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.

AstraZeneca

Status and phase: Completed; Phase 1

Conditions: Healthy Volunteers

Treatments: Drug: AZD2373 subcutaneous injection; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT04269031

D6800C00001

Details and patient eligibility

About

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.

Full description

This study will be conducted as a single-centre, randomised, placebo-controlled, single-blind study to assess the effect of AZD2373 following ascending dose sequential group design administrations to healthy male subjects of African ancestry. The study will include 6 single dose cohorts with the option to include 2 additional cohorts based on emerging data from preceding cohorts in the study.

Approximately 48 male subjects aged 18 to 55 years at the time of informed consent (inclusive) will be randomized with the aim to have 8 subjects participate in each cohort. Within each cohort, 6 subjects will receive AZD2373 and 2 subjects will receive placebo.

Sentinel dosing will be applied for each cohort and will be divided into 2 groups:

• Group 1 (sentinel group): 1 active, 1 placebo;
• Group 2 (the rest of the cohort): 5 active, 1 placebo. The safety data of up to 72 hours post-dose in Group 1 will be reviewed by the Principal Investigator (PI) before the subjects in Group 2 are dosed.

The study will comprise:

• A Screening Period of maximum 35 days;
• A Treatment Period during which subjects will be resident at the Clinical Unit from the day before investigational medicinal product (IMP) administration (Day -1) until at least 72 hours after IMP administration; discharged from the Clinical Unit on Day 4;
• Follow-up Visits on 1, 1.5, 2, 3, 4, 5, 6, and 8 weeks (Visits 3 to 10); and
• A Final Follow up Visit 10 weeks after the last IMP dose.

The visit occurring at 5 weeks post dose (Visit 5) is optional. The expected duration for any subject participating in the study is approximately 10 weeks (excluding an up to 28-day Screening Period).

Enrollment: 30 patients

Sex: Male

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• 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.

Exclusion criteria

• 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:

  1. Alanine aminotransferase or aspartate aminotransferase greater than upper limit of normal and clinically significant as determined by the PI.
  2. White blood cell (WBC) count < 3.0 x 10^9/L.
  3. 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Double Blind

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30 participants in 6 patient groups

Cohort 1

Experimental group

Description:

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

Treatment:

Drug: Placebo

Drug: AZD2373 subcutaneous injection

Cohort 2

Experimental group

Description:

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

Treatment:

Drug: Placebo

Drug: AZD2373 subcutaneous injection

Cohort 3

Experimental group

Description:

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

Treatment:

Drug: Placebo

Drug: AZD2373 subcutaneous injection

Cohort 4

Experimental group

Description:

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

Treatment:

Drug: Placebo

Drug: AZD2373 subcutaneous injection

Cohort 5

Experimental group

Description:

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

Treatment:

Drug: Placebo

Drug: AZD2373 subcutaneous injection

Cohort 6

Experimental group

Description:

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

Treatment:

Drug: Placebo

Drug: AZD2373 subcutaneous injection