Safety and Efficacy of Albuterol Administered by the Halix™ Dry Powder Inhaler in Subjects With Asthma
Condition: Asthma
MeSH terms: Asthma
Study type: Interventional
Phase: Phase 2

Summary: 
      Male and female subjects with mild to moderate asthma will be recruited to enroll in a 2-way
      crossover during which escalating doses of albuterol will be administered at 30 minute
      intervals on a single treatment day. Albuterol will be administered by the Halix albuterol
      unit dose disposable inhaler on one day and by Ventolin albuterol HFA MDI on the other day.
      Assignment to device for albuterol delivery will be by random allocation.
    

Detailed description: 
      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.
    

Intervention name(s): Halix albuterol 90 mcg; albuterol HFA MDI 90 mcg
Intervention type(s): Drug; Drug
Intervention description(s): albuterol unit dose disposable DPI delivers 90 mcg of albuterol in the excipient lactose with each inhalation. Albuterol 90 mcg will be given on one of the treatment days in cumulative doses up to a total dose of 720 mcg; albuterol HFA MDI delivers 90 mcg of albuterol with each inhalation. Albuterol 90 mcg will be given on one of the treatment days in cumulative doses up to a total dose of 1440 mcg
Other intervention name(s): Halix; Ventolin
Intervention MeSH terms: Albuterol
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: 2-way cumulative dose crossover
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Single-dose disposable dry powder inhaler