Prescription Opioid Addiction Treatment Study (POATS)

• The Number of Participants Attaining Successful Opioid Use Outcome by Counseling Condition at End of Phase 1 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  In Phase 1, successful outcome was defined as completing week 12 with self-reported opioid use on no more than 4 days in a month, absence of 2 consecutive opioid-positive urine test results, no additional substance use disorder treatment (other than self-help), and no more than 1 missing urine sample during the 12 weeks.
• The Number of Participants Attaining Successful Opioid Use Outcome by Counseling Condition, Phase 2 End of Treatment [ Time Frame: 12 weeks in Phase 2 period (i.e., 24 weeks into the study) ] [ Designated as safety issue: No ]
  In phase 2, successful outcome was defined as abstaining from opioids during week 12 (the final week of buprenorphine-naloxone stabilization) and during at least 2 of the previous 3 weeks (weeks 9-11). This outcome measure required substantial improvement but not complete abstinence.

• The Number of Participants Attaining Successful Opioid Use Outcome by Counseling Condition Phase 2, 8-week Posttreatment Follow-up [ Time Frame: 24 weeks in Phase 2 period (i.e., 36 weeks into the study) ] [ Designated as safety issue: No ]
  A planned secondary outcome, successful outcome at week 24, that is, 8 weeks after completion of buprenorphine-naloxone taper, was defined the same as at week 12 of Phase 2, that is abstinent from opioids during week 24 and at least 2 of the previous 3 weeks.
• The Number of Participants Attaining Successful Opioid Use Outcomes in Phase 1 by Chronic Pain Condition [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  As a planned secondary analysis, we examined the impact of the two Phase 1 stratification variables on the primary end points. Patients were designated at baseline as having current chronic pain if they reported pain "other than everyday kinds of pain" excluding withdrawal-related pain, for at least 3 months.
• The Number of Participants Attaining Successful Opioid Use Outcomes in Phase 2 by Chronic Pain Condition [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  As a planned secondary analysis, we examined the impact of the two Phase 1 stratification variables on the primary end points. Patients were designated at baseline as having current chronic pain if they reported pain "other than everyday kinds of pain" excluding withdrawal-related pain, for at least 3 months.
• The Number of Participants With and Without Any Lifetime Use of Heroin Attaining Successful Opioid Use Outcomes in Phase 1 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  As a planned secondary analysis, we examined the impact of the two phase 1 stratification variables on the primary outcome.
• The Number of Participants With and Without Any Lifetime Use of Heroin Attaining Successful Opioid Use Outcomes in Phase 2 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  As a planned secondary analysis, we examined the impact of the two phase 1 stratification variables on the primary outcome.

• Withdrawal symptoms
• Craving symptoms
• Reduction in drug use
• Effect of pain
• Safety

The purpose of this study is to determine whether treatment outcome for subjects dependent on prescription opioid analgesics can be improved by adding individual drug counseling to the prescription of buprenorphine/naloxone with standard medical management. This will be examined during: a) an initial four-week treatment with taper; b) a 12-week stabilization treatment for those who do not respond successfully to the initial treatment; and c) a long-term follow-up assessment at 1.5 years, 2.5 years, and 3.5 years after treatment.

This is a randomized 2-phase, open-label; multi-center study conducted in outpatient treatment settings. The main objective of this study is to identify an effective sublingual buprenorphine/naloxone treatment regimen for subjects dependent on prescription opioids. Phase 1 of this study will assess the prevailing one-month detoxification practice. This phase will assess the benefits of individual drug counseling in a short-term treatment paradigm. The second phase of this study will assess the benefit of individual drug counseling in a longer-term treatment paradigm for participants who did not respond successfully to the short-term buprenorphine/naloxone treatment. There is also a long-term follow-up assessment to determine outcomes at 1.5 years, 2.5 years, and 3.5 years after treatment.

