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

Primary Purpose

Prostate Cancer

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Enzalutamide Liquid

Enzalutamide Capsule

About this trial

This is an interventional other trial for Prostate Cancer focused on measuring Castration Resistant Prostate Cancer, Androgen Receptor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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

--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).

Sites / Locations

National Institutes of Health Clinical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

4x40mg Enzalutamide Capsule Followed by 160mg Enzalutamide Liquid

160mg Enzalutamide Liquid Followed by 4x40mg Enzalutamide Capsule

Arm Description

Enzalutamide capsule (Treatment A) followed by enzalutamide liquid (Treatment B)

Enzalutamide liquid (Treatment B) followed by enzalutamide capsule (Treatment A)

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Number of Episodes of Grades 1-5 Nausea and Vomiting on 160mg Enzalutamide Liquid Followed by 4x40mg Enzalutamide Gel Capsule

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.

Number of Participants With Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0

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.

Proportion of Participants With Grade 3 Vomiting Compared Between Two Formulations of Enzalutamide at Each Time Point Using Fishers Exact Test

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.

Full Information

NCT ID

NCT03478904

First Posted

March 21, 2018

Last Updated

April 12, 2021

Sponsor

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT03478904

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2021

Overall Recruitment Status

Terminated

Why Stopped

Study drug is now commercially available in tablet format

Study Start Date

March 10, 2020 (Actual)

Primary Completion Date

November 30, 2020 (Actual)

Study Completion Date

November 30, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

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.

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Prostate Cancer

Keywords

Castration Resistant Prostate Cancer, Androgen Receptor

7. Study Design

Primary Purpose

Other

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

1 (Actual)

8. Arms, Groups, and Interventions

Arm Title

4x40mg Enzalutamide Capsule Followed by 160mg Enzalutamide Liquid

Arm Type

Experimental

Arm Description

Enzalutamide capsule (Treatment A) followed by enzalutamide liquid (Treatment B)

Arm Title

160mg Enzalutamide Liquid Followed by 4x40mg Enzalutamide Capsule

Arm Type

Experimental

Arm Description

Enzalutamide liquid (Treatment B) followed by enzalutamide capsule (Treatment A)

Intervention Type

Drug

Intervention Name(s)

Enzalutamide Liquid

Other Intervention Name(s)

ASP-9785

Intervention Description

Enzalutamide liquid formulation given orally (160mg)

Intervention Type

Drug

Intervention Name(s)

Enzalutamide Capsule

Other Intervention Name(s)

ASP-9785

Intervention Description

Enzalutamide gel capsule (4X 40mg)

Primary Outcome Measure Information:

Title

Description

Time Frame

Day 42

Secondary Outcome Measure Information:

Title

Number of Episodes of Grades 1-5 Nausea and Vomiting on 160mg Enzalutamide Liquid Followed by 4x40mg Enzalutamide Gel Capsule

Description

Time Frame

Day 1, 3, 8, and 42

Title

Number of Participants With Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0

Description

Time Frame

Date treatment consent signed to date off study, approximately 7 months and 24 days.

Title

Proportion of Participants With Grade 3 Vomiting Compared Between Two Formulations of Enzalutamide at Each Time Point Using Fishers Exact Test

Description

Time Frame

Day 1, 3, 8, and 42

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

William D Figg, Pharm.D.

Organizational Affiliation

National Cancer Institute (NCI)

Official's Role

Principal Investigator

Facility Information:

Facility Name

National Institutes of Health Clinical Center

City

Bethesda

State/Province

Maryland

ZIP/Postal Code

20892

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

34333820

Citation

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.

Results Reference

derived

Links:

URL

https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2018-C-0070.html

Description

NIH Clinical Center Detailed Web Page

Learn more about this trial

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

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