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Abiraterone is a selective inhibitor of androgen biosynthesis that potently and irreversibly blocks CYP17, a crucial enzyme in testosterone and estrogen synthesis. A pro-drug of abiraterone, abiraterone acetate (Zytiga®), was developed to overcome its poor bio-availability and is fully converted to the active moiety abiraterone. Abiraterone acetate tablets are administered at a fixed oral dose of 1000mg QD in a fasted state in combination with 10mg prednisolon daily.
Abiraterone acetate has a low solubility in aqueous media and a low permeability. The bioavailability of abiraterone acetate is significantly influenced when ingested with food. Ingesting abiraterone acetate with a low fat or a high fat meal resulted respectively in a 5- or 10-fold increase in AUC0-∞. The high and low fat FDA meals used in these food effect studies differ largely from breakfasts taken in everyday life (ca. 800-1000 cal). A continental breakfast contains 160 to 320 calories of which 25-50% is fat, is more compatible with a normal lifestyle and therefore easily sustainable in daily practice. However, the effect of a continental breakfast on the absorption of abiraterone is unknown yet. Furthermore, increasing healthcare costs are a growing concern in all developed countries. Therefore effort should be invested to keep anticancer treatment affordable. A food intervention resulting in a better absorption and enhanced exposure to abiraterone, can lead to a reduced dose, which could significantly impact health care costs for a tumor which is as prevalent as metastatic prostate cancer.
Therefore the investigators want to perform a bioequivalent study to investigate what dose of abiraterone with a continental breakfast equals the dose of 1000mg taken in fasted conditions.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| group 1 | Other | 1000mg abiraterone fasted followed by 500 mg with breakfast |
|
| group 2 | Other | 500 mg abiraterone with breakfast followed by 1000mg fasted |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| abiraterone | Drug | integested with a continental breakfast |
|
| Measure | Description | Time Frame |
|---|---|---|
| dose finding | determine the equivalent dose of abiraterone when taken with a continental breakfast compared to 1000mg in fasted state | 1.5 year |
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Inclusion Criteria:
Note: informed consent may be obtained prior to start of the specified screening window.
Note: procedures conducted as part of the subject's routine clinical management (e.g. blood count) and obtained prior to signing of informed consent may be utilized for screening or baseline purposes provided these procedures are conducted as specified in the protocol.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| David Burger, PhD | Radboud University Medical Center | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Radboud UMC | Nijmegen | 6500HB | Netherlands |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31515667 | Background | Lubberman FJE, Benoist GE, Gerritsen W, Burger DM, Mehra N, Hamberg P, van Oort I, van Erp NP. A prospective phase I multicentre randomized cross-over pharmacokinetic study to determine the effect of food on abiraterone pharmacokinetics. Cancer Chemother Pharmacol. 2019 Dec;84(6):1179-1185. doi: 10.1007/s00280-019-03952-w. Epub 2019 Sep 12. |
| Label | URL |
|---|---|
| paper | View source |
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| ID | Term |
|---|---|
| D011471 | Prostatic Neoplasms |
| ID | Term |
|---|---|
| D005834 | Genital Neoplasms, Male |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| C089740 | abiraterone |
| D000069501 | Abiraterone Acetate |
| ID | Term |
|---|---|
| D000736 | Androstenes |
| D000731 | Androstanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
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| D005832 |
| Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D011469 | Prostatic Diseases |
| D052801 | Male Urogenital Diseases |
| D011083 |
| Polycyclic Compounds |