| 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 | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10003553 |
| E.1.2 | Term | 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 dose response, efficacy and safety of five doses of GW642444M (3mcg, 6.25mcg, 12.5mcg, 25mcg and 50mcg) over a 28 day treatment period in subjects with persistent asthma. |
|
| E.2.2 | Secondary objectives of the trial |
To characterise the population pharmacokinetics of GW642444 in subjects with
persistent asthma |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Subjects eligible for enrolment in the study must meet all of the following criteria:
1 Aged 12 years of age or older at Visit 1
For sites in the following countries, subjects recruited will be ≥ 18 years of age:
Germany, Hungary, the Russian Federation and France and any other countries where local
regulations or the regulatory status of study medication permit enrolment of adults
only.
2 Male or eligible female subjects
A female is eligible to enter and participate in the study if she is of: Non-child bearing potential (i.e. physiologically incapable of becoming pregnant), including any female who is post-menopausal. Child bearing potential, has a negative pregnancy test at screening, and agrees to one of the following acceptable contraceptive methods used consistently and correctly (i.e. in accordance with the approved product label and the instructions of the physician for the duration of the study – screening to follow-up contact):
• Complete abstinence from intercourse from screening until 2 weeks after the
follow-up contact; or
• Sterilisation of male partner (vasectomy with documentation of azoospermia)
prior to female subject entry into the study, and this male partner is the sole
partner for that subject; or
Implants of levonorgestral inserted for at least 1 month prior to the study
medication administration but not beyond the third successive year following
insertion; or
• Injectable progestogen administered for at least 1 month prior to study
medication administration and administered for 1 month following study
completion; or
• Oral contraceptive (combined or progestogen only) administered for at least one
monthly cycle prior to study medication administration; or
• Double barrier method: condom or occlusive cap (diaphragm or cervical/vault
caps) plus spermicidal agent (foam/gel/film/cream/suppository)
N.B. For German sites female subjects must use a method of birth control other
than the double barrier method
• An intrauterine device (IUD), inserted by a qualified physician, with published
data showing that the highest expected failure rate is less than 1% per year; or
• Estrogenic vaginal ring inserted for at least 1 month prior to study medication
administration; or
• Percutaneous contraceptive patches in place for at least 1 month prior to study
medication administration
Female subjects should not be enrolled if they are pregnant, or lactating, or plan to
become pregnant during the time of study participation.
3 Documented clinical history of persistent asthma, as defined by the National
Institutes of Health [NIH, 2007] first diagnosed at least 6 months prior to Visit 1.
4 Subjects with current reversible airways disease as demonstrated at Visit 1 by an
increase in FEV1 of ≥ 12% and ≥ 200ml over the pre-salbutamol/albuterol FEV1 at
approximately 30 minutes after the inhalation of 400mcg of salbutamol/albuterol via
MDI (spacer permitted for reversibility testing only if required) or one nebulised
salbutamol/albuterol solution.
5 Subjects must be using an inhaled corticosteroid and have been maintained on a
stable dose for 4 weeks prior to Visit 1 at one of the following doses:
Maximum Allowable Concurrent Inhaled Corticosteroid Doses
Asthma Therapy Maximum Daily Dose (mcg/day)
fluticasone propionate MDI CFC/HFA ≤ 880mcg(1)/ ≤1000mcg(2)
fluticasone propionate DPI ≤ 1000mcg
beclomethasone dipropionate ≤ 1680mcg(1)/ ≤ 2000mcg(2)
beclomethasone dipropionate HFA (QVAR) ≤ 640mcg(1)/ ≤ 800mcg(2)
budesonide DPI/MDI ≤ 2000mcg
Flunisolide ≤ 2000mcg
triamcinolone acetonide ≤ 2000mcg
mometasone furoate ≤ 880mcg
Ciclesonide ≤ 320mcg(1)/ ≤ 400mcg(2)
CFC=chlorofluorocarbon HFA=hydrofluoroalkane
(1)Ex-actuator dose
(2)Ex-valve dose
6 Pre-bronchodilator FEV1 between ≥ 40 - ≤ 90% predicted at Visit 1.
NHANES III predicted values will be used for subjects aged ≥ 12 years and
adjustments to predicted values will be made for African American subjects
[Hankinson, 1999].
