Clinical trial NCT01056159: A Cumulative Dose Study to Evaluate the Safety and Efficacy of Albuterol in a Dry Powder Inhaler and an HFA MDI (Hydrofluoroalkane Metered Dose Inhaler)
Official title: Cumulative Dose Comparison of the Efficacy and Safety of Albuterol in a Dry Powder Inhaler and an HFA MDI (Hydrofluoroalkane Metered Dose Inhaler) in Adult Patients With Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Asthma
Keywords: asthma
dry powder inhaler
short-acting beta2-agonist
SABA
bronchoconstriction
bronchodilation
bronchodilator
metered dose inhaler
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2010-01-26
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The study will measure the improvement in lung function in subjects with asthma after inhaling from two inhalers, Albuterol in a dry powder inhaler and albuterol in an HFA (hydrofluoroalkane), metered dose inhaler.

Detailed description: The study objective is to compare the efficacy and safety of albuterol in a dry powder inhaler (DPI) and albuterol in an HFA metered dose inhaler (MDI) after a cumulative dose of 1440mcg administered as 1+1+2+4+8 inhalations (90mcg per inhalation). Another study objective is to compare the pharmacokinetics (metabolism) of albuterol with the two inhalers. The pharmacokinetics of albuterol will be examined in half (24) of the study subjects. To participate in the study, patients must provide written informed consent, washout any prohibited medications and pass all the screen criteria. Once this is done, there will be two treatment visits. At each visit the subject will inhale with both types of inhalers. At each visit, one inhaler will have active drug (albuterol) and one inhaler will have placebo (dummy). The inhaler with the active drug will be switched at the two visits in a random manner. At each visit the subject will inhale with each inhaler a total of 16 times by a specific schedule. The subject will inhale from each inhaler once (1), wait 30 minutes, inhale from each inhaler once (1), wait 30 minutes, inhale from each inhaler twice (2), wait 30 minutes, inhale from each inhaler four times (4), wait 30 minutes, and then inhale from each inhaler eight times (8). The total time to complete the inhalations should be about 2 hours. Following that, there will be a series of assessments taken at regular times with vital signs measured up to 6 hours, ECG (electrocardiogram) assessed up to 4 hours, blood taken to measure potassium and glucose up to 4 hours, lung function evaluated with spirometry up to 6 hours, and for those subjects participating in the pharmacokinetic evaluation blood will be drawn up to 12 hours. The two study treatment visits will be 3 to 14 days apart. Following these visits, there will be a study concluding visit 1 to 5 days later.

Eligibility criteria: Inclusion Criteria:

* Must provide written informed consent,
* Must be between 18-45 years of age,
* Male or Female, females of non-child bearing potential or using reliable contraception
* Asthma for at least 6 months, FEV1 (forced expiratory volume in 1 second) between 50-80% of predicted value, and reversibility greater than or equal to 15% following 180mcg albuterol
* Stable low dose of Inhaled Corticosteroids
* Non-smoker
* Otherwise healthy
* Other criteria apply

Exclusion Criteria:

* Pregnant
* Allergic to albuterol or severe milk protein allergy
* ONLY for subject participating in PK assessments, must not have donated blood within 30 days.
* Other criteria apply

Primary outcomes:
measure: Baseline-adjusted forced expiratory volume in one second (FEV1) 30 minutes after each of the five cumulative doses
timeFrame: At the two study treatment visits, FEV1 (forced expiratory volume in 1 second) will be measured prior to drug administration and 5 times, once at 30 minutes after each of the 5 doses.
Secondary outcomes:
measure: Baseline-adjusted FEV1 (forced expiratory volume in 1 second) AUC0-6 (area under the serum concentration time curve from time 0 to 6 hours) following the administration of the final cumulative dose
timeFrame: At the two study treatment visits, FEV1 (forced expiratory volume in 1 second) will be measured prior to drug administration and 7 time points ( 30 minutes and 1,2,3,4,5 and 6 hours) after the 5th and final dose.
measure: ECGs (electrocardiogram) will assess the maximum and mean change from baseline of the corrected QT interval (QT interval measures the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle) following study drug.
timeFrame: Serial ECGs (electrocardiogram) will be taken at baseline (5 minutes pre-dose), 15 minutes after each dose, and also at 30 minutes, 60 minutes, 2, 3, and 4 hours following the last cumulative dose in order to calculate the corrected QT interval.
measure: Changes in blood pressure will be evaluated by the maximum change (systolic) and minimum change (diastolic) from baseline blood pressure, and the weighted mean change from baseline in systolic and diastolic blood pressure.
timeFrame: Serial measurements of systolic and diastolic blood pressure will be taken at baseline (15 minutes pre-dose), 15 minutes after each dose, and also at 30 minutes, 60 minutes, 2, 3, 4, 5, and 6 hours following the last cumulative dose.
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Teva Clinical Study Site
state: California
city: Los Angeles
country: United States
facility: Teva Clinical Study Site
state: California
city: Denver
country: United States
facility: Teva Clinical Study Site
state: Colorado
city: Lakewood
country: United States
facility: Teva Clinical Study Site
state: Colorado
city: Normal
country: United States
facility: Teva Clinical Study Site
state: Illinois
city: North Dartmouth
country: United States
facility: Teva Clinical Study Site
state: Massachusetts
city: Minneapolis
country: United States
facility: Teva Clinical Study Site
state: Minnesota
city: Bellevue
country: United States
facility: Teva Clinical Study Site
state: Nebraska
city: Lake Oswego
country: United States
facility: Teva Clinical Study Site
state: Oregon
Study officials:
affiliation: Teva Branded
name: Clinical Program Leader
role: STUDY_DIRECTOR
References: