| The American Academy of Pain Medicine Annual Meeting Home Page
|
 |
24th Annual Meeting February 13-16, 2008 Orlando, FL |
|
© 2006 American Academy of Pain Medicine |
||
Thursday, February 14, 2008
150
ALO-01, An Investigational Extended-Release Opioid Formulation Containing Morphine Sulfate and Sequestered Naltrexone: Pharmacodynamic (Drug Liking) Effects
Increased non-medical opioid use has created need for products with reduced abuse-liability.1 ALO-01, an investigational extended-release opioid (IND application for moderate-to-severe chronic pain), contains polymer-coated morphine sulfate pellets with a sequestered naltrexone core intended for release upon crushing/chewing/dissolving. This study assessed pharmacodynamic (eg, drug liking) effects of ALO-01 taken orally as-intended (whole) vs tampered (crushed—mortar and pestle).
Methods
Randomized, double-blind, triple-dummy, single-dose, 4-way crossover study. Nondependent subjects, aged 18-55y, history of recreational opioid use, were recruited by DecisionLine CRC (research ethics board–approved protocol). Qualified subjects who tolerated 120mg morphine sulfate solution [MSS] and discriminated morphine from placebo were administered 1 of 4 study treatments per arm (placebo; two 60mg ALO-01 capsules whole [ALO-01W]; pellets from two 60mg ALO-01 capsules crushed [ALO-01C]; 120mg MSS). Washout was 14-21d. Morphine pharmacokinetics were evaluated for 24h. Pharmacodynamic endpoints: visual analog scale (VAS) for Drug Liking (0=strong disliking; 100=strong liking) and “Feeling High” (0=definitely not; 100=definitely so); Cole/ARCI Stimulation-Euphoria and Abuse Potential scales (higher scores=higher stimulation-euphoria and abuse potential)2; Subjective Drug Value (SDV, perceived dollar value).3
Results
Subjects (n=32) reported similar VAS for Drug Liking and High with ALO-01W vs ALO-01C (Drug Liking, placebo=52.2, ALO-01W=67.6, ALO-01C=68.1, MSS=89.5; High, placebo=15.2, ALO-01W=60.6, ALO-01C=55.0, MSS=90.4). Similarly, no significant differences in mean maximum Stimulation-Euphoria (placebo=6.9, ALO-01W=10.8, ALO-01C=11.9, MSS=18.4) or Abuse Potential (placebo=3.4, ALO-01W=5.9, ALO-01C=6.3, MSS=8.7). Mean maximum SDVs: placebo=$2.73, ALO-01W=$14.22, ALO-01C=$13.72, MSS=$28.85 (p=NS, ALO-01W vs ALO-01C). Placebo yielded lower scores (exception: p=NS ALO-01W vs placebo, Stimulation-Euphoria) and MSS yielded higher scores vs ALO-01W or ALO-01C. Mean Cmax and median Tmax were similar between ALO-01C (80.6ng/mL, 1.0h) and MSS (92.5ng/mL, 1.0h), but different from ALO-01W (18.4ng/mL, 8.0h).
Conclusion
When ALO-01 was crushed, the released naltrexone successfully abated the drug liking/euphoria effects of the morphine and rendered it no more desirable to recreational opioid abusers than intact product.
References: 1. Wright C, Kramer ED, Zalman MA, Smith MY, Haddox JD. Risk identification, risk assessment, and risk management of abusable drug formulations. Drug Alcohol Depend. 2006;83(Suppl 1):S68-S76.
2. Cole, J. O., Orzack, M. H., Beake, B., Bird, M., & Bar-Tal, Y. (1982). Assessment of the abuse liability of buspirone in recreational sedative users. J Clin Psychiatry, 43, 69-75.
3. Griffiths RR, Bigelow GE, Ator NA. Principles of initial experimental drug abuse liability assessment in humans. Drug Alcohol Depend. 2003;70(3 Suppl):S41-S54.
Funding: Alpharma Pharmaceuticals, LLC (formerly Alpharma Branded Products Division Inc.)provided support for this research project.
Conflict of Interest Disclosure: Alpharma Pharmaceuticals LLC, Employee
See more of Poster Abstracts
See more of The 24th Annual Meeting