Trial Outcomes & Findings for A Dose-ranging Study to Evaluate Albuterol and Hydrofluoroalkane in Subjects Ages 12 and Older With Persistent Asthma (NCT NCT01058863)

Last Updated: 2021-11-09

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. The baseline for each study day was the average of the 2 pre-dose FEV1 measurements on that study day. The first baseline spirometry was obtained between 6-11 AM. The highest FEV1 value from two acceptable values was captured for calculation of the efficacy endpoints. Assessments were obtained at approximately 0.5 hours and immediately before dosing, and 5 minutes, 0.25, 0.50, 0.75, 1, 2, 3, 4, 5 and 6 hours after completion of dosing.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

72 participants

Primary outcome timeframe

Day 1 up to Day 30

Results posted on

2021-11-09

Participant Flow

A total of 163 patients were screened and 72 patients were randomized. Most screening failures did not qualify for the study based on reversibility or spirometry criteria.

Participant milestones

Participant milestones
Measure	All Randomized Participants Participants were randomized to one of ten treatment sequences, which indicated the order of the 5 single-dose treatments administered in this 5-way crossover study.
Overall Study STARTED	72
Overall Study Safety and ITT Populations	71
Overall Study Treated With Albuterol Spiromax® 90 mcg	68
Overall Study Treated With Albuterol Spiromax® 180 mcg	68
Overall Study Treated With ProAir® HFA 90 mcg	70
Overall Study Treated With ProAir® HFA 180 mcg	68
Overall Study Treated With Placebo Inhaler	69
Overall Study COMPLETED	68
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Reasons for withdrawal
Measure	All Randomized Participants Participants were randomized to one of ten treatment sequences, which indicated the order of the 5 single-dose treatments administered in this 5-way crossover study.
Overall Study Lost to Follow-up	1
Overall Study Withdrawal by Subject	1
Overall Study Sponsor requested withdrawal	1
Overall Study Randomized in error	1

Baseline Characteristics

A Dose-ranging Study to Evaluate Albuterol and Hydrofluoroalkane in Subjects Ages 12 and Older With Persistent Asthma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Randomized Treated Participants n=71 Participants Participants were randomized to one of ten treatment sequences, which indicated the order of the 5 single-dose treatments administered in this 5-way crossover study.
Age, Continuous	43.3 years STANDARD_DEVIATION 14.78 • n=5 Participants
Age, Customized 12 to <18 years	3 participants n=5 Participants
Age, Customized 18 to 65 years	64 participants n=5 Participants
Age, Customized >65 years	4 participants n=5 Participants
Sex: Female, Male Female	41 Participants n=5 Participants
Sex: Female, Male Male	30 Participants n=5 Participants
Race/Ethnicity, Customized White	54 participants n=5 Participants
Race/Ethnicity, Customized Black or African American	16 participants n=5 Participants
Race/Ethnicity, Customized Asian	1 participants n=5 Participants
Race/Ethnicity, Customized Not Latino or Hispanic	67 participants n=5 Participants
Race/Ethnicity, Customized Latino or Hispanic	4 participants n=5 Participants
Height	169.1 cm STANDARD_DEVIATION 9.49 • n=5 Participants
Weight	89.6 kg STANDARD_DEVIATION 22.77 • n=5 Participants

PRIMARY outcome

Timeframe: Day 1 up to Day 30

Population: Intent to treat population: randomized participants who received at least 1 dose of randomized study medication and had at least 1 post-baseline assessment

Outcome measures

Outcome measures
Measure	Albuterol Spiromax® 90 mcg n=68 Participants A single dose of albuterol 90 mcg delivered with Spiromax®, an inhalation-driven, multi-dose dry powder inhaler. Placebo inhalers used to maintain the blind.	Albuterol Spiromax® 180 mcg n=68 Participants A single dose of albuterol 180 mcg delivered with Spiromax®, an inhalation-driven, multi-dose dry powder inhaler (2 inhalations). Placebo inhalers used to maintain the blind.	ProAir® HFA 90 mcg n=70 Participants A single dose of albuterol 90 mcg delivered with ProAir®, a 'press-and-breathe', metered-dose, aerosol inhaler. Placebo inhalers used to maintain the blind.	ProAir® HFA 180 mcg n=68 Participants A single dose of albuterol 180 mcg delivered with ProAir®, a 'press-and-breathe', metered-dose, aerosol inhaler (2 inhalations). Placebo inhalers used to maintain the blind.	Placebo Inhaler n=69 Participants Placebo delivered with Spiromax®, an inhalation-driven, multi-dose dry powder inhaler, and with ProAir®, a 'press-and-breathe', metered-dose, aerosol inhaler. Placebo inhalers used to maintain the blind.
Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6)	1.21 L*hour Standard Error 0.224	1.39 L*hour Standard Error 0.224	1.12 L*hour Standard Error 0.223	1.33 L*hour Standard Error 0.224	0.24 L*hour Standard Error 0.224

SECONDARY outcome

Timeframe: Day 1 up to Day 30

Population: Intent to treat population: randomized participants who received at least 1 dose of randomized study medication and had at least 1 post-baseline assessment

Percent-predicted FEV1 AUC 0-6 is the area under the effect-time curve from time 0 (pre-dose) up to 6 hours post-dose. Percent-predicted FEV1 is the expected FEV1 taking into account age, height, gender and race, as per the National Health and Nutrition Examination Survey III (NHANES III) reference values. The first baseline spirometry was obtained between 6-11 AM. The highest FEV1 value from two acceptable values was captured for calculation of the efficacy endpoints. Assessments were obtained at approximately 0.5 hours and immediately before dosing, and 5 minutes, 0.25, 0.50, 0.75, 1, 2, 3, 4, 5 and 6 hours after completion of dosing.

Outcome measures

Outcome measures
Measure	Albuterol Spiromax® 90 mcg n=68 Participants A single dose of albuterol 90 mcg delivered with Spiromax®, an inhalation-driven, multi-dose dry powder inhaler. Placebo inhalers used to maintain the blind.	Albuterol Spiromax® 180 mcg n=68 Participants A single dose of albuterol 180 mcg delivered with Spiromax®, an inhalation-driven, multi-dose dry powder inhaler (2 inhalations). Placebo inhalers used to maintain the blind.	ProAir® HFA 90 mcg n=70 Participants A single dose of albuterol 90 mcg delivered with ProAir®, a 'press-and-breathe', metered-dose, aerosol inhaler. Placebo inhalers used to maintain the blind.	ProAir® HFA 180 mcg n=68 Participants A single dose of albuterol 180 mcg delivered with ProAir®, a 'press-and-breathe', metered-dose, aerosol inhaler (2 inhalations). Placebo inhalers used to maintain the blind.	Placebo Inhaler n=69 Participants Placebo delivered with Spiromax®, an inhalation-driven, multi-dose dry powder inhaler, and with ProAir®, a 'press-and-breathe', metered-dose, aerosol inhaler. Placebo inhalers used to maintain the blind.
Baseline-adjusted Percent-Predicted Forced Expiratory Volume in 1 Second (PPFEV1) Area Under the Curve (AUC 0-6)	35.31 % predicted * hour Standard Error 4.497	41.05 % predicted * hour Standard Error 4.495	33.19 % predicted * hour Standard Error 4.461	40.68 % predicted * hour Standard Error 4.496	7.58 % predicted * hour Standard Error 4.482

SECONDARY outcome

Timeframe: Day 1 up to Day 37

Population: Safety population of all randomized participants who received at least one dose of randomized study medication.

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. 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.