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Trial record 85 of 320 for:    FLUTICASONE AND SALMETEROL

Dose Ranging Study of the Salmeterol Component of Fluticasone /Salmeterol Spiromax Compared to Fluticasone Spiromax and Advair Diskus in Asthma Subjects

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ClinicalTrials.gov Identifier: NCT01772368
Recruitment Status : Completed
First Posted : January 21, 2013
Results First Posted : April 12, 2017
Last Update Posted : June 12, 2017
Sponsor:
Information provided by (Responsible Party):
Teva Pharmaceutical Industries ( Teva Branded Pharmaceutical Products, R&D Inc. )

Tracking Information
First Submitted Date  ICMJE January 17, 2013
First Posted Date  ICMJE January 21, 2013
Results First Submitted Date  ICMJE February 28, 2017
Results First Posted Date  ICMJE April 12, 2017
Last Update Posted Date June 12, 2017
Study Start Date  ICMJE January 2013
Actual Primary Completion Date June 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 28, 2017)
Standardized Baseline-Adjusted Area Under the Curve For Forced Expiratory Volume In 1 Second Over 12 Hours Post-dose (FEV1 AUC0-12) [ Time Frame: Pre-dose: 30 minutes prior, within 5 minutes of dose. Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 9, 12 hours ]
Standardized baseline-adjusted FEV1 AUC0-12 was defined as the area under the curve for baseline-adjusted FEV1 measurements from the predose to 12 hours postdose time points using the trapezoidal rule based on actual (not scheduled) time of measurement and was standardized by dividing the actual time of last non-missing FEV1 measurement. Baseline-adjusted FEV1 was calculated as postdose FEV1 after subtracting period-specific baseline FEV1. The period-specific baseline FEV1 was measured at predose within 5 minutes of AM dose administration at each treatment visit. If that value was missing, then FEV1 measured at 30 minutes predose was used as the period-specific baseline.
Original Primary Outcome Measures  ICMJE
 (submitted: January 17, 2013)
Area under curve (AUC) for forced expiratory volume at one second (FEV1) over 12 hours post-dose [ Time Frame: Treatment Visits 1, 2, 3, 4, 5, 6 ]
This is the baseline-adjusted area under curve for Forced Expiratory Volume (in liters) in 1 second from zero to 12 hours post inhaler dose. For each pulmonary function test, the subject will be allowed up to five efforts and can stop once three acceptable and two repeatable efforts have been achieved. If repeatability criteria are not met, the highest FEV1 from the best acceptable effort will be chosen. If acceptability criteria are not met, the highest FEV1 from the best effort will be chosen. All baseline FEV1 values during the treatment period will be obtained between 05:30 and 11:00 AM and must be within ± 1 hour of the time of the screening FEV1 time. The primary analysis will be performed using an analysis of covariance.
Change History Complete list of historical versions of study NCT01772368 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 28, 2017)
  • Change From Baseline at 12 Hours Post-Dose in Forced Expiratory Volume in One Second (FEV1) By Treatment [ Time Frame: Pre-dose: 30 minutes prior, within 5 minutes of dose. Post-dose: 12 hours ]
    The secondary efficacy variable was the change from period-specific baseline in FEV1 at 12 hours, calculated as FEV1 measured at 12 hours postdose after subtracting period-specific baseline FEV1 at each treatment period. The period-specific baseline FEV1 was measured at predose within 5 minutes of AM dose administration at each treatment visit. If that value was missing, then FEV1 measured at 30 minutes predose was used as the period-specific baseline.
  • Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Measurable Concentration (AUC0-t) of Salmeterol [ Time Frame: Predose (0), and at 5, 10, 15 and 30 minutes, 1, 1.5, 2, 3, 4, 8, and 12 hours postdose ]
    Blood samples for measurement of plasma SAL concentrations were obtained during each treatment visit (subjects 18 years of age and older only) and pharmacokinetic parameters were derived. The primary pharmacokinetic parameters were AUC0-t and Cmax for Salmeterol.
  • Maximum Observed Plasma Concentration (Cmax) of Salmeterol [ Time Frame: Predose (0), and at 5, 10, 15 and 30 minutes, 1, 1.5, 2, 3, 4, 8, and 12 hours postdose ]
    Blood samples for measurement of plasma SAL concentrations were obtained during each treatment visit (subjects 18 years of age and older only) and pharmacokinetic parameters were derived. The primary pharmacokinetic parameters were AUC0-t and Cmax for Salmeterol.
  • Time of Maximum Observed Plasma Concentration (Tmax) of Salmeterol [ Time Frame: Predose (0), and at 5, 10, 15 and 30 minutes, 1, 1.5, 2, 3, 4, 8, and 12 hours postdose ]
    Blood samples for measurement of plasma SAL concentrations were obtained during each treatment visit (subjects 18 years of age and older only) and pharmacokinetic parameters were derived.
  • Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period [ Time Frame: Day 1 up to Day 35 ]
    TEAEs were recorded during each double-blind treatment. In addition, at the end of each treatment, patients continued to use 2 inhalations of Fp MDPI 50 mcg (100 mcg total dose) twice daily, so adverse events during this treatment were assigned to Fp MDPI 50 mcg. An adverse event was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an AE which prevents normal daily activities. Relationship of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical in
Original Secondary Outcome Measures  ICMJE
 (submitted: January 17, 2013)
Change from baseline in FEV1 at 12 hours [ Time Frame: Baseline and Treatment Visits 1, 2, 3, 4, 5, 6 ]
During all treatment visits (TV1, TV2, TV3, TV4, TV5, and TV6), the highest FEV1 value from three acceptable and two repeatable maneuvers will be obtained at each serial time point. This FEV1 will be compared to the FEV1 from the Screening Visit.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dose Ranging Study of the Salmeterol Component of Fluticasone /Salmeterol Spiromax Compared to Fluticasone Spiromax and Advair Diskus in Asthma Subjects
Official Title  ICMJE A Six-Period Crossover, Dose-Ranging Study to Evaluate the Efficacy and Safety of Four Doses of FS Spiromax (Fluticasone Propionate/Salmeterol Xinafoate Inhalation Powder) Administered as Single Doses Compared With Single Doses of Fluticasone Propionate Spiromax and Open Label Advair Diskus in Adult and Adolescent Subjects With Persistent Asthma
Brief Summary The primary objective of this study is to evaluate the dose response, efficacy, and safety of 4 different doses of salmeterol Spiromax (6.25, 12.5, 25, and 50 mcg) each combined with a fixed dose of fluticasone propionate (100 mcg) delivered as Fluticasone/Salmeterol Spiromax® Inhalation Powder (FS Spiromax) when administered as a single dose in subjects 12 years of age and older with persistent asthma.
Detailed Description

This was a multicenter, randomized, double-blind and open-label active-controlled, single-dose, 6 period crossover, dose-ranging study conducted in male and female subjects ages 12 years and older with persistent asthma.

Fluticasone propionate multidose dry powder inhaler (Fp MDPI) 50 mcg was provided (to replace the subject's current inhaled corticosteroid (ICS)) throughout the 14 day run-in period and each of the washout periods between treatments. Subjects were instructed to administer 2 inhalations of Fp MDPI 50 mcg (100 mcg total dose) twice daily during the run-in and washout periods. All other medications for the treatment of asthma were discontinued at or prior to the screening visit.

A short-acting β2-adrenergic agonist (SABA), salbuterol HFA, MDI, was provided (to replace the subject's current rescue medication) for symptomatic relief of asthma symptoms in each the run-in, treatment, and washout periods.

Treatment period lasted 5 weeks with a 5 to 7 day washout between each of the six single dose treatments:

  • fluticasone propionate/salmeterol xinafoate multidose dry powder inhaler (FS MDPI) given in doses of 6.25, 12.5, 25, or 50 mcg of salmeterol xinafoate in blinded fashion.
  • fluticasone propionate multidose dry powder inhaler (Fp MDPI) 100 mcg in blinded fashion
  • ADVAIR DISKUS, 100/50 mcg in open-label fashion
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Asthma
Intervention  ICMJE
  • Drug: Fp MDPI

    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.

    Fp at 100 mcg was an active comparator (single dose). Further, participants were instructed to administer two inhalations of Fp MDPI 50 mcg twice daily (100 mcg total dose) during the Run-in (to replace the participant's current inhaled corticosteroid) and Washout Periods between treatments.

