‘AS MDI 90 μg’, ‘Proventil 180 μg’, and ‘Proventil 90 μg’. 
Replace y-axis label with ‘FEV1 Change From Baseline’. 
 
 
 


Albuterol Sulfate Pressurized Inhalation Suspension 
Protocol D6930C00001 (PT007001) 
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Page 36 of 87 
 
 
Table 2.3.2 
Time to Peak FEV1 
Analysis Set: mITT Analysis Set 
 
Placebo 
(N=xxx) 
AS MDI 
90 μg 
(N=xxx) 
AS MDI 
180 μg 
(N=xxx) 
Proventil 
90 μg 
(N=xxx) 
Proventil 
180 μg 
(N=xxx) 
 
 
 
 
 
Subjects with a Post-Dose FEV1, n(%) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
 
 
 
 
 
Time to Peak FEV1 (mins) 
 
 
 
 
 
Median (Min, Max) 
x.x (x.x, x.x) 
x.x (x.x, x.x) 
x.x (x.x, x.x) 
x.x (x.x, x.x) 
x.x (x.x, x.x) 
 
 
 
 
 
Median Difference (95% CI) 
 
 
 
 
 
 
 
 
 
 
Placebo (n=xxx) 
Not Applicable 
x.xxx 
(x.xxx, x.xxx) 
x.xxx 
(x.xxx, x.xxx) 
x.xxx 
(x.xxx, x.xxx) 
x.xxx 
(x.xxx, x.xxx) 
 
 
 
 
 
AS MDI 90 μg (n=xxx) 
 
Not Applicable 
x.xxx 
(x.xxx, x.xxx) 
x.xxx 
(x.xxx, x.xxx) 
x.xxx 
(x.xxx, x.xxx) 
 
 
 
 
 
AS MDI 180 μg (n=xxx) 
 
 
Not Applicable 
x.xxx 
(x.xxx, x.xxx) 
x.xxx 
(x.xxx, x.xxx) 
 
 
 
 
 
Proventil 90 μg (n=xxx) 
 
 
 
Not Applicable 
x.xxx 
(x.xxx, x.xxx) 
 
 
Time to Peak FEV1 (mins) = (time of Peak FEV1 – treatment administration time). Time to peak is calculated only for subjects with a 
post-dose FEV1. 
95% CI’s of the median differences were calculated with Hodges-Lehmann CI’s for paired observations. 
Report generated by program: <study>/sasdir/programs/statout/t020302.sas  <VERSION TYPE>  YYYY-MM-DD xx:xx              (Page n of N)   
 
Notes to Programmer: Use data up to the last assessment for each visit. 
 
 
 


Albuterol Sulfate Pressurized Inhalation Suspension 
Protocol D6930C00001 (PT007001) 
Version 0.1 
13 Mar 2018 
Page 37 of 87 
 
 
Table 2.3.3 
Percentage of Subjects Achieving a 12% or 15% Improvement in FEV1 from Baseline Within 30 Minutes Post-Dose 
Analysis Set: mITT Analysis Set 
 
Reason for 
Placebo 
(N=xxx) 
AS MDI 
90 μg 
(N=xxx) 
AS MDI 
180 μg 
(N=xxx) 
Proventil  
90 μg 
(N=xxx) 
Proventil  
180 μg 
(N=xxx) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
 
 
 
 
 
 
Subjects Achieving 12% 
Improvement in FEV1 from 
Baseline Within 30 Minutes of 
Dose 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
Odds Ratio (95% CI) 
 
 
 
 
 
 
 
 
 
 
 
Placebo (n=xxx) 
Not Applicable 
x.xxx 
(x.xxx, x.xxx) 
x.xxx 
(x.xxx, x.xxx) 
x.xxx 
(x.xxx, x.xxx) 
x.xxx 
(x.xxx, x.xxx) 
 
 
 
 
 
 
AS MDI 90 μg (n=xxx) 
 
Not Applicable 
x.xxx 
(x.xxx, x.xxx) 
x.xxx 
(x.xxx, x.xxx) 
x.xxx 
(x.xxx, x.xxx) 
 
 
 
 
 
 
AS MDI 180 μg (n=xxx) 
 
 
Not Applicable 
x.xxx 
(x.xxx, x.xxx) 
x.xxx 
(x.xxx, x.xxx) 
 
 
 
 
 
 
Proventil 90 μg (n=xxx) 
 
 
 
Not Applicable 
x.xxx 
(x.xxx, x.xxx) 
 
 
 
 
 
 
Subjects Achieving 15% 
Improvement in FEV1 from 
Baseline Within 30 Minutes of 
Dose 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
 
Odds Ratio (95% CI) 
 
 
 
 
 
 
 
 
 
 
 
Placebo (n=xxx) 
Not Applicable 
x.xxx 
(x.xxx, x.xxx) 
x.xxx 
(x.xxx, x.xxx) 
x.xxx 
(x.xxx, x.xxx) 
x.xxx 
(x.xxx, x.xxx) 
 
 
 
 
 
 
AS MDI 90 μg (n=xxx) 
 
Not Applicable 
x.xxx 
(x.xxx, x.xxx) 
x.xxx 
(x.xxx, x.xxx) 
x.xxx 
(x.xxx, x.xxx) 
 
 
 
 
 
 
AS MDI 180 μg (n=xxx) 
 
 
Not Applicable 
x.xxx 
(x.xxx, x.xxx) 
x.xxx 
(x.xxx, x.xxx) 
 
 
 
 
 
 
Proventil 90 μg (n=xxx) 
 
 
 
Not Applicable 
x.xxx 
(x.xxx, x.xxx) 
 
 
 
 
 
 


Albuterol Sulfate Pressurized Inhalation Suspension 
Protocol D6930C00001 (PT007001) 
Version 0.1 
13 Mar 2018 
Page 38 of 87 
 
 
N is the number of subjects with at least one post-dose FEV1 assessment within 30 minutes of dose. 
n is the number of subjects who did or did not achieve 12% or 15% improvement in FEV1 from baseline within 30 minutes of 
dose. 
The odds ratios are calculated from a a generalized mixed effects model with treatment as a fixed effect and the intercept 
for each subject as a random effect.   
 
Report generated by program: PT007001/sasdir/programs/statout/t020303.sas  Version  YYYY-MM-DD xx:xx               (Page n of N) 
 
 
Table 2.3.4 
Time to Onset of 12% Improvement in FEV1 
Analysis Set: mITT Analysis Set 
 
Note to the Programmer: Use shell for Table 2.3.2. 
Replace footnote:  Time to Onset of Response (minutes) = (time of first achievement of a 12% increase in FEV1 from baseline, within 30 minutes of dose – 
treatment administration time). 
 
Table 2.3.5 
Time to Onset of 15% Improvement in FEV1 
Analysis Set: mITT Analysis Set 
 
Note to the Programmer: Use shell for Table 2.3.2. 
Replace footnote:  Time to Onset of Response (minutes) = (time of first achievement of a 15% increase in FEV1 from baseline, within 30 minutes of dose – 
treatment administration time). 
 
 
 


Albuterol Sulfate Pressurized Inhalation Suspension 
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Version 0.1 
13 Mar 2018 
Page 39 of 87 
 
 
Table 2.3.6 
Duration of 12% Improvement in FEV1 
Analysis Set: mITT Analysis Set 
 
Duration of 
Response (mins) 
 
LS Mean Differences Between Treatments 
Placebo 
(N=xxx) 
AS MDI 
90 μg 
(N=xxx) 
AS MDI 
180 μg 
(N=xxx) 
Proventil 
90 μg 
(N=xxx) 
Proventil 
180 μg 
(N=xxx) 
 
 
 
 
 
 
Subjects with a 12% increase in 
FEV1 from baseline, within 30 
minutes of dose, n(%) 
 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
 
 
 
 
 
 
Placebo (n=xxx) 
 
 
 
 
 
 
N 
xx 
 
 
 
 
 
Mean 
xxx.x 
 
 
 
 
 
SD 
xxx.xx 
 
 
 
 
 
Median 
x.x 
 
 
 
 
 
Min, Max 
(x.x, x.x) 
 
 
 
 
 
 LS Mean (SE) 
 
Not Applicable 
  x.xxx 
(x.xxxx)     
  x.xxx 
(x.xxxx)     
  x.xxx 
(x.xxxx)     
  x.xxx 
(x.xxxx)     
 95% CI 
 
 
( x.xxx, x.xxx) ( x.xxx, x.xxx) ( x.xxx, x.xxx) ( x.xxx, x.xxx) 
 P-value 
 
 
x.xxxx 
x.xxxx 
x.xxxx 
x.xxxx 
 
 
 
 
 
 
AS MDI 90 μg (n=xxx) 
 
 
 
 
 
 
N 
xx 
 
 
 
 
 
Mean 
xxx.x 
 
 
 
 
 
SD 
xxx.xx 
 
 
 
 
 
Median 
x.x 
 
 
 
 
 
Min, Max 
(x.x, x.x) 
 
 
 
 
 
 LS Mean (SE) 
 
 
Not Applicable 
  x.xxx 
(x.xxxx)     
  x.xxx 
(x.xxxx)     
  x.xxx 
(x.xxxx)     
 95% CI 
 
 
 
( x.xxx, x.xxx) ( x.xxx, x.xxx) ( x.xxx, x.xxx) 
 P-value 
 
 
 
x.xxxx 
x.xxxx 
x.xxxx 
 
 
 
 
 
 
AS MDI 180 μg (n=xxx) 
 
 
 
 
 
 
N 
xx 
 
 
 
 
 
Mean 
xxx.x 
 
 
 
 
 
SD 
xxx.xx 
 
 
 
 
 
Median 
x.x 
 
 
 
 
 
Min, Max 
(x.x, x.x) 
 
 
 
 
 
 LS Mean (SE) 
 
 
 
Not Applicable 
  x.xxx 
(x.xxxx)     
  x.xxx 
(x.xxxx)     
 95% CI 
 
 
 
 
( x.xxx, x.xxx) ( x.xxx, x.xxx) 
 P-value 
 
 
 
 
x.xxxx 
x.xxxx 
 
 
 
 
 
 


Albuterol Sulfate Pressurized Inhalation Suspension 
Protocol D6930C00001 (PT007001) 
Version 0.1 
13 Mar 2018 
Page 40 of 87 
 
 
Proventil 90 μg (n=xxx) 
 
 
 
 
 
 
N 
xx 
 
 
 
 
 
Mean 
xxx.x 
 
 
 
 
 
SD 
xxx.xx 
 
 
 
 
 
Median 
x.x 
 
 
 
 
 
Min, Max 
(x.x, x.x) 
 
 
 
 
 
 LS Mean (SE) 
 
 
 
 
Not Applicable 
  x.xxx 
(x.xxxx)     
 95% CI 
 
 
 
 
 
( x.xxx, x.xxx) 
 P-value 
 
 
 
 
 
x.xxxx 
 
 
 
 
 
 
Proventil 180 μg (n=xxx) 
 
 
 
 
 
 
N 
xx 
 
 
 
 
 
Mean 
xxx.x 
 
 
 
 
 
SD 
xxx.xx 
 
 
 
 
 
Median 
x.x 
 
 
 
 
 
Min, Max 
(x.x, x.x) 
 
 
 
 
 
 LS Mean (SE) 
 
Shown Above 
Shown Above 
Shown Above 
Shown Above 
Not Applicable 
 95% CI 
 
 
 
 
 
 
 P-value 
 
 
 
 
 
 
 
 
Duration of response (mins) = (time of offset – time of onset) where onset is defined as a ≥ 12% improvement from baseline in FEV1 
within the 30 minutes post dose. If a subject had a 2nd onset of response subsequent to achievement of offset, their data for that 
period was excluded from the duration of response analysis. 
LS Means (SE), 95% CIs, and P-values are from a linear mixed effect model with a random subject effect for the correlation across 
periods and fixed effects for treatment, treatment sequence, and period. 
Report generated by program: <study>/sasdir/programs/statout/t020302.sas  <VERSION TYPE>  YYYY-MM-DD xx:xx              (Page n of N)   
 
Notes to Programmer: Use data up to the last assessment for each visit. 
                                      The linear mixed model will be replaced with a distribution-free method (Hodges-Lehmann) as appropriate to the data. 
Time to Onset of Response (minutes) = (time of first achievement of a 12% increase in FEV1 from baseline, within 30 minutes of dose – treatment administration time). 
Time to Offset of Response:  For responders only:  (time of first assessment  after achievement of response for which the increase from baseline in FEV1 is < 15% (or 12%) – 
treatment administration time). If offset of  FEV1 < 15% (or 12%) is not achieved and the last available assessment is ≥ 15% (or 12%), the time to offset will be defined as (the 
time of the last available assessment – treatment administration time.  Thus, Offset of Response:  For responders only:  the 1st time point after achievement of response for which 
the increase from baseline in FEV1 is < 15% (or 12%). If offset is not achieved according to this definition, and the last available assessment is >= 15% (or 12%), offset will be 
defined as the time of the last available assessment. 
Duration of response is defined n the table footnote above.: 
 
Table 2.3.7 
Duration of 12% Improvement in FEV1: Subjects who Have Assessments at the 180- and 300-Minute Post-Dose Timepoints 
Analysis Set: mITT Analysis Set 
 
 
 
 


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Table 2.3.8 
Duration of 15% Improvement in FEV1 
Analysis Set: mITT Analysis Set 
 
Notes to Programmer: Replace Duration footnote with: Duration of response (mins) = (time of offset – time of onset) where onset is defined as a ≥ 15% 
improvement from baseline in FEV1 within the 30 minutes post dose. If a subject had a 2nd onset of response subsequent to achievement of offset, their data for 
that period was excluded from the duration of response analysis. 
 
