Study to Compare Capsule and Liquid Formulations of Enzalutamide After Single Dose Administration Under Fasting Conditions in Prostate Cancer
| Status: | Recruiting |
|---|---|
| Conditions: | Prostate Cancer, Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - 100 |
| Updated: | 4/6/2019 |
| Start Date: | April 10, 2019 |
| End Date: | December 31, 2020 |
| Contact: | Deneise Francis |
| Email: | deneise.francis@nih.gov |
| Phone: | (301) 435-7964 |
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.
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 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
- Enzalutamide is currently approved for the treatment of patients with 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
- INCLUSION CRITERIA:
- Patients must have histologically or cytologically confirmed prostate cancer confirmed
by the Laboratory of Pathology, NCI or Pathology Department of the Walter Reed
National Military Medical Center.
- 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
- AST(SGOT)/ALT(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 m2 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 NIH for follow-up visits.
- Men age greater than or eual 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 with active treatment for active Hepatitis B and C infections.
- Patients who are taking medications that may alter the metabolism of enzalutamide.
This includes the following: strong or moderate CYP2C8 inhibitors or inducers; strong
CYP3A4 inhibitors or inducers; or CYP2C9, 2C19 or 3A4 substrates with a narrow
therapeutic index. For a current table of Substrates, Inhibitors and Inducers please
access the following website:
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/Drug
InteractionsLabeling/ucm093664.htm
-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).
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
301-496-2563
Phone: 888-624-1937
National Institutes of Health Clinical Center The National Institutes of Health (NIH) Clinical Center in...
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