Prostate cancer often leads to bone metastases, which require adequate pain management with opioids such as oxycodone. This study investigates whether abiraterone - a drug used in the treatment of prostate cancer - affects the pharmacokinetics of oxycodone in order to improve pain management.
Rationale: Oxycodone is an opioid receptor agonist metabolized primarily by CYP3A4, and to a lesser extent by CYP2D6. Abiraterone is an androgen biosynthesis inhibitor prescribed to men with castration resistant prostate cancer (CRPC). The ENABLE study is a follow-up to the ENZYME study in which it was described that enzalutamide increases oxycodone metabolism in patients with CRPC. It is expected that concomitant use of abiraterone has no clinically relevant effect on oxycodone's plasma concentration since it solely inhibits CYP2D6. Therefore, discontinuing abiraterone treatment is not expected to result in toxicity. This might positively affect pain management and pharmacovigilance in patients with CRPC. Objective: To investigate the effect of abiraterone on the pharmacokinetics (PK) of oxycodone following a single dose of 15 mg normal-release oxycodone in men with prostate cancer. Trial design: A prospective, open-label, two-arm parallel clinical study. Subjects will visit the hospital once for approximately nine hours. After screening for hypercapnia, subjects will receive one oral dose of 15 mg (10 mg and 5 mg capsules) normal-release oxycodone. In total, nine blood samples will be collected during the day for the control group and ten blood samples for the abiraterone group. Seven blood samples will be collected at predetermined times (t= 0.5, 1, 1.5, 2, 3, 5, 8 hours) in order to analyze the metabolism of oxycodone. One blood sample will be collected to determine abiraterone serum trough concentrations (abiraterone arm). In addition, two blood samples will be collected for patient characteristics, including one sample for genotyping of CYP3A4 and CYP2D6.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
SUPPORTIVE_CARE
Masking
NONE
Enrollment
29
Single dose of 15 mg oxycodone direct release (both arm 1 and arm 2)
Abiraterone group: 1000 mg abiraterone acetate (at steady state)
Deventer Ziekenhuis
Deventer, Overijssel, Netherlands
RECRUITINGCmax Oxycodone
Maximum measured concentration of oxycodone
Time frame: Measured at one of the time points (t= 0.5, 1, 1.5, 2, 3, 5, 8 hours)
T1/2 oxycodone
Measured half-life of oxycodone
Time frame: t= 0.5, 1, 1.5, 2, 3, 5, 8 hours
AUC0-8h oxycodone
Area under the curve of oxycodone from 0 to 8 hours after ingestion of oxycodone.
Time frame: From 0 to 8 hours after ingestion of oxycodone
Cmax noroxycodone
Maximum measured concentration of noroxycodone
Time frame: Measured at one of the time points (t= 0.5, 1, 1.5, 2, 3, 5, 8 hours)
AUC0-8h noroxycodone
Area under the curve of noroxycodone from 0 to 8 hours after ingestion of oxycodone.
Time frame: From 0 to 8 hours after ingestion of oxycodone
Cmax oxymorphone
Maximum measured concentration of oxymorphone
Time frame: Measured at one of the time points (t= 0.5, 1, 1.5, 2, 3, 5, 8 hours)
AUC0-8h oxymorphone
Area under the curve of oxymorphone from 0 to 8 hours after ingestion of oxycodone.
Time frame: From 0 to 8 hours after ingestion of oxycodone
Cmax noroxymorphone
Maximum measured concentration of noroxymorphone
Time frame: Measured at one of the time points (t= 0.5, 1, 1.5, 2, 3, 5, 8 hours)
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AUC0-8h noroxymorphone
Area under the curve of noroxycodone from 0 to 8 hours after ingestion of oxycodone.
Time frame: From 0 to 8 hours after ingestion of oxycodone