Study to Compare PT007 to Placebo MDI and Open-Label Proventil® HFA in Adult and Adolescent Subjects With Asthma

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03364608
• Collaborator: (none)
• Enrollment: 86
• Locations: 10
• Arms: 5
• Actual Duration (Months): 3.4
• Patients Per Site: 8.6
• Patients Per Site Per Month: 2.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: AS MDI 90 μg; Drug: AS MDI 180 µg; Other: Placebo MDI; Drug: Proventil 90 μg; Drug: Proventil 180 μg	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 86 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official 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 (ANTORA)
• Actual Study Start Date: Dec 15, 2017
• Actual Primary Completion Date: Mar 30, 2018
• Actual Study Completion Date: Mar 30, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: • AS MDI 90 µg (2 actuations of 45 µg/actuation)	Drug: AS MDI 90 μg; AS MDI 90 μg (2 actuations of 45 μg/actuation); Other Names: AS MDI
Experimental: • AS MDI 180 µg (2 actuations of 90 µg/actuation)	Drug: AS MDI 180 µg; AS MDI 180 μg (2 actuations of 90 μg/actuation); Other Names: AS MDI
Placebo Comparator: • Placebo MDI (2 actuations)	Other: Placebo MDI; Placebo MDI (2 actuations)
Active Comparator: • Proventil 90 µg (1 actuation of 90 µg/actuation)	Drug: Proventil 90 μg; Proventil 90 μg (1 actuation of 90 μg/actuation); Other Names: Proventil
Active Comparator: • Proventil 180 µg (2 actuations of 90 µg/actuation)	Drug: Proventil 180 μg; Proventil 180 μg (2 actuations of 90 μg/actuation); Other Names: Proventil

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in FEV1 AUC0-6 [Over 6 hours post dose on Day 1]

   Change from baseline in FEV1 (Forced expiratory volume in 1 second) AUC0-6 (Area under the curve from 0 to 6 hours) (spirometry will be obtained at 5, 15, 30, 45, 60, 120, 180, 240, 300, and 360 minutes post-dose) normalized for length of follow up.

Secondary Outcome Measures

1. Change From Baseline in FEV1 AUC0-4 [Over 4 hours post dose on Day 1]

   Change from baseline in FEV1 (Forced expiratory volume in 1 second) AUC0-4 (Area under the curve from 0 to 4 hours) (spirometry will be obtained at 5, 15, 30, 45, 60, 120, 180, and 240 minutes post-dose) normalized for length of follow up.

2. Peak Change From Baseline in FEV1 [Over 6 hours post dose on Day 1]

   Peak Change from baseline in FEV1 (Forced expiratory volume in 1 second)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria

• Are at least 12 years of age and no older than 65 years

• Have stable (for 6 months) physician-diagnosed asthma with historical documentation of the diagnosis

• Must be receiving 1 of the following required inhaled asthma therapies listed below for at least the last 30 days; Only SABA, which is used as needed for rescue, or Low to medium doses of ICS (alone or in combination with LABA), used regularly as maintenance asthma therapy

• Demonstrate acceptable spirometry performance (ie, meet American Thoracic Society [ATS]/European Respiratory Society [ERS] acceptability/repeatability criteria

• Pre-bronchodilator FEV1 of ≥40 to <90% predicted normal value after withholding SABA for ≥6 hours

• Confirmed FEV1 reversibility to Ventolin, defined as a post-Ventolin increase in FEV1 of ≥15%

• only 2 reversibility testing attempts are allowed

Exclusion Criteria:

• Chronic obstructive pulmonary disease or other significant lung disease (eg, chronic bronchitis, emphysema, bronchiectasis with the need of treatment, cystic fibrosis, or bronchopulmonary dysplasia)

• Oral corticosteroid use (any dose) within 6 weeks

• 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)

• 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)

• Historical or current evidence of a clinically significant disease

• Cancer not in complete remission for at least 5 years

• Hospitalized for psychiatric disorder or attempted suicide within 1 year

• Unable to abstain from protocol-defined prohibited medications during the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Rolling Hills Estates	California	United States	90274
2	Research Site	Stockton	California	United States	95207
3	Research Site	Winter Park	Florida	United States	32789
4	Research Site	North Dartmouth	Massachusetts	United States	02747
5	Research Site	Saint Louis	Missouri	United States	63141
6	Research Site	Raleigh	North Carolina	United States	27607
7	Research Site	Cincinnati	Ohio	United States	45242
8	Research Site	Medford	Oregon	United States	97504
9	Research Site	Spartanburg	South Carolina	United States	29303
10	Research Site	El Paso	Texas	United States	79903

Sponsors and Collaborators

• AstraZeneca

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Jan 12, 2018
• Statistical Analysis Plan - Mar 13, 2018

More Information

Additional Information:

• Protocol
• Statistical Analysis Plan (SAP)

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT03364608
• Other Study ID Numbers: D6930C00001
• First Posted: Dec 6, 2017
• Last Update Posted: Jul 24, 2019
• Last Verified: Jul 1, 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Asthma; Albuterol

Study Results

Participant Flow

Recruitment Details	This study was conducted at 10 sites in the United States, from December 2017 to March 2018. The study was anticipated to run for at least 23 days but not to exceed 68 days.
Pre-assignment Detail	Subjects were randomized into one of 10 treatment sequences. Each sequence comprised all 5 treatments included in this study (ie, AS MDI 90 μg, AS MDI 180 μg, Placebo MDI, Proventil 90 μg, and Proventil 180 μg) in a randomized order

