A study in healthy post-menopausal female volunteers to assess how the test medicine [14C]AZD9833 is taken up, broken down and removed from the body
- Conditions
- ER-positive, HER2-negative breast cancerCancer
- Registration Number
- ISRCTN46127225
- Lead Sponsor
- AstraZeneca (Sweden)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Female
- Target Recruitment
- 6
1. Provision of signed and dated, written informed consent prior to any study-specific procedures
2. Aged between 50 to 70 years inclusive at the time of signing informed consent
3. Healthy post-menopausal females, defined as post-menopausal by fulfilling the following criterion:
3.1. Amenorrhoea for at least 12 months following cessation of all exogenous hormonal treatments and without an alternative medical or surgical cause and confirmed by an FSH result of =30 IU/l
4. Must be willing and able to communicate and participate in the whole study
5. Have a body mass index (BMI) between 19.0 to 35.0 kg/m², weigh at least 50 kg and no more than 100 kg inclusive as measured at screening.
6. Must have regular bowel movements (i.e. average stool production of =1 and =3 stools per day)
1. History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer’s ability to participate in the study
2. History or presence of GI, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs
3. Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP
4. History of or ongoing clinically significant visual disturbances including but not limited to visual hallucinations, migraine with visual symptoms, blurred vision, frequent floaters/flashes associated with other symptoms such as dizziness
5. Any clinically significant abnormalities in clinical chemistry, haematology, or urinalysis results, at screening as judged by the Investigator.
6. Any clinically significant abnormal findings in vital signs at screening as judged by the Investigator, including systolic BP <100 mmHg, diastolic BP <50 mmHg or heart rate <50 bpm. Vital signs outside these limits can be repeated once for confirmation
7. Any clinically significant abnormalities on 12-lead ECG at screening, as judged by the Investigator, including non-sinus rhythms, PR interval <120 msec or >220 msec, ventricular rate <50 bpm or >100 bpm, QRS interval >120 msec, or QTcF >470 msec as a mean of triplicate. ECGs can be repeated once in triplicate if parameters are outside these limits for confirmation
8. Evidence of renal impairment at screening, as indicated by an estimated creatinine clearance (CLcr) of <60 ml/min/1.73m² using the Cockcroft-Gault equation
9. Any positive result on screening for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab), and human immunodeficiency virus (HIV) 1 and 2 antibodies
10. Has received another new chemical entity (defined as a compound which has not been approved for marketing) within 4 weeks prior to Day 1, or less than 5 elimination half-lives + 6 days prior to Day 1, whichever is longer. Note: subjects consented and screened, but not administered IMP in this study or a previous Phase I study, are not excluded
11. Plasma donation within 1 month of screening or any blood donation/loss more than 500 ml during the 3 months prior to screening
12. History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the Investigator or history of hypersensitivity to drugs with a similar chemical structure or class to AZD9833. Hay fever is allowed unless it is active
13. Any known or suspected hypersensitivity or contraindication to the components of the study drug, AZD9833, judged to be clinically relevant by the investigator
14. Current smokers or those who have smoked or used nicotine products (including e-cigarettes) within the 3 months prior to screening
15. A confirmed breath carbon monoxide reading of greater than 10 ppm at screening or admission
16. Positive screen for drugs of abuse at screening or on each admission to the study centre
17. Regular alcohol consumption >14 units per week (1 unit = ½ pint beer, or a 25 mL shot of 40% spirit, 1.5 to 2
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br> 1. Mass balance recovery of total radioactivity in all excreta (urine and faeces): CumAe and Cum%Ae measured by accelerator mass spectrometry from samples taken at timepoints between Day 1 up to Day 10<br> 2. Levels and structures of drug and metabolites in plasma, urine and faeces measured by ultra-performance liquid chromatography coupled to high-resolution mass spectrometry (hrMS)/mass spectrometry (MS) from samples taken at timepoints between Day 1 up to Day 10 (plus any additional samples taken beyond this period if warranted)<br>
- Secondary Outcome Measures
Name Time Method <br> 1. Mass balance recovery of total radioactivity in urine and faeces separately: Ae, %Ae, CumAe and Cum%Ae by interval measured by accelerator mass spectrometry from samples taken at timepoints between Day 1 up to Day 10<br> 2. Assessment of the PK of AZD9833 and total radioactivity by calculation of tmax, Cmax, AUC0-t, AUC0-inf, AUC%extr, t1/2, ?z, CL/F and Vz/F measured by LC-UV-MS from samples taken at timepoints between Day 1 up to Day 10<br> 3. Whole blood:plasma concentration ratios for total radioactivity evaluated using samples taken at timepoints between Day 1 up to Day 10<br> 4. Safety and tolerability information via measures including physical examinations, vital signs, ECGs and laboratory safety tests will be assessed by standard phase 1 unit monitoring at screening, from Day -1 to discharge from the ward on (up to) Day 10<br>