Study to Assess the Safety, Tolerability, and Pharmacokinetics (Movement of Drugs Within the Body) of AZD2693 in Healthy Participants

Healthy Participants Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05107336
• Other study ID #: D7830C00006
• Status: Completed
• Phase: Phase 1
• Start date: November 25, 2021
• Est. completion date: March 21, 2023

Study information

• Verified date: April 2023
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: March 21, 2023
• Est. primary completion date: March 21, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy Participants

Intervention

Drug:
• AZD2693
Participants will receive subcutaneous injection of AZD2693, once per month.
• Placebo
Participants will receive subcutaneous injection of placebo (volume matching to AZD2693 injection [0.9% saline solution]), once per month.

Locations

Country	Name	City	State
Japan	Research Site	Sumida-ku

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)	Safety and tolerability of AZD2693 compared to placebo following multiple dose SC administration in healthy participants will be evaluated.	Until Day 162 (Final/Early termination visit)
Secondary	Maximum observed plasma drug concentration (Cmax) of AZD2693	Cmax of AZD2693 following single dose SC administration of AZD2693 in healthy participants will be characterized.	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)
Secondary	Time to reach peak or maximum observed concentration following drug administration (tmax) of AZD2693	tmax of AZD2693 following single dose SC administration of AZD2693 in healthy participants will be characterized.	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)
Secondary	Terminal elimination rate constant, estimated by log-linear least-squares regression of the terminal part of the concentration-time curve (?z) of AZD2693	?z of AZD2693 following single and multiple doses SC administration of AZD2693 in healthy participants will be characterized.	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)
Secondary	Apparent terminal elimination half-life associated with the terminal slope (?z) of the semi-logarithmic concentration-time curve (t½?z) of AZD2693	t½?z of AZD2693 following single and multiple doses SC administration of AZD2693 in healthy participants will be characterized. The t½?z , estimated as (ln2)/?z	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)
Secondary	Area under the plasma concentration-time curve from time zero to 48 hours after dosing AUC (0-48) of AZD2693	AUC(0-48) of AZD2693 following single and multiple doses SC administration of AZD2693 in healthy participants will be characterized.	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)
Secondary	Area under the plasma concentration-curve from time zero to the time of last quantifiable analyte concentration (AUClast) of AZD2693	AUClast of AZD2693 following single and multiple doses SC administration of AZD2693 in healthy participants will be characterized.	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)
Secondary	Area under the concentration-time curve from time zero extrapolated to infinity. AUCinf is estimated by AUClast + Clast/ ?z where Clast is the last observed quantifiable concentration (AUCinf) of AZD2693	AUCinf of AZD2693 following single dose SC administration of AZD2693 in healthy participants will be characterized.	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)
Secondary	Apparent total body clearance of drug from plasma after extravascular administration (CL/F) of AZD2693	CL/F of AZD2693 following single and multiple dose SC administration of AZD2693 in healthy participants will be characterized. CL/F is calculated as Dose/AUCinf for single dose and for multiple dose it is calculated as Dose/AUCtAUCss.	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)
Secondary	Mean residence time (MRTinf) of AZD2693	MRTinf of AZD2693 following single dose SC administration of AZD2693 in healthy participants will be characterized.	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)
Secondary	Time delay between drug administration and the first observed concentration in plasma (tlag) of AZD2693	tlag of AZD2693 following single and multiple doses SC administration of AZD2693 in healthy participants will be characterized.	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)
Secondary	Apparent volume of distribution for parent drug at terminal phase (extravascular administration) (Vz/F) of AZD2693	Vz/F of AZD2693 following single dose SC administration of AZD2693 in healthy participants will be characterized. Vz/F is estimated by dividing the apparent clearance (CL/F) by ?z.	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)
Secondary	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	AUClast/D of AZD2693 following single and multiple doses SC administration of AZD2693 in healthy participants will be characterized.	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)
Secondary	Area under the plasma concentration-time curve from time zero extrapolated to infinity divided by the dose administered (AUCinf/D) of AZD2693	AUCinf/D of AZD2693 following single dose SC administration of AZD2693 in healthy participants will be characterized.	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)
Secondary	Observed maximum plasma concentration divided by the dose administered (Cmax/D) of AZD2693	Cmax/D of AZD2693 following single and multiple doses SC administration of AZD2693 in healthy participants will be characterized.	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)
Secondary	Time of the last quantifiable concentration (tlast) of AZD2693	tlast of AZD2693 following single and multiple doses SC administration of AZD2693 in healthy participants will be characterized.	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)
Secondary	Maximum observed plasma drug concentration at steady state (Cmax) of AZD2693	Cmax of AZD2693 following multiple dose SC administration of AZD2693 in healthy participants will be characterized.	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)
Secondary	Minimum observed drug concentration at steady state (Cmin) of AZD2693	Cmin of AZD2693 following multiple dose SC administration of AZD2693 in healthy participants will be characterized.	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)
Secondary	Time to reach maximum observed plasma concentration at steady state (tmax) of AZD2693	tmax of AZD2693 following multiple dose SC administration of AZD2693 in healthy participants will be characterized.	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)
Secondary	Area under the concentration-time curve in the dose interval (AUCt) of AZD2693	AUCt of AZD2693 following multiple dose SC administration of AZD2693 in healthy participants will be characterized.	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)
Secondary	Area under the plasma concentration-time curve from time zero extrapolated to infinity divided by the dose administered (AUCt/D) of AZD2693	AUCt/D of AZD2693 following multiple dose SC administration of AZD2693 in healthy participants will be characterized.	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)
Secondary	Accumulation ratio based on Cmax (Rac Cmax) of AZD2693	Rac Cmax of AZD2693 following multiple dose SC administration of AZD2693 in healthy participants will be characterized.	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)
Secondary	Accumulation ratio based on AUC (Rac AUC) of AZD2693	Rac AUC of AZD2693 following multiple dose SC administration of AZD2693 in healthy participants will be characterized.	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)
Secondary	Temporal change parameter in systemic exposure (TCP) of AZD2693	TCP of AZD2693 following multiple dose SC administration of AZD2693 in healthy participants will be characterized.	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)
Secondary	Amount of analyte excreted into the urine from time t1 to t2 (Ae(t1-t2)) for AZD2693	(Ae(t1-t2)) of AZD2693 following single and multiple dose SC administration of AZD2693 in healthy participants will be characterized.	Day 1 and Day 57 (pre-dose and post-dose)
Secondary	Cumulative amount of analyte excreted from time zero through the last sampling interval Ae(0-last) of AZD2693	Ae(0-last) of AZD2693 following single and multiple dose SC administration of AZD2693 in healthy participants will be characterized.	Day 1 and Day 57 (pre-dose and post-dose)
Secondary	Fraction of dose excreted unchanged into the urine from time t1 to t2 fe(t1-t2) of AZD2693	fe(t1-t2) of AZD2693 following single and multiple dose SC administration of AZD2693 in healthy participants will be characterized.	Day 1 and Day 57 (pre-dose and post-dose)
Secondary	Cumulative fraction (percentage) of dose excreted unchanged into the urine from time zero to the last measured time point (fe(0-last)) of AZD2693	fe(0-last) of AZD2693 following single and multiple dose SC administration of AZD2693 in healthy participants will be characterized.	Day 1 and Day 57 (pre-dose and post-dose)
Secondary	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	CLR of AZD2693 following single and multiple dose SC administration of AZD2693 in healthy participants will be characterized.	Day 1 and Day 57 (pre-dose and post-dose)