A Phase 3 placebo-controlled, double-blind, multi-site trial of the alpha-2-adrenergic agonist, lofexidine, for opioid withdrawal.

Abstract

CONTEXT:

Lofexidine is an alpha-2-adrenergic receptor agonist that is approved in the United Kingdom for the treatment of opioid withdrawal symptoms. Lofexidine has been reported to have more significant effects on decreasing opioid withdrawal symptoms with less hypotension than clonidine.

OBJECTIVE:

To demonstrate that lofexidine is well tolerated and effective in the alleviation of observationally defined opioid withdrawal symptoms in opioid dependent individuals undergoing medically supervised opioid detoxification as compared to placebo.

DESIGN:

An inpatient, Phase 3, placebo-controlled, double-blind, randomized multi-site trial with three phases: (1) opioid agonist stabilization phase (days 1-3), (2) detoxification/medication or placebo phase (days 4-8), and (3) post detoxification/medication phase (days 9-11).

SUBJECTS:

Sixty-eight opioid dependent subjects were enrolled at three sites with 35 randomized to lofexidine and 33 to placebo.

MAIN OUTCOME MEASURE:

Modified Himmelsbach Opiate Withdrawal Scale (MHOWS) on study day 5 (second opioid detoxification treatment day).

RESULTS:

Due to significant findings, the study was terminated early. On the study day 5 MHOWS, subjects treated with lofexidine had significantly lower scores (equating to fewer/less severe withdrawal symptoms) than placebo subjects (least squares means 19.5+/-2.1 versus 30.9+/-2.7; p=0.0019). Lofexidine subjects had significantly better retention in treatment than placebo subjects (38.2% versus 15.2%; Log rank test p=0.01).

CONCLUSIONS:

Lofexidine is well tolerated and more efficacious than placebo for reducing opioid withdrawal symptoms in inpatients undergoing medically supervised opioid detoxification.

• Authors: Elmer Yu, Karen Miotto, Evaristo Akerele, Ann Montgomery, Ahmed Elkashef, Robert Walsh, Ivan Montoya, Marian W Fischman, Joseph Collins, Frances McSherry, Kathy Boardman, David K Davies, Charles P O'Brien, Walter Ling, Herbert Kleber, Barbara H Herman
• Journal: Drug and alcohol dependence (Drug Alcohol Depend) Vol. 97 Issue 1-2 Pg. 158-68 (Sep 01 2008) ISSN: 0376-8716 [Print] Ireland
• PMID: 18508207 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Adrenergic alpha-Agonists
• Analgesics, Opioid
• Clonidine
• lofexidine

Topics

• Adrenergic alpha-Agonists (adverse effects, therapeutic use)
• Adult
• Analgesics, Opioid
• Clonidine (adverse effects, analogs & derivatives, therapeutic use)
• Data Collection
• Double-Blind Method
• Female
• Humans
• Male
• Middle Aged
• Psychiatric Status Rating Scales
• Substance Abuse Detection
• Substance Withdrawal Syndrome (drug therapy)
• Survival Analysis
• Treatment Outcome