Table 2.3.9 
Duration of 15% Improvement in FEV1: Subjects who Have Assessments at the 180- and 300-Minute Post-Dose Timepoints 
Analysis Set: mITT Analysis Set 
 
 


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3. Safety 
 
Adverse Events 
 
Table 3.1.1 
Overall Summary of Treatment-Emergent Adverse Events 
Analysis Set: Safety Analysis Set 
 
Placebo 
(N=xxx) 
AS MDI 90 μg 
(N=xxx) 
AS MDI 180 μg 
(N=xxx) 
Proventil 90 μg 
(N=xxx) 
Proventil 180 μg 
(N=xxx) 
n (%) 
[Events] 
n (%) 
[Events] 
n (%) 
[Events] 
n (%) 
[Events] 
n (%) 
[Events] 
Subjects With at Least One TEAE [a] [b] 
xx (xx.x) 
[xxx] 
xx (xx.x) 
[xxx] 
xx (xx.x) 
[xxx] 
xx (xx.x) 
[xxx] 
xx (xx.x) 
[xxx] 
 
 
 
 
 
Subjects With Serious TEAEs 
xx (xx.x) 
[xx.x] 
xx (xx.x) 
[xx.x] 
xx (xx.x) 
[xx.x] 
xx (xx.x) 
[xx.x] 
xx (xx.x) 
[xx.x] 
Subjects With TEAEs Related to Study 
Treatment [c] 
xx (xx.x) 
[xxx] 
xx (xx.x) 
[xxx] 
xx (xx.x) 
[xxx] 
xx (xx.x) 
[xxx] 
xx (xx.x) 
[xxx] 
Subjects With Serious TEAEs Related to Study 
Treatment [c] 
xx (xx.x) 
[xx.x] 
xx (xx.x) 
[xx.x] 
xx (xx.x) 
[xx.x] 
xx (xx.x) 
[xx.x] 
xx (xx.x) 
[xx.x] 
Subjects With TEAEs Leading to Early 
Discontinuation 
xx (xx.x) 
[xx.x] 
xx (xx.x) 
[xx.x] 
xx (xx.x) 
[xx.x] 
xx (xx.x) 
[xx.x] 
xx (xx.x) 
[xx.x] 
 
 
 
 
 
Deaths – All Causes 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
[a] TEAE = Treatment-Emergent Adverse Event 
[a] Only adverse events on a Treatment Day were included in this table. 
[c] Related = Yes or No. 
Report generated by program: PT007001/sasdir/programs/statout/t030101.sas  Version  YYYY-MM-DD  xx:xx               (Page n of N) 
 
 
 


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Table 3.1.2 
Overall Summary of Treatment-Emergent Adverse Events Including Adverse Events on a Treatment Day or During the Washout or Follow-up 
Periods 
Analysis Set: Safety Analysis Set 
 
Placebo 
(N=xxx) 
AS MDI 90 μg 
(N=xxx) 
AS MDI 180 μg 
(N=xxx) 
Proventil 90 μg 
(N=xxx) 
Proventil 180 μg 
(N=xxx) 
n (%) 
[Events] 
n (%) 
[Events] 
n (%) 
[Events] 
n (%) 
[Events] 
n (%) 
[Events] 
Subjects With at Least One TEAE [a] 
xx (xx.x) 
[xxx] 
xx (xx.x) 
[xxx] 
xx (xx.x) 
[xxx] 
xx (xx.x) 
[xxx] 
xx (xx.x) 
[xxx] 
 
 
 
 
 
Subjects With Serious TEAEs 
xx (xx.x) 
[xx.x] 
xx (xx.x) 
[xx.x] 
xx (xx.x) 
[xx.x] 
xx (xx.x) 
[xx.x] 
xx (xx.x) 
[xx.x] 
Subjects With TEAEs Related to Study 
Treatment [b] 
xx (xx.x) 
[xxx] 
xx (xx.x) 
[xxx] 
xx (xx.x) 
[xxx] 
xx (xx.x) 
[xxx] 
xx (xx.x) 
[xxx] 
Subjects With Serious TEAEs Related to Study 
Treatment [b] 
xx (xx.x) 
[xx.x] 
xx (xx.x) 
[xx.x] 
xx (xx.x) 
[xx.x] 
xx (xx.x) 
[xx.x] 
xx (xx.x) 
[xx.x] 
Subjects With TEAEs Leading to Early 
Discontinuation 
xx (xx.x) 
[xx.x] 
xx (xx.x) 
[xx.x] 
xx (xx.x) 
[xx.x] 
xx (xx.x) 
[xx.x] 
xx (xx.x) 
[xx.x] 
 
 
 
 
 
Deaths – All Causes 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
 
 
[a] TEAE = Treatment-Emergent Adverse Event 
[b] Related = Yes or No. 
Report generated by program: PT007001/sasdir/programs/statout/t030102.sas  Version  YYYY-MM-DD  xx:xx               (Page n of N) 
 
 
 


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Table 3.2.1 
Treatment-Emergent Adverse Events by MedDRA Primary System Organ Class and Preferred Term 
Analysis Set: Safety Analysis Set 
 
System Organ Class 
  Preferred Term 
Placebo 
(N=xxx) 
AS MDI 90 μg 
(N=xxx) 
AS MDI 180 μg 
(N=xxx) 
Proventil 90 μg 
(N=xxx) 
Proventil 180 μg 
(N=xxx) 
n (%) 
[Events] 
n (%) 
[Events] 
n (%) 
[Events] 
n (%) 
[Events] 
n (%) 
[Events] 
 
 
 
 
 
 
At Least One TEAE [a] 
xx ( xx.x) 
[xx] 
xx ( xx.x) 
[xx] 
xx ( xx.x) 
[xx] 
xx ( xx.x) 
[xx] 
xx ( xx.x) 
[xx] 
 System Organ Class 1 
xx ( xx.x) 
[xx] 
xx ( xx.x) 
[xx] 
xx ( xx.x) 
[xx] 
xx ( xx.x) 
[xx] 
xx ( xx.x) 
[xx] 
   Preferred Term 1 
xx ( xx.x) 
[xx] 
xx ( xx.x) 
[xx] 
xx ( xx.x) 
[xx] 
xx ( xx.x) 
[xx] 
xx ( xx.x) 
[xx] 
   Preferred Term 2 
xx ( xx.x) 
[xx] 
xx ( xx.x) 
[xx] 
xx ( xx.x) 
[xx] 
xx ( xx.x) 
[xx] 
xx ( xx.x) 
[xx] 
 System Organ Class 2 
xx ( xx.x) 
[xx] 
xx ( xx.x) 
[xx] 
xx ( xx.x) 
[xx] 
xx ( xx.x) 
[xx] 
xx ( xx.x) 
[xx] 
   Preferred Term 1 
xx ( xx.x) 
[xx] 
xx ( xx.x) 
[xx] 
xx ( xx.x) 
[xx] 
xx ( xx.x) 
[xx] 
xx ( xx.x) 
[xx] 
   Preferred Term 2 
xx ( xx.x) 
[xx] 
xx ( xx.x) 
[xx] 
xx ( xx.x) 
[xx] 
xx ( xx.x) 
[xx] 
xx ( xx.x) 
[xx] 
 Etc.… 
 
 
 
 
 
[a]   TEAE = Treatment-Emergent Adverse Event. 
Report generated by program: PT007001/sasdir/programs/statout/t030201.sas  Version  YYYY-MM-DD xx:xx                (Page n of N) 
 
Table 3.2.2 
Treatment-Emergent Adverse Events by MedDRA Primary System Organ Class and Preferred Term Including Events Occurring During the 
Washout or Follow-up Periods: Sensitivity Analysis 
Analysis Set: Safety Analysis Set 
 
Notes to Programmer: Same as Table 3.2.1, however, AEs that occur during the Washout Period or Follow-up periods are attributed to the treatment given in the preceding 
Treatment Period. Add the following footnote: “AEs that occur during the Washout or Follow-up periods are attributed to the treatment given in the preceding Treatment Period.” 
 
Table 3.2.3 
Treatment-Emergent Adverse Events Occurring in >=2% of Subjects in a Treatment by Descending Frequency 
Analysis Set: Safety Analysis Set 
 
Notes to Programmer: Sort preferred terms by descending frequency of number of events across All Subjects. Use the format of Table 3.2.1, but delete the “At Least One” row 
from this Table. SOCs will not be used in this Table. 
 
 


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Table 3.2.4 
Non-serious Treatment-Emergent Adverse Events Occurring in  >=5% of Subjects in a Treatment by MedDRA Primary System Organ Class 
and Preferred Term 
Analysis Set: Safety Analysis Set 
 
Notes to Programmer: use the format of Table 3.2.1. 
 
 


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Table 3.3 
Treatment-Related Treatment-Emergent Adverse Events by MedDRA Primary System Organ Class and Preferred Term 
Analysis Set: Safety Analysis Set 
 
[a]  Related = Yes or No. 
 
Report generated by program: PT007001/sasdir/programs/statout/t0304.sas    Version YYYY-MM-DD xx:xx   (Page n of N) 
 
Notes to Programmer: use the format of Table 3.2.1. 
 
Table 3.4 
Treatment-Emergent Adverse Events Leading to Study Drug Discontinuation by MedDRA Primary System Organ Class and Preferred Term 
Analysis Set: Safety Analysis Set 
 
[a]  A TEAE leading to treatment discontinuation is an AE with ‘Action Taken’ = ‘Drug withdrawn’, or ‘Outcome’ = ‘Fatal’,  
     or ‘Death’ as reason for Seriousness on Adverse Event’ CRF.  
                        
Report generated by program: PT007001/sasdir/programs/statout/t0305.sas  Version  YYYY-MM-DD xx:xx   (Page n of N) 
 
Notes to Programmer: use the format of Table 3.2.1. 
 
 


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Table 3.5 
Listing of Adverse Events Leading to Permanent Discontinuation of Study Treatment 
Analysis Set: All Subjects Randomized 
 
Subject 
ID 
(Age/ 
Gender/ 
Race) 
[a] 
Primary System 
Organ Class 
AE Verbatim 
(Preferred Term)  
Treat. 
Emerg. 
Event 
Serious 
Onset 
Date 
(Study  
Day) 
[b] 
Duration 
of Event 
[c] 
Severity  
Relation
-ship 
Action  
AE 
Treated 
Outcome 
(Death) 
Study Day 
Resolved/ 
Death [b] 
Treatment: AS MDI 180 μg, AS MDI 90 μg, Placebo, Proventil 180 μg, or Proventil 90 μg 
Center # (Investigator): Center ### (xxxxxxxxxx) 
xxxxxx 
(54/F/W) 
xxx xxx xxxxx 
AE 1 
(xxxxxxxxxx) 
Yes 
No 
YYYY-MM-
DD 
(T1_2) 
  
Moderate  Not 
Related 
Dose 
not 
changed 
No 
Recoverin
g/Resolvi
ng (No) 
xxx xxx xxxx 
AE 2  
(xxxxxxxxxx) 
Yes 
Yes 
YYYY-MM-
DD 
(T2_P1) 
xx 
Moderate Related 
Drug 
Interru
pted  
Yes 
Recovered
/Resolved 
(Yes) 
T2_P3 
… 
… 
 
 
 
 
 
 
Race: A=Asian, AIAN=American Indian or Alaska Native, B=Black or African American, NHPI=Native Hawaiian or Other Pacific Islander, 
     O=Other W=White. Gender: F=Female, M=Male. 
SOC = System Organ Class.  
[a]  # indicates that it could not be determined whether the AE had onset during study treatment. 
[b]  A negative number for study day denotes the number of days prior to the start of study treatment. Otherwise, Study Day is Date – 
Date of dose in the Period + 1. Tx = Period. Tx_y = Period and Day within Period. Pxx = Days after dose in the last Treatment 
Period.  
On Study Day 1, an @ indicates that event started before study drug administration.   
On Study Day 1, @@ indicates that event started after study drug administration. 
[c]  Duration of Event = Stop Day - Onset Day + 1 
Report generated by program: PT007001/sasdir/programs/statout/t0305.sas  Version  YYYY-MM-DD xx:xx   (Page n of N) 
 
 
Notes to Programmer: Sort by Actual Treatment, Center, Subject ID, Primary System Organ Class, and Onset Day of AE. Page by Treatment and not by Treatment and Center. 
 
 
 


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Table 3.6.1 
Serious Adverse Events by MedDRA Primary System Organ Class and Preferred Term 
Analysis Set: Safety Analysis Set 
 
Notes to Programmer: Same as Table 3.2.1. 
 
Table 3.6.2 
Serious Adverse Events by MedDRA Primary System Organ Class and Preferred Term Including Events Occurring During the Washout and 
Follow-up Period: Sensitivity Analysis 
Analysis Set: Safety Analysis Set 
 
Notes to Programmer: Same as Table 3.2.1, however, SAEs that occur during the Washout or Follow-up periods are attributed to the treatment given in the preceding Treatment 
Period. Add the following footnote: “SAEs that occur during the Washout or Follow-up periods are attributed to the treatment given in the preceding Treatment Period.” 
 
 
 
 


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Table 3.7.1 
Listing of Serious Adverse Events (SAEs) 
Analysis Set: All Subjects Screened 
Subject 
ID 
Age 
(yrs)/ 
Gender/
Race 
Primary 
System Organ 
Class 
SAE Verbatim 
(Preferred Term) 
Reason for Being 
Serious (Day) [a] 
Treat. 
Emerg. 
[b] 
Onset Day 
[b] 
(Day of Most 
Recent Dose) 
Duration 
of Event 
[c] 
Severity/ 
Relation-
ship 
Action/ 
(Outcome) 
(AE Treated) 
Study 
Day 
Resolved 
[a] 
 
Treatment: AS MDI 180 μg, AS MDI 90 μg, Placebo, Proventil 180 μg, or Proventil 90 μg 
 
Center # (Investigator): Center ### (xxxxxxxxxx) 
 
xxxxxx 
 
70/F/W 
xxxx xxx xx 
xxxx 
xxx xxx xxxxx xxxxxxx 
(xxxxxxxxxxxxxxxxxxx) 
Hospitalization / 
prolongation of 
existing 
Hospitalization 
(T1_1-Tx_y) 
Yes 
5 
(T2_P1) 
4 
Moderate / 
Not 
Related 
None 
(Recovered/Re
solved) 
(Yes) 
Tx_8 
 
 
 
 
 
 
 
 
 
 
Drug 
Interrupted, 
Date Stopped: 
YYYY-12-07; 
AE abated: 
Yes; Date 
restarted: 
YYYY_12_08: 
AE reoccur? 
Yes 
 
Race: A=Asian, AIAN=American Indian or Alaska Native, B=Black or African American, NHPI=Native Hawaiian or Other Pacific Islander, 
      O=Other W=White. Gender: F=Female, M=Male. 
[a]  A negative number for study day denotes the number of days prior to the start of study treatment. Otherwise, Study Day is Date –  
     Date of dose in the Period + 1. Tx = Period. Tx_y = Period and Day within Period. Pxx = Days after dose in the last Treatment  
     Period.  
On Study Day 1, an @ indicates that event started before study drug administration.   
On Study Day 1, @@ indicates that event started after study drug administration. 
[b]  # indicates that it could not be determined whether the AE had onset during study treatment. 
[c]  Duration of Event = Stop Day - Onset Day + 1 
 
Report generated by program: PT007001/sasdir/programs/statout/t030801.sas  Version  YYYY-MM-DD xx:xx               (Page n of N)  
Notes to Programmer:  
Sort by Actual Treatment, Center, Subject ID, Primary System Organ Class Preferred Term, and Onset Day.  
If Reason for Seriousness is Hospitalization or Prolongation of Existing Hospitalization, also present in parentheses the days subject admitted into and discharged from Hospital 
“(Day xx – Day xx)”.  
If the Reason for Seriousness is death, also present the day of death. 
 
 
 


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Table 3.7.2 
Listing of SAE-Specific Report Information 
Analysis Set: Screened 
 
Subject ID 
Diagnosis, Details and 
Relevant Diagnostic Tests 
Last 
Treatment and 
Date  
(YYYY-MM-DD) 
Date of SAE 
Onset  
(YYYY-MM-DD) 
And Most 
Recent Dose 
of Treatment 
Prior to 
Onset of SAE 
Serious Reason 
(YYYY-MM-DD) 
Action Taken With 
Study Drug 
Severity/ 
Relationship/ 
(Outcome) 
(YYYY-MM-DD) 
SAE 
Treated 
Treatment: AS MDI 180 μg, AS MDI 90 μg, Placebo, Proventil 180 μg, or Proventil 90 μg 
Center # / (Investigator):  ### / (xxxxxxxxxx) 
xxxx 
Diagnosis: 
xxxxxxxxxxxxxxxxxxxxxxx 
Details: signs, symptoms, 
time course, and relevant 
medical history.  
Relevant Diagnostic Tests: 
Confirmatory procedures and 
Results, if any. 
C 2015-07-28 2015-07-24 
YYYY-MM-DD 
 
Death (YYYY-MM-DD) 
Autopsy: yes or no 
 
Life-threatening 
 
Hospitalization or 
prolongation of 
existing 
hospitalization  
(YYYY-MM-DD-YYYY-
MM-DD) 
 
A persistent or 
significant 
disability/incapac
ity 
 
Congenital 
anomaly/birth 
defect 
 
A significant 
medical event that 
requires medical 
or surgical 
intervention to 
prevent one of the 
serious outcomes 
listed above. 
 
None 
Drug Interrupted 
(Stopped: YYYY-MM-DD 
SAE Abated: Yes/No 
Treatment Restarted: 
YYYY-MM-DD 
SAE Reoccur: Yes/no) 
Permanently Withdrawn 
(YYYY-MM-DD) 
Moderate / 
Related / 
(Recovered/Re
solved) 
(2015-07-27) 
Yes/No 


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Notes to Programmer: Sort by Center, Subject ID, and Onset Day of SAE. Move ‘Center’ row header to the next page whenever there is not enough room on current page to fit at 
least one row of data underneath this header. In order for the SAE-Specific Report Information to be listed, it will need to be included in the SDTM data sets. 
 
 


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Table 3.8 
Treatment Related Serious Adverse Events by MedDRA Primary System Organ Class and Preferred Term 
Analysis Set: Safety Analysis Set 
 
[a]  Related = Yes or No. 
 
Notes to Programmer: Same as Table 3.2.1. 
 
 
 


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Table 3.9.1 
TEAEs by Primary System Organ Class, Preferred Term, and Highest Severity – Placebo 
Analysis Set: Safety Analysis Set 
 
 
Primary System Organ Class 
   Preferred Term 
Placebo (N=xxx) 
Mild 
n (%) 
Moderate 
 n (%) 
Severe 
 n (%) 
Any Severity 
n (%) 
 
 
 
 
 
At Least One TEAE  
xxx (xxx.x) 
xxx (xxx.x) 
xxx (xxx.x) 
xxx (xxx.x) 
 
 
 
 
 
System Organ Class 1 
xxx (xxx.x) 
xxx (xxx.x) 
xxx (xxx.x) 
xxx (xxx.x) 
Preferred Term 1 
xxx (xxx.x) 
xxx (xxx.x) 
xxx (xxx.x) 
xxx (xxx.x) 
Preferred Term 2 
xxx (xxx.x) 
xxx (xxx.x) 
xxx (xxx.x) 
xxx (xxx.x) 
System Organ Class 2  
xxx (xxx.x) 
xxx (xxx.x) 
xxx (xxx.x) 
xxx (xxx.x) 
Preferred Term 1 
xxx (xxx.x) 
xxx (xxx.x) 
xxx (xxx.x) 
xxx (xxx.x) 
Preferred Term 2 
xxx (xxx.x) 
xxx (xxx.x) 
xxx (xxx.x) 
xxx (xxx.x) 
 
 
 
 
 
…. 
 
 
 
 
Only the highest severity is counted for multiple occurrences of the same adverse event in one individual. 
 
Report generated by program: PT007001/sasdir/programs/statout/t031101.sas  Version  YYYY-MM-DD xx:xx                 (Page n of N) 
 
  
Table 3.9.2 
TEAEs by Primary System Organ Class, Preferred Term, and Highest Severity – AS MDI 90 μg  
Analysis Set: Safety Analysis Set 
 
 
Table 3.9.3 
TEAEs by Primary System Organ Class, Preferred Term, and Highest Severity – AS MDI 180 μg 
Analysis Set: Safety Analysis Set 
 
 
Table 3.9.4 
TEAEs by Primary System Organ Class, Preferred Term, and Highest Severity – Proventil 90 μg  
Analysis Set: Safety Analysis Set 
 
 
Table 3.9.5 
TEAEs by Primary System Organ Class, Preferred Term, and Highest Severity – Proventil 180 μg  
Analysis Set: Safety Analysis Set 
 
 
 


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Table 3.10 
Listing of Deaths 
Analysis Set: All Subjects Screened 
 
Subject ID 
Treatment 
Sequence 
Study Day of Dose of Last 
Treatment Prior to Death [a] 
Days on 
Treat-
ment 
Date and Time 
(YYYY-MM-DD) 
(24 h clock) 
of Death 
Days Since 
Dose 
at Time of 
Death [b] 
Adverse Event Preferred 
Term/Verbatim Term 
 
Study Center # / (Investigator): ### / (xxxxxxxxxx) 
 
 
 
 
 
 
 
xxxxx 
x/x 
TRT A 
Day x 
(YYYY-MM-DD) 
1 
YYYY-MM-DD 
 hh:mm 
x 
Preferred Term/AE verbatim 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Treatment: A = Placebo, B = AS MDI 90 μg, C = AS MDI 180 μg, D = Proventil 90 μg, E = Proventil 180 μg, - = Not Treated. 
This includes all subjects who died while on study and up to 30 Days after final treatment dose. 
TRT = Treatment. 
[a]  Study Day of Dose for Treatment = Study Day 1. 
[b]  Days since Last Dose = Date of death – Date of last dose of study treatment + 1. 
 
Report generated by program: PT007001/sasdir/programs/statout/t0313.sas  Version  YYYY-MM-DD xx:xx   (Page n of N) 
 
Notes to Programmer:  For TRT N, N is the treatment period number of the last treatment received by the subject prior to the death.  
Sort by Study Center and Subject within Study Center.  Move ‘Study Center/Inv’ row header to the next page whenever there is not enough room on current page to fit at least one 
row of data underneath this header.   
 


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Vital Signs 
 
Table 3.11.1 
Vital Sign Parameters  
Analysis Set: Safety Analysis Set 
 
Parameter (unit) 
Visit/Timepoint 
Statistic 
Placebo 
(N=xxx) 
AS MDI 
90 μg 
(N=xxx) 
AS MDI 
180 μg 
(N=xxx) 
Proventil 
90 μg 
(N=xxx) 
Proventil 
180 μg 
(N=xxx) 
 
 
 
 
 
Parameter 1 (unit) 
Screening (Visit 1) Actual Value: 
n 
Mean 
SD 
Median 
Minimum 
Maximum 
 
 xxx 
  x.xxx 
  x.xxx 
  x.xxx 
  x.xx 
  x.xx 
 
 xxx 
  x.xxx 
  x.xxx 
  x.xxx 
  x.xx 
  x.xx 
 
 xxx 
  x.xxx 
  x.xxx 
  x.xxx 
  x.xx 
  x.xx 
 
 xxx 
  x.xxx 
  x.xxx 
  x.xxx 
  x.xx 
  x.xx 
 
 xxx 
  x.xxx 
  x.xxx 
  x.xxx 
  x.xx 
  x.xx 
Baseline (Visit 2 
Pre-Dose) 
Actual Value: 
n 
Mean 
SD 
Median 
Minimum 
Maximum 
 
xxx 
  x.xxx 
  x.xxx 
  x.xxx 
  x.xx 
    x.xx 
 
xxx 
  x.xxx 
  x.xxx 
  x.xxx 
  x.xx  
  x.xx 
 
xxx 
  x.xxx 
  x.xxx 
  x.xxx 
  x.xx  
  x.xx 
 
xxx 
  x.xxx 
  x.xxx 
  x.xxx 
  x.xx  
  x.xx 
 
xxx 
  x.xxx 
  x.xxx 
  x.xxx 
  x.xx  
  x.xx 
Change From Baseline: 
n 
Mean 
SD 
Median 
Minimum 
Maximum 
 
xxx 
  x.xxx 
  x.xxx 
  x.xxx 
  x.xx 
  x.xx 
 
xxx 
  x.xxx 
  x.xxx 
  x.xxx 
  x.xx   
  x.xx 
 
xxx 
  x.xxx 
  x.xxx 
  x.xxx 
  x.xx   
  x.xx 
 
xxx 
  x.xxx 
  x.xxx 
  x.xxx 
  x.xx   
  x.xx 
 
xxx 
  x.xxx 
  x.xxx 
  x.xxx 
  x.xx   
  x.xx 
For parameters Height, Weight, and BMI, only include Screening.  For SPB, DBP, and Heart Rate include Screening, Baseline (Visit 2 Pre-
Dose), Visit 2 (Post-Dose), Visit 3 (Pre-Dose), Visit 3 (Post-Dose), Visit 4 (Pre-Dose), Visit 4 (Post-Dose), Visit 5 (Pre-Dose), Visit 
5 (Post-Dose), Visit 6 (Pre-Dose), Visit 6 (Post-Dose), and End of Treatment. 
Baseline is defined as the last pre-dose measurement taken prior to dosing on Day 1 of a treatment period. 
End of Treatment is defined as the last non-missing on treatment assessment available for the timepoint. 
Report generated by program: PT007001/sasdir/programs/statout/t031101.sas  Version  YYYY-MM-DD xx:xx          (Page n of N)  
 
Notes to Programmer:   
Repeat the parameter at the beginning of each page under column header.  Repeat for all parameters. 
 
 


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4. Subject Data Listings 
 
4.1 Subject Discontinuations/Completions 
 
Listing 1.1 
Study Centers 
Analysis Set: All Subjects Screened 
 
Center 
Investigator 
Location 
xxxxxx 
xxxxxxxxxxxxxxxxxxxxxxxx 
xxxxxxxxxxxxxxxx City Country 
xxxxxx 
xxxxxxxxxxxxxxxxxxxxxxxx 
xxxxxxxxxxxxxxxx City Country 
xxxxxx 
xxxxxxxxxxxxxxxxxxxxxxxx 
xxxxxxxxxxxxxxxx City Country 
Source: xxxxxxx.sas7bdat 
 
Report generated by program: /sasdir/programs/statout/l0101.sas       Version                YYYY-MM-DD xx:xx   (Page n of N) 
 
 
 


Albuterol Sulfate Pressurized Inhalation Suspension 
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Listing 1.2 
Subject Disposition and Demographic Data 
Analysis Set: All Subjects Screened 
 
Subject ID 
(Treatment 
Sequence) 
Age 
(yrs)[a]/ 
Gender 
(Race/Eth
nicity) 
Height(cm)/ 
Weight (kg)/ 
BMI (kg/m2) 
Smoking History 
Randomized? 
(Study Day) 
[d] 
Subject Study Status 
(Date of Last Dose 
[Study Day)} 
(Follow-up Call? Date) 
Date of Death 
[e] 
Smoking 
Status 
 [b] 
Number 
of 
Weeks 
Since 
Day 
Quit 
Number 
of 
Years 
Smoked 
Average 
Number of 
Cigarettes 
Smoked Per 
Day 
Number 
of Pack 
Years 
Smoked 
 [c] 
 
Center # (Investigator): Center ### (xxxxxxxxxx) 
 
Xxxxxx 
(A/B/E/C/D) 
 
Xx/M 
(x/xx) 
 
 
xxx.x/ 
xx.x/ 
xx.x 
Former 
Smoker 
xx.x 
xx 
xx 
xx.x 
Yes/No 
(xx) 
Completed Study 
(YYYY-MM-DD [xxx]) 
(Yes YYYY-DD-MM) 
NA 
 
 
 
 
 
 
 
 
 
