Non-alcoholic Steatohepatitis (NASH)Phase 1NCT02612662
A Study to Assess the Safety and Tolerability of Single Doses of AZD4076 in Healthy Male Subjects
A Phase 1 study testing AZD4076 in people with Non-alcoholic Steatohepatitis (NASH), run by AstraZeneca at 1 site in United States.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 to 50 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Non-alcoholic Steatohepatitis (NASH)
- What is being tested?
- AZD4076
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Nov 2015to 27 Oct 2025
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
- Prolonged QTcF > 450 ms or shortened QTcF < 340 ms or family history of long QT syndrome
- PR(PQ) interval shortening < 120 ms (PR > 110 ms but < 120 ms is acceptable if there is no evidence of ventricular pre-excitation)
- PR (PQ) interval prolongation (> 240 ms) intermittent second (Wenckebach block while asleep is not exclusive) or third degree AV block, or AV dissociation
- Persistent or intermittent complete bundle branch block (BBB), incomplete bundle branch block (IBBB), or intraventricular conduction delay (IVCD) with QRS > 110 ms. Subjects with QRS > 110 ms but < 115 ms are acceptable if there is no evidence of, for example, ventricular hypertrophy or pre-excitation
- Known or suspected history of drug abuse, as judged by the investigator
- Current smokers or those who have smoked or used nicotine products within the 3 months prior to screening
- History of alcohol abuse or excessive intake of alcohol, as judged by the investigator
- Positive screen for drugs of abuse or cotinine (nicotine) at screening or admission to the unit or positive screen for alcohol on admission to the unit prior to the administration of IMP
- History of severe allergy/hypersensitivity or ongoing clinically significant allergy/hypersensitivity, as judged by the investigator or history of hypersensitivity to drugs with a similar chemical structure or class to AZD4076 tetracosasodium
- Excessive intake of caffeine containing drinks or food (e.g., coffee, tea), as judged by the investigator
- Use of drugs with enzyme inducing properties such as St John's Wort within 3 weeks prior to the administration of IMP
- Use of any prescribed or non-prescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, megadose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during the two weeks prior to the administration of IMP or longer if the medication has a long half-life
- Plasma donation within one month of screening or any blood donation/blood loss > 500 mL during the 3 months prior to screening
- Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 3 months of the administration of IMP in this study. The period of exclusion begins three months after the final dose or one month after the last visit whichever is the longest.
- Note: Subjects consented and screened, but not randomized in this study or a previous phase I study, are not excluded.
- Vulnerable subjects, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order
- Involvement of any Astra Zeneca, PAREXEL or study site employee or their close relatives
- Judgment by the investigator that the subject should not participate in the study if they have any ongoing or recent (i.e., during the screening period) minor medical complaints that may interfere with the interpretation of study data or are considered unlikely to comply with study procedures, restrictions and requirements
- Subjects who are vegans or have medical dietary restrictions
- Subjects who cannot communicate reliably with the investigator
- In addition, any of the following is regarded as a criterion for exclusion from the genetic research:
- Previous bone marrow transplant
- Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Single-blind, Placebo-controlled Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD4076 Tetracosasodium Following Single-ascending Dose Administration to Healthy Male Subjects
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
Read the detailed description
This is a Phase 1, randomized, first-in-human (FIH) study to assess the safety, tolerability, and pharmacokinetics (PK) of AZD4076 tetracosasodium following subcutaneous (SC) administration in healthy male subjects at increasing single doses
- Conditions
- Non-alcoholic Steatohepatitis (NASH)
- Being tested
- AZD4076, Placebo
- Keywords
- AZD4076, Healthy male subjects, Safety, Subcutaneous, Tolerability
- Medical subject headings
- Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD4076Drug
Subcutaneous (SC) administration of single ascending doses; there will be no more than 2 mL per syringe/injection
PlaceboDrug
Subcutaneous (SC) administration of single ascending doses; there will be no more than 2 mL per syringe/injection
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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) Receives: 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) Receives: 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) Receives: 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) Receives: 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) Receives: Drug: AZD4076; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The safety and tolerability of AZD4076 by assessment of blood pressure
To assess the safety and tolerability of single doses of AZD4076
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
To characterize the plasma pharmacokinetics of AZD4076
Measured: 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
To characterize the plasma pharmacokinetics of AZD4076
Measured: Predose until 16 weeks postdose
Terminal elimination half-life, estimated as (ln2)/λz [t1/2λz ] assessed for AZD4076 from the plasma data
To characterize the plasma pharmacokinetics of AZD4076
Measured: 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
To characterize the plasma pharmacokinetics of AZD4076
Measured: 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
To characterize the plasma pharmacokinetics of AZD4076
Measured: Predose until 16 weeks postdose
Area under plasma concentration-time curve from time zero extrapolated to infinity [AUC] assessed for AZD4076 from the plasma data
To characterize the plasma pharmacokinetics of AZD4076
Measured: Predose until 16 weeks postdose
Apparent total clearance, estimated as dose divided by AUC [CL/F] assessed for AZD4076 from the plasma data
To characterize the plasma pharmacokinetics of AZD4076
Measured: Predose until 16 weeks postdose
Mean Residence Time [MRT] assessed for AZD4076 from the plasma data
To characterize the plasma pharmacokinetics of AZD4076
Measured: Predose until 16 weeks postdose
Apparent volume of distribution at terminal phase, estimated by dividing the apparent clearance (CL/F) by λz [Vz/F] assessed for AZD4076 from the plasma data
To characterize the plasma pharmacokinetics of AZD4076
Measured: Predose until 16 weeks postdose
Dose normalized maximum plasma concentration divided by dose, calculated by dividing Cmax by the dose administered for [Cmax/D] assessed for AZD4076 from the plasma data
To characterize the plasma pharmacokinetics of AZD4076
Measured: Predose until 16 weeks postdose
Dose normalized area under the plasma concentration-time curve from time zero to time of last quantifiable concentration, calculated by dividing AUC(0-last) by the dose administered [AUC(0 last)/D] assessed for AZD4076 from the plasma data
To characterize the plasma pharmacokinetics of AZD4076
Measured: Predose until 16 weeks postdose
Dose normalized area under the plasma concentration-time curve from time zero extrapolated to infinity divided by dose, calculated by dividing AUC by the dose administered [AUC/D] assessed for AZD4076 from the plasma data
To characterize the plasma pharmacokinetics of AZD4076
Measured: Predose until 16 weeks postdose
Lag-time, taken directly from the individual concentration-time curve [tlag] assessed for AZD4076 from the plasma data
To characterize the plasma pharmacokinetics of AZD4076
Measured: Predose until 16 weeks postdose
Cumulative amount of analyte excreted in urine from time zero to the last sampling interval (72 hours) [Ae(0-t)] assessed for AZD4076 from the urine data
To characterize the pharmacokinetics of AZD4076 in urine
Measured: Predose until 72 hours postdose
Percentage of dose excreted unchanged into the urine from time zero to the last sampling interval (72 hours), estimated by dividing Ae(0-t) by dose [fe(0-t)] assessed for AZD4076 from the urine data
To characterize the pharmacokinetics of AZD4076 in urine
Measured: Predose until 72 hours postdose
Renal clearance, estimated by dividing Ae(0-t) by AUC(0-72) [CLR] assessed for AZD4076 from the urine data
To characterize the pharmacokinetics of AZD4076 in urine
Measured: Predose until 72 hours postdose
Cmax assessed for AZD4076 metabolites from the plasma data
To characterize the plasma pharmacokinetics of AZD4076 metabolites (longmers, shortmers, sum of longmers and shortmers and sum of AZD4076, longmers and shortmers)
Measured: Predose until 16 weeks postdose
tmax assessed for AZD4076 metabolites from the plasma data
To characterize the plasma pharmacokinetics of AZD4076 metabolites (longmers, shortmers, sum of longmers and shortmers and sum of AZD4076, longmers and shortmers)
Measured: Predose until 16 weeks postdose
t1/2λz assessed for AZD4076 metabolites from the plasma data
To characterize the plasma pharmacokinetics of AZD4076 metabolites (longmers, shortmers, sum of longmers and shortmers and sum of AZD4076, longmers and shortmers)
Measured: Predose until 16 weeks postdose
AUC(0-last) assessed forAZD4076 metabolites from the plasma data
To characterize the plasma pharmacokinetics of AZD4076 metabolites (longmers, shortmers, sum of longmers and shortmers and sum of AZD4076, longmers and shortmers)
Measured: Predose until 16 weeks postdose
AUC(0-72h) assessed for AZD4076 metabolites from the plasma data
To characterize the plasma pharmacokinetics of AZD4076 metabolites (longmers, shortmers, sum of longmers and shortmers and sum of AZD4076, longmers and shortmers)
Measured: Predose until 16 weeks postdose
MRT assessed for AZD4076 metabolites from the plasma data
To characterize the plasma pharmacokinetics of AZD4076 metabolites (longmers, shortmers, sum of longmers and shortmers and sum of AZD4076, longmers and shortmers)
Measured: Predose until 16 weeks postdose
tlag assessed for AZD4076 metabolites from the plasma data
To characterize the plasma pharmacokinetics of AZD4076 metabolites (longmers, shortmers, sum of longmers and shortmers and sum of AZD4076, longmers and shortmers)
Measured: Predose until 16 weeks postdose
Vz/F assessed for AZD4076 metabolites from the plasma data
To characterize the plasma pharmacokinetics of AZD4076 metabolites (longmers, shortmers, sum of longmers and shortmers and sum of AZD4076, longmers and shortmers)
Measured: Predose until 16 weeks postdose
Cmax/D assessed for AZD4076 metabolites from the plasma data
To characterize the plasma pharmacokinetics of AZD4076 metabolites (longmers, shortmers, sum of longmers and shortmers and sum of AZD4076, longmers and shortmers)
Measured: Predose until 16 weeks postdose
[AUC(0-last)/D assessed for AZD4076 metabolites from the plasma data
To characterize the plasma pharmacokinetics of AZD4076 metabolites (longmers, shortmers, sum of longmers and shortmers and sum of AZD4076, longmers and shortmers)
Measured: Predose until 16 weeks postdose
AUC/D assessed for AZD4076 metabolites from the plasma data
To characterize the plasma pharmacokinetics of AZD4076 metabolites (longmers, shortmers, sum of longmers and shortmers and sum of AZD4076, longmers and shortmers)
Measured: Predose until 16 weeks postdose
Ae(0-t) assessed for AZD4076 metabolites from the urine data
To characterize the pharmacokinetics of AZD4076 metabolites (longmers, shortmers, sum of longmers and shortmers and sum of AZD4076, longmers and shortmers)
Measured: Predose until 72 hours postdose
fe(0-t) assessed for AZD4076 metabolites from the urine data
To characterize the pharmacokinetics of AZD4076 metabolites (longmers, shortmers, sum of longmers and shortmers and sum of AZD4076, longmers and shortmers)
Measured: Predose until 72 hours postdose
CLR assessed for AZD4076 metabolites from the urine data
To characterize the pharmacokinetics of AZD4076 metabolites (longmers, shortmers, sum of longmers and shortmers and sum of AZD4076, longmers and shortmers)
Measured: Predose until 72 hours postdose
AUC assessed for AZD4076 metabolites from the plasma data
To characterize the plasma pharmacokinetics of AZD4076 metabolites (longmers, shortmers, sum of longmers and shortmers and sum of AZD4076, longmers and shortmers)
Measured: Predose until 16 weeks postdose
CL/F assessed for AZD4076 metabolites from the plasma data
To characterize the plasma pharmacokinetics of AZD4076 metabolites (longmers, shortmers, sum of longmers and shortmers and sum of AZD4076, longmers and shortmers)
Measured: Predose until 16 weeks postdose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Nov 2015 (estimated)
- Study start24 Nov 2015
- Primary completion4 Nov 2017
- Study completion27 Oct 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-alcoholic Steatohepatitis (NASH)Studies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ronald Goldwater, MDCM, M.Sc, CPI, Principal investigator, PAREXEL Early Phase Clinical Unit Baltimore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02612662
- Sponsor's protocol ID
- D5590C00001
- Status last verified
- Oct 2026
- First submitted
- 17 Nov 2015
- Last updated
- 9 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request 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.