AsthmaPhase 3NCT00634829
Single-Dose Cross-Over Study of the Effects of Albuterol-HFA in Exercise Induced Bronchoconstriction
A Phase 3 study testing albuterol (Armstrong Albuterol HFA) and Albuterol Sulfate (Provenetil-HFA) in people with Asthma and Bronchospasm, run by Amphastar Pharmaceuticals, Inc. at 3 sites in United States.
Trial summary
This clinical study will evaluate and establish the protective effects of Amphastar's Albuterol Sulfate HFA Inhalation Aerosol (Albuterol-HFA), in preventing exercise-induced bronchoconstriction (EIB) in adolescent and adult asthmatic patients, in comparison with (1) Proventil®-HFA (Reference drug and Active Control… Read more about this study
- Who is it for?
- Ages 12 to 50 years
- Conditions the study is for
- Asthma, Bronchospasm
- What is being tested?
- albuterol (Armstrong Albuterol HFA) and Albuterol Sulfate (Provenetil-HFA)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 3 sitesUnited States
- Study dates
- Feb 2008to Oct 2008
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 12 to 50 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Male and female subjects, aged 12 - 50 years, and in general good health.
- A documented history of mild to moderate asthma, for at-least 6-months, requiring inhaled B-adrenergic agonists for symptom control.
- Having a history of exercise-induced bronchoconstriction, that can be prevented or relieved by the use of an inhaled B-agonist.
- Satisfying asthma stability requirement, such that over the 30 days prior to the screening, there are no significant changes in asthma therapy and no asthma-related hospitalization or emergency medical visits.
- Being able to withhold treatment with inhaled bronchodilators and/or restricted medications for the minimum washout periods indicated in Appendix II prior to pulmonary function testing at Screening Visit and Clinical Visits 1, 2 and 3.
- Having a baseline forced expiratory volume in the 1st second (FEV1) that is greater than nor equal to 65.0% of predicted normal values.
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- Demonstrating a greater than or equal to 20.0%, but <50.0%, fall in FEV1 during a Standard Exercise Challenge test per current ATS guidance, at Screening.
- Demonstrating satisfactory techniques in the correct use of metered-dose inhaler (MDIs).
- Female patients of child-bearing potential being non-pregnant and non-lactating, and using an acceptable method of contraception.
- Willingness and ability to sign the informed consent and HIPPA forms to participate in this trial.
Who cannot join
- A smoking history of ≥10 pack-years, or having smoked within the past 12 months prior to Screening.
- Any current or past significant respiratory diseases that might significantly interfere with pharmacodynamic response to the study drugs, such as cystic fibrosis, bronchiectasis, emphysema, pulmonary malignancies, etc, other than asthma.
- Clinically significant cardiovascular, hematological, renal, neurologic, hepatic, and endocrine disorders, or psychiatric diseases, or any other significant health conditions that in the opinion of the investigator might interfere with bronchodilator responses.
- Recent upper or lower respiratory tract infection (within 4 weeks) prior to Screening.
- Recent (per Appendix II, Part I) use of orally ingested or systemically administered corticosteroids, B-adrenergic bronchodilators, monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs), B-blockers, or drugs that affect study drug performance.
- Taking >1,000 mcg daily of inhaled beclomethasone dipropionate or budesonide, or >500 mcg daily of inhaled fluticasone propionate, or taking high doses of other orally inhaled corticosteroids that suggest severe asthma state, in the opinion of the investigator, within four weeks of Screening.
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- Demonstrating clinically significant abnormal 12-lead ECG results, upon Screening.
- Any significant physical (e.g., musculoskeletal, overweight, etc) conditions that, in the opinion of the investigator, could limit the subject's ability to perform the exercise challenge test.
- Known intolerance or hypersensitivity to any component of the MDI formulation (albuterol, HFA-134a, oleic acid and alcohol).
- Known or reasonably suspected substance abuses.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Colorado Allergy and Asthma Center
Denver, Colorado, 80230
Colorado Allergy and Asthma Center
Englewood, Colorado, 80112
Colorado Allergy and Asthma Center
Lakewood, Colorado, 80401
About this study
Official title: Randomized, Double-Blind, Controlled, Single-Dose, Three-Treatment, Cross-Over Study of The Protective Effects Of Albuterol-HFA In Preventing Exercise-Induced Bronchoconstriction In Adolescent And Adult Asthmatic Patients
This clinical study will evaluate and establish the protective effects of Amphastar's Albuterol Sulfate HFA Inhalation Aerosol (Albuterol-HFA), in preventing exercise-induced bronchoconstriction (EIB) in adolescent and adult asthmatic patients, in comparison with (1) Proventil®-HFA (Reference drug and Active Control ), and (2) Placebo-HFA control (HFA propellant only). Safety of the test drug, Albuterol-HFA, will also be evaluated in comparison to the Active and Placebo Controls. Analyses will be performed to determine if the Armstrong's Albuterol-HFA has resulted in a significant bronchoprotective effect, with attenuated Max % Fall in FEV1, in comparison to the Placebo-HFA control.
Read the detailed description
The prevalence of exercise-induced bronchoconstriction (EIB) has been reported to be around 70% to 75% among patients with clinically established asthma. Airway cooling and drying are thought to cause the release of inflammatory mediators, such as histamine and leukotrienes, which then mediate clinical EIB symptoms. Pretreatment with a variety of medications will ameliorate EIB. Albuterol has been found to be more effective in minimizing EIB than theophylline, ipratropiom, cromoglycate, etc. Tested using a treadmill exercise challenge, the newer formulations of albuterol MDI with HFA as propellant have been demonstrated to be as effective as those with CFC as propellant in protecting asthma patients from EIB in children and adults.
As a part of the Amphastar Pharmaceuticals' clinical development plan, the current study examines the clinical efficacy of A004, Armstrong Pharmaceuticals' Albuterol HFA oral inhalation MDI, in preventing EIB in adolescent and adult asthmatic patients.
This is a randomized, double-blind, active and placebo-controlled, three-treatment, cross-over study, to be conducted in adolescent and adult patients with mild to moderate asthma and demonstrable EIB.
All subjects will be screened against the inclusion/exclusion criteria for enrollment. A computer-generated randomization code will be created by the Amphastar Pharmaceuticals' IT Department, so that each enrolled subject will receive all three double-blinded treatments in randomized sequence. Each treatment is followed by a standardized exercise challenge and a series of FEV1 measurements during the 90 min post-exercise period. The three crossover Treatment Arms are:
- Treatment T (Armstrong's Test Drug: Albuterol-HFA);
- Treatment R (Reference Drug and Active Control: Proventil®-HFA);
- Treatment P (Placebo-HFA).
By the definition of the crossover design, the three Treatment Arms are expected to consist comparably of 24 evaluable subjects. The consecutive study sessions will be separated by an interval of 1-14 days.
- Conditions
- Asthma, Bronchospasm
- Being tested
- albuterol (Armstrong Albuterol HFA), Albuterol Sulfate (Provenetil-HFA), Placebo-HFA
- Medical subject headings
- Asthma, Bronchial Spasm
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
albuterol (Armstrong Albuterol HFA)Drug
Also called A004, Albuterol-HFA Inhalation Aerosol
2 inhalations of 108 mcg albuterol sulfate prior to exercise, single dose
Albuterol Sulfate (Provenetil-HFA)Drug
Also called Provenetil-HFA, albuterol sulfate-HFA
2 inhalations of Proventil-HFA, 108 mcg/inhalation prior to exercise
Placebo-HFADrug
Placebo containing HFA propellant without active drug substance
| Study group | Role | What they receive |
|---|---|---|
| T | Experimental | Armstrong Albuterol HFA Inhalation Aerosol Receives: Drug: albuterol (Armstrong Albuterol HFA) |
| R | Active comparator | 2 inhalations Proventil-HFA Albuterol Sulfate, 108 mcg, prior to exercise Receives: Drug: Albuterol Sulfate (Provenetil-HFA) |
| P | Placebo comparator | Placebo-HFA Receives: Drug: Placebo-HFA |
What is being measured
The primary outcome is the main question the study is designed to answer.
The maximum percentage fall in FEV1, from the Pre-Exercise FEV1, between Albuterol-HFA and Placebo-HFA.
Measured: 90 minutes post exercise
Secondary outcomes (11)
Evaluation of relative broncho-protective efficacy of Albuterol-HFA, in comparison to the active comparator, Proventil®-HFA, using the Max % fall in Post-Exercise FEV1, from the Pre-exercise FEV1
Measured: 90 minutes post exercise
Pre-exercise FEV1 values (volume in Liters, recorded ), indicative of bronchodilator responsiveness.
Measured: 20-30 min post dose
Number and percentage of subjects who demonstrate a <20.0% fall in FEV1, from the Pre-exercise FEV1.
Measured: 90 min post-exercise
Area Under-the-Curve of percentage fall in FEV1, from the Pre-exercise FEV1.
Measured: 90 min post-exercise
Time to recovery, as the time point where FEV1 recovers from maximum percent fall in FEV1 to be within 5.0% of the Pre-Exercise FEV1 values.
Measured: concurrent with study visit
Number of subjects who cannot complete the exercise at specified intensity and length, due to asthma symptoms.
Measured: concurrent with study visit
Number of subjects requiring B2-agonist rescue inhalations during exercise, and during the 90 min post-exercise period.
Measured: 90 minutes post exercise
The following baseline and post-dose safety parameters before and after each exercise-challenge tests will be assessed: Vital signs: blood pressure (SBP/DBP) and heart rate (HR).
Measured: concurrent with study visit
12-lead ECG: HR, QT and QTc intervals, before and after treatment with Albuterol-HFA, versus the active control, and placebo control.
Measured: concurrent with study visit
Pre-study (Screening) and End-of-Study laboratory tests for CBC, blood chemistry panel, urinalysis and urine pregnancy test.
Measured: Throughout study
Adverse events and side effects will be documented when observed by investigators or reported by subjects.
Measured: throughout study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2008 (estimated)
- Study startFeb 2008
- Primary completionOct 2008
- Study completionOct 2008
Why it stopped: IND voluntarily withdrawn, without prejudice
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amphastar Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00634829
- Sponsor's protocol ID
- API-A004-CLN-D
- Status last verified
- Jul 2013
- First submitted
- 7 Mar 2008
- Last updated
- 15 Jul 2013
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Double-Blind, Controlled, Single-Dose, Three-Treatment, Cross-Over Study of The Protective Effects Of Albuterol-HFA In Preventing Exercise-Induced Bronchoconstriction In Adolescent And Adult Asthmatic Patients
- ClinicalTrials.gov ID
- NCT00634829
- Acronym / sponsor ID
- API-A004-CLN-D
- Conditions
- Asthma, Bronchospasm
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: IND voluntarily withdrawn, without prejudice
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Amphastar Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- Feb 2008
- Primary completion
- Oct 2008 (actual)
- Study completion
- Oct 2008 (actual)
- First posted
- 13 Mar 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This clinical study will evaluate and establish the protective effects of Amphastar's Albuterol Sulfate HFA Inhalation Aerosol (Albuterol-HFA), in preventing exercise-induced bronchoconstriction (EIB) in adolescent and adult asthmatic patients, in comparison with (1) Proventil®-HFA (Reference drug and Active Control ), and (2) Placebo-HFA control (HFA propellant only). Safety of the test drug, Albuterol-HFA, will also be evaluated in comparison to the Active and Placebo Controls. Analyses will be performed to determine if the Armstrong's Albuterol-HFA has resulted in a significant bronchoprotective effect, with attenuated Max % Fall in FEV1, in comparison to the Placebo-HFA control.
Detailed description
The prevalence of exercise-induced bronchoconstriction (EIB) has been reported to be around 70% to 75% among patients with clinically established asthma. Airway cooling and drying are thought to cause the release of inflammatory mediators, such as histamine and leukotrienes, which then mediate clinical EIB symptoms. Pretreatment with a variety of medications will ameliorate EIB. Albuterol has been found to be more effective in minimizing EIB than theophylline, ipratropiom, cromoglycate, etc. Tested using a treadmill exercise challenge, the newer formulations of albuterol MDI with HFA as propellant have been demonstrated to be as effective as those with CFC as propellant in protecting asthma patients from EIB in children and adults.
As a part of the Amphastar Pharmaceuticals' clinical development plan, the current study examines the clinical efficacy of A004, Armstrong Pharmaceuticals' Albuterol HFA oral inhalation MDI, in preventing EIB in adolescent and adult asthmatic patients.
This is a randomized, double-blind, active and placebo-controlled, three-treatment, cross-over study, to be conducted in adolescent and adult patients with mild to moderate asthma and demonstrable EIB.
All subjects will be screened against the inclusion/exclusion criteria for enrollment. A computer-generated randomization code will be created by the Amphastar Pharmaceuticals' IT Department, so that each enrolled subject will receive all three double-blinded treatments in randomized sequence. Each treatment is followed by a standardized exercise challenge and a series of FEV1 measurements during the 90 min post-exercise period. The three crossover Treatment Arms are:
- Treatment T (Armstrong's Test Drug: Albuterol-HFA);
- Treatment R (Reference Drug and Active Control: Proventil®-HFA);
- Treatment P (Placebo-HFA).
By the definition of the crossover design, the three Treatment Arms are expected to consist comparably of 24 evaluable subjects. The consecutive study sessions will be separated by an interval of 1-14 days.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| T | Experimental | Drug: albuterol (Armstrong Albuterol HFA)Armstrong Albuterol HFA Inhalation Aerosol |
| R | Active comparator | Drug: Albuterol Sulfate (Provenetil-HFA)2 inhalations Proventil-HFA Albuterol Sulfate, 108 mcg, prior to exercise |
| P | Placebo comparator | Drug: Placebo-HFAPlacebo-HFA |
Who may qualify
- Ages
- 12 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (10 listed)
- Male and female subjects, aged 12 - 50 years, and in general good health.
- A documented history of mild to moderate asthma, for at-least 6-months, requiring inhaled B-adrenergic agonists for symptom control.
- Having a history of exercise-induced bronchoconstriction, that can be prevented or relieved by the use of an inhaled B-agonist.
- Satisfying asthma stability requirement, such that over the 30 days prior to the screening, there are no significant changes in asthma therapy and no asthma-related hospitalization or emergency medical visits.
- Being able to withhold treatment with inhaled bronchodilators and/or restricted medications for the minimum washout periods indicated in Appendix II prior to pulmonary function testing at Screening Visit and Clinical Visits 1, 2 and 3.
Key exclusion criteria (10 listed)
- A smoking history of ≥10 pack-years, or having smoked within the past 12 months prior to Screening.
- Any current or past significant respiratory diseases that might significantly interfere with pharmacodynamic response to the study drugs, such as cystic fibrosis, bronchiectasis, emphysema, pulmonary malignancies, etc, other than asthma.
- Clinically significant cardiovascular, hematological, renal, neurologic, hepatic, and endocrine disorders, or psychiatric diseases, or any other significant health conditions that in the opinion of the investigator might interfere with bronchodilator responses.
- Recent upper or lower respiratory tract infection (within 4 weeks) prior to Screening.
- Recent (per Appendix II, Part I) use of orally ingested or systemically administered corticosteroids, B-adrenergic bronchodilators, monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs), B-blockers, or drugs that affect study drug performance.
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 |
|---|---|---|
| albuterol (Armstrong Albuterol HFA)Also: A004, Albuterol-HFA Inhalation Aerosol2 inhalations of 108 mcg albuterol sulfate prior to exercise, single dose | Drug | T |
| Albuterol Sulfate (Provenetil-HFA)Also: Provenetil-HFA, albuterol sulfate-HFA2 inhalations of Proventil-HFA, 108 mcg/inhalation prior to exercise | Drug | R |
| Placebo-HFAPlacebo containing HFA propellant without active drug substance | Drug | P |
Primary outcome
The maximum percentage fall in FEV1, from the Pre-Exercise FEV1, between Albuterol-HFA and Placebo-HFA.
Time frame: 90 minutes post exercise
11 secondary outcomes
Evaluation of relative broncho-protective efficacy of Albuterol-HFA, in comparison to the active comparator, Proventil®-HFA, using the Max % fall in Post-Exercise FEV1, from the Pre-exercise FEV1
Time frame: 90 minutes post exercise
Pre-exercise FEV1 values (volume in Liters, recorded ), indicative of bronchodilator responsiveness.
Time frame: 20-30 min post dose
Number and percentage of subjects who demonstrate a <20.0% fall in FEV1, from the Pre-exercise FEV1.
Time frame: 90 min post-exercise
Area Under-the-Curve of percentage fall in FEV1, from the Pre-exercise FEV1.
Time frame: 90 min post-exercise
Time to recovery, as the time point where FEV1 recovers from maximum percent fall in FEV1 to be within 5.0% of the Pre-Exercise FEV1 values.
Time frame: concurrent with study visit
Number of subjects who cannot complete the exercise at specified intensity and length, due to asthma symptoms.
Time frame: concurrent with study visit
Number of subjects requiring B2-agonist rescue inhalations during exercise, and during the 90 min post-exercise period.
Time frame: 90 minutes post exercise
The following baseline and post-dose safety parameters before and after each exercise-challenge tests will be assessed: Vital signs: blood pressure (SBP/DBP) and heart rate (HR).
Time frame: concurrent with study visit
12-lead ECG: HR, QT and QTc intervals, before and after treatment with Albuterol-HFA, versus the active control, and placebo control.
Time frame: concurrent with study visit
Pre-study (Screening) and End-of-Study laboratory tests for CBC, blood chemistry panel, urinalysis and urine pregnancy test.
Time frame: Throughout study
Adverse events and side effects will be documented when observed by investigators or reported by subjects.
Time frame: throughout study
Results and safety
The study was stopped early (reason given: IND voluntarily withdrawn, without prejudice). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2013.
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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.
3 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 albuterol (Armstrong Albuterol HFA) and Albuterol Sulfate (Provenetil-HFA) in people with Asthma and Bronchospasm, run by Amphastar Pharmaceuticals, Inc. at 3 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 10 inclusion and 10 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: stopped early, as of the sponsor's last update on 15 Jul 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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?
The study was stopped early (reason given: IND voluntarily withdrawn, without prejudice). Results are not available in the source record.
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?
The maximum percentage fall in FEV1, from the Pre-Exercise FEV1, between Albuterol-HFA and Placebo-HFA. (time frame: 90 minutes post exercise). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 15 Jul 2013; AzTrials last refreshed its copy on 7 Nov 2026.