search
Back to results

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

Primary Purpose

Opioid Withdrawal (Disorder)

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Standard of Care with Lofexidine
Standard of Care without Lofexidine
Sponsored by
USWM, LLC (dba US WorldMeds)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Opioid Withdrawal (Disorder)

Eligibility Criteria

0 Hours - 6 Days (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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. Infants <7 days of age at the time of randomization. Gestational age ≥35 weeks at birth. Minimum weight ≥1.8 kg at birth. Infant's mother is ≥18 years of age. Intrauterine opiate exposure expected to contribute to NOWS symptoms, as determined by the Principal Investigator and supported by at least one of the following: 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; Positive maternal urine opiate screen during pregnancy or delivery; or Participant urine, meconium, or cord blood or tissue testing positive for opiate metabolites. 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. Can receive medications orally. Exclusion Criteria: Patients who developed NOWS due to prolonged neonatal intensive care unit (NICU) analgesia and sedation therapy. Received treatment for NOWS, including morphine, methadone, buprenorphine, clonidine, or phenobarbital before screening/randomization. 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. 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). Seizures, confirmed by EEG. mFNAST score ≥14. Two consecutive blood pressure measurements greater than 15 minutes apart with a systolic blood pressure <55 mm Hg. Two consecutive heart rate measurements <110 bpm more than 15 minutes apart. 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. 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: Hematocrit values of <40% Platelet count <100,000/μL 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. 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.

Sites / Locations

  • Marshall HealthRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Placebo Comparator

Experimental

Experimental

Experimental

Arm Label

Control

Low Dose Lofexidine

Mid Dose Lofexidine

High Dose Lofexidine

Arm Description

All participants will receive non pharmacologic interventions per the local standard of care (i.e. non-pharmacologic measures and morphine when indicated).

Drug: Lofexidine (LX2) All participants will receive standard of care and be administered 32 µg/kg/day. The daily dose will be divided into 8 equal doses administered every 3 hours. Lofexidine will be tapered to discontinuation.

Drug: Lofexidine (LX2) All participants will receive standard of care and be administered 52 µg/kg/day. The daily dose will be divided into 8 equal doses administered every 3 hours. Lofexidine will be tapered to discontinuation.

Drug: Lofexidine (LX2) All participants will receive standard of care and be administered 80 µg/kg/day. The daily dose will be divided into 8 equal doses administered every 3 hours. Lofexidine will be tapered to discontinuation.

Outcomes

Primary Outcome Measures

Plasma concentrations following single dose and repeated lofexidine administration in participants
To evaluate the pharmacokinetic (PK) parameters of lofexidine granules for reconstitution

Secondary Outcome Measures

Single dose and steady-state maximum concentrations
To evaluate the pharmacokinetic (PK) parameters of lofexidine granules for To evaluate the pharmacokinetic (PK) parameters of lofexidine granules for reconstitution
Extent of accumulation (i.e., Accumulation Ratio [AR]) with repeated dosing
To evaluate the pharmacokinetic (PK) parameters of lofexidine granules for reconstitution
Examination of dose proportionality
To evaluate the pharmacokinetic (PK) parameters of lofexidine granules for reconstitution
Estimation of apparent clearance
To evaluate the pharmacokinetic (PK) parameters of lofexidine granules for reconstitution
Estimation of apparent volume of distribution
To evaluate the pharmacokinetic (PK) parameters of lofexidine granules for reconstitution
Treatment emergent adverse events (TEAEs)
To evaluate the safety of lofexidine during administration in infants experiencing NOWS

Full Information

First Posted
July 18, 2023
Last Updated
October 16, 2023
Sponsor
USWM, LLC (dba US WorldMeds)
Collaborators
National Institute on Drug Abuse (NIDA)
search

1. Study Identification

Unique Protocol Identification Number
NCT06047834
Brief Title
Pharmacokinetic and Safety Study of Oral Lofexidine in Neonates Experiencing Opioid Withdrawal Due to Intrauterine Exposure to Opioids
Official Title
A Phase 2, Open-Label, Randomized, Controlled, Ascending Dose Cohort, Pharmacokinetic and Safety Study of Oral Lofexidine in Neonates Experiencing Opioid Withdrawal Due to Intrauterine Exposure to Opioids
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 2, 2023 (Actual)
Primary Completion Date
May 2024 (Anticipated)
Study Completion Date
May 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
USWM, LLC (dba US WorldMeds)
Collaborators
National Institute on Drug Abuse (NIDA)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Opioid Withdrawal (Disorder)

