A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study to Evaluate the Efficacy and Safety of GW685698X Inhalation Powder 200mcg Twice-Daily, GW685698X Inhalation Powder 200mcg Once-Daily, and GW685698X Inhalation Powder 400mcg Once-Daily in the Morning Compared with Placebo for 8 Weeks in Adolescent and Adult Subjects (12 Years of Age and Older) with Persistent Asthma Symptomatic on Low-Dose ICS Therapy
- Conditions
- Persistent asthma
- Registration Number
- EUCTR2005-001841-40-DE
- Lead Sponsor
- GlaxoSmithKline Research And Development Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 0
A subject will be eligible for inclusion in the run-in period for this study only if all of the following criteria apply:
1.Type of Subject: Outpatient
2.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).
3.Gender: Male or eligible female
Females are eligible to participate only if they are currently non-pregnant and non-lactating. 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 following:
•Male partner who is sterile prior to the female subject’s entry into the study and is the sole sexual partner for that female subject
•Implants of levonorgestrel
•Injectable progestogen
•Oral contraceptive (either combined estrogen/progestin or progestin only)
•Any intrauterine device (IUD) with a documented failure rate of less than 1% per year
•Double-barrier method – spermacide plus a mechanical barrier (e.g., spermacide plus a male condom or a spermacide and female diaphragm)
•The contraceptive transdermal patch, Ortho Evra (if the subject is less than 198 pounds)
•Female subjects should not be enrolled if they plan to become pregnant during the time of study participation. A urine pregnancy test is required for all subjects at all visits.
•Females of childbearing potential who are not sexually active must commit to complete abstinence from intercourse throughout the clinical trial, and for a period after the trial to account for elimination of the drug (minimum of six days)
4.Asthma Diagnosis: Asthma as defined by the National Institutes of Health [National Institute of Health, 2002].
5.Severity of Disease: A best FEV1 of 50% to 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 to 17 years and race adjusted for African-Americans [Crapo, 1989].
6.Reversibility of Disease: Demonstrated a ?12% and 200mL reversibility of FEV1 within 30 minutes following 200 to 400mcg of albuterol/salbutamol inhalation aerosol (or one nebulized albuterol/salbutamol treatment) at Visit 1. If a subject fails to demonstrate an increase in FEV1 ?12% and 200mL, the subject is not eligible for the study and will not be allowed to re-screen.
7.Concurrent 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 following doses:
Anti-Asthma TherapyMaximum Daily Dose (mcg/day)
Fluticasone propionate MDI CFC/HFA?176mcg1/?200mcg2
Fluticasone propionate DPI?200mcg
Beclomethasone dipropionate?420mcg1/?500mcg2
Beclomethasone dipropionate HFA?160mcg1/?200mcg2
Budesonide DPI?400mcg
Flunisolide?1000mcg
Triamcinolone acetonide?1000mcg
Mometasone furoate?200mcg
Ciclesonide?160mcg1/?200mcg2
1.Ex-actuator dose
2.Ex-valve dose
8.Short-Acting Beta2-Agonist: All subjects must be able to replace short-acting beta2-agonists with albuterol/salbutamol HFA inhalation aerosol at Visit 1 for use as-needed for the duration of the study. Nebulized albuterol/salbutamol 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 s
A subject will not be eligible for inclusion in the run-in period for this study if any of the following criteria apply:
1.History of Life-Threatening Asthma: History of life-threatening asthma, defined as an asthma episode that required intubation and/or was associated with hypercapnia, respiratory arrest or hypoxic seizures.
2.Anti-Asthma Medications: Asthma medications listed below must not have been used prior to Visit 1 for the required interval listed below, and not taken during the study:
Within 24 hours of Visit 1
•Oral short-acting beta2-agonists
Within 2 weeks of Visit 1
•Combination therapy containing inhaled beta2-agonists and ICS for asthma (e.g., fluticasone propionate/salmeterol combination, budesonide/formoterol combination)
Note: Subjects must be maintained on a stable dose of ICS within 4 weeks of Visit 1 (see protocol Section 5.2.1).
•Oral beta2-agonists (e.g., bambuterol),Slow-release bronchodilators (e.g., aminophylline, theophylline), Anticholinergics, Long-acting beta2-agonists (e.g., salmeterol), Ketotifen, Nedocromil sodium, Sodium cromoglycate, Oral long-acting beta2-agonists,
Within 4 weeks of Visit 1-Anti-leukotrienes including suppressors of leukotriene production and antagonists
Within 12 weeks of Visit 1-Systemic, oral, parenteral, or depot corticosteroids, Anti-IgE (e.g., omalizumab),
3. Asthma Exacerbation: Any asthma exacerbation requiring oral corticosteroids within 3 months of Visit 1 or any hospitalization due to asthma exacerbation within 6 months of Visit 1.
4. 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 inhaler (i.e., lactose or cellobiose octaacetate).
5. Milk Protein Allergy: History of severe milk protein allergy.
6. Immunosuppressive Medications: A subject must not be using, or require use of, immunosuppressive medications during the study.
NOTE: Immunotherapy for the treatment of allergies is allowed during the study provided that it was initiated prior to Visit 1 and the subject is maintained on a stable daily dose throughout the study period.
At the end of the run-in period, a subject will not be eligible to enter the treatment period of the study if they meet the following criteria:
1. Changes to asthma medication (excluding albuterol/salbutamol HFA inhalation aerosol provided at Visit 1).
2. Occurrence of an upper or lower respiratory tract infection during the run-in period.
3. Asthma exacerbation, defined as any worsening of asthma which required treatment with asthma medications other than albuterol/salbutamol HFA inhalation aerosol and the subject’s regular inhaled corticosteroid therapy, resulted in hospitalization for asthma, or resulted in unscheduled urgent care for acute asthma symptoms requiring intervention during the run-in period.
4. Abnormal oropharyngeal examination at Visit 2 (cultured positive for candidiasis)
5. Non-compliance with completion of the Daily Diary reporting defined as failure to complete all questions on at least 4 out of the last 7 days during the run-in period.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the relative efficacy and safety of GW685698X 200mcg twice daily and GW685698X 400mcg once daily in the morning compared with placebo in adolescent and adult subjects with persistent asthma.;Secondary Objective: ;Primary end point(s): The single efficacy endpoint will be the mean change from baseline at Week 8 (last assessment on treatment using last observation carried forward) in trough (AM pre-dose and pre-rescue bronchodilator) Forced Expiratory Volume in 1 second (FEV1).
- Secondary Outcome Measures
Name Time Method