Trial Outcomes & Findings for A Comparison of the Addiction Liability of Hydrocodone and Sustained Release Morphine (NCT NCT00314340)

Results Overview

The subjective effects of the study drug were evaluated with 3 subscales of the Addiction Research Center Inventory (ARCI). The subscales studied included Morphine-Benzedrine Group which measured euphoria (0-16 with higher numbers indicating more euphoria), the Phenobarbital-Chorpromazine-Alcohol Group which measured sedation (-3 to +11 with higher scores indicating more sedation), and the Lysergic Acid Diethylmide Group which measured dysphoria and agitation (-4 to +10 with higher scores indicating more dysphoria). This inventory consists of 49 true/ false questions which survey major domains of drug effects. The ARCI was measured at six timepoints. Of interest were trough sedation, peak euphoria, and trough dysphoria.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

12 participants

Primary outcome timeframe

0, 60, 120, 180, 240, or 300 minutes

Results posted on

2017-05-30

Participant Flow

Participants were recruited from the UC Davis Medical Center Pain and VA Northern California Pain Clinics in 2007-8. They had to have had chronic pain for more than 3 months and to have self-escalated their dose of a short-acting opioid (i.e., a combination product containing hydrocodone, codeine, or oxycodone)prescribed to treat their pain.

Of 55 patients approached, 18 were evaluated, and 14 met entry criteria and were enrolled. Two withdrew before starting the study. One subject withdrew after starting the study because of insufficient pain relief from the study medications leaving 35 visits by 12 patients for analysis.

Participant milestones

Participant milestones
Measure	All Participants All participants were randomized to receive the ER morphine tablets, 45 mg, hydrocodone 30 mg plus N-acetyl-para-aminophenol 975 mg, or placebo in a 3 way cross over design.
Overall Study STARTED	12
Overall Study ER Morphine	11
Overall Study Hydrocodone Plus APAP	12
Overall Study Placebo	12
Overall Study COMPLETED	11
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	All Participants All participants were randomized to receive the ER morphine tablets, 45 mg, hydrocodone 30 mg plus N-acetyl-para-aminophenol 975 mg, or placebo in a 3 way cross over design.
Overall Study lost interest	1

Baseline Characteristics

A Comparison of the Addiction Liability of Hydrocodone and Sustained Release Morphine

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Prescription Opioid Abusers n=12 Participants The subjective effects of the study drug were evaluated with the short form of the Addiction Research Center Inventory (ARCI. This inventory consists of 49 true/ false questions which survey major domains of drug effects. Participants indicated the pleasurable effects or desirability of the medications on 4 locally developed drug-liking ratings: craving, liking, strong desire, and "want more pain medication." Ratings were made on a 100-mm VAS anchored with 0 at the low end and 10 at the high end. Participants also responded to 11 locally developed drug-effect ratings to assess psychoactive effects. Ratings were again made on a 100-mmVAS anchoredwith 0 at the lowend and 10 at the high end for:"on cloud 9," "high," "good drug effect," "bad drug effect," "impaired,""stoned," "sedated," "confused," "nauseated from," "anxious," and "down". The rating levels over a six hour period were examined to explore the timing of these effects.
Age, Categorical <=18 years	0 Participants n=99 Participants
Age, Categorical Between 18 and 65 years	12 Participants n=99 Participants
Age, Categorical >=65 years	0 Participants n=99 Participants
Age, Continuous	46 years STANDARD_DEVIATION 4 • n=99 Participants
Sex: Female, Male Female	4 Participants n=99 Participants
Sex: Female, Male Male	8 Participants n=99 Participants
Region of Enrollment United States	12 participants n=99 Participants

PRIMARY outcome

Timeframe: 0, 60, 120, 180, 240, or 300 minutes

Population: Treatment effects at baseline, 60, 120, 180, 240, and 300 min were assessed with repeated measures ANOVA. A liner mixed-effects model with inclusion of interaction terms (1) treatment and time and (2) random order visit number and time was performed.

The subjective effects of the study drug were evaluated with 3 subscales of the Addiction Research Center Inventory (ARCI). The subscales studied included Morphine-Benzedrine Group which measured euphoria (0-16 with higher numbers indicating more euphoria), the Phenobarbital-Chorpromazine-Alcohol Group which measured sedation (-3 to +11 with higher scores indicating more sedation), and the Lysergic Acid Diethylmide Group which measured dysphoria and agitation (-4 to +10 with higher scores indicating more dysphoria). This inventory consists of 49 true/ false questions which survey major domains of drug effects. The ARCI was measured at six timepoints. Of interest were trough sedation, peak euphoria, and trough dysphoria.

Outcome measures

Outcome measures
Measure	ER Morphine Tablets, 45mg n=11 Participants Scores of the 5 Addiction Research Center Inventory dimensions did not change significantly between baseline and 300 min under any treatment condition.	Hydrocodone 30 mg Plus N-acetyl-para-aminophenol 975 mg n=12 Participants These findings all argue against the hypothesis that the hydrocodone product induced a greater euphoric or reinforcing effect than that of ER morphine.	Placebo n=12 Participants
3 Scores on the Addiction Research Center Inventory (ARCI) trough sedation	7.6 scores on a scale Standard Deviation 1	5.4 scores on a scale Standard Deviation 0.9	5.2 scores on a scale Standard Deviation 0.8
3 Scores on the Addiction Research Center Inventory (ARCI) peak euphoria	3.3 scores on a scale Standard Deviation 0.8	4.6 scores on a scale Standard Deviation 0.9	3.5 scores on a scale Standard Deviation 1.0
3 Scores on the Addiction Research Center Inventory (ARCI) trough agitation	4.7 scores on a scale Standard Deviation 0.8	4.2 scores on a scale Standard Deviation 0.6	3.6 scores on a scale Standard Deviation 0.5

Adverse Events

Prescription Opioid Abusers

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

Barth Wilsey MD

UC Davis Medical Center

Phone: 916-843-7165

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place