Trial Outcomes & Findings for Palonosetron and Hydroxyzine to Reduce Opioid Withdrawal (NCT NCT00661674)

NCT ID: NCT00661674

Last Updated: 2017-06-05

Results Overview

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

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

10 participants

Primary outcome timeframe

Change from baseline in OOWS score at 180 minutes (15 minutes post naloxone administration)

Results posted on

2017-06-05

Participant Flow

Participant milestones

Participant milestones
Measure
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: Combo Week 3: Palonosetron
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: Combo Week 3: Placebo
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: Combo Week 2: Placebo Week 3: Palonosetron
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 Week 3: Combo
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: Combo Week 2: Palonosetron Week 3: Placebo
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 Week 2: Placebo Week 3: Combo
Overall Study
STARTED
2
2
2
1
2
1
Overall Study
COMPLETED
2
2
2
1
2
1
Overall Study
NOT COMPLETED
0
0
0
0
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Palonosetron and Hydroxyzine to Reduce Opioid Withdrawal

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Overall Study
n=10 Participants
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).
Age, Continuous
21.1 years
STANDARD_DEVIATION 2.18 • n=5 Participants
Sex: Female, Male
Female
0 Participants
n=5 Participants
Sex: Female, Male
Male
10 Participants
n=5 Participants
Region of Enrollment
United States
10 participants
n=5 Participants

PRIMARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure
Placebo
n=10 Participants
Each participant had one session in which they received a placebo tablet pretreatment prior to naloxone-precipitated withdrawal.
Palonosetron
n=10 Participants
Each participant had one session in which they received palonosetron IV pretreatment prior to naloxone-precipitated withdrawal.
Palonosetron + Hydroxyzine
n=10 Participants
Each participant had one session in which they received IV palonosetron + PO hydroxyzine pretreatment prior to naloxone-precipitated withdrawal.
OOWS Score
3.5 units on a scale (OOWS Scale)
Standard Error 0.76
1.0 units on a scale (OOWS Scale)
Standard Error 0.37
0 units on a scale (OOWS Scale)
Standard Error 0.13

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure
Placebo
n=10 Participants
Each participant had one session in which they received a placebo tablet pretreatment prior to naloxone-precipitated withdrawal.
Palonosetron
n=10 Participants
Each participant had one session in which they received palonosetron IV pretreatment prior to naloxone-precipitated withdrawal.
Palonosetron + Hydroxyzine
n=10 Participants
Each participant had one session in which they received IV palonosetron + PO hydroxyzine pretreatment prior to naloxone-precipitated withdrawal.
SOWS Score
6.0 units on a scale (SOWS Scale)
Standard Error 1.86
4.0 units on a scale (SOWS Scale)
Standard Error 1.86
3.5 units on a scale (SOWS Scale)
Standard Error 1.39

Adverse Events

Placebo

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Palonosetron + Placebo

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Palonosetron + Hydroxyzine

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Larry Chu

Stanford University School of Medicine

Phone: (650) 723-6632

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place