The primary purpose of this study is to determine the effect of multiple once daily administrations of enzalutamide on the pharmacokinetics of a single dose of digoxin (P-glycoprotein (P-gp) substrate) and rosuvastatin (breast cancer resistant protein (BCRP) substrate) in participants with prostate cancer. This study will also evaluate the safety and tolerability of multiple once daily administrations of enzalutamide alone and in combination with a single dose of digoxin (P-gp substrate) and rosuvastatin (BCRP substrate) in participants with prostate cancer, as well, assess the pharmacokinetics of enzalutamide and its active metabolite.
Eligible participants will be admitted to the clinical unit on day -1. Participants may be discharged from the clinical unit on day 2 on the condition that all required assessments have been performed and that there are no medical reasons for a longer stay in the clinical unit and participants are able and willing to return to the clinical unit on days 3 to 8 for daily pharmacokinetic sampling. Or, participants may choose to remain in the clinical unit up to the 168 hour postdose (day 8) pharmacokinetic sample collection. Participants will return to the clinical unit on day 35 for an ambulant visit and will be admitted to the clinical unit on day 63. Participants may be discharged from the clinical unit on day 65 on the condition that all required assessments have been performed and that there are no medical reasons for a longer stay in the clinical unit and participants are able and willing to return to the clinical unit on days 66 to 71 for daily pharmacokinetic sampling. Or, participants may choose to remain in the clinical unit up to the 168 hour postdose (day 71) pharmacokinetic sample collection. From day 72 onwards, participants experiencing clinical benefit (determined by the investigator in consultation with the physician responsible for treating the participants' prostate cancer) may roll over into an open label, single arm extension study. Only participants who will be enrolled into the extension study will continue to receive enzalutamide until any discontinuation criterion occurs per the extension study protocol.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
24
Site MD37301
Chisinau, Moldova
Pharmacokinetics (PK) of Digoxin in combination with rosuvastatin in plasma: maximum concentration (Cmax)
Cmax will be recorded from the pharmacokinetic (PK) plasma samples collected.
Time frame: Up to Day 71
Pharmacokinetics (PK) of Digoxin in combination with rosuvastatin in plasma: area under the concentration-time curve from the time of dosing to the last measurable concentration (AUClast)
AUClast will be recorded from the pharmacokinetic (PK) plasma samples collected.
Time frame: Up to Day 71
Pharmacokinetics (PK) of Digoxin in combination with rosuvastatin in plasma: area under the concentration time curve from the time of dosing extrapolated to time infinity (AUCinf)
AUCinf will be recorded from the pharmacokinetic (PK) plasma samples collected.
Time frame: Up to Day 71
Number of participants with Adverse Events (AEs)
Adverse events (AEs) will be coded using medical dictionary for regulatory activities (MedDRA). An AE is any untoward medical occurrence in a participant administered an Investigational Product (IP), and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of IP whether or not considered related to the IP. An AE is considered "serious" if the event: results in death; is life-threatening; results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions; results in congenital anomaly or birth defect; requires inpatient hospitalization (except for planned procedures)or leads to prolongation of hospitalization (except if prolongation of planned hospitalization is not caused by an AE); or other medically important events.
Time frame: Up to Day 101
Number of participants with laboratory value abnormalities and/or adverse events (AEs)
Number of participants with potentially clinically significant laboratory values.
Time frame: Up to Day 101
Number of participants with vital sign abnormalities and /or adverse events (AEs)
Number of participants with potentially clinically significant vital sign values.
Time frame: Up to Day 101
Number of participants with routine 12-lead electrocardiogram (ECG) abnormalities and/or Adverse Events (AEs)
Number of participants with potentially clinically significant ECG values.
Time frame: Up to Day 101
Pharmacokinetics (PK) of enzalutamide and its metabolite (N-desmethyl) in plasma: maximum concentration (Cmax)
Cmax will be recorded from the pharmacokinetic (PK) plasma samples collected.
Time frame: Up to Day 71
Pharmacokinetics (PK) of enzalutamide and its metabolite (N-desmethyl) in plasma: area under the concentration-time curve during a dosing interval, where tau (τ) is the length of the dosing interval (AUCtau)
AUCtau will be recorded from the pharmacokinetic (PK) plasma samples collected.
Time frame: Up to Day 71
Pharmacokinetics (PK) of enzalutamide and its metabolite (N-desmethyl) in plasma: concentration immediately prior to dosing at multiple dosing (Ctrough)
Ctrough will be recorded from the pharmacokinetic (PK) plasma samples collected.
Time frame: Up to Day 71
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