7 Appropriately signed and dated informed consent has been obtained.
8 Capable of withholding salbutamol/albuterol use for ≥ 6 hours prior to clinic visits.
9 In France, a subject will be eligible for inclusion in this study only if either affiliated
to or a beneficiary of a social security category. |
|
| E.4 | Principal exclusion criteria |
1 Culture-documented or suspected bacterial or viral infection of the upper or lower
respiratory tract, sinus or middle ear 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 hypoxia
seizures.
3 Asthma exacerbation requiring treatment with oral corticosteroids within 3 months
prior to Visit 1.
4 Hospitalised for an asthma exacerbation within 6 months of Visit 1.
Hospitalisation is defined as an overnight stay in a hospital.
5 Previously enrolled in this study, or has participated in any study using an
investigational drug during the previous 30 days or will participate simultaneously in
another clinical trial.
6 A subject must not have any clinically significant, uncontrolled condition or disease
state that, in the opinion of the investigator, would put the subject's safety at risk
through study participation or would confound the interpretation of the efficacy
results if the condition/disease exacerbated during the study.
The list of additional excluded conditions/diseases includes, but is not limited to the
following:Please see section 4.3.6 of the exclusion criteria within protocol.
7 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 (i.e. lactose or magnesium stearate).
8 Subjects who are likely to be non-compliant with study medication and other studyrelated
requirements (e.g. attendance at clinic visits or completion of Daily Diary).
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.
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). The number of units of alcohol in a drink can be determined by
multiplying the volume of the drink (in millilitres) by its percentage ABV and
dividing by 1000
10 Current smoker or a smoking history of 10 pack years or more (e.g. 20 cigarettes/day
for 10 years). A subject may not have used tobacco products within the past one
year (i.e., cigarettes, cigars, or pipe tobacco).
11 Administration of systemic, oral or depot corticosteroids or administration of
anti-IgE (e.g. omalizumab [Xolair]) within 12 weeks of Visit 1.
12 Administration of any of the following asthma medications within 14 days of Visit 1: Please see section 4.3.12 of the exclusion within the protocol.
13 Administration of inhaled long-acting β2-agonists (e.g. salmeterol) within 7 days of
Visit 1
14 Administration of any other prescription or over the counter medication which may
affect the course of asthma, or interact with sympathomimetic amines, such as:
Anticonvulsants (barbiturates, hydantoins, and carbamazepine); Polycyclic
antidepressants; β-adrenergic blocking agents; Phenothiazines and Monoamine
oxidase (MAO) inhibitors
15 Administration of a potent P-glycoprotein inhibitor or potent Cytochrome P450 3A4
inhibitor within 4 weeks prior to Visit 1 (e.g. ritonavir and ketoconazole)
16 A subject will not be eligible for this study if he/she is an immediate family member
of the participating Investigator, sub-Investigator, study co-ordinator, or employee of
the participating Investigator.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Mean change from baseline in clinic visit trough (pre-bronchodilator and pre-dose)
FEV1 at the end of the 28-day treatment period. The trough FEV1 will be defined as
the mean of the FEV1 values obtained 23 and 24 hours after dosing on Day 28. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Information not present in EudraCT |
| E.6.2 | Prophylaxis | Information not present in EudraCT |
| E.6.3 | Therapy | Information not present in EudraCT |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | Information not present in EudraCT |
| E.6.9 | Dose response | Information not present in EudraCT |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | Information not present in EudraCT |
| E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
| E.6.13 | Others | Information not present in EudraCT |
| 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) | Information not present in EudraCT |
| 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.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 40 |
| 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
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| 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 |
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