Clinical trial NCT06989983: A Study Designed to Assess the Mass Balance Recovery, Absorption, Metabolism, Excretion of [14C]AZD5462 and the Absolute Bioavailability of AZD5462
Official title: An Open-Label, Two-Period Study Designed to Assess the Mass Balance Recovery, Absorption, Metabolism, Excretion of [14C]AZD5462 and the Absolute Bioavailability of AZD5462 in Healthy Male Participants
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Heart Failure
Keywords: Heart failure
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Quotient Sciences
First posted: 2025-05-25
Enrollment: 8
Sex: MALE
Minimum age (years): 30
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A study to investigate how the body breaks down and gets rid of the test medicine, AZD5462.

To help investigate this, the test medicine is radiolabelled, which means that the test medicine has a radioactive component (carbon-14), 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.

Detailed description: This is an open-label, two-period study designed to assess the mass balance recovery, absorption, metabolism, excretion of \[14C\]AZD5462 and the absolute bioavailability of AZD5462 in healthy male participants.

The study will take place at 1 site in Nottingham, and enrol 8 healthy men aged 30-65 years. The study will include 2 Periods:

* In Period 1 volunteers will receive a single dose of radiolabelled test medicine as a liquid by mouth.
* In Period 2 volunteers will receive a single dose of the test medicine as capsules by mouth and shortly afterwards, a very tiny dose of radiolabelled study medicine by injection into a vein.

The participants will be resident in the clinical unit throughout both study periods for a total of 12 nights. The total study duration is approximately up to 6 weeks.

Eligibility criteria: Inclusion Criteria:

* Healthy males aged 30 to 65 years inclusive
* BMI in the range 18.0 - 32.0 kg/m2 inclusive and body weight ≥ 50 kg and ≤ 100 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
* History of active malignancy within 2 years, or under investigation for any form of cancer
* Participants who do not have suitable veins for multiple venepunctures/cannulation
* Clinically significant abnormal clinical chemistry, haematology or urinalysis
* Any clinically significant abnormalities in vital signs
* Any clinically significant abnormalities on 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 radiolabelled ADME study in the last 12 months.
* Use of any prescribed or non-prescribed medication including antacids, analgesics, herbal remedies, vitamins and minerals
* Current smokers or known or suspected history of alcohol or drug abuse
* Excessive intake of caffeine-containing drinks or food

