Lofexidine Phase 3 Studies Demonstrate Reduced Opioid Withdrawal Symptoms
MAY 10, 2018
Mark Pirner, MD, PhDData from a pooled analysis presented at the American Psychiatric Association’s Annual Meeting, concluded that lofexidine (LUCEMYRA) safely reduces opioid withdrawal symptoms at 3.2 mg/day and 2.4 mg/day to a clinically meaningful extent, facilitating opioid discontinuation treatment.
Investigators from US WorldMeds extracted data from 2 phase 3 placebo-controlled studies that evaluated withdrawal symptoms during the first 7 days of withdrawal from short-acting opioids (heroin or opioid analgesics).
“A better understanding of opioid withdrawal represents an opportunity in the prevention, treatment and recovery process for physical opioid dependence and opioid use disorder,” co-author, Mark Pirner, MD, PhD, Senior Medical Director, Clinical Research and Medical Affairs, US WorldMeds, told MD Magazine. “The lofexidine data demonstrate that, compared with placebo, study participants treated with LUCEMYRA experienced less severe withdrawal symptoms and were significantly more likely to complete opioid withdrawal treatment.
The 2 studies evaluated lofexidine for treatment of opioid withdrawal symptoms in men and women (≥18 years old) undergoing abrupt discontinuation from short-acting opioids like heroin, oxycodone and hydrocodone.
In study 1, subjects were randomized to placebo or lofexidine 3.2 mg/day for 5 days—all subjects received placebo on days 6 and 7— and in study 2, subjects were randomized to placebo or lofexidine 3.2 mg/day or lofexidine 2.4 mg/day for 7 days. The severity of symptoms was assessed per the Short Opiate Withdrawal Scale-Gossop (SOWS-G).
The pooled database studied 865 subjects: 585 randomized to lofexidine and 280 randomized to placebo.
A greater proportion of subjects from the 242 participants in the lofexidine groups (41.3%) completed the 7-day trial versus 77 participants in placebo (27.4%). The most common discontinuation reasons were withdrawal of consent (29% of lofexidine subjects, 32.4% of placebo subjects) and lack of efficacy (15.7% of lofexidine subjects, 31.7% of placebo subjects).
“In both studies, lofexidine treatment was associated with a significantly higher completion rate compared with placebo treatment,” Pirner said. “Patients in the placebo group were more likely to drop out of the study prematurely due to lack of efficacy than patients treated with LUCEMYRA.”
Adverse effects were categorized as related or not related to opioid withdrawal, and most subjects (>80%) reported opioid-withdrawal-related adverse effects—these were more common in the placebo group.
The most common effects that were not related to opioid withdrawal and more common in the lofexidine group were orthostatic hypotension, hypotension and bradycardia.
Most adverse effects were mild or moderate, however serious adverse effects, though infrequent, were reported in 2.1% of lofexidine-treated subjects and 3.6% of placebo-treated subjects. The serious adverse effects were related to hypotension, bradycardia or brief prolonged hospitalization to stabilize withdrawal symptoms.
In the pooled database, QTcF prolongation was reported as an adverse effect in 3 lofexidine-treated subjects and 5 placebo-treated subjects.
Investigators concluded that in the large, pooled database of 865 opioid-dependent subjects, both doses were significantly superior for reducing opioid withdrawal symptoms during the peak.
Patients treated with lofexidine were significantly more likely to complete the 7-day withdrawal period versus placebo-treated subjects. Lofexidine may expand treatment options for withdrawal management when buprenorphine and methadone are unavailable or undesirable.
“When symptoms of withdrawal are misunderstood or under-treated, it can present a significant barrier to successful opioid discontinuation,” Pirner said. “If approved, LUCEMYRA may support people in their individual journey to recovery, which always includes completing withdrawal.”
Lofexidine is an alpha-2 adrenergic receptor agonist that reduces norepinephrine signaling in the brain. It’s currently under review for the management of opioid withdrawal symptoms and facilitation of completion of opioid withdrawal.
There are currently no US Food and Drug Administration (FDA)-approved non-opioid medications available for opioid withdrawal symptoms.
“If approved, LUCEMYRA may help people find meaningful relief from opioid withdrawal symptoms, and in turn, better manage withdrawal and progress to their post-withdrawal treatment plans,” Pirner concluded.
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