Relative Bioavailability Study of Enzalutamide in Prostate Cancer Patients

Study Overview
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Brief Summary
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A multiple dose relative bioavailability study in patients with prostate cancer comparing a capsule and a tablet formulation of enzalutamide.

Official Title
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A Phase I, Open-label, Randomized, Parallel, Relative Bioavailability Study Comparing a Capsule and a Tablet Formulation of Enzalutamide Following Multiple Once Daily Doses of 160 mg Enzalutamide in Male Subjects With Prostate Cancer

Conditions
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Prostate Cancer, Pharmacokinetics of Enzalutamide

Intervention / Treatment
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* Drug: Enzalutamide tablet
* Drug: Enzalutamide capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed prostate cancer (all stages) for whom androgen deprivation therapy is indicated (except when indicated in a neoadjuvant/adjuvant setting). Subjects may be on ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) analogue or orchiectomy (i.e., medical or surgical castration) at study entry. Progressive disease by Prostate-specific antigen (PSA) or imaging. Disease progression for study entry is defined as one or more of the following 3 criteria: PSA progression defined by a minimum of 2 rising PSA levels with an interval of ≥1 week between each determination. The PSA value during the pre-investigational period should be ≥2 μg/L (2 ng/mL); Soft tissue disease progression defined by the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) for soft tissue disease Bone disease progression defined by two or more new lesions on bone scan Exclusion Criteria: Treatment with chemotherapy within 4 weeks prior to enrollment (Day 1 visit) or plans to initiate treatment with chemotherapy during the study. History of seizure or any condition that may predispose to seizure. Also, history of loss of consciousness, or transient ischemic attack within 12 months prior to enrollment (Day 1 visit). Patients who previously received treatment with Enzalutamide. Concomitant use of drugs that are potent inducers and/or inhibitors of CYP3A4 and CYP2C8. Confirmed CYP2C8 poor metabolizer status based on genotyping analysis.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

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: Enzalutamide tablet<br>Multiple once daily oral doses of enzalutamide formulated as a tablet for approximately 8 weeks | Drug: Enzalutamide tablet<br>* Oral<br>* Other names: MDV3100;|
| Active Comparator: Enzalutamide capsule<br>Multiple once daily oral doses of enzalutamide formulated as liquid-filled soft gelatin capsule for approximately 8 weeks | Drug: Enzalutamide capsule<br>* Oral<br>* Other names: MDV3100;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic profile of Enzalutamide under fasted conditions measured by Cmax (Maximum concentration) | Day 56 (fasted) Cmax under steady state conditions of enzalutamide | Day1 through Day 56 (12 samples) | 
| Pharmacokinetic profile of Enzalutamide under fasted conditions measured by AUC0-24h (Area under the concentration-time curve 0-24h) | Day 56 (fasted) AUC0-24h under steady state conditions of enzalutamide | Day1 through Day 56 (12 samples) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic profile of Enzalutamide under fasted and fed conditions | Measured by: Cmax, tmax (Time to attain Cmax), AUC0-24h, Ctrough (Trough concentration), PTR (Peak-trough ratio), CLss/F (Apparent clearance at steady state) | Day 1, 8, 29, 55, 56 and 57 (38 samples) | 
| Pharmacokinetic profile of MDPC0001 alone, MDPC0002 alone and sum of Enzalutamide plus MDPC0002 | Measured by: Ctrough, Cmax, tmax, AUC0-24h, Ctrough (24h after dosing), PTR | Day 8, 29, 55, 56 and 57 (26 samples) | 
| Evaluation of the safety and tolerability of two oral formulations of Enzalutamide assessed through vital signs, adverse events, electrocardiogram and clinical laboratory assessments |  | Day 1 through Day 58 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 1, Prostate cancer, Bioavailability, Food effect, Pharmacokinetics, Xtandi, Enzalutamide, MDV3100