Abstract Details

Title A Drug Candidate for Improving Opioid Analgesia and Attenuating Dependence and Tolerance: An Exploratory Trial of Ibudilast in Morphine Withdrawal and Analgesia in Heroin Addicts

Topic Clinical Neurophysiology

Presentation(s) P07 - (-)

Poster/Presentation
Number 183

Objective

Background BACKGROUND: Previous animal studies have established that systemic ibudilast administration can improve the analgesic potency and efficacy of therapeutic doses of opioids such as morphine and oxycodone. Moreover, in repeat-dose settings, ibudilast attenuated opioid-dependent increases in nucleus accumbens dopamine levels, spontaneous or precipitated opioid withdrawal, and morphine tolerance. Modulation of glial cell activation has been implicated as a general mechanism of these ibudilast actions.

Design/Methods DESIGN/METHODS: Subjects were randomized 1:1:1 (n=10 each) to placebo, low-dose (20 mg BID, 40 mg/day) ibudilast (aka AV411, MN-166), or high-dose AV411 (40 mg BID, 80 mg/day) on day 8 after baseline accommodation to oral morphine (30 mg, QID), which was sustained over the first 14 days. Assessment of opioid analgesic (time and pain sensation of hand in ice water) and physiological (pupil diameter) effects were measured at baseline (Day 4) and at treatment steady state (Day 11) with oral oxycodone dosing (0, 25, & 50 mg).

Results RESULTS: AV411 was well-tolerated in the subjects with no SAEs, no discontinuations due to treatment, and no impact on opioid respiratory changes relative to placebo. Spontaneous withdrawal was monitored between Days 15-21 after final morphine dosing the night of Day 14. Dose-related ibudilast efficacy was observed: Subjective opioid withdrawal scale (SOWS) symptoms and analgesia (McGill pain questionnaire) were significantly (p<0.05) modulated by 80 mg/day AV411 compared to placebo controls and opioid-related pupil constriction was greater in the 80 mg/d AV411 group vs placebo (p<0.05) implicating lessened tolerance.

Conclusions CONCLUSIONS: These data suggest that ibudilast may be useful for treating opioid withdrawal, but further clinical validation is warranted.

Authors/Disclosures
Sandra Comer, PhD PRESENTER	No disclosure on file
Kirk W. Johnson, PhD (XOMA Corp)	No disclosure on file
Massimo Filippi, MD, FAAN (Ospedale San Raffaele, Neuroimaging Research Unit)	Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion, Almirall, Biogen, Merck, Novartis, Roche, Sanofi. Dr. Filippi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion, Biogen, Bristol-Myers Squibb, Merck, Novartis, Roche, Sanofi, Sanofi-Aventis, Sanofi-Genzyme, Takeda. Dr. Filippi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer, Biogen, Celgene, Chiesi Italia SpA, Eli Lilly, Genzyme, Janssen, Merck-Serono, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda, and TEVA. Dr. Filippi has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Nature. The institution of Dr. Filippi has received research support from Biogen Idec, Merck-Serono, Novartis, Roche, the Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla.

��ɫ��

��ɫ��