E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
GW642444 is a new potent and selective inhaled beta-2-receptor agonist, which is being developed for once daily treatment of asthma and COPD. |
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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 determine the 24hour FEV1 after a single dose of GW642444 in mild to moderate asthmatic subjects. |
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E.2.2 | Secondary objectives of the trial |
To determine the duration and extent of bronchodilation of single and repeat doses of inhaled GW642444 (50, 100 and 200mcg) and salmeterol (single dose) in mild to moderate asthmatic subjects.
To assess the systemic pharmacodynamics of GW642444 following single and repeat inhaled doses (50, 100 and 200mcg) and salmeterol (single dose) in mild to moderate asthmatic subjects.
To assess the systemic pharmacokinetics of GW642444 and alpha-phenylcinnamic acid (CC12189) following single and repeat inhaled doses (50, 100 and 200mcg) and salmeterol (single dose) in mild to moderate asthmatic subjects.
To assess the safety and tolerability of a single and repeated inhaled doses of GW642444 (50, 100 and 200mcg) and salmeterol (single dose) in mild to moderate asthmatic subjects.
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Subjects with a documented history of mild to moderate asthma, with the exclusion of other significant pulmonary diseases (e.g. chronic bronchitis, emphysema, bronchiectasis with the need of treatment, cystic fibrosis and bronchopulmonary dysplasia).
Male subjects or female subjects of non child bearing potential (i.e. post-menopausal or surgically sterile) aged between 18 to 70 years. Post-menopausal females are defined as being amenorrhoeic for greater than 2 years with an appropriate clinical profile, e.g. age appropriate, history of vasomotor symptoms. However if indicated this should be confirmed by estradiol and FSH levels consistent with menopause (according to local laboratory ranges) at screening. Pre-menopausal females with a documented (medical report verification) hysterectomy and/or bilateral oophorectomy.
Subjects who are current non-smokers, who have not used any inhaled tobacco products (snuff is permitted) in the 6 month period preceding the screening visit and who have a pack history of 10 pack years.
Subjects with clinically stable asthma within the 4 weeks preceding the screening visit and with a screening pre-bronchodilator FEV1 greater than 60% predicted (having abstained from bronchodilators for the required period). Predicted values are based on the ECCS 1993 normal ranges.
During the screening visit, subjects must demonstrate the presence of reversible airway disease, defined as an increase in FEV1 of 12% over baseline and an absolute change of 300mL within 30 minutes following 400g salbutamol.
Subjects who are able and willing to give written informed consent to take part in the study.
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E.4 | Principal exclusion criteria |
Subjects who have a past or present disease, which as judged by the Investigator and the Medical Monitor, may affect the outcome of this study. These diseases include, but are not limited to, cardiovascular disease, malignancy, hepatic disease, renal disease, haematological disease, neurological disease and endocrine disease.
A mean QTc(B) value at screening >430msec (male) / >450msec (female) or an ECG that is not suitable for QT measurements (e.g. poorly defined termination of the T wave).
A screening Holter ECG tracing that reveals clinically concerning arrhythmias (including ventricular runs of >5 ventricular ectopy, R on T phenomena, bigeminy, trigeminy or quadrigeminy).
Subjects who have suffered a lower respiratory tract infection within 4 weeks of the screening visit, or an upper respiratory tract infection within 2 weeks of the screening visit.
Subjects with a history of life-threatening asthma, defined as an asthma episode that required intubation and/or was associated with either respiratory arrest or hypoxic seizures.
Subjects who have taken high doses of inhaled (> 500mcg FP/day or equivalent) or oral steroids within 6 weeks of the screening visit.
Subjects who have changed their inhaled glucocorticosteroid treatment within the last 6 weeks before screening or can be expected to do so during the study.
Subjects who have received a new chemical entity drug, or have received a marketed compound in a clinical study, within 1 month of the screening visit.
Subjects with a positive pre-study Hepatitis B surface antigen, positive Hepatitis C antibody or HIV (if tested according to site SOPs) result within 3 months of the start of the study.
Subjects with a history of drug or alcohol abuse. Abuse of alcohol is defined as an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units (males) or defined as an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units (females).
Subjects at risk of non-compliance.
Subjects who have a screening haemoglobin values < 110mg/L.
Subjects with known hypersensitivity to salbutamol or any ingredient in this preparation
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E.5 End points |
E.5.1 | Primary end point(s) |
Assessment of FEV1 at 24h after a single dose. |
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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 | 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 | 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 | No |
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 | Yes |
E.8.2.3.1 | Comparator description |
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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 | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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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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 | 4 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 4 |