Trial Outcomes & Findings for A 12-week Study to Compare the Efficacy and Safety of Albuterol Spiromax® Versus a Placebo in People 12 Years and Older With Persistent Asthma (NCT NCT01424813)

Last Updated: 2015-06-26

Results Overview

FEV1 AUC 0-6 is the area under the effect-time curve from time 0 (pre-dose) up to 6 hours post-dose. It represents the weighted average (by the trapezoidal rule) of FEV1 AUC 0-6 measures adjusted for the baseline measure (i.e., change from baseline at each timepoint) recorded on days 1, 8 and 85 of the treatment period. The baseline for each study day was the average of the 2 pre-dose FEV1 measurements on that study day. FEV1 was measured using spirometry. Spirometry assessments were obtained predose at -30 ± 5, and - 5 minutes, then post dose at 5 ± 2, 15 ± 5, 30 ± 5, 45 ± 5 minutes, and at 1hr ± 5 min, 2hr ± 5 min, 3hr ± 5 min, 4hr ± 5 min, 5hr ± 5 min, and 6hr ± 5 min.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

158 participants

Primary outcome timeframe

Day 1, Day 8 and Day 85

Results posted on

2015-06-26

Participant Flow

384 patients screened; 180 patients were excluded on the basis of inclusion criteria, 4 due to exclusion criteria, 21 patients withdrew consent, 1 patient was lost to follow-up before the baseline visit, 6 patients had other reasons, and 14 patients failed to meet randomization criteria at the end of the run-in period.

Participant milestones

Participant milestones
Measure	Placebo MDPI Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks.	Albuterol MDPI Albuterol multi-dose dry powder inhaler (MDPI) at a dose of 720 micrograms per day administered as 2 inhalations of 90 mcg /inhalation four times a day for 12 weeks.
Overall Study STARTED	79	79
Overall Study Treated	79	78
Overall Study COMPLETED	74	77
Overall Study NOT COMPLETED	5	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo MDPI Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks.	Albuterol MDPI Albuterol multi-dose dry powder inhaler (MDPI) at a dose of 720 micrograms per day administered as 2 inhalations of 90 mcg /inhalation four times a day for 12 weeks.
Overall Study Withdrawal by Subject	3	0
Overall Study Protocol Violation	1	0
Overall Study Other	1	2

Baseline Characteristics

A 12-week Study to Compare the Efficacy and Safety of Albuterol Spiromax® Versus a Placebo in People 12 Years and Older With Persistent Asthma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo MDPI n=79 Participants Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks.	Albuterol MDPI n=79 Participants Albuterol multi-dose dry powder inhaler (MDPI) at a dose of 720 micrograms per day administered as 2 inhalations of 90 mcg /inhalation four times a day for 12 weeks.	Total n=158 Participants Total of all reporting groups
Age, Continuous	40.3 years STANDARD_DEVIATION 16.84 • n=5 Participants	37.3 years STANDARD_DEVIATION 16.89 • n=7 Participants	38.8 years STANDARD_DEVIATION 16.88 • n=5 Participants
Age, Customized 12-17 years	14 participants n=5 Participants	16 participants n=7 Participants	30 participants n=5 Participants
Age, Customized 18-64 years	63 participants n=5 Participants	60 participants n=7 Participants	123 participants n=5 Participants
Age, Customized 65+ years	2 participants n=5 Participants	3 participants n=7 Participants	5 participants n=5 Participants
Sex: Female, Male Female	47 Participants n=5 Participants	44 Participants n=7 Participants	91 Participants n=5 Participants
Sex: Female, Male Male	32 Participants n=5 Participants	35 Participants n=7 Participants	67 Participants n=5 Participants
Race/Ethnicity, Customized White	59 participants n=5 Participants	55 participants n=7 Participants	114 participants n=5 Participants
Race/Ethnicity, Customized Black	18 participants n=5 Participants	21 participants n=7 Participants	39 participants n=5 Participants
Race/Ethnicity, Customized Asian	2 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaskan Native	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Race/Ethnicity, Customized Pacific Islander	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Race/Ethnicity, Customized Other	0 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	3 participants n=5 Participants	6 participants n=7 Participants	9 participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	76 participants n=5 Participants	73 participants n=7 Participants	149 participants n=5 Participants
Weight	82.4 kg STANDARD_DEVIATION 21.34 • n=5 Participants	83.4 kg STANDARD_DEVIATION 24.20 • n=7 Participants	82.9 kg STANDARD_DEVIATION 22.75 • n=5 Participants
Height	169.5 cm STANDARD_DEVIATION 9.47 • n=5 Participants	168.9 cm STANDARD_DEVIATION 9.27 • n=7 Participants	169.2 cm STANDARD_DEVIATION 9.35 • n=5 Participants
Body Mass Index	28.6 kg/m^2 STANDARD_DEVIATION 6.92 • n=5 Participants	29.2 kg/m^2 STANDARD_DEVIATION 8.22 • n=7 Participants	28.9 kg/m^2 STANDARD_DEVIATION 7.58 • n=5 Participants

PRIMARY outcome

Timeframe: Day 1, Day 8 and Day 85

Population: Full analysis set which includes all participants in the intent-to-treat (ITT) population who received at least 1 dose of study medication and had at least 1 post-baseline assessment.

Outcome measures

Outcome measures
Measure	Placebo MDPI n=79 Participants Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks.	Albuterol MDPI n=78 Participants Albuterol multi-dose dry powder inhaler (MDPI) at a dose of 720 micrograms per day administered as 2 inhalations of 90 mcg /inhalation four times a day for 12 weeks.
Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) Over the 12-week Treatment Period	0.28 L*hr Standard Error 0.091	1.11 L*hr Standard Error 0.092

SECONDARY outcome

Timeframe: Day 1

Population: Full analysis set

FEV1 AUC 0-6 is the area under the effect-time curve from time 0 (pre-dose) up to 6 hours post-dose. The baseline was the average of the 2 pre-dose FEV1 measurements on that study day. The baseline-adjustment refers to change from baseline at each post dose timepoint recorded on Day 1. FEV1 was measured using spirometry. Spirometry assessments were obtained predose at -30 ± 5, and - 5 minutes, then post dose at 5 ± 2, 15 ± 5, 30 ± 5, 45 ± 5 minutes, and at 1hr ± 5 min, 2hr ± 5 min, 3hr ± 5 min, 4hr ± 5 min, 5hr ± 5 min, and 6hr ± 5 min.

Outcome measures

Outcome measures
Measure	Placebo MDPI n=79 Participants Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks.	Albuterol MDPI n=78 Participants Albuterol multi-dose dry powder inhaler (MDPI) at a dose of 720 micrograms per day administered as 2 inhalations of 90 mcg /inhalation four times a day for 12 weeks.
Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) on Day 1	0.52 L*hr Interval 0.24 to 0.79	1.58 L*hr Interval 1.3 to 1.87

SECONDARY outcome

Timeframe: Day 8

Population: Full analysis set of participants with data at the time point

FEV1 AUC 0-6 is the area under the effect-time curve from time 0 (pre-dose) up to 6 hours post-dose. The baseline was the average of the 2 pre-dose FEV1 measurements on that study day. The baseline-adjustment refers to change from baseline at each post dose timepoint recorded on Day 8. FEV1 was measured using spirometry. Spirometry assessments were obtained predose at -30 ± 5, and - 5 minutes, then post dose at 5 ± 2, 15 ± 5, 30 ± 5, 45 ± 5 minutes, and at 1hr ± 5 min, 2hr ± 5 min, 3hr ± 5 min, 4hr ± 5 min, 5hr ± 5 min, and 6hr ± 5 min.

Outcome measures

Outcome measures
Measure	Placebo MDPI n=78 Participants Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks.	Albuterol MDPI n=78 Participants Albuterol multi-dose dry powder inhaler (MDPI) at a dose of 720 micrograms per day administered as 2 inhalations of 90 mcg /inhalation four times a day for 12 weeks.
Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) on Day 8	0.26 L*hr Interval 0.03 to 0.49	0.99 L*hr Interval 0.76 to 1.22

SECONDARY outcome

Timeframe: Day 85

Population: Full analysis set of participants with data at the time point

FEV1 AUC 0-6 is the area under the effect-time curve from time 0 (pre-dose) up to 6 hours post-dose. The baseline was the average of the 2 pre-dose FEV1 measurements on that study day. The baseline-adjustment refers to change from baseline at each post dose timepoint recorded on Day 85. FEV1 was measured using spirometry. Spirometry assessments were obtained predose at -30 ± 5, and - 5 minutes, then post dose at 5 ± 2, 15 ± 5, 30 ± 5, 45 ± 5 minutes, and at 1hr ± 5 min, 2hr ± 5 min, 3hr ± 5 min, 4hr ± 5 min, 5hr ± 5 min, and 6hr ± 5 min.

Outcome measures

Outcome measures
Measure	Placebo MDPI n=77 Participants Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks.	Albuterol MDPI n=77 Participants Albuterol multi-dose dry powder inhaler (MDPI) at a dose of 720 micrograms per day administered as 2 inhalations of 90 mcg /inhalation four times a day for 12 weeks.
Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) on Day 85	0.06 L*hr Interval -0.15 to 0.28	0.74 L*hr Interval 0.53 to 0.96

SECONDARY outcome

Timeframe: Day 1 to Day 92

Population: Safety analysis set

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.

Outcome measures

Outcome measures
Measure	Placebo MDPI n=79 Participants Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks.	Albuterol MDPI n=78 Participants Albuterol multi-dose dry powder inhaler (MDPI) at a dose of 720 micrograms per day administered as 2 inhalations of 90 mcg /inhalation four times a day for 12 weeks.
Participants With Adverse Events Any adverse event	25 participants	22 participants
Participants With Adverse Events Severe adverse events	1 participants	1 participants
Participants With Adverse Events Treatment-related AE	1 participants	1 participants
Participants With Adverse Events Deaths	0 participants	0 participants
Participants With Adverse Events Other serious AEs	0 participants	0 participants
Participants With Adverse Events Withdrawn from study due to AEs	0 participants	0 participants

SECONDARY outcome

Timeframe: Day 1 (Baseline), Day 85

Population: Safety population. Only participants with both baseline and endpoint physical examination findings are summarized. Two placebo participants were missing endpoint physical examinations.

Physical exam was recorded as normal or abnormal based on physician assessment. Format for results is: Test Baseline/Endpoint HEENT = head, eyes, ears, nose, throat

