24 Participants Needed

Lofexidine for Neonatal Opioid Withdrawal

MA
AD
KN
Overseen ByKim New Senior Director, Clinical Research and Data Sciences
Prior Safety DataThis treatment has passed at least one previous human trial
Approved in 2 JurisdictionsThis treatment is already approved in other countries

Trial Summary

What is the purpose of this trial?

A randomized, open-label, controlled, ascending dose cohort, PK, and safety study assessing standard of care (i.e., non-pharmacologic measures and morphine when indicated) with or without lofexidine for the treatment of opioid withdrawal symptoms in neonates due to intrauterine exposure to opioids, described as neonatal opioid withdrawal syndrome (NOWS) or neonatal abstinence syndrome (NAS). This study has been designed to assess the pharmacokinetics (PK) and safety of the lofexidine in neonates experiencing NOWS. The effectiveness of lofexidine on the severity of NOWS will also be evaluated. Results from this study will be used to support dosing recommendations in neonates and to inform further studies in the pediatric patient population.

Will I have to stop taking my current medications?

The trial does not specify if participants must stop taking their current medications. However, infants who have already received treatment for NOWS with certain medications like morphine, methadone, buprenorphine, clonidine, or phenobarbital before screening are excluded from the study.

What data supports the effectiveness of the drug Lofexidine for treating neonatal opioid withdrawal?

Lofexidine is known to help with opioid withdrawal by reducing symptoms like anxiety and agitation, as it calms the nervous system. It has been used successfully for opioid withdrawal in adults, which suggests it might also help newborns experiencing similar withdrawal symptoms.12345

Is Lofexidine safe for humans?

Lofexidine has been shown in clinical trials to be safe for managing opioid withdrawal symptoms, but it can cause side effects like QT prolongation (a heart rhythm issue), low blood pressure, dizziness when standing up, and slow heart rate.24567

How is the drug Lofexidine unique for treating neonatal opioid withdrawal?

Lofexidine is unique because it is a non-opioid drug that helps manage withdrawal symptoms by reducing the body's stress response (sympathetic outflow) without reinforcing opioid dependence. It works by targeting specific receptors in the body, making it different from other treatments that may involve opioids or have less specificity.12457

Eligibility Criteria

This trial is for newborns under 7 days old, born at or after 35 weeks of gestation, weighing at least 1.8 kg, who are experiencing opioid withdrawal due to their mother's opioid use during pregnancy. The baby must be able to take oral medication and show specific signs of withdrawal. Babies with certain health issues like low heart rate, seizures, low platelet count, or those already treated for withdrawal are excluded.

Inclusion Criteria

Positive maternal urine opiate screen during pregnancy or delivery
My mother used opiates during her pregnancy with me.
I have severe symptoms measured by a specific test or agreed by my care team.
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Exclusion Criteria

I do not have any surgeries planned during or within 30 days after my NOWS treatment, except for circumcision.
Two consecutive blood pressure measurements greater than 15 minutes apart with a systolic blood pressure <55 mm Hg
Clinically significant abnormal ECG at Screening in the judgment of the Principal Investigator, including a QTc interval >480 msec on a Screening ECG. Note: if the QTc interval meets the above criteria, the value may be confirmed by repeating the measurement twice, with each ECG obtained approximately 30-60 minutes apart, and the QTc interval confirmed by a pediatric cardiologist. If the pediatric cardiologist confirms the QTc interval is >480 msec based on two of the three ECGs, the patient will be excluded from participation. If the pediatric cardiologist confirms the QTc interval is ≤480 msec based on two of the three ECGs, the patient may be considered for study entry at the discretion of the Investigator in consultation with the pediatric cardiologist. Patients with a confirmed QTc >480 msec at Screening will be monitored per local standard of care, at least once daily, until the QTc resolves to within normal range. Patients not enrolled in the study will receive additional evaluation and care as clinically indicated
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Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive standard of care and varying doses of Lofexidine for the treatment of opioid withdrawal symptoms

7 days
Daily monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

Treatment Details

Interventions

  • Lofexidine
Trial Overview The study is testing the safety and how the body processes a drug called Lofexidine in babies going through opioid withdrawal (NOWS). It compares standard care alone versus standard care plus Lofexidine to see if it helps reduce symptoms of NOWS more effectively.
Participant Groups
4Treatment groups
Experimental Treatment
Placebo Group
Group I: Dose 3Experimental Treatment1 Intervention
Drug: Lofexidine (LX2) All participants will receive standard of care and 16-24 µg/kg/day of Lofexidine, administered every 6 hours, with the final daily dose level to be decided based upon data collected in participants receiving Dose 2. Lofexidine will be tapered to discontinuation.
Group II: Dose 2Experimental Treatment1 Intervention
Drug: Lofexidine (LX2) All participants will receive standard of care and 20 µg/kg/day of Lofexidine, administered as 5 µg/kg/day every 3 hours. Lofexidine will be tapered to discontinuation.
Group III: Dose 1Experimental Treatment1 Intervention
Drug: Lofexidine (LX2) All participants will receive standard of care and 32 µg/kg/day of Lofexidine, administered as 4 µg/kg/day every 3 hours. Lofexidine will be tapered to discontinuation.
Group IV: ControlPlacebo Group1 Intervention
All participants will receive non pharmacologic interventions per the local standard of care (i.e. non-pharmacologic measures and morphine when indicated).

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

Find a Clinic Near You

Who Is Running the Clinical Trial?

USWM, LLC (dba US WorldMeds)

Lead Sponsor

Trials
24
Recruited
1,800+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials
2,658
Recruited
3,409,000+

Findings from Research

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.
The preclinical discovery of lofexidine for the treatment of opiate addiction.Vartak, AP.[2014]
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.
Effect of lofexidine on cardiac repolarization during treatment of opioid withdrawal.Darpö, B., Pirner, M., Longstreth, J., et al.[2020]
In a review of 11 studies on neonatal opioid withdrawal syndrome (NOWS), methadone was found to be more effective than morphine for primary treatment outcomes, showing no significant difference in treatment duration or hospitalization time between the two.
Buprenorphine demonstrated the shortest treatment and hospitalization durations compared to both morphine and methadone, suggesting it may be a more efficient option for managing NOWS.
Comparative effectiveness of opioid replacement agents for neonatal opioid withdrawal syndrome: a systematic review and meta-analysis.Lee, JJ., Chen, J., Eisler, L., et al.[2022]

References

The preclinical discovery of lofexidine for the treatment of opiate addiction. [2014]
Effect of lofexidine on cardiac repolarization during treatment of opioid withdrawal. [2020]
Comparative effectiveness of opioid replacement agents for neonatal opioid withdrawal syndrome: a systematic review and meta-analysis. [2022]
Lofexidine: A Newly FDA-Approved, Nonopioid Treatment for Opioid Withdrawal. [2020]
Pharmaceutical Approval Update. [2020]
Safety and Efficacy of Lofexidine for Medically Managed Opioid Withdrawal: A Randomized Controlled Clinical Trial. [2020]
The Role of Lofexidine in Management of Opioid Withdrawal. [2023]
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