Problems of Drug
`Dependence, 1994:
`Proceedings of the 56th Annual
`Scientific Meeting, The College on Problems
`of Drug Dependence, Inc.
`
`Volume II: Abstracts
`
`Editor:
`
`Louis S. Harris, Ph.D.
`
`NIDA Research Monograph 153
`1995
`
`U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
`Public Health Service
`National Institutes of Health
`
`National Institute on Drug Abuse
`5600 Fishers Lane
`Rockville, MD 20857
`
`APOTEX EXHIBIT 1011
`Apotex v. Alkermes
`IPR2025-00514
`
`

`

`ACKNOWLEDGMENT
`
`The College on Problems of Drug Dependence, Inc., an independent,
`nonprofit organization, conducts drug testing and evaluations for academic
`institutions, government, and industry. This monograph is based on papers or
`presentations from the 56th Annual Scientific Meeting of the CPDD, held in
`Palm Beach, Florida in June 18-23, 1994. In the interest of rapid
`dissemination, it is published by the National Institute on Drug Abuse in its
`Research Monograph series as reviewed and submitted by the CPDD. Dr.
`Louis S. Harris, Department of Pharmacology and Toxicology, Virginia
`Commonwealth University was the editor of this monograph.
`
`COPYRIGHT STATUS
`
`The National Institute on Drug Abuse has obtained permission from the
`copyright holders to reproduce certain previously published material as noted
`in the text. Further reproduction of this copyrighted material is permitted
`only as part of a reprinting of the entire publication or chapter. For any other
`use, the copyright holder's permission is required. All other material in this
`volume except quoted passages from copyrighted sources is in the public
`domain and may be used or reproduced without permission form the Institute
`or the authors. Citation of the source is appreciated.
`
`Opinions expressed in this volume are those of the authors and do not
`necessarily reflect the opinions or official policy of the National Institute on
`Drug Abuse or any other part of the Department of Health and Human
`Services.
`
`The U.S. Government does not endorse or favor any specific commercial
`product or company. Trade, proprietary, or company names appearing in this
`publication are used only because they are considered essential in the context
`of the studies reported herein.
`
`NIH Publication No. 95-3883
`Printed 1995
`
`NIDA Research Monographs are indexed in the Index Medicus. They are
`selectively included in the coverage of American Statistics Index, BioSciences
`lnfonnation Service, Chemical Abstracts, Current Contents, Psychological
`Abstracts, and Psychopharmacology Abstracts.
`
`ii
`
`

`

`TOLERABILITY STUDY OF A DEPOT FORM OF
`NALTREXONE SUBSTANCE ABUSERS
`T. N. Alim, B. Tai, C. N. Chiang, T. Green, R. B. Rosse,
`T. Lindquist, and S. I. Deutsch
`
`INTRODUCTION: Oral naltrexone has been associated with a high early
`dropout rate. A injectable depot fmm of naltrexone could improve compliance in
`otherwise poorly motivated opiate addicts. A previous sustained release
`preparation of naltrexone using 1.5 mm diameter spheres showed opiate receptor
`blockade but some subjects developed tissue inflammation. In the current study,
`we evaluate the safety and tolerability of a depot form of naltrexone with smaller
`microspheres (105-150 Jlm). SUBJECTS: Eight cocaine dependent males
`( 34.1 years of age, range = 23-45) with no evidence of opiate dependence and
`in good physical health were subjects in the study. One subject on the high dose
`was excluded due to adverse effect of the morphine challenge. DESIGN: The
`study was a double-blind, placebo-controlled two dose inpatient/outpatient
`study. Subjects were evaluated for 64 days. LOW DOSE PHASE (n=4, 3 drug,
`1 placebo): Subjects received 1.2 cc (103 mg) of naltrexone preparation or
`placebo subcutaneously in triceps of each arm (one rum received placebo). When
`subjects did not experience severe side effects to this low dose after 64 days, the
`high dose phase was conducted. HIGH DOSE PHASE (n=4, 3 drug, 1
`placebo): Subjects received 2.4 cc (206 mg) of naltrexone preparation or placebo
`in a similar fashion to the low dose group.-Plasma naltrexone levels were
`obtained during both phases. RESULTS: Subjects generally reported mild
`injection site pain; erythema was observed in most subjects, but was not severe
`and subsided over the course of the study. Induration without pain or discomfort
`was the most persistent side effect. Blood chemistries and CBC did not change
`significantly over the course of the study. Morphine challenge: Subjects in the
`high dose group were challenged with 10 mg IV morphine on days 8, 15, 22,
`and 29 of the inpatient stay. Opiate receptor blockade was observed although
`physiologic and subjective responses were variable. CONCLUSIONS: The
`depot formulation of naltrexone used in this study appeared well-tolerated and
`resulted in plasma levels of 1 ng/ml or greater for more than three weeks. Higher
`doses of opiate agonists may better assess efficacy of this depot formulation of
`naltrexone. Future studies to assess the acceptability, tolerance, and efficacy of
`depot naltrexone in outpatient detoxified opiate addicts appear indicated.
`
`ACKNOWLEDGEMENT:
`
`This research was supported by Inter-Agency Agreement RA-ND-90-10
`between the National Institute on Drug Abuse and the Department of Veteran's
`Affairs.
`
`AFFIT...IA TION:
`
`National Institute on Drug Abuse and the Department of Veteran's Affairs,
`Rockville, MD
`
`253
`
`