Healthy Participants
Conditions
Keywords
Healthy participants
Brief summary
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.
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.
Interventions
DRUG[14C]AZD4954 Oral Solution
Participants in Part 1 will recieve a single dose of \[14C\]AZD4954 oral solution
DRUGAZD4954 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
Sponsors
AstraZeneca
Quotient Sciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Parts 1 and 2 are each single arm regimens
Eligibility
Sex/Gender
MALE
Age
30 Years to 65 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Amount of AZD4954 excreted (Ae) (Part 1) | Urine and faecal samples collected from pre-dose until up to 552 hours post-dose | Mass balance recovery, rates and routes of elimination of total radioactivity of \[14C\] AZD4954 in urine, faeces and all excreta |
| Amount of AZD4954 excreted expressed as a fraction of dose excreted (Fe) (Part 1) | Urine and faecal samples collected from pre-dose until up to 552 hours post-dose | Mass balance recovery, rates and routes of elimination of total radioactivity of \[14C\] AZD4954 in urine, faeces and all excreta |
| Cumulative amount of AZD4954 excreted (CumAe) (Part 1) | Urine and faecal samples collected from pre-dose until up to 552 hours post-dose | Mass balance recovery, rates and routes of elimination of total radioactivity of \[14C\] AZD4954 in urine, faeces and all excreta |
| Cumulative amount of AZD4954 excreted expressed as a fraction of dose excreted (CumFe) (Part 1) | Urine and faecal samples collected from pre-dose until up to 552 hours post-dose | Mass balance recovery, rates and routes of elimination of total radioactivity of \[14C\] AZD4954 in urine, faeces and all excreta |
| Absolute bioavailability (F) based on AUC0-inf (Part 2) | Plasma, urine and faecal samples from pre-dose until up to 336 hours post-dose | Absolute bioavailability of AZD4954 oral and IV administration, adjusted for dose |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum observed concentration (Cmax) for AZD4954 and total radioactivity (Parts 1 and 2) | Plasma, urine, and whole blood samples collected from pre-dose until up to 552 hours post-dose | The PK of AZD4954 and \[14C\]AZD4954 in plasma and urine, and total radioactivity in plasma and whole blood |
| Time of maximum observed concentration (Tmax) for AZD4954 and total radioactivity (Parts 1 and 2) | Plasma, urine, and whole blood samples collected from pre-dose until up to 552 hours post-dose | The PK of AZD4954 and \[14C\]AZD4954 in plasma and urine, and total radioactivity in plasma and whole blood |
| Area under the curve from time 0 extrapolated to infinity (AUC0-inf) for AZD4954 and total radioactivity (Parts 1 and 2) | Plasma, urine, and whole blood samples collected from pre-dose until up to 552 hours post-dose | The PK of AZD4954 and \[14C\]AZD4954 in plasma and urine, and total radioactivity in plasma and whole blood |
| Terminal elimination half-life (T1/2) for AZD4954 and total radioactivity (Parts 1 and 2) | Plasma, urine, and whole blood samples collected from pre-dose until up to 552 hours post-dose | The PK of AZD4954 and \[14C\]AZD4954 in plasma and urine, and total radioactivity in plasma and whole blood |
| Area under the curve (AUC) of circulating total radioactivity accounting for 10% or more of the dose (Part 1) | Plasma, urine and faecal samples collected from pre-dose until up to 552 hours post-dose | Identification of the chemical structure of each metabolite |
| 80% or more of the radioactivity recovered in excreta (Part 1) | Plasma, urine and faecal samples collected from pre-dose until up to 552 hours post-dose | Identification of the chemical structure of each metabolite |
| Disposition of total radioactivity in plasma and in blood (Part 1) | Plasma, and whole blood samples collected from pre-dose until up to 552 hours post-dose | Evaluation of whole blood:plasma concentration ratios for total radioactivity |
Contacts
CONTACTAstraZeneca Clinical Study Information Center
PRINCIPAL_INVESTIGATORSharan Sidhu, MBChB, BAO, MRCS, MFPM
Quotient Sciences
Outcome results
None listed