A 12-Month Study Comparing Fluticasone Propionate/Salmeterol (ADVAIR) DISKUS Combination Product 250/50mcg BID To Fluticasone Propionate (FLOVENT) DISKUS 250 mcg BID In Symptomatic Subjects With Asthma

Asthma Clinical Trial

Official title:

A 52-week, Randomized, Double-Blind, Parallel-Group Study of Fluticasone Propionate/Salmeterol DISKUS Combination Product (FSC) 250/50 mcg BID and Fluticasone Propionate (FP) DISKUS 250 mcg BID in Treatment of Subjects With Asthma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00452699
• Other study ID #: ADA109055
• Status: Completed
• Phase: Phase 4
• First received: March 26, 2007
• Last updated: June 12, 2014
• Start date: May 2007
• Est. completion date: May 2009

Study information

• Verified date: June 2012
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health Canada
• Study type: Interventional

Clinical Trial Summary

This purpose of this study is to show the superiority and long term safety and efficacy of adding a long acting beta agonist (salmeterol) to constant dose of an inhaled corticosteroid (fluticasone propionate) in symptomatic subjects with asthma. The 12-month assessment of asthma control will provide key information on the efficacy and safety of the combination therapy. The safety measure will be an assessment of adverse events

Recruitment information / eligibility

• Status: Completed
• Enrollment: 621
• Est. completion date: May 2009
• Est. primary completion date: May 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

• Subjects eligible for enrollment in the study must meet all of the following criteria:

• Consent: A signed and dated written informed consent must be obtained from the subject and/or subject's legally acceptable representative prior to study participation.

• Type of Subject: Outpatient

• Gender: Male or female Females are eligible to participate only if they are currently non-pregnant and non-lactating.

A female is eligible to enter and participate in the study if she is:

1. of non-child-bearing potential; OR

2. of child-bearing potential but has a negative urinary pregnancy test at Screening (Visit 1 and when specified in Appendix 1) and agrees to take contraceptive precautions (including abstinence) which are adequate to prevent pregnancy during the study.

Acceptable methods of contraception [Hatcher, 2004] are:

• Abstinence

• oral contraceptive (either combined or progestogen only)

• injectable progestogen

• implants of levonorgestrel

• estrogenic vaginal ring

• percutaneous contraceptive devices

• intrauterine device (IUD) or intrauterine system (IUS) with published data showing that the lowest expected failure rate is less than 1% per year

• male partner sterilization (vasectomy with documentation of azoospermia) prior to the female subject's entry into the study and is the sole sexual partner for that female subject

• double barrier method: condom or occlusive cap (diaphragm or cervical/vault caps) plus spermicidal agent

1. Age: A subject must be 12 years of age at Visit 1 (screening).

2. Asthma Diagnosis: A documented diagnosis of persistent asthma, for at least six months, as defined by the following American Thoracic Society definition:

Asthma is a clinical syndrome characterized by increased responsiveness of the airways to a variety of stimuli. The major symptoms of asthma are episodes of dyspnea, wheezing, and cough, which may vary from mild and almost undetectable to severe and unremitting (status asthmaticus). The primary physiological manifestation of this hyperresponsiveness is variable airway obstruction. This can take the form of spontaneous fluctuations in the severity of obstruction, substantial improvements in the severity of obstruction following bronchodilators or corticosteroids, or increased obstruction caused by drugs or other stimuli [American Thoracic Society, 1987].

1. Asthma Medication History: A subject must be using a low to medium dose of an ICS (Table 1) OR a combination of controller medications (Table 2), containing a low (total daily) dose ICS (as defined in Table 1) for at least 4 weeks preceding screening.

Table 1 (ICS Dosage Table) Inhaled Corticosteroid (Dosage (mcg/day))(LowMedium) Beclomethasone dipropionate CFC(168 = 504> 504 = 840) Beclomethasone dipropionate HFA (80 = 240>240 = 640) Triamcinolone acetonide(400 = 1000>1000 = 2000) Flunisolide (500 = 1000> 1000 = 2000) Fluticasone propionate inhalation aerosol (176 = 220> 220 = 440) Fluticasone propionate inhalation powder (100 = 250> 250 = 500) Budesonide1 (200 = 600> 600 =1200) Mometasone (200 = 400> 400 = 800) Ciclesonide (80 = 160>160 = 320)

1.Respules are allowed at a dosage of 250-500mcg/day.

Table 2 (Asthma Controller Medications) Asthma Controller Medication(s) Low dose ICS + Leukotriene modifiers Low dose ICS + Theophylline products Low Dose ICS + Inhaled anticholinergics or combination products (e.g., Atrovent or Combivent) Low Dose ICS + Long acting inhaled anticholinergic (e.g. Spiriva) Low dose ICS+ long acting beta agonist or combination products containing a low dose ICS and a long-acting beta-agonists (e.g. ADVAIR™/SERETIDE™1 100/50 mcg BID or Symbicort 160/9 mcg BID (i.e 80/4.5 mcg two inhalations BID)

1) ADVAIR/SERETIDE =250/50 mcg BID or Symbicort 320/9 mcg BID (i.e 160/4.5 mcg two inhalation BID) are not permitted.

1. Pulmonary function: A pre-albuterol (salbutamol) FEV1 of 50% and 85% of predicted normal value at screening (Visit 1) after withholding asthma medications as detailed in the protocol (Section 6.8.1). Predicted FEV1 will be based on the National Health and Nutrition Examination Survey (NHANES III) predicted normal values for ages 8 years and older [Hankinson, 1999].

2. Reversibility: An increase in FEV1 of 12% over the pre-albuterol (salbutamol) FEV1 within 30 minutes after the inhalation of 2-4 puffs of albuterol (salbutamol). Historical documentation of reversibility will not be permitted.

3. Asthma symptom criteria: Each subject must have experienced asthma symptoms requiring albuterol (salbutamol) use within the 4 weeks preceding screening (Visit 1).

Specific information regarding warnings, precautions, contraindications, adverse events, and other pertinent information on the investigational product that may impact subject eligibility is provided in the IB and the product labels.

Exclusion Criteria:

• Subjects meeting any of the following criteria must not be enrolled in the study:

1. Life-Threatening Asthma: A subject must not have life-threatening asthma. Life-threatening asthma is defined for this protocol as a history of significant asthma episode(s) requiring intubation associated with hypercapnia, respiratory arrest, or hypoxic seizures, or asthma-related syncopal episode(s) within the 12 months prior to screening (Visit 1).

2. Worsening of Asthma: A subject must not have experienced a worsening of asthma which involved an ER visit, hospitalization or use of oral/parenteral corticosteroids within 4 weeks of screening (Visit 1).

3. Intermittent, Seasonal, or Exercise-Induced Asthma Alone: Subjects with only intermittent or seasonal or exercise-induced asthma are excluded from participation in this study.

4. Concurrent Respiratory Disease: A subject must not have current evidence of pneumonia, pneumothorax, atelectasis, pulmonary fibrotic disease, chronic bronchitis, emphysema, chronic obstructive pulmonary disease, or other respiratory abnormalities other than asthma.

5. Concurrent Conditions/Diseases: A subject with historical or current evidence of any clinically significant, co-morbid or uncontrolled condition or disease state that, in the opinion of the investigator, would put the safety of the subject at risk through study participation or would confound the interpretation of the results if the condition/disease exacerbated during the study.

The list of excluded conditions/diseases includes, but is not limited to:

congestive heart failure known aortic aneurysm clinically significant coronary clinically significant cardiac arrhythmia heart disease stroke within 3 months of screening (Visit 1) uncontrolled hypertension coronary artery disease hematologic, hepatic, or renal disease cystic fibrosis poorly controlled peptic ulcer dyspnea by any other cause than asthma gastroesophageal reflux disease (GERD) not controlled by pharmacotherapy and may be causing/contributing to subject's respiratory symptoms thyrotoxicosis hypokalemia immunologic compromise current malignancy1 tuberculosis (current or quiescent) Cushing's or Addison's disease pneumonia, pneumothorax, chronic bronchitis or atelectasis uncontrolled diabetes mellitus recent history of drug or alcohol abuse 1) history of malignancy is acceptable only if subject has been in remission for one year prior to screening (Visit 1; remission = no treatment for the malignancy in the 12 months prior to screening [Visit 1])

• Drug Allergy: A subject must not have had any immediate or delayed hypersensitivity to any beta2-agonist; sympathomimetic drug; any intranasal; inhaled or systemic corticosteroid therapy; lactose; or have a severe milk protein allergy.

• Respiratory Tract Infections: A subject must not have had any sinus, middle ear, oropharyngeal, upper or lower respiratory tract infection symptoms that have not resolved at least 7 days immediately preceding screening (Visit 1).

3. Asthma Medications: Asthma medications listed below must not have been used prior to screening (Visit 1) for the required exclusion period as indicated below:

Medication (Exclusion Period Prior to screening (Visit 1)) Oral or parenteral systemic corticosteroids (4 weeks) Omalizumab (Xolair) (6 months)

1. Concurrent Medications: A subject must not have the concurrent use of any of the following medications that interact with any of the study drugs used in this study, or that may affect the course of asthma or interact with sympathomimetic amines, such as:

• beta-adrenergic receptor blocking agents

• monoamine oxidase (MAO) inhibitors

• tricyclic antidepressants

• ritonavir

• ketoconazole

2. Concurrent use of asthma medications: Concurrent use of all asthma medications (other than protocol defined study and rescue medications and oral/parenteral corticosteroids) are prohibited during the study.

3. Concomitant use of leukotriene modifiers (LTM) for allergies is prohibited. A subject must not be on LTM for treatment of nasal allergies that requires regular maintenance therapy. Substitution with any other antihistamine is permitted.

4. Immunosuppressive Medications: A subject must not be using, or require the use of, immunosuppressive medications during the study.

5. Immunotherapy for the treatment of allergies is not allowed during the study unless the subject has used a constant dose for 4 weeks prior to Screening (Visit 1) and the same dose will be continued throughout the study.

6. Tobacco Use: >10 pack year history or use of any tobacco products within 1 year of screening (Visit 1). This includes cigarettes, cigars, pipe, chewing tobacco, and snuff.

7. Questionable Validity of Consent: A subject must not have any infirmity or disability that would limit the subject's consent.

8. Positive Pregnancy Test (for all females who have had menarche): A current positive pregnancy test.

9. Investigational Medications: A subject must not have had use of any investigational drug within 30 days of screening (Visit 1).

10. Site Affiliation: A subject may not participate if he/she is a participating investigator, sub-investigator, study coordinator, employee of a participating investigator or is in any way associated with the administration of the study. Immediate family members of these individuals are also excluded.

11. Compliance with Study Requirements: A subject may not participate if, in the opinion of the investigator, there are present or anticipated circumstances that will prohibit the subject from being compliant with study visits and procedures (e.g. geographic location that will prohibit subject from required clinic visit schedule).

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• Fluticasone Propionate/salmeterol xinofoate 250/50 mcg BID
Fluticasone Propionate/salmeterol xinofoate 250/50 mcg BID
• Fluticasone propionate 250 mcg BID
Fluticasone propionate 250 mcg BID