 
Xxxxxx 
(A/E/-/-/-) 
Xx/M 
(x/xx) 
 
 
xxx.x/ 
xx.x/ 
xx.x 
Former 
Smoker 
xx.x 
xx 
xx 
xx.x 
Yes/No 
(xx) 
Discontinued 
Investigator’s Decision 
(YYYY-MM-DD [Tx_y]) 
(No) 
 
 
 
 
 
 
 
 
 
 
Xxxxxx 
(B/A/C/E/-) 
 
Xx/M 
(x/xx) 
 
 
xxx.x/ 
xx.x/ 
xx.x 
Former 
Smoker 
xx.x 
xx 
xx 
xx.x 
Yes/No 
(xx) 
Discontinued 
Subject Lost to Follow 
up 
(YYYY-MM-DD [Tx_y]) 
(No) 
 
 
 
 
 
 
 
 
 
 
Xxxxxx 
(B/C/-/-/-) 
Xx/M 
(x/xx) 
 
 
xxx.x/ 
xx.x/ 
xx.x 
Non 
Smoker 
xx.x 
xx 
xx 
xx.x 
No 
(NA) 
Discontinued 
Investigator’s Decision 
(YYYY-MM-DD [Tx_y]) 
(No) 
 
 
 
 
 
 
 
 
 
 
Xxxxxx 
(A/B/E/C/D) 
 
Xx/M 
(x/xx) 
 
 
xxx.x/ 
xx.x/ 
xx.x 
Former 
Smoker 
xx.x 
xx 
xx 
xx.x 
No 
(NA) 
Discontinued 
Adverse Event 
(YYYY-MM-DD [Tx_y]) 
(No) 
Death: YYYY-MM-DD 
Treatment: A = Placebo, B = AS MDI 90 μg, C = AS MDI 180 μg, D = Proventil 90 μg, E = Proventil 180 μg, - = Not Treated. 
Race: A=Asian, AIAN=American Indian or Alaska Native, B=Black or African American, NHPI=Native Hawaiian or Other Pacific Islander, 
      O=Other W=White. Ethnicity: H=Hispanic, NH=Not Hispanic, UNK=Unknown, NR=Not Reported. Gender: F=Female, M=Male. 
[a]   Age = integer part of ((Visit 1 date – Birth date)/365.25) 
[b]   Former Smoker is defined as those who have stopped smoking for at least 6 months prior to first Screening Visit. 


Albuterol Sulfate Pressurized Inhalation Suspension 
Protocol D6930C00001 (PT007001) 
Version 0.1 
13 Mar 2018 
Page 58 of 87 
 
 
[c]   Number of pack years smoked = (number of cigarettes per day / 20) x number of years smoked. 
[d]   Study Day of randomization = date of randomization – first dose of study treatment  
[e]   The Date of Discontinuation is the later of the last visit date, the date of the last dose of study medication, or the date of  
      last contact for subjects lost-to-followup. For subjects not randomized, date of discontinuation Study Day is the last visit 
      date - date of Screening Visit 1;  for treated subjects, Study Day is the date of discontinuation - date of first dose of study  
      treatment + 1.  
  
Source: xxxxxxx.sas7bdat 
 
Report generated by program: PT007001/sasdir/programs/statout/l0102.sas  Version YYYY-MM-DD xx:xx                 (Page n of N) 
 
Notes to Programmer:  
Sort by Center, and Subject ID within Center.   
Last Contact Date on the End of Treatment CRF is date of last contact.  
If Race = Other, concatenate the specified race after ‘O’ within parenthesis, e.g., “O (specified)”.  
Move ‘Study Center/Inv’ row header to the next page whenever there is not enough room on current page to fit at least one row of data underneath this header.   
 
 
 


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Protocol D6930C00001 (PT007001) 
Version 0.1 
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Listing 1.3 
Randomized Treatment, Actual Treatment, and Duration of Treatment 
Analysis Set: All Subjects Randomized 
 
Subject ID 
Randomized 
Treatment 
Sequence 
(Actual 
Treatment 
Sequence) 
Period 1 
Period 2 
Period 3 
Period 4 
Period 5 
Study Day 
of First 
and Last 
Dose of 
Study 
treatment 
in the 
study 
Treatment 
(Start Study Day 
and time – End 
Study Day and 
time)/ 
Duration (days)/ 
Washout Length 
(days) [a] 
Treatment 
(Start Study Day 
and time – End 
Study Day and 
time)/ 
Duration (days)/ 
Washout Length 
(days) [a] 
Treatment 
(Start Study Day 
and time – End 
Study Day and 
time)/ 
Duration (days)/ 
Washout Length 
(days) [a] 
Treatment 
(Start Study Day 
and time – End 
Study Day and 
time)/ 
Duration (days)/ 
Washout Length 
(days) [a] 
Treatment 
(Start Study Day 
and time – End 
Study Day and 
time)/ 
Duration (days)/ 
Washout Length 
(days) [a] 
 
Study Center # / (Investigator): ### / (xxxxxxxxxx) 
 
xxxxx 
 A/B/E/C/D 
(A/B/E/C/D) 
AS MDI 180 μg 
(xxx hh:mm - 
 xxx hh:mm)/ 
29/ 
(7) 
AS MDI 90 μg 
(xxx hh:mm - 
 xxx hh:mm)/ 
25/ 
(7) 
Placebo 
(xxx hh:mm - 
 xxx hh:mm)/ 
25/ 
(7) 
Proventil 180 μg 
(xxx hh:mm - 
 xxx hh:mm)/ 
25/ 
(7) 
Proventil 90 μg 
(xxx hh:mm - 
 xxx hh:mm)/ 
25/ 
(7) 
xxx – xxx 
 
 
 
 
 
 
 
 
xxxxx 
 B/A/C/E/- 
(B/A/C/E/-) 
 
Proventil 180 μg 
(xxx hh:mm - 
 xxx hh:mm)/ 
29/ 
(7) 
AS MDI 180 μg 
(xxx hh:mm - 
 xxx hh:mm)/ 
25/ 
(7) 
Proventil 90 μg 
(xxx hh:mm - 
 xxx hh:mm)/ 
25/ 
(7) 
Placebo 
(xxx hh:mm - 
 xxx hh:mm)/ 
25/ 
(7) 
 
xxx – xxx 
 
 
 
 
 
 
 
 
xxxxx 
 A/B/E/C/D 
(A/E/-/-/-) 
 
AS MDI 90 μg 
(xxx hh:mm - 
 xxx hh:mm)/ 
25/ 
(7) 
Placebo 
(xxx hh:mm - 
 xxx hh:mm)/ 
25/ 
(7) 
 
 
 
xxx – xxx 
 
 
 
 
 
 
 
 
Treatment: A = Placebo, B = AS MDI 90 μg, C = AS MDI 180 μg, D = Proventil 90 μg, E = Proventil 180 μg, - = Not Treated. 
Study Day of First Dose of Drug in the study is defined as the study day of the first dose of study medication in the study (Study 
Day 1) which is the study day of Treatment 1 Day 1 from the Study Drug Administration CRF. 
Study Day of the Last Dose of Study Drug in the study is defined as the Study Day of the last dose of study medication in the study – 
Study Day of first dose of study medication in the study + 1. 
NA = not applicable 
Time is 24 hour clock time. 
[a] Washout length (days) for the subject’s last period is the number of days between the follow-up telephone call and the dose date 
in the last period. The duration of a washout (or follow-up) period = (start date of subsequent treatment (or follow-up telephone 
call) - stop date of previous study treatment. 
 
Source: xxxxxxx.sas7bdat  
 
Report generated by program: PT007001/sasdir/programs/statout/l0103.sas  Version  YYYY-MM-DD xx:              (Page n of N) 


Albuterol Sulfate Pressurized Inhalation Suspension 
Protocol D6930C00001 (PT007001) 
Version 0.1 
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Notes to Programmer: Sort by Center and Subject within Center.  Move ‘Study Center/Inv’ row header to the next page whenever there is not enough room on current page to fit 
at least one row of data underneath this header.   
 
 
 


Albuterol Sulfate Pressurized Inhalation Suspension 
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Version 0.1 
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Page 61 of 87 
 
 
 
Listing 1.4 
Reasons Subjects Were Not Randomized 
Analysis Set: All Subjects Not Randomized 
 
Subject ID 
Date of Screening 
Age 
(yrs) 
Gender 
Race 
Reason Not Randomized 
 
Center # (Investigator): Center ### (xxxxxxxxxx) 
 
xxxxxx 
YYYY-MM-DD 
xx 
Male 
W 
xxxxxxxxxxxxxxx (Inclusion Criterion #n) 
xxxxxx 
YYYY-MM-DD 
xx 
Female 
W 
xxxxxxxxxxxxxx (Inclusion Criterion #n) 
xxxxxx 
YYYY-MM-DD 
xx 
Male 
W 
xxxxxxxxxxxxxx (Inclusion Criterion #n) 
xxxxxx 
YYYY-MM-DD 
xx 
Male 
W 
xxxxxxxxxxxxxx (Inclusion Criterion #n) 
Xxxxxx 
YYYY-MM-DD 
Xx 
Female 
W 
xxxxxxxxxxxxxx (Inclusion Criterion #n) 
Race: A=Asian, AIAN=American Indian or Alaska Native, B=Black or African American, NHPI=Native Hawaiian or Other Pacific Islander, 
      O=Other W=White.  
 
Source: xxxxxxx.sas7bdat  
 
Report generated by program: PT007001/sasdir/programs/statout/l0104.sas  Version YYYY-MM-DD xx:xx                 (Page n of N) 
 
 
Notes to Programmer:  
Sort by Center and Subject ID within Center.  
If Race = Other (“O”), concatenate the specified race after ‘O’ within parenthesis, e.g., “e.g., “O: xxxxxx”.   
Move ‘Study Center/Inv’ row header to the next page whenever there is not enough room on current page to fit at least one row of data underneath this header.  If country is 
shown, move country to the next page if there is not enough room. 
 
 
 


Albuterol Sulfate Pressurized Inhalation Suspension 
Protocol D6930C00001 (PT007001) 
Version 0.1 
13 Mar 2018 
Page 62 of 87 
 
 
 
4.2 Protocol Deviations 
 
Listing 2 
Violation of Inclusion/Exclusion Criteria 
Analysis Set: All Subjects Randomized 
 
Subject ID 
Treatment 
Sequence 
Age (yrs)/ 
Gender 
(Race) 
[a] 
Informed 
Consent 
Signed 
Informed 
Consent 
Study Day 
[a] 
Eligibility 
Visit 
Study Day 
[a] 
Inclusion/ 
Exclusion 
Criteria 
Satisfied 
Type of 
Failed 
Criteria 
 
 
 
Center # (Investigator): Center ### (xxxxxxxxxx) 
 
xxxxxx 
A/B/E/C/D 
 xx/M 
(BA) 
Yes 
-xx 
Visit 1 
 -xx 
No 
Inclusion 
 
 
 
Treatment: A = Placebo, B = AS MDI 90 μg, C = AS MDI 180 μg, D = Proventil 90 μg, E = Proventil 180 μg, - = Not Treated. 
Race: A=Asian, AIAN=American Indian or Alaska Native, B=Black or African American, NHPI=Native Hawaiian or Other Pacific Islander, 
      O=Other W=White. Gender: F=Female, M=Male. 
[a]   A negative number for study day denotes the number of days prior to the start of study treatment. 
 
Source:xxxxxxx.sas7bdat 
 
Report generated by program: PT007001/sasdir/programs/statout/l02.sas Version YYYY-MM-DD xx:xx       (Page n of N) 
 
Notes to Programmer:  
If Race = Other (“O”), concatenate the specified race after ‘O’ within parenthesis, e.g., “O (specified)”.  
Sort by  Center, and Subject ID within Center.   
Move ‘Study Center/Inv’ row header to the next page whenever there is not enough room on current page to fit at least one row of data underneath this header. 
 
 


Albuterol Sulfate Pressurized Inhalation Suspension 
Protocol D6930C00001 (PT007001) 
Version 0.1 
13 Mar 2018 
Page 63 of 87 
 
 
4.3 Screening Lung Function and Reversibility 
 
Listing 3 
Screening Lung Function and Ventolin HFA Reversibility 
Analysis Set: All Subjects Randomized 
 
Subject 
ID 
Treatme
nt 
Sequenc
e 
Age 
(yrs) 
/Gender 
(Race) 
[a] 
Visit Effort Date 
Time of 
Ventolin 
HFA Dose  
(24 h 
clock) 
Pre-Dose 
Post-Dose 
FEV1 (L) 
FVC 
(L) 
PEFR 
(L/min) 
FEV1 (L) 
FVC 
(L) 
PEFR 
(L/min) 
Reversi-
bility % 
Center # (Investigator): Center ### (xxxxxxxxxx) 
xxxxx 
A/B/E/C
/D 
xx/x 
(xxx) 
1 
YYYY-MM-DD 
xx:xx 
x.xxx 
x.xxx 
xxx.xxx 
x.xxx 
x.xxx 
xxx.xxx 
1a 
YYYY-MM-DD 
xx:xx 
x.xxx 
x.xxx 
xxx.xxx 
x.xxx 
x.xxx 
xxx.xxx 
xx.x  
1b 
YYYY-MM-DD 
 
x.xxx 
x.xxx 
xxx.xxx 
x.xxx 
x.xxx 
xxx.xxx 
xx.x  
xxxxx 
B/A/C/E
/- 
xx/x 
(xxx) 
1 
YYYY-MM-DD 
xx:xx 
x.xxx 
x.xxx 
xxx.xxx 
x.xxx 
x.xxx 
xxx.xxx 
xx.x  
xxxxx 
A/B/E/C
/D 
xx/x 
(xxx) 
1 
YYYY-MM-DD 
 
x.xxx 
x.xxx 
xxx.xxx 
x.xxx 
x.xxx 
xxx.xxx 
xx.x (V) 
Treatment: A = Placebo, B = AS MDI 90 μg, C = AS MDI 180 μg, D = Proventil 90 μg, E = Proventil 180 μg, - = Not Treated. 
Race: A=Asian, AIAN=American Indian or Alaska Native, B=Black or African American, NHPI=Native Hawaiian or Other Pacific Islander, 
     O=Other W=White. Gender: F=Female, M=Male. 
NA = not applicable. 
Source: xxxxxxx.sas7bdat 
Report generated by program: PT007001/sasdir/programs/statout/l03.sas  Version YYYY-MM-DD xx:xx   (Page n of N) 
 
 
Notes to Programmer: Sort by Center, and Subject ID within Center.  Move ‘Study Center/Inv’ row header to the next page whenever there is not enough room on current page to 
fit at least one row of data underneath this header.   
 
 


Albuterol Sulfate Pressurized Inhalation Suspension 
Protocol D6930C00001 (PT007001) 
Version 0.1 
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Page 64 of 87 
 
 
4.4 Baseline Characteristics 
 
Listing 4.1 
Asthma Diagnosis 
Analysis Set: All Subjects Randomized 
 
Subject ID 
Treatment Sequence 
Age (yrs)/Gender/Race [a] 
Asthma First Diagnosed 
Date [s] 
Years Prior to First Dose [b] 
 
Center # (Investigator): Center ### (xxxxxxxxxx) 
 
xxxxxx 
 
A/B/E/C/D 
xx / Male/ xxxx 
xx / Female / xxxx 
YYYY-MM 
YYYY-06* 
x.x 
 xx.x 
Treatment: A = Placebo, B = AS MDI 90 μg, C = AS MDI 180 μg, D = Proventil 90 μg, E = Proventil 180 μg, - = Not Treated. 
Race: A=Asian, AIAN=American Indian or Alaska Native, B=Black or African American, NHPI=Native Hawaiian or Other Pacific Islander, 
      O=Other W=White. Gender: F=Female, M=Male. 
[a]   Missing month of Date Asthma First Diagnosed was imputed as June, or the month in which 1st  was the latest before informed  
      consent date; '*' indicates the month displayed was imputed.   
[b]   Months Prior to First Dose When Asthma was First Diagnosed = (Date of First Dose of Study treatment in the study - Date Asthma  
      First Diagnosed)/30.4375. Day of Diagnosis was imputed for all subjects as the 1st of the month. 
 
Source: xxxxxxx.sas7bdat   
 
Report generated by program: PT007001/sasdir/programs/statout/l0401.sas  Version YYYY-MM-DD xx:xx   (Page n of N) 
 
Notes to Programmer: Sort by Center and Subject ID within Center.  Move ‘Study Center/Inv’ row header to the next page whenever there is not enough room on current page to 
fit at least one row of data underneath this header.   
 
 


Albuterol Sulfate Pressurized Inhalation Suspension 
Protocol D6930C00001 (PT007001) 
Version 0.1 
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Page 65 of 87 
 
 
Listing 4.2 
Medical and Surgical History 
Analysis Set: All Subjects Randomized 
 
Subject 
ID 
Treatment 
Sequence 
Age (yrs)/ 
Gender 
(Race) 
[a] 
Category 
System Organ 
Class 
Diagnosis or 
Surgery/ 
(Preferred 
Term) 
Onset Date  
Onset 
Day [a] 
Still 
Present? 
End Date 
(Year/ 
Month) 
End 
Day [b] 
Center # (Investigator): Center ### (xxxxxxxxxx) 
xxxxxx A/B/E/C/D  xx/x 
(xxxx) 
Drug Allergy 
xxxxxxxx 
xxxxx/(xxxx) 
YYYY-MM 
-xxx 
No 
YYYY-MM 
xxx 
 
Malignancy 
xxxxxx 
xxxxx/(xxxx) 
YYYY-MM 
-xxx 
No 
YYYY-MM 
xxx 
 
 
 
 
 
 
 
xxxxxx B/A/C/E/- xx/x 
(xxxx) 
CNS/Neurological xxxxxxxxxxxxxxxx xxxxx/(xxxx) 
YYYY-MM 
-xxx 
No 
YYYY-MM 
xxx 
 
Endocrine/Metabol
ic 
xxxxxxxxxx 
xxxxx/(xxxx) 
YYYY-MM 
-xxx 
Yes 
 
Ongoing 
 
 
 
 
 
 
 
xxxxxx A/B/E/C/D xx/x 
(xxxx) 
Eyes/Ear/Nose/Thr
oat 
xxxxxxxxxxxx 
xxxxx/(xxxx) 
YYYY-MM 
-xx 
No 
YYYY-MM 
xxx 
 
 
 
 
 
 
 
xxxxxx B/A/C/E/- xx/x 
(xxxx) 
Other 
xxxxxxxxxx 
xxxxx/(xxxx) 
YYYY-MM 
-xxx 
No 
YYYY-MM 
xxx 
 
 
Treatment: A = Placebo, B = AS MDI 90 μg, C = AS MDI 180 μg, D = Proventil 90 μg, E = Proventil 180 μg, - = Not Treated. 
Race: A=Asian, AIAN=American Indian or Alaska Native, B=Black or African American, NHPI=Native Hawaiian or Other Pacific Islander, 
     O=Other W=White. Gender: F=Female, M=Male. 
[a]   Onset Day=Onset date of condition – date of the first dose of study treatment. Day was imputed as 1st of the month. Missing month 
     was imputed as June, or the month in which 1st  was the latest before informed consent date; '*' indicates the month  
     displayed was imputed. 
[b]   End Day=End date of condition – date of the first dose of study treatment. Day was imputed as 1st of the month. Missing month 
     was imputed as June, or the month in which 1st  was the latest before informed consent date; ‘*' indicates the month 
     displayed was imputed. 
Source: xxxxxxx.sas7bdat   
Report generated by program: PT007001/sasdir/programs/statout/l0402.sas  Version YYYY-MM-DD xx:xx             (Page n of N)  
 
Notes to Programmer: Sort by Center, Subject ID, and Onset Day.  Move ‘Study Center/Inv’ row header to the next page whenever there is not enough room on current page to fit 
at least one row of data underneath this header.   
 


Albuterol Sulfate Pressurized Inhalation Suspension 
Protocol D6930C00001 (PT007001) 
Version 0.1 
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Page 66 of 87 
 
 
 
Listing 4.3 
Screening Reproductive Status and Pregnancy Test Results 
Analysis Set: All Subjects Randomized 
 
Subject 
ID 
Treatment 
Sequence 
Age (yrs) 
/Gender 
(Race) 
Screening 
Female 
Reproductive 
Status 
If Subject is 
a WOCBP, Was 
Pregnancy 
Test 
Performed? 
Pregnancy Test 
Visit 
[a] 
Visit Date 
Type of 
Pregnancy Test 
Study Day of 
Test [b] 
Result 
 
Center # (Investigator): Center ### (xxxxxxxxxx) 
 
xxxxxx 
A/B/E/C/D 
xx/F/(xxx
x) 
Woman of Non-
Childbearing 
Potential 
(Non-WOCBP) 
 
Visit 1 YYYY-MM-DD 
Not Done  
NA 
NA 
 
 
 
 
 
 
 
 
 
 
xxxxxx 
B/A/C/E/- 
xx/F/(xxx
x) 
Woman of 
Childbearing 
Potential 
(WOCBP) 
Yes 
Visit 2 YYYY-MM-DD 
Serum Pregnancy 
Test 
xxx 
Positive 
 
 
 
 
 
 
 
 
 
 
Treatment: A = Placebo, B = AS MDI 90 μg, C = AS MDI 180 μg, D = Proventil 90 μg, E = Proventil 180 μg, - = Not Treated. 
Race: A=Asian, AIAN=American Indian or Alaska Native, B=Black or African American, NHPI=Native Hawaiian or Other Pacific Islander, 
      O=Other W=White. Gender: F=Female, M=Male. 
[a]    Pregnancy testing at Visit 2 was done prior to randomization. 
[b]    Study Day is defined as date of test – date of the first dose of study treatment. 
 
Source: xxxxxxx.sas7bdat   
 
Report generated by program: PT007001/sasdir/programs/statout/l0403.sas  Version YYYY-MM-DD xx:xx                  (Page n of N) 
 
Notes to Programmer:  
Sort by  Center, Investigator, Subject ID within Center, Visit, and Study Day of Pregnancy Test.  List female subjects only. 
Move ‘Study Center/Inv’ row header to the next page whenever there is not enough room on current page to fit at least one row of data underneath this header.   
 
 


Albuterol Sulfate Pressurized Inhalation Suspension 
Protocol D6930C00001 (PT007001) 
Version 0.1 
13 Mar 2018 
Page 67 of 87 
 
 
Listing 4.4 
Prior, Concomitant, and Post-Treatment Asthma Medications 
Analysis Set: All Subjects Randomized 
 
Subject 
ID 
(Treatm
ent 
Sequenc
e) 
Medication 
Verbatim 
Term 
(Preferred 
Term) 
(ATC Term) 
Dose/ 
Unit/ 
Route/ 
Frequency 
Reason 
for 
Use 
Begin Date 
(YYYY-MM-DD) 
Stop Date 
(YYYY-MM-DD) 
Ongoi
ng 
Duration 
(Days) 
Study Day 
Prior/ 
Concomitant/Post-
Treatment 
Begin 
Day 
[a] 
Stop 
Day 
[a] 
 
Center # (Investigator): Center ### (xxxxxxxxxx) 
 
1001 
(A/B/E/
C/D) 
xxxxxxxxxxxx 
(xxxxxx) 
(xxxxxx) 
90/ MCG/ 
IH/ PRN 
Asthma 
Exacer
bation 
# xxx 
2008-XX-XX 
 
Yes 
 
-22 
 
Yes/Yes/No 
 
 
 
Other, 
<speci
fy> 
2008-XX-XX 
 
Yes 
 
-22 
 
Yes/Yes/No 
Treatment: A = Placebo, B = AS MDI 90 μg, C = AS MDI 180 μg, D = Proventil 90 μg, E = Proventil 180 μg, - = Not Treated. 
All Asthma-related medications taken within 30 days of Screening and while on study are listed.  
Medications were considered to be prior medications if taken prior to the start of study treatment. Medications were considered 
concomitant if they were reported as being taken at any point from the start of randomized study treatment to the last date of study 
treatment. Medications with an onset date on or after the last dose of study treatment were considered post-treatment medications. 
All subjects were allowed sponsor provided Ventolin HFA, and Pulmicort if previously using regularly scheduled ICS or ICS/LABA, during 
the Screening period, and Atrovent and/or Pulmicort during the treatment period which were reported on the Concomitant Medications 
CRF. 
XX = Unknown month or day. 
[a]  A negative number for study day denotes the number of days prior to the start of study treatment. Pxx = Days after dose in last  
     Treatment Period. 
 
Sources: xxxxxxx.sas7bdat    
 
Report generated by program: PT007001/sasdir/programs/statout/l0404.sas    Version               YYYY-MM-DD xx:xx  (Page n of N) 
 
Notes to Programmer:  
Sort by  Center, Subject ID, Preferred Term, and Begin Date of Asthma medication.  Show Anatomic and chemical portion of ATC code. Only medications with Reason for Use of 
Asthma on eCRF will be listed here.  Move ‘Study Center/Inv’ row header to the next page whenever there is not enough room on current page to fit at least one row of data 
underneath this header.   
 
Listing 4.5 
Prior, Concomitant, and Post-Treatment Non-Asthma-Related Medications 
Analysis Set: All Subjects Randomized 
 
Add the following footnote: All non-Asthma-related medications taken within 30 days of Screening and while on study are listed. 
 


Albuterol Sulfate Pressurized Inhalation Suspension 
Protocol D6930C00001 (PT007001) 
Version 0.1 
13 Mar 2018 
Page 68 of 87 
 
 
 
Listing 4.6 
Suspect Drug Assessment for SAEs 
Analysis Set: All Subjects Randomized 
 
Subject ID 
(Treatment 
Sequence) 
SAE Verbatim Term/ 
Preferred Term/ 
Onset Date 
Additional  
Non-Study 
Medication 
at Onset of 
SAE 
Dose/ 
Unit/ 
Route/ 
Frequency 
Started 
Treatment/
Date of 
Most 
Recent 
Study 
Treatment/
Blinded or 
Open/ 
Treatment 
at Onset 
of AE/Non-
study drug 
at onset 
of SAE 
Begin Date/ 
Stop Date 
(YYYY-MM-DD) 
Con-
tin- 
uing 
Duration 
(Days) 
Begin Day/ 
Stop Day 
[a] 
SAE Causally 
Related to This 
Product/Does 
Principal 
Investigator 
feel that SAE 
may be related 
to other 
factor? 
(Specify) 
 
Center # (Investigator): Center ### (xxxxxxxxxx) 
 
xxxx 
(A/B/E/C/D) 
 
Xxxxxxxxxxx/ 
Xxxxxxxxx/ 
YYYY-MM-DD 
Ventolin 
HFA 
90/μg/ 
IH/PRN 
Yes/ 
YYYY-MM-
DD/Blinded 
or Open-
Label/ 
Yes/Yes 
2008-XX-XX 
 
Yes 
 
-22 
Yes / Yes 
(Pre-existing 
/Underlying 
disease or 
Prior or 
Concomitant 
Medication 
 xxxx 
(B/A/C/E/-) 
 
Xxxxxxxxxxx/ 
Xxxxxxxxx/ 
YYYY-MM-DD 
Atrovent 
HFA 
34/μg/ 
IH/QID 
No 
2008-XX-XX/ 
2008-XX-XX 
No 
5 
T1_P1/ 
T1_P5 
No 
 
 
 
 
 
 
 
 
 
 
Treatment: A = Placebo, B = AS MDI 90 μg, C = AS MDI 180 μg, D = Proventil 90 μg, E = Proventil 180 μg, - = Not Treated. 
XX = Unknown month or day. 
[a] A negative number for study day denotes the number of days prior to the start of study treatment. Otherwise, Study Day is Date – 
Date of dose in the Period + 1. Tx_y = Treatment Period and Day within Treatment Pxx = Days after dose in last Treatment Period. 
 
Sources: xxxxx.sas7bdat 
Report generated by program: PT007001/sasdir/programs/statout/l0407.sas   Version    YYYY-MM-DD xx:xx              (Page x of y) 
 
Notes to Programmer: for last column, 2nd question, “Does Principal Investigator feel that SAE may be related to other factor? (Specify)”) is only listed on first line for each 
subject.  
 
 


Albuterol Sulfate Pressurized Inhalation Suspension 
Protocol D6930C00001 (PT007001) 
Version 0.1 
13 Mar 2018 
Page 69 of 87 
 
 
4.5 Dosing 
 
Listing 5.1.1 
Study Drug Administration 
Analysis Set: All Subjects Randomized 
 
Subject ID 
Treatment Sequence 
Visit 
(Study Day [a]) 
Study Drug 
Administered at 
Visit 
Date and Time of  
On-Site Study Dose 
(Study Day [a]) 
Study Medication Component ID 
 
Study Center # / (Investigator):  ### (xxxxxxxxxx) 
 
xxxxxx 
A/E/-/-/- 
Visit x (Tx_y) 
Yes 
YYYY-MM-DD (hh:mm) 
(Tx_y) 
Bxxxxx 
 
 
Visit x (Tx_y) 
Yes 
YYYY-MM-DD (hh:mm) 
(Tx_y) 
Bxxxxx 
 
 
 
 
 
Treatment: A = Placebo, B = AS MDI 90 μg, C = AS MDI 180 μg, D = Proventil 90 μg, E = Proventil 180 μg, - = Not Treated. 
[a]   Study Day is Date – Date of dose in the Period + 1. Tx = Period. Tx_y = Period and Day within Period. Pxx=Days after last  
      dose in the last Treatment Period. 
Source: xxxxxxx.sas7bdat 
Report generated by program: PT007001/sasdir/programs/statout/l050101.sas  Version  YYYY-MM-DD xx:xx  (Page n of N) 
 
 
Notes to Programmer:  
Sort by Center, Subject within Center, Date Dispensed, and Component ID.  
Move ‘Study Center/Inv’ row header to the next page whenever there is not enough room on current page to fit at least one row of data underneath this header.   
 


Albuterol Sulfate Pressurized Inhalation Suspension 
Protocol D6930C00001 (PT007001) 
Version 0.1 
13 Mar 2018 
Page 70 of 87 
 
 
 
` 
 
Listing 5.1.2 
Ventolin HFA and Pulmicort Flexhaler Dispensing 
Analysis Set: All Subjects Randomized 
 
Subject ID 
Treatment Sequence 
Drug 
Dispensed 
Date Dispensed 
Study Day [a] 
of Dispensing 
Study Medication Component ID 
Study Center # / (Investigator):  ### (xxxxxxxxxx) 
 
xxxxxx 
A/E/-/-/- 
Ventolin HFA 
Yes 
YYYY-MM-DD 
Tx_y 
Axxxxx 
 
 
Pulmicort 
Flexhaler 
Yes 
YYYY-MM-DD 
Tx_y 
Axxxxx 
 
 
Ventolin HFA 
Yes 
YYYY-MM-DD 
Tx_y 
Axxxxx 
 
 
 
 
 
Treatment: A = Placebo, B = AS MDI 90 μg, C = AS MDI 180 μg, D = Proventil 90 μg, E = Proventil 180 μg, - = Not Treated. 
[a]   Study Day is Date – Date of dose in the Period + 1. Tx = Period. Tx_y = Period and Day within Period. Pxx = Days after  
     last dose in Period. 
Source: xxxxxxx.sas7bdat    
Report generated by program: PT007001/sasdir/programs/statout/l050102.sas  Version  YYYY-MM-DD xx:xx  (Page n of N) 
 
Notes to Programmer:  
Sort by Center, Subject within Center, Date Dispensed, and Component ID.  
Move ‘Study Center/Inv’ row header to the next page whenever there is not enough room on current page to fit at least one row of data underneath this header.   
 
 
 
 
 


Albuterol Sulfate Pressurized Inhalation Suspension 
Protocol D6930C00001 (PT007001) 
Version 0.1 
13 Mar 2018 
Page 71 of 87 
 
 
 
Listing 5.2 
Exposure to Study Treatment 
Analysis Set: Safety Analysis Set 
 
Subject ID  
(Treatment Sequence)  
Age (yrs)/ 
Gender 
(Race) 
Treatment 
Period 
           Number of Puffs 
Taken 
Expected 
[a] 
 
Center # / (Investigator):  ### (xxxxxxxxxx) 
 
1001 
xx/x (xxxx) 
1 
2 
2 
(A/B/E/C/D) 
xx/x (xxxx) 
2 
2 
x 
 
xx/x (xxxx) 
3 
x 
x 
 
xx/x (xxxx) 
4 
x 
x 
 
xx/x (xxxx) 
5 
x 
x 
 
 
 
 
 
 
 
1002 
xx/x (xxxx) 
1 
1 
x 
(A/B/E/C/D) 
xx/x (xxxx) 
2 
2 
1 
 
xx/x (xxxx) 
3 
1 
2 
 
xx/x (xxxx) 
4 
2 
x 
 
xx/x (xxxx) 
5 
x 
x 
 
 
Treatment: A = Placebo, B = AS MDI 90 μg, C = AS MDI 180 μg, D = Proventil 90 μg, E = Proventil 180 μg, - = Not 
Treated. 
Race: A=Asian, AIAN=American Indian or Alaska Native, B=Black or African American, NHPI=Native Hawaiian or 
Other Pacific Islander, O=Other W=White. Gender: F=Female, M=Male. 
[a]   The expected number of puffs for each treatment day were as follows: 
x 
AS MDI 90 μg (2 actuations of 45 μg/actuation) 
x 
AS MDI 180 μg (2 actuations of 90 μg/actuation) 
x 
Placebo MDI (2 actuations) 
x 
Proventil 90 μg (1 actuation of 90 μg/actuation) 
x 
Proventil 180 μg (2 actuations of 90 μg/actuation) 
 
Source: xxxxxxx.sas7bdat 
Report generated by program: PT007001/sasdir/programs/statout/l0502.sas  Version  YYYY-MM-DD xx:xx              
(Page n of N) 
 
Notes to Programmer:  
Sort by Center, Subject within Center, and Treatment Period.  Move ‘Study Center/Inv’ row header to the next page whenever there is not enough room on current page  
to fit at least one row of data underneath this header.  Treatment is actual treatment. 
 
 


Albuterol Sulfate Pressurized Inhalation Suspension 
Protocol D6930C00001 (PT007001) 
Version 0.1 
13 Mar 2018 
Page 72 of 87 
 
 
 
4.6 Individual Efficacy Data 
 
4.6.1 Efficacy 
 
Listing 6.1 
Subjects Who Failed Restrictions Prior to Spirometry Assessment 
Analysis Set: All Subjects Randomized 
 
Subject 
ID 
Treatment 
Sequence 
 
Visit 
Study Time Window of 
Assessment 
Effort 
Date 
Effort Time 
(24 h clock) 
Prior to Study Visit, Subject has 
Not Had Xanthine 
Containing Products 
for at Least 6 Hours  
Withheld Asthma 
Medications Including 
Corticosteroids for 
at Least 6 Hours 
 
Center # (Investigator): Center ### (xxxxxxxxxx) 
 
xxxxxx 
A/B/E/C/D 
Day 1 
Pre-Dose  
60 Min 
YYYY-MM-DD 
8:14:57 
No 
 
Treatment: A = Placebo, B = AS MDI 90 μg, C = AS MDI 180 μg, D = Proventil 90 μg, E = Proventil 180 μg, - = Not Treated. 
Note that subjects with missing data for either of the 2 restrictions are also listed. 
 
Source: xxxxxxx.sas7bdat   
 
Report generated by program: PT007001/sasdir/programs/statout/l0601.sas   Version   YYYY-MM-DD xx:xx              (Page n of N 
 
Notes to Programmer:  
Sort by Center, Subject ID, and Effort Date.  
Only subjects with ‘No’ or missing responses should be listed.   
Move ‘Study Center/Inv’ row header to the next page whenever there is not enough room on current page to fit at least one row of data underneath this header.   
 
 


Albuterol Sulfate Pressurized Inhalation Suspension 
Protocol D6930C00001 (PT007001) 
Version 0.1 
13 Mar 2018 
Page 73 of 87 
 
 
 
Listing 6.2 
Failure of Stability Criteria 
Analysis Set: All Subjects Randomized 
 
Subject ID  
(Treatment Sequence) 
Treatment 
Visit  
(Date of Spirometry Assessment) 
 
Study Center # / (Investigator):  ### (xxxxxxxxxx) 
 
Xxxxxx (A/B/E/C/D) 
AS MDI 90 μg 
Visit xx 
YYYY-MM-DD 
 
 
Visit xx 
YYYY-MM-DD 
Xxxxxx (B/C/-/-/-) 
Proventil 180 μg 
Visit xx 
YYYY-MM-DD 
 
 
 
 
Treatment: A = Placebo, B = AS MDI 90 μg, C = AS MDI 180 μg, D = Proventil 90 μg, E = Proventil 180 μg, - = Not Treated. 
 
Source: xxxxxxx.sas7bdat  
 
Report generated by program: PT007001/sasdir/programs/statout/l0602.sas  Version  YYYY-MM-DD xx:xx             (Page n of N)             
 
 
Notes to Programmer:  
Sort by Center,Subject ID within Center, and Visit.  
Move ‘Study Center/Inv’ row header to the next page whenever there is not enough room on current page to fit at least one row of data underneath this header.   
 
 
 


Albuterol Sulfate Pressurized Inhalation Suspension 
Protocol D6930C00001 (PT007001) 
Version 0.1 
13 Mar 2018 
Page 74 of 87 
 
 
Listing 6.3 
Reason for Missed Visit 
Analysis Set: All Subjects Randomized 
 
Subject ID  
(Treatment Sequence) 
Treatment 
Visit Missed 
Missed Due to Asthma Related Issues 
 
Study Center # / (Investigator):  ### (xxxxxxxxxx) 
 
Xxxxxx (A/B/E/C/D) 
AS MDI 90 μg 
Visit xx 
Yes 
Xxxxxx (B/C/-/-/-) 
Proventil 180 μg 
Visit xx 
No 
 
 
Visit xx 
Unknown 
Treatment: A = Placebo, B = AS MDI 90 μg, C = AS MDI 180 μg, D = Proventil 90 μg, E = Proventil 180 μg, - = Not Treated. 
 
Source: xxxxxxx.sas7bdat  
 
Report generated by program: PT007001/sasdir/programs/statout/l0603.sas  Version  YYYY-MM-DD xx:xx                (Page n of N)          
 
 
Notes to Programmer: 
Sort by Center, Subject ID within Center, and Visit. 
Move ‘Study Center/Inv’ row header to the next page whenever there is not enough room on current page to fit at least one row of data underneath this header.   
 
 
 


Albuterol Sulfate Pressurized Inhalation Suspension 
Protocol D6930C00001 (PT007001) 
Version 0.1 
13 Mar 2018 
Page 75 of 87 
 
 
 
Listing 6.4 
Spirometry Measurements 
Analysis Set: All Subjects Randomized 
 
Subject 
ID 
(Treatme
nt 
Sequence
) 
 
Age 
(yrs)/ 
Gender/ 
Race/ 
Height 
(cm)  
 Visit 
Treatment/ 
Treatment 
Date/Time 
(24 h clock) 
Assessment 
Date (Study 
Day) [a] 
Rescue 
Ventolin 
HFA used? 
(Time) 
Nominal Time 
of 
Assessment 
(Actual Time 
of 
Assessment 
24 h clock) 
Spirometry Assessments 
Raw Value 
[Predicted Value at Screening] 
(Percent of Predicted Value) 
(grade) [b]  
FEV1 (L) 
FEV6 
(L) 
FVC (L) 
FEV1/ 
FVC(%) 
FEF 
25-75 
(L/sec) 
PEFR 
(L/Min) 
PEFT 
(ms) 
 
Center # (Investigator): Center ### (xxxxxxxxxx) 
 
Xxxxxx 
(A/B/E/C
/D) 
53/F/W/xx
x 
 Visit 1 
 
YYYY-MM-DD 
(-xx) 
NA 
(xx:xx 
AM/PM) 
 60 Min Pre-
Dose (xx:xx) 
x.xxx 
[x.xxx] 
(xx.x%) 
(x) 
x.xxx 
x.xxx 
[x.xxx] 
(xx.x%) 
(x) 
xx.x 
x.xxx 
[x.xxx] 
(xx.x%) 
xxx.xxx 
[xxx.xxx] 
(xx.x%) 
(x, x) 
xxx 
 
 
Repeat for 
Visit 1a, 
1b, 2, 3, 
4, and 5 
and any 
other 
visits. 
A/  
YYYY-MM-DD/ 
hh:mm 
YYYY-MM-DD 
(Tx_y) 
Yes 
(xxxxxx) 
15 Min Post-
Dose (xx:xx) 
x.xxx 
(xx.x%) 
(x) 
x.xxx 
x.xxx 
(xx.x%) 
(x) 
xx.x 
x.xxx 
(xx.x%) 
xxx.xxx  
(xx.x%) 
(x, x) 
xxx 
Treatment: A = Placebo, B = AS MDI 90 μg, C = AS MDI 180 μg, D = Proventil 90 μg, E = Proventil 180 μg, - = Not Treated. 
Race: A=Asian, AIAN=American Indian or Alaska Native, B=Black or African American, NHPI=Native Hawaiian or Other Pacific Islander, 
      O=Other W=White. Gender: F=Female, M=Male. 
NA = Not applicable. 
[a]  Study Day is Date – Date of dose in the Period + 1. Tx = Period. Tx_y = Period and Day within Period. Pxx = Days after  
     dose in last Treatment Period. 
[b]  Grade is coded: 1=Acceptable  2=Borderline Acceptable  3=Unacceptable.  
 
Source: xxxxxxx.sas7bdat  
Report generated by program: PT007001/sasdir/programs/statout/l0604.sas   Version YYYY-MM-DD xx:xx            (Page n of N)  
 
Notes to Programmer:  
Sort by Center,Subject ID, Assessment Date, and Nominal Time of Assessment.  
Show Predicted Value only for Screening Visits.  
Nominal time of assessment  is the SAP-specified derived time window.   
Move ‘Study Center/Inv’ row header to the next page whenever there is not enough room on current page to fit at least one row of data underneath this header.   


Albuterol Sulfate Pressurized Inhalation Suspension 
Protocol D6930C00001 (PT007001) 
Version 0.1 
13 Mar 2018 
Page 76 of 87 
 
 
Listing 6.5 
Spirometry Derived Endpoints 
Analysis Set: All Subjects Randomized 
 
Subject 
ID 
(Treatme
nt 
Sequence
) 
 
Age 
(yrs)/ 
Gender/ 
Race/ 
Height 
(cm) 
 Visit 
Assessment 
Date 
(Study 
Day) [a] 
Timepoint 
Spirometry Derived Endpoints  
Change 
from 
Baseline 
in FEV1  
AUC0-6 
Change 
from 
Baseline 
in FEV1  
AUC0-4 
Peak 
change 
from 
baseline 
in FEV1 
(L) 
Change 
from 
baseline 
in FEV1 
(L) 
Time to 
Peak FEV1 
(hours) 
Achieved 
Improvement 
in FEV1 from 
Baseline 
Within 30 
Minutes of 
Dose 
Time to 
Onset of 
Response 
(minutes) 
Duration of 
Response 
(minutes) 
12% 
15% 
12% 
15% 
12% 
15% 
 
Center # (Investigator): Center ### (xxxxxxxxxx) 
 
Xxxxxx 
(A/B/E/C
/D) 
53/F/W/xx
x 
 Visit 2 YYYY-MM-DD 
(Tx_y) 
60 Min 
Pre-Dose 
 
 
 
x.xxx 
 
 
 
 
 
 
 
 
 
Repeat 
for 
Visit 
1a, 1b, 
2, 3, 4, 
and 5 
and any 
other 
visits, 
and 
include 
all pre- 
and 
post-
dose 
timepoin
ts. 
YYYY-MM-DD 
(xx) 
30 Min 
Post-Dose 
x.xxx 
x.xxx 
x.xxx 
x.xxx 
x.xx 
 
Yes 
No 
x.xx 
 
x.xx 
x.xx 
 
x.xx 
Treatment: A = Placebo, B = AS MDI 90 μg, C = AS MDI 180 μg, D = Proventil 90 μg, E = Proventil 180 μg, - = Not Treated. 
Race: A=Asian, AIAN=American Indian or Alaska Native, B=Black or African American, NHPI=Native Hawaiian or Other Pacific Islander, 
      O=Other W=White. Gender: F=Female, M=Male. 
NA = Not applicable. 
[a]  Study Day is Date – Date of dose in the Period + 1. Tx = Period. Tx_y = Period and Day within Period. Pxx = Days after  
     dose in last Treatment Period. 
 
Source: xxxxxxx.sas7bdat  


Albuterol Sulfate Pressurized Inhalation Suspension 
Protocol D6930C00001 (PT007001) 
Version 0.1 
13 Mar 2018 
Page 77 of 87 
 
 
Report generated by program: PT007001/sasdir/programs/statout/l0605.sas   Version YYYY-MM-DD xx:xx            (Page n of N)  
 
Notes to Programmer:  
Report FEV1 AUC0-6, FEV1 AUC0-4, Peak change from baseline in FEV1, and Time to Peak FEV1, only at the last timepoint for each treatment period. 
Report Achieved 12% Improvement in FEV1 from Baseline Within 30 Minutes of Dose, Achieved 15% Improvement in FEV1 from Baseline Within 30 Minutes of Dose, Time to 
Onset of Response, and Duration of Response only at 30 minute post-dose timepoint. 
Sort by Center,Subject ID, Assessment Date, and Timepoint.  
Move ‘Study Center/Inv’ row header to the next page whenever there is not enough room on current page to fit at least one row of data underneath this header.   
 
 


Albuterol Sulfate Pressurized Inhalation Suspension 
Protocol D6930C00001 (PT007001) 
Version 0.1 
13 Mar 2018 
Page 78 of 87 
 
 
4.7 Adverse Event Listings 
 
Listing 7.1 
Adverse Events by Primary System Organ Class, Preferred Term, Treatment, Country, Center, Subject ID, and Onset Day 
Analysis Set: All Subjects Randomized 
 
Primary System Organ Class:  xxxxxxxxxxxxxxxxx 
Preferred Term 
Treatment 
Center # 
(Investigator) 
Subject ID 
(Treatment 
Sequence) 
Age 
(yrs) 
/Gender 
(Race) 
Treatment 
Emergent 
/ Serious 
AE? [a] 
Onset 
Date (Day) 
[b] / Occur 
before or 
after start 
of a 
treatment 
 On Day 1 
 
Duration 
of  
Event 
[c] 
Severity / 
Relationship 
Action 
(Outcome)  
(AE Treated) 
Study 
Day 
Resolved 
/Death 
[b] 
 
 
 
 
xxxxxxxxxxxxxxxx 
xxxxxxxxxx
xxxxxx  
xxxxxxxxx ### 
(xxxxxxxxxx) 
Xxxxxx 
(A/B/E/C/D) 
Xx/F 
(xxxx) 
Yes / No YYYY-MM-DD 
(T1_P1) 
xx 
Moderate / 
Related 
Not 
Applicable(Re
covered/Resol
ved) (Yes) 
T1_P5 
 
Xx/F 
(xxxx) 
Yes / No YYYY-MM-DD 
(T2_P2) 
xx 
Moderate/ 
Not Related 
Drug 
Interrupted(R
ecovering/Res
olving)g 
(Yes) 
 
 
 
 
 
 
 
 
 
xxxxxxxxxx
xxxxxx  
xxxxxxxxx 
### 
(xxxxxxxxxx) 
Xxxxxx 
(A/B/E/C/D) 
Xx/F 
(xxxx) 
Yes / 
Yes 
YYYY-MM-DD 
(T1_P1) 
xx 
xxxxxxxx/ 
xxxxxxxxx 
Dose not 
changed 
(Recovered/Re
solved with 
sequelae)(No) 
T1_P7 
xxxxxxxx 
### 
(xxxxxxxxxx) 
Xxxxxx 
(A/B/E/C/D) 
Xx/F 
(xxxx) 
Yes / No YYYY-MMDD 
(T2_P2) 
xx 
xxxxxxxx/ 
xxxxxxxxx 
Dose not 
changed 
(Recovered/Re
solved with 
sequelae)(No) 
 
… 
 
 
 
 
 
 
 
 
xxxxxxxxxxxxxxxxxxx
xxxx 
xxxxxxxxxx
xxxxxx  
xxxxxxxxxx 
### 
(xxxxxxxxxx) 
Xxxxxx 
(A/B/E/C/D) 
Xx/F 
(xxxx) 
# /No 
YYYY-MM-DD 
(T1_P1) 
xx 
xxxxxxxx/ 
xxxxxxxxx 
Dose not 
changed 
(Recovered/Re
solved with 
sequelae)(Yes
) 
 
Xxxxxx 
(A/B/E/C/D) 
Xx/F 
(xxxx) 
Yes / 
Yes 
YYYY-MM-DD 
(T2_P2) 
xx 
xxxxxxxx/ 
xxxxxxxxx 
Drug 
withdrawn 
(Recovering/R
esolving) 
 


Albuterol Sulfate Pressurized Inhalation Suspension 
Protocol D6930C00001 (PT007001) 
Version 0.1 
13 Mar 2018 
Page 79 of 87 
 
 
(Yes) 
 
 
 
 
 
 
Treatment: A = Placebo, B = AS MDI 90 μg, C = AS MDI 180 μg, D = Proventil 90 μg, E = Proventil 180 μg, - = Not Treated. 
Race: A=Asian, AIAN=American Indian or Alaska Native, B=Black or African American, NHPI=Native Hawaiian or Other Pacific Islander, 
     O=Other W=White. Gender: F=Female, M=Male. 
[a]  # indicates that it could not be determined whether the AE had onset during study treatment. 
[b]  A negative number for study day denotes the number of days prior to the start of study treatment. Otherwise, Study Day is Date – 
Date of dose in the Period + 1. Tx = Period. Tx_y = Period and Day within Period. Pxx = Days after dose in last Treatment Period. 
 On Study Day 1, an @ indicates that event started before study drug administration.   
 On Study Day 1, @@ indicates that event started after study drug administration. 
[c]  Duration of Event = Stop Day - Onset Day + 1.  
Source: xxxx.sas7bdat 
Report generated by program: PT007001/sasdir/programs/statout/l0701.sas  Version YYYY-MM-DD xx:xx                 (Page n of N) 
 
Notes to Programmer:  
Sort by Primary System Organ Class, Preferred Term, Actual Treatment, Center, Subject ID within Center, and Onset Day.  
Put a blank line after each Center. Present the preferred term, treatment, center (investigator name), Subject ID (Actual Treatment and Age/gender/Race only if start a new value 
or at the first line of each page. 
When a date of onset or date resolved is only partial, put full date in parenthesis under Study Day. 
Move ‘Study Center/Inv’ row header to the next page whenever there is not enough room on current page to fit at least one row of data underneath this header.   
 
 
 


Albuterol Sulfate Pressurized Inhalation Suspension 
Protocol D6930C00001 (PT007001) 
Version 0.1 
13 Mar 2018 
Page 80 of 87 
 
 
 
Listing 7.2 
Glossary of Adverse Event Preferred Terms vs. Investigator’s Verbatim 
 
MedDRA Adverse Event Coding Dictionary 
Investigator’s AE Verbatim 
Primary System Organ Class 
Preferred Term 
 
xxxxxxxxxxxxxxx 
 
xxxxxxxxxxxxxxxxxxxxxxxxxx 
 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
xxxxxxxxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
xxxxxxxxxxxx 
 
 
 
xxxxxx 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxxxx 
 
 
xxxxxxxxxx 
 
xxxxxxxxxxxxxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
 
 
 
xxxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxxxxxx 
 
 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx 
MedDra Version xx.x was used for coding. 
 
Source: xxxxxxx.sas7bdat   
 
Report generated by program: PT007001/sasdir/programs/statout/l0702.sas  Version YYYY-MM-DD xx:xx                  (Page n of N) 
 
 
Notes to Programmer: Sort by Primary System Organ Class, Preferred Term, and Verbatim Term. List all unique investigators’ AE verbatim.   
 
 
 


Albuterol Sulfate Pressurized Inhalation Suspension 
Protocol D6930C00001 (PT007001) 
Version 0.1 
13 Mar 2018 
Page 81 of 87 
 
 
Listing 7.3 
Adverse Events by Treatment, Center, Subject ID, and Onset Day 
Analysis Set: All Subjects Randomized 
 
Subject ID 
(Treatment 
Sequence) 
Age 
(yrs)/ 
Gender 
(Race) 
Onset Date 
(Day) 
[a]/ Occur 
before or 
after start 
of a 
treatment 
 On Day 1 
Primary System 
Organ Class 
AE Verbatim  
(Preferred 
Term) 
Treat. 
Emerg. 
[b] 
Event 
Seriou
s 
Duration 
of Event 
[c] 
Severity 
Relation
-ship 
Action 
AE 
Treated
? 
Outcome 
(Death?) 
Day 
Resolved/ 
Death [a] 
Treatment: AS MDI 
Center # (Investigator): Center ### (xxxxxxxxxx) 
xxxxx 
(A/B/E/C/D) 
Xx/F 
(xxxx) 
YYYY-MM-DD 
(T1_P1) 
xxx xxx xxxxx AE 1 
(xxxxxxxxxxxx
) 
Yes 
No 
 
Moderate 
 
Not 
related 
Dose not 
changed 
No 
Recoveri
ng/Resol
ving 
YYYY-MM-DD 
(T1_P1) 
xxx xxx xxxx AE 2  
(xxxxxxxxxx) 
No 
No 
xx 
Moderate  Related 
Drug 
Interrup
ted  
Yes Not 
Recovere
d/Not 
Resolved 
(Yes) 
T1_P3 
… 
… 
 
 
 
 
 
Treatment: A = Placebo, B = AS MDI 90 μg, C = AS MDI 180 μg, D = Proventil 90 μg, E = Proventil 180 μg, - = Not Treated. 
Race: A=Asian, AIAN=American Indian or Alaska Native, B=Black or African American, NHPI=Native Hawaiian or Other Pacific Islander, 
     O=Other W=White. Gender: F=Female, M=Male. 
[a]  A negative number for study day denotes the number of days prior to the start of study treatment. Otherwise, Study Day is Date –  
     Date of dose in the Period + 1. Tx = Period. Tx_y = Period and Day within Period. Pxx = Days after dose in the last Treatment 
    Period. 
    On Study Day 1, an @ indicates that event started before study drug administration.   
    On Study Day 1, @@ indicates that event started after study drug administration. 
[b]  # indicates that it could not be determined whether the AE had onset during study treatment. 
[c]  Duration of Event = Stop Day - Onset Day + 1. 
Sources: adae.sas7bdat 
Report generated by program: PT007001/sasdir/programs/statout/l0703.sas  Version YYYY-MM-DD xx:xx                 (Page n of N) 
 
Notes to Programmer:  
Sort by Actual Treatment, Center, Subject ID, Primary System Organ Class, Preferred Term, and Onset Day.  Put a blank line after each subject.  
Present the preferred term, latest treatment, center (investigator name), Subject ID, and Age/gender/Race when value changes start a new value or at the first line of each page 
Move ‘Study Center/Inv’ row header to the next page whenever there is not enough room on current page to fit at least one row of data underneath this header.   
If Ongoing is ticked on CRF, show ‘Ongoing’ under Study Day Resolved. 


