The Effects of Castration on the Pharmacokinetics of Zolpidem After Single Dose Administration In Men With Prostate Cancer Undergoing Androgen Deprivation Therapy Compared to Normal Healthy Females

NCT03436745 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 18005818-C-0058
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Insomnia is associated with difficulty sleeping. The drug zolpidem is widely prescribed for insomnia. Women have reported worse effects from the drug than men. Women have higher amounts of zolpidem in their body that may persist after waking. Drug exposure may also depend on male hormones that change during prostate cancer therapy. Researchers want to see if these findings can provide a more-accurate dose to healthy women and men with prostate cancer. Objective: To study amounts of zolpidem in men who have been diagnosed with prostate cancer before they are castrated and after, and to compare these results to healthy women s. Eligibility: Men ages 18 and older who have been diagnosed with prostate cancer who are planning to receive androgen deprivation therapy (ADT) Healthy women age 18 and older Design: Participants will be screened with: Blood tests Physical exam Electrocardiogram (EKG) heart test Male participants will confirm their prostate cancer. This can be done with a tumor sample tissue from a previous surgery or a report from a doctor. Female participants may have a pregnancy test. Participants will be admitted to the clinic in the evening and stay overnight. They will: Take a 5 mg zolpidem tablet on an empty stomach around 11 p.m. Have blood drawn multiple times Have physical exams and EKGs Answer questions about their symptoms and medicines they are taking Male participants will have ADT as part of their standard cancer treatment. After that, the testosterone in their blood will be measured. They will repeat the overnight clinic stay. Participants will get a follow-up phone call after each stay.

Conditions

Prostatic Neoplasms

Keywords

Insomnia; Enzyme Expression; PSA; TESTOSTERONE; Recommended Dose

Outcome Measures

Primary Outcomes (1)

• Change in Area Under the Plasma Concentration 0-8Hour (Hr)(AUC0-8hr) Values in Males Between Pre-Androgen Deprivation Therapy (ADT) and Post-ADT

  AUC is a measure of the serum concentration of Zolpidem over time. It is used to characterize drug absorption. The AUC values will be compared between the time points for males to see if the AUC increases significantly. Pre-ADT males will be subtracted from the paired values in males once they are post-ADT and tested for a difference using a paired t-test with a two-sided 0.05 significance level, or a Wilcoxon signed rank test if the paired differences are not normally distributed.

  pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, and 8-hours post-dose.

Secondary Outcomes (1)

• Comparison of Area Under the Plasma Concentration 0-8Hour (Hr)(AUC0-8hr) Values Between Post-Androgen Deprivation Therapy (ADT) Males and Healthy Female Participants

  pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, and 8-hours post-dose.

Other Outcomes (1)

• Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0).

  Study Period 1, Day 1 to Day 3 (female &male cohort). From first intervention, Study Period Day 1 to 3 days after removal from study treatment, approximately 3 days. Study Period 2, Day 1 to Day 3 (male cohort) after removal from study treatment, =3 days.

Study Arms (2)

Female

ACTIVE COMPARATOR

Single 5 mg oral dose of zolpidem

Drug: Zolpidem; Diagnostic Test: ECG

Zolpidem pre and post castration

EXPERIMENTAL

5 mg oral dose of zolpidem prior to undergoing androgen deprivation therapy (ADT) followed by 5 mg oral dose of zolpidem after ADT and testosterone reaches castrate levels

Drug: Zolpidem; Diagnostic Test: ECG

Interventions

Zolpidem DRUG

In men with prostate cancer, males (pre-castration, n=8-10) will receive oral zolpidem in the form of a 5 mg tablet. Blood samples will be collected for pharmacokinetic analysis at pre-dose and 0.5, 1, 2, 4, and 8-hours post-dose. This cohort of men will then undergo androgen deprivation therapy with standard doses of goserelin. When castrate testosterone levels reach \<50 ng/dL (post-castration), they will receive another 5 mg single dose of zolpidem followed by 8-hr pharmacokinetic (PK) evaluation of zolpidem and its metabolites. Normal healthy females (n=5-8) will receive treatment with a single dose of 5 mg tablet of zolpidem followed by 8-hr PK evaluation of zolpidem and its metabolites. Blood samples will be collected for PK analysis at pre-dose and 0.5, 1, 2, 4, and 8-hours post-dose.

