A Study to Assess the Mass Balance and ADME of [14C]AZD5004 and the Absolute Bioavailability of AZD5004

An Open-Label Study to Assess the Mass Balance Recovery, Absorption, Metabolism, Excretion of [14C]AZD5004 and Absolute Bioavailability of AZD5004 in Healthy Male Participants

This study in healthy volunteers aims to answer these questions:

• Does the test medicine cause any important side effects?
• What are the blood levels of the test medicine and how quickly does the body get rid of it?
• How much of the test medicine taken by mouth gets into the bloodstream?
• How does the body break down and get rid of the test medicine?

This study will take place at one site in Nottingham, United Kingdom, and plans to enrol 8 healthy men aged 30-65 years, who will be involved in both parts of the study.

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: AZD5004 film-coated tablet; Drug: [14C]AZD5004 Solution for Infusion; Drug: [14C]AZD5004 Oral Solution

Detailed Description

In this 2-part study, healthy volunteers will be given three doses of test medicine to find out how the body breaks down and gets rid of the test medicine. Two doses will be 'radiolabelled' - they will contain a small amount of radioactivity (Carbon-14) so that it can be tracked in the body. The amount of radiactivity is less than 6 days of the average radiation exposure received in the UK each year, and slightly less than the radiation dose that would result from a single head x-ray or two leg x-rays.

This study in healthy volunteers aims to answer these questions:

• Does the test medicine cause any important side effects?
• What are the blood levels of the test medicine and how quickly does the body get rid of it?
• How much of the test medicine taken by mouth gets into the bloodstream?
• How does the body break down and get rid of the test medicine?

This study will take place at one site in Nottingham, United Kingdom.

It plans to enrol 8 healthy men aged 30-65 years, who will be involved in both parts of the study.

In Part 1, volunteers will receive a single dose of the test medicine by mouth and, on the same day, a very tiny dose of radiolabelled study medicine by injection into a vein. After a minimum of 7 days, in Part 2, volunteers will receive a dose of test medicine containing a very tiny amount of radio label, by mouth. They'll stay in the clinic for up to 6 nights in Part 1 and 8 nights in Part 2 and take up to 7 weeks to finish the study.

We'll collect blood and urine samples to do safety tests. Over a period of at least 15 days, we'll take many blood samples. In Part 2 volunteers will collect all their urine and faeces so that we can measure the amount of test medicine and its breakdown products.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Ruddington, United Kingdom, NG11 6JS
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy males aged 30 to 65 years inclusive
• BMI in the range 18.0 - 35.0 kg/m2 and body weight ≥63 kg
• Regular bowel movements (i.e. average stool production of ≥1 and ≤3 stools per day)

Exclusion Criteria:

• History of any clinically significant disease or disorder
• History or presence of clinically significant gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs
• History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity
• Excessive intake of caffeine containing drinks or food
• History/family history of medullary thyroid carcinoma or multiple endocrine neoplasia
• Uncontrolled thyroid disease
• History of acute pancreatitis or gallstones
• Serum triglyceride concentrations > 1000 mg/dL (11 mmol/L)
• Any history of significant inflammatory bowel disease, gastroparesis, or other severe disease or prior surgery affecting the upper GI tract
• Participants who do not have suitable veins for multiple venepunctures/cannulation
• Clinically significant abnormal clinical chemistry, haematology or urinalysis
• Significant hepatic disease
• Any clinically significant abnormalities in rhythm, conduction, or morphology of the resting ECG and any clinically important abnormalities in the 12-lead ECG
• Abnormal renal function
• Radiation exposure exceeding 5 mSv in the last 12 months or 10 mSv in the last 5 years, occupationally exposed worker, or have been administered IMP in a [14C] ADME study in the last 12 months.
• Use of any prescribed or non-prescribed medication
• Current smokers or known or suspected history of alcohol or drug abuse.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AZD5004; A single dose of AZD5004 film-coated tablet and a single dose of [14C]AZD5004 Solution for Infusion (Part 1) A single dose of [14C]AZD5004 Oral Solution (Part 2)	Drug: AZD5004 film-coated tablet; oral, fasted; Other Names: AZD5004; Drug: [14C]AZD5004 Solution for Infusion; intravenous, fasted; Other Names: [14C]AZD5004; Drug: [14C]AZD5004 Oral Solution; oral, fasted; Other Names: [14C]AZD5004

