A Randomized Double-Blind Placebo-Controlled, Parallel-Group, Multicenter, Study to Evaluate the Efficacy and Safety of GW685698X Inhalation Powder 200mcg, 400mcg, 600mcg and 800mcg Administered Once Daily in the Morning and Fluticasone Propionate 500mcg BID via DISKUS Inhalation Powder Compared with Placebo for 8 Weeks in Adolescent and Adult Subjects (=12 years old) with Persistent Asthma Symptomatic on Moderate-Dose ICS Therapy
- Conditions
- Patients with persistent bronchial asthma symptomatic on moderate dose inhaled corticosteroid therapy.
- Registration Number
- EUCTR2005-001122-87-LV
- Lead Sponsor
- GlaxoSmithKline Research and Development
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- Not specified
Type of Subject: Outpatient
Age: 12 years of age or older at Visit 1 (or =18 years of age or older if local regulations or the regulatory status of study medication permit enrollment of adults only).
Gender: Male or Eligible Female
To be eligible for entry into the study, females of childbearing potential must commit to consistent and correct use of an acceptable method of birth control, as defined by the protocol.
(A serum pregnancy test is required for all females. This test will be performed at the initial screening visit (Visit 1) and Visit 7. In addition, a urine pregnancy test will be performed on the morning of the double-blind treatment visit, prior to randomization, (Visit 2) and at Visits 3 through 6.)
Asthma Diagnosis: Asthma as defined by the National Institutes of Health [National Institutes of Health, 2002].
Severity of Disease: A best FEV1 of 50% 80% of the predicted value during Visit 1 based on the Standardization of Lung Function Tests [European Respiratory Society, 1993] standards for 18 years and older or Polgar [Polgar, 1971] standards for 12-17 years and race adjusted for African-Americans [American Thoracic Society, 1991].
Reversibility of Disease: Demonstrated a = 12% and = 200mL reversibility of FEV1 within 30-minutes following 2-4 inhalations of albuterol/salbutamol/salbutamol inhalation aerosol (or one nebulized treatment with albuterol/salbutamol/salbutamol solution) at the Screening Visit. If a subject fails to demonstrate an increase in FEV1 =12% and =200mL, then the subject is not eligible for the study and will not be allowed to rescreen.
Current Anti-Asthma Therapy: Subjects must be using an inhaled corticosteroid for at least 3 months prior to Visit 1 and be maintained on a stable dose for four weeks prior to Visit 1 at one of the doses outlined in section 5.2.1 of the protocol.
Short-Acting Beta- 2-Agonists: All subjects must be able to replace short-acting beta-2-agonists with albuterol/salbutamol HFA inhalation aerosol at Visit 1for use as needed for the duration of the study. Nebulized albuterol/salbutamol HFA will not be allowed during the study with the exception of its use during reversibility testing at Visit 1. Subjects must be able to withhold all inhaled short-acting beta sympathomimetic bronchodilators for at least 6 hours prior to study visits.
Informed Consent: All subjects must be able and willing to give written informed consent to take part in the study.
Compliance: Subjects must be able to comply with all the study requirements.
At the end of the run-in period, a subject will be eligible to enter the treatment period of the study if he/she meets the following criteria at Visit 2:
Reproducibility: Morning pre-dose percent predicted FEV1 of between 50% and 80% of their predicted normal and within ±15% of the best pre-albuterol/salbutamol HFA FEV1 at Visit 1.
Demonstrated and reported, in a daily diary, symptoms of asthma (a score of = 1 on the daytime or nighttime asthma symptom scores) on at least 4 of the last 7 consecutive days of the run-in period or daily albuterol/salbutamol HFA use must have been used on at least 4 of the last 7 consecutive days of the run-in period.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
History of Life-threatening asthma: Defined for this protocol as an asthma episode that required intubation and/or was associated with hypercapnea, respiratory arrest or hypoxic seizures.
Respiratory Infection: History of respiratory tract infection and/or exacerbation of asthma within 4 weeks of Visit 1.
Asthma Exacerbation: Any asthma exacerbation requiring oral corticosteroids within 3 months of Visit 1. A subject must not have had any hospitalization for asthma within 6 months prior to Visit 1.
Concurrent Respiratory Disease: A subject must not have current evidence of pneumonia, pneumothorax, atelectasis, pulmonary fibrotic disease, bronchopulmonary dysplasia, chronic bronchitis, emphysema, chronic obstructive pulmomary disease, or other respiratory abnormatlities other than asthma
Other Concurrent Diseases/Abnormalities: A subjects must not have any clinically significant, uncontrolled condition or disease state, that in the opinion of the investigator, would put the safety of the patient at risk through study participation or would confound the interpretation of the efficacy results if the condition/disease exacerbated during the study.
The list of additional excluded conditions/diseases includes, but is not limited to the following: Congestive heart failure, known aortic aneurysm, clinically significant coronary heart disease, clinically significant cardiac arrhythmia, stroke within 3 months of Visit 1, uncontrolled hypertension*, poorly controlled peptic ulcer, hematologic, hepatic, or renal disease, immunologic compromise, current malignancy**, tuberculosis (current or quiescent), Cushing’s disease, Addison’s disease, uncontrolled diabetes mellitus, recent history of drug or alcohol abuse
*systolic BP>170, or diastolic BP >100, **history of malignancy is acceptable only if subject has been in remission for one year prior to Visit 1 (remission = no current evidence of malignancy and no treatment for the malignancy in the 12 months prior to Visit 1)
Oropharyngeal Examination: A subject will not be eligible for the run-in if he/she has an abnormal orophryngeal exam at Visit 1 (culture positive test for candidiasis) (Section 6.3.3).
Drug Allergy: Any adverse reaction including immediate or delayed hypersensitivity to any beta2-agonist, sympathomimetic drug, or any intranasal, inhaled, or systemic corticosteroid therapy. Known or suspected sensitivity to the constituents of the new powder inhaler (i.e. lactose or GW857238X).
Milk Protein Allergy: History of severe milk protein allergy.
Immunosuppressive Medications: A subject must not be using, or require use, of immunosuppressive medications during the study.
Tobacco Use. A subject may not have used tobacco products within the past one year (i.e., cigarettes, cigars, or pipe tobacco) or have historical use of >10 pack years (e.g. 20 cigarettes/day for 10 years).
Corticosteroid Use: Administration of systemic, oral or depot corticosteroids within 12 weeks of Visit 1.
Potent Cytochrome P450 34A (CYP34A) inhibitors: Patients who are receiving potent CYP3A4 inhibitors within 4 weeks of Visit 1(e.g., ritonavir, ketoconazole, itraconzole).
Clinical Laboratory Abnormalities: Clinically significant abnormal laboratory tests during Visit 1 which are still abnormal upon repeat analysis and are not believed to be due to disease(s) present. Each Investigator will use his/her own discretion in determining the clinical significance of the abnormality. When in doubt, GlaxoSmit
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method