Healthy Participants
Conditions
Keywords
Healthy Participants
Brief summary
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.
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.
Interventions
DRUGAZD5004 film-coated tablet
oral, fasted
DRUG[14C]AZD5004 Solution for Infusion
intravenous, fasted
DRUG[14C]AZD5004 Oral Solution
oral, fasted
Sponsors
Quotient Sciences
AstraZeneca
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
30 Years to 65 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative amount of AZD5004 excreted expressed as a percentage of the dose administered (CumFe) - Part 2 | Urine and faecal samples collected from pre-dose until 168 hours post dose | Mass balance recovery of total radioactivity (TR) in urine, faeces and all excreta (urine and faeces combined) |
| Absolute bioavailability - Part 1 | Plasma sample collection from pre-dose to 110 hrs post-dose | Absolute bioavailability (F) based on AUC0-inf of oral and IV administration, adjusted for dose |
| Amount of AZD5004 excreted (Ae) - Part 2 | Urine and faecal samples collected from pre-dose until 168 hours post-dose | Mass balance recovery of total radioactivity (TR) in urine, faeces and all excreta (urine and faeces combined) |
| Amount of AZD5004 excreted expressed as a percentage of the dose administered (Fe) - Part 2 | Urine and faecal samples collected from pre-dose until 168 hours post dose | Mass balance recovery of total radioactivity (TR) in urine, faeces and all excreta (urine and faeces combined) |
| Cumulative amount of AZD5004 excreted (CumAe) - Part 2 | Urine and faecal samples collected from pre-dose until 168 hours post dose | Mass balance recovery of total radioactivity (TR) in urine, faeces and all excreta (urine and faeces combined) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum observed concentration (Cmax) for AZD5004 and total radioactivity (TR) - Part 1 and Part 2 | 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 | Pharmacokinetics (PK) ofAZD5004 and \[14C\]AZD5004 in plasma |
| Area under the curve from time 0 extrapolated to infinity (AUC0-inf) for AZD5004 - Part 1 and Part 2 | 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 | Pharmacokinetics (PK) of AZD5004 and \[14C\]AZD5004 in plasma |
| Area under the curve (AUC) of circulating plasma total radioactivity (TR) or accounting for 10% or more of the dose in excreta - Part 2 | Plasma, urine and faecal samples from pre-dose until 168 hours post-dose | 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 |
| Blood:plasma concentration ratios - Part 2 | Whole blood and plasma samples collected from pre-dose until 168 hoours post-dose | Blood:plasma concentration ratios for total radioactivity (TR) |
| Number of subjects with treatment-related adverse events - Part 1 and 2 | Through study duration, approximately 7 weeks | To provide additional safety and tolerability information for AZD5004 by assessing the incidence of AEs |
Countries
United Kingdom
Outcome results
None listed