Therapeutic Equivalence of Two Formulations of Fluticasone Propionate and Salmeterol Inhalation Powder in Subjects With Asthma
Condition: Asthma
MeSH terms: Asthma
Intervention: Fluticasone Propionate and Salmeterol Inhalation Powder; Fluticasone Propionate and Salmeterol Inhalation Powder; Placebo Inhalation Powder
Intervention description: 100/50 mcg per actuation; 100/50 mcg per actuation; No active content
Intervention MeSH terms: Fluticasone; Xhance; Salmeterol Xinafoate; Fluticasone-Salmeterol Drug Combination
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 999.0
Sex: All
Minimum age: 12 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      A randomized, multiple-dose, blinded, placebo-controlled, parallel-group, multiple-center
      bioequivalence study with pharmacodynamic endpoints
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or non-pregnant, non-lactating female, ≥ 12 years and ≤ 75 years of age.

          2. Signed informed consent form that meets all criteria of current Food and Drug
             Administration (FDA) regulations. For subjects who are considered minors in the state
             the study is being conducted (< 18 years in most states), the parent or legal guardian
             should sign the consent form and the child will be required to sign a subject "assent"
             form.

          3. Body mass index (BMI) between 18 kg/m2 and 39 kg/m2, inclusive, for subjects > 18
             years old. For subjects 12 to 18 years old, BMI between 15 kg/m2 and 35 kg/m2,
             inclusive.

          4. Female subjects who are of non-childbearing potential must meet one of the following
             criteria:

               -  surgically sterile (e.g., bilateral oophorectomy, tubal ligation, hysterectomy or
                  permanent sterilization procedures), with the procedure performed at least 3
                  months before initial dosing

               -  naturally postmenopausal (no menses) for at least 1 year before initial dosing
                  and/or has a documented FSH level ≥ 40 mIU/mL at screening

               -  pre-menarchal

          5. Females of childbearing potential must not be pregnant or lactating at Screening or
             Randomization as confirmed by a negative serum pregnancy test with a sensitivity of 25
             mIU/mL of human chorionic gonadotropin at Screening, and a negative urine pregnancy
             test with a sensitivity of less than 50 mIU/mL at all other visits. The subject may
             enter the placebo run-in period prior to receipt of test results at Screening, if not
             yet received from the clinical laboratory, but should be evaluated by the Investigator
             for continued participation once test results are received.

             Women of childbearing potential must agree to the use of a reliable method of
             contraception (e.g., total abstinence, intrauterine device, a double-barrier method,
             oral, transdermal, injected or implanted non- or hormonal contraceptive), throughout
             the study. A sterile sexual partner is not considered an adequate form of birth
             control. Subjects on hormonal contraceptives must have been on the same hormonal
             contraceptive for at least one month before the Screening and continue throughout the
             duration of the study.

          6. Diagnosis of asthma (based on National Asthma Education and Prevention Program [NAEPP]
             guidelines) at least 12 weeks before Screening.

          7. Pre-bronchodilator FEV1 ≥ 40% and ≤ 85% of predicted at Screening and Randomization.

          8. Airway reversibility ≥ 15% of FEV1 within 30 minutes after receiving 4 puffs of
             albuterol inhalation (360 mcg, pressurized metered-dose inhaler) at Screening.

          9. Able to discontinue use of their asthma medications during the run-in period and for
             the remainder of the study.

         10. Able to replace current short-acting beta-agonists [SABAs] with the study supplied
             salbutamol/albuterol rescue inhaler for use as needed for the duration of the study.
             Subjects must be able to withhold all SABAs for at least 6 hours before lung function
             assessments on study visits.

         11. Able to continue on stable regimen of theophylline for the duration of the study and
             able to withhold theophylline as judged by the Investigator for the required time
             intervals before study visits. See Section 10.2.4 for required washouts.

         12. Able to discontinue oral corticosteroids, parenteral corticosteroids and oral SABAs
             for the time intervals before study visits as specified in Section 10.2.4.

         13. Able to perform valid and reproducible pulmonary function tests as per ATS American
             Thoracic Society including no evidence of spirometry effort-induced
             bronchoconstriction.

         14. Currently non-smoking (including vapor cigarettes), no use of any tobacco products
             within 1 year prior to Screening and has ≤ 10 pack-years smoking of historical use
             (i.e., one pack per day for 10 years).

         15. Ability to use the inhalation products correctly.

        Exclusion Criteria:

          1. Life-threatening asthma, defined as a history of asthma episode(s) requiring
             intubation, and/or associated with hypercapnoea; respiratory arrest or hypoxic
             seizures, asthma related syncopal episode(s), or asthma-related hospitalizations
             within one year before Screening or during the run-in period.

