Clinical Endpoint Bioequivalence Study of Fluticasone Propionate & Salmeterol Xinafoate (100mg/50mg)

Inclusion Criteria:

1. Male and female subjects must be 12 years of age or older.

2. Females must not be of childbearing potential or if of childbearing potential, mustcommit to consistent use of a form of birth control which is medically effective, inthe judgment of the investigator. Women of childbearing potential (WOCBP) for thisstudy is defined as those women between menarche and menopause who have not undergonepermanent sterilization. For this study, the only procedures considered to result inpermanent sterilization are hysterectomy, bilateral tubectomy, or bilateraloophorectomy. Please note this does not include women having undergone bilateral tubal ligation (BTL); such women are considered WOCBP until all menses stop for 12 months without analternative medical explanation. All WOCBP must undergo pregnancy testing as describedin the protocol, without exceptions.

3. Be able to provide written informed consent or, in the case of adolescents, informedassent in addition to an informed consent form (ICF) signed by the adolescent'sparent(s) or legal guardian(s).

4. Be current non-smokers and also may not have used tobacco products (e.g., cigarettes,e-cigarettes, cigars, pipe tobacco) within the year prior to Visit 1, and have 10years or less (10 pack-years for cigarettes) of historical use. Also, a negative urinecotinine test at Screening Visit is required for study participation. Repeat urinecotinine testing is not allowed.

5. Have persistent asthma, as defined by the National Asthma Education and PreventionProgram, for at least 12 weeks before Visit 1. If the subject is naïve to the study site, investigators must use appropriate means toensure the subject's asthma diagnosis (subject history, pharmacy records, chartrecords, etc.), and this documentation must be present in the subject's sourcedocuments prior to randomization.

6. FEV1 at Visit 1 (screening) and Visit 2 (randomization) of: ≥40% and ≤85% predictednormal value (for age ≥18 years), or ≥65% and ≤85% predicted normal value (for ages 12to 17 years)

7. Demonstrate ≥15% reversibility of FEV1 between 10 and 30 minutes following 360 μg ofalbuterol inhalation. This may be demonstrated at the Screening Visit or anytime inthe period leading up to Visit 2 (randomization). Note: If the subject fails to achieve ≥15% reversibility at Visit 1 but meets allother screening eligibility criteria, the subject may return one time on a differentday within 7 days to repeat Screening Visit spirometry provided the following are met:

8. ≥ 10% reversibility and

9. The Investigator believes that a greater reversibility may be achieved on anotherattempt. Repeat of Visit 1 (Screening Visit) spirometry is allowed only once.

10. Be able to discontinue controller asthma medication (including LTM, inhaledcorticosteroids [ICS] and long-acting β-agonists (LABAs]) during the Run-in Period andTreatment Period.

11. Be able to replace current short-acting β-agonists (SABAs) with the study-suppliedalbuterol (or equivalent) rescue medication inhaler for use as needed for the durationof the study (subjects should be able to withhold all inhaled SABAs for a least 6hours before lung function assessments during study visits).

12. Must not have been treated (for any reason) with oral or parenteral corticosteroidsfor at least 1 month before Visit 1 and must not have used oral SABAs (not inhaled)for at least 12 hours before Visit 1 and for the remainder of the study. Use oforal/parenteral corticosteroids and oral SABAs is prohibited after Visit 1.

13. Subjects may continue using short-acting forms of theophylline (withheld at least 12hours before study visits), twice daily controlled-release forms of theophylline (withheld at least 24 hours before study visits), and once daily controlled-releaseforms of theophylline (withheld at least 36 hours before study visits). Subjects mustbe judged by the investigator as able to withhold these medications for the specifiedminimum time intervals before each site visit. These medications may not undergo a significant adjustment (other than adjustments tomaintain therapeutic blood levels) of dosage, formulation, or dosing interval for theduration of the study.

