The pharmacokinetics study aims to evaluate the safety of Z7200 (budesonide/formoterol) in
comparison with Symbicort Turbohaler (budesonide/formoterol), assessing the bioequivalence
of the two products. Namely the study will compare the total systemic bioavailability (as an
indicator of safety), and it will compare the pulmonary bioavailability (as a possible
surrogate indicator of efficacy). This study will be performed in healthy subjects.
Minimum age: 18 Years.
Maximum age: 45 Years.
Gender(s): Both.
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.