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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects; Relative Bioavailability; Castration Resistant Prostate Cancer (CRPC); MDV3100
• Intervention / Treatment: Drug: MDV3100

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 14050
    • Parexel International GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment A; Single dose of 4 liquid-filled capsules of MDV3100 reference formulation	Drug: MDV3100; Oral; Other Names: Xtandi; enzalutamide
Experimental: Treatment B; Single dose of 2 tablets of MDV3100 formulation tablet B	Drug: MDV3100; Oral; Other Names: Xtandi; enzalutamide
Experimental: Treatment C; Single dose of 2 tablets of MDV3100 formulation tablet C	Drug: MDV3100; Oral; Other Names: Xtandi; enzalutamide

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Astellas Pharma Europe B.V.
• Collaborators: Medivation, Inc.

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: July 26, 2013
• First Submitted That Met QC Criteria: July 26, 2013
• First Posted (Estimate): July 30, 2013

Study Record Updates

• Last Update Posted (Estimate): July 30, 2013
• Last Update Submitted That Met QC Criteria: July 26, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Keywords: Phase I; Xtandi; Enzalutamide; Relative bioavailability of MDV3100; Immediate release oral formulation
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: 9785-CL-0010; 2012-002502-49 (EudraCT Number)