Trial Outcomes & Findings for 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 (NCT NCT03436745)

Last Updated: 2025-02-11

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

12 participants

Primary outcome timeframe

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

Results posted on

2025-02-11

Participant Flow

Participant milestones

Participant milestones
Measure	Healthy Female Cohort: One Time Zolpidem Single 5 mg oral dose of zolpidem Dose Level 2 Zolpidem: 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.	Prostate Cancer Cohort: Zolpidem Pre and Post Castration 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 Dose Level 1a -\> Dose Level 1b. Zolpidem: 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.	Enrolled But Not Treated Participant was enrolled but not treated.
Overall Study STARTED	10	1	1
Overall Study Follow-up Period Completed	10	1	0
Overall Study COMPLETED	10	1	0
Overall Study NOT COMPLETED	0	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Healthy Female Cohort: One Time Zolpidem Single 5 mg oral dose of zolpidem Dose Level 2 Zolpidem: 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.	Prostate Cancer Cohort: Zolpidem Pre and Post Castration 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 Dose Level 1a -\> Dose Level 1b. Zolpidem: 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.	Enrolled But Not Treated Participant was enrolled but not treated.
Overall Study Ineligible	0	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

PRIMARY outcome

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

Outcome measures

Outcome measures
Measure	Prostate Cancer Cohort: Zolpidem Pre-Castration n=1 Participants Zolpidem: In men with prostate cancer, males (pre-castration) will receive oral zolpidem in the form of a 5 mg tablet.	Prostate Cancer Cohort: Zolpidem Post Castration n=1 Participants This cohort of men will 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.
Change in Area Under the Plasma Concentration 0-8Hour (Hr)(AUC0-8hr) Values in Males Between Pre-Androgen Deprivation Therapy (ADT) and Post-ADT	484.65 Hr*ng/mL 95% confidence interval cannot be calculated because we only have 1 male enrolled, so we cannot scientifically make a comparison.	473.05 Hr*ng/mL 95% confidence interval cannot be calculated because we only have 1 male enrolled, so we cannot scientifically make a comparison.

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Prostate Cancer Cohort: Zolpidem Pre-Castration n=10 Participants Zolpidem: In men with prostate cancer, males (pre-castration) will receive oral zolpidem in the form of a 5 mg tablet.	Prostate Cancer Cohort: Zolpidem Post Castration n=1 Participants This cohort of men will 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.
Comparison of Area Under the Plasma Concentration 0-8Hour (Hr)(AUC0-8hr) Values Between Post-Androgen Deprivation Therapy (ADT) Males and Healthy Female Participants	242 Hr*ng/mL Interval 7.2 to 478.05	473.05 Hr*ng/mL 95% confidence interval cannot be calculated because we only have 1 male enrolled, so we cannot scientifically make a comparison.

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). 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.

Outcome measures

Outcome measures
Measure	Prostate Cancer Cohort: Zolpidem Pre-Castration n=10 Participants Zolpidem: In men with prostate cancer, males (pre-castration) will receive oral zolpidem in the form of a 5 mg tablet.	Prostate Cancer Cohort: Zolpidem Post Castration n=1 Participants This cohort of men will 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.
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0).	1 Participants	1 Participants

Adverse Events

Healthy Female Cohort: One Time Zolpidem

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Prostate Cancer Cohort: Zolpidem Pre and Post Castration

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Healthy Female Cohort: One Time Zolpidem n=10 participants at risk Normal healthy females (n=5-8) will receive treatment with a single dose of 5 mg tablet of zolpidem.	Prostate Cancer Cohort: Zolpidem Pre and Post Castration n=1 participants at risk 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: In men with prostate cancer, males (pre-castration) will receive oral zolpidem in the form of a 5 mg tablet. 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.
Injury, poisoning and procedural complications Bruising	10.0% 1/10 • Number of events 1 • 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.	0.00% 0/1 • 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.
General disorders Fatigue	0.00% 0/10 • 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.	100.0% 1/1 • Number of events 1 • 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.
Gastrointestinal disorders Gastroesophageal reflux disease	10.0% 1/10 • Number of events 1 • 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.	0.00% 0/1 • 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.
Gastrointestinal disorders Toothache	10.0% 1/10 • Number of events 1 • 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.	0.00% 0/1 • 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.

Additional Information

William D. Figg, Pharm.D.

National Cancer Institute

Phone: 240-760-6179

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Prostate Cancer Cohort: Zolpidem Pre and Post Castration n=1 Participants 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 Dose Level 1a -\> Dose Level 1b. Zolpidem: 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.	Healthy Female Cohort: One Time Zolpidem n=10 Participants Single 5 mg oral dose of zolpidem Dose Level 2 Zolpidem: 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.	Enrolled But Not Treated n=1 Participants Participant was enrolled but not treated.	Total n=12 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants	10 Participants n=7 Participants	0 Participants n=5 Participants	11 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Age, Continuous	64 years STANDARD_DEVIATION 0 • n=5 Participants	27.6 years STANDARD_DEVIATION 4.2 • n=7 Participants	75 years STANDARD_DEVIATION 0 • n=5 Participants	34.58 years STANDARD_DEVIATION 16.91 • n=4 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	10 Participants n=7 Participants	0 Participants n=5 Participants	10 Participants n=4 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1 Participants n=5 Participants	7 Participants n=7 Participants	1 Participants n=5 Participants	9 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	6 Participants n=7 Participants	0 Participants n=5 Participants	6 Participants n=4 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants	4 Participants n=7 Participants	1 Participants n=5 Participants	6 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United States	1 participants n=5 Participants	10 participants n=7 Participants	1 participants n=5 Participants	12 participants n=4 Participants