| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Out-patients with persistent bronchial asthma, currently symptomatic on low dose inhaled corticosteroids. |
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| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 7.1 |
| E.1.2 | Level | 4 |
| E.1.2 | Classification code | 10003553 |
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| 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 is to evaluate the efficacy of 500µg GW799943X am dosing, 500mcg GW799943X pm dosing, and 1000µg of GW799943X am dosing once-daily inhaled via the ROTADISK™/ DISKHALER™ compared with placebo over a 28-day treatment period.
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| E.2.2 | Secondary objectives of the trial |
The secondary objectives are to evaluate the safety of 500µg AM, 500µg PM and 1000µg of GW799943X AM administered once-daily via the ROTADISK™/ DISKHALER™ compared with placebo over a 28-day treatment period and to compare the relative efficacy and safety of 500µg and 1000µg of GW799943X once-daily with fluticasone propionate 250µg BD.
To evaluate the effect of time of dosing (morning vs evening) of GW799943X 500µg once daily, administered by inhalation via the ROTADISK/DISKHALER upon efficacy and safety during the 28-day treatment period.
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| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
1.Male and females aged 18 - 65 years inclusive on the day the subject gives consent to participate in the study.
A female is eligible to enter and participate in the study if she is of:
a.Non childbearing potential or
b.Child-bearing potential, has a negative pregnancy test (urine) at entry, and agrees to an acceptable contraceptive method when used consistently and correctly •
2.Documented clinical history of mild/moderate persistent asthma first diagnosed at least 6 months prior to Visit 1.
3.Using an inhaled corticosteroids for a least 3 months prior to Visit 1 at one of the following doses:
Asthma Therapy fluticasone propionate MDI CFC/HFA fluticasone propionate DPI beclomethasone dipropionate beclomethasone dipropionate HFA (QVAR) budesonide DPI flunisolide triamcinolone acetonide mometasone furoate ciclesonide Maximum Daily Dose (mcg/day) ≤176mcg1/≤200mcg2 ≤200mcg ≤420mcg1/≤500mcg2 ≤160mcg1/≤200mcg2 ≤400mcg ≤1000mcg ≤1000mcg ≤200mcg ≤160mcg1/≤200mcg2 .
4.Able and willing to give written informed consent to take part in the study.
5.Able to comply with all the study requirements.
6.A pre-dose pre-bronchodilator peak exploratory flow (PEF) of between 50-80% predicted at Visit 1 (European Community for Coal and Steel [ECCS, 1993]) predicted values will be used for subjects aged ≥ 18 to 65 years.
7.Increase in PEF of ≥ 15% 20 minutes after inhalation of 200-400μg salbutamol/albuterol at Visit 1.
At the end of the Run-In period, subjects must fulfil the following additional criteria from Daily Record Card recordings in order to enter the treatment period of the study.
1.A pre-dose pre-bronchodilator FEV1 of 50-80% predicted normal at Visit 2.
2.Daily asthma symptom score (day-time and night-time) of ≥ 1 on at least four of the last seven consecutive days of the run-in period and a total score of ≥ 7 over the last 7 consecutive days.
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| E.4 | Principal exclusion criteria |
A subject will not be eligible for inclusion in this study if any of the following criteria apply:
1. History of upper or lower respiratory tract infection and/or exacerbation of asthma within 4 weeks of Visit 1.
2. History of life-threatening asthma, defined as an asthma episode that required intubation and/or was associated with hypercapnoea, respiratory arrest or hypoxic seizures.
3.A history of 2 or more asthma exacerbations requiring treatment with oral corticosteroids or requiring hospitalisation in the 6 months before Visit 1.
4.Previously enrolled in this study, or currently participating or have participated in another study during the last 3 months (if the study involves a new chemical entity) or 2 months (if the product is already launched and commercially available).
5.Past or present disease which, as judged by the Investigator, may affect the outcome of this study. These diseases include, but are not limited to, cardiovascular disease, malignancy, hepatic disease, renal disease, haematologic disease, neurological disease, endocrine disease or pulmonary disease (including, but not confined to, chronic bronchitis, emphysema, bronchiectasis with the need of treatment, cystic fibrosis and bronchopulmonary dysplasia).
6.Known or suspected sensitivity to the constituents of ROTADISKs (e.g. lactose) or severe milk protein allergy.
7.Undergoing allergen desensitisation therapy.
8.Subjects who are likely to be non-compliant with study medication and other study-related requirements (e.g. attendance at clinic visits or completion of daily record cards).
9.Neurological or psychiatric disease or history of drug or alcohol abuse which would interfere with the subject’s proper completion of the protocol requirements.
10.Is a current smoker or has a smoking history of 10 pack years or more (e.g. 20 cigarettes/day for 10 years). A current smoker is defined as a subject who is currently smoking or who stopped smoking within 6 months of Visit 1.
11.Administration of systemic, oral or depot corticosteroids within 8 weeks of Visit 1.
12.Administration of anti-leukotrienes, including suppressors of leukotriene production and antagonists within 4 weeks of Visit 1.
13.Administration of combination therapy for asthma containing β2-agonists and/or inhaled corticosteroids within 2 weeks of Visit 1.
14.Administration of known potent inhibitors of CYP 3A4 (e.g. ritonavir, ketoconazole) within 4 weeks of Visit 1.
15.Administration of bronchodilators (theophyllines, slow release bronchodilators, oral β2-agonists, long-acting-inhaled β2-agonists, and anticholinergics) within 2 weeks of Visit 1. (Usage of inhaled SABA is permitted - see Section 9.1)
16.Administration of ketotifen within 2 weeks of Visit 1.
17.Pregnant or lactating females.
At the end of the Run-In period subjects must not meet any of the following additional criteria in order to enter the treatment period of the study.
1.Evidence of clinically significant abnormality, as judged by the investigator, in the haematological, biochemical or urinalysis screen at Visit 1.
2.Evidence of clinically significant abnormality, as judged by the investigator, in the 12-lead ECG at Visit 1.
3.Changes in asthma medication (excluding rescue salbutamol/albuterol provided at Visit 1).
4.Occurrence of an upper or lower respiratory tract infection during the run-in period.
5.Exacerbation of asthma during the run-in period. (An exacerbation of asthma is defined as any clinical worsening of asthma that requires treatment with anything other than rescue salbutamol/albuterol or the subjects ICS.)
6.Non-compliance with completion of the DRC. (Subjects must have completed PEF and symptom data for at least 4 of the last 7 consecutive days of the run-in period.)
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| Mean change from baseline in (pre-dose and pre-bronchodilator) daily trough morning peak expiratory flow (PEF) during the 28-day treatment period. |
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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 | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | Yes |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Yes |
| 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) | 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) | Yes |
| 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. Each subject will attend a follow up visit 1 week after last study drug dose has been administered. |
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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 | 0 |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
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