A Randomized, Cumulative Dose, Open-label, 2-period Crossover, Multi-center Study to Assess the Safety, Efficacy, PK, and Extrapulmonary Pharmacodynamics (PD) of Cumulative Doses of Albuterol Sulfate Pressurized Inhalation Suspension (Hereafter Referred to as AS MDI) Compared to Cumulative Doses of Proventil® Hydrofluoroalkane (HFA; Hereafter Referred to as Proventil) as an Active Control in Subjects With Mild to Moderate Asthma (ASPEN)
Phase: PHASE2
Conditions: Asthma
Sponsor: AstraZeneca

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Albuterol Sulfate Pressurized Inhalation Suspension (PT007) Cumulative 
Dose Study in Subjects With Mild to Moderate Asthma
Sponsor: AstraZeneca AB, 151 85 Södertälje, Sweden

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CLINICAL STUDY PROTOCOL SYNOPSIS
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Albuterol Sulfate Pressurized Inhalation Suspension (PT007) Cumulative 
Dose Study in Subjects With Mild to Moderate Asthma
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Study sites and number of subjects planned
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Outcome Measures
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TABLE OF CONTENTS
PAGE
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1.
INTRODUCTION
1.1
Background and rationale for conducting this study
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1.2
Rationale for study design, doses and control groups
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Figure 1
Study Design Flow Chart
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1.5
Study governance and oversight
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2.
STUDY OBJECTIVES
2.1
Primary objective
Primary Objective
Outcome Measure
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2.2
Secondary objectives
Secondary Objectives
Outcome Measure 
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2.3
Safety objectives
Safety Objective
Outcome Measure 
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2.4
PK substudy
PK Objective
Outcome Measure
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2.5
Exploratory objectives – not applicable
3.
SUBJECT SELECTION, ENROLLMENT, RANDOMIZATION, 
RESTRICTIONS, DISCONTINUATION AND WITHDRAWAL
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3.1
Inclusion criteria
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3.2
Exclusion criteria
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3.3
Subject enrollment and randomization
3.3.1
Randomization criteria
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3.3.2
Subject identification
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3.3.3
Screen failures
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3.4
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3.6
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3.7
Methods for unblinding – not applicable
3.8
Restrictions
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3.8.1
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3.8.2
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3.9
Discontinuation of study drug
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4.
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Table 1
Schedule of Events
Procedures
Screeninga
Treatment Phase
Follow-up
For details see 
Section
Visit 1
Visit 
1a/1b
Visit 2
Randomization 
(TP 1)
Day 1
Visit 3b
(TP 2)
PDV (if 
applicable)c
TC
3-7 days 
after final 
dose
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Table 1
Schedule of Events
Procedures
Screeninga
Treatment Phase
Follow-up
For details see 
Section
Visit 1
Visit 
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Visit 2
Randomization 
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Day 1
Visit 3b
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applicable)c
TC
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Table 2
Timed Assessments at Each Treatment Visit (Visit 2 and Visit 3)
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Pre-Dose
(minutes) 
Doses 1 through 4
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Dose 5
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-30
0
15
30
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30
60
120
180
240
300
360
480
600
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Screening Period (Visits 1, and Visits 1a/1b if applicable)
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Treatment periods
4.2.1
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STUDY ASSESSMENTS
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Assessment of FEV1
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5.1.4
FEV1 baseline stability criteria
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Safety assessments
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Medical/surgical history and physical examination
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5.2.2
SBP and DBP
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7DEOH
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5.2.3
Clinical laboratory testing
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Table 3.
List of Laboratory Tests to be Performed at Screening
Hematology
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3ODWHOHWFRXQW
+HPDWRFULW
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5HGEORRGFHOOFRXQW
0HDQFRUSXVFXODUYROXPH
Clinical chemistry
Liver enzyme and other liver function tests
Other clinical chemistry
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$OEXPLQ
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&DOFLXP
%LOLUXELQWRWDO
&KORULGH
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3KRVSKDWH
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3URWHLQWRWDO
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6RGLXP
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7ULJO\FHULGHV

8UHD
Other tests:
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D
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EHSHUIRUPHGDW9LVLWEHIRUHUDQGRPL]DWLRQ

5.2.4
ECG
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5.3
Other assessments – not applicable
5.4
PK substudy
5.4.1
Collection of samples
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5.4.2
Determination of drug concentration
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5.4.3
Storage and destruction of PK samples
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5.5
Pharmacodynamics
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5.6
Genetics – not applicable
5.7
Biomarker analysis – not applicable
6.
SAFETY REPORTING AND MEDICAL MANAGEMENT
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6.1
Definition of AEs
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6.2
Definitions of SAE
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6.3
Recording of AEs
6.3.1
Performing AE assessments
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6.3.2
Pre-randomization AEs
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6.3.3
AEs based on signs and symptoms
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6.3.4
AEs based on examinations and tests
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6.3.5
Disease under study
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6.3.6
Severity
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6.3.7
Relationship to study drug
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6.4
Reporting of SAEs
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6.4.1
Supplemental investigations of SAEs
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6.4.2
Post-study follow-up of AEs
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6.4.3
Notification of post-treatment SAEs
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6.4.4
IRB notification of SAEs
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6.4.5
Health Authority Safety Reports
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6.5
Overdose
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6.6
Pregnancy
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6.6.1
Maternal exposure
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6.6.2
Paternal exposure 
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6.7
Medication error
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6.8
Management of study drug-related toxicities – not applicable
7.
INVESTIGATIONAL PRODUCT AND OTHER TREATMENTS
7.1
Identity of investigational product(s)
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Product Name 
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Dose and treatment regimens
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Sponsor-provided background asthma therapies
Ventolin
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7.3.2
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7.5
Compliance
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7.6
Accountability
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7.7
Concomitant and other treatments 
7.7.1
Prior medications
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Table 6
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)
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7.7.2
Concomitant medications
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7.7.2.1
Required concomitant medications
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7.7.2.2
Allowed allergy medications
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Table 7
Allowed Allergy Medications
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7.7.3
Prohibited medications
7.7.3.1
Prohibited asthma and allergy medications and washout periods
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Table 8
Prohibited Asthma and Allergy Medications That Must be 
Discontinued at Visit 1 and Required Washout Period Prior to the 
Next Visit
Medication
Minimum Washout Period Prior to the Next Visit
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7.7.3.2
Prohibited non-asthma and non-respiratory medications
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Table 9
Prohibited Non-Asthma and Non-Respiratory Medications
Class of Medication
Minimum Cessation Period Prior to Visit 1 
and Prohibited Throughout the Study
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7.7.4
Other concomitant treatment
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8.
STATISTICAL ANALYSES
8.1
Statistical considerations
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8.2
Sample size estimate
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8.3
Definitions of analysis sets
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7KHSafety analysis setLVGHILQHGDVDOOVXEMHFWVZKRDUHUDQGRPL]HGWR
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7KHPK analysis setLVGHILQHGDVVXEMHFWVLQWKH6DIHW\DQDO\VLVVHWZKR
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8.4
Outcome measures for analyses
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8.5
Methods for statistical analyses
8.5.1
Primary efficacy analysis
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8.5.2
Secondary efficacy analysis
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8.5.3
Data validation and transformation
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8.5.4
Extrapulmonary PD analysis
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8.5.5
PK substudy: PK analysis
8.5.5.1
PK parameters
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8.5.5.2
Handling of values below the limit of quantification
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8.5.5.3
Statistical analysis of PK data
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8.5.6
Safety analyses
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Adverse events
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8.5.7
Handling of missing data
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Statistical software
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9.
STUDY AND DATA MANAGEMENT BY THE SPONSOR
9.1
Training of study site staff
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9.2
Monitoring of the study
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9.2.1
Study agreements
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9.2.2
Archiving of study documents
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9.3
Study timetable and end of study
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10.
ETHICAL AND REGULATORY REQUIREMENTS
10.1
Ethical conduct of the study
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Subject data protection
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10.4
Informed consent
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10.5
Changes to the clinical study protocol and ICF
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10.6
Audits and inspections
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11.
LIST OF REFERENCES
Ahrens 1984
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ATS/ERS Task Force 2005
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EPR-3 2007
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Global Initiative for Asthma 2017
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Miller et al 2005
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Philipson 2002
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Tripp et al 2008
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Appendix A
Spirometry Assessment Criteria
Spirometry Assessment Criteria
Acceptable Versus Usable Tests
Acceptable Tests must meet the following Criteria:
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Figure A2-1 Example of a Usable Spirogram
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Pre-dose Assessments
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Post-dose Assessments
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Appendix B
Spirometry Performance Recommendations
Spirometry Performance Recommendations
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FEV1 MANEUVERS
Equipment Requirements
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Table A1-1.
Recommended Minimal Scale Factors for Time, Volume and Flow 
on Graphical Output
Parameter
Instrument Display
Hardcopy Graphical 
Output
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Resolution Required
Scale Factor
Resolution Required
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Table A1-2.
Summary of Equipment Quality Control
Test
Minimal 
Interval
Action
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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 
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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
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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
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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.
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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
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Appendix F
Investigator’s Agreement and Signature Page
Investigator’s Agreement and Signature Page
Study Title:
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Study Number:
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Final Date:
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