Overview

Pharmacokinetic and Safety Study of Oral Lofexidine in Neonates Experiencing Opioid Withdrawal Due to Intrauterine Exposure to Opioids

Status:
Recruiting
Trial end date:
2026-05-01
Target enrollment:
0
Participant gender:
All
Summary
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.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
USWM, LLC (dba US WorldMeds)
Collaborator:
National Institute on Drug Abuse (NIDA)
Treatments:
Clonidine
Lofexidine
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.