Using Lofexidine to Treat Opioid Withdrawal in Newborns

A Phase 2, Open-Label, Randomized, Controlled, Dose Cohort, Pharmacokinetic and Safety Study of Oral Lofexidine in Neonates Experiencing Opioid Withdrawal Due to Intrauterine Exposure to Opioids

This study is testing if adding lofexidine to standard care can help newborns with opioid withdrawal feel better and reduce their symptoms.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 0 Hours to 6 Days
• Sex: All
• Sponsor: USWM, LLC (dba US WorldMeds) (Industry-sponsored)
• Locations: 1 site (Huntington, West Virginia)
• Trial ID: NCT06047834 on ClinicalTrials.gov

What this trial studies

This study evaluates the pharmacokinetics and safety of lofexidine in neonates experiencing opioid withdrawal due to intrauterine exposure to opioids. It compares standard care practices, which may include non-pharmacologic measures and morphine, with the addition of lofexidine. The study aims to determine the effectiveness of lofexidine in reducing the severity of neonatal opioid withdrawal syndrome (NOWS) and to establish appropriate dosing recommendations for this vulnerable population. The trial is randomized and open-label, involving infants less than 7 days old who meet specific eligibility criteria.

Who should consider this trial

Good fit: Ideal candidates for this study are infants less than 7 days old with a gestational age of at least 35 weeks who have been exposed to opioids in utero.

Not a fit: Patients who are not experiencing opioid withdrawal symptoms or those who do not meet the specific inclusion criteria will not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option for managing opioid withdrawal symptoms in neonates, potentially improving their health outcomes.

How similar studies have performed: While there is limited data on the use of lofexidine in neonates, similar studies on opioid withdrawal treatments have shown promise, making this approach potentially beneficial yet somewhat novel.

Eligibility criteria

Inclusion Criteria:

1. Written informed consent obtained from the patient's parent or legally authorized representative(s) (LAR)/guardian(s) in accordance with local laws and Institutional Review Board (IRB) requirements.
2. Infants \<7 days of age at the time of randomization.
3. Gestational age ≥35 weeks at birth.
4. Minimum weight ≥1.8 kg at birth.
5. Infant's mother is ≥18 years of age.
6. Intrauterine opiate exposure expected to contribute to NOWS symptoms, as determined by the Principal Investigator and supported by at least one of the following:

   1. Maternal history of opiate use during pregnancy as confirmed by diagnosis of opioid use disorder (OUD) according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), treatment for OUD, treatment with an opioid prescribed by a licensed physician or health care worker, documentation of opiate use in maternal medical record, and/or maternal self-reported opiate use;
   2. Positive maternal urine opiate screen during pregnancy or delivery; or
   3. Participant urine, meconium, or cord blood or tissue testing positive for opiate metabolites.
7. Symptomatic with 2 consecutive scores ≥8 on the mFNAST at sites using the mFNAST OR at least one score ≥1 on the ESC assessment and with agreement from the clinical care team at sites using the ESC approach to care. Note: The study team should use the same NOWS scoring method (i.e., mFNAST or ESC assessment) to determine the patient's eligibility as is used to assess NOWS symptoms per the local standard of care.
8. Can receive medications orally.

Exclusion Criteria:

1. Patients who developed NOWS due to prolonged neonatal intensive care unit (NICU) analgesia and sedation therapy.
2. Received treatment for NOWS, including morphine, methadone, buprenorphine, clonidine, or phenobarbital before screening/randomization.
3. Prenatal exposure to an investigational drug, device, or biological agent other than investigational formulations of buprenorphine or methadone administered as part of treatment for maternal opioid dependence.
4. Any anticipated or scheduled surgery during the patient's inpatient treatment for NOWS through approximately 30 days after completion of their treatment for NOWS (not including circumcision).
5. Seizures, confirmed by EEG.
6. mFNAST score ≥14.
7. Two consecutive blood pressure measurements greater than 15 minutes apart with a systolic blood pressure \<55 mm Hg.
8. Two consecutive heart rate measurements \<110 bpm more than 15 minutes apart.
9. 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.
10. Have clinically significant abnormal laboratory values on laboratory tests completed for clinical reasons, including laboratory values outside the normal range as determined by the local lab that would put the patient at undue risk, as determined by the Principal Investigator, including either of the following:

    1. Hematocrit values of \<40%
    2. Platelet count \<100,000/μL
11. Requiring sustained treatment with IV fluids or supplemental oxygen. Note: Patients with a transient need for IV fluids or supplemental oxygen may be considered for inclusion in the study at the Investigator's discretion.
12. Any congenital malformations or acute medical illness, condition, or clinical finding that, in the opinion of the Principal Investigator and/or the Sponsor, would put the patient at undue risk for study participation or interfere with the patient's ability to complete the study, including concerns related to medication administration or patient survival.

Where this trial is running

Huntington, West Virginia

• Marshall Health — Huntington, West Virginia, United States (Recruiting)

Study contacts

• Study coordinator: Amanda DeVore Sr Clinical Research Specialist

Conditions Opioid Withdrawal