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This is a Phase 3B, 12-week, multicenter, open-label study to evaluate the relationship between albuterol sulfate (ABS) eMDPI and clinical asthma exacerbation (CAE) in adult participants at least 18 years of age with exacerbation-prone asthma. The ABS eMDPI dose will be 90 micrograms (mcg), 1 to 2 inhalations every 4 hours as needed, but participant dosing will not be limited to this dosing regimen. The purpose of this study is to evaluate the relationship between albuterol dosing and CAE.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ABS eMDPI | Experimental | Participants will receive 90 mcg of ABS via an eMDPI (sitting on the upper part of the device for the purposes of detecting and storing usage information), 1 to 2 inhalations every 4 hours, as needed for 12 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Albuterol Sulfate | Drug | Albuterol sulfate will be administered as per the dose and schedule specified in the arm. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Clinical Asthma Exacerbation (CAE) Rate: Percentage of Participants Who Experienced at Least 1 Moderate or Severe CAE | CAE was an occurrence of either severe CAE or moderate CAE. Severe CAE was defined as a CAE that involved worsening asthma such that the treating physician elected to administer prednisone (or equivalent glucocorticoid treatment) at least 10 milligrams (mg) prednisone equivalent above Baseline, for at least 3 days; and an unscheduled provider visit such as an office visit, urgent care visit, emergency care visit, or hospitalization. Moderate CAE was defined as a CAE that involved worsening asthma such that the treating physician elected to administer prednisone (or equivalent glucocorticoid treatment) at least 10 mg prednisone equivalent above Baseline, for at least 3 days, or an unscheduled provider visit such as an office visit, urgent care visit, emergency care visit, or hospitalization associated with an increase in asthma therapy that did not qualify for severe CAE as defined above. | Baseline (Day 1) to Week 12 |
| Total Number of Inhalations in the Days Preceding the Peak of a Severe CAE | Severe CAE was defined as a CAE that involved worsening asthma such that the treating physician elected to administer prednisone (or equivalent glucocorticoid treatment) at least 10 mg prednisone equivalent above Baseline, for at least 3 days; and an unscheduled provider visit such as an office visit, urgent care visit, emergency care visit, or hospitalization. Total number of inhalations taken in 1 day (that is, the 24-hour period on the day prior to the date of the CAE symptom peak) and at 3, 5, 7, 10, 14, and 21 days preceding the date of the severe CAE symptom peak were reported. | Baseline to Week 12 |
| Number of Days Prior to the Peak of a Severe CAE When Albuterol Use Increased | Severe CAE was defined as a CAE that involved worsening asthma such that the treating physician elected to administer prednisone (or equivalent glucocorticoid treatment) at least 10 mg prednisone equivalent above Baseline, for at least 3 days; and an unscheduled provider visit such as an office visit, urgent care visit, emergency care visit, or hospitalization. Number of days prior to the peak of a severe CAE when albuterol use first increased to greater than (>) 4, >12, and >20 inhalations was reported. Participants were counted in more than 1 category (that is, all of the >20 inhalation participants were also counted in the >12 category, and in the >4 category). |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Adverse Events (AEs) | AE was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by investigator on a scale of mild, moderate and severe, with severe= an inability to carry out usual activities. Relation of AE to treatment was determined by investigator. SAEs included death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of serious and non-serious AEs regardless of causality is located in 'Reported Adverse Events module'. |
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Inclusion Criteria:
The participant has had at least 1 episode of a severe CAE over the past 12 months before screening. If on a biologic (for example, omalizumab, mepolizumab, or reslizumab) and/or post-bronchial thermoplasty, exacerbation has occurred after these interventions.
The participant is using a moderate-dose inhaled corticosteroid (ICS) equivalent to at least 440 mcg daily of fluticasone propionate.
The participant's baseline asthma therapy regimen, including oral corticosteroids, leukotriene antagonists, 5-lipoxygenase inhibitors, long-acting beta agonist (LABA), long-acting muscarinic agent, or cromolyn, biologicals, theophylline, or mepolizumab, is allowed.
The participant must be willing and able to comply with study requirements as specified in the protocol, including the use of a wearable accelerometer for the subset of participants who consent to use of the device.
The participant is willing to discontinue all other rescue or maintenance short-acting beta 2 agonist (SABA) or antimuscarinic agents and replace them with the study-provided ABS eMDPI for the duration of the trial.
Women of childbearing potential (not surgically sterile or at least 2 years postmenopausal) must have exclusively same-sex partners or use a highly effective method of birth control and must agree to continue the use of this method for the duration of the study and for 30 days after discontinuation of the investigational medicinal product (IMP).
Exclusion Criteria:
The participant has any clinically significant medical condition (treated or untreated) that, in the opinion of the investigator, would interfere with participation in the study.
The participant has any other confounding underlying lung disorder other than asthma.
