A Study to Compare Capsule and Tablet Forms of MDV3100 (Enzalutamide) After Administration of a Single Set Dose Under Fasted Conditions in Healthy Male Subjects

Study Overview
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Brief Summary
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A study to evaluate the bioavailability (BA) of a single oral dose of MDV3100 (enzalutamide) formulated as a solid spray dried tablet compared to oral liquid-filled capsules, and the safety and tolerability of oral formulations. Subjects are admitted to the clinic from days 1 to 5, followed by outpatient assessments up to Day 50. They return to the clinic for an end of study visit (ESV) 7-10 days after the last pharmacokinetic (PK) sampling or after early withdrawal.

Official Title
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A Phase I, Single-center, Open-label, Randomized, Parallel, Relative Bioavailability Study Comparing a Capsule and Tablet Formulations of Enzalutamide Following a Single 160 mg Dose Under Fasted Conditions in Healthy Male Subjects

Conditions
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Healthy Subjects, Castration Resistant Prostate Cancer (CRPC), Relative Bioavailability, MDV3100

Intervention / Treatment
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* Drug: MDV3100


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject has a body mass index (BMI) range of 18.5 - 29.9 kg/m2, inclusive. The subject weighs at least 50 kg (screening). Male subject and his female spouse/partner who is of childbearing potential must be using highly effective contraception consisting of two forms of birth control (one of which must be a barrier method) starting at screening and continue throughout the study period and for 3 months after final study drug administration. Male subject must not donate sperm starting at screening and throughout the study period and for at least 3 months after final study drug administration. Exclusion Criteria: Known or suspected hypersensitivity to enzalutamide, or any components of the formulation used. Confirmed CYP2C8 poor metabolizer status based on genotyping analysis. Any history of seizure including a febrile seizure in childhood, loss of consciousness, transient ischemic attack, or any condition that may pre-dispose to seizure. The subject has/had febrile illness or symptomatic, viral, bacterial (including upper respiratory infection), or fungal (non-cutaneous) infection within 1 week prior to first clinic check in. Use of grapefruit or marmalade in the week prior to admission to the Clinical Unit, as reported by the subject. Any significant blood loss, donated one unit (450 mL) of blood or more, or received a transfusion of any blood or blood products within 60 days or donated plasma within 7 days prior to clinic admission on Day -1.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A<br>Single dose of 4 liquid-filled capsules of MDV3100 reference formulation | Drug: MDV3100<br>* Oral<br>* Other names: Xtandi;|
| Experimental: Treatment B<br>Single dose of 2 tablets of MDV3100 formulation tablet B | Drug: MDV3100<br>* Oral<br>* Other names: Xtandi;|
| Experimental: Treatment C<br>Single dose of 2 tablets of MDV3100 formulation tablet C | Drug: MDV3100<br>* Oral<br>* Other names: Xtandi;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative BA of capsule and tablet formulations of enzalutamide following a single dose of enzalutamide under fasted conditions | AUC0-t (Area Under Curve from time zero to last quantifiable sample), AUC0-inf (AUC extrapolated to infinity), Cmax (Maximum concentration) | Day 1 through Day 50 (26 times) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative BA of capsule and tablet formulations of enzalutamide following a single dose of enzalutamide under fasted conditions | AUC0-72h (AUC from time zero to 72h post dose), AUC0-t, AUC0-inf, %AUC (Percentage of AUC), Cmax, tmax (Time to attain Cmax), λz (Terminal elimination rate constant), t1/2 (Terminal elimination half life), (MPR) metabolites to parent ratio, MPR(molecular weight corrected [MWC]), %AUC, CL/F (apparent oral clearance), Vz/F (apparent volume of distribution) | Day 1 through Day 50 (26 times) | 
| Safety and tolerability of oral formulations of enzalutamide | adverse events, physical examination, vital signs, clinical laboratory tests, 12-lead Electrocardiogram (ECG) | Screening through ESV (7-10 days after the last pharmacokinetic (PK) sampling or after early withdrawal) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase I, Enzalutamide, Relative bioavailability of MDV3100, Immediate release oral formulation, Xtandi