To investigate the effect of enzalutamide on the pharmacokinetics (PK) of oxycodone following a single 15 mg oral dose of normal-release oxycodone in men with prostate cancer.
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms benign
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Difference in pharmacokinetics of oxycodone in the presence and absence of
enzalutamide, expressed in Cmax and AUC0-t.
Secondary outcome
Differences in pharmacokinetics in the presence and absence of enzalutamide,
expressed in:
1. Maximum plasmaconcentration (Cmax) of noroxycodone, oxymorphone and
noroxymorphone;
2. Area under the plasma concentration versus time curve from time zero to the
time (t) corresponding to the last quantifiable concentration (AUC0-t) of
noroxycodone, oxymorphone and noroxymorphone;
3. Area under the concentration-time curve from time zero to infinity with
extrapolation of the terminal phase (AUC0-*) of oxycodone and its metabolites
noroxycodone, oxymorphone and noroxymorphone;
4. Terminal half-life (t1/2) of oxycodone and its metabolites noroxycodone,
oxymorphone and noroxymorphone.
Background summary
Oxycodone is an opioid receptor agonist that is metabolized mainly in the liver
by CYP3A4 and 2D6 enzymes. Enzalutamide is one of the next-generation endocrine
agents used in patients with (nonmetastatic and metastatic) CRPC. Because
enzalutamide is a strong inducer of CYP3A4, it is expected that enzalutamide
will reduce the analgesic effects of oxycodone, which is also metabolised along
this pathway. This could have an important impact on patients* pain-related
quality of life and on the effective and safe use of oxycodone and
enzalutamide.
Study objective
To investigate the effect of enzalutamide on the pharmacokinetics (PK) of
oxycodone following a single 15 mg oral dose of normal-release oxycodone in men
with prostate cancer.
Study design
A prospective, open-label, two arm parallel study.
Intervention
Subjects will receive a single oral dose of normal-release oxycodone 15 mg.
Study burden and risks
The subjects will visit the hospital once. During this visit they will receive
a single oral dose of normal-release oxycodone 15 mg after which nine blood
samples (4 ml each) will be collected at seven different times. Oxycodone is a
licensed product with a known mechanism of action and side effects. Because it
involves a single dose, the risk is low. Moreover, all subjects will be
observed for eight hours after intake of the medication on a nursing ward in
the hospital and a physician will be available to supervise.
Subjects are men with prostate cancer who are in general an older population.
During this study we are aware of the increased risk of side effects in
elderly. The experimental group will include men who already use enzalutamide.
The control group will be men with prostate cancer (not treated with
enzalutamide) to equalize for multiple factors affecting oxycodone metabolism,
among which gender, impaired hepatic and renal function and comedication.
Nico Bolkesteinlaan 75
Deventer 7416 SE
NL
Nico Bolkesteinlaan 75
Deventer 7416 SE
NL
Listed location countries
Age
Inclusion criteria
- Males aged >= 18 years;
- Diagnosed prostate cancer;
- Treated with enzalutamide 160 mg once daily for 40 days (arm 1)
Exclusion criteria
- a body mass index (BMI) outside the range of 18 to 30 kg/m2;
- known metastases in the liver that would affect drug metabolism;
- Child-Pugh classification B or C that would affect drug metabolism;
- known CYP3A4 or CYP2D6 polymorphisms that would affect drug metabolism
(patients with a known CYP3A4 or CYP2D6 polymorphism afterwards will be
replaced);
- known moderate-severe renal dysfunction (GFR <60 ml/min/1.73m2) that would
affect drug metabolism;
- gastrointestinal disorders that would potentially alter absorption;
- previous gastric bypass or gastric band surgery;
- known allergy, hypersensitivity or intolerance to normal-release oxycodone;
- a history of drug abuse or treatment for abuse;
- dose-reduction or >=5 successive days of treatment interruption of
enzalutamide within 40 days prior to the study day (arm 1);
- treatment with enzalutamide within 40 days prior to the study day (arm 2);
- use of oxycodone normal-release within 24 hour prior to oxycodone intake or
use of oxycodone extended-release within 2 days prior to oxycodone intake;
- use of other medication that would affect oxycodone metabolism, see section
5.2 and appendix B of the study protocol;
- use of other medication that would affect enzalutamide metabolism, see
section 5.2 and appendix B of the study protocol (arm 1).
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
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In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2020-005087-66-NL |
| CCMO | NL75669.075.20 |