Clinical trial NCT05107336: Study to Assess the Safety, Tolerability, and Pharmacokinetics (Movement of Drugs Within the Body) of AZD2693 in Healthy Participants
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Participants
Keywords: Pharmacokinetics
Healthy Japanese Participants
Non-alcoholic fatty liver disease
Non-alcoholic steatohepatitis
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2021-11-04
Enrollment: 44
Sex: ALL
Minimum age (years): 20
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

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
* Participants with a significant COVID-19 illness within 6 months of enrollment
* History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity
* Received another new chemical entity (defined as a compound which has not been approved for marketing) within 30 days of last Follow-up to first dose of study intervention of this study or 5 half-lives from last dose to first dose of study intervention, whichever is the longest
* Participants who have previously received AZD2693
* Previous enrollment or randomization into the present study

Primary outcomes:
measure: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Until Day 162 (Final/Early termination visit)
Secondary outcomes:
measure: Maximum observed plasma drug concentration (Cmax) of AZD2693
timeFrame: 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)
measure: Time to reach peak or maximum observed concentration following drug administration (tmax) of AZD2693
timeFrame: 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)
measure: Terminal elimination rate constant, estimated by log-linear least-squares regression of the terminal part of the concentration-time curve (λz) of AZD2693
timeFrame: 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)
measure: Apparent terminal elimination half-life associated with the terminal slope (λz) of the semi-logarithmic concentration-time curve (t½λz) of AZD2693
timeFrame: 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)
measure: Area under the plasma concentration-time curve from time zero to 48 hours after dosing AUC (0-48) of AZD2693
timeFrame: 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)
measure: Area under the plasma concentration-curve from time zero to the time of last quantifiable analyte concentration (AUClast) of AZD2693
timeFrame: 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)
measure: 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
timeFrame: 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)
measure: Apparent total body clearance of drug from plasma after extravascular administration (CL/F) of AZD2693
timeFrame: 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)
measure: Mean residence time (MRTinf) of AZD2693
timeFrame: 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)
measure: Time delay between drug administration and the first observed concentration in plasma (tlag) of AZD2693
timeFrame: 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)
measure: Apparent volume of distribution for parent drug at terminal phase (extravascular administration) (Vz/F) of AZD2693
timeFrame: 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)
measure: 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
timeFrame: 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)
measure: Area under the plasma concentration-time curve from time zero extrapolated to infinity divided by the dose administered (AUCinf/D) of AZD2693
timeFrame: 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)
measure: Observed maximum plasma concentration divided by the dose administered (Cmax/D) of AZD2693
timeFrame: 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)
measure: Time of the last quantifiable concentration (tlast) of AZD2693
timeFrame: 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)
measure: Maximum observed plasma drug concentration at steady state (Cmax) of AZD2693
timeFrame: 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)
measure: Minimum observed drug concentration at steady state (Cmin) of AZD2693
timeFrame: 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)
measure: Time to reach maximum observed plasma concentration at steady state (tmax) of AZD2693
timeFrame: 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)
measure: Area under the concentration-time curve in the dose interval (AUCτ) of AZD2693
timeFrame: 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)
measure: Area under the plasma concentration-time curve from time zero extrapolated to infinity divided by the dose administered (AUCτ/D) of AZD2693
timeFrame: 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)
measure: Accumulation ratio based on Cmax (Rac Cmax) of AZD2693
timeFrame: 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)
measure: Accumulation ratio based on AUC (Rac AUC) of AZD2693
timeFrame: 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)
measure: Temporal change parameter in systemic exposure (TCP) of AZD2693
timeFrame: 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)
measure: Amount of analyte excreted into the urine from time t1 to t2 (Ae(t1-t2)) for AZD2693
timeFrame: Day 1 and Day 57 (pre-dose and post-dose)
measure: Cumulative amount of analyte excreted from time zero through the last sampling interval Ae(0-last) of AZD2693
timeFrame: Day 1 and Day 57 (pre-dose and post-dose)
measure: Fraction of dose excreted unchanged into the urine from time t1 to t2 fe(t1-t2) of AZD2693
timeFrame: Day 1 and Day 57 (pre-dose and post-dose)
measure: Cumulative fraction (percentage) of dose excreted unchanged into the urine from time zero to the last measured time point (fe(0-last)) of AZD2693
timeFrame: Day 1 and Day 57 (pre-dose and post-dose)
measure: 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
timeFrame: Day 1 and Day 57 (pre-dose and post-dose)
Other outcomes:
Locations:
city: Sumida-ku
country: Japan
facility: Research Site
Study officials:
References: