A First-in-human Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AZD2373 After Single Dose Administration in Healthy Male Subjects of African Ancestry.

NCT04269031 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: D6800C00001
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1 study to assess the the safety, tolerability and pharmacokinetics (PK) of AZD2373, following subcutaneous (SC) administration of single ascending doses (SAD) of AZD2373 in healthy male subjects of African ancestry.

Conditions

Healthy Volunteers

Keywords

First-in-Human; Randomized; Single-blind; Placebo controlled; AZD2373; Single Ascending Dose; Sentinel Dosing

Outcome Measures

Primary Outcomes (1)

• Number of subjects with adverse events and/or abnormal findings in vital signs, and/or clinical laboratory assessments and/or physical examination and/or electrocardiogram (ECG) evaluation and/or telemetry and/or injection site reactions

  To assess adverse events as a variable of safety and tolerability of subcutaneous (SC) single ascending dose (SAD) administrations of AZD2373

  Screening Visit to final Follow-up Visit (Week 10 post last dose)

Secondary Outcomes (17)

• Area under plasma concentration-time curve from time zero extrapolated to infinity (AUC)

  Visit 2 to final Follow-up Visit (Week 10 post last dose)

• Area under the plasma concentration curve from time zero to the time of last quantifiable analyte concentration (AUClast)

  Visit 2 to final Follow-up Visit (Week 10 post last dose)

• Area under the plasma concentration-time curve from time zero to 72 hours after dosing [AUC(0-72)]

  Visit 2 to final Follow-up Visit (Week 10 post last dose)

• Area under the plasma concentration-time curve from time zero to 48 hours after dosing [AUC (0-48)]

  Visit 2 to final Follow-up Visit (Week 10 post last dose)

• Observed maximum plasma concentration (Cmax)

  Visit 2 to final Follow-up Visit (Week 10 post last dose)

Study Arms (6)

Cohort 1

EXPERIMENTAL

On Day 1, randomized subjects will receive a subcutaneous (SC) injection of AZD2373 dose 1 (6 subjects) or matching placebo (2 subjects).

Drug: AZD2373 subcutaneous injection; Drug: Placebo

Cohort 2

EXPERIMENTAL

On Day 1, randomized subjects will receive a SC injection of AZD2373 dose 2 (6 subjects) or matching placebo (2 subjects).

Drug: AZD2373 subcutaneous injection; Drug: Placebo

Cohort 3

EXPERIMENTAL

On Day 1, randomized subjects will receive a SC injection of AZD2373 dose 3 (6 subjects) or matching placebo (2 subjects).

Drug: AZD2373 subcutaneous injection; Drug: Placebo

Cohort 4

EXPERIMENTAL

On Day 1, randomized subjects will receive a SC injection of AZD2373 dose 4 (6 subjects) or matching placebo (2 subjects).

Drug: AZD2373 subcutaneous injection; Drug: Placebo

Cohort 5

EXPERIMENTAL

On Day 1, randomized subjects will receive a SC injection of AZD2373 dose 5 (6 subjects) or matching placebo (2 subjects).

Drug: AZD2373 subcutaneous injection; Drug: Placebo

Cohort 6

EXPERIMENTAL

On Day 1, randomized subjects will receive a SC injection of AZD2373 dose 6 (6 subjects) or matching placebo (2 subjects).

Drug: AZD2373 subcutaneous injection; Drug: Placebo

Interventions

AZD2373 subcutaneous injection DRUG

Randomised subjects will receive a single ascending dose of AZD2373 by SC injection (dose 1, dose 2, dose 3, dose 4, dose 5 and dose 6).

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5; Cohort 6

Placebo DRUG

Randomised subjects will receive a single ascending dose of placebo (saline solution) by SC injection.

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5; Cohort 6

Eligibility Criteria

• Age: 18 Years - 55 Years
• Gender Eligibility Details: Male 18-55 years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Provision of signed and dated, written informed consent prior to any study specific procedures.
• Healthy male subjects of West African ancestry aged 18 to 55 years (inclusive, at time of informed consent) with suitable veins for cannulation or repeated venipuncture.
• Have a body mass index (BMI) between 18 and 35 kg/m\^2 (inclusive) and weigh at least 50 kg and no more than 120 kg (inclusive).
• Provision of signed, written and dated informed consent for study participation which includes mandatory genotyping (study objective). NOTE: If a subject would decline to participate in the mandatory genotyping component of the study, the subject will not be included in the study.

You may not qualify if:

• Subjects with known ancestry outside of West Africa.
• History of any clinically important disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study.
• 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 prior to administration of IMP on Study Day 1.
• Any laboratory values with the following deviations:
• Alanine aminotransferase or aspartate aminotransferase greater than upper limit of normal and clinically significant as determined by the PI.
• White blood cell (WBC) count \< 3.0 x 10\^9/L.
• Hemoglobin (Hb) below lower limit normal .
• Any clinically important abnormalities in clinical chemistry, hematology or urinalysis results, other than those described above, as judged by the PI.

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Sites (1)

Research Site

Brooklyn, Maryland, 21225, United States

Location

Related Publications (1)

• Bruggeman LA, Sedor JR, O'Toole JF. Apolipoprotein L1 and mechanisms of kidney disease susceptibility. Curr Opin Nephrol Hypertens. 2021 May 1;30(3):317-323. doi: 10.1097/MNH.0000000000000704.

  PMID: 33767059 DERIVED

Study Officials

• Ronald Goldwater, Dr.

  PAREXEL Early Phase Clinical Unit Baltimore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This study is single-blind (in which the study center staff remain blinded during the clinical conduct of a given cohort) with regard to treatment (AZD2373 or placebo) at each dose level. Study subjects will be blinded to treatment allocation throughout the study.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2020
• First Posted: February 13, 2020
• Study Start: February 13, 2020
• Primary Completion: August 31, 2021
• Study Completion: August 31, 2021
• Last Updated: July 10, 2023

Record last verified: 2023-07

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 patient-level 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)