Efficacy, Pharmacokinetics (PK), Safety and Tolerability Study of Inhaled AZD8871
Condition: Chronic Obstructive Pulmonary Disease COPD
MeSH terms: Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Study type: Interventional
Phase: Phase 2

Summary: 
      This is a study to evaluate the effects of AZD8871 in patients with COPD. Adult male or
      female patients with moderate to severe COPD, who agree to be in this study, will receive 3
      treatments, i.e. 2 different doses of AZD8871 and placebo (dummy medication containing no
      drug) at once a day for 2 weeks, in a random order. To make the comparison between AZD8871
      and placebo as fair as possible, this study is "double blinded." This means that neither
      patient nor the study doctor will know in which order the 3 treatments will be given. This
      study will include patients who are between 40 and 80 years of age. In total there will be 42
      patients participating in this study at two study centers in the United Kingdom and Germany.
      The study will have a total of 12 visits for each patient spanning for a period of 4 to 6
      months. The study is anticipated to run for approximately 8 months and should not exceed 10
      months.
    

Detailed description: 
      This is a proof-of-concept, randomised, double-blind, placebo-controlled, 3-way, complete
      crossover William's design, multiple dose study to investigate the efficacy, PK, safety, and
      tolerability of 2 dose levels of AZD8871 and placebo, administered using a dry powder inhaler
      (DPI) device once daily, for 2 weeks, in patients with moderate to severe COPD. AZD8871 is a
      new chemical entity with the combined properties of a LAMA and a LABA in a single molecule.
      AZD8871 is being developed as an inhaled long-acting bronchodilator for the maintenance
      treatment of COPD.

      The objective of the study is to assess the efficacy, safety and PK of AZD8871 after a 14-day
      treatment period at 2 different doses in patients with moderate to severe COPD. The target
      population includes male and female (non-childbearing potential) adult patients with clinical
      diagnosis of moderate to severe COPD. The crossover design has been chosen to avoid
      inter-patient variability and optimize sample size. By randomly assigning treatment sequence,
      differences in baseline characteristics of the treatment groups will be minimised. The
      inclusion of a placebo arm is considered the most reliable method to minimise patient and
      Investigator bias. The proposed dose levels of AZD8871 in this study are 100 and 600 µg of
      AZD8871 given by inhalation once daily for 14 days through a single dose DPI. Doses have been
      selected based on the safety, tolerability, PK and pharmacodynamics (PD) information
      generated in previous clinical trials with AZD8871. The wash-out period proposed for this
      current study is a minimum of 28 days and up to 35 days in order to avoid any carry over
      effect between periods. The broad dose range selected (6 fold range from 100 to 600 µg) has
      been chosen to span the likely therapeutic dose and facilitate the dose selection for future
      studies. Considering the expected efficacy in patients with COPD and the available data to
      date, it is anticipated the benefits will outweigh the risks and support the continued
      investigation of AZD8871 in clinical studies.
    

Intervention name(s): AZD8871 100 µg; AZD8871 600 µg; Placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): The subjects will receive one dose of AZD8871 100 µg single dose DPI.; The subjects will receive AZD8871, 600 µg single dose DPI.; The subject will receive Placebo single dose DPI.
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: AZD8871; long-acting muscarinic antagonist (LAMA); long-acting β2-agonist (LABA); inhaled long-acting bronchodilator; pharmacokinetics; safety; tolerability; efficacy; Phase IIa; Muscarinic receptor antagonist β2 adrenoceptor agonist (MABA)