Primary outcomes:
measure: Amount of AZD5462 excreted (Ae) - Period 1
timeFrame: Urine and faecal samples collected from pre-dose until 168 hours post-dose
measure: Amount of AZD5462 excreted expressed as a percentage of the dose administered (Fe) - Period 1
timeFrame: Urine and faecal samples collected from pre-dose until 168 hours post-dose
measure: Cumulative amount of AZD5462 excreted (CumAe) - Period 1
timeFrame: Urine and faecal samples collected from pre-dose until 168 hours post-dose
measure: Cumulative amount of AZD5462 excreted expressed as a percentage of the dose administered (CumFe) - Period 1
timeFrame: Urine and faecal samples collected from pre-dose until 168 hours post-dose
measure: Absolute bioavailability - Period 2
timeFrame: Plasma sample collection from pre-dose to 72 hours post-dose
Secondary outcomes:
measure: Time of maximum observed concentration (tmax) for AZD5462 and total radioactivity - Period 1
timeFrame: Plasma sample collection from pre-dose to 168 hours post-dose
measure: Maximum observed concentration (Cmax) for AZD5462 and total radioactivity - Period 1
timeFrame: Plasma sample collection from pre-dose to 168 hours post-dose
measure: Area under the curve from time 0 to the time of last measurable concentration (AUC0-t) for AZD5462 and total radioactivity - Period 1
timeFrame: Plasma sample collection from pre-dose to 168 hours post-dose
measure: 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 (AUC0-extrap) for AZD5462 and total radioactivity - Period 1
timeFrame: Plasma sample collection from pre-dose to 168 hours post-dose
measure: Terminal elimination half-life (t1/2) for AZD5462 and total radioactivity - Period 1
timeFrame: Plasma sample collection from pre-dose to 168 hours post-dose
measure: First order rate constant associated with the terminal (log-linear) portion of the curve (λz) for AZD5462 and total radioactivity - Period 1
timeFrame: Plasma sample collection from pre-dose to 168 hours post-dose
measure: Total body clearance calculated after a single extravascular administration where F (fraction of dose bioavailable) is unknown (CL/F) for AZD5462 and total radioactivity - Period 1
timeFrame: Plasma sample collection from pre-dose to 168 hours post-dose
measure: Renal clearance calculated using plasma AUC (CLR) for AZD5462 and total radioactivity - Period 1
timeFrame: Plasma sample collection from pre-dose to 168 hours post-dose
measure: 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) for AZD5462 and total radioactivity - Period 1
timeFrame: Plasma sample collection from pre-dose to 168 hours post-dose
measure: Area under the curve (AUC) of circulating plasma total radioactivity (TR) or accounting for 10% or more of the dose in excreta - Period 1
timeFrame: Plasma, urine and faecal samples from pre-dose until 168 hours post-dose
measure: Blood:plasma concentration ratios - Period 1
timeFrame: Whole blood samples and plasma samples collected from pre-dose until 168 hours post-dose
measure: Amount of unchanged AZD5462 excreted in urine (Ae) - Period 2
timeFrame: Urine sample collection from pre-dose to 72 hours post-dose
measure: Amount of unchanged AZD5462 excreted in urine expressed as a percentage of the radioactive dose administered (Fe) - Period 2
timeFrame: Urine sample collection from pre-dose to 72 hours post-dose
measure: Cumulative amount of unchanged AZD5462 excreted in urine (CumAe) - Period 2
timeFrame: Urine sample collection from pre-dose to 72 hours post-dose
measure: Cumulative amount of unchanged AZD5462 excreted in urine expressed as a percentage of the radioactive dose administered (CumFe) - Period 2
timeFrame: Urine sample collection from pre-dose to 72 hours post-dose
measure: Area under the curve from time 0 extrapolated to infinity (AUC0-inf) for AZD5462 and total radioactivity - Period 1
timeFrame: Plasma sample collection from pre-dose to 168 hours post-dose
measure: Time of maximum observed concentration (tmax) for AZD5462 and [14C]AZD5462 - Period 2
timeFrame: Plasma sample collection from pre-dose to 72 hours post-dose
measure: Maximum observed concentration (Cmax) for AZD5462 and [14C]AZD5462 - Period 2
timeFrame: Plasma sample collection from pre-dose to 72 hours post-dose
measure: Area under the curve from time 0 extrapolated to infinity (AUC0-inf) for AZD5462 and [14C]AZD5462 - Period 2
timeFrame: Plasma sample collection from pre-dose to 72 hours post-dose
measure: Area under the curve from time 0 to the time of last measurable concentration (AUC0-t) for AZD5462 and [14C]AZD5462 - Period 2
timeFrame: Plasma sample collection from pre-dose to 72 hours post-dose
measure: 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 (AUC0-extrap) for AZD5462 and [14C]AZD5462- Period 2
timeFrame: Plasma sample collection from pre-dose to 72 hours post-dose
measure: Terminal elimination half-life (t1/2) for AZD5462 and [14C]AZD5462 - Period 2
timeFrame: Plasma sample collection from pre-dose to 72 hours post-dose
measure: First order rate constant associated with the terminal (log-linear) portion of the curve (λz) for AZD5462 and [14C]AZD5462 - Period 2
timeFrame: Plasma sample collection from pre-dose to 72 hours post-dose
measure: Total body clearance calculated after a single IV administration (CL) for AZD5462 and [14C]AZD5462 - Period 2
timeFrame: Plasma sample collection from pre-dose to 72 hours post-dose
measure: Total body clearance calculated after a single extravascular administration where F (fraction of dose bioavailable) is unknown (CL/F) for AZD5462 and [14C]AZD5462 - Period 2
timeFrame: Plasma sample collection from pre-dose to 72 hours post-dose
measure: Volume of distribution based on the terminal phase calculated using AUC(0-inf) after a single IV administration (Vz) for AZD5462 and [14C]AZD5462 - Period 2
timeFrame: Plasma sample collection from pre-dose to 72 hours post-dose
measure: Apparent volume of distribution at steady state after a single IV administration (Vss) for AZD5462 and [14C]AZD5462 - Period 2
timeFrame: Plasma sample collection from pre-dose to 72 hours post-dose
measure: 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) for AZD5462 and [14C]AZD5462 - Period 2
timeFrame: Plasma sample collection from pre-dose to 72 hours post-dose
measure: Number of subjects with treatment-related adverse events - Periods 1 and 2
timeFrame: Through study duration, an average of 7 weeks
Other outcomes:
Locations:
city: Ruddington
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Quotient Sciences
name: Philip Evans, MBChB, MRCS (Ed)
role: PRINCIPAL_INVESTIGATOR
References: