Opioid Withdrawal Management for Opioid Use Disorder

Overseen By Kelly E Dunn, PhD, MBA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Maryland, Baltimore

Must not be taking: Methadone, Buprenorphine, Alcohol, Benzodiazepines

Disqualifiers: Pregnancy, Hypotension, Bradycardia, Myocardial infarction, 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

Compensation: Varies

Number of Visits: 1

60 Participants Needed

Trial Summary

What is the purpose of this trial?

Evaluate individual differences in the expression of opioid withdrawal symptoms in persons with opioid use disorder (OUD) while completing a clinically-indicated medication taper.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on methadone or buprenorphine maintenance treatment, you cannot participate in the trial.

What data supports the idea that Opioid Withdrawal Management for Opioid Use Disorder is an effective drug?

The available research shows that lofexidine, when used in combination with naloxone, helps reduce withdrawal symptoms and cravings during detoxification. In a study comparing lofexidine/naloxone to lofexidine/placebo, patients who received naloxone experienced lower levels of withdrawal by the end of detoxification. Another study compared lofexidine with other drugs like buprenorphine/naloxone and methadone, showing that lofexidine can be effective in managing withdrawal symptoms. However, the research also indicates that lofexidine does not significantly speed up the withdrawal process compared to other treatments. ^{1 2 3 4 5}

What safety data is available for opioid withdrawal treatments like Lofexidine?

Safety data for Lofexidine, a non-opioid treatment for opioid withdrawal, is available from several studies. A randomized controlled clinical trial investigated its safety and efficacy for treating opioid withdrawal syndrome. Another study reviewed its pharmacology, efficacy, and safety following FDA approval. Additionally, research examined its effects on cardiac repolarization during treatment. Lofexidine has been evaluated in combination with oral naltrexone for opioid use disorder relapse prevention, focusing on safety and treatment compliance. ^{1 4 6 7 8}

Is the drug Lofexidine, also known as Lucemyra, a promising treatment for opioid withdrawal?

Yes, Lofexidine is a promising drug for managing opioid withdrawal. It is a non-opioid medication that helps reduce withdrawal symptoms by calming the body's response to stopping opioids. It has been approved in several countries and has shown effectiveness and safety in clinical trials. ^{1 2 3 6 9}

Research Team

Kelly E Dunn, Ph.D, M.B.A.

Principal Investigator

Johns Hopkins University

Eligibility Criteria

This trial is for adults aged 18-65 with opioid use disorder who are physically dependent on opioids and interested in tapering off. It's not for those dependent on alcohol or benzodiazepines, pregnant or breastfeeding women, people on methadone/buprenorphine treatment, or those with significant heart issues, mental health disorders, active hepatitis B/C infections with abnormal liver tests.

Inclusion Criteria

Opioid-positive urine sample

I am between 18 and 65 years old.

Exclusion Criteria

Clinically significant hypotension (<90/60mmHg) or bradycardia (<45bpm)

I have hepatitis B or C, but my liver is functioning normally.

Significant mental health or physical disorder, or life circumstances, that is expected to interfere with study participation

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Morphine Stabilization

Participants are maintained on morphine for stabilization and undergo naloxone challenges to assess withdrawal symptoms

5 days

Daily monitoring

Lofexidine-assisted Taper

Participants are tapered off morphine using lofexidine to manage withdrawal symptoms

5 days

Daily monitoring

Transition to Aftercare

Participants transition to buprenorphine maintenance or receive oral naltrexone and an injection of Vivitrol

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Lofexidine
• Morphine
• Naloxone
• Naloxone + Lofexidine

Trial Overview The study is testing how different treatments affect opioid withdrawal symptoms during a medication taper. Treatments include Naloxone combined with a placebo or lofexidine (a non-opioid medication), and Morphine as comparisons to understand individual responses to withdrawal.

Participant Groups

Group I: Within-subject design Experimental Treatment 4 Interventions

All participants will undergo the same study design, which includes morphine stabilization (days 1-5), two naloxone challenges (scheduled during morphine stabilization), lofexidine-assisted taper (days 6-10), and transition to aftercare (day 11).

Lofexidine is already approved in United States, United Kingdom for the following indications:

Approved in United States as Lucemyra for:

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

Approved in United Kingdom as BritLofex for:

• Management of opioid withdrawal symptoms

Who Is Running the Clinical Trial?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Findings from Research

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 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]

In a randomized controlled trial involving 80 opiate-dependent individuals, both buprenorphine/naloxone and methadone/lofexidine showed similar overall outcomes in managing opiate withdrawal symptoms and treatment retention.

However, during the induction phase, withdrawal symptoms decreased more slowly and cravings were higher in the buprenorphine/naloxone group, while methadone/lofexidine led to earlier peak withdrawal symptoms during detoxification.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buprenorphine/naloxone versus methadone and lofexidine in community stabilisation and detoxification: A randomised controlled trial of low dose short-term opiate-dependent individuals. Law, FD., Diaper, AM., Melichar, JK., et al.[2018]

Lofexidine (LFX) at a dose of 2.4 mg/day was found to significantly improve control over opioid cravings in individuals with opioid use disorder when combined with naltrexone (NTX), compared to a placebo group.

While LFX showed promise in enhancing treatment compliance and reducing opioid cravings, it also had a higher withdrawal rate due to medication intolerance, indicating the need for careful monitoring and potential dose adjustments in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lofexidine in Combination With Oral Naltrexone for Opioid Use Disorder Relapse Prevention: A Pilot Randomized, Double-Blind, Placebo-Controlled Study. Hermes, G., Hyman, SM., Fogelman, N., et al.[2020]

In a double-blind, randomized trial involving 89 opiate-dependent patients, lofexidine combined with naloxone did not significantly improve detoxification completion rates compared to lofexidine with placebo.

Patients receiving naloxone experienced lower withdrawal levels throughout detoxification, indicating it may help manage cravings, but it did not significantly speed up the overall resolution of withdrawal symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effectiveness of combined naloxone/lofexidine in opiate detoxification: results from a double-blind randomized and placebo-controlled trial. Beswick, T., Best, D., Bearn, J., et al.[2016]

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]

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 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]

In a case series of 17 patients undergoing inpatient treatment for opioid withdrawal, lofexidine was found to effectively reduce withdrawal symptoms, with 65% of patients showing decreased clinical opioid withdrawal scale (COWS) scores from intake to discharge.

Lofexidine was well-tolerated, with stable blood pressure and a decrease in heart rate over time, indicating its safety in a clinical setting, although barriers such as cost and accessibility remain challenges for broader use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lofexidine for acute opioid withdrawal: A clinical case series. Renfro, ML., Loera, LJ., Tirado, CF., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Pharmaceutical Approval Update. [2020]

2. England pubmed.ncbi.nlm.nih.gov

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

3. United States pubmed.ncbi.nlm.nih.gov

Buprenorphine/naloxone versus methadone and lofexidine in community stabilisation and detoxification: A randomised controlled trial of low dose short-term opiate-dependent individuals. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Lofexidine in Combination With Oral Naltrexone for Opioid Use Disorder Relapse Prevention: A Pilot Randomized, Double-Blind, Placebo-Controlled Study. [2020]

5. England pubmed.ncbi.nlm.nih.gov

The effectiveness of combined naloxone/lofexidine in opiate detoxification: results from a double-blind randomized and placebo-controlled trial. [2016]

6. Ireland pubmed.ncbi.nlm.nih.gov

Effect of lofexidine on cardiac repolarization during treatment of opioid withdrawal. [2020]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Lofexidine for Medically Managed Opioid Withdrawal: A Randomized Controlled Clinical Trial. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Lofexidine: A Newly FDA-Approved, Nonopioid Treatment for Opioid Withdrawal. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

Lofexidine for acute opioid withdrawal: A clinical case series. [2022]