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autonoma de Buenos Aires	Buenos Aires
Argentina	GSK Investigational Site	La Plata	Buenos Aires
Argentina	GSK Investigational Site	Nueve de Julio	Buenos Aires
Argentina	GSK Investigational Site	Vicente López	Buenos Aires
Brazil	GSK Investigational Site	Belo Horizonte	Minas Gerais
Brazil	GSK Investigational Site	Porto Alegre	Rio Grande Do Sul
Brazil	GSK Investigational Site	Recife	Pernambuco
Brazil	GSK Investigational Site	Salvador	Bahía
Canada	GSK Investigational Site	Charlottetown	Prince Edward Island
Canada	GSK Investigational Site	Mississauga	Ontario
Canada	GSK Investigational Site	Saskatoon	Saskatchewan
Philippines	GSK Investigational Site	Cavite
Philippines	GSK Investigational Site	Lipa City
Philippines	GSK Investigational Site	Quezon City
United States	GSK Investigational Site	Asheville	North Carolina
United States	GSK Investigational Site	Austin	Texas
United States	GSK Investigational Site	Bethesda	Maryland
United States	GSK Investigational Site	Billings	Montana
United States	GSK Investigational Site	Bozeman	Montana
United States	GSK Investigational Site	Cherry Hill	New Jersey
United States	GSK Investigational Site	Cincinnati	Ohio
United States	GSK Investigational Site	Columbus	Georgia
United States	GSK Investigational Site	Conyers	Georgia
United States	GSK Investigational Site	Coral Gables	Florida
United States	GSK Investigational Site	Corsicana	Texas
United States	GSK Investigational Site	Denver	Colorado
United States	GSK Investigational Site	Denver	Colorado
United States	GSK Investigational Site	East Providence	Rhode Island
United States	GSK Investigational Site	El Paso	Texas
United States	GSK Investigational Site	Fort Collins	Colorado
United States	GSK Investigational Site	Fort Collins	Colorado
United States	GSK Investigational Site	Fountain Valley	California
United States	GSK Investigational Site	Gaffney	South Carolina
United States	GSK Investigational Site	Great Neck	New York
United States	GSK Investigational Site	High Point	North Carolina
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Lilburn	Georgia
United States	GSK Investigational Site	Little Rock	Arkansas
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Metairie	Louisiana
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	Olympia	Washington
United States	GSK Investigational Site	Omaha	Nebraska
United States	GSK Investigational Site	Orangeburg	South Carolina
United States	GSK Investigational Site	Pensacola	Florida
United States	GSK Investigational Site	Philadelphia	Pennsylvania
United States	GSK Investigational Site	Philadelphia	Pennsylvania
United States	GSK Investigational Site	Pittsburgh	Pennsylvania
United States	GSK Investigational Site	Pittsburgh	Pennsylvania
United States	GSK Investigational Site	Portland	Oregon
United States	GSK Investigational Site	Providence	Rhode Island
United States	GSK Investigational Site	Providence	Rhode Island
United States	GSK Investigational Site	Rancho Mirage	California
United States	GSK Investigational Site	Richmond	Virginia
United States	GSK Investigational Site	Richmond	Virginia
United States	GSK Investigational Site	Riverside	California
United States	GSK Investigational Site	San Jose	California
United States	GSK Investigational Site	Scottsdale	Arizona
United States	GSK Investigational Site	South Bend	Indiana
United States	GSK Investigational Site	Spartanburg	South Carolina
United States	GSK Investigational Site	St. Louis	Missouri
United States	GSK Investigational Site	Stamford	Connecticut
United States	GSK Investigational Site	Tallahassee	Florida
United States	GSK Investigational Site	Tamarac	Florida
United States	GSK Investigational Site	Tigard	Oregon
United States	GSK Investigational Site	Union	South Carolina
United States	GSK Investigational Site	Utica	New York
United States	GSK Investigational Site	West Allis	Wisconsin
United States	GSK Investigational Site	Wheaton	Maryland
United States	GSK Investigational Site	Ypsilanti	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Canada,  Philippines, 

References & Publications (2)

Anderson WH, Koshy BT, Huang L, Mosteller M, Stinnett SW, Condreay LD, Ortega H. Genetic analysis of asthma exacerbations. Ann Allergy Asthma Immunol. 2013 Jun;110(6):416-422.e2. doi: 10.1016/j.anai.2013.04.002. — View Citation

Katial RK, Bernstein D, Prazma CM, Lincourt WR, Stempel DA. Long-term treatment with fluticasone propionate/salmeterol via Diskus improves asthma control versus fluticasone propionate alone. Allergy Asthma Proc. 2011 Mar-Apr;32(2):127-36. doi: 10.2500/aap.2011.32.3426. Epub 2010 Dec 28. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Change From Baseline in Pre-dose FEV1 Over Weeks 1-52	Pulmonary function was measured by forced expiratory volume in one second (FEV1), which is the volume of air exhaled from the lungs in one second. Change from baseline was calculated as the average of the Week 1 through Week 52 values minus the baseline value.	Baseline and Week 1 through Week 52	No
Secondary	Mean Change From Baseline in AM PEF Over Weeks 1-52	Morning (AM) peak expiratory flow (PEF) is defined as the maximum volume of air exhaled in liters per minute. Change from baseline was calculated as the average of the Week 1 through Week 52 values minus the baseline value.	Baseline and Week 1 through Week 52	No
Secondary	Mean Change From Baseline in the Percentage of Symptom-free Days Over Weeks 1-52	A symptom-free day was defined as a day without asthma symptoms, as measured via the daily asthma symptom score (measuring symptoms during the day and previous night) on a 6-point scale (ranging from 0 to 5). A symptom score of 0=no symptoms, 1=symptoms for one short period, 2=symptoms for two or more short periods, 3=symptoms that did not affect normal daily activities, 4=symptoms that did affect normal daily activities, 5=symptoms so severe that daily activities could not be performed. Change from baseline was calculated as the average of the Week 1-Week 52 values minus the baseline value.	Baseline and Week 1 through Week 52	No
Secondary	Rate of Asthma Attacks Per Participant Per Year	The rate of asthma attacks was defined as the mean number of attacks per participant per year. An asthma attack was defined as a 20% decrease in AM PEF, a 70% increase in albuterol use, or the occurrence of an asthma exacerbation requiring oral steroids or hospitalization.	Week 1 through Week 52	No