Clinical Trials/NCT05107336

NCT05107336

Completed

Phase 1

A Randomised, Single-Blind, Placebo-Controlled, Phase I Study to Assess the Safety, Tolerability, and Pharmacokinetics of AZD2693 Following Multiple Subcutaneous Dose Administration in Healthy Participants

AstraZeneca1 site in 1 country44 target enrollmentNovember 25, 2021

ConditionsHealthy Participants

InterventionsAZD2693 Placebo

DrugsAZD2693 Placebo

Overview

Phase: Phase 1
Intervention: AZD2693
Conditions: Healthy Participants
Sponsor: AstraZeneca
Enrollment: 44
Locations: 1
Primary Endpoint: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Status: Completed
Last Updated: 9 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This Phase I, randomised, single-blind, placebo-controlled study has been designed to assess the safety, tolerability, and pharmacokinetics (PK) of AZD2693 following subcutaneous (SC) administration of AZD2693 in healthy participants

Detailed Description

The study will be performed at a single study center in Japan. The study will comprise of following periods: * Screening Period of maximum 28 days. * An 8-week Treatment Period during which participants will be randomized to receive multiple doses of AZD2693 or placebo at the study center. * A Follow-up Period of 15 weeks post last dose of study intervention consisting of 8 Follow-up Visits. Participants will be enrolled in 4 consecutive cohorts of 11 participants where 8 participants will be randomized to receive AZD2693 and 3 participants will be randomized to receive placebo. A participant is considered to have completed the study if the participant has completed all phases of the study including the last visit.

Registry

clinicaltrials.gov

Start Date

November 25, 2021

End Date

March 21, 2023

Last Updated

9 months ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

AstraZeneca

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring
•Participants who are of Japanese ethnicity (Japanese participant is defined as having both parents and 4 grandparents who are ethnically Japanese and this also includes second and third generation Japanese whose parents or grandparents are living in a country other than Japan)
•Participants who are of Non-Asian ethnicities. A Non-Asian Participant is defined as having both parents and grandparents who are ethnically Non-Asian.
•Body mass index within the range 18 to 32 kg/m\^2
•Male and/or female participants of non-child bearing potential

Exclusion Criteria

•History of any clinically important disease or disorder
•History or presence of gastrointestinal, hepatic, or renal disease or condition known to interfere with absorption, distribution, metabolism or excretion of drugs
•Participants with known autoimmune disease or on-treatment with immune-modulatory drugs
•Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks of the first dose of study intervention
•Any clinically significant cardiovascular event within the last 6 months prior to the Screening Visit
•Any clinically important abnormalities in clinical chemistry, haematology or urinalysis results and any abnormal vital signs
•Any clinically important abnormalities in rhythm, conduction or morphology of the resting electrocardiogram (ECG) and any clinically important abnormalities in the 12-Lead ECG
•Blood dyscrasias with increased risk of bleeding including idiopathic thrombocytopenic purpura and thrombotic thrombocytopenic purpura or symptoms of increased risk of bleeding
•History of major bleed or high-risk of bleeding diathesis
•Participants with a positive diagnostic nucleic acid test for Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), at Screening Visit. Participants who test positive for Coronavirus disease 2019 (COVID-19) at Screening Visit

Arms & Interventions

Cohort 1: AZD2693

Japanese Participants will receive Dose A of AZD2693.

Intervention: AZD2693

Cohort 2: AZD2693

Japanese Participants will receive Dose B of AZD2693.

Intervention: AZD2693

Cohort 3: AZD2693

Japanese Participants will receive Dose C of AZD2693.

Intervention: AZD2693

Cohort 4: AZD2693

Non-Asian Participants will receive Dose C of AZD2693

Intervention: AZD2693

Placebo

Japanese and Non-Asian Participants will receive placebo matching Dose A, B, and C to AZD2693.

Intervention: Placebo

Outcomes

Primary Outcomes

Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

Time Frame: Until Day 162 (Final/Early termination visit)

Safety and tolerability of AZD2693 compared to placebo following multiple dose SC administration in healthy participants will be evaluated.

Secondary Outcomes

Maximum observed plasma drug concentration (Cmax) of AZD2693(Day 1 and Day 57 (pre-dose and post-dose), Day 8, Day 29 (pre-dose only), and days 64, 78, 92, 106, 120, 134, 148, and 162 (Final/ET visit))
Time to reach peak or maximum observed concentration following drug administration (tmax) of AZD2693(Day 1 and Day 57 (pre-dose and post-dose), Day 8, Day 29 (pre-dose only), and days 64, 78, 92, 106, 120, 134, 148, and 162 (Final/ET visit))
Area under the plasma concentration-time curve from time zero to 48 hours after dosing AUC (0-48) of AZD2693(Day 1 and Day 57 (pre-dose and post-dose), Day 8, Day 29 (pre-dose only), and days 64, 78, 92, 106, 120, 134, 148, and 162 (Final/ET visit))
Area under the plasma concentration-curve from time zero to the time of last quantifiable analyte concentration (AUClast) of AZD2693(Day 1 and Day 57 (pre-dose and post-dose), Day 8, Day 29 (pre-dose only), and days 64, 78, 92, 106, 120, 134, 148, and 162 (Final/ET visit))
Apparent volume of distribution for parent drug at terminal phase (extravascular administration) (Vz/F) of AZD2693(Day 1 and Day 57 (pre-dose and post-dose), Day 8, Day 29 (pre-dose only), and days 64, 78, 92, 106, 120, 134, 148, and 162 (Final/ET visit))
Mean residence time (MRTinf) of AZD2693(Day 1 and Day 57 (pre-dose and post-dose), Day 8, Day 29 (pre-dose only), and days 64, 78, 92, 106, 120, 134, 148, and 162 (Final/ET visit))
Time delay between drug administration and the first observed concentration in plasma (tlag) of AZD2693(Day 1 and Day 57 (pre-dose and post-dose), Day 8, Day 29 (pre-dose only), and days 64, 78, 92, 106, 120, 134, 148, and 162 (Final/ET visit))
Observed maximum plasma concentration divided by the dose administered (Cmax/D) of AZD2693(Day 1 and Day 57 (pre-dose and post-dose), Day 8, Day 29 (pre-dose only), and days 64, 78, 92, 106, 120, 134, 148, and 162 (Final/ET visit))
Terminal elimination rate constant, estimated by log-linear least-squares regression of the terminal part of the concentration-time curve (λz) of AZD2693(Day 1 and Day 57 (pre-dose and post-dose), Day 8, Day 29 (pre-dose only), and days 64, 78, 92, 106, 120, 134, 148, and 162 (Final/ET visit))
Minimum observed drug concentration at steady state (Cmin) of AZD2693(Day 1 and Day 57 (pre-dose and post-dose), Day 8, Day 29 (pre-dose only), and days 64, 78, 92, 106, 120, 134, 148, and 162 (Final/ET visit))
Accumulation ratio based on AUC (Rac AUC) of AZD2693(Day 1 and Day 57 (pre-dose and post-dose), Day 8, Day 29 (pre-dose only), and days 64, 78, 92, 106, 120, 134, 148, and 162 (Final/ET visit))
Cumulative amount of analyte excreted from time zero through the last sampling interval Ae(0-last) of AZD2693(Day 1 and Day 57 (pre-dose and post-dose))
Apparent terminal elimination half-life associated with the terminal slope (λz) of the semi-logarithmic concentration-time curve (t½λz) of AZD2693(Day 1 and Day 57 (pre-dose and post-dose), Day 8, Day 29 (pre-dose only), and days 64, 78, 92, 106, 120, 134, 148, and 162 (Final/ET visit))
Apparent total body clearance of drug from plasma after extravascular administration (CL/F) of AZD2693(Day 1 and Day 57 (pre-dose and post-dose), Day 8, Day 29 (pre-dose only), and days 64, 78, 92, 106, 120, 134, 148, and 162 (Final/ET visit))
Area under the plasma concentration-time curve from time zero to time of last quantifiable analyte concentration divided by the dose administered (AUClast/D) of AZD2693(Day 1 and Day 57 (pre-dose and post-dose), Day 8, Day 29 (pre-dose only), and days 64, 78, 92, 106, 120, 134, 148, and 162 (Final/ET visit))
Area under the plasma concentration-time curve from time zero extrapolated to infinity divided by the dose administered (AUCinf/D) of AZD2693(Day 1 and Day 57 (pre-dose and post-dose), Day 8, Day 29 (pre-dose only), and days 64, 78, 92, 106, 120, 134, 148, and 162 (Final/ET visit))
Time of the last quantifiable concentration (tlast) of AZD2693(Day 1 and Day 57 (pre-dose and post-dose), Day 8, Day 29 (pre-dose only), and days 64, 78, 92, 106, 120, 134, 148, and 162 (Final/ET visit))
Temporal change parameter in systemic exposure (TCP) of AZD2693(Day 1 and Day 57 (pre-dose and post-dose), Day 8, Day 29 (pre-dose only), and days 64, 78, 92, 106, 120, 134, 148, and 162 (Final/ET visit))
Area under the concentration-time curve from time zero extrapolated to infinity. AUCinf is estimated by AUClast + Clast/ λz where Clast is the last observed quantifiable concentration (AUCinf) of AZD2693(Day 1 and Day 57 (pre-dose and post-dose), Day 8, Day 29 (pre-dose only), and days 64, 78, 92, 106, 120, 134, 148, and 162 (Final/ET visit))
Maximum observed plasma drug concentration at steady state (Cmax) of AZD2693(Day 1 and Day 57 (pre-dose and post-dose), Day 8, Day 29 (pre-dose only), and days 64, 78, 92, 106, 120, 134, 148, and 162 (Final/ET visit))
Time to reach maximum observed plasma concentration at steady state (tmax) of AZD2693(Day 1 and Day 57 (pre-dose and post-dose), Day 8, Day 29 (pre-dose only), and days 64, 78, 92, 106, 120, 134, 148, and 162 (Final/ET visit))
Area under the concentration-time curve in the dose interval (AUCτ) of AZD2693(Day 1 and Day 57 (pre-dose and post-dose), Day 8, Day 29 (pre-dose only), and days 64, 78, 92, 106, 120, 134, 148, and 162 (Final/ET visit))
Cumulative fraction (percentage) of dose excreted unchanged into the urine from time zero to the last measured time point (fe(0-last)) of AZD2693(Day 1 and Day 57 (pre-dose and post-dose))
Area under the plasma concentration-time curve from time zero extrapolated to infinity divided by the dose administered (AUCτ/D) of AZD2693(Day 1 and Day 57 (pre-dose and post-dose), Day 8, Day 29 (pre-dose only), and days 64, 78, 92, 106, 120, 134, 148, and 162 (Final/ET visit))
Accumulation ratio based on Cmax (Rac Cmax) of AZD2693(Day 1 and Day 57 (pre-dose and post-dose), Day 8, Day 29 (pre-dose only), and days 64, 78, 92, 106, 120, 134, 148, and 162 (Final/ET visit))
Amount of analyte excreted into the urine from time t1 to t2 (Ae(t1-t2)) for AZD2693(Day 1 and Day 57 (pre-dose and post-dose))
Fraction of dose excreted unchanged into the urine from time t1 to t2 fe(t1-t2) of AZD2693(Day 1 and Day 57 (pre-dose and post-dose))
Renal clearance of drug from plasma, estimated by dividing Ae(0-t) by AUC(0-t) where the 0-t interval is the same for both Ae and AUC (CLR) of AZD2693(Day 1 and Day 57 (pre-dose and post-dose))