A Clinical Study to Evaluate Z7200 (Budesonide/Formoterol) Pharmacokinetics Profile in Healthy Volunteers
Condition: Asthma
Intervention: Z7200 without oral activated charcoal; Symbicort Turbohaler without oral activated charcoal; Z7200 with oral activated charcoal; Symbicort Turbohaler with oral activated charcoal
Intervention description: 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).
Intervention MeSH terms: Budesonide; Formoterol Fumarate; Budesonide, Formoterol Fumarate Drug Combination; Charcoal
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 90.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers

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.
    

Eligibility criteria:

        Main Inclusion Criteria:

          -  Male or female 18 to 45 years of age.

          -  If female, is currently not pregnant/breast feeding/ or attempting to become pregnant
             has a negative serum pregnancy test, or is of non-childbearing potential or is of
             child-bearing potential, willing to commit to using a consistent and acceptable method
             of birth control or is of child-bearing potential and not sexually active

          -  Body mass index (BMI) of 18.5 to 29.9 kg/m² inclusive and a body weight ≥50 kg.

        Main Exclusion Criteria:

          -  FEV1 value less than 80% of the predicted value and FEV1/FVC ratio <0.7.

          -  History or current evidence of a clinically significant disease or disorder capable of
             altering the absorption, metabolism, distribution or elimination of drugs.

          -  History or current evidence of a clinically significant disease including, but not
             limited to: cardiovascular, hepatic, renal, haematological, neuropsychological,
             endocrine, gastrointestinal or pulmonary.

          -  Presence of glaucoma, cataracts, ocular herpes simplex, malignancy, regardless of the
             clinical significance or current stability of the disease.

          -  History or presence of silent infections, including positive tests for HIV1, HIV2,
             Hepatitis B and Hepatitis C.

          -  Bacterial or viral infection of the upper respiratory tract (including the common cold
             and flu), sinus, or middle ear within 2 weeks of dosing.

          -  Lower respiratory tract infection/pneumonia within the past 3 months.

          -  Presence of any disease or condition or regular concomitant treatment (including
             vitamins and herbal products) known to interfere with the absorption, distribution,
             metabolism or excretion of drugs.

          -  Screening haemoglobin value of less than 1g/dL above the ULN (or 10g/L)

          -  History of recurrent vasovagal collapses.

          -  History of anaphylactic/anaphylactoid reactions.

          -  History of seizures including febrile seizures excluding childhood febrile
             convulsions.

          -  Unable to demonstrate proper inhalation techniques involved in using the delivery
             devices at screening.

          -  Exposure to any investigational drug within 90 days of the Screening Visit.

          -  Known or suspected hypersensitivity or idiosyncratic reaction to any steroid, any β2
             agonist,or to lactose monohydrate, leucine or Tween 80.

          -  History of allergy to milk protein.

          -  Use of an inhaled corticosteroid within 30 days or systemic corticosteroid within 60
             days of the Screening Visit.

          -  Use of medications or herbal medicines that are strong cytochrome P450 3A4 (CYP3A4)
             inhibitors or inducers within 30 days prior to Screening Visit

          -  Any clinically significant abnormal laboratory value or physical finding that may
             interfere with the interpretation of test results or cause a health risk for the
             subject if he/she participates in the study.

          -  Use of caffeine containing beverages more than 600 mg of caffeine/day.

          -  Current smokers or ex-smokers who have stopped smoking for less than 10 years.

          -  Recent or current (suspected) drug abuse or positive result in the drugs abuse test.

          -  Recent or current alcohol abuse (regular drinking more than 21 units per week for
             males and more than 14 units per week for females [1 unit = 4 cl spirits or
             equivalent]).

          -  Predictable poor compliance, intolerance to charcoal solution, or inability to
             communicate well with the study centre personnel or inability to participate in all
             treatment periods.

          -  The subject is not able to understand and comply with protocol requirements,
             instructions and protocol-stated restrictions, has participated in a clinical research
             study within the previous three months or has previously been enrolled in this study.