Safety and Efficacy of Albuterol Administered by the Halix™ Dry Powder Inhaler in Subjects With Asthma

Study Design: This is a phase 2A, open label, cumulative dose, randomized 2-way crossover study designed to assess the safety, efficacy, pharmacodynamics, pharmacokinetics (PK), and extrapulmonary pharmacodynamics of cumulative doses of Halix™ albuterol 90mcg compared with cumulative doses of Ventolin HFA MDI. After completing all screening assessments and meeting all eligibility criteria \[including SABA-free screening forced expiratory volume in 1 second (FEV1) ≥50% to \<85% of that predicted for age, gender, height, and ethnicity\], enrolled subjects will withdraw from use of Ventolin MDI with substitution of Atrovent HFA as the only inhaled bronchodilator for at least 72 hours before each of 2 Treatment Days. On each Treatment Day study treatments will consist of single doses of study drug (albuterol) administered at 30-minute intervals as follows: Halix™ albuterol UDDI - 1 + 1 + 2 + 4 inhalations \[90 mcg per inhalation\] Ventolin albuterol MDI -- 2 + 2 + 4 + 8 inhalations \[90 mcg (1 puff) per inhalation\] The order in which each treatment will be administered to a subject will be based on randomization to one of 2 possible sequences. Equal numbers of subjects will be assigned to each sequence. The beginning of each Treatment Day will be separated by a washout period of at least 72 hours after the preceding Treatment Day; the washout period not to exceed 240 hours. After Treatment Day 2, subjects will be assessed at an End-of-Study (EOS) Visit which will occur 1 to 5 days after the last administration of study drug. Prior to each Treatment Day, the subject must not have used \>8 actuations of (non-study drug) rescue Ventolin MDI on each of 3 or more days during the previous 7 days and must not have used any non-study drug rescue Ventolin MDI during the 72 hours prior to the start of the Treatment Day. The Treatment Day will not proceed if either of these instances has occurred. Within the 75 minutes prior to the first study drug dose on each of the 2 Treatment Days, the following procedures will be performed: vital signs (BP and HR), ECG, collection of urine for pregnancy test if subject is a WOCBP, collection of blood for baseline glucose, potassium, and PK, and spirometry at 60 minutes and at 30 minutes prior to the anticipated time of first study drug dose. The average of the FEV1 at 60 minutes and 30 minutes prior to the first study drug dose on Treatment Day 1 must be ≥ 50% and \< 85% of percent predicted in order for the Treatment Day to proceed. On Treatment Day 2, the average of the FEV1 at 60 minutes and 30 minutes obtained predose must be ≥ 50% and \<85% of predicted in order for Treatment Day 2 to proceed. After the first study drug dose on Treatment Day 1 and on Treatment Day 2, and after each of the following two cumulative doses on each Treatment Day, subjects will undergo spirometry at 5 (+ 2) minutes and at 25 (+/- 2) minutes post-dose. Blood for glucose, potassium and PK sample will be collected at 15 (+/- 5) minutes after the first study drug dose and after each of the following two cumulative doses and vital signs and ECG will be performed at 15 (+/- 5) minutes after the first study drug dose and after each of the following two cumulative doses. Following the last cumulative study drug dose on each Treatment Day, blood for PK sample will be collected at 10, 20, 45, 120, 180, 240, 300, 360, 480, 600 and 720 minutes after the last dose. After the last cumulative dose, spirometry will be performed at 5 (+ 2) minutes and at 25 (+/- 2) minutes. ECG and vital signs will be performed at 15 (+/-5) minutes after the last cumulative dose. After the last cumulative dose, blood will be collected for glucose and potassium at 45 and 120 minutes. Vital signs (BP and HR) will be measured hourly after the last cumulative dose up to 360 minutes and at 480, 600, and 720 minutes after the last dose. The time of each study drug dose will be recorded as the time of the last inhalation of study drug for each individual cumulative dose administered when multiple inhalations are required to administer the dose. After Treatment Day 2, subjects will be assessed at an End-of-Study (EOS) that will occur 1 to 5 days after the day of the last administration of study drug.