Using pregabalin and lofexidine to help treat opioid withdrawal in outpatients

Pregabalin Plus Lofexidine for the Outpatient Treatment of Opioid Withdrawal

This study is testing if a combination of two medications, pregabalin and lofexidine, can help adults with opioid use disorder feel better during withdrawal and make it easier for them to start a new treatment.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 150 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Pennsylvania (other)
• Locations: 2 sites (Baltimore, Maryland and 1 other locations)
• Trial ID: NCT05995535 on ClinicalTrials.gov

What this trial studies

This trial evaluates the effectiveness and safety of combining lofexidine with pregabalin compared to a placebo in managing opioid withdrawal symptoms in outpatient settings. Participants, who are adults with opioid use disorder interested in extended-release injectable naltrexone, will be randomized to receive either the active treatment or placebo. The study aims to determine if this combination can improve withdrawal management and facilitate a smoother transition to naltrexone treatment. The trial builds on previous inpatient findings that suggested the combination was more effective than placebo in reducing withdrawal symptoms.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with a diagnosed opioid use disorder who have experienced withdrawal symptoms and are interested in opioid antagonist treatment.

Not a fit: Patients with current psychotic disorders or other significant medical or psychiatric conditions that could interfere with study participation may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve the management of opioid withdrawal, leading to better patient outcomes and increased retention in treatment programs.

How similar studies have performed: Previous studies have shown that lofexidine combined with pregabalin is effective in managing opioid withdrawal in inpatient settings, suggesting potential for success in outpatient settings as well.

Eligibility criteria

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 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.

Exclusion Criteria:

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

Where this trial is running

Baltimore, Maryland and 1 other locations

• Mountain Manor Treatment Center — Baltimore, Maryland, United States (NOT_YET_RECRUITING)
• University of Pennsylvania, Treatment Research Center — Philadelphia, Pennsylvania, United States (RECRUITING)

Study contacts

• Study coordinator: Kyle M Kampman, MD

Conditions: Opiate Withdrawal Syndrome, Opioid Use