Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Palonosetron and Hydroxyzine to Reduce Opioid Withdrawal

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00661674
Recruitment Status : Completed
First Posted : April 18, 2008
Results First Posted : June 5, 2017
Last Update Posted : June 5, 2017
Sponsor:
Information provided by (Responsible Party):
Larry Fu-nien Chu, Stanford University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Triple (Participant, Care Provider, Outcomes Assessor);   Primary Purpose: Treatment
Condition Substance-Related Disorders
Interventions Drug: Palonosetron
Drug: Hydroxyzine
Other: Placebo
Enrollment 10
Recruitment Details  
Pre-assignment Details  
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
Hide 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 [1] 2 [2] 2 [3] 2 [4] 1 [5] 2 [6] 1 [7]
Completed 2 [8] 2 [9] 2 [10] 1 [11] 2 [12] 1 [13]
Not Completed 0 0 0 0 0 0
[1]
Only 1 intervention per sequence was given each week based on sequence assignment
[2]
Participants 1 & 10 were assigned to sequence 1
[3]
Participants 2 & 3 were assigned to sequence 2
[4]
Participants 4 & 7 were assigned to sequence 3
[5]
Participant 5 was assigned to sequence 4
[6]
Participants 6 & 8 were assigned to sequence 5
[7]
Participant 9 was assigned to sequence 6
[8]
Participants 1 & 10 completed sequence 1
[9]
Participants 2 & 3 completed sequence 2
[10]
Participants 4 & 7 completed sequence 3
[11]
Participant 5 completed sequence 4
[12]
Participants 6 & 8 completed sequence 5
[13]
Participant 9 completed sequence 6
Arm/Group Title Overall Study
Hide 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 Number of Baseline Participants 10
Hide Baseline Analysis Population Description
10 healthy male volunteers recruited from the San Francisco Bay Area. All study sessions took place at the Stanford University School of Medicine, Department of Anesthesia.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 10 participants
21.1  (2.18)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants
Female
0
   0.0%
Male
10
 100.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 10 participants
10
1.Primary Outcome
Title OOWS Score
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Palonosetron Palonosetron + Hydroxyzine
Hide 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.
Overall Number of Participants Analyzed 10 10 10
Mean (Standard Error)
Unit of Measure: units on a scale (OOWS Scale)
3.5  (0.76) 1.0  (0.37) 0  (0.13)
Hide 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 [Not Specified]
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 [Not Specified]
2.Secondary Outcome
Title SOWS Score
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Palonosetron Palonosetron + Hydroxyzine
Hide 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.
Overall Number of Participants Analyzed 10 10 10
Mean (Standard Error)
Unit of Measure: units on a scale (SOWS Scale)
6.0  (1.86) 4.0  (1.86) 3.5  (1.39)
Hide 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 [Not Specified]
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 [Not Specified]
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).
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo Palonosetron + Placebo Palonosetron + Hydroxyzine
Hide 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 (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Hide Serious Adverse Events
Placebo Palonosetron + Placebo Palonosetron + Hydroxyzine
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/10 (0.00%)   0/10 (0.00%)   0/10 (0.00%) 
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Placebo Palonosetron + Placebo Palonosetron + Hydroxyzine
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/10 (0.00%)   0/10 (0.00%)   0/10 (0.00%) 
Results are not necessarily generalizable to patients with chronic opioid exposure.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Larry Chu
Organization: Stanford University School of Medicine
Phone: (650) 723-6632
EMail: lchu@stanford.edu
Publications:
Layout table for additonal information
Responsible Party: Larry Fu-nien Chu, Stanford University
ClinicalTrials.gov Identifier: NCT00661674    
Other Study ID Numbers: SU-04152008-1099
First Submitted: April 15, 2008
First Posted: April 18, 2008
Results First Submitted: February 8, 2016
Results First Posted: June 5, 2017
Last Update Posted: June 5, 2017