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

NCT04994106 | Completed Phase 1 FDA Drug

• 1 other identifier: D9090C00001
• Study Type: interventional
• Target: 98
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Participants

Keywords

Healthy participants of Japanese descent; First-in-Human; 2-part study

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Maximum observed plasma (peak) drug concentration (Cmax) for AZD5462

  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

  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

  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

  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)

Study Arms (17)

Cohort A1: AZD5462 Dose 1

EXPERIMENTAL

Randomized healthy participants will receive Dose 1 of AZD5462.

Drug: AZD5462

Cohort A2: AZD5462 Dose 2

EXPERIMENTAL

Randomized healthy participants will receive Dose 2 of AZD5462.

Drug: AZD5462

Cohort A3: AZD5462 Dose 3

EXPERIMENTAL

Randomized healthy participants will receive Dose 3 of AZD5462.

Drug: AZD5462

Cohort A4 Japanese descent: AZD5462 Dose 3

EXPERIMENTAL

Randomized participants of Japanese descent will receive Dose 3 of AZD5462.

Drug: AZD5462

Cohort A5: AZD5462 Dose 4

EXPERIMENTAL

Randomized healthy participants will receive Dose 4 of AZD5462.

Drug: AZD5462

Cohort A6 Japanese descent: AZD5462 Dose 4

EXPERIMENTAL

Randomized participants of Japanese descent will receive Dose 4 of AZD5462.

Drug: AZD5462

Cohort A7: AZD5462 Dose 5

EXPERIMENTAL

Randomized healthy participants will receive Dose 5 of AZD5462.

Drug: AZD5462

Cohort A8 Japanese descent: AZD5462 Dose 5

EXPERIMENTAL

Randomized participants of Japanese descent will receive Dose 5 of AZD5462.

Drug: AZD5462

Part A: Placebo (Healthy Participants)

PLACEBO COMPARATOR

Randomized healthy participants will receive Placebo matched to AZD5462.

Drug: Placebo

Part A: Placebo (Japanese descent participants)

PLACEBO COMPARATOR

Randomized participants of Japanese descent will receive Placebo matched to AZD5462.

Drug: Placebo

Cohort B1: AZD5462 Dose 1

EXPERIMENTAL

Randomized healthy participants will receive Dose 1 of AZD5462.

Drug: AZD5462

Cohort B2: AZD5462 Dose 2

EXPERIMENTAL

Randomized healthy participants will receive Dose 2 of AZD5462.

Drug: AZD5462

Cohort B3: AZD5462 Dose 3

EXPERIMENTAL

Randomized healthy participants will receive Dose 3 of AZD5462.

Drug: AZD5462

Cohort B4: AZD5462 Dose 4

EXPERIMENTAL

Randomized healthy participants will receive Dose 4 of AZD5462.

Drug: AZD5462

Cohort B5 Japanese descent: AZD5462 Dose 4

EXPERIMENTAL

Randomized participants of Japanese descent will receive Dose 4 of AZD5462.

Drug: AZD5462

Part B: Placebo (Healthy participants)

PLACEBO COMPARATOR

Randomized healthy participants will receive Placebo matched to AZD5462.

Drug: Placebo

Part B: Placebo (Japanese descent participants)

PLACEBO COMPARATOR

Randomized participants of Japanese descent will receive Placebo matched to AZD5462.

Drug: Placebo

Interventions

AZD5462 DRUG

Participants will receive AZD5462, at dose levels of 1 to 5 in part A and at 1 to 4 in part B, respectively.

Cohort A1: AZD5462 Dose 1; Cohort A2: AZD5462 Dose 2; Cohort A3: AZD5462 Dose 3; Cohort A4 Japanese descent: AZD5462 Dose 3; Cohort A5: AZD5462 Dose 4; Cohort A6 Japanese descent: AZD5462 Dose 4; Cohort A7: AZD5462 Dose 5; Cohort A8 Japanese descent: AZD5462 Dose 5; Cohort B1: AZD5462 Dose 1; Cohort B2: AZD5462 Dose 2; Cohort B3: AZD5462 Dose 3; Cohort B4: AZD5462 Dose 4; Cohort B5 Japanese descent: AZD5462 Dose 4

Placebo DRUG

Participants will receive Placebo matched to AZD5462.

Part A: Placebo (Healthy Participants); Part A: Placebo (Japanese descent participants); Part B: Placebo (Healthy participants); Part B: Placebo (Japanese descent participants)

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Glendale, California, 91206, United States

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: This study is single blind with regard to treatment (AZD5462 or placebo). This means that the Principal Investigator, all clinical staff involved in the clinical study (except for the unblinded Pharmacist), the participants, and the site monitor will remain blinded, unless safety concerns or a regulatory requirement necessitate unblinding.
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is randomized single-blind, and placebo-controlled study

Study Record Dates

• First Submitted: July 29, 2021
• First Posted: August 6, 2021
• Study Start: July 27, 2021
• Primary Completion: September 20, 2022
• Study Completion: September 20, 2022
• Last Updated: October 5, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will share
• 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.
• 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.

Locations

US (1)