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

Phase 1

Completed

Conditions: Prostatic Neoplasms

Interventions: Drug: Zolpidem
Diagnostic Test: ECG

Registration Number: NCT03436745

Lead Sponsor: National Cancer Institute (NCI)

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.

Detailed Description: Background:

* Zolpidem is currently approved for the treatment of patients with insomnia.

* Women reported experiencing an increased incidence of adverse effects than men, resulting in a reduction of the recommended dose of zolpidem for women.

* Zolpidem metabolism is affected by both age and gender; the recommended dose for the elderly and female populations is 5mg daily.

* Subsequent studies have shown that women experience greater exposure to zolpidem than men, potentially due to androgen-driven differences in enzyme expression.

* A preclinical study showed that castrated male rats exhibited zolpidem pharmacokinetics similar to that of female rats, providing further evidence to suggest that zolpidem pharmacokinetics are androgen-driven.

Objectives:

-To evaluate the effect of castration on the pharmacokinetics of a single 5-mg dose of zolpidem in participants with prostate cancer undergoing androgen deprivation therapy (previous post-castration therapy) compared to normal healthy females.

Eligibility:

* Participants with prostate cancer (rising prostate-specific antigen (PSA) and greater than or equal to 100 ng/dL)

* Females in good health condition or without significant diseases

* After androgen deprivation therapy, castrate testosterone levels \<50 ng/dL

* Eastern Cooperative Oncology Group (ECOG) 0-1

Design:

* Comparative, single-dose pharmacokinetic study.

* Men with prostate cancer (pre-castration) and normal healthy females will receive treatment with a single dose of 5 mg tablet of zolpidem followed by 8-hour pharmacokinetic evaluation of zolpidem and its metabolites.

* Men will then undergo androgen deprivation therapy and when castrate testosterone levels \<50 ng/dL (post-castration), they will receive another 5 mg single dose of zolpidem followed by 8-hour pharmacokinetic evaluation of zolpidem and its metabolites.

* Normal healthy females will receive treatment with a single dose of 5 mg tablet of zolpidem followed by 8-hour pharmacokinetic evaluation of zolpidem and its metabolites.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 12

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Female	Zolpidem	Single 5 mg oral dose of zolpidem
Female	ECG	Single 5 mg oral dose of zolpidem
Zolpidem pre and post castration	ECG	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
Zolpidem pre and post castration	Zolpidem	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

Primary Outcome Measures

Name	Time	Method
Change in Area Under the Plasma Concentration 0-8Hour (Hr)(AUC0-8hr) Values in Males Between Pre-Androgen Deprivation Therapy (ADT) and Post-ADT	pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, and 8-hours post-dose.	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.

Secondary Outcome Measures

Name	Time	Method
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.	AUC is a measure of the serum concentration of Zolpidem over time. It is used to characterize drug absorption. AUC values will be compared between those of post-ADT males and healthy females to assess whether AUC values are approximately equivalent between post-ADT males and healthy females.