Relative Potency of Formoterol Novolizer® 12 µg Compared to Formoterol Aerolizer® 12 µg
Condition: Asthma
MeSH terms: Asthma
Intervention: Formatris 24µg; Formatris 12µg; Foradil P 24µg; Foradil P 12µg
Intervention description: 12µg Formoterol Novolizer#1 + 12µg Formoterol Novolizer#2 + Placebo Aerolizer#1 + Placebo Aerolizer #2; 12µg Formoterol Novolizer#1 + Placebo Novolizer#2 + Placebo Aerolizer#1 + Placebo Aerolizer #2; Placebo Novolizer#1 + Placebo Novolizer#2 + 12µg Formoterol Aerolizer#1 + 12µg Formoterol Aerolizer #2; Placebo Novolizer#1 + Placebo Novolizer#2 + 12µg Formoterol Aerolizer#1 + Placebo Aerolizer #2
Intervention MeSH terms: Formoterol Fumarate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 44.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to estimate the relative potency for bronchoprotective effect of
      formoterol Novolizer 12 µg (test) compared to formoterol Aerolizer 12 µg (reference).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female patients aged from 18 to 60 years (inclusive).

          2. Patients with asthma indicated by

               -  history of asthma symptoms and

               -  airway hyperresponsiveness to methacholine with a provocation concentration of
                  methacholine that cause a 20% decrease in FEV1 (PC20) ≤8 mg/ml at Visit 1.

          3. Patients with stable asthma condition with baseline forced expiratory volume in the
             first second (FEV1) ≥70% predicted at first visit.

          4. The PC20 methacholine should increase at least 4-fold after inhaling 24 μg of
             formoterol Aerolizer (2 applications of 12 μg) at Visit 2.

          5. Able to be taught correct inhalation technique for both devices at screening.

        Exclusion Criteria:

          1. Known hypersensitivity to formoterol, lactose, or methacholine.

          2. History of life-threatening asthma in the last three years.

          3. Major malignancies including pheochromocytoma within the last 5 years. Exception will
             be considered where malignancies have been resolved as judged by investigator.

          4. Pregnancy, breast-feeding, planned pregnancy during the study, or women of
             child-bearing potential not using adequate contraception. These methods include total
             abstinence (no sexual intercourse), oral contraceptives, an intrauterine device (IUD),
             an etonogestrel implant (Implanon), or medroxyprogesterone acetate injections
             (Depo-Provera shots). If one of these cannot be used, using contraceptive foam and a
             condom are recommended.

             Lack of suitability for the study:

          5. Screening visit 2 has to be postponed repeatedly.

          6. Evidence of respiratory tract infection within 4 weeks before the study (screening
             visit 1).

          7. Seasonal or episodic exposure to an allergen or occupational chemical sensitizer which
             are likely to vary in symptom presentation and severity during the course of the study
             (e.g. ragweed sensitive patients in Iowa during Aug-Oct). This does not apply to
             patients who can be well controlled on therapy.

          8. History of non-reversible pulmonary disease; chronic obstructive pulmonary disease
             (COPD), cystic fibrosis, bronchiectasis, or pulmonary fibrosis.

          9. History of severe cardiovascular, renal, neurologic, liver or endocrine dysfunction
             (patients with well-controlled hypertension, hypercholesterolemia, thyroid disease or
             diabetes may be included if medication for these diseases does not affect methacholine
             challenge or formoterol metabolism).

         10. History of hemophilia or coagulation disease.

         11. Electrocardiogram (ECG) abnormalities of clinical relevance, in particular abnormal
             prolongation of QT-interval (QTc according to Bazett in women ≥450 msec, in men ≥430
             msec).

         12. Potassium level below lower limit of laboratory normal range plus 0.3 mmol/l as safety
             margin.

         13. Exacerbation of bronchial asthma requiring emergency department visit or
             hospitalization during the last 3 months prior to this study.

         14. Prior or concomitant treatment with systemic glucocorticosteroids during the last 3
             months (a short course of oral corticosteroids for asthma is permissible if for <10
             days and at least 30 days have passed).

         15. Use of long-acting ß2-agonists in last 3 weeks before the first methacholine challenge
             or during the study

         16. Change in dosage of other controller therapy (inhaled glucocorticosteroids,
             leukotriene modifier, slow-release theophylline) during the last 3 weeks before the
             first methacholine challenge or during the study.

         17. Use of short-acting ß2-agonists more than thrice a week in the previous month.

         18. Inability to temporary withhold the following medications/substances before lung
             function test:

               -  short-acting ß2-agonists and short-acting anticholinergics at least 6 hours,

               -  regular long-acting ß2-agonists at least 3 weeks,

               -  long-acting anticholinergics at least 36 hours,

               -  inhaled glucocorticosteroids at least 2 hours

               -  Disodium cromoglycate (DSCG) at least 24 hours,

               -  slow release theophylline at least 48 hours,

               -  rapid release theophylline at least 24 hours,

               -  caffeine at least 4 hours

         19. Patients with aspirin induced bronchospasm.

         20. Any treatment with ß2-antagonists (including eye drops).

         21. Non-cooperative patients, inability to perform outcome measurement correctly.

         22. Inability to measure PC20 methacholine after 24 μg of formoterol Aerolizer (PC20 >128
             mg/ml).

         23. Current smokers or regular smokers during last 12 months or more than 10 pack-year
             history.

         24. Drug or alcohol abuse which would interfere with the patient's proper completion of
             the protocol assignment.

             Administrative reasons:

         25. Participation in another clinical study within 1 month prior to or during this study

         26. Lack of ability or willingness to give informed consent.

         27. Lack of willingness to have personal study related data collected, archived or
             transmitted according to protocol.

         28. Personnel involved in the planning or conduct of the study.

         29. Anticipated non-availability for study visits/procedures.