Determining the Effect of Abiraterone on the Metabolism of Oxycodone in Men With Prostate Cancer (the ENABLE Study)

Prior treatment

• Use of oxycodone short acting \<48 hours, or long acting \<96 hours prior to the study day;
• Use of other opioids in the 14 days prior to the study day (see also appendix A);
• Use of other medication that has pharmacokinetic or pharmacodynamics interactions with oxycodone (see also appendix A);
• Arm 1: dose reduction or successive days of treatment interruption within 10 days prior to the study day (arm 1);
• Arm 2: treatment with abiraterone within 10 days prior to the study day;
• Known metastases in the liver that would affect drug metabolism;
• Subjects with significant respiratory depression resulting in the need of oxygen therapy or objective hypoventilation (respiratory rate \<12/min);
• Subjects who started their first cycle of chemotherapy during the 2 weeks before the study day;
• Major surgery within 1 month prior to screening or planned surgery;
• Patients receiving opioid substitution therapy for opioid addiction (e.g. methadone or buprenorphine) and/or suffering from opioid withdrawal
• Previous gastric bypass or gastric band surgery.

Other illness

• If any type of abnormality; active or symptomatic viral hepatitis or chronic liver disease (e.g. classification with Child-Pugh B, Child-Pugh C);
• Subjects with, a history of bronchial asthma, chronic obstructive pulmonary disease or pulmonary heart disease;
• A history of drug abuse
• Patients with evidence of clinically significant gastrointestinal disease;

Lab values

• Moderate-severe renal dysfunction (GFR \<60 ml/min/1.73m2) that affects drug metabolism ;

Other

• A body mass index (BMI) outside the range of 18 - 30 kg/m2;
• If hypersensitive to oxycodone;
• patients suffering from diarrhea
• Patients with a CYP3A4 or CYP2D6 polymorphism;
• Hypercapnia (venous pCO2 outside the range of 5.5 - 6.7; pH outside the range 7.30 - 7.40);
• Patients who are contraindicated for blood sampling;
• Unable to swallow solid, oral dosage forms whole with water;
• Participation in a clinical trial study at the time of enrolment or within 30 days or 5 half-lives of enrolment, whichever is longer;

• Diagnosed prostate cancer;
• Males aged 18 years or older;
• Treated with abiraterone 1000 mg once daily for at least 10 days (abiraterone arm).
• Not treated with abiraterone 1000 mg once daily for at least 10 days (control arm).