Exercise-Induced Bronchoconstriction (EIB)
Conditions
Keywords
Exercise-Induced Bronchoconstriction (EIB), Spiromax®, Albuterol sulfate
Brief summary
The primary objective of this study is to evaluate the efficacy of a single dose (2 inhalations, 180 mcg total) of Albuterol SPIROMAX (90 mcg per inhalation) versus placebo in patients with EIB.
Detailed description
This study is a single-dose, randomized, double-blind, placebo-controlled, 2-treatment, 2-sequence, 2-way crossover, multicenter study in patients with a documented history of EIB, with or without underlying asthma. Each patient will participate in the study for approximately 5 weeks. Each patient will complete 2 screening visits (SV1 and SV2), 2 treatment visits (TV1 and TV2), and a follow-up telephone call (FV).
Interventions
Albuterol Spiromax is an inhalation-driven, multi-dose dry powder inhaler (DPI) containing a blend of albuterol sulfate with alpha-lactose monohydrate. Each actuation represents a dose of 90 mcg of albuterol sulfate. Participants received one dose of two inhalations (180 mcg).
DRUGPlacebo Spiromax
Placebo Spiromax is an inhalation-driven, multi-dose dry powder inhaler (DPI) delivering placebo to match the experimental drug. Participants received one dose of two inhalations.
Sponsors
Teva Branded Pharmaceutical Products R&D, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Informed consent/assent: For patients 18 to 50 years of age, inclusive, written informed consent signed and dated by the patient before conducting any study related procedures and review of Health Insurance Portability and Accountability Act of 1996 (HIPAA) authorization; for patients 12 to 17 years of age, inclusive, written informed consent signed and dated by the parent/legal guardian and written assent signed and dated by the patient before conducting any study related procedure and review of HIPAA authorization. * Male or female patients 12 to 50 years of age, inclusive, as of SV1. * If female, is currently not pregnant, breastfeeding, or attempting to become pregnant, has a negative serum pregnancy test, and is of non-childbearing potential. * Documented history of EIB, with or without underlying asthma. The underlying asthma must be well-controlled (in the investigator's judgment) as per the National Asthma Education and Prevention Program, Expert Panel Report (NAEPP, EPR-3). * Other criteria apply.
Exclusion criteria
* Requires a rescue bronchodilator following the exercise challenge at SV1 for a decrease in FEV1 that does not return to within 20% of their pre-exercise challenge FEV1 within 30 minutes after administration of the rescue medication. * Pregnant, nursing, or plans to become pregnant or donate gametes (ova or sperm) for in vitro fertilization during the study period or for 30 days after the patient's last study related visit (for eligible patients only-if applicable). * Participation in any investigational drug trial within the 30 days preceding SV1 or planned participation in another investigational drug trial at any time during this trial. * A known hypersensitivity to albuterol or any of the excipients in the formulation. * History of severe milk protein allergy. * History of a respiratory infection or disorder (including, but not limited to bronchitis, pneumonia, otitis media, acute or chronic sinusitis, influenza, etc) that has not resolved within the 2 weeks preceding SV1. * Other criteria apply.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Percentage Fall From Baseline in Forced Expiratory Volume in 1 Second (FEV1) up to 60 Minutes After the Exercise Challenge | Days 1 and 7; up to 60 minutes post-exercise challenge | A centralized spirometry data collection system was used to reduce FEV1 variability between and within patients and between each participating study center. The percentage fall was defined as 100\*(baseline-post baseline)/baseline. The baseline FEV1 is the test day FEV1 measured 5 minutes before the exercise challenge (30 minutes postdose). FEV1 post exercise challenge were measured 5 (±5), 10 (±5), 15 (±5), 30 (±5), and 60 (±10) minutes after completion of the exercise challenge. The exercise challenge consisted of the participant running on a motor-driven treadmill (with adjustable speed and incline). The treadmill was set at a speed and incline sufficient to increase the participant's heart rate to ≥80% of the maximum rate for age (220 bpm-age in years) for a period of either 6, 7, or 8 minutes using a stepped-exercise protocol in accordance with ATS guidelines (American Thoracic Society 2000). Conditions were repeated for subsequent challenges. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Whose Maximum Percentage Decrease From the Baseline Forced Expiratory Volume in 1 Second (FEV1) Post-Exercise Challenge Was <10% | Days 1 and 7; up to 60 minutes post-exercise challenge | Participants were classified as protected if the maximum percentage decrease from baseline FEV1 after exercise was less than 10%. Data represents the percentage of participants who were classified as protected. |
| Participants Whose Maximum Percentage Decrease From the Baseline Forced Expiratory Volume in 1 Second (FEV1) Post-Exercise Challenge Was >20% | Days 1 and 7; up to 60 minutes post-exercise challenge | Participants were classified as unprotected if the maximum percentage decrease from baseline FEV1 after exercise was more than 20%. Data represents the number of participants who were classified as unprotected. |
Countries
United States
Participant flow
Pre-assignment details
A total of 64 patients with EIB were screened. Of the 26 patients who did not participate in the study, 23 were excluded on the basis of inclusion/exclusion criteria, 2 patients withdrew consent, and 1 patient was withdrawn for other reason(s) before the baseline visit.
Participants by arm
| Arm | Count |
|---|---|
| Albuterol Spiromax / Placebo Spiromax Albuterol Spiromax, 180 mcg (2 inhalations of 90 mcg/inhalation), single dose on Day 1. Placebo Spiromax (2 inhalations), single dose on approximately Day 7. | 19 |
| Placebo Spiromax / Albuterol Spiromax Placebo Spiromax, (2 inhalations), single dose on Day 1. Albuterol Spiromax 180 mcg (2 inhalations of 90 mcg/inhalation), single dose on approximately Day 7. | 19 |
| Total | 38 |
Baseline characteristics
| Characteristic | Albuterol Spiromax / Placebo Spiromax | Placebo Spiromax / Albuterol Spiromax | Total |
|---|---|---|---|
| Age, Continuous | 31.7 years STANDARD_DEVIATION 7.11 | 31.9 years STANDARD_DEVIATION 8.87 | 31.8 years STANDARD_DEVIATION 7.93 |
| Age, Customized <18 years | 1 participants | 1 participants | 2 participants |
| Age, Customized >=18 years | 18 participants | 18 participants | 36 participants |
| Body Mass Index | 28.1 kg/m^2 STANDARD_DEVIATION 4 | 25.3 kg/m^2 STANDARD_DEVIATION 4.58 | 26.7 kg/m^2 STANDARD_DEVIATION 4.47 |
| Height | 171.4 cm STANDARD_DEVIATION 12.06 | 169.8 cm STANDARD_DEVIATION 11.46 | 170.6 cm STANDARD_DEVIATION 11.63 |
| Race/Ethnicity, Customized Asian | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Black | 4 participants | 2 participants | 6 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 2 participants | 2 participants | 4 participants |
| Race/Ethnicity, Customized Non-Hispanic and non-Latino | 17 participants | 17 participants | 34 participants |
| Race/Ethnicity, Customized Other | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized White | 14 participants | 16 participants | 30 participants |
| Sex: Female, Male Female | 9 Participants | 10 Participants | 19 Participants |
| Sex: Female, Male Male | 10 Participants | 9 Participants | 19 Participants |
| Weight | 82.7 kg STANDARD_DEVIATION 15.54 | 74.2 kg STANDARD_DEVIATION 21.04 | 78.4 kg STANDARD_DEVIATION 18.75 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 38 | 0 / 38 |
| serious Total, serious adverse events | 0 / 38 | 0 / 38 |
Outcome results
Primary
Maximum Percentage Fall From Baseline in Forced Expiratory Volume in 1 Second (FEV1) up to 60 Minutes After the Exercise Challenge
A centralized spirometry data collection system was used to reduce FEV1 variability between and within patients and between each participating study center. The percentage fall was defined as 100\*(baseline-post baseline)/baseline. The baseline FEV1 is the test day FEV1 measured 5 minutes before the exercise challenge (30 minutes postdose). FEV1 post exercise challenge were measured 5 (±5), 10 (±5), 15 (±5), 30 (±5), and 60 (±10) minutes after completion of the exercise challenge. The exercise challenge consisted of the participant running on a motor-driven treadmill (with adjustable speed and incline). The treadmill was set at a speed and incline sufficient to increase the participant's heart rate to ≥80% of the maximum rate for age (220 bpm-age in years) for a period of either 6, 7, or 8 minutes using a stepped-exercise protocol in accordance with ATS guidelines (American Thoracic Society 2000). Conditions were repeated for subsequent challenges.
Time frame: Days 1 and 7; up to 60 minutes post-exercise challenge
Population: Full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Albuterol Spiromax 180 mcg | Maximum Percentage Fall From Baseline in Forced Expiratory Volume in 1 Second (FEV1) up to 60 Minutes After the Exercise Challenge | 6.21 percentage change from baseline FEV1 | Standard Error 1.443 |
| Placebo Spiromax | Maximum Percentage Fall From Baseline in Forced Expiratory Volume in 1 Second (FEV1) up to 60 Minutes After the Exercise Challenge | 22.38 percentage change from baseline FEV1 | Standard Error 1.444 |
p-value: <0.000195% CI: [-20.19, -12.14]mixed-effect analysis of covariance
Secondary
Participants Whose Maximum Percentage Decrease From the Baseline Forced Expiratory Volume in 1 Second (FEV1) Post-Exercise Challenge Was >20%
Participants were classified as unprotected if the maximum percentage decrease from baseline FEV1 after exercise was more than 20%. Data represents the number of participants who were classified as unprotected.
Time frame: Days 1 and 7; up to 60 minutes post-exercise challenge
Population: Full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Albuterol Spiromax 180 mcg | Participants Whose Maximum Percentage Decrease From the Baseline Forced Expiratory Volume in 1 Second (FEV1) Post-Exercise Challenge Was >20% | 1 participants |
| Placebo Spiromax | Participants Whose Maximum Percentage Decrease From the Baseline Forced Expiratory Volume in 1 Second (FEV1) Post-Exercise Challenge Was >20% | 22 participants |
Secondary
Percentage of Participants Whose Maximum Percentage Decrease From the Baseline Forced Expiratory Volume in 1 Second (FEV1) Post-Exercise Challenge Was <10%
Participants were classified as protected if the maximum percentage decrease from baseline FEV1 after exercise was less than 10%. Data represents the percentage of participants who were classified as protected.
Time frame: Days 1 and 7; up to 60 minutes post-exercise challenge
Population: Full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Albuterol Spiromax 180 mcg | Percentage of Participants Whose Maximum Percentage Decrease From the Baseline Forced Expiratory Volume in 1 Second (FEV1) Post-Exercise Challenge Was <10% | 84.21 percentage of participants |
| Placebo Spiromax | Percentage of Participants Whose Maximum Percentage Decrease From the Baseline Forced Expiratory Volume in 1 Second (FEV1) Post-Exercise Challenge Was <10% | 15.79 percentage of participants |
p-value: <0.000195% CI: [0.53, 0.84]Regression, Logistic