Trial Outcomes & Findings for A Twelve Month Long Term Safety Study to Evaluate the Safety of Albuterol in a Dry Powder Inhaler With Both Repeated and as Needed Dosing (NCT NCT01218009)

Last Updated: 2015-05-20

Results Overview

Adverse events (AEs) summarized in this table are those that began or worsened after treatment with study drug (treatment-emergent AEs). An adverse event was defined in the protocol 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 the investigator on a scale of mild, moderate and severe, with severe= an AE which prevents normal daily activities. Relation of AE to treatment was determined by the investigator. Serious AEs include 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 patient and required medical intervention to prevent the previously listed serious outcomes.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

331 participants

Primary outcome timeframe

Day 1 to Day 49 (study termination)

Results posted on

2015-05-20

Participant Flow

Four hundred fifty-two patients were screened and 331 randomized into the study.

Participant milestones

Participant milestones
Measure	Albuterol Spiromax Albuterol multi-dose dry powder inhaler (Spiromax) at a dose of 720 micrograms per day administered as 2 inhalations of 90 mcg /inhalation four times a day for the 12 week double-blind period. Participants then continue into the 40 week open-label period in which they take albuterol multi-dose dry powder inhaler (Spiromax) inhalations of 90 mcg /inhalation as required (PRN).	Placebo Spiromax Placebo delivered using a multi-dose dry powder inhaler (Spiromax) as 2 inhalations four times a day for the 12 week double-blind period. Participants then continue into the 40 week open-label period in which they administer albuterol multi-dose dry powder inhaler (Spiromax) inhalations of 90 mcg /inhalation as required (PRN).
Overall Study STARTED	166	165
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	166	165

Reasons for withdrawal

Reasons for withdrawal
Measure	Albuterol Spiromax Albuterol multi-dose dry powder inhaler (Spiromax) at a dose of 720 micrograms per day administered as 2 inhalations of 90 mcg /inhalation four times a day for the 12 week double-blind period. Participants then continue into the 40 week open-label period in which they take albuterol multi-dose dry powder inhaler (Spiromax) inhalations of 90 mcg /inhalation as required (PRN).	Placebo Spiromax Placebo delivered using a multi-dose dry powder inhaler (Spiromax) as 2 inhalations four times a day for the 12 week double-blind period. Participants then continue into the 40 week open-label period in which they administer albuterol multi-dose dry powder inhaler (Spiromax) inhalations of 90 mcg /inhalation as required (PRN).
Overall Study Protocol Violation	2	1
Overall Study Withdrawal by Subject	3	1
Overall Study Sponsor terminated study	161	163

Baseline Characteristics

A Twelve Month Long Term Safety Study to Evaluate the Safety of Albuterol in a Dry Powder Inhaler With Both Repeated and as Needed Dosing

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Albuterol Spiromax n=166 Participants Albuterol multi-dose dry powder inhaler (Spiromax) at a dose of 720 micrograms per day administered as 2 inhalations of 90 mcg /inhalation four times a day for the 12 week double-blind period. Participants then continue into the 40 week open-label period in which they take albuterol multi-dose dry powder inhaler (Spiromax) inhalations of 90 mcg /inhalation as required (PRN).	Placebo Spiromax n=165 Participants Placebo delivered using a multi-dose dry powder inhaler (Spiromax) as 2 inhalations four times a day for the 12 week double-blind period. Participants then continue into the 40 week open-label period in which they administer albuterol multi-dose dry powder inhaler (Spiromax) inhalations of 90 mcg /inhalation as required (PRN).	Total n=331 Participants Total of all reporting groups
Age, Continuous	37.9 years STANDARD_DEVIATION 14.07 • n=5 Participants	38.0 years STANDARD_DEVIATION 14.91 • n=7 Participants	37.9 years STANDARD_DEVIATION 14.47 • n=5 Participants
Sex: Female, Male Female	105 Participants n=5 Participants	122 Participants n=7 Participants	227 Participants n=5 Participants
Sex: Female, Male Male	61 Participants n=5 Participants	43 Participants n=7 Participants	104 Participants n=5 Participants
Race/Ethnicity, Customized White	140 participants n=5 Participants	132 participants n=7 Participants	272 participants n=5 Participants
Race/Ethnicity, Customized Black	19 participants n=5 Participants	28 participants n=7 Participants	47 participants n=5 Participants
Race/Ethnicity, Customized Asian	4 participants n=5 Participants	1 participants n=7 Participants	5 participants n=5 Participants
Race/Ethnicity, Customized North American or Alaska Native	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Other	2 participants n=5 Participants	4 participants n=7 Participants	6 participants n=5 Participants
Ethnicity Hispanic	20 participants n=5 Participants	21 participants n=7 Participants	41 participants n=5 Participants
Ethnicity Not Hispanic	146 participants n=5 Participants	144 participants n=7 Participants	290 participants n=5 Participants
Height	66.1 inches STANDARD_DEVIATION 3.59 • n=5 Participants	65.7 inches STANDARD_DEVIATION 3.86 • n=7 Participants	65.9 inches STANDARD_DEVIATION 3.73 • n=5 Participants
Weight	184 pounds STANDARD_DEVIATION 49.7 • n=5 Participants	179 pounds STANDARD_DEVIATION 48.2 • n=7 Participants	182 pounds STANDARD_DEVIATION 48.9 • n=5 Participants

PRIMARY outcome

Timeframe: Day 1 to Day 49 (study termination)

Population: Safety population

Outcome measures

Outcome measures
Measure	Placebo Spiromax n=165 Participants Placebo delivered using a multi-dose dry powder inhaler (Spiromax) as 2 inhalations four times a day for the 12 week double-blind period. Participants then continue into the 40 week open-label period in which they administer albuterol multi-dose dry powder inhaler (Spiromax) inhalations of 90 mcg /inhalation as required (PRN).	Albuterol Spiromax n=166 Participants Albuterol multi-dose dry powder inhaler (Spiromax) at a dose of 720 micrograms per day administered as 2 inhalations of 90 mcg /inhalation four times a day for the 12 week double-blind period. Participants then continue into the 40 week open-label period in which they take albuterol multi-dose dry powder inhaler (Spiromax) inhalations of 90 mcg /inhalation as required (PRN).
Participants With Treatment-Emergent Adverse Events Any adverse event	58 participants	59 participants
Participants With Treatment-Emergent Adverse Events Treatment-related adverse event	3 participants	3 participants
Participants With Treatment-Emergent Adverse Events Withdrawn from study due to adverse event	0 participants	0 participants
Participants With Treatment-Emergent Adverse Events Serious adverse event	1 participants	1 participants
Participants With Treatment-Emergent Adverse Events Treatment-related serious adverse event	0 participants	0 participants
Participants With Treatment-Emergent Adverse Events Mild adverse event	32 participants	29 participants
Participants With Treatment-Emergent Adverse Events Moderate adverse event	29 participants	35 participants
Participants With Treatment-Emergent Adverse Events Severe adverse event	4 participants	2 participants
Participants With Treatment-Emergent Adverse Events AE class: Investigations	3 participants	3 participants
Participants With Treatment-Emergent Adverse Events AE class: Infections and infestations	34 participants	31 participants
Participants With Treatment-Emergent Adverse Events AE class: General and administrative site conditi	1 participants	1 participants
Participants With Treatment-Emergent Adverse Events AE class: Psychiatric	1 participants	1 participants
Participants With Treatment-Emergent Adverse Events AE class: Respiratory, thoracic and mediastinal	11 participants	12 participants
Participants With Treatment-Emergent Adverse Events AE class: Gastrointestinal	5 participants	9 participants
Participants With Treatment-Emergent Adverse Events AE class: Nervous system	6 participants	7 participants
Participants With Treatment-Emergent Adverse Events AE class: Injury, poisoning and procedural compli	2 participants	4 participants
Participants With Treatment-Emergent Adverse Events AE class: Musculoskeletal and connective tissue	4 participants	2 participants
Participants With Treatment-Emergent Adverse Events AE class: Renal and urinary	1 participants	2 participants
Participants With Treatment-Emergent Adverse Events AE class: Ear and labyrinth	1 participants	2 participants
Participants With Treatment-Emergent Adverse Events AE class: Skin and subcutaneous tissue	0 participants	2 participants
Participants With Treatment-Emergent Adverse Events AE class: Social circumstances	0 participants	1 participants
Participants With Treatment-Emergent Adverse Events AE class: Cardiac	2 participants	0 participants
Participants With Treatment-Emergent Adverse Events AE class: Eye	1 participants	0 participants
Participants With Treatment-Emergent Adverse Events AE class: Blood and lymphatic system	1 participants	0 participants
Participants With Treatment-Emergent Adverse Events Neoplasm benign, malignant + unspecified	1 participants	0 participants

