Palonosetron and Hydroxyzine to Reduce Opioid Withdrawal

• Sponsor: Stanford University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00661674
• Collaborator: (none)
• Enrollment: 10
• Location: 1
• Arms: 6
• Duration (Months): 4
• Patients Per Site Per Month: 2.5

Study Details

Study Description

Brief Summary

Opioid medications are commonly used for pain relief. When given over time, physical dependence can occur. This results in unpleasant side effects--such as agitation and nausea--if opioid medications are suddenly stopped. We are interested in knowing if a medication named Ondansetron can help ease or prevent symptoms associated with opioid withdrawal. We are also interested in knowing if a similar (but more potent FDA-approved drug, palonosetron) can more effectively treat withdrawal symptoms with or without combination with an antihistamine called hydroxyzine (vistaril).

Condition or Disease	Intervention/Treatment	Phase
Substance-Related Disorders	Drug: Palonosetron; Drug: Hydroxyzine; Other: Placebo	N/A

Detailed Description

We hope to learn if Palonosetron and/or combination with hydroxyzine can be used to prevent or attenuate the signs and symptoms of opioid withdrawal. If we find that it can help prevent these symptoms, it may become a new treatment that can aid patients suffering from these symptoms.

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: There were three treatment arms to the study: Placebo, Palonosetron, and Palonosetron + Hydroxyzine (Combo). Participants were not randomized in between these arms, all participants completed each arm of the study in a cross-over study methodology (Placebo, Palonosetron, Palonosetron + Hydroxyzene (combo). Participants were individually randomized into the order in which they participated in each arm. Per sequence each individual participant underwent the following randomization schedule: Participant 1: Placebo, Combo, Palonosetron Participant 2: Palonosetron, Combo, Placebo Participant 3: Palonosetron, Combo, Placebo Participant 4: Combo, Placebo, Palonosetron Participant 5: Placebo, Palonosetron, Combo Participant 6: Combo, Palonosetron, Placebo Participant 7: Combo, Placebo, Palonosetron Participant 8: Combo, Palonosetron, Placebo Participant 9: Palonosetron, Placebo, Combo Participant 10: Placebo, Combo, PalonosetronThere were three treatment arms to the study: Placebo, Palonosetron, and Palonosetron + Hydroxyzine (Combo). Participants were not randomized in between these arms, all participants completed each arm of the study in a cross-over study methodology (Placebo, Palonosetron, Palonosetron + Hydroxyzene (combo). Participants were individually randomized into the order in which they participated in each arm.Per sequence each individual participant underwent the following randomization schedule:Participant 1: Placebo, Combo, Palonosetron Participant 2: Palonosetron, Combo, Placebo Participant 3: Palonosetron, Combo, Placebo Participant 4: Combo, Placebo, Palonosetron Participant 5: Placebo, Palonosetron, Combo Participant 6: Combo, Palonosetron, Placebo Participant 7: Combo, Placebo, Palonosetron Participant 8: Combo, Palonosetron, Placebo Participant 9: Palonosetron, Placebo, Combo Participant 10: Placebo, Combo, Palonosetron
• Masking: Triple (Participant, Care Provider, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Examination of Palonosetron and Hydroxyzine Pre-treatment as a Possible Method to Reduce the Objective Signs of Experimentally-induced Acute Opioid Withdrawal in Humans: a Double-blind, Randomized, Placebo-controlled Crossover Study
• Study Start Date: Apr 1, 2008
• Actual Primary Completion Date: Aug 1, 2008
