Identifying Key Characteristics and Habits of the Recreational Drug User

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1 Identifying Key Characteristics and Habits of the Recreational Drug User Beatrice Setnik, PhD VP Scientific & Medical Affairs, Early Phase CBI Abuse Deterrent Formulations Summit Alexandria, VA March 7, 2017

2 Introduction The non-dependent, recreational drug user is the most frequently used population in human abuse potential (HAP) studies for regulatory submissions A formal definition of recreational drug use has not been established Represent a subset of the drug abusing population Distinct patterns of use Image: INC Research, LLC 2

3 Regulatory Guidances Defining the Population FDA These studies are generally conducted in a drug-experienced, recreational user poupluation 1 HAP studies should be conducted in experienced recreational drug users who have a recent history of using drugs in the same general pharmacological class as the test drug (e.g. sedative, stimulant, opioid, or hallucinogen). Typically, subjects who qualify for the study have had numerous recent recreational experiences with the drug class. 2 Health Canada Abuse liability studies are usually carried out in non-dependent, recreational (non-therapeutic) drug users 3,4 1. Abuse-deterrent opioids-evaluation and labeling. Guidance for Industry. U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). April Assessment of abuse potential of drugs. Guidance for Industry. U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). January Guidance document: Tamper-resistant formulations of opioid drug products. Minister of Health. Health Products and Food Branch. Health Canada. March 30, Guidance document: Clinical assessment of abuse liability for drugs with central nervous system activity. Minister of Health. Health Products and Food Branch. Health Canada. December 07, INC Research, LLC 3

4 Exclusion Criteria - Defining the Population During screening, a thorough recreational drug history should be taken from each potential subject that details the drugs used, the frequency of use (overall number of times used and the typical amount used), and the time since last use. Individuals should be excluded from participation in the study if they are currently dependent on a drug (other than caffeine or nicotine) or if they are in drug treatment or recovery. 1. Assessment of abuse potential of drugs. Guidance for Industry. U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). January INC Research, LLC 4

5 Determining Drug Dependency DSM- IV vs DSM 5 Approximately 2% in a sample of 667 subjects met criteria for dependence Hopyan T, Geoffroy P,k Hirata Y, Sokolowska M, Setnik B. Redefining the recreational drug user population in human abuse potential studies. J Clin Pharmacol (6): INC Research, LLC 5

6 Drug Abusing Populations Novice/ First Time User Non-dependent, Recreational Drug User Dependent, Drug User Addict 2014 INC Research, LLC 6

7 Number of Patients Progression of Routes of Abuse Table. Route of administration of OxyContin abuse reported at the time of initial use vs at time of admission to Addictive Disease Unit in patients with and without reported concomitant pain Oral Intranasal Intravenous pain (N=53) no pain (N=51) pain (N=53) no pain (N=64) Initial Use Time of Admission Hays L, Kirsh KL, Passik SD. Seeking drug treatment for Oxycontin abuse: A chart review of consecutive admissions to a substance abuse treatment facility in Kentucky. J Natl Compr Canc Netw (3): INC Research, LLC 7

8 Percentage of Patients (%) Progression of Routes of Abuse Table. Route of administration of opioid abuse reported at the time of initial use (N=112) vs at time of admission to addiction treatment (N=133) Mean duration from initial use to time of admission = 19.2 months Initial use Time of admission oral intranasal intravenous Hays L, Profile of OxyContin addiction. J Addict Diseases (4): INC Research, LLC 8

9 Defining Recreational Drug Use General definition: Recent recreational drug use (use for non-medical reasons, e.g. to get high ) in the past year or past 30 to 90 days. e.g. recreational opioid use 10 times in the past year with 1 or more uses in the past 2-3 months 1-4 Additional criteria added for alternate routes of administration e.g. intranasal use of opioid 3 times in the past year 1,3,5 1. Schoedel KA, Rolleri RL, Faulknor JY, et al. Assessing subjective and physiologic effects following intranasal administration of a new formulation of immediate release oxycodone HCl (Oxecta TM ) tablets in nondependent recreational opioid users. J Opioid Manag. 2012; 8(5): Setnik B, Roland CL, Cleveland JM, Webster L. The abuse potential of Remoxy, an extended-release formulation of oxycodone, compared with immediate- and extendedrelease oxycodone. Pain Med. 2011; 12(4): Setnik B, Goli V, Levy-Cooperman N, Mills C, Shram M, Smith I. Assessing the subjective and physiological effects of intranasally administered crushed extended-release morphine formulations with and without a sequestered naltrexone core in recreational opioid users. Pain Res Manag. 2013; 18(4):e55 e Setnik B, Sommerville K, Goli V, Han L, Webster L. Assessment of pharmacodynamic effects following oral administration of crushed morphine sulfate and naltrexone hydrochloride extended-release capsules compared with crushed morphine sulfate controlled-release tablets and placebo in nondependent recreational opioid users. Pain Med. 2013; 14(8): Harris SC, Cipriano A, Colucci SV, et al. Intranasal Abuse Potential, Pharmacokinetics, and Safety of Once-Daily, Single-Entity, Extended-Release Hydrocodone (HYD) in Recreational Opioid Users. Pain Med. 2016; 17(5): INC Research, LLC 9

10 Recreational Opioid Users Key Characteristics Recreational opioid users in Canada (N=174) and the US (N=80) completed a survey on drug use Majority first took an opioid for nonmedical purposes between years (US; 63%) and years (Canada; 35%) Most prevalent reasons for first taking an opioid were reported as to treat pain (US 55%; Canada 26%) and to feel high or stoned (US 38%; Canada 59%) The most commonly abused opioid (past year) were oxycodone, Tylenol with codeine, and morphine in Canada and hydrocodone, oxycodone and Tylenol with codeine in the US. Oxycodone was indicated as being the opioid that is most enjoyed to get high (88% Canada, 75% US) Swallowing intact and crushed drug, as well as intranasal administration were most commonly reported Setnik B, Roland C, Goli V et al. Self-reports of prescription opioid abuse and diversion among recreational opioid users in a Canadian and a United States city. J Opioid Manag (6): INC Research, LLC 10

11 Recreational Opioid Users Key Characteristics Recreational opioid users in Canada (N=174) and the US (N=80) completed a survey on drug use The most common sources of opioid was either free (47% CAN-66% US) or bought (52% US 60% CAN) from a friend/family member Bought from a stranger (13% US 25% CAN) or obtained from one doctor (10% CAN-12% US) were the next most common sources Most subjects in Canada (74%) and US (66%) indicated using other drugs with opioids to get high Marijuana (79 CAN; 92% US) and alcohol (65 US -68% CAN) were the most commonly combined drugs Setnik B, Roland C, Goli V et al. Self-reports of prescription opioid abuse and diversion among recreational opioid users in a Canadian and a United States city. J Opioid Manag (6): INC Research, LLC 11

12 Recreational Drug Users Key Characteristics In a database of 5018 self-reported recreational opioid users Most were males (72.7%) compared to females (27.3%) and between the ages of (89.7%) Less than half were smokers (45%) with fairly even distribution across males (45.9%) and females (42.6%) The majority preferred taking opioids orally (51.8%) followed by intranasal (36%), intravenous (10.2%) and patch (2.0%) Other reported drugs of abuse included THC (52%), sedatives (20%), stimulants (18%) and hallucinogens (10%) 2014 INC Research, LLC 12

13 Recreational Drug Users Key Characteristics In a database of 120 self-reported recreational opioid users The mean number of reported alcoholic drinks/week was 5.87 (5.17 females; range 0-24); 6.06 males; range 0-60) Opioid Used Oxycodone Oxycodone/APAP Codeine Oxycontin Morphine Codeine/Tylenol #3 Hydrocodone Hydromorphone/Dilaudid Opium Vicodin Fentanyl Heroin Oral (N=105) Route of Administration Intranasal (N=97) Average Number of Times Used in Past 8 Weeks Smoking/ Inhalation (N=4) Oral Intranasal Smoking/ Inhalation 64 (61.0) 56 (57.7) (21.34) 18.9 (31.55) - 39 (37.1) 26 (26.8) (42.21) 17.8 (39.80) - 23 (21.9) 4 (4.1) 1 (25.0) 18 (17.1) 21 (21.6) 1 (25.0) 10 (9.5) 10 (10.3) 0 11 (10.5) 3 (3.1) (7.54) 17.7 (14.72) 10.5 (9.43) 9.0 (9.67) 6 (5.7) 5 (5.2) (24.75) 6 (5.7) 8 (8.2) (3.69) 4.0 (2.00) 14.1 (13.29) 10.2 (8.21) 2.0 (-) 21.0 (8.22) 7.7 (10.50) 1 (1.0) 0 1 (25.0) (1.0) (2.1) (7.2) 2 (50.0) (-) 3.0 (-) 10.0 (-) (5.66) 9.7 (8.36) (-) 2014 INC Research, LLC 13

14 Perspectives from Recreational Drug Users Subject interviews in 5 recreational drug users Don t consider themselves as abusers Ability to function at work/home Take drugs to feel good, reduce stress/anxiety Ways of abusing OxyNEO (Contin) (e.g. microwaving) but lose drug in process Prefer immediate release formulations because less filler Don t want to spend more than 5 minutes on tampering drugs Prescription opioids are readily accessible on the street (high quantities/little time) Tend to snort smaller volumes over the course of an evening Studies shouldn t limit age to 55 years 2014 INC Research, LLC 14

15 Study Considerations - Recreational Drug Users Drug abuse history Routes of administration Smoking status Scheduling (including smoking breaks) Positive urine drug screens (10-15% at screening) Contraband items Subject safety 2014 INC Research, LLC 15

16 Summary Standardized definition needed Recreational users are a distinct drug using population Have opioid/route preferences Special considerations compared to health volunteer populations 2014 INC Research, LLC 16

17 For more information contact: Beatrice Setnik, PhD VP Scientific & Medical Affairs, INC Research INC Research, LLC 17

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