PRIMARY outcome

Timeframe: Days -15 to -8 (Screening), Week 12, Week 52

Population: Safety population. The study was terminated prior to the during study evaluations.

A complete physical examination was planned at study screening, week 12 and week 52 or early termination/discontinuation of the participant. At weeks 12 and 52,the qualified healthcare professional was to evaluate whether each physical finding is a new finding, worsening, improvement or resolution of an existing condition compared with the baseline physical exam. Where possible, the same qualified healthcare professional that performed the physical examination at study screening should perform all the scheduled physical examinations.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Days -15 to -8 (Screening), Week 12, Week 52

Population: Safety population. The study was terminated prior to the during study evaluations.

Blood samples were to collected for laboratory evaluations at the screening visit and at weeks 12 and 52 or early termination/discontinuation of the participant. The blood samples were to be drawn after an overnight fast of at least 6 hours and analyzed by a central laboratory.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Days -15 to -8 (Screening), Week 12, Week 52

Population: Safety population. The study was terminated prior to the during study evaluations.

A standard 12-lead ECG was to be performed at screening and at week 12 and week 52 (TV15) or early termination/discontinuation of the participant. The ECG recording methods were to be centralized and standardized across all study subjects.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Days -15 to -8 (Screening), Week 12, Week 52

Population: Safety population. The study was terminated prior to the during study evaluations.

Vital sign measurements (heart rate and blood pressure) were to be evaluated as part of the safety profile assessment. The participant was to be seated at least 2 minutes before vital signs were performed. Either an electronic or manual sphygmomanometer could be used.

Outcome measures

Outcome data not reported

POST_HOC outcome

Timeframe: Days -15 to -8 (Screening), up to Day 49 (End of study)

Population: Safety population

Vital sign measurements (heart rate and blood pressure) were evaluated as part of the safety profile assessment. The participant was seated at least 2 minutes before vital signs were performed. Either an electronic or manual sphygmomanometer was used.

Outcome measures

Outcome measures
Measure	Placebo Spiromax n=165 Participants Placebo delivered using a multi-dose dry powder inhaler (Spiromax) as 2 inhalations four times a day for the 12 week double-blind period. Participants then continue into the 40 week open-label period in which they administer albuterol multi-dose dry powder inhaler (Spiromax) inhalations of 90 mcg /inhalation as required (PRN).	Albuterol Spiromax n=166 Participants Albuterol multi-dose dry powder inhaler (Spiromax) at a dose of 720 micrograms per day administered as 2 inhalations of 90 mcg /inhalation four times a day for the 12 week double-blind period. Participants then continue into the 40 week open-label period in which they take albuterol multi-dose dry powder inhaler (Spiromax) inhalations of 90 mcg /inhalation as required (PRN).
Blood Pressure at Screening and End of Study End of Study Systolic BP (n=164, 164)	118.2 mmHg Standard Deviation 12.99	118.4 mmHg Standard Deviation 13.50
Blood Pressure at Screening and End of Study Screening Diastolic BP (n=166, 165)	75.2 mmHg Standard Deviation 9.08	75.5 mmHg Standard Deviation 9.24
Blood Pressure at Screening and End of Study End of Study Diastolic BP (n=164, 164)	75.2 mmHg Standard Deviation 8.79	75.7 mmHg Standard Deviation 9.54
Blood Pressure at Screening and End of Study Screening Systolic BP (n=166, 165)	118.0 mmHg Standard Deviation 13.70	119.4 mmHg Standard Deviation 13.39

POST_HOC outcome

Timeframe: Days -15 to -8 (Screening), up to Day 49 (End of study)

Population: Safety population

Outcome measures

Outcome measures
Measure	Placebo Spiromax n=165 Participants Placebo delivered using a multi-dose dry powder inhaler (Spiromax) as 2 inhalations four times a day for the 12 week double-blind period. Participants then continue into the 40 week open-label period in which they administer albuterol multi-dose dry powder inhaler (Spiromax) inhalations of 90 mcg /inhalation as required (PRN).	Albuterol Spiromax n=166 Participants Albuterol multi-dose dry powder inhaler (Spiromax) at a dose of 720 micrograms per day administered as 2 inhalations of 90 mcg /inhalation four times a day for the 12 week double-blind period. Participants then continue into the 40 week open-label period in which they take albuterol multi-dose dry powder inhaler (Spiromax) inhalations of 90 mcg /inhalation as required (PRN).
Pulse at Screening and End of Study Screening (n=166, 165)	71.8 beats/minute Standard Deviation 10.03	71.0 beats/minute Standard Deviation 8.57
Pulse at Screening and End of Study End of study (n=164, 164)	73.0 beats/minute Standard Deviation 9.48	72.1 beats/minute Standard Deviation 9.34

Adverse Events

Albuterol Spiromax

Serious events: 1 serious events

Other events: 16 other events

Deaths: 0 deaths

Placebo Spiromax

Serious events: 1 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Albuterol Spiromax n=166 participants at risk Albuterol multi-dose dry powder inhaler (Spiromax) at a dose of 720 micrograms per day administered as 2 inhalations of 90 mcg /inhalation four times a day for the 12 week double-blind period. Participants then continue into the 40 week open-label period in which they take albuterol multi-dose dry powder inhaler (Spiromax) inhalations of 90 mcg /inhalation as required (PRN).	Placebo Spiromax n=165 participants at risk Placebo delivered using a multi-dose dry powder inhaler (Spiromax) as 2 inhalations four times a day for the 12 week double-blind period. Participants then continue into the 40 week open-label period in which they administer albuterol multi-dose dry powder inhaler (Spiromax) inhalations of 90 mcg /inhalation as required (PRN).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal adenocarcinoma	0.00% 0/166 • Day 1 to Day 49 (study termination)	0.61% 1/165 • Day 1 to Day 49 (study termination)
Respiratory, thoracic and mediastinal disorders Asthma	0.60% 1/166 • Day 1 to Day 49 (study termination)	0.00% 0/165 • Day 1 to Day 49 (study termination)

Other adverse events

Other adverse events
Measure	Albuterol Spiromax n=166 participants at risk Albuterol multi-dose dry powder inhaler (Spiromax) at a dose of 720 micrograms per day administered as 2 inhalations of 90 mcg /inhalation four times a day for the 12 week double-blind period. Participants then continue into the 40 week open-label period in which they take albuterol multi-dose dry powder inhaler (Spiromax) inhalations of 90 mcg /inhalation as required (PRN).	Placebo Spiromax n=165 participants at risk Placebo delivered using a multi-dose dry powder inhaler (Spiromax) as 2 inhalations four times a day for the 12 week double-blind period. Participants then continue into the 40 week open-label period in which they administer albuterol multi-dose dry powder inhaler (Spiromax) inhalations of 90 mcg /inhalation as required (PRN).
Infections and infestations Nasopharyngitis	3.6% 6/166 • Day 1 to Day 49 (study termination)	6.1% 10/165 • Day 1 to Day 49 (study termination)
Infections and infestations Upper respiratory tract infection	6.0% 10/166 • Day 1 to Day 49 (study termination)	6.7% 11/165 • Day 1 to Day 49 (study termination)

Additional Information

Director, Clinical Research

Teva Branded Pharmaceutical Products, R&D Inc.

Phone: 1-215-591-3000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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
Publication restrictions are in place

Restriction type: OTHER