          2. Allergy or significant history of hypersensitivity, idiosyncratic reactions, or
             intolerance to any sympathomimetic drug (e.g., salmeterol or albuterol), or any
             inhaled, intranasal, or systemic corticosteroid therapy, or milk proteins.

          3. History of cystic fibrosis, bronchiectasis, or co-morbid respiratory or sinus
             diseases, including chronic obstructive pulmonary disease, chronic bronchitis,
             emphysema, tuberculosis, pulmonary carcinoma, pulmonary fibrosis, pulmonary
             hypertension that, in the opinion of the Investigator, would compromise subject safety
             or interfere with the evaluations.

          4. Evidence of viral or bacterial upper or lower respiratory tract infections (e.g.,
             pneumonia, viral bronchitis, sinobronchitis, etc.), sinus infection, or middle ear
             infection within four weeks before Screening or during the run-in period.

          5. Current evidence or history of cardiovascular disorders, including uncontrolled
             hypertension, uncontrolled coronary artery disease, known aortic or cerebral aneurysm,
             myocardial infarction or stroke, and/or current coronary insufficiency that, in the
             opinion of the Investigator, would compromise subject safety or interfere with the
             evaluations.

          6. Cardiac arrhythmia or 12-lead ECG abnormalities that, in the opinion of the
             Investigator, would compromise subject safety or interfere with the evaluations; or a
             QTc > 440 ms for males and > 460 ms for females using Fredericia formula.

          7. Subjects receiving or who may require during the study non-potassium sparing diuretics
             or medications with the potential to affect the course of asthma or to interact with
             sympathomimetic amines within 30 days before Screening. Examples include but not
             limited to beta blockers, oral decongestants, benzodiazepines, digitalis,
             phenothiazines, polycyclic antidepressants, monoamine oxidase inhibitors.

          8. History of posterior subcapsular cataracts or glaucoma that, in the opinion of the
             Investigator, would compromise subject safety.

          9. Any clinically significant finding on physical exam or clinical labs that, in the
             opinion of the Investigator, would compromise subject's safety or data integrity.

         10. History or current evidence of significant renal, hepatic, cardiovascular (including
             ECG with evidence of ischemic heart disease, congestive heart failure, and cardiac
             dysrhythmia), neurologic, hematologic, endocrine, psychiatric dysfunction, or any
             other significant medical illness or disorder in the opinion of the Investigator,
             would compromise subject safety or interfere with the evaluations.

         11. History of convulsive disorders.

         12. History of hyperthyroidism.

         13. History of uncontrolled diabetes.

         14. History of paradoxical bronchospasm.

         15. Use of inhaled SABAs within 6 hours before Screening or use of rescue medication
             within 6 hours before Randomization.

         16. Use of oral SABAs within 12 hours before Screening.

         17. Use of oral or parenteral corticosteroids within one month before Screening.

         18. Use of muscarinic beta2-agonists (MABAs), ipratropium bromide, or ipratropium bromide
             with albuterol within 24 hours before Screening.

         19. Use of cromolyn sodium within 24 hours before Screening.

         20. Use of antihistamines (other than cetirizine, desloratadine, or diphenhydramine),
             including fexofenadine and loratadine, within 48 hours before Screening or
             Randomization.

         21. Use of cetirizine within 36 hours before Screening or Randomization.

         22. Use of desloratadine within 96 hours before Screening or Randomization.

         23. Use of diphenhydramine within 24 hours before Screening or Randomization.

         24. Use of inhaled long-acting beta2-agonists (LABAs) (e.g., salmeterol, formoterol) or
             combination products containing bronchodilators (e.g., Symbicort) within 24 hours
             before Screening.

         25. Use of tiotropium within one week before Screening.

         26. Exercise within 6 hours before Screening.

         27. Use of leukotriene modifiers within 24 hours before Screening.

         28. Any surgery within 6 months before Screening that, in the opinion of the Investigator,
             would compromise subject safety or integrity of the study data.

         29. Biological treatment for asthma, approved or investigational 6 months before Screening
             and throughout the study.

         30. Receipt of any drug as part of a research study within 30 days before Screening.

         31. Positive test results for drugs of abuse, alcohol or cotinine at Screening. Exceptions
             will be permitted for positive screens for opiates or stimulants provided there is a
             documented prescription for the patient with supporting medical history and diagnosis.

         32. Employees of the Investigator or research center or their immediate family members.

         33. Previous participation in this study.

         34. Inability to understand the requirements of the study and the relative information and
             are unable or not willing to comply with the study protocol.