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute bioavailability - Part 1	Absolute bioavailability (F) based on AUC0-inf of oral and IV administration, adjusted for dose	Plasma sample collection from pre-dose to 110 hrs post-dose
Amount of AZD5004 excreted (Ae) - Part 2	Mass balance recovery of total radioactivity (TR) in urine, faeces and all excreta (urine and faeces combined)	Urine and faecal samples collected from pre-dose until 168 hours post-dose
Amount of AZD5004 excreted expressed as a percentage of the dose administered (Fe) - Part 2	Mass balance recovery of total radioactivity (TR) in urine, faeces and all excreta (urine and faeces combined)	Urine and faecal samples collected from pre-dose until 168 hours post dose
Cumulative amount of AZD5004 excreted (CumAe) - Part 2	Mass balance recovery of total radioactivity (TR) in urine, faeces and all excreta (urine and faeces combined)	Urine and faecal samples collected from pre-dose until 168 hours post dose
Cumulative amount of AZD5004 excreted expressed as a percentage of the dose administered (CumFe) - Part 2	Mass balance recovery of total radioactivity (TR) in urine, faeces and all excreta (urine and faeces combined)	Urine and faecal samples collected from pre-dose until 168 hours post dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum observed concentration (Cmax) for AZD5004 and total radioactivity (TR) - Part 1 and Part 2	Pharmacokinetics (PK) ofAZD5004 and [14C]AZD5004 in plasma	Plasma sample collection from pre-dose to 110 hours post-dose in Part 1 and from pre-dose to 168 hours post-dose in Part 2
Area under the curve from time 0 extrapolated to infinity (AUC0-inf) for AZD5004 - Part 1 and Part 2	Pharmacokinetics (PK) of AZD5004 and [14C]AZD5004 in plasma	Plasma sample collection from pre-dose to 110 hours post-dose in Part 1 and from pre-dose to 168 hours post-dose in Part 2
Area under the curve (AUC) of circulating plasma total radioactivity (TR) or accounting for 10% or more of the dose in excreta - Part 2	Identification of the chemical structure of each metabolite accounting for more than 10% by AUC of circulating total radioactivity (TR) or accounting for 10% or more of the dose in excreta	Plasma, urine and faecal samples from pre-dose until 168 hours post-dose
Blood:plasma concentration ratios - Part 2	Blood:plasma concentration ratios for total radioactivity (TR)	Whole blood and plasma samples collected from pre-dose until 168 hoours post-dose
Number of subjects with treatment-related adverse events - Part 1 and 2	To provide additional safety and tolerability information for AZD5004 by assessing the incidence of AEs	Through study duration, approximately 7 weeks

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Quotient Sciences
• Investigators: Principal Investigator: Sharan Sidhu, MBChB, BAO, MRCS, MFPM, Quotient Sciences

Study record dates

Study Major Dates

• Study Start (Actual): March 6, 2025
• Primary Completion (Actual): May 5, 2025
• Study Completion (Actual): May 5, 2025

Study Registration Dates

• First Submitted: February 27, 2025
• First Submitted That Met QC Criteria: February 27, 2025
• First Posted (Actual): March 4, 2025

Study Record Updates

• Last Update Posted (Actual): May 28, 2025
• Last Update Submitted That Met QC Criteria: May 27, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Healthy Participants
• Additional Relevant MeSH Terms: Pharmaceutical Solutions
• Other Study ID Numbers: D7260C00010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual participant-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests 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 approved.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD Sharing Access Criteria

When a request has been approved AstraZeneca will provide access to the anonymized individual participant-level data via secure research environment Vivli.org.

Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No