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Genital Neoplasms, Male

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Genital Diseases, Male

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Prostatic Diseases

Male Urogenital Diseases

Multiple once daily oral doses of enzalutamide formulated as a tablet for approximately 8 weeks

Multiple once daily oral doses of enzalutamide formulated as liquid-filled soft gelatin capsule for approximately 8 weeks

Enzalutamide tablet

Enzalutamide capsule

Clinical Study Manager

A multiple dose relative bioavailability study in patients with prostate cancer comparing a capsule and a tablet formulation of enzalutamide.

Relative Bioavailability Study of Enzalutamide in Prostate Cancer Patients

A Phase I, Open-label, Randomized, Parallel, Relative Bioavailability Study Comparing a Capsule and a Tablet Formulation of Enzalutamide Following Multiple Once Daily Doses of 160 mg Enzalutamide in Male Subjects With Prostate Cancer

Day 56 (fasted) Cmax under steady state conditions of enzalutamide

Day 56 (fasted) AUC0-24h under steady state conditions of enzalutamide

Measured by: Cmax, tmax (Time to attain Cmax), AUC0-24h, Ctrough (Trough concentration), PTR (Peak-trough ratio), CLss/F (Apparent clearance at steady state)

Measured by: Ctrough, Cmax, tmax, AUC0-24h, Ctrough (24h after dosing), PTR

Medivation, Inc.

Astellas Pharma Europe B.V.

Symptoms and General Pathology

Neoplasm Metastasis

All Drugs and Chemicals

Nicotine

Enrolled subjects will receive a single dose of 9 mCi (333 MBq) 18F-DCFPyL Injection followed by a single PET/CT scan acquired at 1-2 hours post-dosing. After initial 18F-DCFPyL PET/CT, the patients with positive 18F-DCFPyL PET/CT imaging will be treated with enzalutamide (160 mg po id) for M0CRPC disease within less than two weeks. 18F-DCFPyL PET/CT scan will then be repeated 90 days after the start of enzalutamide treatment.

Marie-Christine Dubé, PhD

Marilyn Savard

Marie-Christine Dube, PhD

Frédéric Pouliot, MD

This study aimed to evaluate the diagnostic performance of 18F-DCFPyL (PyL) PET/CT in subjects presenting not previously treated for castration resistant prostate cancer and showing negative or equivocal findings per institutional standard of care conventional imaging

Prostate cancer (PCa) is the most common solid organ cancer in North American men and is initially androgen sensitive. Therefore, castration and/or androgen receptor blockade remains the central palliative treatment once PCa has metastasized or failed to locoregional therapies. Because androgen deprivation therapy is not curative, all patients will eventually progress to the metastatic castration-resistant prostate cancer state. About 5% of prostate cancers will be metastatic by conventional imaging techniques at diagnosis while most patients achieving CRPC state will first be localized and then progress to metastatic state later in the disease course. Therefore, a significant proportion of patients will progress through an intermediary state of disease defined as the non-metastatic CRPC state (M0CRPC). Over the last year and a half, M0CRPC treatment landscape has completely changed with demonstrating the benefits of second-generation antiandrogens (darolutamide, enzalutamide and apalutamide) to prevent progression of M0CRPC patients. Enzalutamide have then been approved by the Federal Drug Administration and Health Canada for the treatment of M0CRPC.

On the other hand, conventional imaging techniques based on bone turnover (bone scan (BS)) or anatomical features (magnetic resonance imaging (MRI) or computed tomography (CT)) have important limitations and poor accuracy. Bone scans (BS) is the commonest imaging technique used to detect bone metastases in the clinics. BS does not image directly cancer cells, but the effect of cancer on the bone. Other pathologies such as fractures, degenerative arthritis and other benign bone lesions can also cause focal uptake on BS and lead to false-positive results. Another drawback of BS is its poor sensitivity to image small metastases confined to bone marrow. These limitations stress the importance to improve PCa imaging by using new imaging modalities.

Because novel agents targeting the androgen synthesis and receptor axis (e.g. enzalutamide), bone metastasis (radium-223) and microtubules assembly (docetaxel, cabazitaxel) have been shown to increase metastatic CRPC patients overall survival, a burning question is to determine if the non-metastatic CRPC status is real. There is growing evidence that newer imaging techniques using positron emission tomography can improve metastasis detection accuracy and may refine PCa patient prognostic stratification and treatment eligibility.

Detecting Metastases by PyL PET/CT in Subjects Starting Enzalutamide for Untreated Castration Resistant Prostate Cancer.

Detection and Monitoring of Metastasis by 18F-DCFPyL PET/CT in Subjects Starting Enzalutamide for Untreated Castration Resistant Prostate Cancer and Negative, Equivocal, or Oligometastatic Disease on Conventional Imaging (PROSTEP-002)

Number of metastasis per compartment (bone, visceral, lymph node) determined by 18F-DCFPyL-PET/CT when PSA is \<1 ng/mL, 1 to 5 ng/mL and \> 5 ng/mL.

Analyze if a patient shows one or several lesions with a 18F-DCFPyL uptake more than that of the liver.

Number of patients presenting with metastases per compartment (bone, visceral, lymph node) determined by 18F-DCFPyL-PSMA PET/CT that were negative or equivocal on conventional imaging. determined by 18F-DCFPyL-PET/CT.

Determine the changes in 18F-DCFPyL-PSMA sum metastasis SUVmax (or any other radiomic PET parameter) for each patient and the changes of 18F-DCFPyL-PSMA SUVmax (or any other radiomic PET parameter) in each lesion after 3 months of enzalutamide.

Astellas Pharma Europe Ltd.

CHU de Quebec-Universite Laval

Rare Diseases

Kennedy Disease

Androgens

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
Relative Bioavailability Study of Enzalutamide in Prostate Cancer Patients	NCT01902251	Prostate Cancer Pharmacokinetic...	Enzalutamide ta... Enzalutamide ca...	18 Years -	Astellas Pharma Inc
Detecting Metastases by PyL PET/CT in Subjects Starting Enzalutamide for Untreated Castration Resistant Prostate Cancer.	NCT04655365	Prostate Cancer	Enzalutamide ca...	18 Years -	CHU de Quebec-Universite Laval
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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