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NCT02645253

A Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD7594 Inhaled Formulation in Healthy Japanese Men

Completed Phase 1 Results posted Last updated 19 February 2018
What this trial tests

Phase 1 trial testing AZD7594 inhalation powder (200 μg) in Asthma in 27 participants. Completed in 17 April 2016.

Timeline
12 January 2016
Primary endpoint
17 April 2016
17 April 2016

Quick facts

Lead sponsorAstraZeneca
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingsingle
Primary purposebasic science
Enrollment27
Start date12 January 2016
Primary completion17 April 2016
Estimated completion17 April 2016
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

AstraZeneca — full company profile →

Who can join

Adults 20 to 45, male only, with Asthma or Chronic Obstructive Pulmonary Disease COPD. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Safety and Tolerability of AZD7594 by Assessment of the Number of Participants With Adverse Events Primary · At screening (Day -28, Day -02 and Day -1), Treatment period (Days 1 to 20) and Follow-up (Day 29).

To assess the safety and tolerability of single and multiple doses of AZD7594

Any AE
GroupValue95% CI
AZD7594 200 μg3
AZD7594 400 μg1
AZD7594 1600 μg1
Total AZD75945
Placebo1
All Subjects6
Any AE with outcome = death
GroupValue95% CI
AZD7594 200 μg0
AZD7594 400 μg0
AZD7594 1600 μg0
Total AZD75940
Placebo0
All Subjects0
Any SAE including events with outcome =death
GroupValue95% CI
AZD7594 200 μg0
AZD7594 400 μg0
AZD7594 1600 μg0
Total AZD75940
Placebo0
All Subjects0
Any AE leading to discontinuation of IP
GroupValue95% CI
AZD7594 200 μg0
AZD7594 400 μg0
AZD7594 1600 μg0
Total AZD75940
Placebo0
All Subjects0
Rate and Extent of Absorption of AZD7594 (Inhalation/ Administration Via DPI) by Assessment of the Observed Maximum Plasma Concentration (Cmax) Secondary · Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.

Assessment of the plasma PK following a single dose of AZD7594. Cmax was defined as observed maximum plasma concentration, taken directly from the individual concentration-time curve.

GroupValue95% CI
AZD7594 200 μg56.05± 22.0
AZD7594 400 μg76.93± 34.4
AZD7594 1600 μg430.8± 22.4
Rate and Extent of Absorption of AZD7594 (Inhalation/ Administration Via DPI) by Assessment of the Time to Reach Maximum Plasma Concentration (Tmax) Secondary · Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.

Assessment of the plasma PK following a single dose of AZD7594. tmax was defined as time to reach maximum plasma concentration, taken directly from the individual concentration-time curve.

GroupValue95% CI
AZD7594 200 μg0.250.25 – 0.98
AZD7594 400 μg0.520.25 – 3.00
AZD7594 1600 μg0.500.25 – 4.00
Rate and Extent of Absorption of AZD7594 (Inhalation/ Administration Via DPI) by Assessment of the Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to the Time of Last Quantifiable Analyte Concentration (AUC [0-last]) Secondary · Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose

Assessment of the plasma PK following a single dose of AZD7594. AUC (0-last) was defined as the area under the plasma concentration-time curve from time zero to the time of last quantifiable analyte concentration.

GroupValue95% CI
AZD7594 200 μg1314± 28.2
AZD7594 400 μg2736± 12.2
AZD7594 1600 μg13960± 18.2
Rate and Extent of Absorption of AZD7594 (Inhalation/ Administration Via DPI) by Assessment of the AUC From Time Zero to 24 Hours After Dosing (AUC [0-24]). Secondary · Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose

Assessment of the plasma PK following a single dose of AZD7594. AUC (0-24) was defined as area under the plasma concentration-time curve from time zero to 24 hours after dosing.

GroupValue95% CI
AZD7594 200 μg681.1± 11.5
AZD7594 400 μg1084± 19.4
AZD7594 1600 μg6060± 18.4
Rate and Extent of Absorption of AZD7594 (Inhalation/ Administration Via DPI) by Assessment of the AUC From Time Zero Extrapolated to Infinity (AUC). Secondary · Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose

Assessment of the plasma PK following a single dose of AZD7594. AUC was defined as area under the plasma concentration-time curve from time zero extrapolated to infinity. AUC is estimated by AUC(0-last) + Clast/λz where Clast is the last observed quantifiable concentration. NOTE: No results were available for participants belonging to AZD7594 2ug and AZD7594 400ug groups.

GroupValue95% CI
AZD7594 200 μgNA± NA
AZD7594 400 μgNA± NA
AZD7594 1600 μg18260± 22.9
Rate and Extent of Absorption of AZD7594 by Assessment of the Terminal Elimination Rate Constant, Estimated by Log-linear Least Squares Regression of the Terminal Part of the Concentration-time Curve(Lamda z or λz). Secondary · Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose

Assessment of the plasma PK following a single dose of AZD7594. λz was defined as terminal elimination rate constant, estimated by log-linear least squares regression of the terminal part of the concentration-time curve.

GroupValue95% CI
AZD7594 200 μg0.015573± 24.5
AZD7594 400 μg0.011058± 18.3
AZD7594 1600 μg0.013862± 21.4
Rate and Extent of Absorption of AZD7594 (Inhalation/ Administration Via DPI) by Assessment of the Half-life Associated With the Terminal Slope of a Semi-logarithmic Concentration-time Curve (t1/2λz). Secondary · Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose

Assessment of the plasma PK following a single dose of AZD7594. t1/2λz was defined as half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve. NOTE: No results were available for participants belonging to AZD7594 400ug group.

GroupValue95% CI
AZD7594 200 μg39.88± 5.441
AZD7594 400 μgNA± NA
AZD7594 1600 μg43.57± 3.815
Rate and Extent of Absorption of AZD7594 (Inhalation/ Administration Via DPI) by Assessment of the Mean Residence Time From Time Zero Extrapolated to Infinity (MRT). Secondary · Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose

Assessment of the plasma PK following a single dose of AZD7594. MRT was defined as Mean residence time from time zero extrapolated to infinity. NOTE: No results were available for participants belonging to AZD7594 200ug and AZD7594 400ug groups.

GroupValue95% CI
AZD7594 200 μgNA± NA
AZD7594 400 μgNA± NA
AZD7594 1600 μg65.03± 4.7
Rate and Extent of Absorption of AZD7594 by Assessment of the Apparent Total Body Clearance After Extravascular Administration Estimated as Dose Divided by AUC (AZD7594) (CL/F). Secondary · Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.

Assessment of the plasma PK following a single dose of AZD7594. CL/F was defined as apparent total body clearance after extravascular administration estimated as dose divided by AUC (AZD7594). NOTE: No results were available for participants belonging to AZD7594 200ug and AZD7594 400ug groups.

GroupValue95% CI
AZD7594 200 μgNA± NA
AZD7594 400 μgNA± NA
AZD7594 1600 μg144.5± 22.9
Rate and Extent of Absorption of AZD7594 by Assessment of the Apparent Volume of Distribution During the Terminal Phase After Extravascular Administration, Estimated by Dividing CL/F by Lamda z (Vz/F) Secondary · Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.

Assessment of the plasma PK following a single dose of AZD7594. Vz/F was defined as apparent volume of distribution during the terminal phase after extravascular administration, estimated by dividing the apparent clearance (CL/F) by λz. NOTE: No results were available for participants belonging to AZD7594 200ug and AZD7594 400ug groups.

GroupValue95% CI
AZD7594 200 μgNA± NA
AZD7594 400 μgNA± NA
AZD7594 1600 μg9297± 24.1
Rate and Extent of Absorption of AZD7594 by Assessment of the Cmax Divided by the Dose Administered (Cmax/D). Secondary · Day 1: pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose

Assessment of the plasma PK following a single dose of AZD7594. Cmax/D was defined as observed maximum plasma concentration divided by the dose administered.

GroupValue95% CI
AZD7594 200 μg169.9± 22.0
AZD7594 400 μg116.7± 34.4
AZD7594 1600 μg163.2± 22.4

Adverse events — posted to ClinicalTrials.gov

Time frame: Serious adverse events (SAEs) were recorded from the signing of informed consent and adverse events (AEs) were recorded from randomization until the final follow-up visit.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

AZD7594 200 μg
Serious: 0/7 (0%)
Deaths:
AZD7594 400 μg
Serious: 0/7 (0%)
Deaths:
AZD7594 1600 μg
Serious: 0/7 (0%)
Deaths:
Palcebo
Serious: 0/6 (0%)
Deaths:
Total AZD7594
Serious: 0/21 (0%)
Deaths:
All Subjects
Serious: 0/27 (0%)
Deaths:
Other adverse events (6 terms — click to expand)

ReactionSystemAZD7594 200 μgAZD7594 400 μgAZD7594 1600 μgPalceboTotal AZD7594All Subjects
Dry throatRespiratory, thoracic and mediastinal disorders
Nasal congestionRespiratory, thoracic and mediastinal disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
FolliculitisInfections and infestations
GoutMetabolism and nutrition disorders
PresyncopeNervous system disorders

Data from ClinicalTrials.gov NCT02645253 adverse events section.

Sponsor's own description

This is a randomized, single-blind, placebo-controlled, sequential-group study to assess the safety and tolerability as well as how the drug (AZD7594) affects the body (pharmacodynamics \[PD\]) and how the body affects the drug (pharmacokinetics \[PK\]) when AZD7594 is given as single and multiple ascending doses once daily by inhalation to healthy male Japanese subjects, compared with placebo (non-active drug)

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Mechanisms, Pathophysiology and Currently Proposed Treatments of Chronic Obstructive Pulmonary Disease.
    Rodrigues SO, Cunha CMCD, Soares GMV, Silva PL, et al · · 2021 · cited 61× · PMID 34681202 · DOI 10.3390/ph14100979
  2. Experimental Glucocorticoid Receptor Agonists for the Treatment of Asthma: A Systematic Review.
    Rogliani P, Ritondo BL, Puxeddu E, Pane G, et al · · 2020 · cited 14× · PMID 32982485 · DOI 10.2147/jep.s237480
  3. Safety, pharmacokinetics and pharmacodynamics of the selective glucocorticoid receptor modulator AZD7594, following inhalation in healthy Japanese volunteers.
    Prothon S, Wählby Hamrén U, Tehler U, Yoon E, et al · · 2019 · cited 6× · PMID 31814707 · DOI 10.2147/dddt.s215170

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Other recruiting trials for Asthma

Currently open trials in the same condition.

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Trials by the same sponsor.

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing