Combining Pregabalin (LYRICA®) With Lofexidine (LUCEMYRATM) to Treat OPIOID Withdrawal

An inpatient detoxification study where pregabalin (PBG) will be given orally at a starting dose of up to 600 mg daily (group 1) tapered to 100 mg daily over 7 days; given with lofexidine (LFX) starting at 2.16 mg daily and declining to 0.72 mg over 7 days. On day 8, subjects are offered an injection of XR-NTX if they provide a urine sample that is negative for opioids and buprenorphine and pass a naloxone challenge. All subjects, regardless of whether or not they receive XR-NTX, will be given a referral and appointment for follow-up treatment when they leave the inpatient detoxification program.

Inclusion criteria

• Male and/or female subjects ≥ 18 years of age
• Meet DSM-5 criteria for an Opioid Use Disorder with physiologic features. Have 2 or more of the 11 DSM 5 criteria for opioid disorder including tolerance and withdrawal features in the last 12 months
• Interested in opioid antagonist treatment
• Have used opioids in 20 or more of the last 30 days
• Have a stable address in the local area; not planning to move; have documents for ID check
• Absence of medical or psychiatric conditions that are likely to interfere with study participation
• Have a 12 lead ECG demonstrating a QTc ≤450 msec and a QRS interval ≤120 msec. The site PI has the final determination for inclusion into the study for ECGs unless there is a question of QT prolongation or other factors (QTc/Fre uses the Frederica formula (QTc = QT/RR(1/3)). If consultation is needed, the PENN cardiologists and the medical monitor should be contacted
• If female, have a negative pregnancy test and uses adequate contraception if of childbearing potential

Exclusion criteria

• Current psychotic disorder (bipolar I, schizophrenia, major depression with psychotic features,) as defined by the MINI
• An alcohol, benzodiazepine, or other sedative use disorder with physiological features that require medication for detoxification
• History of allergy or other serious adverse event due to treatment with pregabalin, XR-NTX, or lofexidine
• Pending incarceration in the next 30 days
• Homicidal or otherwise behaviorally disturbed requiring immediate attention.
• High Risk for suicide as determined by answering 'yes' to questions 4 and/or 5 on C-SSRS at screening
• Blood pressure <90 mm Hg (systolic) or <60 mm Hg (diastolic). If this value is out of normal range, the investigator and a study clinician will decide subject inclusion or exclusion on a case-by-case basis
• Heart rate and/or pulse<50 bpm at screening-sitting
• An Estimated Glomerular Filtration Rate eGFR<90 mL/min/1.73m2
• A History of, or current Seizure disorder (excluding childhood febrile seizures)
• 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
• Pregnant or breastfeeding
• Currently taking sympathomimetic drugs, or a thiazolidinedione antidiabetic
• An ALT and/or AST test that is at >4X the top limit of normal
• A Child-Pugh score >7
• Currently receiving opioids for pain management
• In a treatment study where medication was administered in the last 30 days
• 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
• In a methadone maintenance or buprenorphine treatment program within the last 30 days