A Single Inhalation Dose Study to Assess Efficacy, Pharmacokinetics (PK), Safety and Tolerability of AZD8871 in Patients With Long-term Lung Diseases.
Condition: Chronic Obstructive Pulmonary Disease
MeSH terms: Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Study type: Interventional
Phase: Phase 2

Summary: 
      This study will evaluate the efficacy and safety data of AZD8871 in patients with moderate to
      severe chronic obstructive pulmonary disease (COPD). This study will determine the 24-hour
      efficacy (lung function) profile of AZD8871 600 μg relative to placebo dry powder inhaler
      (DPI) based on trough forced expiratory volume in 1 second (FEV1) following repeated dosing
      (2 weeks). Anoro® Ellipta® (umeclidinium/vilanterol) once daily is included as an active
      control. This study aims at providing a novel approach to the treatment of COPD with greater
      efficacy than single-mechanism bronchodilators, equivalent to long-acting muscarinic
      antagonist (LAMA) and long-acting β2-agonist (LABA) administered as free- or fixed-dose
      combination therapies, with an equivalent or superior safety and tolerability profile.
    

Detailed description: 
      This randomized, double-blind, placebo and active-controlled crossover study will be
      conducted at 5 sites in Germany and the United Kingdom (UK). Approximately 180 patients will
      be screened in order to randomize 72 patients into the study. Based on previous studies
      estimate, it is anticipated that 54 patients will be evaluable (study completers) assuming an
      approximate 25% dropout rate. A subset of 36 patients, who will have specifically consented
      for pharmacokinetics (PK), will undergo PK assessments. The study will consist of -

        -  A Screening period: Will last up to 28 days and consists of 2 Screening visits (Visit 1
           and Visit 2) and a run-in period (between a minimum of 14 and a maximum of 28 days; from
           Visit 2 to Visit 3).

        -  Three treatment periods (Visit 3; 14 days each; each separated by a wash-out period of
           42 to 49 days) and

        -  A Follow-up Visit: 42 days (up to 49 days) after last investigational product (IP)
           administration.

      Patients will be requested to stop their usual COPD therapy after signing the informed
      consent form (ICF) at Visit 1 and will be maintained on a mono-component inhaled
      corticosteroid (ICS) therapy, if required. Patients that were taking any LAMA will be
      maintained with ipratropium (34 µg × 2 puffs 4 times per day) between Visit 1 and Visit 2. In
      addition, salbutamol 100 µg will be provided as rescue medication during the study as needed
      (rescue medication has to be discontinued 6 hours before any pulmonary function test). Visit
      1 and Visit 2 could be performed on the same day if no wash-out of prior medication is
      required and the patient visits the site in fasting condition. In case any wash-out of prior
      medication is required, then Visit 2 will be performed after the wash-out is complete. If
      reversibility criteria and forced expiratory volume in 1 second (FEV1) predicted values are
      fulfilled according to inclusion criteria, the patient will be started on run-in period to
      assess clinical stability. If reversibility criteria or FEV1 predicted values are not met,
      pulmonary function tests could be rescheduled at the latest, up to Day 14. During the run in
      period, all patients will receive ipratropium 34 µg × 2 puffs 4 times per day (must be
      discontinued 8 hours prior to previous any pulmonary function test). A paper diary will be
      used to collect adverse events (AEs) and concomitant medication during run-in and wash-out
      periods.

      Eligible patients will be randomized in 1:1:1:1:1:1 ratio to 1 of 6 treatment sequences and
      will receive orally 1 of the following 3 treatments sequence in the form of inhalation powder
      using DPI :

        -  AZD8871 600 µg once daily (double-blind).

        -  Anoro® Ellipta® (55 µg umeclidinium [UMEC]/ 22 µg vilanterol [VI]) once daily
           (double-blind).

        -  Placebo (double-blind). Study treatment administration during all the visits at the
           sites (Day 1, Day 2, Day 8, and Day 14 of each treatment period) will be supervised by
           study personnel.

      During the treatment period Visits, safety and tolerability assessments and pulmonary
      function measurements will be taken pre-dose and up to 24 hours (Day 1) and up to 4 hours
      (Day 8) post-dose, respectively.

      At Visits 3 to 11, a subset of 36 patients will undergo PK assessments. Blood samples will be
      collected pre-dose and up to 24 hours post dose.

      In follow-up visit, AEs, safety laboratory, electrocardiogram (ECG), vital signs and physical
      examination will be assessed.

      The study includes 12 visits and the entire study period is scheduled to take from a minimum
      of 6.5 months (182 days) to a maximum of 7.5 months (217 days) for each individual patient.
      The estimated study duration is 12 months.
    

Intervention name(s): AZD8871; Anoro® Ellipta®
Intervention type(s): Drug; Drug
Intervention description(s): Randomized patients will receive 14 repeated daily doses of AZD8871 600 µg inhalation powder via DPI.; Randomized patients will receive 14 repeated daily doses of Anoro® Ellipta® (55 µg/22 µg) inhalation powder via DPI.
Other intervention name(s): Anoro® - Umeclidinium/Vilanterol; Ellipta® - Device
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Moderate to severe COPD; Muscarinic receptor antagonist; β2 adrenoceptor agonist (MABA); Long-acting muscarinic antagonist (LAMA); Long-acting β2-agonist (LABA); Inhaled long-acting bronchodilator; Small airways disease (obstructive bronchiolitis); Parenchymal destruction (emphysema),