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
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).
GSK Clnical Trials Call Center, La Plata 1900, Argentina
GSK Clinical Trials Call Center, Buenos Aires 1425, Argentina
GSK Clinical Trials Call Center, 9 de Julio B6500BWQ, Argentina
GSK Clinical Trials Call Center, Vincente Lopez 1602, Argentina
GSK Clinical Trials Call Center, Porto Alegre 40110-160, Brazil
GSK Clinical Trials Call Center, Belo Horizonte 30.130-100, Brazil
GSK Clinical Trials Call Center, Recife 50670-420, Brazil
GSK Clinical Trials Call Center, Porto Alegre 900035-903, Brazil
GSK Clinical Trials Call Center, Salvador 411940-455, Brazil
GSK Clinical Trials Call Center, Quezon City 1101, Philippines
GSK Clinical Trials Call Center, Lipa City 4217, Philippines
GSK Clinical Trials Call Center, Cavite 4114, Philippines
GSK Clinical Trials Call Center, Scottsdale, Arizona 85251, United States
GSK Clinical Trials Call Center, Little Rock, Arkansas 72205, United States
GSK Clinical Trials Call Center, Fountain Valley, California 92708, United States
GSK Clinical Trials Call Center, Rancho Mirage, California 92270, United States
GSK Clinical Trials Call Center, Los Angeles, California 90095, United States
GSK Clinical Trials Call Center, San Jose, California 95117, United States
GSK Clinical Trials Call Center, Vista, California 92084, United States
GSK Clinical Trials Call Center, Riverside, California 92506, United States
GSK Clinical Trials Call Center, Ft. Collins, Colorado 80526, United States
GSK Clinical Trials Call Center, Fort Collins, Colorado 80528, United States
GSK Clinical Trials Call Center, Denver, Colorado 80206, United States
GSK Clinical Trials Call Center, Denver, Colorado 80230, United States
GSK Clinical Trials Call Center, Stamford, Connecticut 06902, United States
GSK Clinical Trials Call Center, Tallahassee, Florida 32308, United States
GSK Clinical Trials Call Center, Pensacola, Florida 32504, United States
GSK Clinical Trials Call Center, Coral Gables, Florida 33134, United States
GSK Clinical Trials Call Center, Miami, Florida 33176, United States
GSK Clinical Trials Call Center, Tamarac, Florida 33321, United States
GSK Clinical Trials Call Center, Atlanta, Georgia 30342, United States
GSK Clinical Trials Call Center, Conyers, Georgia 30013, United States
GSK Clinical Trials Call Center, Columbus, Georgia 31904, United States
GSK Clinical Trials Call Center, Lilburn, Georgia 30047, United States
GSK Clinical Trials Call Center, South Bend, Indiana 46617, United States
GSK Clinical Trials Call Center, Metairie, Louisiana 70006, United States
GSK Clinical Trials Call Center, Bethesda, Maryland 20814, United States
GSK Clinical Trials Call Center, Wheaton, Maryland 20902, United States
GSK Clinical Trials Call Center, Ypsilanti, Michigan 48197, United States
GSK Clinical Trials Call Center, St. Louis, Missouri 63104, United States
GSK Clinical Trials Call Center, Billings, Montana 59102, United States
GSK Clinical Trials Call Center, Bozeman, Montana 59718, United States
GSK Clinical Trials Call Center, Omaha, Nebraska 68130, United States
GSK Clinical Trials Call Center, Cherry Hill, New Jersey 08003, United States
GSK Clinical Trials Call Center, Utica, New York 13502, United States
GSK Clinical Trials Call Center, New York, New York 10021, United States
GSK Clinical Trials Call Center, Great Neck, New York 11023, United States
GSK Clinical Trials Call Center, High Point, North Carolina 27262, United States
GSK Clinical Trials Call Center, Asheville, North Carolina 28801, United States
GSK Clinical Trials Call Center, Cincinnati, Ohio 45231, United States
GSK Clinical Trials Call Center, Mississauga, Ontario L4W 1N2, Canada
GSK Clinical Trials Call Center, Portland, Oregon 97213, United States
GSK Clinical Trials Call Center, Tigard, Oregon 97223, United States
GSK Clinical Trials Call Center, Pittsburgh, Pennsylvania 15243, United States
GSK Clinical Trials Call Center, Pittsburgh, Pennsylvania 15241, United States
GSK Clinical Trials Call Center, Philadelphia, Pennsylvania 19107, United States
GSK Clinical Trials Call Center, Philadelphia, Pennsylvania 19140, United States
GSK Clinical Trials Call Center, Charlottetown, Prince Edward Island C1A 5Y9, Canada
GSK Clinical Trials Call Center, Providence, Rhode Island 02906, United States
GSK Clinical Trials Call Center, East Providence, Rhode Island 02914, United States
GSK Clinical Trials Call Center, Lincoln, Rhode Island 02865, United States
GSK Clinical Trials Call Center, Saskatoon, Saskatchewan S7K 7H9, Canada
GSK Clinical Trials Call Center, Orangeburg, South Carolina 29118, United States
GSK Clinical Trials Call Center, Gaffney, South Carolina 29340, United States
GSK Clinical Trials Call Center, Spartanburg, South Carolina 29303, United States
GSK Clinical Trials Call Center, Orangeburg, South Carolina 29118, United States
GSK Clinical Trials Call Center, Union, South Carolina 29309, United States
GSK Clinical Trials Call Center, Austin, Texas 78750, United States
GSK Clinical Trials Call Center, Houston, Texas 77054, United States
GSK Clinical Trials Call Center, Houston, Texas 77030, United States
GSK Clinical Trials Call Center, Corsicana, Texas 75110, United States
GSK Clinical Trials Call Center, El Paso, Texas 79925, United States
GSK Clinical Trials Call Center, Richmond, Virginia 23225, United States
GSK Clinical Trials Call Center, Spokane, Washington 99204, United States
GSK Clinical Trials Call Center, Seattle, Washington 98105, United States
GSK Clinical Trials Call Center, Lacey, Washington 98516, United States
GSK Clinical Trials Call Center, West Allis, Wisconsin 53227, United States
