Pharmacokinetics of Enzalutamide, Prostate Cancer
Conditions
Keywords
Phase 1, Prostate cancer, Bioavailability, Food effect, Pharmacokinetics, Xtandi, Enzalutamide, MDV3100
Brief summary
A multiple dose relative bioavailability study in patients with prostate cancer comparing a capsule and a tablet formulation of enzalutamide.
Interventions
Oral
Oral
Sponsors
Medivation, Inc.
Astellas Pharma Europe B.V.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic profile of Enzalutamide under fasted conditions measured by Cmax (Maximum concentration) | Day1 through Day 56 (12 samples) | Day 56 (fasted) Cmax under steady state conditions of enzalutamide |
| Pharmacokinetic profile of Enzalutamide under fasted conditions measured by AUC0-24h (Area under the concentration-time curve 0-24h) | Day1 through Day 56 (12 samples) | Day 56 (fasted) AUC0-24h under steady state conditions of enzalutamide |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic profile of Enzalutamide under fasted and fed conditions | Day 1, 8, 29, 55, 56 and 57 (38 samples) | Measured by: Cmax, tmax (Time to attain Cmax), AUC0-24h, Ctrough (Trough concentration), PTR (Peak-trough ratio), CLss/F (Apparent clearance at steady state) |
| Pharmacokinetic profile of MDPC0001 alone, MDPC0002 alone and sum of Enzalutamide plus MDPC0002 | Day 8, 29, 55, 56 and 57 (26 samples) | Measured by: Ctrough, Cmax, tmax, AUC0-24h, Ctrough (24h after dosing), PTR |
| 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 | — |
Countries
United States
Outcome results
None listed