Study of Fluticasone Propionate MDPI Compared With Fluticasone/Salmeterol MDPI in Adolescent and Adult Patients With Persistent Asthma
Condition: Asthma
MeSH terms: Asthma
Intervention: FS MDPI; Fp MDPI; Placebo MDPI; albuterol/salbutamol; Beclomethasone dipropionate
Intervention description: 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 and contained within a reservoir. A metered dose of drug is delivered to a dose cup via an air pulse activated when the cap is opened.
During the treatment period, participants were randomized to either 100/12.5 mcg Fp/Sx or 50/12.5 mcg Fp/Sx in the morning and evening for a total daily dose of 200/25 mcg or 100/25 mcg Fp/Sx.
Participants were instructed to rinse their mouth and expectorate (not swallow) after study drug administration.; Fp MDPI is an inhalation-driven multidose dry powder inhaler (MDPI) containing fluticasone propionate dispersed in a lactose monohydrate excipient and contained within a reservoir. A metered dose of drug is delivered to a dose cup via an air pulse activated when the cap is opened.
During the treatment period, participants were randomized to either 100 mcg or 50 mcg of Fp one inhalation twice a day for a total daily dose of 200 mcg or 100 mcg.
Participants were instructed to rinse their mouth and expectorate (not swallow) after study drug administration.; Placebo administered via a multidose dry powder inhaler (MDPI) one puff in the morning and one puff in the evening for 12 weeks.; 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).; QVAR (beclomethasone dipropionate) 40 mcg inhalation aerosol is a pressurized MDI that contains a Food and Drug Administration (FDA)-approved formulation of beclomethasone dipropionate. Patients took 1 puff twice a day from open-label QVAR 40 mcg hydrofluoroalkane (specifically, HFA-134a) metered-dose inhaler (MDI) for the duration of the Run-in Period (14-21 days) and prior to randomization. A clinically equivalent dose of inhaled corticosteroid (ICS) was substituted in countries where QVAR 40 mcg was not available.
Intervention MeSH terms: Fluticasone; Xhance; Beclomethasone; Albuterol; Salmeterol Xinafoate; Adrenergic Agonists
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 787.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No
Keywords: fluticasone propionate; multidose dry powder inhaler

Summary:

      The primary objective of this study was to evaluate the efficacy of fluticasone propionate
      multidose dry powder inhaler (Fp MDPI) and fluticasone propionate/salmeterol xinafoate
      multidose dry powder inhaler (FS MDPI) when administered over 12 weeks in patients 12 years
      of age and older with persistent asthma.

      Study drug and placebo was supplied in Teva multidose dry powder inhaler (MDPI) devices and
      provided for participants to use at home. Participants performed spirometry at every visit.
      Each participant was given a diary at each visit for use until the next visit. Rescue
      medication (albuterol/salbutamol) was dispensed at each visit, if needed, as determined by
      the investigational center personnel.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Best pre-bronchodilator forced expiratory volume in 1 second (FEV1) of 40 to 85% of
             their predicted normal value.

          2. Current Asthma Therapy: Patients must have a short-acting β2-agonist (for rescue use)
             for a minimum of 8 weeks before the Screening Visit (SV) and a low-dose inhaled
             corticosteroid (ICS). The low-dose ICS may be either as ICS monotherapy or as an
             ICS/long-acting beta agonist (LABA) combination. The ICS component of the patient's
             asthma therapy should be stable for a minimum of 1 months before providing consent.

          3. Reversibility of Disease: Patients must have at least 15% reversibility (all patients)
             and at least a 200 mL increase from baseline FEV1 (patients age 18 and older) within
             30 minutes after 2 to 4 inhalations of albuterol/salbutamol at the SV. Note: Patients
             who do not qualify for the study due to failure to meet reversibility will be
             permitted to perform a retest once within 7 days.

          4. Patients must provide written informed consent/assent. For minor patients (ages 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). Note: Age requirements are as specified by local
             regulations.

          5. Outpatient >= 12 years of age on the date of consent/assent. In countries where the
             local regulations permit enrollment of adult patients only, patients must be 18 years
             of age and older.

          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 asthma
             medication) for at least 30 days.

          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 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.

         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 MDI inhalation aerosol 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. A history of a life-threatening asthma exacerbation (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 30 days of the SV.

          4. The patient has previously participated as a randomized patient in a study of Fp MDPI
             or FS MDPI.

          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.

          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 must 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 on stable immunotherapy 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.

         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 (HIV),
             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