Study to Compare Capsule and Liquid Formulations of Enzalutamide After Single Dose Administration Under Fasting Conditions in Prostate Cancer

April 12, 2021 updated by: William Figg, National Cancer Institute (NCI)

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Background:

  • Enzalutamide is currently approved for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC)
  • The marketed (reference) formulation of enzalutamide is a liquid-filled, soft gelatin capsule containing 40 mg enzalutamide dissolved in Labrasol; four such capsules are required to deliver a 160 mg dose
  • The four-capsule regimen is inconvenient because of the number of capsules that must be taken, particularly in light of the fact that cancer patients usually have to take multiple drugs.
  • Additionally, some patients may not be able to swallow pills; therefore, alternate methods of oral administration are necessary

Objectives:

-To evaluate the bioequivalence, safety, and tolerability of two oral formulations of enzalutamide following a single 160 mg dose in male subjects with prostate cancer under fasting conditions.

Eligibility:

-Male subjects with prostate cancer

Design:

  • Comparative, randomized, open-label, single-dose, 2-way crossover bioavailability, safety and tolerability study
  • Subjects will be randomized in Period 1 to one of two sequences: AB or BA. Following a minimum 42-day washout period, subjects will be crossed over in Period 2 to receive the treatment that they did not receive in Period 1.
  • Treatment A will be the standard capsule (reference) formulation; Treatment B will be the liquid formulation (test product)
  • Blood samples will be collected for pharmacokinetic analysis

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
1

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Institutes of Health Clinical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

  • INCLUSION CRITERIA:
  • 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

OR

--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.
  • Men age greater than or equal to 18 years of age. Children are excluded because prostate cancer is not common in pediatric populations. Women are not eligible because this disease occurs only in men
  • The effects of enzalutamide on the developing human fetus are unknown. For this reason men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) throughout the course of the study and for 3 months after the last dose. Should a woman become pregnant or suspect she is pregnant while her partner is participating in this study, she should inform her treating physician immediately.

EXCLUSION CRITERIA:

  • 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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 4x40mg Enzalutamide Capsule Followed by 160mg Enzalutamide Liquid
Enzalutamide capsule (Treatment A) followed by enzalutamide liquid (Treatment B)
Drug: Enzalutamide Liquid
Enzalutamide liquid formulation given orally (160mg)
Other Names:
  • ASP-9785
Drug: Enzalutamide Capsule
Enzalutamide gel capsule (4X 40mg)
Other Names:
  • ASP-9785
Experimental: 160mg Enzalutamide Liquid Followed by 4x40mg Enzalutamide Capsule
Enzalutamide liquid (Treatment B) followed by enzalutamide capsule (Treatment A)
Drug: Enzalutamide Liquid
Enzalutamide liquid formulation given orally (160mg)
Other Names:
  • ASP-9785
Drug: Enzalutamide Capsule
Enzalutamide gel capsule (4X 40mg)
Other Names:
  • ASP-9785

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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
Time Frame: Day 42

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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of Episodes of Grades 1-5 Nausea and Vomiting on 160mg Enzalutamide Liquid Followed by 4x40mg Enzalutamide Gel Capsule
Time Frame: Day 1, 3, 8, and 42
Nausea and vomiting adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe or medically significant but not immediately life-threatening, Grade 4 is life threatening consequences, and Grade 5 is death related to adverse event.
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
Time Frame: Date treatment consent signed to date off study, approximately 7 months and 24 days.
Here is the number of participants with non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence.
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
Time Frame: Day 1, 3, 8, and 42
Proportion of participants with Grade 3 vomiting assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0., compared between two formulations of enzalutamide at each time point using Fishers exact test.
Day 1, 3, 8, and 42

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 10, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 30, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 30, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 21, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 24, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 27, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 10, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 12, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 180070
  • 18-C-0070

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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