Mild Persistent AsthmaPhase 3NCT02584257

Pharmacodynamic Bioequivalence of Metered Dose Inhalers of Albuterol Sulfate in Patients With Stable Mild Asthma

A Phase 3 study testing methacholine chloride, ProAir HFA and Lupin albuterol HFA MDI in people with Mild Persistent Asthma, run by Lupin, Inc. at 17 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The purpose of this study is to demonstrate the pharmacodynamic bioequivalence of the test product to the reference product, using bronchoprovocation (methacholine challenge testing) in adult patients with stable mild asthma. Read more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Mild Persistent Asthma
What is being tested?: methacholine chloride, ProAir HFA and Lupin albuterol HFA MDI
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 217 participants
Where: 17 sitesUnited States
Study dates: Apr 2016to Sep 2016
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Male and non-pregnant female subjects (18-65 years of age)
Stable mild asthmatics based on National Asthma Education and Prevention Program (NAEPP) guidelines.
Forced Expiratory Volume in 1 second ( FEV1) ≥ 80% of predicted. Airway responsiveness to methacholine demonstrated by a pre-albuterol dose (baseline) PC20 ≤ 8 mg/ml.
Nonsmokers for at least 1 year prior to the study and a maximum smoking history of five pack-years (the equivalent of one pack per day for five years).
Written informed consent.

Who cannot join

Conditions which could alter airway reactivity to methacholine (e.g., pneumonia, upper respiratory tract infection, lower respiratory tract, viral bronchitis and/or sinobronchitis) within six weeks preceding the screening visit.
History of seasonal asthma exacerbations, in which case the patient should be studied outside of the relevant allergen season.
History of cystic fibrosis, bronchiectasis or other respiratory diseases.
History of cardiovascular, renal, neurologic, liver or endocrine dysfunction, or chronic condition that could put the safety of the patient at risk during the study or affect the efficacy and safety analyses during the study.
Treatment in an emergency room, urgent care center, or hospitalization for acute asthmatic symptoms within the past 6 months or need for daily oral corticosteroids within past 3 months.
Known intolerance or hypersensitivity to any component of the albuterol metered dose inhaler (MDI).

Trial locations and contacts

17 sites in 1 country.

City, postcode or hospital

17 sites in 1 country

United States17 sites

Investigational Research Center Site #109
Baltimore, Maryland, 21236
Investigational Research Center Site #115
Bellevue, Nebraska, 68123
Investigational Research Center Site #105
Bethesda, Maryland, 20814
Investigational Research Center Site #111
Cincinnati, Ohio, 45231
Investigational Research Center Site #110
Huntington Beach, California, 92647
Investigational Research Center Site #101
Medford, Oregon, 97504
Investigational Research Center Site #114
Mission Viejo, California, 92691
Investigational Research Center Site #103
North Dartmouth, Massachusetts, 02747
Investigational Research Center Site #107
Portland, Oregon, 97202
Investigational Research Center Site #102
Raleigh, North Carolina, 27607
Investigational Research Center Site #113
Rolling Hills Estates, California, 90274
Investigational Research Center Site #112
San Diego, California, 92123
Investigational Research Center Site #116
San Jose, California, 95117
Investigational Research Center Site #104
Skillman, New Jersey, 08558
Investigational Research Center Site #108
St Louis, Missouri, 63141
Investigational Research Center Site #106
Tallahassee, Florida, 32308
Investigational Research Center Site #118
Tulsa, Oklahoma, 74136

Other trials in United States

About this study

Official title: Comparison of the Pharmacodynamic Profile of Test and Reference Metered Dose Inhalers (MDIs) Containing Albuterol Sulfate Using Bronchoprovocation in Adult Patients With Stable Mild Asthma

Read the detailed description

A Multicenter, Double-Blind, Double-Dummy, Placebo-Controlled, 5-Treatment, Randomized, Crossover Study to Demonstrate the Pharmacodynamic Bioequivalence of Test and Reference Metered Dose Inhalers containing Albuterol Sulfate using Bronchoprovocation in Adult Patients with Stable Mild Asthma

Conditions: Mild Persistent Asthma
Being tested: methacholine chloride, placebo ProAir HFA, ProAir HFA, Lupin albuterol HFA MDI, placebo Lupin albuterol HFA MDI

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

methacholine chlorideOther
placebo ProAir HFADrug
ProAir HFADrug
Lupin albuterol HFA MDIDrug
placebo Lupin albuterol HFA MDIDrug

Study groups in NCT02584257
Study group	Role	What they receive
Placebo dose	Placebo comparator	Placebo dose: 1 actuation each from 2 different placebo ProAir HFA inhalation aerosols and one actuation each from 2 different placebo Lupin albuterol HFA MDI inhalation aerosols Receives: Other: methacholine chloride; Drug: placebo ProAir HFA; Drug: placebo Lupin albuterol HFA MDI
90 mcg ProAir HFA	Active comparator	90 mcg of ProAir HFA: 1 actuation each from ProAir HFA inhalation aerosol and the placebo ProAir HFA inhalation aerosol and 1 actuation each from 2 different placebo Lupin albuterol HFA MDI inhalation aerosols Receives: Other: methacholine chloride; Drug: placebo ProAir HFA; Drug: ProAir HFA; Drug: placebo Lupin albuterol HFA MDI
180 mcg ProAir HFA	Active comparator	180 mcg of ProAir HFA: 1 actuation each from 2 different ProAir HFA inhalation aerosols and 1 actuation each from 2 different placebo Lupin albuterol HFA MDI inhalation aerosols Receives: Other: methacholine chloride; Drug: ProAir HFA; Drug: placebo Lupin albuterol HFA MDI
90 mcg Lupin albuterol HFA MDI	Experimental	90 mcg of Lupin albuterol HFA MDI product: 1 actuation each from the Lupin albuterol HFA MDI inhalation aerosol and the placebo Lupin albuterol HFA MDI inhalation aerosol and 1 actuation each from 2 different placebo ProAir HFA inhalation aerosols Receives: Other: methacholine chloride; Drug: placebo ProAir HFA; Drug: Lupin albuterol HFA MDI; Drug: placebo Lupin albuterol HFA MDI
180 mcg Lupin albuterol HFA MDI	Experimental	180 mcg of Lupin albuterol HFA MDI: 1 actuation each from 2 different Lupin albuterol HFA MDI inhalation aerosols and 1 actuation each from 2 different placebo ProAir HFA product inhalation aerosols Receives: Other: methacholine chloride; Drug: placebo ProAir HFA; Drug: Lupin albuterol HFA MDI

What is being measured

The primary outcome is the main question the study is designed to answer.

Post-dose PC20 Concentration After Receiving Differing Doses of Test, Reference, or Placebo
The primary efficacy endpoint was the postdose PC20 following administration of differing doses of albuterol (or placebo) by inhalation. The 20% reduction in FEV1 was determined relative to the saline stage FEV1 measured before albuterol or placebo administration. Additionally, an analysis of superiority to placebo was performed for the T and R products prior to the BE determination. In this study the ITT and PP populations were identical.
Measured: Post-dose at Visits 2-6 of the study, a total of approximately 4 weeks.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Apr 2016Sep 2016

First posted22 Oct 2015 (estimated)
Study startApr 2016
Primary completionAug 2016
Study completionSep 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Mild Persistent AsthmaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind
Who is masked: Participant, Care provider
Enrolment: 217 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02584257
Sponsor's protocol ID: AS-MDI-301
Status last verified: Nov 2020
First submitted: 12 Oct 2015
Last updated: 4 Dec 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: No

Study at a glance

From the registry record, last updated by the sponsor on 4 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Comparison of the Pharmacodynamic Profile of Test and Reference Metered Dose Inhalers (MDIs) Containing Albuterol Sulfate Using Bronchoprovocation in Adult Patients With Stable Mild Asthma
ClinicalTrials.gov ID: NCT02584257
Acronym / sponsor ID: AS-MDI-301
Conditions: Mild Persistent Asthma
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 217 participants (actual)
Lead sponsor: Lupin, Inc.Industry (pharma, biotech, devices)
Study start: Apr 2016
Primary completion: Aug 2016 (actual)
Study completion: Sep 2016 (actual)
First posted: 22 Oct 2015 (estimated)
Results: Posted 18 Nov 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, care provider)
Number of arms: 5

Arm	Type	Receives
Placebo dose	Placebo comparator	Other: methacholine chloride, Drug: placebo ProAir HFA, Drug: placebo Lupin albuterol HFA MDIPlacebo dose: 1 actuation each from 2 different placebo ProAir HFA inhalation aerosols and one actuation each from 2 different placebo Lupin albuterol HFA MDI inhalation aerosols
90 mcg ProAir HFA	Active comparator	Other: methacholine chloride, Drug: placebo ProAir HFA, Drug: ProAir HFA, Drug: placebo Lupin albuterol HFA MDI90 mcg of ProAir HFA: 1 actuation each from ProAir HFA inhalation aerosol and the placebo ProAir HFA inhalation aerosol and 1 actuation each from 2 different placebo Lupin albuterol HFA MDI inhalation aerosols
180 mcg ProAir HFA	Active comparator	Other: methacholine chloride, Drug: ProAir HFA, Drug: placebo Lupin albuterol HFA MDI180 mcg of ProAir HFA: 1 actuation each from 2 different ProAir HFA inhalation aerosols and 1 actuation each from 2 different placebo Lupin albuterol HFA MDI inhalation aerosols
90 mcg Lupin albuterol HFA MDI	Experimental	Other: methacholine chloride, Drug: placebo ProAir HFA, Drug: Lupin albuterol HFA MDI, Drug: placebo Lupin albuterol HFA MDI90 mcg of Lupin albuterol HFA MDI product: 1 actuation each from the Lupin albuterol HFA MDI inhalation aerosol and the placebo Lupin albuterol HFA MDI inhalation aerosol and 1 actuation each from 2 different placebo ProAir HFA inhalation aerosols
180 mcg Lupin albuterol HFA MDI	Experimental	Other: methacholine chloride, Drug: placebo ProAir HFA, Drug: Lupin albuterol HFA MDI180 mcg of Lupin albuterol HFA MDI: 1 actuation each from 2 different Lupin albuterol HFA MDI inhalation aerosols and 1 actuation each from 2 different placebo ProAir HFA product inhalation aerosols

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Male and non-pregnant female subjects (18-65 years of age)
Stable mild asthmatics based on National Asthma Education and Prevention Program (NAEPP) guidelines.
Forced Expiratory Volume in 1 second ( FEV1) ≥ 80% of predicted. Airway responsiveness to methacholine demonstrated by a pre-albuterol dose (baseline) PC20 ≤ 8 mg/ml.
Nonsmokers for at least 1 year prior to the study and a maximum smoking history of five pack-years (the equivalent of one pack per day for five years).
Written informed consent.

Key exclusion criteria (6 listed)

Conditions which could alter airway reactivity to methacholine (e.g., pneumonia, upper respiratory tract infection, lower respiratory tract, viral bronchitis and/or sinobronchitis) within six weeks preceding the screening visit.
History of seasonal asthma exacerbations, in which case the patient should be studied outside of the relevant allergen season.
History of cystic fibrosis, bronchiectasis or other respiratory diseases.
History of cardiovascular, renal, neurologic, liver or endocrine dysfunction, or chronic condition that could put the safety of the patient at risk during the study or affect the efficacy and safety analyses during the study.
Treatment in an emergency room, urgent care center, or hospitalization for acute asthmatic symptoms within the past 6 months or need for daily oral corticosteroids within past 3 months.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
methacholine chloride	Other	180 mcg Lupin albuterol HFA MDI, 180 mcg ProAir HFA, 90 mcg Lupin albuterol HFA MDI, 90 mcg ProAir HFA, Placebo dose
placebo ProAir HFA	Drug	180 mcg Lupin albuterol HFA MDI, 90 mcg Lupin albuterol HFA MDI, 90 mcg ProAir HFA, Placebo dose
ProAir HFA	Drug	180 mcg ProAir HFA, 90 mcg ProAir HFA
Lupin albuterol HFA MDI	Drug	180 mcg Lupin albuterol HFA MDI, 90 mcg Lupin albuterol HFA MDI
placebo Lupin albuterol HFA MDI	Drug	180 mcg ProAir HFA, 90 mcg Lupin albuterol HFA MDI, 90 mcg ProAir HFA, Placebo dose

Primary outcome

Post-dose PC20 Concentration After Receiving Differing Doses of Test, Reference, or Placebo
Time frame: Post-dose at Visits 2-6 of the study, a total of approximately 4 weeks.
The primary efficacy endpoint was the postdose PC20 following administration of differing doses of albuterol (or placebo) by inhalation. The 20% reduction in FEV1 was determined relative to the saline stage FEV1 measured before albuterol or placebo administration. Additionally, an analysis of superiority to placebo was performed for the T and R products prior to the BE determination. In this study the ITT and PP populations were identical.

Results and safety

Results posted to the registry on 18 Nov 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
PBO-R90-T180-R180-T90	9	9
R90-R180-PBO-T90-T180	9	9
R180-T90-R90-T180-PBO	9	9
T90-T180-R180-PBO-R90	8	8
T180-PBO-T90-R90-R180	10	10
T90-R180-T180-R90-PBO	10	10
T180-T90-PBO-R180-R90	18	17
R90-PBO-R180-T180-T90	9	9
R180-R90-T90-PBO-T180	9	9

Primary outcome: Post-dose PC20 Concentration After Receiving Differing Doses of Test, Reference, or Placebo

Time frame: Post-dose at Visits 2-6 of the study, a total of approximately 4 weeks.. Least squares mean (Standard Error). Unit: log(mg/mL)

Measure	Placebo Dose n = 82	90 mcg ProAir HFA n = 83	180 mcg ProAir HFA n = 83	90 mcg Lupin Albuterol HFA MDI n = 80	180 mcg Lupin Albuterol HFA MDI n = 81
Value	0.608 (0.239)	3.779 (0.238)	4.432 (0.238)	3.928 (0.241)	4.481 (0.240)

Placebo Dose vs 90 mcg ProAir HFA: Least Square Means Differences: 3.171 (95% CI 2.732 to 3.610), p <0.0001, Brief Mixed Models Analysis
Placebo Dose vs 180 mcg ProAir HFA: Least Square Means Differences: 3.824 (95% CI 3.384 to 4.263), p <0.0001, Brief Mixed Models Analysis
Placebo Dose vs 90 mcg Lupin Albuterol HFA MDI: Least Square Means Differences: 3.320 (95% CI 2.876 to 3.764), p <0.0001, Brief Mixed Models Analysis

Population analysed: Intent-to-Treat population included all randomized patients who completed at least 2 treatment periods with valid PC20 FEV1 measurements.Treatment was assigned based upon treatment to which patients had been randomized regardless of which treatment they actually received. This was primary population for comparisons of T and R products to placebo.

Adverse events

Time frame: All AE/SAEs (including treatment-emergent AEs) were assessed throughout the study visits and followed to resolution/satisfaction. AEs were recorded starting after the patient had signed the informed consent form and assessed at all visits. Each AE was evaluated for date/time of onset, duration, intensity, and causal relationship with the investigational product or other factors. (5 months) First Patient Screened: 12-Apr 2016 & Last Patient Visit: 12 Aug 2016. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo Dose	0 of 89 (0%)	3 of 89 (3.4%)	0 of 89
90 mcg ProAir HFA	0 of 90 (0%)	4 of 90 (4.4%)	0 of 90
180 mcg ProAir HFA	0 of 89 (0%)	1 of 89 (1.1%)	0 of 89
90 mcg Lupin Albuterol HFA MDI	0 of 88 (0%)	8 of 88 (9.1%)	0 of 88
180 mcg Lupin Albuterol HFA MDI	0 of 89 (0%)	1 of 89 (1.1%)	0 of 89

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

17 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing methacholine chloride, ProAir HFA and Lupin albuterol HFA MDI in people with Mild Persistent Asthma, run by Lupin, Inc. at 17 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Nov 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Post-dose PC20 Concentration After Receiving Differing Doses of Test, Reference, or Placebo (time frame: Post-dose at Visits 2-6 of the study, a total of approximately 4 weeks.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02584257.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Dec 2020.