The participant has used an investigational drug within 5 half-lives of it being discontinued or 1 month of baseline visit, whichever is longer.
The participant is a pregnant or lactating woman, or plans to become pregnant during the study. Note: Any woman becoming pregnant during the study will be withdrawn from the study.
The participant is known to be allergic to albuterol or any of the excipients in the IMP or rescue medication formulation (that is, lactose). Dietary lactose intolerance does not exclude the participant from inclusion in the study or as per the investigator's medical discretion.
The participant has a history or presence of "silent" infections, including positive testing for human immunodeficiency virus types 1 and 2, hepatitis B, hepatitis C, and tuberculosis.
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| Name | Affiliation | Role |
|---|---|---|
| Teva Medical Expert, MD | Teva Branded Pharmaceutical Products R&D, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Teva Investigational Site 13964 | Litchfield Park | Arizona | 85340 | United States | ||
| Teva Investigational Site 13959 |
A total of 449 participants with exacerbation-prone asthma were screened, of which 397 participants at 45 investigational centers in the US met entry criteria and were considered to be eligible for enrollment into the study.
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| ID | Title | Description |
|---|---|---|
| FG000 | ABS eMDPI | Participants received 90 micrograms (mcg) of albuterol sulfate (ABS) via a multidose dry powder inhaler (MDPI) with an eModule (eMDPI) (sitting on the upper part of the device for the purposes of detecting and storing usage information), 1 to 2 inhalations every 4 hours, as needed for 12 weeks. ABS eMDPI was a rescue/reliever agent that included an eModule on top of the approved PROAIR RESPICLICK® inhaler. Participants were allowed to continue use of other asthma and non-asthma medications as advised by their physician without changes unless deemed necessary by their physician. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Feb 22, 2017 | Apr 12, 2019 |
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| Baseline to Week 12 |
| Number of Albuterol Uses in the 24 Hours Preceding a Severe CAE | Severe CAE was defined as a CAE that involved worsening asthma such that the treating physician elected to administer prednisone (or equivalent glucocorticoid treatment) at least 10 mg prednisone equivalent above Baseline, for at least 3 days; and an unscheduled provider visit such as an office visit, urgent care visit, emergency care visit, or hospitalization. Number of albuterol inhalations used in the 24 hours preceeding a severe CAE is reported. | Baseline to Week 12 |
| Baseline up to week 12 |
| Bakersfield |
| California |
| 93301 |
| United States |
| Teva Investigational Site 13954 | Los Angeles | California | 90048 | United States |
| Teva Investigational Site 13923 | Orange | California | 92868 | United States |
| Teva Investigational Site 13961 | Riverside | California | 92506 | United States |
| Teva Investigational Site 13933 | Centennial | Colorado | 80112 | United States |
| Teva Investigational Site 13946 | Clearwater | Florida | 33765 | United States |
| Teva Investigational Site 13921 | Loxahatchee Groves | Florida | 33470 | United States |
| Teva Investigational Site 13942 | Miami | Florida | 33176 | United States |
| Teva Investigational Site 13927 | Miami | Florida | 33186 | United States |
| Teva Investigational Site 13948 | Orlando | Florida | 32803 | United States |
| Teva Investigational Site 13934 | Orlando | Florida | 32819 | United States |
| Teva Investigational Site 13931 | Ormond Beach | Florida | 32174 | United States |
| Teva Investigational Site 13926 | Sarasota | Florida | 34239 | United States |
| Teva Investigational Site 13963 | Savannah | Georgia | 31406 | United States |
| Teva Investigational Site 13943 | Michigan City | Indiana | 46360 | United States |
| Teva Investigational Site 13925 | Overland Park | Kansas | 66210 | United States |
| Teva Investigational Site 13958 | Fort Mitchell | Kentucky | 41017 | United States |
| Teva Investigational Site 13940 | Owensboro | Kentucky | 42301 | United States |
| Teva Investigational Site 13937 | Bangor | Maine | 04401 | United States |
| Teva Investigational Site 13965 | St Louis | Missouri | 63141 | United States |
| Teva Investigational Site 13919 | Missoula | Montana | 59808 | United States |
| Teva Investigational Site 13947 | Bellevue | Nebraska | 68123-4303 | United States |
| Teva Investigational Site 13960 | Brick | New Jersey | 08724 | United States |
| Teva Investigational Site 13932 | Piscataway | New Jersey | 08854 | United States |
| Teva Investigational Site 13922 | Verona | New Jersey | 07044 | United States |
| Teva Investigational Site 13945 | Rochester | New York | 14618 | United States |
| Teva Investigational Site 13936 | High Point | North Carolina | 27262 | United States |
| Teva Investigational Site 13953 | Cincinnati | Ohio | 45231 | United States |
| Teva Investigational Site 13928 | Edmond | Oklahoma | 73034 | United States |
| Teva Investigational Site 13955 | Oklahoma City | Oklahoma | 73131 | United States |
| Teva Investigational Site 13949 | East Providence | Rhode Island | 02914 | United States |
| Teva Investigational Site 13929 | Charleston | South Carolina | 29407 | United States |
| Teva Investigational Site 13941 | Greenville | South Carolina | 29607 | United States |
| Teva Investigational Site 13951 | Greenville | South Carolina | 29615 | United States |
