Pregabalin Plus Lofexidine for the Outpatient Treatment of Opioid Withdrawal (UH3)

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.

Study Overview

• Status: Recruiting
• Conditions: Opioid Use; Opiate Withdrawal Syndrome
• Intervention / Treatment: Drug: LFX/PGB; Drug: LFX/PLA-PGB

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Kyle M Kampman, MD; Phone Number: 215-746-2764; Email: Kampman@pennmedicine.upenn.edu
• Study Contact Backup: Name: Matthew R Taylor; Phone Number: 215-746-0467; Email: matthew.taylor@pennmedicine.upenn.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21229-3618
      • Not yet recruiting
      • Mountain Manor Treatment Center
      • Principal Investigator: Marc Fishman, MD
      • Contact: kevin Wenzel; Phone Number: 4102331400; Email: kwenzel@marylandtreatment.org
      • Contact: Marc Fishman, MD; Phone Number: 4102331400; Email: Mfishman@marylandtreatment.org
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania, Treatment Research Center
      • Contact: Sabrina A Poole, PsyD; Phone Number: 2157468802; Email: spoole@pennmedicine.upenn.edu
      • Principal Investigator: Kyle M Kampman, MD
      • Contact: Kyle Kampman, MD; Phone Number: (215)222-3200; Email: kampman@mail.med.upenn.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LFX/PGB; 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; lofexidine tablets 0.18mg tabs pregabalin capsules 100mg and 25mg; Other Names: lyrica; Lucemyra; Drug: LFX/PLA-PGB; lofexidine tablets 0.18mg tabs pregabalin capsules 0mg; Other Names: Lucemyra; placebo pregabalin
Active Comparator: LFX/PLA-PGB; 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; lofexidine tablets 0.18mg tabs pregabalin capsules 100mg and 25mg; Other Names: lyrica; Lucemyra; Drug: LFX/PLA-PGB; lofexidine tablets 0.18mg tabs pregabalin capsules 0mg; Other Names: Lucemyra; placebo pregabalin

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2024
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2026

Study Registration Dates

• First Submitted: August 1, 2023
• First Submitted That Met QC Criteria: August 15, 2023
• First Posted (Actual): August 16, 2023

Study Record Updates

• Last Update Posted (Actual): February 13, 2026
• Last Update Submitted That Met QC Criteria: February 10, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Substance Withdrawal Syndrome; Amino Acids, Peptides, and Proteins; Organic Chemicals; Acids, Acyclic; Carboxylic Acids; Amino Acids; gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Pregabalin; lofexidine
• Other Study ID Numbers: 854046

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No