| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 12.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10001705 |
| E.1.2 | Term | Allergic asthma |
|
| 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 bronchoprotective effect of treatment with repeat inhaled doses of inhaled fluticasone furoate(GW685698)/GW642444M combination 100mcg/25 mcg and fluticasone furoate 100mcg on the early asthmatic response (EAR) to inhaled allergen at 22-23 hours post-dose in mild asthmatic subjects compared with placebo |
|
| E.2.2 | Secondary objectives of the trial |
| To evaluate the bronchoprotective effect of treatment with repeat inhaled doses of inhaled fluticasone furoate/GW642444M combination 100mcg/25 mcg on the early asthmatic response (EAR) to inhaled allergen at 22-23 hours post-dose in mild asthmatic subjects compared with fluticasone furoate 100mcg |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
A subject will be eligible for inclusion in this study only if all of the following criteria apply:
1. Males and females aged 18 to 65 years inclusive.
2. AST, ALT, alkaline phosphatase and bilirubin 1.5xULN (isolated bilirubin
>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)
3. Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
4. Body mass index within the range 18.5-35.0 kilograms/metre2 (kg/m2).
5. A female subject is eligible to participate if she is of:
• Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol < 40 pg/ml (<140 pmol/L) is confirmatory]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods in Section 8.1 if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.
• Child-bearing potential and agrees to use one of the contraception methods listed in Section 8.1 for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until 5 terminal half-live post-last dose.
6. Documented history of bronchial asthma, first diagnosed at least 6 months prior to the screening visit and currently being treated only with intermittent short-acting beta -agonist therapy by inhalation.
7. Pre-bronchodilator FEV1 >70% of predicted at screening.
8. Subjects who are current non-smokers who have not used any tobacco products in the 6-month period preceding the screening visit and have a pack history of not more than 10 pack years.
[number of pack years = (number of cigarettes per day/20) x number of years smoked]
9. Demonstration of a positive wheal and flare reaction (at least 3 mm relative to negative control) to at least one allergen from a battery of allergens (including house dust mite, grass pollen and cat hair) on skin prick testing at screening, or within 12 months of study start.
10. Methacholine challenge PC20 < 8 mg/mL at screening or previous (in last 6 months) AMP (PC20 of < 60 mg ml−1), histamine (PC20 of <: 8 mg ml−1) or methacholine challenge that confirms the diagnosis of asthma.
11. Screening allergen challenge demonstrates that the subject experiences an early asthmatic response. The early asthmatic response must include a fall in FEV1 of at least 20% from the post saline value, on at least one occasion, between 5 and 30 minutes after the final concentration of allergen.
12. Signed and dated written informed consent is obtained from the subject
13. The subject is able to understand and comply with the protocol requirements, instructions and protocol-stated restrictions.
|
|
| E.4 | Principal exclusion criteria |
A subject will not be eligible for inclusion in this study if any of the following criteria apply:
1. Past or present disease, which as judged by the investigator or medical monitor, may affect the outcome of this study. These diseases include, but are not limited to, cardiovascular disease, malignancy, gastrointestinal disease, hepatic disease, renal disease, haematological disease, neurological disease, endocrine disease or pulmonary disease (including but not confined to chronic bronchitis, emphysema, bronchiectasis or pulmonary fibrosis).
2. Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
3. Clinically significant abnormalities in safety laboratory analysis at screening.
4. Subject is hypertensive at screening. Hypertension at screening is defined as persistent systolic BP >150 mmHg or diastolic BP > 90mmHg. Subject with controlled hypertension may be included.
5. Respiratory tract infection and/or exacerbation of asthma within 4 weeks prior to the first dose of study medication.
6. History of life-threatening asthma, defined as an asthma episode that required intubation and/or was associated with hypercapnoea, respiratory arrest and/or hypoxic seizures.
7. Symptomatic with hay fever at screening or predicted to have symptomatic hayfever during days 21-29 of a treatment period of the study.
8. Administration of oral or injectable steroids within 5 weeks of screening or intranasal and/or inhaled steroids within 4 weeks of the screening visit.
9. Unable to abstain from other medications including non-steroidal anti-inflammatory drugs (NSAIDs), anti-depressant drugs, anti-asthma anti-rhinitis or hay fever medication, other than antihypertensive medication and paracetamol (up to 4 g per day) for the treatment of minor ailments e.g. headache from 14 days before screening until the follow-up visit.
10. Unable to abstain from short acting beta agonists as described in the concomitant medications and non-drug therapies section.
11. Unable to abstain from antihistamines as described in the concomitant medications and non-drug therapies section.
12. If, after 2 concurrent administrations of saline during the allergen challenge at screening the subjects still have a fall in FEV1 of greater than 10%.
13. The subject has participated in a study with a new molecular entity during the previous 3 months or has participated in 4 or more clinical studies in the previous 12 months prior to the first dosing day.
14. History of milk protein allergy.
15. History of being unable to tolerate or complete allergen challenge tests.
16. Subject is undergoing allergen desensitisation therapy.
17. A known hypersensitivity to corticosteroids.
18. Any adverse reaction including immediate or delayed hypersensitivity to any β2 agonist or sympathomimetic drug, or known or suspected sensitivity to the constituents of GW642444M inhalation powder (e.g., lactose, magnesium stearate).
19. There is a risk of non-compliance with study procedures.
20. History of blood donation (500 mL) within 3 months of starting the clinical study.
21. Subject is mentally or legally incapacitated.
22. Consumption of seville oranges, pummelos (members of the grapefruit family) or grapefruit juice from 14 days prior to the first dose of study medication.
23. The subject regularly drinks more than 28 units of alcohol in a week if male, or 21 units per week if female. One unit of alcohol is defined as a medium (125 ml) glass of wine, half a pint (250 ml) of beer or one measure (25 ml) of spirits.
24. The subject has a screening QTcB or F value of >450msec.
25. A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
26. The subject has tested positive for HIV antibodies.
27. The subject has a positive pre-study urine cotinine/ breath carbon monoxide test or urine drug or urine or breath alcohol screen. A minimum list of drugs that will be screened for include Amphetamines, Barbituates, Cocaine, Opiates, Cannabinoids and Benzodiazepines.
28. Pregnant females as determined by positive urine hCG test at screening or prior to dosing.
29. Lactating females.
30. Subjects who are kept due to regulatory or juridical order in an institution.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Weighted mean change from baseline in FEV1 between 0-2 hours, following the 22-23 hour post treatment allergen challenge on Day 29 |
|
| 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 | No |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| 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 | Yes |
| 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
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 3 |
| 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 |
|
| 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
|
| End of trial is last subject last visit. |
|
| 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 | 8 |
| E.8.9.1 | In the Member State concerned days | 0 |
| 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 | 8 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
