Lofexidine + Pregabalin for Opioid Withdrawal

(UH3 Trial)

Recruiting at 1 trial location

Overseen By Matthew R Taylor

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Pennsylvania

Must be taking: Opioid antagonists

Must not be taking: Sympathomimetics, Thiazolidinediones, CYP2D6 inhibitors, others

Disqualifiers: Psychotic disorders, Sedative use, Seizure disorder, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 10 days

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of combining two drugs, lofexidine and pregabalin, in managing opioid withdrawal symptoms. The goal is to determine if this combination eases the transition to extended-release naltrexone, a medication that blocks opioid effects. The study seeks individuals with an opioid use disorder who have experienced tolerance and withdrawal in the past year and have used opioids frequently. Participants should be interested in medication to help stop opioid use and have a stable living situation. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, including opioids for pain management, sympathomimetic drugs, thiazolidinedione antidiabetics, and medications that strongly or moderately inhibit CYP2D6, like fluoxetine or paroxetine.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using lofexidine to aid opioid withdrawal is generally safe and well-tolerated. People taking lofexidine often experience fewer withdrawal symptoms, such as stomach cramps and trouble sleeping. Combining pregabalin with lofexidine might also be safe and could reduce withdrawal symptoms more effectively than lofexidine alone. However, more research is needed to fully understand the safety of using pregabalin and lofexidine together. Prospective trial participants should know that these treatments have shown promise in easing withdrawal, but individual experiences can differ. It is crucial to consult a healthcare provider about potential risks. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for opioid withdrawal?

Researchers are excited about Lofexidine combined with Pregabalin for opioid withdrawal because it offers a unique approach compared to current treatments. Most standard therapies focus on managing withdrawal symptoms through opioid replacements or other medications like methadone or buprenorphine. However, Lofexidine, an alpha-2 adrenergic receptor agonist, helps reduce withdrawal symptoms without using opioids, while Pregabalin targets anxiety and discomfort by modulating nerve signals. This combination aims to provide a more comprehensive relief from withdrawal symptoms without the risk of opioid dependency. Additionally, the specific dosing schedule of Lofexidine and Pregabalin might optimize their effectiveness and minimize side effects, offering a potentially safer and more efficient treatment option.

What evidence suggests that this trial's treatments could be effective for opioid withdrawal?

This trial will compare the effectiveness of two treatment regimens for managing opioid withdrawal symptoms. One group of participants will receive a combination of lofexidine and pregabalin. Research has shown that using lofexidine with pregabalin may help manage withdrawal symptoms in people with opioid use disorder. Studies have found that this combination works better than lofexidine alone in reducing withdrawal symptoms and keeping patients in treatment. Lofexidine is already known to be effective and is approved by the FDA for managing opioid withdrawal symptoms. Pregabalin, often used for nerve pain, helps by reducing anxiety and discomfort during withdrawal. These findings suggest that the lofexidine/pregabalin combination could be a promising option for those looking to manage withdrawal symptoms and move on to further treatment. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with opioid use disorder who've used opioids on most days in the past month and are interested in naltrexone treatment. They must have a stable address, no severe medical or psychiatric conditions, not be pregnant or breastfeeding, and meet specific heart health criteria.

Inclusion Criteria

Interested in opioid antagonist treatment

Used opioids in 20 or more of the last 30 days

Have documents for ID check

Exclusion Criteria

High risk for suicide as determined by answering 'yes' to questions 4 and/or 5 on C-SSRS

ALT and/or AST >4X upper limit of normal

Homicidal or otherwise behaviorally disturbed requiring immediate attention

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants are randomized to receive either lofexidine/pregabalin or lofexidine/placebo for withdrawal management over 10 days

10 days

Daily visits for medication administration and monitoring

Transition to XR-NTX

Participants who complete withdrawal management are offered extended-release injectable naltrexone (XR-NTX)

Up to 2 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Lofexidine/Pregabalin

Trial Overview The study tests if combining lofexidine with pregabalin (LFX/PGB) or its placebo (LFX/PLA-PGB) helps manage withdrawal symptoms in outpatients seeking to start extended-release injectable naltrexone therapy. Participants are randomly assigned to one of these two groups.

How Is the Trial Designed?

Group I: LFX/PGB Experimental Treatment 2 Interventions

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

Group II: LFX/PLA-PGB Active Control 2 Interventions

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

Lofexidine/Pregabalin is already approved in United States, United Kingdom, European Union for the following indications:

Approved in United States as Lucemyra for:

• Mitigation of withdrawal symptoms to facilitate abrupt discontinuation of opioids in adults

Approved in United Kingdom as Lofexidine for:

• Management of opioid withdrawal symptoms

Approved in United States as Lyrica for:

• Neuropathic pain
• Seizures

Approved in European Union as Pregabalin for:

• Neuropathic pain
• Epilepsy
• Generalized anxiety disorder

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Published Research Related to This Trial

Lofexidine is an effective option for managing symptoms of opiate withdrawal by reducing sympathetic outflow, but it remains largely experimental in the US and Canada despite its approval in other regions since the 1980s.

The development of lofexidine has faced challenges due to market factors and regulatory considerations, but recent clinical trials are starting to rectify past oversights by exploring improved formulations and specific enantiomers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The preclinical discovery of lofexidine for the treatment of opiate addiction. Vartak, AP.[2014]

Lofexidine, at doses of 2.16 mg and 2.88 mg per day, significantly reduced opioid withdrawal symptoms compared to placebo in a study involving 603 participants over 7 days, demonstrating its efficacy as a nonopioid treatment for opioid withdrawal syndrome.

The study also found that lofexidine improved completion rates of the withdrawal program by 14% and 12% compared to placebo, indicating it not only helps manage symptoms but also encourages patients to complete the treatment process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Lofexidine for Medically Managed Opioid Withdrawal: A Randomized Controlled Clinical Trial. Fishman, M., Tirado, C., Alam, D., et al.[2020]

Lofexidine, an alpha-2 agonist, has been shown to effectively manage acute withdrawal symptoms from opiate addiction, helping to alleviate issues like anxiety and gastrointestinal upset caused by increased noradrenaline during withdrawal.

The use of Lofexidine is considered safe and could serve as a valuable tool in withdrawal programs, potentially aiding individuals before they transition to maintenance treatments like methadone or buprenorphine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Comprehensive Update of Lofexidine for the Management of Opioid Withdrawal Symptoms. Urits, I., Patel, A., Zusman, R., et al.[2021]

Lofexidine has been recently FDA approved for treating opioid withdrawal symptoms in adults and has shown effectiveness in randomized controlled trials compared to placebo.

The safety profile of lofexidine is favorable, and its efficacy is comparable to other first- and second-line treatments for opioid withdrawal, although its higher cost may limit its accessibility in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lofexidine: A Newly FDA-Approved, Nonopioid Treatment for Opioid Withdrawal. Doughty, B., Morgenson, D., Brooks, T.[2020]

Lofexidine hydrochloride (Lucemyra) is effective in managing opioid withdrawal symptoms, providing a non-opioid treatment option for individuals undergoing detoxification.

Erenumab-aooe (Aimovig) has been shown to significantly reduce the frequency of migraine attacks, offering a targeted approach to migraine prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmaceutical Approval Update. Choy, M.[2020]

Lofexidine, a non-opioid treatment for opioid withdrawal, was studied in 681 participants, showing small, temporary increases in QTcF (a measure of heart rhythm) during the first 24 hours, which resolved by Day 4.

By Day 7, QTcF levels decreased from baseline in all groups, suggesting that while lofexidine can cause transient changes in heart rhythm, it may ultimately have a stabilizing effect, likely due to its sympatholytic actions that alter autonomic tone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of lofexidine on cardiac repolarization during treatment of opioid withdrawal. Darpö, B., Pirner, M., Longstreth, J., et al.[2020]

Pregabalin, which targets calcium channels in neurons, was successfully used by a 43-year-old patient to manage withdrawal symptoms during opiate detoxification, suggesting its potential efficacy in this context.

This case highlights that Pregabalin may help control withdrawal symptoms and prevent relapse in opiate-dependent patients, marking the first report of its use for this purpose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pregabalin for the reduction of opiate withdrawal symptoms]. Kämmerer, N., Lemenager, T., Grosshans, M., et al.[2015]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05995535

Pregabalin Plus Lofexidine for the Outpatient Treatment ... Results were that the conditions were equally safe, and that lofexidine/pregabalin was more effective in reducing subjective withdrawal and keeping patients in ...

2. reporter.nih.gov reporter.nih.gov/project-details/9852022

Combining Pregabalin with Lofexidine - NIH RePORTER PROJECT NARRATIVE This study aims to identify a pregabalin/lofexidine combination that decreases the dysphoria and other subjective effects of opi oi d wi ...

3. trial.medpath.com trial.medpath.com/clinical-trial/a21ef51ba8cf6ab6/combining-pregabalin-lofexidine-naltrexone

Combining Pregabalin (LYRICA®) With Lofexidine ... - MedPath Combining Pregabalin (LYRICA®) With Lofexidine (LUCEMYRATM) to Treat OPIOID Withdrawal ... Outcome data and publication updates. Subscribe. Free ...

4. cdek.pharmacy.purdue.edu cdek.pharmacy.purdue.edu/trial/NCT04218240/

Trial | NCT04218240 Combining Pregabalin (LYRICA®) With Lofexidine (LUCEMYRATM): Can it Increase the Success of Transition to Naltrexone? Snapshot.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7377538/

A Comprehensive Update of Lofexidine for the Management ... Lofexidine is effective and safe and is FDA approved for the management of withdrawal symptoms. It does carry warnings for side effects.

6. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/40/NCT04218240/Prot_SAP_002.pdf

Pregabalin Plus Lofexidine for the Outpatient Treatment of ... If the current trial shows that a PGB/LFX combination is likely to be safe effective, and reduces opioid withdrawal related subjective effects, ...

7. mayoclinic.org mayoclinic.org/drugs-supplements/lofexidine-oral-route/description/drg-20443753

Lofexidine (oral route) - Side effects & dosage Lofexidine is used to help reduce withdrawal symptoms (eg, stomach cramps, muscle spasms or twitching, yawning, runny eyes, trouble sleeping, pounding of the ...

8. pharmacy.hsc.wvu.edu pharmacy.hsc.wvu.edu/media/2958/lucemyra-lofexidine.pdf

Lucemyra Generic Name1,2,3,4: Lofexidine Manufacturer1, ... Overall, lofexidine had favorable outcomes with respect to alleviating symptoms of opioid withdrawal, resulted in longer patient retention in treatment, higher ...