Outcome measures

Outcome measures
Measure	Placebo MDPI n=77 Participants Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks.	Albuterol MDPI n=78 Participants Albuterol multi-dose dry powder inhaler (MDPI) at a dose of 720 micrograms per day administered as 2 inhalations of 90 mcg /inhalation four times a day for 12 weeks.
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group Lymph nodes Abnormal/Abnormal	0 participants	0 participants
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group Abdomen Abnormal/Abnormal	1 participants	0 participants
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group Musculoskeletal Normal/Normal	74 participants	76 participants
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group Musculoskeletal Normal/Abnormal	0 participants	1 participants
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group Musculoskeletal Abnormal/Normal	3 participants	1 participants
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group Musculoskeletal Abnormal/Abnormal	0 participants	0 participants
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group Skin Normal/Normal	75 participants	73 participants
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group Skin Normal/Abnormal	0 participants	1 participants
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group Skin Abnormal/Normal	2 participants	4 participants
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group Skin Abnormal/Abnormal	0 participants	0 participants
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group Lymph nodes Normal/Normal	77 participants	78 participants
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group Lymph nodes Normal/Abnormal	0 participants	0 participants
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group Lymph nodes Abnormal/Normal	0 participants	0 participants
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group General appearance Normal/Normal	76 participants	76 participants
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group General appearance Normal/Abnormal	0 participants	0 participants
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group General appearance Abnormal/Normal	1 participants	1 participants
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group General appearance Abnormal/Abnormal	0 participants	1 participants
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group HEENT Normal/Normal	46 participants	50 participants
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group HEENT Normal/Abnormal	12 participants	5 participants
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group HEENT Abnormal/Normal	11 participants	12 participants
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group HEENT Abnormal/Abnormal	8 participants	11 participants
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group Chest and Lungs Normal/Normal	66 participants	67 participants
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group Chest and Lungs Normal/Abnormal	8 participants	4 participants
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group Chest and Lungs Abnormal/Normal	2 participants	7 participants
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group Chest and Lungs Abnormal/abnormal	1 participants	0 participants
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group Heart Normal/Normal	76 participants	77 participants
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group Heart Normal/Abnormal	0 participants	0 participants
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group Heart Abnormal/Normal	1 participants	1 participants
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group Heart Abnormal/Abnormal	0 participants	0 participants
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group Abdomen Normal/Normal	75 participants	77 participants
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group Abdomen Normal/Abnormal	1 participants	0 participants
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group Abdomen Abnormal/Normal	0 participants	1 participants
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group Neurological Normal/Normal	76 participants	78 participants
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group Neurological Normal/Abnormal	1 participants	0 participants
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group Neurological Abnormal/Normal	0 participants	0 participants
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group Neurological Abnormal/Abnormal	0 participants	0 participants

SECONDARY outcome

Timeframe: Day 8, Day 85

Population: Safety population

For both standard and serial vital signs, participants were seated for at least 5 minutes before vital signs were assessed. Heart rate was obtained prior to the blood pressure measurement. Serial heart rate and blood pressure were conducted in the sitting position prior to the spirometry assessment; baseline measures were taken pre-dose at -30 ± 5 and -5 minutes on Day 1. Day 85 serial vital sign measures were taken in the sitting position prior to spirometry assessments pre-dose at -30 ± 5 and -5 minutes, then post-dose at 30 (±5) minutes, 1hr (± 10 min), 2hr (± 10 min), 3hr (± 10 min), 4hr (± 10 min), 5hr (± 10 min) and 6 hr (± 10 min). Serial heart rate and blood pressure measurements that were elevated to the following criteria were considered clinically significant: Systolic blood pressure: \> 160 beats/minute Diastolic blood pressure: \>100 beats/minute Heart rate: \>120 beats/minute

Outcome measures

Outcome measures
Measure	Placebo MDPI n=79 Participants Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks.	Albuterol MDPI n=78 Participants Albuterol multi-dose dry powder inhaler (MDPI) at a dose of 720 micrograms per day administered as 2 inhalations of 90 mcg /inhalation four times a day for 12 weeks.
Participants With Clinically Significant Vital Sign Assessments Systolic blood pressure - high	3 participants	0 participants
Participants With Clinically Significant Vital Sign Assessments Diastolic blood pressure - high	3 participants	1 participants
Participants With Clinically Significant Vital Sign Assessments Heart rate - high	0 participants	1 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 1, Day 8, Day 85

Albuterol MDPI

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Placebo MDPI

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Albuterol MDPI n=78 participants at risk Albuterol multi-dose dry powder inhaler (MDPI) at a dose of 720 micrograms per day administered as 2 inhalations of 90 mcg /inhalation four times a day for 12 weeks.	Placebo MDPI n=79 participants at risk Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks.
Infections and infestations Upper respiratory tract infection	3.8% 3/78 • Number of events 3 • Day 1 to Day 92	6.3% 5/79 • Number of events 5 • Day 1 to Day 92
Nervous system disorders Headache	3.8% 3/78 • Number of events 4 • Day 1 to Day 92	5.1% 4/79 • Number of events 5 • Day 1 to Day 92

Additional Information

Director, Clinical Research

Teva Branded Pharmaceutical Products, R&D Inc.

Phone: 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