Pregabalin Plus Lofexidine for the Outpatient Treatment of Opioid Withdrawal

Inclusion 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 2or more of the 11 criteria for an OUD including tolerance and withdrawal within thelast 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 studyparticipation

8. Has 12 lead ECG demonstrating a QTc ≤450 msec and a QRS ≤120 msec. Site PI has finaldetermination for study inclusion if readings exceed these limits. The PENNcardiologists and medical monitor are available for consultation when needed

9. Negative pregnancy test and using adequate contraception if of childbearingpotential.

Exclusion Criteria:

1. Current psychotic disorder (bipolar I, schizophrenia, major depression that is notin remission

2. Alcohol, benzodiazepine, or other sedative use disorder with physiological featuresthat require medication for detoxification

3. Allergy or other serious adverse event due to treatment with pregabalin, XR-NTX, orlofexidine

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 onC-SSRS

7. Blood pressure <90 mm Hg (systolic) or <60 mm Hg (diastolic). If value out of normalrange, the investigator and study Clinician will decide subject inclusion/exclusionon 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 theinformed consent as demonstrated by failing to answer 9/10 questions correctly onthe quiz

13. Pregnant or breastfeeding

15. Currently taking sympathomimetic drugs, or a thiazolidinedione antidiabetic

16. ALT and/or AST >4X upper limit of normal

17. A Child-Pugh score >7

18. Currently receiving opioids for pain management

19. In a treatment study where medication was administered in the last 30 days

20. Currently using medications that are known to be strong or moderate inhibitors ofCYP2D6 such as fluoxetine, paroxetine, mirabegron, bupropion, quinidine,terbinafine, cimetidine, cinacalcet, duloxetine, or fluvoxamine

21. In a methadone maintenance or buprenorphine treatment program within the last 30days