The Sponsor is developing the test medicine, AZD9833 for the potential treatment of estrogen receptor (ER)-positive breast cancer. This single-part, healthy volunteer study will try to identify how the test medicine is taken up, broken down and removed from the body. 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 study will take place at one non-NHS site, and will consist of a single study period involving up to 6 post-menopausal female volunteers, aged between 50 to 70 years.
The Sponsor is developing the test medicine, AZD9833 for the potential treatment of estrogen receptor (ER)-positive breast cancer. Breast cancer is the second most common type of cancer in the UK and worldwide. Most women diagnosed with breast cancer are over the age of 50, but younger women and men can also get breast cancer. AZD9833 has the potential to prevent ER activity and increase overall survival in advanced breast cancer patients. This single-part, healthy volunteer study will try to identify how the test medicine is taken up, broken down and removed from the body. 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 study will take place at one non-NHS site, and will consist of a single study period involving up to 6 post-menopausal female volunteers, aged between 50 to 70 years. On Day 1, volunteers will receive a 75 mg dose of \[14C\]AZD9833 oral solution in the fasted state (on an empty stomach). Volunteer's blood, urine and faeces will be taken throughout the study for analysis of the test medicine and it's breakdown products (metabolites) and for volunteer safety. Volunteers will remain in the clinical unit until Day 8, however if the relevant radioactivity criteria have not been met, volunteers may be required to remain at the clinic until Day 10. If relevant criteria have not been met at this point, home collections of urine and/or faeces may be required. Volunteers are expected to be involved in this study for approximately 6 weeks from screening to discharge.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
6
Oral Solution, 75 mg (NMT 0.67 MBq) - oral, fasted
Research Site
Ruddington, United Kingdom
The cumulative amount of AZD9833 excreted (CumAe)
Assessment of the total radioactivity by measuring the cumulative amount of AZD9833 excreted
Time frame: Urine and faecal samples collected from pre-dose until 168 hours post-dose
The cumulative amount of AZD9833 excreted, expressed as a percentage of the radioactive dose administered (Cum%Ae)
Assessment of the total radioactivity, expressed as a percentage, by measuring the cumulative amount of AZD9833 excreted
Time frame: Urine and faecal samples collected from pre-dose until 168 hours post-dose
Assessment of metabolites in plasma by liquid chromatography-radiochemical-detection and subsequent mass spectrometry
Assessment of metabolites in plasma by liquid chromatography-radiochemical-detection and subsequent mass spectrometry
Time frame: Plasma samples collected from pre-dose until 168 hours post-dose
Assessment of metabolites in urine by liquid chromatography-radiochemical-detection and subsequent mass spectrometry
Assessment of metabolites in urine by liquid chromatography-radiochemical-detection and subsequent mass spectrometry
Time frame: Urine samples collected from pre-dose until 168 hours post-dose
Assessment of metabolites in faeces by liquid chromatography-radiochemical-detection and subsequent mass spectrometry
Assessment of metabolites in faeces by liquid chromatography-radiochemical-detection and subsequent mass spectrometry
Time frame: Faeces samples collected from pre-dose until 168 hours post-dose
The amount of total radioactivity eliminated in urine (Ae)
Assessment of the total radioactivity, by measuring the amount of AZD9833 excreted in urine by interval
Time frame: Urine samples collected from pre-dose until 168 hours post-dose
The amount of total radioactivity eliminated in urine expressed as a percentage of the radioactive dose administered (%Ae)
Assessment of the total radioactivity, expressed as a percentage, by measuring the amount of AZD9833 excreted in urine by interval
Time frame: Urine samples collected from pre-dose until 168 hours post-dose
The cumulative amount of AZD9833 excreted in urine (CumAe)
Assessment of the total radioactivity by measuring the cumulative amount of AZD9833 excreted in faeces.
Time frame: Urine samples collected from pre-dose until 168 hours post-dose
The cumulative amount of AZD9833 excreted in urine, expressed as a percentage of the radioactive dose administered (Cum%Ae)
Assessment of the total radioactivity, expressed as a percentage, by measuring the cumulative amount of AZD9833 excreted in urine
Time frame: Urine samples collected from pre-dose until 168 hours post-dose
The amount of total radioactivity eliminated in faeces (Ae)
Assessment of the total radioactivity, by measuring the amount of AZD9833 excreted in faeces by interval
Time frame: Faeces samples collected from pre-dose until 168 hours post-dose
The amount of total radioactivity eliminated in faeces expressed as a percentage of the radioactive dose administered (%Ae)
Assessment of the total radioactivity, expressed as a percentage, by measuring the amount of AZD9833 excreted in faeces by interval
Time frame: Faeces samples collected from pre-dose until 168 hours post-dose
The cumulative amount of AZD9833 excreted in faeces (CumAe)
Assessment of the total radioactivity by measuring the cumulative amount of AZD9833 excreted in faeces.
Time frame: Faeces samples collected from pre-dose until 168 hours post-dose
The cumulative amount of AZD9833 excreted in faeces, expressed as a percentage of the radioactive dose administered (Cum%Ae)
Assessment of the total radioactivity, expressed as a percentage, by measuring the cumulative amount of AZD9833 excreted in faeces
Time frame: Faeces samples collected from pre-dose until 168 hours post-dose
Time to maximum concentration (tmax) for AZD9833 and total radioactivity
Assessment of pharmacokinetics of AZD9833 and total radioactivity by measuring the time to maximum concentration (tmax)
Time frame: Collection of plasma samples from pre-dose to 168 hours post-dose
Maximum observed concentration (cmax) for AZD9833 and total radioactivity
Assessment of pharmacokinetics of AZD9833 and total radioactivity by measuring the maximum observed concentration (cmax)
Time frame: Collection of plasma samples from pre-dose to 168 hours post-dose
Area under the curve from time 0 to the time of last measurable concentration for AZD9833 and total radioactivity (AUC0-t)
Assessment of pharmacokinetics of AZD9833 and total radioactivity by measuring the area under the curve from time 0 to the time of last measurable concentration
Time frame: Collection of plasma samples from pre-dose to 168 hours post-dose
Area under the curve from time 0 extrapolated to infinity for AZD9833 and total radioactivity (AUC0-inf)
Assessment of pharmacokinetics of AZD9833 and total radioactivity by measuring the area under the curve from time 0 extrapolated to infinity
Time frame: Collection of plasma samples 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 (AUC%extr) and total radioactivity
Assessment of pharmacokinetics of AZD9833 and total radioactivity by measuring the 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
Time frame: Collection of plasma samples from pre-dose to 168 hours post-dose
Terminal elimination half-life for AZD9833 (t1/2) and total radioactivity
Assessment of pharmacokinetics of AZD9833 and total radioactivity by measuring the terminal elimination half-life
Time frame: Collection of plasma samples from pre-dose to 168 hours post-dose
First order rate constant associated with the terminal (log-linear) portion of the curve for AZD9833 (λz) and total radioactivity
Assessment of pharmacokinetics of AZD9833 and total radioactivity by measuring the First order rate constant associated with the terminal (log-linear) portion of the curve
Time frame: Collection of plasma samples from pre-dose to 168 hours post-dose
Total body clearance calculated after a single extravascular administration for AZD9833 (CL/F) and total radioactivity
Assessment of pharmacokinetics of AZD9833 and total radioactivity by measuring the total body clearance calculated after a single extravascular administration
Time frame: Collection of plasma samples from pre-dose to 168 hours post-dose
Apparent volume of distribution based on the terminal phase for AZD9833 (Vz/F) and total radioactivity
Assessment of pharmacokinetics of AZD9833 and total radioactivity by measuring the apparent volume of distribution based on the terminal phase
Time frame: Collection of plasma samples from pre-dose to 168 hours post-dose
Renal clearance for AZD9833 (CLr) and total radioactivity
Assessment of pharmacokinetics of AZD9833 and total radioactivity by measuring the renal clearance
Time frame: Collection of plasma samples from pre-dose to 168 hours post-dose
Evaluation of whole blood:plasma concentration ratios for total radioactivity
Assessment of total radioactivity in whole blood and plasma
Time frame: Collection of blood samples until 168 hours post dose
Number of AE's experienced by subjects
Safety and tolerability assessed through the incidence of AEs
Time frame: AEs recorded from the time of informed consent until the follow up visit (approx 6 weeks)
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