Safety, Tolerability and Pharmacokinetics of Multiple Ascending Doses of AZD8871 in Healthy Male Japanese Subjects
Condition: Chronic Obstructive Pulmonary Disease - COPD
MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Study type: Interventional
Phase: Phase 1

Summary: 
      AZD8871 is a new chemical entity possessing long-acting dual-pharmacology (muscarinic
      receptor antagonist and β2 adrenoceptor agonist [MABA]) in a single molecule. This type of
      agent presents a novel approach to the treatment of chronic obstructive pulmonary disease
      (COPD) and potentially asthma (in combination with an inhaled corticosteroid). AZD8871 is
      being developed for inhalation, formulated with alpha lactose monohydrate and delivered by
      dry powder inhaler (DPI) that allows delivery of a single dose of the study drug.

      The primary objective is to investigate the safety and tolerability of AZD8871 at steady
      state in healthy male Japanese subjects.
    

Detailed description: 
      This is a Phase I, single centre, randomised, single blind, placebo-controlled study to
      investigate the safety, tolerability and pharmacokinetics (PK) of single and multiple
      ascending doses of inhaled AZD8871 in healthy male Japanese subjects.

      All subjects will sign an Informed Consent Form before starting any study-related procedures.

      Twenty-four healthy subjects, aged 20 to 55 years, will participate in 3 cohorts. All
      subjects will be admitted to the unit the day preceding the 1st dose and will be housed in
      the unit until 96 hours (4 days) post last dose of investigational medicinal product (IMP)
      (Day 20).

      Eight subjects will participate in each cohort and will receive either AZD8871 or placebo,
      randomised 3:1 (6 subjects to receive AZD8871:2 subjects to receive placebo). Each subject
      will only be dosed in 1 cohort. The study design allows a gradual escalation of dose (Cohorts
      2 and 3) with intensive safety monitoring to ensure the safety of the subjects.

      In Cohort 1, subjects will receive only a single dose of AZD8871 300 µg or placebo on Day 1,
      followed by once daily dosing on Days 5 to 16. The dosing schedule of all cohorts will be
      single dose of IMP (active or placebo) on Day 1, followed by once daily dosing on Days 5 to
      16. Within 5 to 7 days of discharge from the unit, there will be two follow-up visits.

      Following each cohort, a maximum dose of 2 times the dose administered in the previous cohort
      will be considered for the subsequent cohort. However, the planned dose for Cohort 2 is 600
      µg and for Cohort 3 is 900 µg. Dosing of Cohorts 2 and 3 will be preceded by a SRC meeting,
      which will confirm the adequacy of the planned doses. A minimum of 5 subjects on active
      treatment need to complete dosing per cohort in order to proceed to the next dose level.

      The total duration of the study for each subject will be approximately 58 days (from
      Screening [up to -28 days before randomization] to Final Follow up visit [Day 30]).
    

Intervention name(s): AZD8871; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Powder for inhalation administered via single dose DPI 300 and 600 µg/inhalation.; Powder for inhalation administered via single dose DPI
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Single center, randomized, single blind, placebo-controlled study.
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: Chronic obstructive pulmonary disease (COPD); Asthma; AZD8871; muscarinic receptor antagonist and β2 adrenoceptor agonist (MABA); Phase I; Safety; Tolerability; Pharmacokinetics; long-acting muscarinic antagonist (LAMA); long-acting β2-agonist (LABA); Japanese