| Teva Investigational Site 13938 | Spartanburg | South Carolina | 29303 | United States |
| Teva Investigational Site 13924 | Knoxville | Tennessee | 37909 | United States |
| Teva Investigational Site 13962 | Boerne | Texas | 78006 | United States |
| Teva Investigational Site 13920 | Dallas | Texas | 75231 | United States |
| Teva Investigational Site 13930 | Houston | Texas | 77099 | United States |
| Teva Investigational Site 13939 | San Antonio | Texas | 78230 | United States |
| Teva Investigational Site 13957 | San Antonio | Texas | 78251 | United States |
| Teva Investigational Site 13952 | South Burlington | Vermont | 05403 | United States |
| Teva Investigational Site 13956 | Fairfax | Virginia | 22030 | United States |
| Used ABS eMDPI at Least Once |
|
| COMPLETED |
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| NOT COMPLETED |
|
|
The intent-to-treat (ITT) analysis set included all enrolled participants regardless of whether a participant took any investigational medicinal product (IMP).
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| ID | Title | Description |
|---|---|---|
| BG000 | ABS eMDPI | Participants received 90 mcg of ABS via eMDPI (sitting on the upper part of the device for the purposes of detecting and storing usage information), 1 to 2 inhalations every 4 hours, as needed for 12 weeks. ABS eMDPI was a rescue/reliever agent that included an eModule on top of the approved PROAIR RESPICLICK® inhaler. Participants were allowed to continue use of other asthma and non-asthma medications as advised by their physician without changes unless deemed necessary by their physician. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
| ||||||||||||||||||
| Number of Asthma Exacerbations in the Past 12 Months | Here, 'number analyzed' signifies number of participants with asthma exacerbations. | Mean | Standard Deviation | exacerbations |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Clinical Asthma Exacerbation (CAE) Rate: Percentage of Participants Who Experienced at Least 1 Moderate or Severe CAE | CAE was an occurrence of either severe CAE or moderate CAE. Severe CAE was defined as a CAE that involved worsening asthma such that the treating physician elected to administer prednisone (or equivalent glucocorticoid treatment) at least 10 milligrams (mg) prednisone equivalent above Baseline, for at least 3 days; and an unscheduled provider visit such as an office visit, urgent care visit, emergency care visit, or hospitalization. Moderate CAE was defined as a CAE that involved worsening asthma such that the treating physician elected to administer prednisone (or equivalent glucocorticoid treatment) at least 10 mg prednisone equivalent above Baseline, for at least 3 days, or an unscheduled provider visit such as an office visit, urgent care visit, emergency care visit, or hospitalization associated with an increase in asthma therapy that did not qualify for severe CAE as defined above. | ITT analysis set included all enrolled participants regardless of whether a participant took any IMP. | Posted | Number | percentage of participants | Baseline (Day 1) to Week 12 |
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| ||||||||||||||||||||||||||
| Primary | Total Number of Inhalations in the Days Preceding the Peak of a Severe CAE | Severe CAE was defined as a CAE that involved worsening asthma such that the treating physician elected to administer prednisone (or equivalent glucocorticoid treatment) at least 10 mg prednisone equivalent above Baseline, for at least 3 days; and an unscheduled provider visit such as an office visit, urgent care visit, emergency care visit, or hospitalization. Total number of inhalations taken in 1 day (that is, the 24-hour period on the day prior to the date of the CAE symptom peak) and at 3, 5, 7, 10, 14, and 21 days preceding the date of the severe CAE symptom peak were reported. | ITT analysis set included all enrolled participants regardless of whether a participant took any IMP. Here, 'overall number of participants analyzed' signifies number of participants experiencing at least 1 severe CAE. Here, 'number analyzed' signifies participants who reported albuterol use in specified time interval. | Posted | Mean | Standard Deviation | inhalations | Baseline to Week 12 |
| |||||||||||||||||||||||||||
| Primary | Number of Days Prior to the Peak of a Severe CAE When Albuterol Use Increased | Severe CAE was defined as a CAE that involved worsening asthma such that the treating physician elected to administer prednisone (or equivalent glucocorticoid treatment) at least 10 mg prednisone equivalent above Baseline, for at least 3 days; and an unscheduled provider visit such as an office visit, urgent care visit, emergency care visit, or hospitalization. Number of days prior to the peak of a severe CAE when albuterol use first increased to greater than (>) 4, >12, and >20 inhalations was reported. Participants were counted in more than 1 category (that is, all of the >20 inhalation participants were also counted in the >12 category, and in the >4 category). | ITT analysis set included all enrolled participants regardless of whether a participant took any IMP. Here, 'overall number of participants analyzed'= number of participants experiencing at least 1 severe CAE. 'Number analyzed'= participants who had any single day prior to CAE where their albuterol use exceeded 4, 12, or 20 inhalations in that day. | Posted | Mean | Standard Deviation | days | Baseline to Week 12 |
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| Primary | Number of Albuterol Uses in the 24 Hours Preceding a Severe CAE | Severe CAE was defined as a CAE that involved worsening asthma such that the treating physician elected to administer prednisone (or equivalent glucocorticoid treatment) at least 10 mg prednisone equivalent above Baseline, for at least 3 days; and an unscheduled provider visit such as an office visit, urgent care visit, emergency care visit, or hospitalization. Number of albuterol inhalations used in the 24 hours preceeding a severe CAE is reported. | ITT analysis set included all enrolled participants regardless of whether a participant took any IMP. Here, 'overall number of participants analyzed' signifies number of participants who experienced at least 1 severe CAE and reported albuterol use in the 24 hours preceding a severe CAE. | Posted | Mean | Standard Deviation | inhalations | Baseline to Week 12 |
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| Secondary | Number of Participants With Adverse Events (AEs) | AE was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by investigator on a scale of mild, moderate and severe, with severe= an inability to carry out usual activities. Relation of AE to treatment was determined by investigator. SAEs included death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of serious and non-serious AEs regardless of causality is located in 'Reported Adverse Events module'. | ITT analysis set included all enrolled participants regardless of whether a participant took any IMP. | Posted | Count of Participants | Participants | Baseline up to week 12 |
|
Baseline up to Week 12
ITT analysis set included all enrolled participants regardless of whether a participant took any IMP.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | ABS eMDPI | Participants received 90 mcg of ABS via eMDPI (sitting on the upper part of the device for the purposes of detecting and storing usage information), 1 to 2 inhalations every 4 hours, as needed for 12 weeks. ABS eMDPI was a rescue/reliever agent that included an eModule on top of the approved PROAIR RESPICLICK® inhaler. Participants were allowed to continue use of other asthma and non-asthma medications as advised by their physician without changes unless deemed necessary by their physician. | 0 | 397 | 6 | 397 | 68 | 397 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute myocardial infarction | Cardiac disorders | MedDRA v19.1 | Systematic Assessment |
| |
| Myocardial infarction | Cardiac disorders | MedDRA v19.1 | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA v19.1 | Systematic Assessment |
| |
| Gastroenteritis salmonella | Infections and infestations | MedDRA v19.1 | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA v19.1 | Systematic Assessment |
| |
| Facial bones fracture | Injury, poisoning and procedural complications | MedDRA v19.1 | Systematic Assessment |
| |
| Fractured sacrum | Injury, poisoning and procedural complications | MedDRA v19.1 | Systematic Assessment |
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| Humerus fracture | Injury, poisoning and procedural complications | MedDRA v19.1 | Systematic Assessment |
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| Ilium fracture | Injury, poisoning and procedural complications | MedDRA v19.1 | Systematic Assessment |
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| Pubis fracture | Injury, poisoning and procedural complications | MedDRA v19.1 | Systematic Assessment |
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| Rib fracture | Injury, poisoning and procedural complications | MedDRA v19.1 | Systematic Assessment |
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| Road traffic accident | Injury, poisoning and procedural complications | MedDRA v19.1 | Systematic Assessment |
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| Dehydration | Metabolism and nutrition disorders | MedDRA v19.1 | Systematic Assessment |
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| Hypokalaemia | Metabolism and nutrition disorders | MedDRA v19.1 | Systematic Assessment |
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| Migraine | Nervous system disorders | MedDRA v19.1 | Systematic Assessment |
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| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA v19.1 | Systematic Assessment |
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| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA v19.1 | Systematic Assessment |
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| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA v19.1 | Systematic Assessment |
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| Deep vein thrombosis | Vascular disorders | MedDRA v19.1 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA v19.1 | Systematic Assessment |
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Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Director, Clinical Research | Teva Branded Pharmaceutical Products, R&D Inc. | 215-591-3000 | ustevatrials@tevapharm.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 9, 2018 | Apr 12, 2019 | SAP_001.pdf |
| ID | Term |
|---|---|
| D001249 | Asthma |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012130 | Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D000420 | Albuterol |
| ID | Term |
|---|---|
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D000588 | Amines |
| D010627 | Phenethylamines |
| D005021 | Ethylamines |
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| Unknown or Not Reported |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| Other |
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