• Opiate Dependence
• Substance-related Disorders
• Opioid-related Disorders

• Behavioral: Standard Medical Management (SMM) of Prescription Opiate Abuse
  Standard Medical Management in Phase 1 will consist of one hour-long initial visit; one individual 15-20 minute visit later in Week 1; one individual 15-20 minute visit per week through the end of Week 4; one 15-20 minute SMM visit at Week 6 and at Week 8. And in Phase 2, one 30-60 minute initial visit; one 15-20 minute follow-up visit later in Week 1; one individual session (15-20 minutes) per week through Week 12. In addition, participants in Phase 1 will receive BUP/NX at between 8 to 32mg/day; tapering to zero between weeks three and four. Those referred to Phase 2 will receive up to 32 mg/day for three months tapering to zero during month four.
• Behavioral: Enhanced Medical Management (EMM) of Prescription Opiate Abuse
  Enhanced Medical Management in Phase 1 will consist of SMM plus two individual sessions with a counselor per week (45 minutes each) through Weeks 1-4, and one 45-minute counseling visit at Week 6 and at Week 8. And in Phase 2, EMM will consist of the SMM plus two individual sessions with a counselor per week (45 minutes each) during Weeks 1-6 and one individual session with a counselor per week (45 minutes each) during Weeks 7-12. In addition, participants in Phase 1 will receive BUP/NX at between 8 to 32mg/day; tapering to zero between weeks three and four. Those referred to Phase 2 will receive up to 32 mg/day for three months tapering to zero during month four.

• Experimental: Buprenorphine/Nx with EMM
  Intervention: Behavioral: Enhanced Medical Management (EMM) of Prescription Opiate Abuse
• Active Comparator: Buprenorphine/Nx with SMM
  Intervention: Behavioral: Standard Medical Management (SMM) of Prescription Opiate Abuse

• Weiss RD, Potter JS, Fiellin DA, Byrne M, Connery HS, Dickinson W, Gardin J, Griffin ML, Gourevitch MN, Haller DL, Hasson AL, Huang Z, Jacobs P, Kosinski AS, Lindblad R, McCance-Katz EF, Provost SE, Selzer J, Somoza EC, Sonne SC, Ling W. Adjunctive counseling during brief and extended buprenorphine-naloxone treatment for prescription opioid dependence: a 2-phase randomized controlled trial. Arch Gen Psychiatry. 2011 Dec;68(12):1238-46. Epub 2011 Nov 7.
• Weiss RD, Potter JS, Provost SE, Huang Z, Jacobs P, Hasson A, Lindblad R, Connery HS, Prather K, Ling W. A multi-site, two-phase, Prescription Opioid Addiction Treatment Study (POATS): rationale, design, and methodology. Contemp Clin Trials. 2010 Mar;31(2):189-99. Epub 2010 Jan 29.
• Potter JS, Prather K, Kropp F, Byrne M, Sullivan CR, Mohamedi N, Copersino ML, Weiss RD. A method to diagnose opioid dependence resulting from heroin versus prescription opioids using the Composite International Diagnostic Interview. Contemp Clin Trials. 2010 Mar;31(2):185-8. Epub 2010 Jan 14.
• Weiss RD, Potter JS, Copersino ML, Prather K, Jacobs P, Provost S, Chim D, Selzer J, Ling W. Conducting clinical research with prescription opioid dependence: defining the population. Am J Addict. 2010 Mar-Apr;19(2):141-6.
• Upadhyay J, Maleki N, Potter J, Elman I, Rudrauf D, Knudsen J, Wallin D, Pendse G, McDonald L, Griffin M, Anderson J, Nutile L, Renshaw P, Weiss R, Becerra L, Borsook D. Alterations in brain structure and functional connectivity in prescription opioid-dependent patients. Brain. 2010 Jul;133(Pt 7):2098-114. Epub 2010 Jun 16.
• Dreifuss JA, Griffin ML, Frost K, Fitzmaurice GM, Potter JS, Fiellin DA, Selzer J, Hatch-Maillette M, Sonne SC, Weiss RD. Patient characteristics associated with buprenorphine/naloxone treatment outcome for prescription opioid dependence: Results from a multisite study. Drug Alcohol Depend. 2013 Jan 18. doi:pii: S0376-8716(12)00486-3. 10.1016/j.drugalcdep.2012.12.010. [Epub ahead of print]

Inclusion Criteria:

• 18 years old or older
• Physically dependent on opioids
• Meet DSM-IV criteria for opioid dependence

Exclusion Criteria:

• Known allergy or sensitivity to buprenorphine or naloxone
• Unstable psychiatric disorder
• Pregnant or lactating females
• Liver function test results greater than 5 times the upper limit of normal range