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Control
Arm Type
Placebo Comparator
Arm Description
All participants will receive non pharmacologic interventions per the local standard of care (i.e. non-pharmacologic measures and morphine when indicated).
Arm Title
Low Dose Lofexidine
Arm Type
Experimental
Arm Description
Drug: Lofexidine (LX2) All participants will receive standard of care and be administered 32 µg/kg/day. The daily dose will be divided into 8 equal doses administered every 3 hours. Lofexidine will be tapered to discontinuation.
Arm Title
Mid Dose Lofexidine
Arm Type
Experimental
Arm Description
Drug: Lofexidine (LX2) All participants will receive standard of care and be administered 52 µg/kg/day. The daily dose will be divided into 8 equal doses administered every 3 hours. Lofexidine will be tapered to discontinuation.
Arm Title
High Dose Lofexidine
Arm Type
Experimental
Arm Description
Drug: Lofexidine (LX2) All participants will receive standard of care and be administered 80 µg/kg/day. The daily dose will be divided into 8 equal doses administered every 3 hours. Lofexidine will be tapered to discontinuation.
Intervention Type
Drug
Intervention Name(s)
Standard of Care with Lofexidine
Intervention Description
Participants will be randomized 3:1 to treatment with standard of care with or without lofexidine. Subjects randomized to standard of care with lofexidine will be sequentially assigned to 1 of 3 escalating dose levels (in terms of lofexidine base): low dose, mid dose, or high dose.
Intervention Type
Other
Intervention Name(s)
Standard of Care without Lofexidine
Intervention Description
Participants will be randomized 3:1 to treatment with standard of care with or without lofexidine. Subjects randomized to standard of care without lofexidine wilt receive non-pharmacologic measures and morphine when indicated.
Primary Outcome Measure Information:
Title
Plasma concentrations following single dose and repeated lofexidine administration in participants
Description
To evaluate the pharmacokinetic (PK) parameters of lofexidine granules for reconstitution
Time Frame
Day 1 through Day 7
Secondary Outcome Measure Information:
Title
Single dose and steady-state maximum concentrations
Description
To evaluate the pharmacokinetic (PK) parameters of lofexidine granules for To evaluate the pharmacokinetic (PK) parameters of lofexidine granules for reconstitution
Time Frame
Day 1 through Day 7
Title
Extent of accumulation (i.e., Accumulation Ratio [AR]) with repeated dosing
Description
To evaluate the pharmacokinetic (PK) parameters of lofexidine granules for reconstitution
Time Frame
Day 1 through Day 7
Title
Examination of dose proportionality
Description
To evaluate the pharmacokinetic (PK) parameters of lofexidine granules for reconstitution
Time Frame
Day 1 through Day 7
Title
Estimation of apparent clearance
Description
To evaluate the pharmacokinetic (PK) parameters of lofexidine granules for reconstitution
Time Frame
Day 1 through Day 7
Title
Estimation of apparent volume of distribution
Description
To evaluate the pharmacokinetic (PK) parameters of lofexidine granules for reconstitution
Time Frame
Day 1 through Day 7
Title
Treatment emergent adverse events (TEAEs)
Description
To evaluate the safety of lofexidine during administration in infants experiencing NOWS
Time Frame
Day 1 through 30 day follow-up

10. Eligibility

Sex
All
Minimum Age & Unit of Time
0 Hours
Maximum Age & Unit of Time
6 Days
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Infants <7 days of age at the time of randomization. Gestational age ≥35 weeks at birth. Minimum weight ≥1.8 kg at birth. Infant's mother is ≥18 years of age. Intrauterine opiate exposure expected to contribute to NOWS symptoms, as determined by the Principal Investigator and supported by at least one of the following: 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; Positive maternal urine opiate screen during pregnancy or delivery; or Participant urine, meconium, or cord blood or tissue testing positive for opiate metabolites. 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. Can receive medications orally. Exclusion Criteria: Patients who developed NOWS due to prolonged neonatal intensive care unit (NICU) analgesia and sedation therapy. Received treatment for NOWS, including morphine, methadone, buprenorphine, clonidine, or phenobarbital before screening/randomization. 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. 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). Seizures, confirmed by EEG. mFNAST score ≥14. Two consecutive blood pressure measurements greater than 15 minutes apart with a systolic blood pressure <55 mm Hg. Two consecutive heart rate measurements <110 bpm more than 15 minutes apart. 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. 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: Hematocrit values of <40% Platelet count <100,000/μL 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. 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Medical Affairs
Phone
1-888-900-8796
Email
medinfo@usworldmeds.com
Facility Information:
Facility Name
Marshall Health
City
Huntington
State/Province
West Virginia
ZIP/Postal Code
25701
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Todd Davies, PhD
Email
daviest@marshall.edu

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs