Relative Bioavailability Study of Enzalutamide in Prostate Cancer Patients

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

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

Study Overview

• Status: Completed
• Conditions: Prostate Cancer; Pharmacokinetics of Enzalutamide
• Intervention / Treatment: Drug: Enzalutamide tablet; Drug: Enzalutamide capsule

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80045
      • University of Colorado - Anschutz Medical Campus
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Medical Center
  • Texas
    • San Antonio, Texas, United States, 78229
      • South Texas Accelerated Research Therapeutics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Enzalutamide tablet; Multiple once daily oral doses of enzalutamide formulated as a tablet for approximately 8 weeks	Drug: Enzalutamide tablet; Oral; Other Names: Xtandi; MDV3100
ACTIVE_COMPARATOR: Enzalutamide capsule; Multiple once daily oral doses of enzalutamide formulated as liquid-filled soft gelatin capsule for approximately 8 weeks	Drug: Enzalutamide capsule; Oral; Other Names: Xtandi; MDV3100

What is the study measuring?

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

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• Link to Results on JAPIC - enter 140588 in the JapicCTI-RNo. field

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (ACTUAL): October 1, 2013
• Study Completion (ACTUAL): October 1, 2013

Study Registration Dates

• First Submitted: July 15, 2013
• First Submitted That Met QC Criteria: July 15, 2013
• First Posted (ESTIMATE): July 18, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): September 9, 2014
• Last Update Submitted That Met QC Criteria: September 8, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Prostate cancer; Food effect; Phase 1; Bioavailability; Xtandi; MDV3100; Enzalutamide
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: 9785-CL-0003