A Study to Assess the Safety, Tolerability, and Pharmacokinetics of AZD5462 Following Single and Multiple Ascending Dose Administration to Healthy Volunteers

A Phase I Randomized, Single-blind, Placebo-controlled Study to Assess the Safety, Tolerability, and Pharmacokinetics of AZD5462 Following Single and Multiple Ascending Dose Administration to Healthy Volunteers

This study will assess the safety, tolerability, and pharmacokinetic (PK) of AZD5462 following single ascending dose (SAD) and multiple ascending dose (MAD) administration in healthy male and female participants and healthy participants of Japanese descent.

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: AZD5462; Drug: Placebo

Detailed Description

This Phase I, First in Human (FIH), randomized single-blind, placebo-controlled study will consist of 2 parts (Part A and Part B) with an interleaved study design.

Part A of the study will be a sequential SAD design with 5 dose levels planned to be investigated across 8 cohorts, of which 3 cohorts will solely comprise of participants of Japanese descent. Within each cohort, 6 participants will be randomized to receive AZD5462 and 2 participants randomized to receive placebo.

Part B of the study will be a sequential MAD design with 4 dose levels of AZD5462 planned to be investigated across 5 cohorts, of which 1 cohort will comprise solely of participants of Japanese descent. Within each cohort 6 participants will be randomized to receive AZD5462 and 2 participants randomized to receive placebo.

The duration for participants randomized to Part A of the study is 5 to 6 weeks, and for Part B, 6 to 7 weeks.

• Study Type: Interventional
• Enrollment (Actual): 98
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Glendale, California, United States, 91206
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy male and female (of non-childbearing potential) participants aged 18 to 50 years of age and healthy participants of Japanese descent, 20 to 50 years of age, with suitable veins for cannulation or repeated venipuncture
• Females must have a negative pregnancy test at the Screening Visit
• Have a body mass index between 18 and 32 kg/m^2 inclusive and weigh at least 50 kg and no more than 105 kg inclusive
• For cohorts comprised solely of participants of Japanese descent, a participant will be considered of Japanese descent only if both parents and all grandparents are Japanese

Exclusion Criteria:

• History of any clinically important disease or disorder
• History or presence of gastrointestinal, hepatic or renal disease or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs
• Any clinically important illness, medical/surgical procedure or trauma within 4 weeks of the first administration of study drug
• Any clinically important abnormalities in clinical chemistry, hematology or urinalysis results
• Any positive result on Screening for serum hepatitis B surface antigen, hepatitis C antibody, and Human immunodeficiency virus
• 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
• History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, or history of hypersensitivity to drugs with a similar chemical structure or class to AZD5462
• Use of any prescribed or nonprescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, mega dose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during the 2 weeks or 5 half-lives of the medication, whichever is longer, prior to the first administration of study drug
• Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 30 days (or 5 half-lives, whichever is the longest) of the first administration of study drug in this study
• Clinical signs and symptoms consistent with Coronavirus disease 2019, eg, fever, dry cough, dyspnea, sore throat, fatigue, or confirmed infection by appropriate laboratory test within the last 4 weeks prior to Screening or on admission

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

17

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A1: AZD5462 Dose 1; Randomized healthy participants will receive Dose 1 of AZD5462.	Drug: AZD5462; Participants will receive AZD5462, at dose levels of 1 to 5 in part A and at 1 to 4 in part B, respectively.
Experimental: Cohort A2: AZD5462 Dose 2; Randomized healthy participants will receive Dose 2 of AZD5462.	Drug: AZD5462; Participants will receive AZD5462, at dose levels of 1 to 5 in part A and at 1 to 4 in part B, respectively.
Experimental: Cohort A3: AZD5462 Dose 3; Randomized healthy participants will receive Dose 3 of AZD5462.	Drug: AZD5462; Participants will receive AZD5462, at dose levels of 1 to 5 in part A and at 1 to 4 in part B, respectively.
Experimental: Cohort A4 Japanese descent: AZD5462 Dose 3; Randomized participants of Japanese descent will receive Dose 3 of AZD5462.	Drug: AZD5462; Participants will receive AZD5462, at dose levels of 1 to 5 in part A and at 1 to 4 in part B, respectively.
Experimental: Cohort A5: AZD5462 Dose 4; Randomized healthy participants will receive Dose 4 of AZD5462.	Drug: AZD5462; Participants will receive AZD5462, at dose levels of 1 to 5 in part A and at 1 to 4 in part B, respectively.
Experimental: Cohort A6 Japanese descent: AZD5462 Dose 4; Randomized participants of Japanese descent will receive Dose 4 of AZD5462.	Drug: AZD5462; Participants will receive AZD5462, at dose levels of 1 to 5 in part A and at 1 to 4 in part B, respectively.
Experimental: Cohort A7: AZD5462 Dose 5; Randomized healthy participants will receive Dose 5 of AZD5462.	Drug: AZD5462; Participants will receive AZD5462, at dose levels of 1 to 5 in part A and at 1 to 4 in part B, respectively.
Experimental: Cohort A8 Japanese descent: AZD5462 Dose 5; Randomized participants of Japanese descent will receive Dose 5 of AZD5462.	Drug: AZD5462; Participants will receive AZD5462, at dose levels of 1 to 5 in part A and at 1 to 4 in part B, respectively.
Placebo Comparator: Part A: Placebo (Healthy Participants); Randomized healthy participants will receive Placebo matched to AZD5462.	Drug: Placebo; Participants will receive Placebo matched to AZD5462.
Placebo Comparator: Part A: Placebo (Japanese descent participants); Randomized participants of Japanese descent will receive Placebo matched to AZD5462.	Drug: Placebo; Participants will receive Placebo matched to AZD5462.
Experimental: Cohort B1: AZD5462 Dose 1; Randomized healthy participants will receive Dose 1 of AZD5462.	Drug: AZD5462; Participants will receive AZD5462, at dose levels of 1 to 5 in part A and at 1 to 4 in part B, respectively.
Experimental: Cohort B2: AZD5462 Dose 2; Randomized healthy participants will receive Dose 2 of AZD5462.	Drug: AZD5462; Participants will receive AZD5462, at dose levels of 1 to 5 in part A and at 1 to 4 in part B, respectively.
Experimental: Cohort B3: AZD5462 Dose 3; Randomized healthy participants will receive Dose 3 of AZD5462.	Drug: AZD5462; Participants will receive AZD5462, at dose levels of 1 to 5 in part A and at 1 to 4 in part B, respectively.
Experimental: Cohort B4: AZD5462 Dose 4; Randomized healthy participants will receive Dose 4 of AZD5462.	Drug: AZD5462; Participants will receive AZD5462, at dose levels of 1 to 5 in part A and at 1 to 4 in part B, respectively.
Experimental: Cohort B5 Japanese descent: AZD5462 Dose 4; Randomized participants of Japanese descent will receive Dose 4 of AZD5462.	Drug: AZD5462; Participants will receive AZD5462, at dose levels of 1 to 5 in part A and at 1 to 4 in part B, respectively.
Placebo Comparator: Part B: Placebo (Healthy participants); Randomized healthy participants will receive Placebo matched to AZD5462.	Drug: Placebo; Participants will receive Placebo matched to AZD5462.
Placebo Comparator: Part B: Placebo (Japanese descent participants); Randomized participants of Japanese descent will receive Placebo matched to AZD5462.	Drug: Placebo; Participants will receive Placebo matched to AZD5462.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events	Assessment of the safety and tolerability of AZD5462 following administration of single ascending doses (Part A) and multiple ascending doses (Part B).	Upto Follow-up (Part A: Day 10 ± 3; Part B: Day 19 ± 3)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum observed plasma (peak) drug concentration (Cmax) for AZD5462	Characterization of the single dose and steady state PK of AZD5462 following administration.	Part A: Day 1 (pre-dose and post-dose), and Days 2, 3, and 10 (post-dose); Part B: Days 1 to 19 (pre and post-doses)
Area under the plasma concentration curve from zero to the last quantifiable concentration (AUClast) for AZD5462	Characterization of the single dose and steady state PK of AZD5462 following administration.	Part A: Day 1 (pre-dose and post-dose), and Days 2, 3, and 10 (post-dose); Part B: Days 1 to 19 (pre and post-doses)
Area under plasma concentration time curve from zero to infinity (AUCinf) for AZD5462	Characterization of the single dose and steady state PK of AZD5462 following administration.	Part A: Day 1 (pre-dose and post-dose), and Days 2, 3, and 10 (post-dose); Part B: Days 1 to 19 (pre and post-doses)
Renal clearance of drug from plasma (CLR) for AZD5462	Characterization of the single dose and steady state PK of AZD5462 following administration.	Part A: Day 1 (pre-dose and post-dose), and Days 2, 3, and 10 (post-dose); Part B: Days 1 to 19 (pre and post-doses)

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): July 27, 2021
• Primary Completion (Actual): September 20, 2022
• Study Completion (Actual): September 20, 2022

Study Registration Dates

• First Submitted: July 29, 2021
• First Submitted That Met QC Criteria: July 29, 2021
• First Posted (Actual): August 6, 2021

Study Record Updates

• Last Update Posted (Actual): October 5, 2022
• Last Update Submitted That Met QC Criteria: October 4, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: First-in-Human; Healthy participants of Japanese descent; 2-part study
• Other Study ID Numbers: D9090C00001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com /ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

IPD Sharing Time Frame

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at:

https://astrazenecagrouptrials.pharmacm.com /ST/Submission/Disclosure.

IPD Sharing Access Criteria

When a request has been approved AstraZeneca will provide access to the de-identified individual patientlevel data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at:

https://astrazenecagrouptrials.pharmacm.com /ST/Submission/Disclosure.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No