A Study Designed to Assess the Mass Balance Recovery, Absorption, Metabolism, Excretion of [14C]AZD4954 and the Absolute Bioavailability of AZD4954

An Open-Label Study to Assess the Mass Balance Recovery, Absorption, Metabolism, Excretion of [14C]AZD4954 and Absolute Bioavailability of AZD4954 in Healthy Male Participants

This study in healthy volunteers aims to explore blood levels and side effects of the test medicine, and look at how it is broken down when injected into a vein or given as a liquid by mouth. The test medicine will be radiolabelled with a small amount of carbon-14 so it can be tracked in the body.

This two-part study will take place at one site in Nottingham, United Kingdom, and will enroll 8 healthy men in each part, aged 30-65 years.

Study Overview

• Status: Not yet recruiting
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: [14C]AZD4954 Oral Solution; Drug: AZD4954 film-coated tablet; Drug: [14C]AZD4954 Solution for Infusion

Detailed Description

This study in healthy volunteers aims to explore blood levels and side effects of the test medicine, and look at how it is broken down when injected into a vein or given as a liquid by mouth. The test medicine will be radiolabelled with a small amount of carbon-14 so it can be tracked in the body.

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

It is planned to enroll 8 healthy male participants in each part, aged 30-65 years.

In part 1 volunteers will receive a single dose of radiolabelled test medicine as a liquid by mouth. They'll stay in the clinic for up to 24 nights, attend 1 outpatient visit, and take up to 8 weeks to finish the study.

In part 2 volunteers will receive a single dose of test medicine by mouth and, shortly afterwards, a very tiny dose of radiolabelled study medicine by injection into a vein. They'll stay in the clinic for up to 15 nights, attend 1 outpatient visit, and take up to 7 weeks to finish the study.

Blood and urine samples will be collected to do safety tests. Blood, urine and faecal samples will be collected to measure the amount of test medicine and its breakdown products.

• Study Type: Interventional
• Enrollment (Estimated): 16
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

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 of 18.0 to 35.0 kg/m2 inclusive
• Regular bowel movements (i.e. average stool production of ≥1 and ≤3 stools per day)

Exclusion Criteria:

• Serious adverse reaction or serious hypersensitivity to any drug or formulation excipients
• Presence or history of clinically significant allergy requiring treatment
• History of clinically significant cardiovascular, renal, hepatic, respiratory, dermatological or gastrointestinal disease, and neurological or psychiatric disorder
• History of cholecystectomy or gall stones
• History of GI surgery
• Acute diarrhoea or constipation in the 7 days before the predicted Day 1
• Participants who do not have suitable veins for multiple venepunctures/cannulation
• Clinically significant abnormal clinical chemistry, haematology, coagulation or urinalysis
• Evidence of renal impairment at screening
• Participants who have received any IMP in a clinical research study within the 90 days prior to Day 1
• Participants who have previously been administered IMP in this study
• Radiation exposure exceeding 5 mSv in the last 12 months or 10 mSv in the last 5 years
• Participants who have been administered IMP in an ADME study in the last 12 months
• Donation of blood or plasma within the previous 3 months or loss of greater than 400 mL of blood
• Use of any prescribed or non-prescribed medication including antacids, gastric pH modifying agents, analgesics, herbal remedies, vitamins and minerals within 2 weeks of dosing
• Current smokers or known or suspected history of alcohol or drug abuse
• Excessive intake of caffeine-containing drinks or food

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1; Participants in Part 1 will receive a single dose of [14C]AZD4954 Oral Solution.	Drug: [14C]AZD4954 Oral Solution; Participants in Part 1 will recieve a single dose of [14C]AZD4954 oral solution
Experimental: Part 2; Participants in Part 2 will receive a single unlabelled oral dose of AZD4954 tablet and a radiolabelled IV microtracer dose of [14C]AZD4954.	Drug: AZD4954 film-coated tablet; Participants in Part 2 will receive a single dose of AZD4954 film-coated tablet by mouth; Drug: [14C]AZD4954 Solution for Infusion; Participants in Part 2 will receive a single very tiny dose of radiolabelled [14C]AZD4954 Solution for Infusion as a slow injection into a vein

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Amount of AZD4954 excreted (Ae) (Part 1)	Mass balance recovery, rates and routes of elimination of total radioactivity of [14C] AZD4954 in urine, faeces and all excreta	Urine and faecal samples collected from pre-dose until up to 552 hours post-dose
Amount of AZD4954 excreted expressed as a fraction of dose excreted (Fe) (Part 1)	Mass balance recovery, rates and routes of elimination of total radioactivity of [14C] AZD4954 in urine, faeces and all excreta	Urine and faecal samples collected from pre-dose until up to 552 hours post-dose
Cumulative amount of AZD4954 excreted (CumAe) (Part 1)	Mass balance recovery, rates and routes of elimination of total radioactivity of [14C] AZD4954 in urine, faeces and all excreta	Urine and faecal samples collected from pre-dose until up to 552 hours post-dose
Cumulative amount of AZD4954 excreted expressed as a fraction of dose excreted (CumFe) (Part 1)	Mass balance recovery, rates and routes of elimination of total radioactivity of [14C] AZD4954 in urine, faeces and all excreta	Urine and faecal samples collected from pre-dose until up to 552 hours post-dose
Absolute bioavailability (F) based on AUC0-inf (Part 2)	Absolute bioavailability of AZD4954 oral and IV administration, adjusted for dose	Plasma, urine and faecal samples from pre-dose until up to 336 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum observed concentration (Cmax) for AZD4954 and total radioactivity (Parts 1 and 2)	The PK of AZD4954 and [14C]AZD4954 in plasma and urine, and total radioactivity in plasma and whole blood	Plasma, urine, and whole blood samples collected from pre-dose until up to 552 hours post-dose
Time of maximum observed concentration (Tmax) for AZD4954 and total radioactivity (Parts 1 and 2)	The PK of AZD4954 and [14C]AZD4954 in plasma and urine, and total radioactivity in plasma and whole blood	Plasma, urine, and whole blood samples collected from pre-dose until up to 552 hours post-dose
Area under the curve from time 0 extrapolated to infinity (AUC0-inf) for AZD4954 and total radioactivity (Parts 1 and 2)	The PK of AZD4954 and [14C]AZD4954 in plasma and urine, and total radioactivity in plasma and whole blood	Plasma, urine, and whole blood samples collected from pre-dose until up to 552 hours post-dose
Terminal elimination half-life (T1/2) for AZD4954 and total radioactivity (Parts 1 and 2)	The PK of AZD4954 and [14C]AZD4954 in plasma and urine, and total radioactivity in plasma and whole blood	Plasma, urine, and whole blood samples collected from pre-dose until up to 552 hours post-dose
Area under the curve (AUC) of circulating total radioactivity accounting for 10% or more of the dose (Part 1)	Identification of the chemical structure of each metabolite	Plasma, urine and faecal samples collected from pre-dose until up to 552 hours post-dose
80% or more of the radioactivity recovered in excreta (Part 1)	Identification of the chemical structure of each metabolite	Plasma, urine and faecal samples collected from pre-dose until up to 552 hours post-dose
Disposition of total radioactivity in plasma and in blood (Part 1)	Evaluation of whole blood:plasma concentration ratios for total radioactivity	Plasma, and whole blood samples collected from pre-dose until up to 552 hours post-dose

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 (Estimated): October 19, 2026
• Primary Completion (Estimated): December 17, 2026
• Study Completion (Estimated): December 17, 2026

Study Registration Dates

• First Submitted: September 4, 2026
• First Submitted That Met QC Criteria: September 4, 2026
• First Posted (Actual): September 10, 2026

Study Record Updates

• Last Update Posted (Actual): September 10, 2026
• Last Update Submitted That Met QC Criteria: September 4, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Healthy participants
• Other Study ID Numbers: D7300C00005

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 patient-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 shared.
• 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 rerefer to our disclosure commitment athttps://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environmentVivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Drug and device information, study documents

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