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

Combining Pregabalin (LYRICA®) With Lofexidine (LUCEMYRATM): Can it Increase the Success of Transition to Naltrexone?

A phase II double-blind placebo-controlled parallel group clinical trial that will randomize 90 subjects to investigate whether pregabalin (PGB) combined with Lofexidine (LFX) can reduce opioid withdrawal-related subjective effects, and investigate, whether the PGB/LFX combination can increase the proportion of patients with an opioid use disorder (OUD) who complete detoxification and transition to antagonist treatment with extended-release injectable naltrexone (XR-NTX).

Study Overview

• Status: Completed
• Conditions: Opioid Withdrawal
• Intervention / Treatment: Drug: Pregabalin 200 MG capsules; Drug: Lofexidine 0.18Mg Tab; Drug: Placebo oral tablet

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21229
      • Mountain Manor Treatment Center
  • New York
    • New York, New York, United States, 10019
      • John Mariani
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Treatment Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

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 2 or more of the 11 DSM 5 criteria for opioid disorder including tolerance and withdrawal features in the last 12 months
3. Interested in opioid antagonist treatment
4. Have used opioids in 20 or more of the last 30 days
5. Have a stable address in the local area; not planning to move; have documents for ID check
6. Absence of medical or psychiatric conditions that are likely to interfere with study participation
7. 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
8. If female, have a negative pregnancy test and uses adequate contraception if of childbearing potential

Exclusion Criteria:

1. Current psychotic disorder (bipolar I, schizophrenia, major depression with psychotic features,) as defined by the MINI
2. An alcohol, benzodiazepine, or other sedative use disorder with physiological features that require medication for detoxification
3. History of allergy or other serious adverse event due to treatment with pregabalin, XR-NTX, or lofexidine
4. Pending incarceration 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 at screening
7. 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
8. Heart rate and/or pulse<50 bpm at screening-sitting
9. An Estimated Glomerular Filtration Rate eGFR<90 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. Pregnant or breastfeeding
13. Currently taking sympathomimetic drugs, or a thiazolidinedione antidiabetic
14. An ALT and/or AST test that is at >4X the top 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: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PGB/LFX; 0.54 mg lofexidine and 200 mg Pregabalin on days 1 -7 with taper for pregabalin and lofexidine starting on day 5	Drug: Pregabalin 200 MG capsules; oral pregabalin 200 mg capsules given with a taper on day 5; Other Names: lyrica; Drug: Lofexidine 0.18Mg Tab; lofexidine 0.18 tab given with a taper starting on day 5; Other Names: lucemyra
Active Comparator: Lofexidine and PLACEBO; 0.54 mg lofexidine and Placebo (PLB) on days 1-7 with taper for lofexidine starting on day 5	Drug: Lofexidine 0.18Mg Tab; lofexidine 0.18 tab given with a taper starting on day 5; Other Names: lucemyra; Drug: Placebo oral tablet; oral Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjective Opioid Withdrawal Scale-Gossop (SOWS) Scale Score	mild = 1-10 moderate=11-20 severe=21-30 higher number equals worse score	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Completion of Withdrawal Management	proportion of participants who completed the 7-day detoxification	7 days

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Investigators: Study Director: Stuart Watson, Office of Research Administration, Univ. of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): December 17, 2020
• Primary Completion (Actual): March 23, 2023
• Study Completion (Actual): March 23, 2023

Study Registration Dates

• First Submitted: January 2, 2020
• First Submitted That Met QC Criteria: January 2, 2020
• First Posted (Actual): January 6, 2020

Study Record Updates

• Last Update Posted (Actual): August 28, 2024
• Last Update Submitted That Met QC Criteria: August 27, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Substance Withdrawal Syndrome; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anti-Anxiety Agents; Narcotic Antagonists; Anticonvulsants; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Pregabalin; Lofexidine
• Other Study ID Numbers: 1UG3DA049694-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Not at this time

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No