Bronchoprovocation Study to Demonstrate the Pharmacodynamic Bioequivalence of Albuterol Sulfate HFA Inhalation Aerosol (E.Q. 90 mcg of Albuterol Base/Inh) of Macleods Pharmaceuticals Ltd
brief summary
This is a pharmacodynamic bioequivalence bronchoprovocation study using single-dose, double-blind, double-dummy, randomized, study consisting of four study treatments (zero dose \[Placebo\], E.Q. 90 mcg Base dose of R inhalation aerosol, E.Q. 180 mcg Base dose of R inhalation aerosol, E.Q. 90 mcg Base dose of T inhalation aerosol) and four Periods (Period 1 to Period 4). Randomization procedure at Period 1 will assign any one study treatment to be administered in each Period in a cross-over manner. By the end of Period 4, a subject who completes dosing in all four Periods would have administered all four treatments in the study. The efficacy variable, post-dose PC20 obtained during each Period is the provocative concentration of the methacholine challenge agent required to reduce the FEV1 by 20% following administration of differing doses of albuterol (or placebo) by inhalation. The 20% reduction in FEV1 is determined as compared to post-saline FEV1 measured before the Placebo or Albuterol administration. The pharmacodynamic equivalence will be based on the dose-scale method of analysis of the post-dose PC20 If the 90% confidence interval for the relative bioavailability (F) falls within 67.00% -150.00% then it will be considered that pharmacodynamic equivalence is established.
detailed description
The study consists of screening period (up to 10 days) and four study treatments/ study treatment periods (Period 1, Period 2, Period 3, and Period 4) and a telephonic contact on 2nd day (±1 day) after Period 4 dosing day/last dose of study treatment.
To participate in the study, every subject must provide a signed written informed consent. After obtaining consent subject's eligibility to participate in the study will be confirmed during the screening period.
The study involves bronchoprovocation study using methacholine as challenge agent. Therefore a methacholine challenge test (MCT) will be conducted during screening and at each Period. A MCT involves four steps; Step 1 to Step 4.
In Step 1 (Pre-challenge): Pre-saline/Baseline spirometry will be conducted In Step 2 (saline): saline control test and spirometry: Subjects will be nebulized with normal saline for 1 minute by tidal breathing method. FEV1 will be obtained at about 30 seconds and 90 seconds post-nebulization.
In Step 3 (challenge) methacholine administration and spirometry: Subjects will be nebulized with doubling concentrations of methacholine for 1 minute. Nebulization will start from the lowest methacholine concentration followed by higher doubling concentration until FEV1 value reduces more than or equal to 20% relative to post-saline FEV1 or the highest methacholine concentration is administered or subject is clinically unstable (whichever comes first). After each concentration is nebulized, subject's heart rate will be measured using pulse oximeter and well-being will be checked. FEV1 will be obtained at about 30 seconds and 90 seconds post-nebulization of each methacholine concentration. FEV1 maneuver should meet the acceptability criteria. Each FEV1 will be checked for 20% fall relative to FEV1 obtained in Step 2.
In Step 4 (subject recovery and spirometry): Oral inhalations of recovery medication (Albuterol HFA inhalation aerosol \[E.Q. 90 mcg albuterol base/inh\]) will be administered to expedite the return of the FEV1 within 90% of FEV1 obtained in Step 1.
During the study Screening-MCT A will be conducted to assess airway responsiveness to methacholine demonstrated by pre-albuterol dose (baseline/Scr-MCTA) PC20 ≤1.56 mg/mL.
Screening-MCT B will be conducted to assess airway responsiveness to methacholine demonstrated by post-two-albuterol-doses (Albuterol HFA inhalation aerosol \[90 mcg of albuterol base/inh\] Period MCT will be conducted to obtain post-dose PC20 for the primary endpoint. Study treatment dosing will be administered after Step 2 is completed and before initiation of Step 3. Subjects will administer one oral inhalation from four different inhalers with one minute interval between each oral inhalation.
official title
A Prospective, Randomized, Single-dose, Double-blind, Double-dummy, Four-period, Four-treatment Crossover Pivotal Bronchoprovocation Study to Demonstrate the Pharmacodynamic Bioequivalence of Albuterol Sulfate HFA Inhalation Aerosol (E.Q. 90 mcg of Albuterol Base/Inh) (of Macleods Pharmaceuticals Ltd.) to Albuterol Sulfate HFA Inhalation Aerosol (E.Q. 90 mcg of Albuterol Base/Inh) (Distributed by Teva Pharmaceuticals USA, Inc.) in Adult Patients With Stable Mild Asthma