Albuterol Sulfate Pressurized Inhalation Suspension 
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4.8 Laboratory Values 
 
Listing 8.1 
Laboratory Test Results (Hematology Panel) 
Analysis Set: All Subjects Randomized 
 
Subject ID 
(Treatment 
Sequence) 
Age 
(yrs)/ 
Gender 
(Race) 
Visit  
(Study Day [a]) 
Collection 
Date 
(Study Day) 
[a] 
Nominal 
Time of 
Collection 
(24 hr clock) 
Lab Name  
Lab 
Parameter 
(Unit) 
Assay 
Value 
Reference 
Range 
Low-High 
Flag 
[b] 
 
 
Center # (Investigator): Center ### (xxxxxxxxxx) 
 
xxxxxx 
(A/B/E/C/D
) 
 
 
Xx/F 
(xxxx) 
Visit 1  
(-xx) 
 
YYYY-MM-DD 
(-xx) 
NA (hh:mm) 
 
xxxxxx 
xxxxxxxxx 
xxx 
xxx-xxx 
L/H 
 
 
 
Visit 6 
(Tx_Py) 
YYYY-MM-DD 
(Tx_Py) 
Post-
Treamtent Day 
(hh:mm) 
 
xxxxxx 
xxxxxxxxx 
xxx 
xxx-xxx 
L/H 
 
 
 
 
 
 
 
 
 
 
 
 
Treatment: A = Placebo, B = AS MDI 90 μg, C = AS MDI 180 μg, D = Proventil 90 μg, E = Proventil 180 μg, - = Not Treated. 
Race: A=Asian, AIAN=American Indian or Alaska Native, B=Black or African American, NHPI=Native Hawaiian or Other Pacific Islander, 
      O=Other W=White. Gender: F=Female, M=Male. 
NA = Not Applicable. 
[a]  A negative number for study day denotes the number of days prior to the start of study treatment. Otherwise, Study Day is Date – 
Date of dose in the Period + 1. Tx = Period. Tx_y = Period and Day within Period. Pxx = Days after dose in last Treatment Period. 
[b]  N = Normal; L = Low; H = High; Abn. = Abnormal; I=Indeterminate. 
 
Source: adlb.sas7bdat  
 
Report generated by program: PT007001/sasdir/programs/statout/l0801.sas  Version YYYY-MM-DD xx:xx                  (Page n of N)  
 
Notes to Programmer:  
Sort by Actual Treatment, Center, Subject ID, Date of Visit, Nominal Time of Collection, and Lab Parameter.  Thus, show Screening Visit 1 before Visit 6. Visit 1 will not have a 
treatment time. . 
Move ‘Study Center/Inv’ row header to the next page whenever there is not enough room on current page to fit at least one row of data underneath this header.   
 
 
Listing 8.2 
Laboratory Test Results (Chemistry Panel and Kidney Function) 
Analysis Set: All Subjects Randomized 


Albuterol Sulfate Pressurized Inhalation Suspension 
Protocol D6930C00001 (PT007001) 
Version 0.1 
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Listing 8.3 
Laboratory Test Comments 
Analysis Set: All Subjects Randomized 
 
Subject ID 
(Treatment 
Sequence) 
Visit  
(Study Day [a]) 
Collection 
Date 
(Study Day 
[a]) 
Nominal 
Time of 
Collection 
(24 h 
clock) 
Lab 
Name 
Lab Group 
Lab 
Parameter 
(Unit) 
Assay 
Value 
Reference 
Range 
Low-High 
Flag 
[b] 
Result 
Comments 
 
Center # (Investigator): Center ### (xxxxxxxxxx) 
 
xxxxxx 
(A/B/E/C/D) 
 
Visit 6 
(Tx_Py) 
 
YYYY-MM-DD 
(Tx_y)  
Post-
Treatment 
Day 
(hh:mm) 
 
LabCorp 
Chemistry 
Bicarbonate 
(mmol/L) 
18.000 
19-34 
L 
xxxxxx 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Treatment: A = Placebo, B = AS MDI 90 μg, C = AS MDI 180 μg, D = Proventil 90 μg, E = Proventil 180 μg, - = Not Treated. 
Race: A=Asian, AIAN=American Indian or Alaska Native, B=Black or African American, NHPI=Native Hawaiian or Other Pacific Islander, 
      O=Other W=White. Gender: F=Female, M=Male. 
NA = Not Applicable. 
[a]  A negative number for study day denotes the number of days prior to the start of study treatment. Otherwise, Study Day is Date – 
Date of dose in the Period + 1. Tx = Period. Tx_y = Period and Day within Period. Pxx = Days after dose in last Treatment Period. 
[b]  N = Normal; L = Low; H = High; Abn. = Abnormal; I=Indeterminate.  
 
Source: adlb.sas7bdat    
 
Report generated by program: PT007001/sasdir/programs/statout/l0803.sas  Version YYYY-MM-DD xx:xx                 (Page n of N)   
 
Notes to Programmer:  
Sort by Actual Treatment, Center, Subject ID, Date of Visit, Nominal Time of Collection, and Lab Parameter.   
Move ‘Study Center/Inv’ row header to the next page whenever there is not enough room on current page to fit at least one row of data underneath this header.   
 
 
 


Albuterol Sulfate Pressurized Inhalation Suspension 
Protocol D6930C00001 (PT007001) 
Version 0.1 
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Page 84 of 87 
 
 
 
4.9 Other Clinical Observations and Measurements 
 
Listing 9.1 
Vital Signs, Weight, and Height 
Analysis Set: All Subjects Randomized 
 
Subject ID 
(Treatment 
Sequence) 
Age (yrs)/ 
Gender 
(Race) 
Visit 
Visit Date 
(Study Day) 
[a] 
Time of 
treatment 
(24 h 
clock) 
Nominal Time of 
Assessment 
 
Systolic 
BP 
(Change 
from 
baseline) 
[b] 
(mmHg) 
Diastolic 
BP 
(Change 
from 
baseline) 
[b] 
(mmHg) 
Heart 
Rate 
(BPM) 
Height 
(cm) 
Weight 
(kg) 
BMI 
(kg/m^2) 
Center # (Investigator): Center ### (xxxxxxxxxx) 
Xxxxxx 
(A/B/E/C/D
) 
Xx/F 
(xxxx) 
Screening 
Visit 1  
YYYY-MM-DD 
(Tx_y) 
NA 
 
xxx 
xxx 
xxx 
xxx 
xxx.x 
xxx.x 
 
Xx/F 
(xxxx) 
Screening 
Visit 2 
YYYY-MM-DD 
(Tx_y) 
NA 
 
xxx 
xxx 
xxx 
xxx 
xxx.x 
xxx.x 
 
Xx/F 
(xxxx) 
Visit x  
YYYY-MM-DD 
(Tx_y) 
hh:mm 
NA 
 
xxx 
xxx 
xxx 
xxx 
xxx.x 
xxx.x 
 
Xx/F 
(xxxx) 
Visit x  
YYYY-MM-DD 
(Tx_y) 
hh:mm 
Pre-Dose  
 
xxx  
xxx  
xxx  
 
 
 
 
 
Unsch. 
YYYY-MM-DD 
(Tx_y) 
hh:mm 
 
xxx (xx) xxx (xx) xxx (xx) 
 
 
 
Treatment: A = Placebo, B = AS MDI 90 μg, C = AS MDI 180 μg, D = Proventil 90 μg, E = Proventil 180 μg, - = Not Treated. 
Race: A=Asian, AIAN=American Indian or Alaska Native, B=Black or African American, NHPI=Native Hawaiian or Other Pacific Islander, 
     O=Other W=White. Gender: F=Female, M=Male. 
NA = Not Applicable. 
[a]  A negative number for study day denotes the number of days prior to the start of study treatment. Otherwise, Study Day is Date – 
     Date of dose in the Period + 1. Tx = Period. Tx_y = Period and Day within Period. Pxx = Days after dose in last Treatment Period. 
[b]  For change from baseline, baseline is defined as the last pre-dose measurement taken prior to dosing on Day 1 of a treatment  
    period.  
Source: advs.sas7bdat 
Report generated by program: PT007001/sasdir/programs/statout/l0901.sas  Version    YYYY-MM-DD xx:xx              (Page n of N) 
 


Albuterol Sulfate Pressurized Inhalation Suspension 
Protocol D6930C00001 (PT007001) 
Version 0.1 
13 Mar 2018 
Page 85 of 87 
 
 
Notes to Programmer:  Sort by Actual Treatment, Center, Subject ID, Date of Visit, and Nominal Time of Assessment.  Nominal time of assessment of Pre-Dose should be provided 
for all assessments prior to the study drug dose on a day; Post-Dose values are those after the  study drug dose was given on a day. If an assessment is not Pre-Dose or Post-Dose, 
then show ‘NA’ instead. 
Move ‘Study Center/Inv’ row header to the next page whenever there is not enough room on current page to fit at least one row of data underneath this header. 
 
 


Albuterol Sulfate Pressurized Inhalation Suspension 
Protocol D6930C00001 (PT007001) 
Version 0.1 
13 Mar 2018 
Page 86 of 87 
 
 
 
Listing 9.2 
12-Lead Electrocardiogram (ECG) 
Analysis Set: All Subjects Randomized 
 
Subject ID 
(Treatment 
Sequence) 
Age 
(yrs)/ 
Gender 
(Race) 
Visit 
Visit Date 
(Study Day) [a] 
Treatment 
Time  
(24 h 
clock) 
Nominal Time of Assessment 
Heart 
Rate 
 (BPM) 
Interval Raw Value 
Any 
Clinically 
Significant 
Abnormalities 
on a Study 
Day? [b] 
RR 
(ms) 
PR 
(ns) 
QRS Axis 
(degrees) 
QRS 
(ms) 
QT 
(ms) 
QTcF 
(ms) 
Center # (Investigator): Center ### (xxxxxxxxxx) 
xxxxx 
(A/B/E/C/D) 
Xx/F 
(xxxx) 
Visit 1 
YYYY-MM-DD 
(-xx) 
NA 
NA 
xx.x 
xxx 
xxx 
xx 
xxx 
xxx 
xx 
No 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Visit 6 
YYYY-MM-DD 
(Tx_1) 
 
Post-Dose 
xx.x 
xx.x xx.x 
xx.x 
xx.x xx.x xx.x 
Yes 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Unscheduled 
YYYY-MM-DD 
(Tx_Py) 
NA 
NA 
xx.x 
xx.x xx.x 
xx.x 
xx.x xx.x xx.x 
No 
 
 
Etc… 
 
 
 
 
 
 
 
 
 
 
Treatment: A = Placebo, B = AS MDI 90 μg, C = AS MDI 180 μg, D = Proventil 90 μg, E = Proventil 180 μg, - = Not Treated. 
Race: A=Asian, AIAN=American Indian or Alaska Native, B=Black or African American, NHPI=Native Hawaiian or Other Pacific Islander, 
      O=Other W=White. Gender: F=Female, M=Male. 
[a]  A negative number for study day denotes the number of days prior to the start of study treatment. Otherwise, Study Day is Date – 
Date of dose in the Period + 1. Tx = Period. Tx_y = Period and Day within Period. Pxx = Days after dose in last Treatment Period. 
[b]  Abnormalities at Screening Visits and Pre-Dose on Day 1 of Treatment Period 1 were noted on the Medical History CRF;  
     Abnormalities Post-Dose on Day 1 of Treatment Period 1 or afterward were noted on the Adverse Events CRF. 
 
Source: eg.sas7bdat   
Report generated by program: PT007001/sasdir/programs/statout/l0902.sas  Version YYYY-MM-DD xx:xx                 (Page n of N)  
 
Notes to Programmer:  Sort by Actual Treatment, Center, Subject ID, Date of Visit, and Nominal Time of Assessment.  Nominal time of assessment of Pre-Dose should be provided 
for all assessments prior to the study drug dose on a day; Post-Dose values are those after the  study drug dose was given on a day .If an assessment is not Pre-Dose or Post-Dose, 
then show ‘NA’ instead. 
Move ‘Study Center/Inv’ row header to the next page whenever there is not enough room on current page to fit at least one row of data underneath this header. 
 
 


Albuterol Sulfate Pressurized Inhalation Suspension 
Protocol D6930C00001 (PT007001) 
Version 0.1 
13 Mar 2018 
Page 87 of 87 
 
 
 
Listing 9.3 
Comments 
Analysis Set: All Subjects Randomized 
 
Subject 
ID 
Treatment 
Sequence 
Age (yrs)/ 
Gender 
(Race) 
Visit 
 
Comment Applies To: 
Comments 
 
Study Center # / (Investigator):  ### (xxxxxxxxxx) 
 
xxxxx 
A/B/E/C/D 
Xx/M (xxxx) 
Screening Visit 1 
Screening Visit 1a 
Screening Visit 1b 
Visit 2 Visit 3 … 
 
Premature 
Discontinuation 
Telephone Follow-up 
Unscheduled 
 
Subject Eligibility 
Study Medication 
Adverse Event 
Vital Signs 
12-Lead ECG 
Laboratory Results 
Spirometry 
Visit Scheduling 
Other: xxxxxxxxxxxxxxx 
xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx
xxxxxxxxxxxx 
Treatment: A = Placebo, B = AS MDI 90 μg, C = AS MDI 180 μg, D = Proventil 90 μg, E = Proventil 180 μg, - = Not Treated. 
Race: A=Asian, AIAN=American Indian or Alaska Native, B=Black or African American, NHPI=Native Hawaiian or Other Pacific Islander, 
      O=Other W=White. Gender: F=Female, M=Male. 
 
Source: xxxxxxx.sas7bdat 
Report generated by program: PT007001/sasdir/programs/statout/l0904.sas  Version  YYYY-MM-DD xx:xx       (Page n of N) 
 
 
Notes to Programmer:  
Sort by Center, Investigator, Subject ID, Visit, Study Day, and category that comment applies to (Subject Eligibility, Study Medication, etc…).   
Move ‘Study Center/Inv’ row header to the next page whenever there is not enough room on current page to fit at least one row of data underneath this header.   
Column and text in YELLOW is optional for studies where one or more ‘Visits’ are not associated with a Study Day.