A Study to Assess the Safety and Tolerability of Single Doses of AZD4076 in Healthy Male Subjects

NCT02612662 | Completed Phase 1

• 1 other identifier: D5590C00001
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This is a first-in-human (FIH) study designed to evaluate the safety, tolerability, and pharmacokinetics (PK) of AZD4076 tetracosasodium in healthy male subjects at increasing single doses

Conditions

Non-alcoholic Steatohepatitis (NASH)

Keywords

AZD4076; Healthy male subjects; Safety; Subcutaneous; Tolerability

Outcome Measures

Primary Outcomes (13)

• The safety and tolerability of AZD4076 by assessment of blood pressure

  To assess the safety and tolerability of single doses of AZD4076

  From screening until 16 weeks postdose, up to 5 months

• The safety and tolerability of AZD4076 by assessment of pulse

  To assess the safety and tolerability of single doses of AZD4076

  From screening until 16 weeks postdose, up to 5 months

• The safety and tolerability of AZD4076 by assessment of oral temperature

  To assess the safety and tolerability of single doses of AZD4076

  From screening until 72 hours postdose

• The safety and tolerability of AZD4076 by assessment of electrocardiogram readings

  To assess the safety and tolerability of single doses of AZD4076

  From screening until 16 weeks postdose, up to 5 months

• The safety and tolerability of AZD4076 by assessment of digital electrocardiogram readings

  To assess the safety and tolerability of single doses of AZD4076

  From predose until 72 hours postdose

• The safety and tolerability of AZD4076 by assessment of cardiac telemetry

  To assess the safety and tolerability of single doses of AZD4076 by telemetry monitoring and paper printouts

  On Day -1 and predose until 72 hours postdose

• The safety and tolerability of AZD4076 by assessment of physical examination

  This is a composite of the general appearance, skin, cardiovascular, respiratory, abdomen, head, and neck (including ears, eyes, nose, and throat), lymph nodes, thyroid, musculoskeletal and neurological systems

  From screening until 16 weeks postdose, up to 5 months

• The safety and tolerability of AZD4076 by assessing hematology

  To assess the safety and tolerability of single doses of AZD4076

  From screening until 16 weeks postdose, up to 5 months

• The safety and tolerability of AZD4076 by assessing the injection site

  This includes assessment of erythema/redness, swelling, induration, pruritus and pain at injection site

  Postdose until 72 hours

• The safety and tolerability of AZD4076 by assessming the number of adverse events

  To assess the safety and tolerability of single doses of AZD4076

  From screening until 16 weeks postdose, up to 5 months

• The safety and tolerability of AZD4076 by assessing clinical chemistry

  To assess the safety and tolerability of single doses of AZD4076

  From screening until 16 weeks postdose, up to 5 months

• The safety and tolerability of AZD4076 by assessing urinalysis

  To assess the safety and tolerability of single doses of AZD4076

  From screening until 16 weeks postdose, up to 5 months

• The safety and tolerability of AZD4076 by assessing the number of participants with adverse events

  To assess the safety and tolerability of single doses of AZD4076

  From screening until 16 weeks postdose, up to 5 months

Secondary Outcomes (32)

• Observed maximum plasma concentration, taken directly from the individual concentration-time curve [Cmax] assessed for AZD4076 from the plasma data

  Predose until 16 weeks postdose

• Time to reach maximum concentration, taken directly from the individual concentration-time curve [tmax] assessed for AZD4076 from the plasma data

  Predose until 16 weeks postdose

• Terminal elimination half-life, estimated as (ln2)/λz [t1/2λz ] assessed for AZD4076 from the plasma data

  Predose until 16 weeks postdose

• Area under the plasma concentration-curve from time zero to 72h after drug administration [AUC(0-72h)] assessed for AZD4076 from the plasma data

  Predose until 16 weeks postdose

• Area under the plasma concentration-curve from time zero to the time of last quantifiable concentration [AUC(0-last)] assessed for AZD4076 from the plasma data

  Predose until 16 weeks postdose

Study Arms (6)

Cohort 1

EXPERIMENTAL

Subjects will be fasted for at least 10 hours before dosing and until 4 hours after dosing of a single dose of AZD4076 tetracosasodium or placebo (high doses may be fractionated)

Drug: AZD4076; Drug: Placebo

Cohort 2

EXPERIMENTAL

Subjects will be fasted for at least 10 hours before dosing and until 4 hours after dosing of a single dose of AZD4076 tetracosasodium or placebo (high doses may be fractionated)

Drug: AZD4076; Drug: Placebo

Cohort 3

EXPERIMENTAL

Subjects will be fasted for at least 10 hours before dosing and until 4 hours after dosing of a single dose of AZD4076 tetracosasodium or placebo (high doses may be fractionated)

Drug: AZD4076; Drug: Placebo

Cohort 4

EXPERIMENTAL

Subjects will be fasted for at least 10 hours before dosing and until 4 hours after dosing of a single dose of AZD4076 tetracosasodium or placebo (high doses may be fractionated)

Drug: AZD4076; Drug: Placebo

Cohort 5

EXPERIMENTAL

Subjects will be fasted for at least 10 hours before dosing and until 4 hours after dosing of a single dose of AZD4076 tetracosasodium or placebo (high doses may be fractionated)

Drug: AZD4076; Drug: Placebo

Cohort 6

EXPERIMENTAL

Subjects will be fasted for at least 10 hours before dosing and until 4 hours after dosing of a single dose of AZD4076 tetracosasodium or placebo (high doses may be fractionated)

Drug: AZD4076; Drug: Placebo

Interventions

AZD4076 DRUG

Subcutaneous (SC) administration of single ascending doses; there will be no more than 2 mL per syringe/injection

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

Placebo DRUG

Subcutaneous (SC) administration of single ascending doses; there will be no more than 2 mL per syringe/injection

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

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• 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 aged 18 - 50 years with suitable veins for cannulation or repeated venipuncture
• Have a body mass index (BMI) between 18 and 30 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive
• Provision of signed, written and dated informed consent for optional genetic research

You may not qualify if:

• History or presence of any clinically significant 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 hepatic or renal disease, or any other condition known to interfere with distribution, metabolism, or excretion of drugs
• History or presence of significant neurological or psychiatric disease/mental illness (as judged by the investigator)
• Suspicion of or known Gilbert's syndrome based on liver function tests
• Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the administration of IMP
• Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis results, as judged by the investigator
• Any positive result on screening for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody and human immunodeficiency virus (HIV)
• Serum Creatinine greater than the ULN.
• Platelet count outside the normal range.
• AST, ALT, or GGT greater than the ULN.
• Abnormal vital signs, after 10 minutes supine rest, defined as any of the following:
• Systolic BP (SBP) \< 90mmHg or ≥ 140 mmHg
• Diastolic BP (DBP) \< 50mmHg or ≥ 90 mmHg
• Pulse \< 45 or \> 85 beats per minute (bpm)
• Any clinically significant abnormalities in rhythm, conduction or morphology of the resting ECG and any clinically significant abnormalities in the 12-lead ECG, as considered by the investigator that may interfere with the interpretation of QTc interval changes, including abnormal ST-T-wave morphology, particularly in the protocol defined primary lead or left ventricular hypertrophy

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Brooklyn, Maryland, 21225, United States

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Study Officials

• Ronald Goldwater, MDCM, M.Sc, CPI

  PAREXEL Early Phase Clinical Unit Baltimore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2015
• First Posted: November 24, 2015
• Study Start: November 24, 2015
• Primary Completion: November 4, 2017
• Study Completion: October 27, 2025
• Last Updated: November 19, 2025

Record last verified: 2025-11

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 rerefer 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)