    Other Names:
    • fluticasone propionate
    • inhaled corticosteroid
    • Fp Spiromax
  • Drug: FS MDPI
    FS MDPI is an inhalation-driven multidose dry powder inhaler (MDPI) containing fluticasone propionate and salmeterol xinafoate 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. The fluticasone propionate component was a fixed dose of 100 mcg. The salmeterol xinofoate dosage varied: 6.25, 12.5, 25 or 50 mcg.
    Other Names:
    • fluticasone propionate
    • inhaled corticosteroid
    • Salmeterol xinafoate
    • β2 adrenoceptor agonist
    • FS Spiromax
  • Drug: Advair Diskus
    ADVAIR DISKUS (100/50 mcg fluticasone propionate/salmeterol xinafoate) consists of a dry powder formulation of fluticasone propionate and salmeterol xinafoate in a lactose excipient. The dry powder is contained within individual blisters on a double foil strip within the device. Activation of the device opens a single blister of medication which is then dispersed into the air-stream by patient inhalation.
    Other Names:
    • fluticasone propionate
    • inhaled corticosteroid
    • salmeterol xinafoate
    • β2 adrenoceptor agonist
  • Drug: Albuterol
    Albuterol (Pro-Air) 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).
    Other Names:
    • Pro-Air
    • short-acting β2-adrenergic agonists
Study Arms  ICMJE
  • Experimental: FS MDPI 100/6.25 mcg
    Subjects inhaled a single dose of 100 mcg fluticasone propionate and 6.25 mcg salmeterol xinafoate.
    Interventions:
    • Drug: FS MDPI
    • Drug: Albuterol
  • Experimental: FS MDPI 100/12.5mcg
    Subjects inhaled a single dose of 100 mcg fluticasone propionate and 12.5 mcg salmeterol xinafoate.
    Interventions:
    • Drug: FS MDPI
    • Drug: Albuterol
  • Experimental: FS MDPI 100/25
    Subjects inhaled a single dose of 100 mcg fluticasone propionate and 25 mcg salmeterol xinafoate.
    Interventions:
    • Drug: FS MDPI
    • Drug: Albuterol
  • Experimental: FS MDPI 100/50
    Subjects inhaled a single dose of 100 mcg fluticasone propionate and 50 mcg salmeterol xinafoate.
    Interventions:
    • Drug: FS MDPI
    • Drug: Albuterol
  • Active Comparator: Fp MDPI 100 mcg
    Subjects inhaled a single dose of 100 mcg fluticasone propionate.
    Interventions:
    • Drug: Fp MDPI
    • Drug: Albuterol
  • Active Comparator: Advair Diskus 100/50 mcg
    Subjects inhaled a single dose of 100 mcg fluticasone propionate and 50 mcg salmeterol xinafoate. This arm is the only arm which is open-label because the inhaler device was different than the MDPI used in the other treatment arms.
    Interventions:
    • Drug: Advair Diskus
    • Drug: Albuterol
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 17, 2013)
72
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE June 2013
Actual Primary Completion Date June 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Written informed consent/assent
  • General good health
  • Diagnosis of asthma as defined by the National Institutes of Health (NIH)
  • A best FEV1 of 40%-85% of the predicted normal value during the screening visit (SV)
  • Subjects need to demonstrate a ≥ 15% reversibility of FEV1 within 30 minutes following 4 inhalations of albuterol inhalation aerosol (if required, spacers are permitted for reversibility testing) at the SV.
  • Other inclusion criteria apply

Exclusion Criteria:

  • History of life-threatening asthma that is defined for this protocol as an asthma episode that required intubation.
  • Culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus, or middle ear that is not resolved within 2 weeks prior to the SV.
  • Any asthma exacerbation requiring oral corticosteroids within 3 months of the SV. A subject must not have had any hospitalization for asthma within 6 months prior to the SV.
  • Taking long-acting β-agonists within 2 weeks of the SV
  • Other exclusion criteria apply.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01772368
Other Study ID Numbers  ICMJE FSS-AS-201
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Teva Pharmaceutical Industries ( Teva Branded Pharmaceutical Products, R&D Inc. )
Study Sponsor  ICMJE Teva Branded Pharmaceutical Products, R&D Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Teva Pharmaceutical Industries
Verification Date May 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP