Clinical Efficacy Study of Salmeterol Xinafoate/Fluticasone Propionate in Asthma

Study Overview
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Brief Summary
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This is a study to establish the equivalence of OT329 Solis and Advair Diskus when administered by inhalation in patients with asthma.

Official Title
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Clinical Endpoint Study of Salmeterol Xinafoate/Fluticasone Propionate Combination for Comparison of a Test and Reference Product in Patients With Asthma

Conditions
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Asthma

Intervention / Treatment
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* Drug: OT329 (combination of fluticasone propionate and salmeterol xinafoate)
* Drug: Advair Diskus (combination of fluticasone propionate and salmeterol xinafoate)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females ≥ 18 years old of non-child bearing potential or of child bearing potential committing to consistent and correct use of an acceptable method of birth control Subjects with a reliable clinical history of asthma documented at least 12 weeks prior to screening Subjects with a pre-bronchodilator FEV1 of > 40% and <85% of the predicted value during the screening visit and on the first day of treatment Subjects who are currently non-smoking and have not used tobacco products (i.e., cigarettes, cigars, pipe tobacco) within the past year, and had < 10 pack-years of historical use Subjects with > 15% reversibility of FEV1 within 30 minutes following 360 mcg of albuterol inhalation (pMDI). Note: This test may be repeated on a different day if the patient fails the first attempt; and if the patient achieves at least 10% reversibility and the Investigator thinks that a second attempt is appropriate Subjects who are able to discontinue their asthma medications (inhaled corticosteroids and long-acting beta agonists) during the run-in period and for the remainder of the study Subjects who are able to replace current short-acting beta agonists (SABAs) with salbutamol/albuterol inhaler for use as needed for the duration of the study (subjects should be able to withhold all inhaled SABAs for at least 6 hours prior to lung function assessments on study visits) Subjects who are able to continue the following medications without a significant adjustment of dosage, formulation, or dosing interval for the duration of the study, and judged able by the investigator to withhold them for the specified minimum time intervals prior to each clinic visit: short-acting forms of theophylline for 12 hours, twice-a-day controlled release forms of theophylline for 24 hours, once-a-day controlled-release forms of theophylline for 36 hours Subjects who are able to discontinue the following medications for the specified minimum time intervals prior to the run-in period and for the remainder of the study: oral and parenteral corticosteroids for 1 month and oral short-acting beta agonists for 12 hours Subjects who are able and willing to give their written informed consent to participate in the study. ********************************************************** Exclusion Criteria: Female Subjects who are pregnant or breastfeeding Subjects who have life-threatening asthma in the last 10 years, as defined as a history of asthma episode(s) requiring intubation, and/or associated with hypercapnoea; respiratory arrest or hypoxic seizures, asthma-related syncopal episodes(s), or hospitalizations within the past year or during the run-in period Subjects with evidence or history of clinically significant disease or abnormality including congestive heart failure, uncontrolled hypertension, uncontrolled coronary artery disease, myocardial infarction, or cardiac dysrhythmia. In addition, historical or current evidence of significant hematologic, hepatic, neurologic, psychiatric, renal, or other diseases that in the opinion of the investigator, would put the patient at risk through study participation, or would affect the study analyses if the disease exacerbated during the study Subjects with a hypersensitivity to any sympathomimetic drug (e.g. Salmeterol or salbutamol/albuterol) or any inhaled, intranasal or systemic corticosteroid therapy Subjects who are on other medications with the potential to affect the course of asthma or to interact with sympathomimetic amines (e.g. beta blockers, oral decongestants, benzodiazepines, digitalis, phenothiazines, polycyclic antidepressants, monoamine oxidase inhibitors) Subjects with a viral or bacterial upper or lower respiratory tract infection or sinus or middle ear infection within 4 weeks prior to the screening visit or during the run-in period Subjects with any factors (e.g. infirmity, disability, or geographic location) that the investigator feel would likely limit the patient's compliance with the study protocol or scheduled clinic visits Subjects who have used any investigational drug in any clinical trial within 1 month of receiving the first dose of OT329 Solis™ study medication Subjects who cannot communicate reliably or who are unlikely to co-operate with the requirements of the study, in the opinion of the Investigator Subjects with a milk protein allergy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OT329 Solis<br>OT329 Solis (twice daily inhalation throughout the study) | Drug: OT329 (combination of fluticasone propionate and salmeterol xinafoate)<br>* Fluticasone propionate (100 mcg) and salmeterol xinafoate (50 mcg) administered by Solis dry powder inhaler<br>|
| Active Comparator: Advair Diskus<br>Advair Diskus (twice daily inhalation throughout the study) | Drug: Advair Diskus (combination of fluticasone propionate and salmeterol xinafoate)<br>* Fluticasone propionate (100 mcg) and salmeterol xinafoate (50 mcg) administered by Diskus dry powder inhaler<br>|
| Placebo Comparator: Placebo<br>Placebo (twice daily inhalation throughout the study) | Drug: Placebo<br>* Placebo (lactose) administered via the Solis dry powder inhaler<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Serial FEV1-time Curve (AUC 0-12h) | Bioequivalence comparison of lung function (FEV1) for 12 hours after the first dose on Day 1 following OT329 Solis and Advair Diskus treatment. Serial lung function measurements were made pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose. | 0-12 hours after dosing on Day 1 | 
| FEV1 Trough | Bioequivalence comparison of trough lung function (FEV1) after 4 weeks of treatment with OT329 SOLIS or ADVAIR DISKUS. | Post-4 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events |  | From Screen (Day -28) until 1 week post last treatment |