Pregabalin Plus Lofexidine for the Outpatient Treatment of Opioid Withdrawal

Study Overview
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Brief Summary
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A placebo-controlled trial in which male and female outpatients with an opioid use disorder who express interest in extended-release injectable naltrexone (XR-NTX) are randomized 1:1 to lofexidine/pregabalin or lofexidine/pregabalin placebo for withdrawal management and offered XR-NTX if after completing withdrawal.

Detailed Description
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A placebo-controlled trial in which male and female outpatients with an opioid use disorder who express interest in extended-release injectable naltrexone (XR-NTX) are randomized 1:1 to lofexidine/pregabalin or lofexidine/pregabalin placebo for withdrawal management and offered XR-NTX if after completing withdrawal. It follows a UG3 study in which 90 inpatients with an OUD who expressed interest in XR-NTX were randomized 2:1 to withdrawal management with lofexidine/pregabalin or lofexidine/placebo pregabalin. Results were that the conditions were equally safe, and that lofexidine/pregabalin was more effective in reducing subjective withdrawal and keeping patients in treatment than lofexidine/placebo pregabalin. The objectives are to study the safety and effectiveness of lofexidine/pregabalin compared to lofexidine/placebo for managing opioid withdrawal and transitioning to XR-NTX in outpatient settings.

Official Title
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Pregabalin Plus Lofexidine for the Outpatient Treatment of Opioid Withdrawal

Conditions
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Opiate Withdrawal Syndrome, Opioid Use

Intervention / Treatment
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* Drug: LFX/PGB
* Drug: LFX/PLA-PGB


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and/or female subjects ≥ 18 years of age 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 Interested in opioid antagonist treatment Used opioids in 20 or more of the last 30 days A stable address in the local area; not planning to move in the next 60 days. Have documents for ID check Absence of medical or psychiatric conditions that are likely to interfere with study participation 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 Negative pregnancy test and using adequate contraception if of childbearing potential. Exclusion Criteria: Current psychotic disorder (bipolar I, schizophrenia, major depression that is not in remission Alcohol, benzodiazepine, or other sedative use disorder with physiological features that require medication for detoxification Allergy or other serious adverse event due to treatment with pregabalin, XR-NTX, or lofexidine Pending incarceration or plans to leave the immediate area 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 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 Heart rate and/or pulse<50 bpm at screening-sitting An Estimated Glomerular Filtration Rate eGFR<70 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 12. Pregnant or breastfeeding 13. Currently taking sympathomimetic drugs, or a thiazolidinedione antidiabetic ALT and/or AST >4X upper 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Active pregabalin plus lofexidine versus placebo pregabalin plus lofexidine
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LFX/PGB<br>PGB/day 1=400mg, day 2-7=600mg each day, day 8=400mg, day 9=200mg, day 10=100mg LFX/day 1=1.62mg, day 2-7=2.16mg each day, day 8=1.44mg, day 9=0.72mg, day 10=0.72mg | Drug: LFX/PGB<br>* lofexidine tablets 0.18mg tabs pregabalin capsules 100mg and 25mg<br>* Other names: lyrica;Drug: LFX/PLA-PGB<br>* lofexidine tablets 0.18mg tabs pregabalin capsules 0mg<br>* Other names: placebo pregabalin;|
| Active Comparator: LFX/PLA-PGB<br>PLA-PGB/day 1-7= 0mg each day, day 8, 9, and 10 =0mg each day LFX/ day 1=1.62mg, day 2-7=2.16mg each day, day 8=1.44mg, day 9=0.72mg, day 10=0.72mg | Drug: LFX/PGB<br>* lofexidine tablets 0.18mg tabs pregabalin capsules 100mg and 25mg<br>* Other names: lyrica;Drug: LFX/PLA-PGB<br>* lofexidine tablets 0.18mg tabs pregabalin capsules 0mg<br>* Other names: placebo pregabalin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjective Opioid Withdrawal Scale (SOWS) scores | Subjective patient reported Opioid Withdrawal measured by the SOWS, (0-30); 0 = no withdrawal/30 = severe withdrawal | 10 days per subject, through study completion (N=150) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Study detox completion | Proportion that receives one or more doses of study medication and completed withdrawal (Completing withdrawal management will be defined as having received at least 1 dose of study medication on day 8 and completing the SOWS-Gossop assessment on day 8); and proportion that transition to XR-NTX; adverse events | 10 days per subject, through study completion (N=150) | 
| XR-NTX IM injection | proportion that receives 380mg dose of extended-release naltrexone | upto 2 days per subject (N=150) |