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

NCT01772368 | Completed Phase 2 Results

• 1 other identifier: FSS-AS-201
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 10

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.

Conditions

Asthma

Keywords

Asthma; dry powder inhaler; long-acting beta2-agonist; bronchodilation; bronchodilator; metered dose inhaler; inhaled corticosteroid

Outcome Measures

Primary Outcomes (1)

• Standardized Baseline-Adjusted Area Under the Curve For Forced Expiratory Volume In 1 Second Over 12 Hours Post-dose (FEV1 AUC0-12)

  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.

  Pre-dose: 30 minutes prior, within 5 minutes of dose. Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 9, 12 hours

Secondary Outcomes (5)

• Change From Baseline at 12 Hours Post-Dose in Forced Expiratory Volume in One Second (FEV1) By Treatment

  Pre-dose: 30 minutes prior, within 5 minutes of dose. Post-dose: 12 hours

• Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Measurable Concentration (AUC0-t) of Salmeterol

  Predose (0), and at 5, 10, 15 and 30 minutes, 1, 1.5, 2, 3, 4, 8, and 12 hours postdose

• Maximum Observed Plasma Concentration (Cmax) of Salmeterol

  Predose (0), and at 5, 10, 15 and 30 minutes, 1, 1.5, 2, 3, 4, 8, and 12 hours postdose

• Time of Maximum Observed Plasma Concentration (Tmax) of Salmeterol

  Predose (0), and at 5, 10, 15 and 30 minutes, 1, 1.5, 2, 3, 4, 8, and 12 hours postdose

• Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period

  Day 1 up to Day 35

Study Arms (6)

FS MDPI 100/6.25 mcg

EXPERIMENTAL

Subjects inhaled a single dose of 100 mcg fluticasone propionate and 6.25 mcg salmeterol xinafoate.

Drug: FS MDPI; Drug: Albuterol

FS MDPI 100/12.5mcg

EXPERIMENTAL

Subjects inhaled a single dose of 100 mcg fluticasone propionate and 12.5 mcg salmeterol xinafoate.

Drug: FS MDPI; Drug: Albuterol

FS MDPI 100/25

EXPERIMENTAL

Subjects inhaled a single dose of 100 mcg fluticasone propionate and 25 mcg salmeterol xinafoate.

Drug: FS MDPI; Drug: Albuterol

FS MDPI 100/50

EXPERIMENTAL

Subjects inhaled a single dose of 100 mcg fluticasone propionate and 50 mcg salmeterol xinafoate.

Drug: FS MDPI; Drug: Albuterol

Fp MDPI 100 mcg

ACTIVE COMPARATOR

Subjects inhaled a single dose of 100 mcg fluticasone propionate.

Drug: Fp MDPI; Drug: Albuterol

Advair Diskus 100/50 mcg

ACTIVE COMPARATOR

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.

Drug: Advair Diskus; Drug: Albuterol

Interventions

Fp MDPI DRUG

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.

Also known as: fluticasone propionate, inhaled corticosteroid, Fp Spiromax

Fp MDPI 100 mcg

FS MDPI DRUG

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.

Also known as: fluticasone propionate, inhaled corticosteroid, Salmeterol xinafoate, β2 adrenoceptor agonist, FS Spiromax

FS MDPI 100/12.5mcg; FS MDPI 100/25; FS MDPI 100/50; FS MDPI 100/6.25 mcg

Advair Diskus DRUG

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.

Also known as: fluticasone propionate, inhaled corticosteroid, salmeterol xinafoate, β2 adrenoceptor agonist

Advair Diskus 100/50 mcg

Albuterol DRUG

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).

Also known as: Pro-Air, short-acting β2-adrenergic agonists

Advair Diskus 100/50 mcg; FS MDPI 100/12.5mcg; FS MDPI 100/25; FS MDPI 100/50; FS MDPI 100/6.25 mcg; Fp MDPI 100 mcg

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Teva Branded Pharmaceutical Products R&D, Inc.: lead

Study Sites (10)

Teva Investigational Site 10453

Denver, Colorado, United States

Location

Teva Investigational Site 10452

North Dartmouth, Massachusetts, United States

Location

Teva Investigational Site 10455

St Louis, Missouri, United States

Location

Teva Investigational Site 10454

Skillman, New Jersey, United States

Location

Teva Investigational Site 10448

Raleigh, North Carolina, United States

Location

Teva Investigational Site 10451

Medford, Oregon, United States

Location

Teva Investigational Site 10449

Portland, Oregon, United States

Location

Teva Investigational Site 10457

El Paso, Texas, United States

Location

Teva Investigational Site 10450

New Braunfels, Texas, United States

Location

Teva Investigational Site 10456

San Antonio, Texas, United States

Location

MeSH Terms

Conditions

Asthma

Interventions

Fluticasone; Salmeterol Xinafoate; Fluticasone-Salmeterol Drug Combination; Albuterol; Procaterol

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Androstadienes; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines; Drug Combinations; Pharmaceutical Preparations; Hydroxyquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Director, Clinical Research
• Organization: Teva Branded Pharmaceutical Products, R&D Inc.

1-215-591-3000

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2013
• First Posted: January 21, 2013
• Study Start: January 1, 2013
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: June 12, 2017
• Results First Posted: April 12, 2017

Record last verified: 2017-05

Locations

US (10)