A Clinical Study to Evaluate Z7200 (Budesonide/Formoterol) Pharmacokinetics Profile in Healthy Volunteers
Condition: Asthma
Study type: Interventional
Phase: Phase 1

Summary: 
      The primary objective was:

      - to assess the bioequivalence of a single dose (two inhalations) of the test product
      compared to the reference product, with and without charcoal blockade.

      The secondary objectives were:

        -  to assess the pharmacokinetic profile of budesonide and formoterol in plasma after a
           single dose (two inhalations) of the test product and the reference product, with and
           without charcoal blockade.

        -  to assess the safety and tolerability of the test product and the reference product,
           with and without charcoal blockade.
    

Detailed description: 
      This was a single center, open label, randomized, five-period crossover, single-dose study in
      healthy volunteers aged 18 to 45 years. A total of 90 volunteers were enrolled, with 9
      subjects in each of the 10 treatment sequences.

      The study consisted of 5 treatment periods, each lasting approximately 48h, separated by a
      washout period of a minimum of 5 days. RS01 and/or Symbicort Turbohaler device use training
      was provided on Day -1 and Day 1 of each treatment period. Subjects were screened for
      eligibility to participate in the study -28 to -2 days prior to the first treatment period,
      and were randomized to one of 10 treatment sequencies containing the following 5 treatment
      arms on Day 1 of the first treatment period:

      Treatment A: Z7200 without oral activated charcoal* Treatment B1: Symbicort 1 without oral
      activated charcoal* Treatment B2: Symbicort 2 without oral activated charcoal* Treatment C:
      Z7200 with oral activated charcoal** Treatment D: Symbicort with oral activated charcoal**

      Subjects were admitted to the clinical unit at 8.00 on the morning of Day -1, and were dosed
      on the morning of Day 1 following an overnight fast (minimum of 8h). On Day 2, following
      collection of the 24-h PK blood sample, subjects were discharged.

      * Subjects who received treatments A, B1 and B2 rinsed their mouth vigorously with 50 mL
      water for 3 to 5 sec immediately after the second inhalation.

      ** A charcoal blockade was used to prevent absorption from oropharyngeal and GI tract, in
      order to assess the pulmonary deposition of budesonide and formoterol, with periods performed
      without a charcoal blockade allowing the assessment of the total systemic exposure to the
      drug.
    

Intervention name(s): Z7200 without oral activated charcoal; Symbicort Turbohaler without oral activated charcoal; Z7200 with oral activated charcoal; Symbicort Turbohaler with oral activated charcoal
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): 160 ug budesonide and 4.5 ug formoterol fumarate dihydrate, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler (Treatment A).; 320 ug budesonide and 9 ug formoterol fumarate dihydrate, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation (Treatments B1 and B2).; 160 ug budesonide and 4.5 ug formoterol fumarate dihydrate, administered as two inhalations (2 x Z7200 capsules) of budesonide 80 ug/inhalation and formoterol 2.25 ug/inhalation, using an RS01 inhaler with a charcoal blockade (Treatment C).; 320 ug budesonide and 9 ug formoterol fumarate dihydrate, administered as two inhalations of budesonide 160 ug/inhalation and formoterol 4.5 ug/inhalation from a Symbicort Turbohaler, with charcoal blockade (Treatment D).
Other intervention name(s): budesonide/formoterol; budesonide/formoterol; budesonide/formoterol with coadministration of charcoal; budesonide/formoterol with coadministration of charcoal
Intervention MeSH terms: Budesonide; Formoterol Fumarate; Budesonide, Formoterol Fumarate Drug Combination; Charcoal
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment