A 3-period Crossover Study With GSK573719 as Monotherapy in Adult Subjects With Asthma
Condition: Asthma
MeSH terms: Asthma
Intervention: GSK573719 Active treatment or Placebo; GSK573719 (Sub-group cohort); Salbutamol/Albuterol
Intervention description: Eligible subjects will be randomised to a sequence of three treatments from 8 possible arms: 7 active drug doses (15.6mcg, 31.25 mc, 62.5mcg 125mcg or 250mcg GSK573719 once daily; 15.6mcg or 31.25 mcg GSK573719 taken twice daily) or matched placebo.; Subjects at selected Sub-group sites (approximately 30% of the total population) will have additional serial assessments and procedures (including blood and urine samples for pharmacokinetic analysis) at the start (Day 1) and at the end (Days 14 and 15) of each treatment period. On Day 14 of each treatment period subjects will remain overnight at the clinic for 24-hour assessments, including spirometry, ECGs, and 24-hour Holter monitoring.; Salbutamol/Albuterol, short-activing beta agonist provided to all subjects to be taken as needed for the relief of asthma symptoms.throughout the study period, including washout periods
Intervention MeSH terms: Albuterol
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 350.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Asthma; Pharmacokinetics; GSK573719; Adults; Pharmacogenetics

Summary:

      This is a multi-national, randomized, double-blind, 3-period crossover, incomplete block
      design to evaluate 5 once-daily and 2 twice-daily doses of GSK573719 in combination with
      placebo. The study will explore the dose range of GSK573719 in asthmatic subjects who are
      currently using non-ICS controller medications. Subjects will participate in the study for up
      to a maximum of 14 weeks. At randomization subjects will be stratified by age to ensure
      adequate exposure to GSK573719 throughout the expected age range. The primary endpoint will
      be trough FEV1 obtained 24 hours after the last morning dose on Day 14 of each treatment
      sequence.

      A sub-group of subjects at selected sites (approximately 30% of the total population) will
      have additional serial assessments for spirometry, ECG and Holter, and pharmacokinetic
      sampling at the start and end of each treatment period. Safety assessments will include
      monitoring for adverse events, laboratory tests, asthma symptom assessments and twice daily
      PEF evaluation. Consenting subjects will have a blood sample taken for pharmacogenetic
      analysis.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Written informed consent

          -  Outpatient (sub-group will have 3 overnight stays at clinic)

          -  Diagnosis of asthma (NIH 2007) for at least 6 months

          -  Male or Eligible female (females of child-bearing potential must use acceptable method
             of birth control)

          -  A best AM pre-bronchodilator FEV1 of 60% to 85% of predicted normal value at Screening

          -  Reversibility of disease demonstrated by at least 12% and 200mL increase in FEV1 .

          -  Subjects must have been prescribed a non-corticosteroid controller at least 3 months
             preceding Visit 1, and/or a short-acting beta 2 agonist, without the use of inhaled
             corticosteroids in the 4 weeks prior to Visit 1

          -  Subjects must be able to replace their current short-acting Beta-2-agonist with
             albuterol/salbutamol aerosol inhaler for the duration of the study

          -  Subjects must be judged capable of withholding albuterol/salbutamol for at least 4
             hours prior to study visits

        Exclusion Criteria:

          -  History of life threatening asthma

          -  Severe asthma exacerbation

          -  Respiratory infection within expected to affect subject's ability to participate

          -  Concurrent respiratory disease

          -  Current smoker or smoking history of 10 pack years or more

          -  Diseases preventing use of anticholinergics

          -  Other clinically significant, uncontrolled condition or disease which would pose a
             safety risk to the patient, or confound interpretation of study results

          -  Drug allergy to any Beta-2-agonist, sympathomimetic drug, intranasal, inhaled or
             systemic corticosteroid therapy

          -  Known or suspected sensitivity to the constituents of the Novel DPI (ie lactose)

          -  History of severe milk protein allergy

          -  Administration of prescription or over-the-counter medication that would significantly
             affect the course of asthma, or interact with the study drug

          -  Any infirmity, disability or disease of a child or family member likely to impair
             compliance

          -  Alcohol or substance abuse history

          -  Viral hepatitis B surface antigen or Hepatitis C antibody

          -  Known HIV-positive history.

          -  Affiliation with investigator or site staff