Abiraterone's effect on oxycodone metabolism in men with prostate cancer

The Effect of Abiraterone on the Metabolism of Oxycodone

We will test whether taking abiraterone changes how oxycodone is broken down in men with prostate cancer.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 29 (estimated)
• Ages: 18 Years and up
• Sex: Male
• Sponsor: Deventer Ziekenhuis (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Deventer, Overijssel)
• Trial ID: NCT07001709 on ClinicalTrials.gov

What this trial studies

This open-label, two-arm parallel study compares oxycodone pharmacokinetics in men with prostate cancer who are taking abiraterone versus those who are not. Each participant receives a single 15 mg dose of immediate-release oxycodone and stays about nine hours at the hospital for serial blood sampling to measure drug levels. The abiraterone arm requires at least 10 days of prior abiraterone treatment while the control arm must not have used abiraterone in the prior 10 days. Results will determine whether abiraterone meaningfully alters oxycodone plasma concentrations and inform pain-management decisions in castration-resistant prostate cancer.

Who should consider this trial

Good fit: Men aged 18 or older with prostate cancer who either have been taking abiraterone 1000 mg daily for at least 10 days or have not taken abiraterone in the prior 10 days, and who meet BMI and medication-interaction criteria, are eligible.

Not a fit: Patients with recent opioid use, those taking medications that interact with oxycodone, individuals with liver disease or abnormal labs, diarrheal illness, BMI outside 18–30, or oxycodone hypersensitivity are excluded and unlikely to benefit from participation.

Why it matters

Potential benefit: If abiraterone does not alter oxycodone levels, clinicians may be able to continue both treatments without changing opioid dosing, improving pain control and safety.

How similar studies have performed: A prior ENZYME study showed enzalutamide increases oxycodone metabolism, but abiraterone's effect is less studied and is expected to be minimal given its CYP2D6 inhibition profile.

Eligibility criteria

Inclusion Criteria:

* 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).

Exclusion Criteria:

* 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;
* A body mass index (BMI) outside the range of 18 - 30 kg/m2;
* If hypersensitive to oxycodone;
* patients suffering from diarrhea
* If any type of abnormality; active or symptomatic viral hepatitis or chronic liver disease (e.g. classification with Child-Pugh B, Child-Pugh C);
* Known metastases in the liver that would affect drug metabolism;
* Patients with a CYP3A4 or CYP2D6 polymorphism;
* Moderate-severe renal dysfunction (GFR \<60 ml/min/1.73m2) that affects drug metabolism ;
* Subjects with significant respiratory depression resulting in the need of oxygen therapy or objective hypoventilation (respiratory rate \<12/min);
* Hypercapnia (venous pCO2 outside the range of 5.5 - 6.7; pH outside the range 7.30 - 7.40);
* Subjects with, a history of bronchial asthma, chronic obstructive pulmonary disease or pulmonary heart disease;
* 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;
* A history of drug abuse
* Patients receiving opioid substitution therapy for opioid addiction (e.g. methadone or buprenorphine) and/or suffering from opioid withdrawal
* Patients with evidence of clinically significant gastrointestinal disease;
* 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;
* Previous gastric bypass or gastric band surgery.

Where this trial is running

Deventer, Overijssel

• Deventer Ziekenhuis — Deventer, Overijssel, Netherlands (Recruiting)

Study contacts

• Study coordinator: Frank Jansman, Prof. dr.

Conditions Prostate Cancer; Pain Cancer