A study in healthy male volunteers to assess how the radiolabelled test medicine enters, is broken down and is removed from the body when given by mouth in the form of a tablet and liquid, and when given by short infusion into a vei
- Conditions
- Breast and prostate cancerCancerMalignant neoplasm of breast, Malignant neoplasm of prostate
- Registration Number
- ISRCTN15620353
- Lead Sponsor
- AstraZeneca (Sweden)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- Male
- Target Recruitment
- 8
1. Provision of signed and dated, written informed consent prior to any study-specific procedures
2. Must be willing and able to communicate and participate in the whole study
3. Healthy males aged 30 to 65 years inclusive at the time of signing the informed consent
4. Must be vasectomised (at least 6 months prior to screening) and must agree to adhere to the contraception requirements
5. Body mass index (BMI) of 18.0 to 32.0 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)
7. Provision of signed, written and dated informed consent for optional genetic research. If a subject declines to participate in the genetic component of the study, there will be no penalty or loss of benefit to the subject. The subject will not be excluded from other aspects of the study described in this protocol.
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 of any clinically significant disease or disorder (e.g. cardiovascular, pulmonary, GI (including but not limited to refractory nausea and vomiting, malabsorption syndrome, chronic GI diseases, previous cholecystectomy, inability to swallow the formulated product or previous significant bowel resection, or other condition that would preclude adequate absorption of capivasertib), liver, renal, neurological, musculoskeletal, endocrine, metabolic, malignant, psychiatric, major physical impairment, skin abnormalities and glucose metabolism abnormalities) which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, or influence the ADME of drugs.
3. History of latent or chronic infections (e.g. tuberculosis, recurrent sinusitis, genital herpes, urinary tract infections) or at risk of infection (surgery, trauma or significant infection within previous 90 days, history of skin abscesses within previous 90 days)
4. Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of IMP
5. 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 capivasertib. Hay fever is allowed unless it is active.
6. Any known or suspected hypersensitivity or contraindication to the components of the study drug, capivasertib, judged to be clinically relevant by the investigator
7. History of severe COVID-19 (e.g. hospitalisation, extracorporeal membrane oxygenation, mechanically ventilated) in the last 6 months
8. Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator or delegate at screening
9. Any clinically significant abnormal findings in vital signs, at screening or pre-dose, as judged by the investigator
10. QTcF >450 msec or QT >500 msec or other clinically significant ECG abnormality, as judged by the investigator, at screening or pre-dose, or a history of additional risk factors for Torsades de Points (e.g. heart failure, hypokalaemia, family history of long QT syndrome), which in the opinion of the Investigator may put the volunteer at risk.
11. Evidence of current SARS-CoV-2 infection within 2 weeks of first IMP administration
12. Any clinically significant abnormalities in clinical chemistry, haematology, or urinalysis results, as judged by the investigator
13. Total bilirubin (TBL) =1.5 × ULN or =3 × ULN in the presence of documented Gilbert’s syndrome (unconjugated hyperbilirubinemia)
14. Clinically significant abnormal fasting blood glucose or triglycerides at screening
15. Any positive result on screening for serum hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab), and human immunodeficiency virus (HIV) 1 and 2 antibody
16. Evidence of renal impairment at screening, as indicated by an estimated CLcr of <70
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br> Part 1:<br> Levels of drug and metabolites in blood assessed using high-performance liquid chromatography (HPLC) analysis of blood samples taken at 22 timepoints between Day 1 and Day 5<br><br> Part 2:<br> Absorption, distribution, metabolism, and excretion (ADME) characteristics calculated from levels of drug and metabolites in blood, faeces, urine and saliva assessed using HPLC analysis of samples collected throughout the trial between day 1 and (up to) day 10<br>
- Secondary Outcome Measures
Name Time Method <br> Part 1:<br> 1. Other safety 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 Day 5<br><br> Part 2:<br> 1. Chemical structure identification of breakdown products of the test medicine accounting for more than 10% of circulating total radioactivity or accounting for 10% or more of the dose in excreta, assessed by high-resolution mass spectrometry and HPLC analysis of samples collected throughout the trial between Day 1 and (up to) Day 10<br> 2. Other safety measures (including physical examinations, vital signs, ECGs and laboratory safety tests) assessed by standard phase 1 unit monitoring, at screening, from Day -1 to discharge from the ward on Day 10<br>