ALTA - ALbuterol/Budesonide Treatment in Acute Airway Obstruction. A Randomized, Double-blind, 2-period, Cross-over Study Evaluating Efficacy and Safety of Repeated Doses of PT027 Compared to PT007 in Patients With Asthma and Acute Airway Obstruction Induced by Repeated Mannitol Challenges
Phase: PHASE3
Conditions: Asthma
Sponsor: AstraZeneca

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Clinical Study Protocol
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ALTA - ALbuterol/budesonide Treatment in Acute Airway 
Obstruction
A randomized, double-blind, 2-period, cross-over study evaluating 
efficacy and safety of repeated doses of PT027 compared to PT007 
in patients with asthma and acute airway obstruction induced by 
repeated mannitol challenges
Sponsor Name: AstraZeneca AB
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Brief Title: 37FRPSDUHGWR37LQSDWLHQWVZLWKDVWKPDZLWKPDQQLWROLQGXFHGDFXWH
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TMP-0010225
SUMMARY OF CHANGES TABLE
DOCUMENT HISTORY
Document
Date
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TMP-0010225
Section Number and Name
Description of Change
Brief Rationale
7KURXJKRXWWKHGRFXPHQW
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TMP-0010225
TABLE OF CONTENTS
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TMP-0010225
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LIST OF FIGURES
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LIST OF TABLES
7DEOH 
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LIST OF APPENDICES
Appendix A
5HJXODWRU\(WKLFDODQG6WXG\2YHUVLJKW&RQVLGHUDWLRQV 
Appendix B
$GYHUVH(YHQWV'HILQLWLRQVDQG3URFHGXUHVIRU5HFRUGLQJ(YDOXDWLQJ
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Appendix C
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Appendix D
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Appendix E
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Appendix F
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TMP-0010225
2
INTRODUCTION
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4
STUDY DESIGN
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4.2
Scientific Rationale for Study Design
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TMP-0010225
Figure 3
Illustration of the Aspects of FEV1 and Symptoms That may be 
Evaluated to Support Objectives (During Visits 2 and 3)
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TMP-0010225
4.2.1 Participant Input into Design
7KH$/7$VWXG\GHVLJQZDVUHYLHZHGE\SDWLHQWVZLWKDVWKPDDFFRUGLQJWRVWDQGDUGSDWLHQW
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4.3
Justification for Dose
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4.4
End-of-Study Definition
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TMP-0010225
5
STUDY POPULATION
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5.1
Inclusion Criteria
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Sex
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TMP-0010225
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TMP-0010225
5.2
Exclusion Criteria
3DUWLFLSDQWVDUHH[FOXGHGIURPWKHVWXG\LIDQ\RIWKHIROORZLQJFULWHULDDSSO\
Medical Conditions
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5.3
Lifestyle Considerations
5.3.1
Meals and Dietary Restrictions
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5.3.2
Caffeine, Alcohol, and Tobacco
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5.3.3
Activity
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5.4
Screen Failures
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TMP-0010225
6
STUDY INTERVENTION(S) AND CONCOMITANT 
MEDICATIONS
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6.1
Study Intervention(s) Administered
6.1.1
Investigational Products
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Table 6
Investigational Products
Arm name
3DUWDQG
3DUWDQG 
Intervention 
name
37
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Type 
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Dose 
formulation
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strengths
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Route of 
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labeling
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6.2
Preparation, Handling, Storage, and Accountability
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6.2.1
Metered Dose Inhaler Handling
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6.3
Assignment to Study Intervention
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6.4
Study Intervention Compliance
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6.5
Dose Modification
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6.6
Continued Access to Study Intervention After the End of the 
Study
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6.7
Treatment of Overdose
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Prior and Concomitant Therapy
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7
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL
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Discontinuation of Study Intervention
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Participant Withdrawal from the Study
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FEV1 Baseline, Mannitol Challenge Positive Reactivity, and FEV1
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High-level Schema of Study Stability Criteria FEV1 and PD15 Mannitol

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8
STUDY ASSESSMENTS AND PROCEDURES
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Administrative and General/Baseline Procedures
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Efficacy Assessments
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8.2.1
Lung Function Test: Spirometry
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8.2.2
Asthma Impairment and Risk Questionnaire (AIRQ®)
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8.2.3
Severity per National Asthma Education and Prevention Program
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Modified Borg Scale
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Mannitol Challenge Test
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8.2.6
Perceived Onset of Effect
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Safety Assessments
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Physical Examinations
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Vital Signs
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8.3.3
Safety Spirometry
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Electrocardiograms
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8.3.5
Clinical Safety Laboratory Assessments
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Table 7
Laboratory Safety Variables
Hematology/Hemostasis (whole blood)
Clinical Chemistry (serum or plasma)
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Blood Eosinophil Measurement
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8.4
Adverse Events, Serious Adverse Events, and Other Safety 
Reporting
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8.4.1
Time Period and Frequency for Collecting AE and SAE Information
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Adverse Event Variables

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8.4.4 Adverse Events Based on Examinations and Tests
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8.4.5 Adverse Events Based on Signs and Symptoms
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8.4.6 Hy’s Law
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8.4.7 Disease Under Study
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8.4.8
Reporting of Serious Adverse Events
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8.4.9
Pregnancy
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8.4.10
Medication Error, Drug Abuse, and Drug Misuse
8.4.10.1
Timelines
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8.4.10.2
Medication Error
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8.4.10.3
Drug Abuse
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8.4.10.4
Drug Misuse
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8.4.11
Reporting of Overdose
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8.4.12
Medical Device Deficiencies
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8.5
Pharmacokinetics
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8.6
Immunogenicity Assessments
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TMP-0010225
8.7
Pharmacodynamics
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8.8
Optional Genomics Initiative
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8.9
Biomarkers
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8.9.1
Mandatory Biomarker Sample Collection
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8.9.1.1
Urinary Leukotrienes including LTE4
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8.9.1.2
Serum cAMP, cAMP Mobilizing Analytes, and Additional Exploratory Blood 
Inflammatory Biomarkers
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TMP-0010225
8.9.1.3
Beta Receptor and Corticosteroid Receptor Expression Genetics
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8.9.2
Optional Biomarker Sample Collection
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8.9.3
Other Study-Related Biomarker Research
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8.10
Study Participant Feedback Questionnaire
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TMP-0010225
Objectives
Hypothesis
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Objectives
Hypothesis
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TMP-0010225
Sample Size Re-estimation
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SRVWPDQQLWROFKDOOHQJHSUHGRVH SUHILQDOGRVHRIUHVFXHUHOLHYHU$VDPSOHVL]HRI
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TMP-0010225
FKDQJHIURPEDVHOLQH)(9 HQGSRLQWVLH)(9 $8&W QRUPDOL]HGE\WLPHDQGWKRVHDW
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SRVWPDQQLWROFKDOOHQJHIRUZKLFKWKHQRQLQIHULRULW\OLPLWZLOOEH P/
9.3
Populations for Analyses
7KHDQDO\VHVSRSXODWLRQVDUHGHILQHGLQ7DEOH
Table 10
Populations for Analysis
Population/Analysis Set
Description
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$OOSDUWLFLSDQWVZKRVLJQWKH,&)
0RGLILHGUDQGRPL]HGDQDO\VLV
VHWP56
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9.4
Statistical Analyses
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9.4.1
General Considerations
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TMP-0010225
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GHWDLOVZLOOEHGHVFULEHGLQWKH6$3
Table 11
Baseline for Primary/Secondary Endpoints and Safety Parameters 
Definitions
Category/Assessment
Baseline Definition
Endpoints/Parameters
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SODQQHGWREHSUHVHQWHGIRUSRROHG3DUWDQGGDWDDQGWKHVDPHUHSRUWLQJVWUDWHJ\DSSOLHV
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DQG3DUWDQG IRUSHUFHQWDJHIDOOIURPEDVHOLQHPLQ)(9 WRSRVWPDQQLWROFKDOOHQJH
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9.4.2
Adjustment for Multiple Comparisons
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6SHFLILFDOO\W\SHHUURUFRQWUROZLOOEHFRQWUROOHGE\WUDQVIHUULQJDOSKDVSHQGLQJWR
VXEVHTXHQWHQGSRLQWVLQWKHWHVWLQJKLHUDUFK\GHSHQGHQWRQWKHVWDWLVWLFDOVLJQLILFDQFHRIWKH
WHVWLQJ
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TMP-0010225
Figure 5
Hierarchical Testing Structure
9.4.3
Efficacy
9.4.3.1
Primary Endpoint
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TMP-0010225
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9.4.5
Other Analyses
1RRWKHUDQDO\VHVDUHSODQQHG
9.5
Interim Analyses
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TMP-0010225
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9.6
Data Monitoring Committees
9.6.1
AstraZeneca Internal Advisory Board
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TMP-0010225
10
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS

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TMP-0010225
Appendix A
Regulatory, Ethical, and Study Oversight Considerations
A 1
Regulatory and Ethical Considerations
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TMP-0010225
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Regulatory Reporting Requirements for Serious Breaches
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A 2
Financial Disclosure
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A 3
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A 7
Source Documents
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A 9
Publication Policy
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TMP-0010225
Appendix B
Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting
B 1
Definition of Adverse Events
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B 2
Definition of Serious Adverse Events
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Life-threatening
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TMP-0010225
Appendix C
Handling of Human Biological Samples
C 1
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TMP-0010225
Appendix D
Optional Genomics Initiative Sample
D 1
Use/Analysis of DNA
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D 2
Genetic Research Plan and Procedures
Selection of Genetic Research Population
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Withdrawal of Consent for Genetic Research
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TMP-0010225
Appendix E
Actions Required in Cases of Increases in Liver Biochemistry 
and Evaluation of Hy’s Law
E 1
Introduction
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E 2
Definitions
Potential Hy’s Law
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E 3
Identification of Potential Hy’s Law Cases
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TMP-0010225
E 4
Investigator Follow-up
E 4.1
Potential Hy’s Law Criteria not met
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Potential Hy’s Law Criteria met
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TMP-0010225
E 5
Review and Assessment of Potential Hy’s Law Cases
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TMP-0010225
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E 6
Laboratory Tests
Hy’s Law Lab Kit for Central Laboratories
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TMP-0010225
E 7
References
Aithal et al 2011
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TMP-0010225
Appendix F
Instructions for Handling and Use of Oral Inhaler Device
F 1
Instructions For Use - Clinic

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TMP-0010225

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TMP-0010225

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TMP-0010225
F 2
Instructions For Use – Participant

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TMP-0010225
Appendix G
Protocol Version History
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CSP Version 3.0, Amendment 2: (03 February 2023)
Overall Rationale for the Modification:
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Summary of Changes:
List of Substantial Modifications
Section Number and Name
Description of Change
Brief Rationale
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TMP-0010225
11
REFERENCES
AAFA 2020
$VWKPDDQG$OOHUJ\)RXQGDWLRQRI$PHULFD>$VWKPDGLVSDULWLHVLQ$PHULFD D
URDGPDSWRUHGXFLQJEXUGHQRQUDFLDODQGHWKQLFPLQRULWLHV@$YDLODEOHIURP
KWWSVDDIDRUJDVWKPDGLVSDULWLHV
Anderson 2011
$QGHUVRQ6'%URQFKLDOFKDOOHQJHWHVWVXVHIXOQHVVDYDLODELOLW\ DQGOLPLWDWLRQV%UHDWKH
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Beuther et al 2021
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LPSDLUPHQWDQGULVNTXHVWLRQQDLUH$,54&RQWUROOHYHOLVDVVRFLDWHGZLWKIXWXUHULVNRI
H[DFHUEDWLRQV >DEVWUDFW@-$OOHUJ\&OLQ,PPXQRO6XSSOHPHQW $%
Chipps et al 2021
&KLSSV%($OEHUV)&5HLOO\/-RKQVVRQ(&DSSHOOHWWL&3DSL$(IILFDF\DQGVDIHW\RI
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PRGHUDWHWRVHYHUHDVWKPDUDWLRQDOHDQGGHVLJQRIWKHUDQGRPLVHGGRXEOHEOLQGDFWLYH
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GINA 2021
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DQGSUHYHQWLRQ$YDLODEOHIURPZZZJLQDVWKPDRUJ
Hallstrand et al 2018
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VWDQGDUGRQEURQFKLDOFKDOOHQJHWHVWLQJSDWKRSK\VLRORJ\DQGPHWKRGRORJ\ RILQGLUHFWDLUZD\
FKDOOHQJHWHVWLQJ(XU5HVSLU- 
Hankinson et al 1999
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SIGNATURE PAGE
This is a representation of an electronic record that was signed
electronically and this page is the manifestation of the electronic signature
Document Name: d6930c00017-csp-v4
Document Title:
D6930C00017 Clinical Study Protocol version 4
Document ID:
Doc ID-004813887
Version Label:
4.0 CURRENT LATEST APPROVED
Server Date
(dd-MMM-yyyy HH:mm ‘UTC’Z)
Signed by
Meaning of Signature
12-Jul-2023 14:30 UTC
Management Approval
12-Jul-2023 16:35 UTC
Content Approval
12-Jul-2023 14:41 UTC
Management Approval
Notes: (1) Document details as stored in ANGEL, an AstraZeneca document management system.
PPD
PPD
PPD