Study Stopped
Study drug is now commercially available in tablet format
Study to Compare Capsule and Liquid Formulations of Enzalutamide After Single Dose Administration Under Fasting Conditions in Prostate Cancer
2 other identifiers
interventional
1
1 country
1
Brief Summary
Background: Enzalutamide is given to treat metastatic prostate cancer. But it takes 4 pills to deliver the effective dose. This can be difficult for people already taking multiple drugs. And swallowing may be difficult for some people. Researchers want to test out a new way of giving enzalutamide by mouth. They want to see if giving a person the liquid taken from inside the standard 4 gelatin capsules is handled by the body in the same way as giving them the capsules whole. Objectives: To compare how capsule and liquid forms of enzalutamide are handled by people with prostate cancer. Eligibility: Men at least 18 years old with prostate cancer Design: Participants will be screened with a heart test (electrocardiogram), medical history, and physical exam. A tissue sample or lab reports will be reviewed. During the study, participants will repeat screening tests and have urine tests. Participants will be randomly assigned to get the study drug in one of two orders: either the as capsules then the liquid form (Arm A) or as the liquid form then the capsule form (Arm B). Participants will be counseled about birth control. The study will have 2 periods with a minimum 42 day break in between. On Day 1 of Period 1 and Day 1 of Period 2, participants will be admitted to the hospital. They will get one dose of the study drug. They cannot eat or drink anything except water for at least 10 hours before and for 4 hours after the study drug. Their blood will be sampled over 24 hours. Lunch and dinner will be served. Participants will answer questions after taking the liquid form. Participants will have blood drawn on Day 3, Day 8, and Day 42.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1 prostate-cancer
Started Mar 2020
Shorter than P25 for phase_1 prostate-cancer
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 21, 2018
CompletedFirst Posted
Study publicly available on registry
March 27, 2018
CompletedStudy Start
First participant enrolled
March 10, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 30, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
November 30, 2020
CompletedResults Posted
Study results publicly available
May 10, 2021
CompletedMay 10, 2021
April 1, 2021
9 months
March 21, 2018
April 12, 2021
April 12, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Area Under Curve (AUC) for the First Period of Administration and Second Period of Administration of Two Formulations of Enzalutamide and the Active Metabolite of Enzalutamide Following a Single 160mg Dose
AUC is the cumulative drug exposure (drug concentration \* time) for this single dose over a 42-day sampling period. Participants were randomized to receive Enzalutamide gel capsule 4x40mg (Treatment A) followed by enzalutamide liquid 160mg orally (Treatment B), or Enzalutamide liquid 160mg orally (Treatment B) followed by enzalutamide gel capsule 4x40mg (Treatment A). The difference in the AUCs were calculated following a published non-parametric and noncompartmental approach. A difference of less than 20% difference in the AUC for the test version vs. the standard formulation would permit the two formulations to be considered bioequivalent." \*The calculated AUC values for N-Desmethyl Enzalutamide of the "4x40mg Enzalutamide Capsule" formulation was influenced by detectable concentrations of N-Desmethyl Enzalutamide (an active metabolite of Enzalutamide) following the 42 Day washout period between the two doses.
Day 42
Secondary Outcomes (3)
Number of Episodes of Grades 1-5 Nausea and Vomiting on 160mg Enzalutamide Liquid Followed by 4x40mg Enzalutamide Gel Capsule
Day 1, 3, 8, and 42
Number of Participants With Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0
Date treatment consent signed to date off study, approximately 7 months and 24 days.
Proportion of Participants With Grade 3 Vomiting Compared Between Two Formulations of Enzalutamide at Each Time Point Using Fishers Exact Test
Day 1, 3, 8, and 42
Study Arms (2)
4x40mg Enzalutamide Capsule Followed by 160mg Enzalutamide Liquid
EXPERIMENTALEnzalutamide capsule (Treatment A) followed by enzalutamide liquid (Treatment B)
160mg Enzalutamide Liquid Followed by 4x40mg Enzalutamide Capsule
EXPERIMENTALEnzalutamide liquid (Treatment B) followed by enzalutamide capsule (Treatment A)
Interventions
Enzalutamide liquid formulation given orally (160mg)
Enzalutamide gel capsule (4X 40mg)
Eligibility Criteria
You may qualify if:
- Patients must have histologically or cytologically confirmed prostate cancer.
- Note: If histopathological documentation is unavailable, a clinical course consistent with prostate cancer is acceptable.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
- Patients must have adequate organ and marrow function as defined below:
- Hemoglobin greater than or equal to 9 g/dL
- leukocytes greater than or equal to 3000/mcL
- absolute neutrophil count greater than or equal to 1500/mcL
- platelets greater than or equal to 150000/mcL
- total bilirubin within normal institutional limits
- Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT)/ alanine aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT) less than or equal to X institutional upper limit of normal
- creatinine within normal institutional limits
- creatinine clearance greater than or equal to 30 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal (calculated via Cockcroft-Gault equation)
- Patients must not have other concurrent malignancies (within the past 2 years with the exception of non-melanoma skin cancer and Rai Stage 0 chronic lymphocytic leukemia), in situ carcinoma of any site, or life threatening illnesses, including untreated infection (must be at least 1 week off intravenous antibiotic therapy before beginning enzalutamide).
- Ability of subject to understand and the willingness to sign a written informed consent document.
- Willingness to travel to National Institutes of Health (NIH) for follow-up visits.
- +2 more criteria
You may not qualify if:
- Patients who are receiving any other investigational agents (in the past 28 days) or herbal medications (within 7 days).
- Patients must not be on enzalutamide within five half-lives before the first planned dose of the study drug or anticipating to start enzalutamide within the next 3 months of the first planned dose of study drug
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to enzalutamide or other agents used in study.
- Clinically significant cardiac disease, e.g. New York Heart Association (NYHA) classes III-IV; uncontrolled angina, uncontrolled arrhythmia or uncontrolled hypertension, myocardial infarction in the previous 6 months as confirmed by an electrocardiogram (ECG).
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Patients who are taking medications that may alter the metabolism of enzalutamide. This includes the following: strong or moderate cytochrome P450 family 2 subfamily C member 8 (CYP2C8) inhibitors or inducers; strong cytochrome P450 family 3 subfamily A member 4 (CYP3A4) inhibitors or inducers; or Cytochrome P450 2C9 (CYP2C9), 2C19 or 3A4 substrates with a narrow therapeutic index.
- History of seizure, including any febrile seizure, loss of consciousness, or transient ischemic attach, or any condition that may pre-dispose to seizure (e.g. prior stroke, brain arteriovenous malformation, head trauma with loss of consciousness requiring hospitalization).
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Related Publications (1)
Cordes LM, Schmidt KT, Peer CJ, Chau CH, Redmond E, Francis D, Karzai F, Madan RA, Figg WD. Study to Compare Capsule and Liquid Formulations of Enzalutamide After Single-Dose Administration Under Fasting Conditions in Prostate Cancer. Oncologist. 2021 Sep;26(9):729-e1493. doi: 10.1002/onco.13919. Epub 2021 Aug 14.
PMID: 34333820DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- William D. Figg, Pharm.D.
- Organization
- National Cancer Institute
Study Officials
- PRINCIPAL INVESTIGATOR
William D Figg, Pharm.D.
National Cancer Institute (NCI)
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- OTHER
- Intervention Model
- CROSSOVER
- Sponsor Type
- NIH
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
March 21, 2018
First Posted
March 27, 2018
Study Start
March 10, 2020
Primary Completion
November 30, 2020
Study Completion
November 30, 2020
Last Updated
May 10, 2021
Results First Posted
May 10, 2021
Record last verified: 2021-04
Data Sharing
- IPD Sharing
- Will not share