• Actual Study Completion Date: Aug 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sequence 1: Placebo, Combo, Palonosetron At T = 0 (minutes), healthy (non-opioid dependent, non-substance abuser) male volunteers (N=10) were pre-treated with either placebo (0.9% normal saline), palonosetron IV (0.75mg), or palonosetron IV (0.75mg) and hydroxyzine per os (PO) (100mg) in a crossover study design. This was followed at T = 30 by intravenous morphine (10mg/70kg). At T = 165, 10mg/70kg naloxone IV was given to precipitate opioid withdrawal. The objective opioid withdrawal score (OOWS) and subjective opioid withdrawal score (SOWS) were determined 5 and 15 minutes after naloxone administration (T = 170, 180, respectively). Baseline measurements were recorded at T = -30 and T = -15. Week 1: Placebo Week 2: Palonosetron + Hydroxyzine Combo Week 3: Palonosetron	Drug: Palonosetron; Over 3 study visits, patients will receive one of the following treatment regimens: Placebo saline IV and sugar pill 0.75 mg Palonosetron IV and sugar pill 0.75 mg Palonosetron IV and 100 mg hydroxyzine PO; Other Names: Aloxi ; Drug: Hydroxyzine; Over 3 study visits, patients will receive one of the following treatment regimens: Placebo saline IV and sugar pill 0.75 mg Palonosetron IV and sugar pill 0.75 mg Palonosetron IV and 100 mg hydroxyzine PO; Other Names: Vistaril, Atarax ; Other: Placebo; Over 3 study visits, patients will receive one of the following treatment regimens: Placebo saline IV and sugar pill 0.75 mg Palonosetron IV and sugar pill 0.75 mg Palonosetron IV and 100 mg hydroxyzine PO
Experimental: Sequence 2: Palonosetron, Combo, Placebo At T = 0 (minutes), healthy (non-opioid dependent, non-substance abuser) male volunteers (N=10) were pre-treated with either placebo (0.9% normal saline), palonosetron IV (0.75mg), or palonosetron IV (0.75mg) and hydroxyzine per os (PO) (100mg) in a crossover study design. This was followed at T = 30 by intravenous morphine (10mg/70kg). At T = 165, 10mg/70kg naloxone IV was given to precipitate opioid withdrawal. The objective opioid withdrawal score (OOWS) and subjective opioid withdrawal score (SOWS) were determined 5 and 15 minutes after naloxone administration (T = 170, 180, respectively). Baseline measurements were recorded at T = -30 and T = -15. Week 1: Palonosetron Week 2: Palonosetron + Hydroxyzine Combo Week 3: Placebo	Drug: Palonosetron; Over 3 study visits, patients will receive one of the following treatment regimens: Placebo saline IV and sugar pill 0.75 mg Palonosetron IV and sugar pill 0.75 mg Palonosetron IV and 100 mg hydroxyzine PO; Other Names: Aloxi ; Drug: Hydroxyzine; Over 3 study visits, patients will receive one of the following treatment regimens: Placebo saline IV and sugar pill 0.75 mg Palonosetron IV and sugar pill 0.75 mg Palonosetron IV and 100 mg hydroxyzine PO; Other Names: Vistaril, Atarax ; Other: Placebo; Over 3 study visits, patients will receive one of the following treatment regimens: Placebo saline IV and sugar pill 0.75 mg Palonosetron IV and sugar pill 0.75 mg Palonosetron IV and 100 mg hydroxyzine PO
Experimental: Sequence 3: Combo, Placebo, Palonosetron At T = 0 (minutes), healthy (non-opioid dependent, non-substance abuser) male volunteers (N=10) were pre-treated with either placebo (0.9% normal saline), palonosetron IV (0.75mg), or palonosetron IV (0.75mg) and hydroxyzine per os (PO) (100mg) in a crossover study design. This was followed at T = 30 by intravenous morphine (10mg/70kg). At T = 165, 10mg/70kg naloxone IV was given to precipitate opioid withdrawal. The objective opioid withdrawal score (OOWS) and subjective opioid withdrawal score (SOWS) were determined 5 and 15 minutes after naloxone administration (T = 170, 180, respectively). Baseline measurements were recorded at T = -30 and T = -15. Week 1: Palonosetron + Hydroxyzine Combo Week 2: Placebo Week 3: Palonosetron	Drug: Palonosetron; Over 3 study visits, patients will receive one of the following treatment regimens: Placebo saline IV and sugar pill 0.75 mg Palonosetron IV and sugar pill 0.75 mg Palonosetron IV and 100 mg hydroxyzine PO; Other Names: Aloxi ; Drug: Hydroxyzine; Over 3 study visits, patients will receive one of the following treatment regimens: Placebo saline IV and sugar pill 0.75 mg Palonosetron IV and sugar pill 0.75 mg Palonosetron IV and 100 mg hydroxyzine PO; Other Names: Vistaril, Atarax ; Other: Placebo; Over 3 study visits, patients will receive one of the following treatment regimens: Placebo saline IV and sugar pill 0.75 mg Palonosetron IV and sugar pill 0.75 mg Palonosetron IV and 100 mg hydroxyzine PO
Experimental: Sequence 4: Placebo, Palonosetron, Combo At T = 0 (minutes), healthy (non-opioid dependent, non-substance abuser) male volunteers (N=10) were pre-treated with either placebo (0.9% normal saline), palonosetron IV (0.75mg), or palonosetron IV (0.75mg) and hydroxyzine per os (PO) (100mg) in a crossover study design. This was followed at T = 30 by intravenous morphine (10mg/70kg). At T = 165, 10mg/70kg naloxone IV was given to precipitate opioid withdrawal. The objective opioid withdrawal score (OOWS) and subjective opioid withdrawal score (SOWS) were determined 5 and 15 minutes after naloxone administration (T = 170, 180, respectively). Baseline measurements were recorded at T = -30 and T = -15. Week 1: Placebo Week 2: Palonosetron only Week 3: Palonosetron + Hydroxyzine Combo	Drug: Palonosetron; Over 3 study visits, patients will receive one of the following treatment regimens: Placebo saline IV and sugar pill 0.75 mg Palonosetron IV and sugar pill 0.75 mg Palonosetron IV and 100 mg hydroxyzine PO; Other Names: Aloxi ; Drug: Hydroxyzine; Over 3 study visits, patients will receive one of the following treatment regimens: Placebo saline IV and sugar pill 0.75 mg Palonosetron IV and sugar pill 0.75 mg Palonosetron IV and 100 mg hydroxyzine PO; Other Names: Vistaril, Atarax ; Other: Placebo; Over 3 study visits, patients will receive one of the following treatment regimens: Placebo saline IV and sugar pill 0.75 mg Palonosetron IV and sugar pill 0.75 mg Palonosetron IV and 100 mg hydroxyzine PO
Experimental: Sequence 5: Combo, Palonosetron, Placebo At T = 0 (minutes), healthy (non-opioid dependent, non-substance abuser) male volunteers (N=10) were pre-treated with either placebo (0.9% normal saline), palonosetron IV (0.75mg), or palonosetron IV (0.75mg) and hydroxyzine per os (PO) (100mg) in a crossover study design. This was followed at T = 30 by intravenous morphine (10mg/70kg). At T = 165, 10mg/70kg naloxone IV was given to precipitate opioid withdrawal. The objective opioid withdrawal score (OOWS) and subjective opioid withdrawal score (SOWS) were determined 5 and 15 minutes after naloxone administration (T = 170, 180, respectively). Baseline measurements were recorded at T = -30 and T = -15. Week 1: Palonosetron + Hydroxyzine Combo Week 2: Palonosetron only Week 3: Placebo	Drug: Palonosetron; Over 3 study visits, patients will receive one of the following treatment regimens: Placebo saline IV and sugar pill 0.75 mg Palonosetron IV and sugar pill 0.75 mg Palonosetron IV and 100 mg hydroxyzine PO; Other Names: Aloxi ; Drug: Hydroxyzine; Over 3 study visits, patients will receive one of the following treatment regimens: Placebo saline IV and sugar pill 0.75 mg Palonosetron IV and sugar pill 0.75 mg Palonosetron IV and 100 mg hydroxyzine PO; Other Names: Vistaril, Atarax ; Other: Placebo; Over 3 study visits, patients will receive one of the following treatment regimens: Placebo saline IV and sugar pill 0.75 mg Palonosetron IV and sugar pill 0.75 mg Palonosetron IV and 100 mg hydroxyzine PO
Experimental: Sequence 6: Palonosetron, Placebo, Combo At T = 0 (minutes), healthy (non-opioid dependent, non-substance abuser) male volunteers (N=10) were pre-treated with either placebo (0.9% normal saline), palonosetron IV (0.75mg), or palonosetron IV (0.75mg) and hydroxyzine per os (PO) (100mg) in a crossover study design. This was followed at T = 30 by intravenous morphine (10mg/70kg). At T = 165, 10mg/70kg naloxone IV was given to precipitate opioid withdrawal. The objective opioid withdrawal score (OOWS) and subjective opioid withdrawal score (SOWS) were determined 5 and 15 minutes after naloxone administration (T = 170, 180, respectively). Baseline measurements were recorded at T = -30 and T = -15. Week 1: Palonosetron only Week 2: Placebo Week 3:Palonosetron + Hydroxyzine Combo	Drug: Palonosetron; Over 3 study visits, patients will receive one of the following treatment regimens: Placebo saline IV and sugar pill 0.75 mg Palonosetron IV and sugar pill 0.75 mg Palonosetron IV and 100 mg hydroxyzine PO; Other Names: Aloxi ; Drug: Hydroxyzine; Over 3 study visits, patients will receive one of the following treatment regimens: Placebo saline IV and sugar pill 0.75 mg Palonosetron IV and sugar pill 0.75 mg Palonosetron IV and 100 mg hydroxyzine PO; Other Names: Vistaril, Atarax ; Other: Placebo; Over 3 study visits, patients will receive one of the following treatment regimens: Placebo saline IV and sugar pill 0.75 mg Palonosetron IV and sugar pill 0.75 mg Palonosetron IV and 100 mg hydroxyzine PO

