Study of Dose-response to Bronchodilator and Dose-finding in Child 2.5 to 6 Years - Study Golden
Condition: Asthma
Study type: Interventional
Phase: Phase 2

Summary: 
      In older children and adults, bronchodilator (BD) dose-effect relationship is part of the
      characteristics of asthma disease. There are no data on BD dose-response relationship in
      wheezy preschool children whose disease pathophysiology is poorly understood, but may, in
      part, takes on the characteristics of asthma.

      The investigators assume that 1) in young children interrupter resistance (Rint) could be
      used to measure a BD effect 2) the response to BD may vary depending on the dose used 3) the
      dose-response relationship could depend on the environment and gene polymorphism ADBR2.

      This is a prospective phase II study on dose-response relationship and description of the
      dose-response curve design using a "sparse" and a modeling approach MCP-Mod.

      The dose-response relationship will be modeled by sparse data. The investigators will test
      two doses per child in four designs that will be drawn. These doses will be assessed using
      Rint technique by a person blinded to the actual dose delivered to the child.

      Measurements of 90 children will estimate E0, Imax and D50 (pharmacokinetic constants) with
      an accuracy of 3.5%, 8.9% and 25.7% respectively.

      The bronchodilator used in the study is the Salbutamol as Ventolin ® (GSK) suspension for
      inhalation as an aerosol at a dose of 100μg per puff. Ventolin ® is used as part of the MA
      (No. 344 387-3)
    

Detailed description: 
      In older children and adults, bronchodilator (BD) dose-effect relationship is part of the
      characteristics of asthma disease. There are no data on BD dose-response relationship in
      wheezy preschool children whose disease pathophysiology is poorly understood, but may, in
      part, takes on the characteristics of asthma.

      We assume that 1) in young children interrupter resistance (Rint) could be used to measure a
      BD effect 2) the response to BD may vary depending on the dose used 3) the dose-response
      relationship could depend on the environment and gene polymorphism ADBR2.

      This is a prospective phase II study on dose-response relationship and description of the
      dose-response curve design using a "sparse" and a modeling approach MCP-Mod.

      The dose-response relationship will be modeled by sparse data. We will test two doses per
      child in four designs that will be drawn. These doses will be assessed using Rint technique
      by a person blinded to the actual dose delivered to the child.

      Measurements of 90 children will estimate E0, Imax and D50 (pharmacokinetic constants) with
      an accuracy of 3.5%, 8.9% and 25.7% respectively.

      The bronchodilator used in the study is the Salbutamol as Ventolin ® (GSK) suspension for
      inhalation as an aerosol at a dose of 100μg per puff. Ventolin ® is used as part of the MA
      (No. 344 387-3) clinical implications The demonstration, first, of the possibility for Rint
      to detect a dose-response to BD will lead, secondly, to the determination of the minimum dose
      required for the detection of a reversibility in young children using Rint. It will end a
      long-standing debate about whether, when no Rint change is observed after BD administration
      in a young child, the child has actually no reversibility or the BD dose used was not
      sufficient to demonstrate one.

      Moreover, the demonstration of a BD dose-response relationship in young children will suggest
      similarity between wheezy young children and older children and adults with asthma bronchial
      behaviour that may have possible therapeutic implications.
    

Intervention name(s): salbutamol; Salbutamol - dose2; Salbutamol -dose3; salbutamol -dose4
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Metered dose inhaler, 100µg+300µg per puff, administered one day; Metered dose inhaler, 100µg+500µg per puff, administered one day; Metered dose inhaler, 200µg+600µg per puff, administered one day; Metered dose inhaler, 200µg+200µg per puff, administered one day
Other intervention name(s): Salbutamol -100µg+300µg; salbutamol -100µg+500µg; salbutamol -200µg+600µg; salbutamol -200µg+200µg
Intervention MeSH terms: Albuterol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Pediatrics; Bronchial wheeze; bronchodilator; lung function; airway resistance