Also known as: Ambien, Zolpimist, Edluar

Female; Zolpidem pre and post castration

ECG DIAGNOSTIC_TEST

Screening and baseline.

Also known as: Electrocardiogram

Female; Zolpidem pre and post castration

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically or cytologically confirmed prostate cancer. Note: If histologic documentation is unavailable, a clinical course consistent with prostate cancer is acceptable.
• Patients must be eligible for and must be planning to undergo androgen deprivation therapy
• Testosterone levels greater than or equal to 100 ng/dL
• Patients must have progressive prostate cancer as indicated by either prostate-specific antigen (PSA) progression (PSA progression is defined as two consecutively rising PSAs above the nadir post- definitive therapy and an absolute value greater than 1.0 ng/mL separated by at least 2 weeks) or radiographic progression based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or Prostate Cancer Working Group 3 (PCWG3).
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
• Patients must have normal organ and marrow function as defined below:
• Hemoglobin greater than or equal to 9 g/dL
• leukocytes greater than or equal to 3,000/mcL
• absolute neutrophil count greater than or equal to 1,500/mcL
• platelets greater than or equal to 150,000/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 institutional upper limit of normal
• creatinine within normal institutional limits OR creatinine clearance greater than or equal to 60 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 zolpidem).
• Ability of subject to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Patients who are receiving any other investigational agents (in the past 28 days) or herbal medications (within 1 day).
• Patients who have received systemic chemotherapy for prostate cancer will not be eligible.
• Known hypersensitivity to Zolpidem or chemically related compounds; history of serious adverse reactions or hypersensitivity to any drug.
• 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.
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with zolpidem. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
• Patients with known active treatment for Hepatitis B and C infections.
• Patients who are taking medications that may alter the metabolism of zolpidem. This includes strong Cytochrome P450 3A4 (CYP3A4) inhibitors or inducers or CYP3A4 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/DrugInteractionsLabeling/ucm093664.htm
• History or presence of hepatic or gastrointestinal diseases, or other condition that interferes with drug absorption, distribution, excretion or metabolism.
• Patients currently taking other sedative hypnotic medications Patients with a known history of psychiatric issues
• Patients at risk for fall or who have had recent fractures
• Patients of Asian descent
• Chronic therapy with any drugs, except contraceptives
• History of hepatic, kidney, lungs, gastrointestinal, epileptic, hematologic or psychiatric disease; hypotension or hypertension, of any etiology, that requires pharmacological treatment; history of myocardial infarction, angina and/or heart failure.
• Use of regular medications within 2 weeks prior study enrollment or use of any medications within one week prior to study enrollment, except contraceptives or cases which, based on drugs or metabolites half-life, complete elimination can be assumed.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Prostatic Neoplasms; Sleep Initiation and Maintenance Disorders

Interventions

Zolpidem; Electrocardiography

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heart Function Tests; Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis; Electrodiagnosis

Results Point of Contact

• Title: William D. Figg, Pharm.D.
• Organization: National Cancer Institute

figgw@mail.nih.gov

240-760-6179

Study Officials

• William D Figg, Pharm.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Investigator

Study Record Dates

• First Submitted: February 16, 2018
• First Posted: February 19, 2018
• Study Start: January 22, 2019
• Primary Completion: January 30, 2024
• Study Completion: January 30, 2024
• Last Updated: February 11, 2025
• Results First Posted: February 11, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely.
• Access Criteria: Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI).

Locations

US (1)