Outcome Measures

Primary Outcome Measures

1. OOWS Score [Change from baseline in OOWS score at 180 minutes (15 minutes post naloxone administration)]

   The OOWS is a 13-item instrument documenting physically observable signs of withdrawal, which are rated as present (1) or absent (0) during the observation period. Maximum score possible = 13, minimum score possible = 0. T=15 minutes post naloxone administration coordinates with T = 180 (min) for the entire study session. OOWS scores at T=180 is the primary outcome measure of the study compared with baseline OOWS scores at T=-30 (30 minutes prior to study medication administration). Reported time frames are in relation to time past since administration of study medications. Mean post-Naloxone OOWS scores (+/- SEM) were determined for pretreatment groups

Secondary Outcome Measures

1. SOWS Score [Change from baseline in SOWS score at 180 minutes (15 minutes post naloxone administration)]

   The SOWS score is composed of 16 subjective symptoms rated on a scale of 0 to 4 (0=not at all, 4=extremely) based on what subjects were experiencing at the time of testing. 15 minutes post naloxone administration coordinates with T = 180 (min) for the entire study session. The highest score possible (64) would indicate that the individual was experiencing every symptom of opioid withdrawal to the fullest extent possible while the lowest score (0) would indicate that the individual was not experiencing any symptoms of opioid withdrawal. Mean post-naloxone SOWS scores (+/- SEM) were computed for pretreatment groups: Placebo, palonosetron, and palonosetron with hydroxyzine

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 35 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Healthy males

• Ages 18-35

• No allergies to morphine or palonosetron

• No history of addiction or substance abuse

Exclusion Criteria:

• Female

• Younger than 18 or older than 35

• History of substance abuse

• Raynaud's disease or coronary artery disease

• Allergies to morphine or palonosetron

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University School of Medicine	Stanford	California	United States	94305

Sponsors and Collaborators

• Stanford University

Investigators

• Principal Investigator: Dr Larry Fu-nien Chu, Stanford University

Study Documents (Full-Text)

None provided.

