Pharmacokinetics
Conditions
Brief summary
A Study in Healthy Male Subjects Designed to Evaluate the Pharmacokinetic Profile of Abiraterone Following Administration of Immediate Release Formulations
Detailed description
This was a single centre, 2 part, open-label study in healthy male subjects. Parts 1 and 2 were conducted in separate cohorts of subjects; subjects were not permitted to participate in both parts. Part 1 was a part-randomised, 4 period crossover study planned to include 24 healthy male subjects. Part 2 was a randomised 2-period crossover study in 12 healthy male subjects. The aim was to evaluate the pharmacokinetic profiles of abiraterone following administration of immediate release prototype formulations in healthy male subjects.
Interventions
DRUGAbiraterone Acetate
Abiraterone acetate immediate release formulations
Sponsors
Zentiva, k.s.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy males 2. Age 18 to 55 years of age at the time of signing informed consent 3. Expressed a desire not to father children in the near future (within 6 months of last IMP dose); males under 40 years of age must have been vasectomised 4. Body mass index (BMI) of 18.5 to 30.0 kg/m2 as measured at screening 5. Willing and able to communicate and participate in the whole study 6. Provided written informed consent 7. Agreed to adhere to the contraception requirements defined in Section 9.4 of the protocol
Exclusion criteria
1. Subjects who received any IMP in a clinical research study within the 3 months or 90 days prior to Day 1 Period 1 2. Males with a pregnant female partner 3. Subjects were unable or unwilling to consume the standard high-fat breakfast (Part 2) 4. Subjects were study site employees, or immediate family members of a study site or sponsor employee 5. Subjects who had previously been enrolled in this study. Subjects who had taken part in Part 1 were not permitted to take part in Part 2 6. History of any drug or alcohol abuse in the past 2 years prior to screening 7. Regular alcohol consumption in males \>21 units per week (1 unit = ½ pint beer, or a 25 mL shot of 40% spirit, 1.5 to 2 Units = 125 mL glass of wine, depending on type) as confirmed by a repeat of the first positive alcohol breath test at screening or admission 8. Current smokers and those who had smoked within the last 12 months. A confirmed breath carbon monoxide (CO) reading of greater than 10 ppm, as confirmed by repeat of the first test at screening or admission 9. Current users of e-cigarettes and nicotine replacement products and those who had used these products within the last 12 months prior to screening 10. Subjects without suitable veins for multiple venepunctures/cannulation as assessed by the investigator or delegate at screening 11. Clinically significant abnormal biochemistry, haematology or urinalysis at screening as judged by the investigator 12. Serum potassium below the lower limit of the laboratory reference range at screening 13. Alanine aminotransferase \>1.5× upper limit of laboratory reference range at screening 14. Total bilirubin \>1.5× upper limit of laboratory reference range at screening 15. Confirmed positive drugs of abuse test result 16. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) orhuman immunodeficiency virus (HIV) results at screening 17. Systolic blood pressure (BP) \>140 mmHg, diastolic blood pressure \>90 mmHg (systolic blood pressure up to 150 mmHg allowed in subjects \>45 years of age) at screening or Period 1 Day 1 pre-dose 18. History of clinically significant cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal disease, neurological or psychiatric disorder, as judged by the investigator 19. Subjects with a history of cholecystectomy or gall stones 20. Serious adverse reaction or serious hypersensitivity to any drug 21. History of any hypersensitivity reaction to abiraterone or the formulation excipients regardless of severity 22. Subjects with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption, lactose intolerance 23. Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever was allowed unless it was active 24. Donation or loss of greater than 400 mL of blood within the previous 3 months prior to screening 25. Subjects who were taking, or had taken, any prescribed or over-the-counter drug (other than 4 g of paracetamol per day) or herbal remedies in the 14 days before Day 1, Period 1. Exceptions may have been applied on a case by case basis, if considered not to interfere with the objectives of the study, as agreed by the PI 26. Use of known strong CYP3A4 inducers, including St John's Wort, in the 30 days prior to Period 1 Day 1 27. Failure to satisfy the investigator of fitness to participate for any other reason
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Abiraterone Cmax | 24h | maximal concentration of abiraterone in human plasma |
| Abiraterone AUC | 24h | total exposure up to 24h of abiraterone in human plasma |
Countries
United Kingdom
Outcome results
None listed