Clinical Efficacy Study of Salmeterol Xinafoate/Fluticasone Propionate in Asthma

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

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

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: OT329 (combination of fluticasone propionate and salmeterol xinafoate); Drug: Advair Diskus (combination of fluticasone propionate and salmeterol xinafoate); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 879
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Goodyear, Arizona, United States, 85395
      • Oriel Investigative Site
    • Tempe, Arizona, United States, 85283
      • Oriel Investigative Site
  • California
    • Anaheim, California, United States, 92801
      • Oriel Investigative Site
    • Los Angeles, California, United States, 90017
      • Oriel Investigative Site
    • Los Angeles, California, United States, 90048
      • Oriel Invetigative Site
    • Mission Viejo, California, United States, 92691
      • Oriel Investigative Site
  • Colorado
    • Centennial, Colorado, United States, 80112
      • Oriel Investigative Site
  • Florida
    • Clearwater, Florida, United States, 33756
      • Oriel Investigative Site
    • Coral Gables, Florida, United States, 33134
      • Oriel Investigative Site
    • Homestead, Florida, United States, 33030
      • Oriel Investigative Site
    • Jupiter, Florida, United States, 33458
      • Oriel Investigative Site
    • Kissimee, Florida, United States, 34741
      • Oriel Investigative Site
    • Miami, Florida, United States, 33165
      • Oriel Investigative Site
    • New Port Richie, Florida, United States, 34652
      • Oriel Investigative Site
    • Orlando, Florida, United States, 32806
      • Oriel Investigative Site
    • Tallahassee, Florida, United States, 32308
      • Oriel Investigative Site
  • Georgia
    • Lawrenceville, Georgia, United States, 30046
      • Oriel Investigative Site
  • Iowa
    • Iowa City, Iowa, United States, 52240
      • Oriel Investigative Site
  • Massachusetts
    • North Dartmouth, Massachusetts, United States, 02747
      • Oriel Investigative Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55402
      • Oriel Therapeutics Site
  • Missouri
    • St. Louis, Missouri, United States, 63141
      • Oriel Investigative Site
  • Nebraska
    • Bellevue, Nebraska, United States, 68123
      • Oriel Investigative Site
    • Omaha, Nebraska, United States, 68114
      • Oriel Investigative Site
  • New Jersey
    • Skillman, New Jersey, United States, 08558
      • Oriel Investigative Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87108
      • Oriel Investigative Site
  • New York
    • New York, New York, United States, 10018
      • Oriel Investigative Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28277
      • Oriel Investigative Site
    • Raleigh, North Carolina, United States, 27607
      • Oriel Investigative Site
    • Winston-Salem, North Carolina, United States, 27103
      • Oriel Investigative Site
  • Ohio
    • Cincinnati, Ohio, United States, 45231
      • Oriel Investigative Site
    • Cincinnati, Ohio, United States, 45242
      • Oriel Investigative Site
    • Middleburg Heights, Ohio, United States, 44130
      • Oriel Investigative Site
    • Toledo, Ohio, United States, 43617
      • Oriel Investigative Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73120
      • Oriel Investigative Site
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Oriel Investigative Site
    • Medford, Oregon, United States, 97504
      • Oriel Investigative Site
    • Portland, Oregon, United States, 97202
      • Oriel Investigative Site
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • Oriel Investigative Site
    • Warwick, Rhode Island, United States, 02886
      • Oriel Investigative Site
  • South Carolina
    • Rock Hill, South Carolina, United States, 29732
      • Oriel Investigative Site
  • Texas
    • Austin, Texas, United States, 78750
      • Oriel Investigative Site
    • Austin, Texas, United States, 78756
      • Oriel Investigative Site
    • Houston, Texas, United States, 77055
      • Oriel Investigative Site
    • Houston, Texas, United States, 77099
      • Oriel Investigative Site
    • Plano, Texas, United States, 75093
      • Oriel Investigative Site
  • Virginia
    • Richmond, Virginia, United States, 23229
      • Oriel Investigative Site
  • Washington
    • Tacoma, Washington, United States, 98405
      • Oriel Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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
2. Subjects with a reliable clinical history of asthma documented at least 12 weeks prior to screening
3. 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
4. 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
5. 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
6. 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
7. 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)
8. 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
9. 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

10. Subjects who are able and willing to give their written informed consent to participate in the study.

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    Exclusion Criteria:

11. Female Subjects who are pregnant or breastfeeding
12. 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
13. 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
14. Subjects with a hypersensitivity to any sympathomimetic drug (e.g. Salmeterol or salbutamol/albuterol) or any inhaled, intranasal or systemic corticosteroid therapy
15. 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)
16. 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
17. 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
18. Subjects who have used any investigational drug in any clinical trial within 1 month of receiving the first dose of OT329 Solis™ study medication
19. Subjects who cannot communicate reliably or who are unlikely to co-operate with the requirements of the study, in the opinion of the Investigator
20. Subjects with a milk protein allergy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Oriel Therapeutics
• Investigators: Study Director: Rick Fuller, MD FRCP, Oriel Therapeutics

Publications and helpful links

General Publications

• Longphre MV, Getz EB, Fuller R. Clinical Bioequivalence of OT329 SOLIS and ADVAIR DISKUS in Adults with Asthma. Ann Am Thorac Soc. 2017 Feb;14(2):182-189. doi: 10.1513/AnnalsATS.201606-436OC.

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: October 6, 2014
• First Submitted That Met QC Criteria: October 8, 2014
• First Posted (Estimate): October 9, 2014

Study Record Updates

• Last Update Posted (Actual): June 15, 2017
• Last Update Submitted That Met QC Criteria: March 28, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Adrenergic Agonists; Dermatologic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Sympathomimetics; Fluticasone; Xhance; Salmeterol Xinafoate; Fluticasone-Salmeterol Drug Combination
• Other Study ID Numbers: OTT329/305

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Results delayed pending FDA review/approval of drug.