Arm/Group Title	Subjects
Arm/Group Description	ITT Analysis set
Period Title: Overall Study
STARTED	86
Placebo MDI	82
AS MDI 90 µg	81
AS MDI 180 µg	81
Proventil 90 µg	82
Proventil 180 µg	79
COMPLETED	78
NOT COMPLETED	8

Baseline Characteristics

Arm/Group Title	Overall Study
Arm/Group Description	Safety Set
Overall Participants	86
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	42.7 (13.4)
Sex: Female, Male (Count of Participants)
Female	47 54.7%
Male	39 45.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	14 16.3%
Not Hispanic or Latino	72 83.7%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 1.2%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	20 23.3%
White	62 72.1%
More than one race	0 0%
Unknown or Not Reported	3 3.5%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in FEV1 AUC0-6
Description	Change from baseline in FEV1 (Forced expiratory volume in 1 second) AUC0-6 (Area under the curve from 0 to 6 hours) (spirometry will be obtained at 5, 15, 30, 45, 60, 120, 180, 240, 300, and 360 minutes post-dose) normalized for length of follow up.
Time Frame	Over 6 hours post dose on Day 1

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title	AS MDI 180 µg	AS MDI 90 µg	Proventil 180 µg	Proventil 90 µg	Placebo MDI
Arm/Group Description	(2 actuations of 90 µg/actuation)	(2 actuations of 45 µg/actuation)	(2 actuations of 90 µg/actuation)	(1 actuation of 90 µg/actuation)	(2 actuations)
Measure Participants	79	79	77	78	78
Least Squares Mean (95% Confidence Interval) [Liters]	0.266	0.203	0.282	0.240	0.070

2. Secondary Outcome

Title	Change From Baseline in FEV1 AUC0-4
Description	Change from baseline in FEV1 (Forced expiratory volume in 1 second) AUC0-4 (Area under the curve from 0 to 4 hours) (spirometry will be obtained at 5, 15, 30, 45, 60, 120, 180, and 240 minutes post-dose) normalized for length of follow up.
Time Frame	Over 4 hours post dose on Day 1

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title	AS MDI 180 µg	AS MDI 90 µg	Proventil 180 µg	Proventil 90 µg	Placebo MDI
Arm/Group Description	(2 actuations of 90 µg/actuation)	(2 actuations of 45 µg/actuation)	(2 actuations of 90 µg/actuation)	(1 actuation of 90 µg/actuation)	(2 actuations)
Measure Participants	79	79	77	78	78
Least Squares Mean (95% Confidence Interval) [Liters]	0.331	0.263	0.349	0.297	0.080

3. Secondary Outcome

Title	Peak Change From Baseline in FEV1
Description	Peak Change from baseline in FEV1 (Forced expiratory volume in 1 second)
Time Frame	Over 6 hours post dose on Day 1

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title	AS MDI 180 µg	AS MDI 90 µg	Proventil 180 µg	Proventil 90 µg	Placebo MDI
Arm/Group Description	(2 actuations of 90 µg/actuation)	(2 actuations of 45 µg/actuation)	(2 actuations of 90 µg/actuation)	(1 actuation of 90 µg/actuation)	(2 actuations)
Measure Participants	79	79	77	78	78
Least Squares Mean (95% Confidence Interval) [Liters]	0.509	0.433	0.516	0.472	0.233

Adverse Events

Time Frame	Adverse events were collected from the time the subject signed informed consent throughout the treatment period and up to 14 days following the last dose of study drug
Adverse Event Reporting Description	Serious Adverse Events were collected from the time the subject signed informed consent throughout the treatment period and up to approximately 68 days, which includes screening and follow up (3-7 days after last dose of study drug).
Arm/Group Title	Placebo MDI		AS MDI 90 µg		Proventil 180 µg		Proventil 90 µg		• Proventil 180 µg
Arm/Group Description	(2 actuations)		(2 actuations of 45 µg/actuation)		(2 actuations of 90 µg/actuation)		(1 actuation of 90 µg/actuation)		(2 actuations of 90 µg/actuation)
All Cause Mortality
	Placebo MDI		AS MDI 90 µg		Proventil 180 µg		Proventil 90 µg		• Proventil 180 µg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/82 (0%)		0/81 (0%)		0/81 (0%)		0/82 (0%)		0/79 (0%)
Serious Adverse Events
	Placebo MDI		AS MDI 90 µg		Proventil 180 µg		Proventil 90 µg		• Proventil 180 µg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/82 (0%)		0/81 (0%)		0/81 (0%)		0/82 (0%)		0/79 (0%)
Other (Not Including Serious) Adverse Events
	Placebo MDI		AS MDI 90 µg		Proventil 180 µg		Proventil 90 µg		• Proventil 180 µg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/82 (0%)		0/81 (0%)		0/81 (0%)		0/82 (0%)		0/79 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Drafts of any and all publications or presentations of this study must be submitted at least 30 days prior to submission for publication or presentation to Pearl Therapeutics for review, approval, and to ensure consistency. Pearl Therapeutics has the right to request appropriate modification to correct facts and to represent it's opinions, or the opinions of the publication committee, if these differ with the proposed publication.