Efficacy and Safety Study of Fluticasone Proponate Inhalation Solution in Adult and Adolescent Asthma
Condition: Asthma
MeSH terms: Asthma
Intervention: fluticasone propionate inhalation solution; budesonide suspension
Intervention description: 1 mg BID inhalation for 12 weeks with one possible chance to change to 0.5 mg BID; 2 mg BID inhalation for 12 weeks with one possible chance to change to 1 mg BID
Intervention MeSH terms: Fluticasone; Xhance; Budesonide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Investigator)
Enrollment: 316.0
Sex: All
Minimum age: 17 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: fluticasone propionate inhalation solution; budesonide suspension for inhalation; efficacy; severe persistent asthma; pharmacokinetics; safety

Summary:

      This is a multicentre, randomized, single-blind, active-controlled, parallel-group phase III
      local registration study for a treatment period of 12 weeks. This study aims to assess the
      effectiveness and safety of fluticasone propionate 1mg via nebulizer BID in treatment of
      Chinese adult and adolescent patients with severe persistent asthma for a treatment period of
      12 weeks versus budesonide 2mg via nebulizer BID. The steady-state plasma pharmacokinetics of
      fluticasone propionate inhalation solution will also be assessed.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Chinese male or female outpatients aged >=17 years and <=70 years

          -  A female is eligible to enter and participate in this study if she is:

        Non-childbearing potential (i.e. physiologically incapable of becoming pregnant, including
        any female who is pre-menarchal, post-menopausal), or Child-bearing potential, has a
        negative urinary pregnancy test at screening and agrees to take contraceptive precautions
        (including abstinence) (referring to appendix 1: Highly Effective Methods For Avoidance Of
        Pregnancy In Women Of Childbearing Potential) which, in the opinion of the investigator are
        adequate to prevent pregnancy during the study.

          -  A documented clinical history of asthma for a period of at least 12 weeks prior to
             Visit 1 based on the Guidance of Asthma Management and Prevention 2008 in China (refer
             to appendix 2).

          -  Demonstrated >=12% and >=200mL reversibility of FEV1 within 15-30minutes following
             inhalation of 200-400ug of salbutamol aerosol within 12 months prior to visit 1 or at
             the Screening Visit.

          -  Subjects have pre-bronchodilator FEV1% predicted between >=40% and <80% at visit 1.

          -  Subjects on a stable dose at least 2 weeks with high dose ICS (eg. Fluticasone
             Propionate 500ug twice daily or other ICS with equivalence doses, refer to Appendix 3)
             or moderate dose ICS plus LABA (eg. Fluticasone Propionate/Salmoterol 250/50ug , twice
             daily; or Budesonide/Formoterol Fumarate in maintainance160/4.5ug, two inhalation,
             twice daily; or other product equivalence doses).

          -  Subjects and/or their legally acceptable representative (if applicable) is willing to
             give informed consent to participate in the study, and having ability to comply with
             study procedures (including patients can use Nebulizer correctly, be able to
             understand and complete the diary cards and be able to record their PEF using a peak
             flow meter). The subjects and/or their legally acceptable representative (if
             applicable) will need to give additional informed consent to be eligible for blood
             pharmacokinetic samplings.

        Exclusion Criteria:

          -  History of Life-threatening asthma: Defined for this protocol as an asthma episode
             that required intubation and/or was associated with hypercapnea, respiratory arrest or
             hypoxic seizures.

          -  Bacterial or viral infection of the upper or lower respiratory tract, sinus or middle
             ear that is not resolved within 4 weeks of visit 1 and led to a change in asthma
             management or, in the opinion of the investigator, is expected to affect the subject's
             asthma status or the subject's ability to participate in the study.

          -  A subject must not have current evidence of pneumonia, pneumothorax, atelectasis,
             pulmonary fibrotic disease, bronchopulmonary dysplasia, chronic bronchitis, emphysema,
             chronic obstructive pulmonary disease, or other respiratory abnormalities other than
             asthma.

          -  Subjects have any clinically significant, uncontrolled condition or disease state
             that, in the opinion of the investigator, would put the safety of the patient at risk
             through study participation or would confound the interpretation of the efficacy
             results if the condition/disease exacerbated during the study.

          -  Subjects will not b eligible for the run-in if he/she has clinical visual evidence of
             candidias at visit 1.

          -  Current smoker or a smoking history of 10 pack years or more. A subject may not have
             used inhaled tobacco products (i.e., cigarettes, cigars or pipe tobacco) within the
             past 3 months.

          -  Patients who are pregnant or lactating.

          -  Patients having any known or suspected hypersensitivity to corticosteroids or the
             excipients of study drug, including Polysorbate 20, Sorbitan monolaurate, Monosodium
             phosphate dehydrate, Dibasic sodium phosphate anhydrous, Sodium Chloride and Water for
             Injection.

          -  Patients who have evidence of alcohol abuse.

          -  Patients who will have a pre-planned surgery operation in 6 months.

          -  Liver function tests: aspartate aminotransferase (AST) / alanine aminotransferase
             (ALT) >= 2 × upper limit of normal (ULN) or alkaline phosphatase (ALP) / bilirubin
             >1.5 × ULN (isolated bilirubin >1.5 × ULN is acceptable if bilirubin is fractionated
             and direct bilirubin <35%).

          -  Has QTc >= 450 msec or >= 480 msec for patients with bundle branch block at the time
             of screening.

          -  A subject will not be eligible for this study if he/she is an immediate family member
             of the participating Investigator, sub Investigator, study coordinator, or employee of
             the participating Investigator.

          -  No subject is permitted to perform night shift work from Visit 1 until completion of
             the study treatment period.

          -  Use of the following medications within the following time intervals prior to visit 1
             or during the study: Medication / No use within the following time intervals prior to
             Screening (Visit 1) or at any time during the study Systemic or oral corticosteroids /
             2 weeks Depot corticosteroids /12 weeks Anti-IgE (e.g. Xolair)/ 12 weeks Oral
             long-acting beta2-agonists (e.g. bambuterol) and inhaled long-acting beta2-agonists
             (e.g. salmeterol, formoterol) or combination products containing inhaled long-acting
             beta2-agonists (e.g. Seretide, Symbicort) / 12 hours (the stable dose of ICS/LABA
             combination within 2 weeks prior to Visit 1 could be continued during the run-in
             period) Theophyllines, slow-release bronchodilators, anticholinergics, ketotifen,
             nedocromil sodium, sodium cromoglycate, Anti-leukotrienes including suppressors of
             leukotriene production and antagonists / 1 day Inhaled short-acting beta2-agonist / 4
             hours (salbutamol will be supplied for rescue during the study) Potent Cytochrome P450
             3A4 inhibitors(e.g. ritonavir, ketoconazole, itraconzole) / 4 weeks Prescription or
             over the counter medication that would significantly affect the course of asthma, or
             interact with sympathomimetic amines, such as: anticonvulsants (barbiturates,
             hydantoins, carbamazepine); polycyclic antidepressants; beta-adrenergic blocking
             agents; phenothiazines and monoamine oxidase (MAO) inhibitors /1 day Chinese
             traditional medicines used for treatment of asthma and other allergic diseases / 1
             week Any other investigational drug / 30 days or within 5 half lives, whichever is
             longer