More Information

Publications

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• Responsible Party: Larry Fu-nien Chu, Professor of Anesthesia, Stanford University
• ClinicalTrials.gov Identifier: NCT00661674
• Other Study ID Numbers: SU-04152008-1099
• First Posted: Apr 18, 2008
• Last Update Posted: Jun 5, 2017
• Last Verified: Apr 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Larry Fu-nien Chu, Professor of Anesthesia, Stanford University: Palonosetron; Hydroxyzine; Acute opioid withdrawal
• Additional relevant MeSH terms: Substance-Related Disorders; Palonosetron; Hydroxyzine

Study Results

Participant Flow

Arm/Group Title	Sequence 1: Placebo, Combo, Palonosetron	Sequence 2: Palonosetron, Combo, Placebo	Sequence 3: Combo, Placebo, Palonosetron	Sequence 4: Placebo, Palonosetron, Combo	Sequence 5: Combo, Palonosetron, Placebo	Sequence 6: Palonosetron, Placebo, Combo
Arm/Group Description	At T = 0 (minutes), healthy (non-opioid dependent, non-substance abuser) male volunteers (N=10) were pre-treated with either placebo (0.9% normal saline), palonosetron IV (0.75mg), or palonosetron IV (0.75mg) and hydroxyzine per os (PO) (100mg) in a crossover study design. This was followed at T = 30 by intravenous morphine (10mg/70kg). At T = 165, 10mg/70kg naloxone IV was given to precipitate opioid withdrawal. The objective opioid withdrawal score (OOWS) and subjective opioid withdrawal score (SOWS) were determined 5 and 15 minutes after naloxone administration (T = 170, 180, respectively). Baseline measurements were recorded at T = -30 and T = -15. Week 1: Placebo Week 2: Combo Week 3: Palonosetron	At T = 0 (minutes), healthy (non-opioid dependent, non-substance abuser) male volunteers (N=10) were pre-treated with either placebo (0.9% normal saline), palonosetron IV (0.75mg), or palonosetron IV (0.75mg) and hydroxyzine per os (PO) (100mg) in a crossover study design. This was followed at T = 30 by intravenous morphine (10mg/70kg). At T = 165, 10mg/70kg naloxone IV was given to precipitate opioid withdrawal. The objective opioid withdrawal score (OOWS) and subjective opioid withdrawal score (SOWS) were determined 5 and 15 minutes after naloxone administration (T = 170, 180, respectively). Baseline measurements were recorded at T = -30 and T = -15. Week 1: Palonosetron Week 2: Combo Week 3: Placebo	At T = 0 (minutes), healthy (non-opioid dependent, non-substance abuser) male volunteers (N=10) were pre-treated with either placebo (0.9% normal saline), palonosetron IV (0.75mg), or palonosetron IV (0.75mg) and hydroxyzine per os (PO) (100mg) in a crossover study design. This was followed at T = 30 by intravenous morphine (10mg/70kg). At T = 165, 10mg/70kg naloxone IV was given to precipitate opioid withdrawal. The objective opioid withdrawal score (OOWS) and subjective opioid withdrawal score (SOWS) were determined 5 and 15 minutes after naloxone administration (T = 170, 180, respectively). Baseline measurements were recorded at T = -30 and T = -15. Week 1: Combo Week 2: Placebo Week 3: Palonosetron	At T = 0 (minutes), healthy (non-opioid dependent, non-substance abuser) male volunteers (N=10) were pre-treated with either placebo (0.9% normal saline), palonosetron IV (0.75mg), or palonosetron IV (0.75mg) and hydroxyzine per os (PO) (100mg) in a crossover study design. This was followed at T = 30 by intravenous morphine (10mg/70kg). At T = 165, 10mg/70kg naloxone IV was given to precipitate opioid withdrawal. The objective opioid withdrawal score (OOWS) and subjective opioid withdrawal score (SOWS) were determined 5 and 15 minutes after naloxone administration (T = 170, 180, respectively). Baseline measurements were recorded at T = -30 and T = -15. Week 1: Placebo Week 2: Palonosetron Week 3: Combo	At T = 0 (minutes), healthy (non-opioid dependent, non-substance abuser) male volunteers (N=10) were pre-treated with either placebo (0.9% normal saline), palonosetron IV (0.75mg), or palonosetron IV (0.75mg) and hydroxyzine per os (PO) (100mg) in a crossover study design. This was followed at T = 30 by intravenous morphine (10mg/70kg). At T = 165, 10mg/70kg naloxone IV was given to precipitate opioid withdrawal. The objective opioid withdrawal score (OOWS) and subjective opioid withdrawal score (SOWS) were determined 5 and 15 minutes after naloxone administration (T = 170, 180, respectively). Baseline measurements were recorded at T = -30 and T = -15. Week 1: Combo Week 2: Palonosetron Week 3: Placebo	At T = 0 (minutes), healthy (non-opioid dependent, non-substance abuser) male volunteers (N=10) were pre-treated with either placebo (0.9% normal saline), palonosetron IV (0.75mg), or palonosetron IV (0.75mg) and hydroxyzine per os (PO) (100mg) in a crossover study design. This was followed at T = 30 by intravenous morphine (10mg/70kg). At T = 165, 10mg/70kg naloxone IV was given to precipitate opioid withdrawal. The objective opioid withdrawal score (OOWS) and subjective opioid withdrawal score (SOWS) were determined 5 and 15 minutes after naloxone administration (T = 170, 180, respectively). Baseline measurements were recorded at T = -30 and T = -15. Week 1: Palonosetron Week 2: Placebo Week 3: Combo
Period Title: Overall Study
STARTED	2	2	2	1	2	1
COMPLETED	2	2	2	1	2	1
NOT COMPLETED	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Overall Study
Arm/Group Description	Over three study sessions each spaced one week apart participants received either placebo IV + PO, Palonosetron IV (0.75 mg) + placebo PO, or Palonosetron IV (0.75 mg) + Hydroxyzine PO (100mg).
Overall Participants	10
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	21.1 (2.18)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	10 100%
Region of Enrollment (participants) [Number]
United States	10 100%

Outcome Measures

1. Primary Outcome

Title	OOWS Score
Description	The OOWS is a 13-item instrument documenting physically observable signs of withdrawal, which are rated as present (1) or absent (0) during the observation period. Maximum score possible = 13, minimum score possible = 0. T=15 minutes post naloxone administration coordinates with T = 180 (min) for the entire study session. OOWS scores at T=180 is the primary outcome measure of the study compared with baseline OOWS scores at T=-30 (30 minutes prior to study medication administration). Reported time frames are in relation to time past since administration of study medications. Mean post-Naloxone OOWS scores (+/- SEM) were determined for pretreatment groups
Time Frame	Change from baseline in OOWS score at 180 minutes (15 minutes post naloxone administration)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Palonosetron	Palonosetron + Hydroxyzine
Arm/Group Description	Each participant had one session in which they received a placebo tablet pretreatment prior to naloxone-precipitated withdrawal.	Each participant had one session in which they received palonosetron IV pretreatment prior to naloxone-precipitated withdrawal.	Each participant had one session in which they received IV palonosetron + PO hydroxyzine pretreatment prior to naloxone-precipitated withdrawal.
Measure Participants	10	10	10
Mean (Standard Error) [units on a scale (OOWS Scale)]	3.5 (0.76)	1.0 (0.37)	0 (0.13)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Palonosetron, Palonosetron + Hydroxyzine
	Comments	Null Hypothesis: There will be no difference in OOWS scores when comparing treatment groups (Palonosetron & Palonosetron + Hydroxyzine) with placebo. Analysis of the data obtained in our prior study indicated that analysis of 10 individuals would provide 90% power to detect a treatment effect. Therefore, we examined the effect of three different pretreatments on naloxone-induced opiate withdrawal signs in 10 healthy individuals.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments	p-value represents comparison between OOWS scores at T=180 and the baseline measurements at T=-30.
	Method	Friedman Test
	Comments

2. Secondary Outcome

Title	SOWS Score
Description	The SOWS score is composed of 16 subjective symptoms rated on a scale of 0 to 4 (0=not at all, 4=extremely) based on what subjects were experiencing at the time of testing. 15 minutes post naloxone administration coordinates with T = 180 (min) for the entire study session. The highest score possible (64) would indicate that the individual was experiencing every symptom of opioid withdrawal to the fullest extent possible while the lowest score (0) would indicate that the individual was not experiencing any symptoms of opioid withdrawal. Mean post-naloxone SOWS scores (+/- SEM) were computed for pretreatment groups: Placebo, palonosetron, and palonosetron with hydroxyzine
Time Frame	Change from baseline in SOWS score at 180 minutes (15 minutes post naloxone administration)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Palonosetron	Palonosetron + Hydroxyzine
Arm/Group Description	Each participant had one session in which they received a placebo tablet pretreatment prior to naloxone-precipitated withdrawal.	Each participant had one session in which they received palonosetron IV pretreatment prior to naloxone-precipitated withdrawal.	Each participant had one session in which they received IV palonosetron + PO hydroxyzine pretreatment prior to naloxone-precipitated withdrawal.
Measure Participants	10	10	10
Mean (Standard Error) [units on a scale (SOWS Scale)]	6.0 (1.86)	4.0 (1.86)	3.5 (1.39)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Palonosetron, Palonosetron + Hydroxyzine
	Comments	Null Hypothesis: There will be no difference in SOWS scores when comparing the 2 treatment groups (Palonosetron & Palonosetron + Hydroxyzine) with placebo. Analysis of the data obtained in our prior study indicated that analysis of 10 individuals would provide 90% power to detect a treatment effect. Therefore, we examined the effect of three different pretreatments on naloxone-induced opiate withdrawal signs in 10 healthy individuals.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2244
	Comments	p-value represents comparison between SOWS scores at T=180 and the baseline measurements at T=-30.
	Method	Friedman Test
	Comments

Adverse Events

Time Frame	Data on adverse events was recorded throughout the duration of the study including study session #1 (week 1), study session #2 (week 2) and study session #3 (week 3).
Arm/Group Title	Placebo		Palonosetron + Placebo		Palonosetron + Hydroxyzine
Arm/Group Description	At timepoint T = 0 (minutes), healthy (non-opioid dependent, non-substance abuser) male volunteers (N=10) were pre-treated with placebo (0.9% normal saline) in a crossover study design. Participants returned for three study sessions, each one week apart to receive all three study combinations. This was followed at T = 30 by intravenous morphine (10mg/70kg). At T = 165, 10mg/70kg naloxone IV was given to precipitate opioid withdrawal. The objective opioid withdrawal score (OOWS) and subjective opioid withdrawal score (SOWS) were determined 5 and 15 minutes after naloxone administration (T = 170, 180, respectively). Baseline measurements were recorded at T = -30 and T = -15.		At timepoint T = 0 (minutes), healthy (non-opioid dependent, non-substance abuser) male volunteers (N=10) were pre-treated with palonosetron IV (0.75mg) in a crossover study design. Participants returned for three study sessions, each one week apart to receive all three study drug combinations. This was followed at T = 30 by intravenous morphine (10mg/70kg). At T = 165, 10mg/70kg naloxone IV was given to precipitate opioid withdrawal. The objective opioid withdrawal score (OOWS) and subjective opioid withdrawal score (SOWS) were determined 5 and 15 minutes after naloxone administration (T = 170, 180, respectively). Baseline measurements were recorded at T = -30 and T = -15.		At timepoint T = 0 (minutes), healthy (non-opioid dependent, non-substance abuser) male volunteers (N=10) were pre-treated with palonosetron IV (0.75mg) and hydroxyzine per os (PO) (100mg) in a crossover study design. Participants returned for three study sessions, each one week apart to receive all three study combinations. This was followed at T = 30 by intravenous morphine (10mg/70kg). At T = 165, 10mg/70kg naloxone IV was given to precipitate opioid withdrawal. The objective opioid withdrawal score (OOWS) and subjective opioid withdrawal score (SOWS) were determined 5 and 15 minutes after naloxone administration (T = 170, 180, respectively). Baseline measurements were recorded at T = -30 and T = -15.
All Cause Mortality
	Placebo		Palonosetron + Placebo		Palonosetron + Hydroxyzine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Palonosetron + Placebo		Palonosetron + Hydroxyzine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Palonosetron + Placebo		Palonosetron + Hydroxyzine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)		0/10 (0%)

Limitations/Caveats

Results are not necessarily generalizable to patients with chronic opioid exposure.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.