E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
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 |
The primary objective of this study was to demonstrate that FSC DISKUS 250/50 BID is superior to FP DISKUS 250 BID at increasing pulmonary function as measured by forced expiratory volume in one second (FEV1) over a 52-week treatment period. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives were to compare the efficacy of the two treatment groups with respect to the following parameters: morning (AM) peak expiratory flow (PEF), percent of symptom-free days, and the
incidence of asthma attacks. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.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.
2.Type of Subject: Outpatient
3.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:
a. of non-child-bearing potential;
OR
b. 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.
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.
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E.4 | Principal exclusion criteria |
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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Mean change from baseline in pre-dose FEV1 over Weeks 1-52 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
•Morning peak flow; percentage of symptom free days; asthma attack rate
•Morning peak flow (AM PEF) Percentage of symptom-free days Asthma attack rate (per subject per year)
•Comparison of improvement in lung function as measured by FEV1 between ADVAIR DISKUS 250/50 mcg BID vs FLOVENT DISKUS mcg BID over 52 weeks
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |