Pregabalin Plus Lofexidine for the Outpatient Treatment of Opioid Withdrawal

Eligibility Criteria

• 1. Male and/or female subjects ≥ 18 years of age
• 2. Meet DSM-5 criteria for an Opioid Use Disorder with physiologic features. Have met 2 or more of the 11 criteria for an OUD including tolerance and withdrawal within the last 12 months
• 3. Interested in opioid antagonist treatment
• 4. Used opioids in 20 or more of the last 30 days
• 5. A stable address in the local area; not planning to move in the next 60 days.
• 6. Have documents for ID check
• 7. Absence of medical or psychiatric conditions that are likely to interfere with study participation
• 8. Has 12 lead ECG demonstrating a QTc ≤450 msec and a QRS ≤120 msec. Site PI has final determination for study inclusion if readings exceed these limits. The PENN cardiologists and medical monitor are available for consultation when needed
• 9. Negative pregnancy test and using adequate contraception if of childbearing potential.
• 1. Current psychotic disorder (bipolar I, schizophrenia, major depression that is not in remission
• 2. Alcohol, benzodiazepine, or other sedative use disorder with physiological features that require medication for detoxification
• 3. Allergy or other serious adverse event due to treatment with pregabalin, XR-NTX, or lofexidine
• 4. Pending incarceration or plans to leave the immediate area in the next 30 days
• 5. Homicidal or otherwise behaviorally disturbed requiring immediate attention
• 6. High risk for suicide as determined by answering 'yes' to questions 4 and/or 5 on C-SSRS
• 7. Blood pressure \<90 mm Hg (systolic) or \<60 mm Hg (diastolic). If value out of normal range, the investigator and study Clinician will decide subject inclusion/exclusion on case-by-case basis
• 8. Heart rate and/or pulse\<50 bpm at screening-sitting
• 9. An Estimated Glomerular Filtration Rate eGFR\<70 mL/min/1.73m2
• 10. A History of, or current Seizure disorder (excluding childhood febrile seizures)
• 11. Inability to read and/or understand English. For example, unable to understand the informed consent as demonstrated by failing to answer 9/10 questions correctly on the quiz
• 12. 12. Pregnant or breastfeeding
• 13. 13. Currently taking sympathomimetic drugs, or a thiazolidinedione antidiabetic
• 14. ALT and/or AST \>4X upper limit of normal
• 15. A Child-Pugh score \>7
• 16. Currently receiving opioids for pain management
• 17. In a treatment study where medication was administered in the last 30 days
• 18. Currently using medications that are known to be strong or moderate inhibitors of CYP2D6 such as fluoxetine, paroxetine, mirabegron, bupropion, quinidine, terbinafine, cimetidine, cinacalcet, duloxetine, or fluvoxamine
• 19. In a methadone maintenance or buprenorphine treatment program within the last 30 days