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| Name | Class |
|---|---|
| Quotient Sciences | INDUSTRY |
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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.
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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| AZD5462 | Experimental | In Period 1, participants will receive one oral dose of [14C]AZD5462. In Period 2, participants will receive one oral dose of AZD5462 and one intravenous dose of [14C]AZD5462. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AZD5462 film-coated tablet | Drug | Oral, fasted |
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| Measure | Description | Time Frame |
|---|---|---|
| Amount of AZD5462 excreted (Ae) - Period 1 | Mass balance recovery of total radioactivity of [14C]AZD5462 in urine and faecal samples | Urine and faecal samples collected from pre-dose until 168 hours post-dose |
| Amount of AZD5462 excreted expressed as a percentage of the dose administered (Fe) - Period 1 | Mass balance recovery of total radioactivity of [14C]AZD5462 in urine and faecal samples | Urine and faecal samples collected from pre-dose until 168 hours post-dose |
| Cumulative amount of AZD5462 excreted (CumAe) - Period 1 | Mass balance recovery of total radioactivity of [14C]AZD5462 in urine and faecal samples | Urine and faecal samples collected from pre-dose until 168 hours post-dose |
| Cumulative amount of AZD5462 excreted expressed as a percentage of the dose administered (CumFe) - Period 1 | Mass balance recovery of total radioactivity of [14C]AZD5462 in urine and faecal samples | Urine and faecal samples collected from pre-dose until 168 hours post-dose |
| Absolute bioavailability - Period 2 | Absolute bioavailability (F) based on AUC0-inf of oral and IV administration, adjusted for dose | Plasma sample collection from pre-dose to 72 hours post-dose |
| Measure | Description | Time Frame |
|---|---|---|
| Time of maximum observed concentration (tmax) for AZD5462 and total radioactivity - Period 1 | PK of AZD5462 and [14C]AZD5462 in plasma | Plasma sample collection from pre-dose to 168 hours post-dose |
| Maximum observed concentration (Cmax) for AZD5462 and total radioactivity - Period 1 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Philip Evans, MBChB, MRCS (Ed) | Quotient Sciences | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Ruddington | NG11 6JS | United Kingdom |
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.
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 at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
When a request has been approved AstraZeneca will provide access to the anonymized individual patient-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.
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| [14C]AZD5462 Solution for Infusion | Drug | Intravenous, fasted |
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| [14C]AZD5462 Oral Solution | Drug | Oral, fasted |
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PK of AZD5462 and [14C]AZD5462 in plasma |
| Plasma sample collection from pre-dose to 168 hours post-dose |
| Area under the curve from time 0 to the time of last measurable concentration (AUC0-t) for AZD5462 and total radioactivity - Period 1 | PK of AZD5462 and [14C]AZD5462 in plasma | Plasma sample collection from pre-dose to 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 (AUC0-extrap) for AZD5462 and total radioactivity - Period 1 | PK of AZD5462 and [14C]AZD5462 in plasma | Plasma sample collection from pre-dose to 168 hours post-dose |
| Terminal elimination half-life (t1/2) for AZD5462 and total radioactivity - Period 1 | PK of AZD5462 and [14C]AZD5462 in plasma | Plasma sample collection from pre-dose to 168 hours post-dose |
| First order rate constant associated with the terminal (log-linear) portion of the curve (λz) for AZD5462 and total radioactivity - Period 1 | PK of AZD5462 and [14C]AZD5462 in plasma | Plasma sample collection from pre-dose to 168 hours post-dose |
| 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 | PK of AZD5462 and [14C]AZD5462 in plasma | Plasma sample collection from pre-dose to 168 hours post-dose |
| Renal clearance calculated using plasma AUC (CLR) for AZD5462 and total radioactivity - Period 1 | PK of AZD5462 and [14C]AZD5462 in plasma and urine | Plasma sample collection from pre-dose to 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) for AZD5462 and total radioactivity - Period 1 | PK of AZD5462 and [14C]AZD5462 in plasma and urine | Plasma sample collection from pre-dose to 168 hours post-dose |
| Area under the curve (AUC) of circulating plasma total radioactivity (TR) or accounting for 10% or more of the dose in excreta - Period 1 | Identification of the chemical structure of each metabolite accounting for more than 10% by AUC of circulating TR or accounting for 10% or more of the dose in urine and faeces | Plasma, urine and faecal samples from pre-dose until 168 hours post-dose |
| Blood:plasma concentration ratios - Period 1 | Blood:plasma concentration ratios of total radioactivity | Whole blood samples and plasma samples collected from pre-dose until 168 hours post-dose |
| Amount of unchanged AZD5462 excreted in urine (Ae) - Period 2 | Recovery of total radioactivity of [14C]AZD5462 in urine | Urine sample collection from pre-dose to 72 hours post-dose |
| Amount of unchanged AZD5462 excreted in urine expressed as a percentage of the radioactive dose administered (Fe) - Period 2 | Recovery of total radioactivity of [14C]AZD5462 in urine | Urine sample collection from pre-dose to 72 hours post-dose |
| Cumulative amount of unchanged AZD5462 excreted in urine (CumAe) - Period 2 | Recovery of total radioactivity of [14C]AZD5462 in urine | Urine sample collection from pre-dose to 72 hours post-dose |
| Cumulative amount of unchanged AZD5462 excreted in urine expressed as a percentage of the radioactive dose administered (CumFe) - Period 2 | Recovery of total radioactivity of [14C]AZD5462 in urine | Urine sample collection from pre-dose to 72 hours post-dose |
| Area under the curve from time 0 extrapolated to infinity (AUC0-inf) for AZD5462 and total radioactivity - Period 1 | PK of AZD5462 and [14C]AZD5462 in plasma | Plasma sample collection from pre-dose to 168 hours post-dose |
| Time of maximum observed concentration (tmax) for AZD5462 and [14C]AZD5462 - Period 2 | PK of AZD5462 and [14C]AZD5462 in plasma | Plasma sample collection from pre-dose to 72 hours post-dose |
| Maximum observed concentration (Cmax) for AZD5462 and [14C]AZD5462 - Period 2 | PK of AZD5462 and [14C]AZD5462 in plasma | Plasma sample collection from pre-dose to 72 hours post-dose |
| Area under the curve from time 0 extrapolated to infinity (AUC0-inf) for AZD5462 and [14C]AZD5462 - Period 2 | PK of AZD5462 and [14C]AZD5462 in plasma | Plasma sample collection from pre-dose to 72 hours post-dose |
| Area under the curve from time 0 to the time of last measurable concentration (AUC0-t) for AZD5462 and [14C]AZD5462 - Period 2 | PK of AZD5462 and [14C]AZD5462 in plasma | Plasma sample collection from pre-dose to 72 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 (AUC0-extrap) for AZD5462 and [14C]AZD5462- Period 2 | PK of AZD5462 and [14C]AZD5462 in plasma | Plasma sample collection from pre-dose to 72 hours post-dose |
| Terminal elimination half-life (t1/2) for AZD5462 and [14C]AZD5462 - Period 2 | PK of AZD5462 and [14C]AZD5462 in plasma | Plasma sample collection from pre-dose to 72 hours post-dose |
| First order rate constant associated with the terminal (log-linear) portion of the curve (λz) for AZD5462 and [14C]AZD5462 - Period 2 | PK of AZD5462 and [14C]AZD5462 in plasma | Plasma sample collection from pre-dose to 72 hours post-dose |
| Total body clearance calculated after a single IV administration (CL) for AZD5462 and [14C]AZD5462 - Period 2 | PK of AZD5462 and [14C]AZD5462 in plasma | Plasma sample collection from pre-dose to 72 hours post-dose |
| 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 | PK of AZD5462 and [14C]AZD5462 in plasma | Plasma sample collection from pre-dose to 72 hours post-dose |
| 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 | PK of AZD5462 and [14C]AZD5462 in plasma | Plasma sample collection from pre-dose to 72 hours post-dose |
| Apparent volume of distribution at steady state after a single IV administration (Vss) for AZD5462 and [14C]AZD5462 - Period 2 | PK of AZD5462 and [14C]AZD5462 in plasma | Plasma sample collection from pre-dose to 72 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) for AZD5462 and [14C]AZD5462 - Period 2 | PK of AZD5462 and [14C]AZD5462 in plasma | Plasma sample collection from pre-dose to 72 hours post-dose |
| Number of subjects with treatment-related adverse events - Periods 1 and 2 | To provide additional safety and tolerability information for AZD5462 | Through study duration, an average of 7 weeks |
| ID | Term |
|---|---|
| D006333 | Heart Failure |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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