Long-Term Safety Study of Fluticasone Propionate (Fp) Multidose Dry Powder Inhaler (MDPI) and Fluticasone Propionate/Salmeterol (FS) MDPI in Patients With Persistent Asthma
Condition: Persistent Asthma
MeSH terms: Asthma
Intervention: Fp MDPI; FS MDPI; FLOVENT HFA; ADVAIR DISKUS; albuterol/salbutamol HFA
Intervention description: Fp MDPI is an inhalation-driven multidose dry powder inhaler (MDPI) containing fluticasone propionate dispersed in a lactose monohydrate excipient.
During the treatment period, participants were randomized to either 100 mcg or 200 mcg of Fp one inhalation twice a day for a total daily dose of 200 mcg or 400 mcg. Study drug was administered in the morning and in the evening.; FS MDPI is an inhalation-driven multidose dry powder inhaler (MDPI) containing fluticasone propionate (Fp) and salmeterol xinafoate (Sx) dispersed in a lactose monohydrate excipient.
During the treatment period, participants were randomized to either Fp/Sx MDPI 100/12.5 mcg or Fp/Sx MDPI 100/12.5 mcg twice a day for a total daily dose of 200/25 mcg or 400/25 mcg Fp/Sx. Study drug was administered in the morning and in the evening.; FLOVENT HFA is a hydrofluoroalkane (HFA) inhaler containing fluticasone propionate.
During the treatment period, participants were randomized to either 110 mcg or 220 mcg of FLOVENT two puffs, twice a day for a total daily dose of 440 mcg or 880 mcg. Study drug was administered in the morning and in the evening.; ADVAIR DISKUS contains a dry powder formulation of fluticasone propionate (Fp) and salmeterol xinafoate (Sx) in a lactose excipient.
During the treatment period, participants were randomized to Fp 250 mcg/Sx 50 mcg or Fp 500 mcg/Sx 50 mcg one inhalation, twice a day for a total daily dose of 500/100 mcg or 1000/100 mcg. Study drug was administered in the morning and in the evening.; A short-acting β2-adrenergic agonists (SABA), albuterol/salbutamol hydrofluoroalkane (HFA) metered dose inhaler (MDI), was provided to be used as needed for the relief of asthma symptoms during both the run-in and treatment periods (to replace the subject's current rescue medication).
Intervention MeSH terms: Fluticasone; Xhance; Albuterol; Salmeterol Xinafoate; Fluticasone-Salmeterol Drug Combination; Adrenergic Agonists
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 758.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No

Summary:

      The primary objective of the study is to evaluate the long-term safety of fluticasone
      propionate (Fp) inhalation powder in 2 strengths and fluticasone propionate/salmeterol
      inhalation (FS) powder in 2 strengths when administered with the Teva multidose dry powder
      inhaler (MDPI) device over 26 weeks in patients with persistent asthma.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Best pre-bronchodilator forced expiratory volume in 1 second (FEV1) of greater than
             40% of their predicted normal value.

          2. Patients must have a treatment regimen that includes a short-acting β2 agonist (SABA)
             (albuterol) for use as needed and either an inhaled corticosteroid (ICS) or an
             ICS/long-acting β2 agonist (LABA) as a preventative treatment for a minimum of 8 weeks
             before the SV. Patients currently taking low-dose ICS without LABA are not eligible
             for this study. Patients currently taking low-dose ICS/LABA may only be entered into
             the mid ICS strength. All patients must have been maintained on a stable dose of ICS
             or ICS/LABA for 4 weeks prior to the SV (or pre-SV if necessary) at 1 qualifying doses

          3. To meet reversibility of disease criteria, the patient must demonstrate a ≥12%
             reversibility of FEV1 (and 200 mL for patients aged18 years and older) within 30
             minutes following 4 inhalations of albuterol at the SV. Historic reversibility within
             the past 12 months of the SV may be used to meet this criterion.

          4. Written informed consent/assent is obtained. For adult patients (aged 18 years and
             older, or as applicable per local regulations), the written informed consent form
             (ICF) must be signed and dated by the patient before conducting any study-related
             procedure. For minor patients (aged 12 to 17 years, or as applicable per local
             regulations), the written ICF must be signed and dated by the parent/legal guardian
             and the written assent form must be signed and dated by the patient (if applicable)
             before conducting any study-related procedure. Note: Age requirements are as specified
             by local regulations.

          5. Outpatient >= 12 years of age on the date of consent/assent. .

          6. Asthma diagnosis: The patient has a diagnosis of asthma as defined by the National
             Institutes of Health (NIH). The asthma diagnosis has been present for a minimum of 3
             months and has been stable (defined as no exacerbations and no changes in medication)
             for at least 30 days before providing informed consent.

          7. The patient is able to perform acceptable and repeatable spirometry.

          8. The patient is able to perform peak expiratory flow (PEF) with a handheld peak flow
             meter.

          9. The patient is able to use a metered-dose inhaler (MDI) device without a spacer device
             and a MDPI device.

         10. The patient is able to withhold (as judged by the investigator) his or her regimen of
             ICS or study drug, and rescue medication for at least 6 hours before the SV and before
             all treatment visits where spirometry is performed.

         11. The patient/parent/legal guardian/caregiver is capable of understanding the
             requirements, risks, and benefits of study participation, and, as judged by the
             investigator, capable of giving informed consent/assent and being compliant with all
             study requirements.

         12. SABAs: All patients must be able to replace their current SABA with
             albuterol/salbutamol HFA inhalation aerosol at the SV for use as needed for the
             duration of the study.

         13. Female patients may not be pregnant, breastfeeding, or attempting to become pregnant.

               -  -Other criteria may apply, please contact the investigator for more information

        Exclusion Criteria:

          1. The patient has a history of a life-threatening asthma exacerbation that is defined
             for this protocol as an asthma episode that required intubation and/or was associated
             with hypercapnea, respiratory arrest, or hypoxic seizures.

          2. The patient is pregnant or lactating, or plans to become pregnant during the study
             period or for 30 days after the study.

          3. The patient has participated as a randomized patient in any investigational drug study
             within the 30 days preceding the SV (or prescreening visit, as applicable) or plans to
             participate in another investigational drug study at any time during this study.

          4. The patient has previously participated in an Fp MDPI or FS MDPI study.

          5. The patient has a known hypersensitivity to any corticosteroid, salmeterol, or any of
             the excipients in the study drug or rescue medication formulation (ie, lactose).

          6. The patient has been treated with any known strong cytochrome P450 (CYP) 3A4
             inhibitors (eg, azole antifungals, ritonavir, or clarithromycin) within 30 days before
             the SV or plans to be treated with any strong CYP3A4 inhibitor during the study.

          7. The patient has been treated with any of the prohibited medications during the
             prescribed (per protocol) washout periods before the SV.

          8. The patient currently smokes or has a smoking history of 10 pack-years or more (a
             pack-year is defined as smoking 1 pack of cigarettes/day for 1 year). The patient may
             not have used tobacco products within the past year (eg, cigarettes, cigars, chewing
             tobacco, or pipe tobacco).

          9. The patient has a culture-documented or suspected bacterial or viral infection of the
             upper or lower respiratory tract, sinus, or middle ear that has not resolved at least
             2 weeks before the SV.

         10. The patient has a history of alcohol or drug abuse within 2 years preceding the SV.

         11. The patient has had an asthma exacerbation requiring systemic corticosteroids within
             30 days before the SV, or has had any hospitalization for asthma within 2 months
             before the SV.

         12. Initiation or dose escalation of immunotherapy (administered by any route) is planned
             during the study period. However, patients who initiated immunotherapy 90 days or more
             before the SV and have been on a stable (maintenance) dose for 30 days or more before
             the SV may be considered for inclusion.

         13. The patient has used immunosuppressive medications within 4 weeks before the SV.

         14. The patient is unable to tolerate or unwilling to comply with the appropriate washout
             periods and withholding of all applicable medications. (Patients that require
             continuous treatment with β-blockers, monoamine oxidase inhibitors, tricyclic
             antidepressants, anticholinergics, and/or systemic corticosteroids are excluded).

         15. The patient has untreated oral candidiasis at the SV. Patients with clinical visual
             evidence of oral candidiasis who agree to receive treatment and comply with
             appropriate medical monitoring may enter the study.

         16. The patient has a history of a positive test for human immunodeficiency virus, active
             hepatitis B virus, or hepatitis C infection.

         17. The patient is either an employee or an immediate relative of an employee of the
             clinical investigational center.

         18. A member of the patient's household is participating in the study at the same time.
             However, after the enrolled patient completes or discontinues participation in the
             study, another patient from the same household may be screened.

         19. The patient has a disease/condition that in the medical judgment of the investigator
             would put the safety of the patient at risk through participation or that could affect
             the efficacy or safety analysis if the disease/condition worsened during the study.

               -  Other criteria may apply, please contact the investigator for more information

        Criteria for Randomization:

        Patients were randomized into the study if they met all of the following criteria:

          1. The patient continued to be in general good health, meeting the entry criteria.

          2. The patient continued to have a predose/pre-albuterol FEV1 at the randomization visit
             (RV) that was ≥40% of predicted normal.

          3. The patient had no clinically significant abnormal laboratory test results or ECG
             findings at the screening visit.

          4. The patient had no significant changes in asthma medications during run-in, excluding
             the albuterol/salbutamol HFA (90 mcg ex actuator) or equivalent used as rescue
             medication as supplied per protocol.

          5. The patient did not have a upper respiratory tract infection (URI) or lower
             respiratory tract infection (LRI) during the run in period. Patients who developed a
             URI or LRI during the run in period could be discontinued from the study and allowed
             to re-screen 2 weeks after resolution of symptoms.

          6. The patient had no asthma exacerbation during the run in period, defined as any
             worsening of asthma requiring any significant treatment other than rescue
             albuterol/salbutamol HFA (90 mcg ex actuator) or equivalent or the patient's run-in
             MDPI. This included requiring the use of systemic corticosteroids and/or emergency
             department (ED) visit or hospitalization or an increase in the patient's regularly
             prescribed nonsteroidal maintenance treatment. Urgent care/ED visits where the
             treatment was limited to a single dose of nebulized albuterol/salbutamol did not meet
             the criteria of an asthma exacerbation.

          7. The patient had no clinical visual evidence (on oropharyngeal examination) of
             oropharyngeal candidiasis.

          8. The patient did not experience an adverse event that would result in failure to
             continue to meet selection criteria.

          9. The patient did not use any of the prohibited concomitant medications during the run
             in period.

         10. The patient complied with completion of the daily diary, defined as follows:

               -  completion of AM and PM asthma symptom scores on 4 or more of the 7 days
                  immediately preceding the RV.

               -  completion of rescue medication use (whether used or not) on 4 or more of the 7
                  days immediately preceding the RV.

               -  completion of AM peak expiratory flow (PEF) measurements on 4 or more of the 7
                  days immediately preceding the RV.

               -  recording of AM and PM asthma inhalation therapy use on 4 or more of the 7 days
                  immediately preceding the RV.