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

NCT04218240 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 1UG3DA049694-01
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 3

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).

Conditions

Opioid Withdrawal

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Completion of Withdrawal Management

  7 days

Study Arms (2)

PGB/LFX;

EXPERIMENTAL

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; Drug: Lofexidine 0.18Mg Tab

Lofexidine and PLACEBO

ACTIVE COMPARATOR

0.54 mg lofexidine and Placebo (PLB) on days 1-7 with taper for lofexidine starting on day 5

Drug: Placebo oral tablet; Drug: Lofexidine 0.18Mg Tab

Interventions

Pregabalin 200 MG capsules DRUG

oral pregabalin 200 mg capsules given with a taper on day 5

Also known as: lyrica

PGB/LFX;

Placebo oral tablet DRUG

oral Placebo

Lofexidine and PLACEBO

Lofexidine 0.18Mg Tab DRUG

lofexidine 0.18 tab given with a taper starting on day 5

Also known as: lucemyra

Lofexidine and PLACEBO; PGB/LFX;

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and/or female subjects ≥ 18 years of age
• 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
• Interested in opioid antagonist treatment
• Have used opioids in 20 or more of the last 30 days
• Have a stable address in the local area; not planning to move; have documents for ID check
• Absence of medical or psychiatric conditions that are likely to interfere with study participation
• If female, have a negative pregnancy test and uses adequate contraception if of childbearing potential

You may not qualify if:

• Current psychotic disorder (bipolar I, schizophrenia, major depression with psychotic features,) as defined by the MINI
• An alcohol, benzodiazepine, or other sedative use disorder with physiological features that require medication for detoxification
• History of allergy or other serious adverse event due to treatment with pregabalin, XR-NTX, or lofexidine
• Pending incarceration 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 at screening
• Heart rate and/or pulse\<50 bpm at screening-sitting
• An Estimated Glomerular Filtration Rate eGFR\<90 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
• Pregnant or breastfeeding
• Currently taking sympathomimetic drugs, or a thiazolidinedione antidiabetic
• An ALT and/or AST test that is at \>4X the top limit of normal
• A Child-Pugh score \>7
• Currently receiving opioids for pain management

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (3)

Mountain Manor Treatment Center

Baltimore, Maryland, 21229, United States

Location

John Mariani

New York, New York, 10019, United States

Location

Treatment Research Center

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Interventions

Pregabalin; lofexidine

Intervention Hierarchy (Ancestors)

gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Kyle M. Kampman, MD
• Organization: University of Pennsylvania

kampman@pennmedicine.upenn.edu

2157462764

Study Officials

• Stuart Watson

  Office of Research Administration, Univ. of Pennsylvania

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Psychiatry

Model Details: 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.

Study Record Dates

• First Submitted: January 2, 2020
• First Posted: January 6, 2020
• Study Start: December 17, 2020
• Primary Completion: August 31, 2023
• Study Completion: August 31, 2023
• Last Updated: September 19, 2024
• Results First Posted: May 20, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)