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

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

Enzalutamide liquid formulation given orally (160mg)

Enzalutamide Liquid

Enzalutamide Capsule

William D Figg, Pharm.D.

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.

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

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.

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.

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 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.

National Cancer Institute (NCI)

Principal Investigator

No participants were enrolled to receive Enzalutamide capsule (Treatment A) followed by enzalutamide liquid (Treatment B)

Enzalutamide Liquid: Enzalutamide liquid formulation given orally (160mg)

Enzalutamide Capsule: Enzalutamide gel capsule (4X 40mg)

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

Enzalutamide Liquid: Enzalutamide liquid formulation given orally (160mg)

Enzalutamide Capsule: Enzalutamide gel capsule (4X 40mg)

160mg Enzalutamide Liquid Followed by 4x40mg Enzalutamide Capsule

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

William D. Figg, Pharm.D.

Day 42 - Enzalutamide

Day 42 - N-Desmethyl Enzalutamide

Enzalutamide Liquid: Enzalutamide liquid formulation given orally (160mg)

160mg Enzalutamide Liquid

Enzalutamide Capsule: Enzalutamide gel capsule (4X 40mg)

4x40mg Enzalutamide Capsule

No participants were enrolled to receive Enzalutamide capsule (Treatment A) followed by enzalutamide liquid (Treatment B).

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

Nausea Day 1

Nausea Day 3

Nausea Day 8

Nausea Day 42

Vomiting Day 1

Vomiting Day 3

Vomiting Day 8

Vomiting Day 42

Grade 1

Grade 2

Grade 3 is severe or medically significant but not life-threatening.

Grade 3

Grade 4 is life-threatening consequences.

Grade 4

Grade 5 is death related to adverse event.

Grade 5

No participants were enrolled to receive Enzalutamide capsule (Treatment A) followed by enzalutamide liquid (Treatment B); Enzalutamide Liquid: Enzalutamide liquid formulation given orally (160mg); Enzalutamide Capsule: Enzalutamide gel capsule (4X 40mg)

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

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

This outcome measure was not done. Planned comparisons between the two formulations of enzalutamide at each time point using Fishers exact test were not conducted due to limited study accrual (n=1).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Study to Compare Capsule and Liquid Formulations of Enzalutamide After Single Dose Administration Under Fasting Conditions in Prostate Cancer	NCT03478904	Prostate Cancer	Enzalutamide Li... Enzalutamide Ca...	18 Years -	National Institutes of Health Clinical Center (CC)
Study to Compare Capsule and Liquid Formulations of Enzalutamide After Single Dose Administration Under Fasting Conditions in Prostate Cancer	NCT03478904	Prostate Cancer	Enzalutamide Li... Enzalutamide Ca...	18 Years -	National Institutes of Health Clinical Center (CC)

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