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

• ClinicalTrials.gov Identifier: NCT04218240
• Recruitment Status: Recruiting
• First Posted: January 6, 2020
• Last Update Posted: January 27, 2022
• Sponsor: University of Pennsylvania
• Information provided by (Responsible Party): Kyle Kampman, University of Pennsylvania

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Opioid Withdrawal	Drug: Pregabalin 200 MG capsules; Drug: Placebo oral tablet; Drug: Lofexidine 0.18Mg Tab	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 90 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: for the primary comparison of longitudinal subjective withdrawal measures, comparing the groups on rate of decrease across detox days, using a linear group by time effect for the mixed effects models described above. We have one primary outcome, so use an alpha level of 0.05, and we use two-sided tests. 90 subjects, 30 from each of three sites, who will be randomized into two groups, with 30 assigned to Lofexidine plus Placebo, and 60 to Lofexidine plus a starting daily dose of 400 mg of pregabalin and increasing to 600mg Pregabalin on day 2.
• Masking: Triple (Participant, Care Provider, Investigator)
• Masking Description: The Penn Investigational Drug Service (IDS) will prepare blinded pregabalin capsules by over encapsulation of the drug into capsules shells matching the placebo capsules. Blinded pregabalin capsules will be packaged into blister packs along with lofexidine tablets, in separate compartments that are labeled for dosing times on days 1-7 and ship them to the research sites.
• Primary Purpose: Treatment
• Official Title: Combining Pregabalin (LYRICA®) With Lofexidine (LUCEMYRATM): Can it Increase the Success of Transition to Naltrexone?
• Actual Study Start Date: December 20, 2020
• Estimated Primary Completion Date: August 31, 2022
• Estimated Study Completion Date: August 31, 2022

Arms and Interventions

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 Name: lyrica; Drug: Lofexidine 0.18Mg Tab; lofexidine 0.18 tab given with a taper starting on day 5; Other Name: 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: Placebo oral tablet; oral Placebo; Drug: Lofexidine 0.18Mg Tab; lofexidine 0.18 tab given with a taper starting on day 5; Other Name: lucemyra

Outcome Measures

Primary Outcome Measures :

1. withdrawal [ Time Frame: 7 days ]
   reduction of withdrawal

Secondary Outcome Measures :

1. complete detoxification [ Time Frame: 7 days ]
   Proportion of subjects who complete the 7 day detoxification

Eligibility Criteria

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

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 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

Contacts and Locations

Contacts

Contact: kyle kampman, M.D.; 215-746-2764; kampman@pennmedicine.upenn.edu

Contact: George E Woody, M.D.; 325-746-7702; woodyg@pennmedicine.upenn.edu

Locations

United States, Maryland

Mountain Manor Treatment Center; Recruiting

Baltimore, Maryland, United States, 21229

Contact: Marc Fishman, MD 410-916-6839 mjfishman@comcast.net

Contact: Kevin Wenzel, PhD 561-542-4282 kwenzel@mountainmanor.org

United States, New York

John Mariani; Active, not recruiting

New York, New York, United States, 10019

United States, Pennsylvania

Treatment Research Center; Recruiting

Philadelphia, Pennsylvania, United States, 19104

Contact: Kyle Kampman, M.D. 215-746-2764 kampman@pennmedicine.upenn.edu

Contact: George Woody, M.D. 215-746-7702 woodyg@pennmedicine.upenn.edu

Sponsors and Collaborators

University of Pennsylvania

Investigators

• Study Director: Stuart Watson; Office of Research Administration, Univ. of Pennsylvania

More Information

• Responsible Party: Kyle Kampman, Professor Psychiatry, University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT04218240
• Other Study ID Numbers: 1UG3DA049694-01 ( U.S. NIH Grant/Contract )
• First Posted: January 6, 2020
• Last Update Posted: January 27, 2022
• Last Verified: January 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: Not at this time

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Substance Withdrawal Syndrome; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Lofexidine; Pregabalin; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anticonvulsants; Calcium Channel Blockers; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Calcium-Regulating Hormones and Agents; Anti-Anxiety Agents; Tranquilizing Agents; Central Nervous System Depressants; Psychotropic Drugs; Antihypertensive Agents; Narcotic Antagonists; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents