A Clinical Trial in Healthy Volunteers and Patients With Mild Asthma to Investigate a New Medicine (AZD4604) for the Treatment of Asthma
Condition: Asthma
MeSH terms: Asthma
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a first in human clinical study. Part 1 of the clinical study will assess the safety
      and tolerability, as well as the single dose pharmacokinetics (PK), of inhaled AZD4604 in
      healthy volunteers (Part 1a, single ascending dose [SAD]). The single dose administration
      will be performed with dry powder inhaler (DPI) formulation of AZD4604. When at least 4
      cohorts of the SAD part of the study have been completed, AZD4604 will be administered as a
      single intravenous (IV) or oral (PO) dose to 2 different cohorts of healthy volunteers (Part
      1b). The main purpose is to compare the PK between IV, oral and inhaled administration to
      further characterize the PK properties of AZD4604 by the various administration routes. The
      results will be used to improve future study design and interpretation. In Part 2 (Multiple
      ascending dose [MAD]), AZD4604 will be administered at multiple doses (twice daily [BID], 7
      days) to healthy volunteers. In Part 3, AZD4604 will be administered at multiple doses to
      patients with mild asthma at dose levels assessed in Part 2. The multiple-dose administration
      will be performed with DPI-formulated AZD4604.
    

Detailed description: 
      Part 1a of the study will be a randomized, single-blind, placebo-controlled, SAD, sequential
      group design study. Seven inhaled dose levels of AZD4604 are planned to be investigated in
      cohorts of 8 healthy volunteers, with 6 healthy volunteers randomly assigned to inhaled
      AZD4604 and 2 healthy volunteers randomly assigned to inhaled placebo in each cohort.

      Part 1a will comprise of:

        -  A Screening Visit within 28 days before dosing.

        -  A Treatment Period (Day -1 to Day 7, in the Clinical Unit) with a single inhaled dose of
           AZD4604 or corresponding placebo on Day 1. Although the anticipated systemic exposure
           and risk for potential adverse systemic effects are considered to be low for AZD4604,
           healthy volunteers will remain resident at site for additional 6 days of monitoring.

        -  A Final Assessment on day of discharge.

      In Part 1b, AZD4604 will be administered as a single IV or a PO dose to healthy volunteers in
      order to compare the PK between IV, PO and inhaled administration. Part 1b will be open-label
      and consist of 2 dose cohorts, IV and PO, with 6 healthy volunteers in each.

      Part 1b will comprise of:

        -  A washout period of at least 2 weeks for the healthy volunteers who received inhaled
           dosing in Part 1a will occur before IV or PO dosing in Part 1b. All healthy volunteers
           will have a Screening Visit within 28 days of dosing.

        -  A Treatment Period (Day -1 to Day 3, in the Clinical Unit) with a single IV or PO dose
           of AZD4604 on Day 1.

        -  A Follow-up Visit within 6 ± 1 day after dosing.

      Part 2 of the study will be a randomized, single-blind, placebo-controlled, MAD, sequential
      group design. This part of the study will be conducted in up to 32 healthy volunteers.

      Part 2 will comprise of:

        -  A Screening Visit within 28 days before first dosing.

        -  A Treatment Period (Day -1 to Day 12 in the Clinical Unit) with twice daily (BID)
           inhaled doses of AZD4604 or placebo on Day 1 to Day 6 (12-hour [+/- 30 minutes]
           intervals between doses), and a single inhaled dose on Day 7. The healthy volunteers
           will remain resident at site for additional 6 days of monitoring, which is predicted to
           allow sufficient time for near complete washout (estimated time for > 97% of the dose to
           have been eliminated) of any target engagement from the lungs. Healthy volunteers will
           remain in the Clinical Unit for the duration of the treatment period and will be
           discharged on Day 13, 6 days after administration of the last dose.

        -  A Final Assessment on day of discharge.

      Part 3 of the study will be a randomized, single-blind, placebo-controlled, multiple-dose, PK
      and pharmacodynamic (PD) study part, with daily non-residential visits during the Treatment
      Period. This part of the study will be conducted in at least 45 patients with mild asthma (16
      patients in Cohorts 1 and 2 and at least 29 patients in the Proof of Mechanism [PoM] Cohort).

      Part 3 will comprise of:

        -  A Screening Visit within 42 days before first dosing.

        -  A Treatment Period (Day -3 to Day 15 as daily non-residential visits) with BID inhaled
           doses of AZD4604 or placebo on Day 1 to Day 9 (12-hour intervals between doses), and a
           single inhaled dose on Day 10. Dosing will take place at the clinical site and patients
           will need to visit the site twice daily on Day 1 to Day 9. The anticipated systemic
           exposure and risk for potential adverse systemic effects are considered to be low for
           AZD4604, therefore, patients will not be required to be resident at site during the
           Treatment Period.

        -  A Final Assessment (Day 16) on the last day of the Treatment Period.
    

Intervention name(s): AZD4604 for inhalation via DPI; Placebo for AZD4604 for inhalation via DPI; AZD4604 for IV administration; AZD4604 for oral administration; AZD4604 for inhalation via DPI
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention description(s): Healthy volunteers will receive AZD4604 administered with a DPI. The dose is expected to be administered between 10 to 45 minutes, depending upon dose. The dose will be administered after an overnight fast of at least 10 hours. Healthy volunteers will be allowed to drink water to prevent dehydration until 1 hour before dosing.; Part 1a: An additional cohort of healthy volunteers will receive a placebo administered with a DPI.
Part 2: Healthy volunteers will receive placebo administered with a DPI. They will receive BID doses on Day 1 to Day 6, and a single dose will be administered on Day 7.
Part 3: Patients will receive placebo administered with a DPI. They will receive BID doses on Day 1 to Day 9, and a single dose will be administered on Day 10.; Healthy volunteers will receive a single IV dose of AZD4604 administered over 20 minutes. The dose will be administered after an overnight fast of at least 10 hours. Healthy volunteers will be allowed to drink water to prevent dehydration until 1 hour before dosing.; Healthy volunteers will receive a single PO dose of AZD4604. The dose will be administered after an overnight fast of at least 10 hours. Healthy volunteers will be allowed to drink water to prevent dehydration until 1 hour before dosing.; Patients with mild asthma will also receive AZD4604 administered with a DPI. Patients will receive BID doses on Day 1 to Day 9 (morning and evening with 12-hour intervals between doses), and a single morning dose will be administered on Day 10. On Day 1 and Day 10, the morning dose will be administered after an overnight fast of 10 hours. For all other doses, the dose will be administered after a 1-hour fast.
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: AZD4604; Placebo-controlled; Pharmacokinetics; First in Human; Single Ascending Dose; Multiple Ascending Dose; Inhaled Janus Kinase (JAK) Inhibitor