An ADME Study of [14C]AZD0780 in Healthy Male Subjects

NCT05817461 | Completed Phase 1

• 1 other identifier: D7960C00004
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

The Sponsor is developing a new test medicine, AZD0780, with the aim to lower low-density lipoprotein cholesterol (LDL-C, fatty deposits) levels and cardiovascular (heart disease) risk, when given on top of standard care. This two-part healthy volunteer study will try to identify how the test medicine is taken up, broken down and removed from the body. To help investigate this, the test medicine is radiolabelled, which means that the test medicine has a radioactive component (carbon-14; also referred as 14C) which helps us to track where the test medicine is in the body. The safety and tolerability of the test medicine will also be studied. This study will take place at one non-NHS site, enrolling up to 8 male volunteers aged between 30 and 55 years.

Conditions

Cardiovascular Diseases

Keywords

Dyslipidaemia

Outcome Measures

Primary Outcomes (27)

• Absolute bioavailability (F) - Part 1

  Absolute bioavailability based on AUC0-inf of oral formulation compared to IV adjusted for dose

  Plasma sample collection from pre-dose to 168 hours post-dose

• Area under the curve from time 0 extrapolated to infinity for AZD0780 and total radioactivity (AUC0-inf) - Part 1

  PK of AZD0780 and \[14C\]AZD0780 in plasma

  Plasma sample collection from pre-dose until 168 hours post-dose

• Time to maximum concentration (tmax) for AZD0780 and total radioactivity - Part 1

  PK of AZD0780 and \[14C\]AZD0780 in plasma

  Plasma sample collection from pre-dose until 168 hours post-dose

• Maximum observed concentration (Cmax) for AZD0780 and total radioactivity - Part 1

  PK of AZD0780 and \[14C\]AZD0780 in plasma

  Plasma sample collection from pre-dose until 168 hours post-dose

• Area under the curve from time 0 to the time of last measurable concentration for AZD0780 and total radioactivity (AUC0-t) - Part 1

  PK of AZD0780 and \[14C\]AZD0780 in plasma

  Plasma sample collection from pre-dose until 168 hours post-dose

• Area under the curve from time of the last measurable concentration to infinity as a percentage of the area under the curve extrapolated to infinity (AUCextrap) and total radioactivity - Part 1

  PK of AZD0780 and \[14C\]AZD0780 in plasma

  Plasma sample collection from pre-dose until 168 hours post-dose

• Terminal elimination half-life for AZD0780 (t1/2) and total radioactivity - Part 1

  PK of AZD0780 and \[14C\]AZD0780 in plasma

  Plasma sample collection from pre-dose until 168 hours post-dose

• First order rate constant associated with the terminal (log-linear) portion of the curve for AZD0780 (λz) and total radioactivity - Part 1

  PK of AZD0780 and \[14C\]AZD0780 in plasma

  Plasma sample collection from pre-dose until 168 hours post-dose

• Total body clearance calculated after a single IV administration (CL) - Part 1

  PK of AZD0780 and \[14C\]AZD0780 in plasma

  Plasma sample collection from pre-dose until 168 hours post-dose

• Total body clearance calculated after a single extravascular administration where F (fraction of dose bioavailable) is unknown (CL/F) - Part 1

  PK of AZD0780 and \[14C\]AZD0780 in plasma

  Plasma sample collection from pre-dose until 168 hours post-dose

• Volume of distribution based on the terminal phase calculated using AUC(0-inf) after a single IV administration (Vz) - Part 1

  PK of AZD0780 and \[14C\]AZD0780 in plasma

  Plasma sample collection from pre-dose until 168 hours post-dose

• Volume of distribution at steady state after a single IV administration (Vss) - Part 1

  PK of AZD0780 and \[14C\]AZD0780 in plasma

  Plasma sample collection from pre-dose until 168 hours post-dose

• Apparent volume of distribution based on the terminal phase calculated using AUC(0-inf) after a single extravascular administration where F (fraction of dose bioavailable) is unknown (Vz/F) - Part 1

  PK of AZD0780 and \[14C\]AZD0780 in plasma

  Plasma sample collection from pre-dose until 168 hours post-dose

• Amount of AZD0780 excreted (Ae) - Part 2

  Mass balance of total radioactivity (TR) of \[14C\]AZD0780 in urine and faecal samples

  Urine and faecal samples collected from pre-dose until 240 hours post-dose

• Amount of AZD0780 excreted expressed as a fraction of dose excreted (%Ae) - Part 2

  Mass balance of total radioactivity (TR) of \[14C\]AZD0780 in urine and faecal samples

  Urine and faecal samples collected from pre-dose until 240 hours post-dose

• The cumulative amount of AZD0780 exreted (CumAe) - Part 2

  Mass balance of total radioactivity (TR) of \[14C\]AZD0780 in urine and faecal samples

  Urine and faecal samples collected from pre-dose until 240 hours post-dose

• Cumulative amount of AZD0780 excreted expressed as a fraction of dose excreted (Cum%Ae) - Part 2

  Mass balance of total radioactivity (TR) of \[14C\]AZD0780 in urine and faecal samples

  Urine and faecal samples collected from pre-dose until 240 hours post-dose

• Time to maximum concentration (tmax) for AZD0780 and total radioactivity - Part 2

  PK of AZD0780 in urine and faeces

  Urine and faecal samples collected from pre-dose until 240 hours post-dose

• Maximum observed concentration (Cmax) for AZD0780 and total radioactivity - Part 2

  PK of AZD0780 in urine and faeces

  Urine and faecal samples collected from pre-dose until 240 hours post-dose

• Area under the curve from time 0 to the time of last measurable concentration for AZD0780 and total radioactivity (AUC0-t) - Part 2

  PK of AZD0780 in urine and faeces

  Urine and faecal samples collected from pre-dose until 240 hours post-dose

• Area under the curve from time 0 extrapolated to infinity for AZD0780 and total radioactivity (AUC0-inf) - Part 2

  PK of AZD0780 in urine and faeces

  Urine and faecal samples collected from pre-dose until 240 hours post-dose

• Area under the curve from time of the last measurable concentration to infinity as a percentage of the area under the curve extrapolated to infinity (AUCextrap) and total radioactivity - Part 2

  PK of AZD0780 in urine and faeces

  Urine and faecal samples collected from pre-dose until 240 hours post-dose

• Terminal elimination half-life for AZD0780 (t1/2) and total radioactivity - Part 2

  PK of AZD0780 in urine and faeces

  Urine and faecal samples collected from pre-dose until 240 hours post-dose

• First order rate constant associated with the terminal (log-linear) portion of the curve for AZD0780 (λz) and total radioactivity - Part 2

  PK of AZD0780 in urine and faeces

  Urine and faecal samples collected from pre-dose until 240 hours post-dose

• Total body clearance calculated after a single extravascular administration where F (fraction of dose bioavailable) is unknown (CL/F) - Part 2

  PK of AZD0780 in urine and faeces

  Urine and faecal samples collected from pre-dose until 240 hours post-dose

• Apparent volume of distribution based on the terminal phase calculated using AUC(0-inf) after a single extravascular administration where F (fraction of dose bioavailable) is unknown (Vz/F) - Part 2

  PK of AZD0780 in urine and faeces

  Urine and faecal samples collected from pre-dose until 240 hours post-dose

• Renal clearance calculated using plasma AUC (CLR) - Part 2

  PK of AZD0780 in urine and faeces

  Urine and faecal samples collected from pre-dose until 240 hours post-dose

Secondary Outcomes (3)

• Number of subjects with treatment-related adverse events - Part 1 and Part 2

  Through study duration, an average of 10 weeks

• Blood:plasma concentration ratios - Part 2

  Whole blood samples and plasma samples collected from pre-dose until 240 hours post-dose

• Identification of the chemical structure of each metabolite accounting for more than 10% by AUC of circulating TR (plasma) or accounting for 10% or more of the dose in urine and faeces - Part 2

  Plasma, urine and faecal samples collected from pre-dose until 240 hours post-dose

Study Arms (1)

AZD0780

EXPERIMENTAL

In Part 1, one oral dose of AZD0780 and one intravenous dose of \[14C\]AZD0780. In Part 2, one oral dose of \[14C\]AZD0780

Drug: AZD0780 tablet; Drug: [14C]AZD0780 Solution for Infusion; Drug: [14C]AZD0780 Oral Solution

Interventions

AZD0780 tablet DRUG

oral, fasted

Also known as: AZD0780

AZD0780

[14C]AZD0780 Solution for Infusion DRUG

intravenous

Also known as: [14C]AZD0780

AZD0780

[14C]AZD0780 Oral Solution DRUG

oral, fasted

Also known as: [14C]AZD0780

AZD0780

Eligibility Criteria

• Age: 30 Years - 55 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.
• Must be willing and able to communicate and participate in the whole study.
• Healthy male subjects aged 30 to 55 years inclusive at the time of signing informed consent.
• Must agree to adhere to the contraception requirements defined in the Clinical Protocol
• Body mass index (BMI) between 18.0 and 32.0 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive.
• Must have regular bowel movements (i.e. average stool production of ≥1 and ≤3 stools per day).

You may not qualify if:

• History of any clinically significant disease or disorder (e.g. cardiovascular, pulmonary, GI, liver, renal, neurological, musculoskeletal ,endocrine, metabolic, malignant, psychiatric, major physical impairment, skin abnormalities and glucose metabolism abnormalities) which, in the opinion of the investigator, may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer's ability to participate in the study.
• History or presence of clinically significant GI, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
• Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP.
• History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the investigator or history of hypersensitivity to drugs with a similar chemical structure or class to AZD0780. Hay fever is allowed unless it is active.
• Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator or delegate at screening
• Evidence of current SARS-CoV-2 infection
• Any clinically significant abnormalities in clinical chemistry, haematology or urinalysis as judged by the investigator. Subjects with Gilbert's Syndrome are not allowed.
• Clinically significant abnormal findings in vital signs, at screening or admission, as judged by the investigator.
• Clinically significant abnormalities on 12-lead ECG, at screening or admission, as judged by the investigator.
• Any positive result on screening for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab), and human immunodeficiency virus (HIV) 1 and 2 antibody
• Evidence of renal impairment at screening, as indicated by an estimated creatinine clearance (CLcr) of \<80 mL/min using the Cockcroft-Gault equation
• Has received another new chemical entity (defined as a compound which has not been approved for marketing) within the 90 days prior to Day 1, or less than 5 elimination half-lives prior to Day 1, whichever is longer. Note: subjects consented and screened, but not randomised in this study or a previous Phase I study, are not excluded.
• Subjects who report to have previously received AZD0780.
• Radiation exposure, including that from the present study, excluding background radiation but including diagnostic x-rays and other medical exposures, exceeding 5 mSv in the last 12 months or 10 mSv in the last 5 years. No occupationally exposed worker, as defined in the Ionising Radiation Regulations 2017, shall participate in the study.
• Subjects who have been administered IMP in an ADME study in the last 12 months.

Sponsors & Collaborators

• AstraZeneca: lead
• Quotient Sciences: collaborator

Study Sites (1)

Research Site

Ruddington, NG11 6JS, United Kingdom

Location

Related Links

• D7960C00004 CSR Synopsis
• Results posted on AZCT.com

MeSH Terms

Conditions

Cardiovascular Diseases; Dyslipidemias

Condition Hierarchy (Ancestors)

Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Somasekhara Menakuru, MBBS, MS, MRCS, DPM, MFPM

  Quotient Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 5, 2023
• First Posted: April 18, 2023
• Study Start: April 19, 2023
• Primary Completion: June 6, 2023
• Study Completion: June 6, 2023
• Last Updated: June 11, 2025

Record last verified: 2025-06

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 deidentified 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

GB (1)