Efficacy And Safety Of GW642444M Comparing Placebo In Adolescent And Adult Subjects With Persistent Asthma.
Condition: Asthma
MeSH terms: Asthma
Intervention: GW642444M; Placebo
Intervention description: GW642444M; Placebo mulit-dose dry powder inhaler
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 614.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No
Keywords: dose ranging; placebo; asthma; safety; efficacy; pharmacokinetics

Summary:

      This study is designed to determine if the investigational drug is effective and safe in
      individuals with asthma
    

Eligibility criteria:

        Inclusion criteria:

          -  Aged 12 years of age or older at Visit 1 For sites in the following countries,
             subjects recruited will be ³ 18 years of age: Germany, Hungary and the Russian
             Federation and any other countries where local regulations or the regulatory status of
             study medication permit enrolment of adults only.

          -  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.

          -  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.

          -  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.

          -  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 (≤ 880mcg1/
        ≤1000mcg2) fluticasone propionate DPI(≤ 1000mcg) beclomethasone dipropionate(≤ 1680mcg1/ ≤
        2000mcg2) beclomethasone dipropionate HFA (QVAR)(≤ 640mcg1/ ≤ 800mcg2) budesonide DPI/MDI(≤
        2000mcg) Flunisolide(≤ 2000mcg) triamcinolone acetonide(≤ 2000mcg) mometasone furoate(≤
        880mcg) Ciclesonide(≤ 320mcg1/ ≤ 400mcg2)

        CFC=chlorofluorocarbon HFA=hydrofluoroalkane

          1. Ex-actuator dose

          2. Ex-valve dose

               -  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].

               -  Appropriately signed and dated informed consent has been obtained.

               -  Capable of withholding salbutamol/albuterol use for ≥ 6 hours prior to clinic
                  visits.

               -  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.

        Exclusion criteria:

          -  An exacerbation of asthma within 4 weeks of Visit 1, or a culture documented or
             suspected bacterial or viral infection of the upper or lower respiratory tract, sinus
             or middle ear within 4 weeks of Visit 1 that led to a change in asthma management, or
             in the opinion of the Investigator is expected to affect the subjects asthma status or
             the subjects ability to participate in the study.

          -  History of life-threatening asthma, defined as an asthma episode that required
             intubation and/or was associated with hypercapnoea, respiratory arrest or hypoxia
             seizures.

          -  Asthma exacerbation requiring treatment with oral corticosteroids within 3 months
             prior to Visit 1.

          -  Hospitalised for an asthma exacerbation within 6 months of Visit 1. Hospitalisation is
             defined as an overnight stay in a hospital.

          -  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.

          -  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:

        congestive heart failure, known aortic aneurysm clinically significant coronary heart
        disease, clinically significant cardiac arrhythmia stroke within 3 months of Visit 1,
        uncontrolled hypertension1 poorly controlled peptic ulcer, haematologic, hepatic, or renal
        disease immunologic compromise, current malignancy2 tuberculosis (current or untreated3),
        Cushing's disease Addison's disease, uncontrolled diabetes mellitus uncontrolled thyroid
        disorder, recent history of drug or alcohol abuse neurological disease, pulmonary disease4

          1. systolic blood pressure 160, or diastolic blood pressure >100

          2. history of malignancy is acceptable only if subject has been in remission for one year
             prior to Visit 1 (remission = no current evidence of malignancy and no treatment for
             the malignancy in the 12 months prior to Visit 1)

          3. Subjects with a history of tuberculosis who have received an approved prophylactic
             treatment regimen or an approved active treatment regimen and who have no evidence of
             active disease for a minimum of 2 years may be enrolled [American Thoracic Society
             Documents, 2005] [American Thoracic Society (ATS), 2003]

          4. Including but not limited to chronic bronchitis, emphysema, bronchiectasis with the
             need of treatment, cystic fibrosis, bronchopulmonary dysplasia, and chronic
             obstructive pulmonary disease.

               -  Any adverse reaction including immediate or delayed hypersensitivity to any
                  ß2-agonist or sympathomimetic drug, or known (i.e., patients with a history of
                  severe milk protein allergy) or suspected sensitivity to the constituents of
                  GW642444M inhalation powder (e.g., lactose or magnesium stearate).

               -  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 Diary).

               -  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

          -  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).

          -  Administration of systemic, oral or depot corticosteroids or administration of
             anti-IgE (e.g. omalizumab [Xolair]) within 12 weeks of Visit 1.

          -  Administration of the following asthma medications within 14 days of Visit 1:

          -  Theophyllines

          -  Oral β2-agonists (e.g. bambuterol)

          -  Slow-release bronchodilators

          -  Anticholinergics - short or long-acting

          -  Oral long acting antihistamines

          -  Oral leukotriene receptor antagonists (e.g. montelukast)