E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
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 Therapy Maximum 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 short-acting beta-sympathomimetic bronchodilators for at least 6 hours prior to study visits. 9. Informed Consent: All subjects must be able and willing to give written informed consent to take part in the study. 10. 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 they meet the following criteria: 1. Morning pre-dose percent predicted FEV1 of 50% to 80% of their predicted normal and within 15% of the pre-albuterol/salbutamol HFA inhalation aerosol FEV1 at Visit 1. 2. Have 4 or more days when the subject required albuterol/salbutamol HFA inhalation aerosol during the 7 days immediately preceding Visit 1 or a 24 hour asthma symptom score of 1 on at least 4 of the last 7 days immediately preceding Visit 1.
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E.4 | Principal exclusion criteria |
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.
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E.5 End points |
E.5.1 | 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). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
To evaluate the optimal dose interval of 400mcg of GW685698X in persistent bronchial asthmatics. |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the trial will occur when the last subject has attended the last follow up visit. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 9 |