14. Be able to answer questions regarding asthma status and be able to document deviceusage and asthma status on a twice daily basis. NOTE: Placebo inhaler use (i.e., compliance) must be at least 75% of the planned dosestaken as assessed at Visit 2 via eDiary, for the subject to be considered eligible tocontinue in the study.

15. Demonstrate proper use of MDI and dry-powder inhaler devices.

Exclusion Criteria:

1. Have a FEV1 reversibility of <15% at Visit 1.

2. Are unable to discontinue ICS, LABA, or LTM.

3. Have a history of life-threatening asthma, defined as an asthma episode (at any timein the past) associated with any of the following: respiratory arrest or intubation,hypercapnia, hypoxic seizures, or syncopal episode.

4. Have a hospitalization within the year prior to Screening due to an asthmaexacerbation.

5. Have exercise-induced asthma as the only asthma-related diagnosis that does notrequire daily asthma control medicine.

6. Have evidence or history of congestive heart failure, uncontrolled hypertension,uncontrolled coronary artery disease, myocardial infarction, or cardiac dysrhythmia.

7. Have evidence or history of any disease (hematologic, hepatic, neurologic,psychiatric, renal, or other) that in the opinion of the investigator, would put thesubject at risk through study participation, or would affect the study analyses if thedisease exacerbated during the study.

8. Have any other relevant pulmonary disease except for asthma, including but not limitedto chronic obstructive pulmonary disease (COPD), interstitial lung disease, cysticfibrosis, bronchiectasis, chronic bronchitis, emphysema, active pulmonarytuberculosis, pulmonary carcinoma, pulmonary fibrosis, or pulmonary hypertension.

9. Have obstructive sleep apnea severe enough to warrant a prescription for biphasic orcontinuous positive-airway pressure therapy (BiPAP or CPAP), regardless of subjectcompliance with this therapy.

10. Taking any of the following medications:

• Oral or parenteral beta blockers (excluding eye drops)

• Strong cytochrome P450 3A4 inhibitors

• Anti-IgE therapy, Xolair (omalizumab)

• Monoamine oxidase (MAO) Inhibitors

• Monoclonal antibodies/biologic agents which may affect the course of asthma (suchas mepolizumab, reslizumab, lebrizumab, and others)

11. Had a viral or bacterial, upper or lower respiratory tract infection or sinus ormiddle ear infection within 4 weeks before Screening (Visit 1), or have such aninfection during the Run-in Period.

12. Participated in an interventional study or used any investigational drug for anydisease within 30 days (or 5 half-lives, if this is longer than 30 days) before Visit 1, or participated in this interventional study under the current protocol (Protocolnumber: FLSAP100/50-PVCL-2) at any time previously.

13. Are hypersensitive to any β2-agonist sympathomimetic drug, or any intranasal, inhaled,or systemic corticosteroid therapy or any component of these combination medicationsincluding severe milk protein hypersensitivity.

14. Are exhibiting any factors (e.g., infirmity, disability, or geographic location,inability to follow instructions or study compliance requirements) that theinvestigator believes would likely limit the subject's compliance with the studyprotocol or scheduled site visits. This includes recent history (defined as 3 monthsprior to study entry) of substance abuse or uncontrolled psychiatric or neurologicalbehavior that would render the subject incapable of reliably following studyrequirements, in the judgment of the investigator.

15. Have an affiliation with the participating site; in other words, subject may not be animmediate family member of any study site staff and may not be employed directly orindirectly by the study site.

16. Have a positive urine drug screen at Screening Visit.

• Exceptions are made for a positive drug screen only for opiates, stimulants,barbiturates, tricyclics, or benzodiazepines if there is a documentedprescription with supporting medical history and diagnosis, and the PrincipalInvestigator assesses that there are no safety concerns with subjectparticipation.

• Screened subjects with a urine drug screen positive formarijuana/tetrahydrocannabinol are not eligible for study participation, withoutexceptions.

• Repeat drug screening is not allowed.

17. Have a positive urine cotinine screen at Screening Visit. Repeat cotinine testing isnot allowed.