Buprenorphine for Opioid Use Disorder in Pregnancy

(MOMs-INO Trial)

No longer recruiting at 9 trial locations

Overseen By Frankie Kropp, MS

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: T. John Winhusen, PhD

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months postpartum

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how different forms of buprenorphine, a medication for opioid addiction, affect the brain development of infants whose mothers participated in a previous study on opioid use during pregnancy. Researchers compare an injectable form of buprenorphine to a sublingual (under-the-tongue) version to determine which better supports these infants. The trial specifically targets caregivers of infants born to mothers involved in the original study. As a Phase 3 trial, it represents the final step before FDA approval, providing an opportunity to contribute to significant advancements in infant care.

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

The protocol does not specify whether you need to stop taking your current medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Studies have shown that buprenorphine is a safe option for treating opioid use disorder during pregnancy. Research indicates that the extended-release injection form of buprenorphine (BUP-XR) does not increase risk and meets safety standards for pregnant women.

Evidence also supports the safety of the sublingual (under-the-tongue) version for pregnant women. The combination of buprenorphine and naloxone, often used in this form, is considered safe during pregnancy. Both forms help manage opioid dependence without adding risks to the pregnancy.

In summary, whether injected or taken under the tongue, buprenorphine is generally well-tolerated during pregnancy, supporting healthy outcomes for both mother and baby. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about buprenorphine treatments for opioid use disorder in pregnancy because they offer flexibility and tailored dosing for expectant mothers. Unlike traditional oral options, the Buprenorphine Injection (BUP-XR) provides a long-acting, weekly or monthly subcutaneous delivery. This could improve adherence and provide consistent medication levels. The Buprenorphine Sublingual Product (BUP-SL), on the other hand, allows for daily dosing that can be adjusted based on cravings and withdrawal symptoms. Both approaches aim to support maternal and fetal health by maintaining stability during pregnancy and postpartum.

What evidence suggests that this trial's treatments could be effective for opioid use disorder in pregnancy?

Research has shown that buprenorphine effectively treats opioid use disorder (OUD) in pregnant women. In this trial, participants may receive either the injection form or the under-the-tongue (sublingual) form of buprenorphine. Studies have found that both forms can improve health outcomes for mothers and their babies. The injection form maintains steady drug levels without increasing risk, which is beneficial during pregnancy. The under-the-tongue form is also effective and often yields better results than methadone, another treatment option. Overall, buprenorphine is a strong choice for managing OUD in pregnant women. ^{1 3 5 6 7}

Who Is on the Research Team?

T. John Winhusen, PhD

Principal Investigator

University of Cincinnati

Are You a Good Fit for This Trial?

This trial is for caretakers of infants born to mothers who were part of the MOMs trial, which looked at opioid use disorder treatments during pregnancy. The study focuses on how two forms of buprenorphine affect the baby's brain development.

Inclusion Criteria

The participant must be the caretaker of an infant that was delivered as part of the MOMs trial.

Exclusion Criteria

I'm sorry, I cannot provide a plain and simple language summary of a criterion if there is no criterion provided. Please provide me with the criterion you would like me to simplify.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either weekly subcutaneous Buprenorphine Injection or daily sublingual buprenorphine during pregnancy and postpartum

12 months postpartum

Follow-up

Participants are monitored for infant neurodevelopmental outcomes using the Bayley Scales of Infant Development and Child Behavior Checklist

24 months postpartum

What Are the Treatments Tested in This Trial?

Interventions

• Buprenorphine Injection
• Buprenorphine Sublingual Product

Trial Overview

The sub-study compares extended-release buprenorphine injections (BUP-XR) with sublingual products (BUP-SL) to see their impact on infant neurodevelopment. It extends research from the main MOMs trial involving expectant mothers with opioid addiction.

How Is the Trial Designed?

Group I: BUP-XR Experimental Treatment 1 Intervention

Weekly subcutaneous Buprenorphine Injection (CAM2038) during pregnancy. During the 12-month postpartum phase, participants who are breastfeeding will continue receiving subcutaneous Buprenorphine Injection weekly; participants who are not breastfeeding will receive subcutaneous Buprenorphine Injection monthly. The target doses will be 24 mg for the weekly formulation and 96 mg for the monthly formulation, but the actual dose may be lower or higher as determined by the prescribing clinician (e.g., based on craving/withdrawal experienced by the participant, etc.).

Group II: BUP-SL Active Control 1 Intervention

Daily sublingual buprenorphine, with or without naloxone, based on site preference, during pregnancy and during the 12-month postpartum phase. The target dose will be 16 mg daily, but the actual dose may be lower or higher as determined by the prescribing clinician (e.g., based on craving/withdrawal experienced by the participant, etc.).

Who Is Running the Clinical Trial?

T. John Winhusen, PhD

Lead Sponsor

Trials

5

Recruited

750+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

The Emmes Company, LLC

Industry Sponsor

Trials

149

Recruited

1,052,000+

Peter Ronco

The Emmes Company, LLC

Chief Executive Officer since 2023

BSc from Nottingham University

Dr. Joe Sliman

The Emmes Company, LLC

Chief Medical Officer since 2020

MD from Uniformed Services University of the Health Sciences, MPH from Johns Hopkins University, BSc in Molecular and Cell Biology from Pennsylvania State University

Published Research Related to This Trial

In a study involving three opioid-dependent pregnant women, daily sublingual buprenorphine (8 or 12 mg) for 15-16 weeks was found to be safe and effective, resulting in normal birth outcomes.

Neonatal abstinence syndrome was relatively mild, with symptoms like tremors and hyperactivity, and did not require pharmacological treatment, indicating that buprenorphine can be a viable option for treating opioid dependence in pregnant women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buprenorphine treatment of pregnant opioid--dependent women: maternal and neonatal outcomes. Johnson, RE., Jones, HE., Jasinski, DR., et al.[2019]

Sublingual buprenorphine was found to be effective in managing neonatal abstinence syndrome, with a shorter average treatment duration of 22 days compared to 32 days for standard oral neonatal opium solution.

The study suggests that buprenorphine is well tolerated and safe for neonates, with a reduced length of hospital stay (27 days for buprenorphine vs. 38 days for standard care), indicating its potential as a novel treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sublingual buprenorphine for treatment of neonatal abstinence syndrome: a randomized trial. Kraft, WK., Gibson, E., Dysart, K., et al.[2021]

Infants exposed to buprenorphine alone had a significantly higher rate of neonatal abstinence syndrome (54.6%) compared to those exposed to the buprenorphine and naloxone combination (35.3%), suggesting that the combination product may be safer for fetal outcomes.

The study indicates that while the combined buprenorphine and naloxone product is associated with lower odds of neonatal abstinence syndrome, these results were not statistically significant after adjusting for other factors, indicating that both treatments are acceptable options for managing opioid use disorder during pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buprenorphine and Naloxone Versus Buprenorphine for Opioid Use Disorder in Pregnancy: A Cohort Study. Mullins, N., Galvin, SL., Ramage, M., et al.[2021]

Two case studies of pregnant patients with opioid use disorder (OUD) who switched from sublingual buprenorphine to monthly injections of Sublocade® showed no adverse outcomes for either the mothers or their babies, suggesting potential safety in this treatment during pregnancy.

Both patients maintained positive urine drug screens for buprenorphine throughout their pregnancies without experiencing withdrawal symptoms or birth anomalies, indicating that Sublocade may be a viable option for managing OUD in pregnant women, although further research is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous Extended-Release Buprenorphine Use in Pregnancy. Towers, CV., Deisher, H.[2022]

Increasing access to buprenorphine, a treatment for opioid use disorder, is crucial for reducing overdose deaths, but limited availability of buprenorphine monoproduct is a significant barrier.

The requirement to prescribe buprenorphine as a combination product with naloxone may lead to adverse effects that are more serious than previously thought, potentially harming the patient-provider relationship and increasing stigma, which can hinder access to care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Naloxone Component of Buprenorphine/Naloxone: Discouraging Misuse, but at What Cost? Gregg, J., Hartley, J., Lawrence, D., et al.[2023]

In a study of 13 pregnant women receiving sublingual buprenorphine, it was found that the plasma concentrations of the drug were significantly lower during pregnancy compared to the postpartum period, indicating that pregnant women may require higher doses to achieve similar therapeutic effects.

The research showed that specific pharmacokinetic parameters, such as the area under the plasma concentration-time curve and maximum buprenorphine concentrations, were significantly reduced during pregnancy, suggesting an increased clearance of the drug in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-adjusted plasma concentrations of sublingual buprenorphine are lower during than after pregnancy. Bastian, JR., Chen, H., Zhang, H., et al.[2023]

From 2006 to 2010, the number of pregnant women treated for opioid use disorder nearly doubled, highlighting a significant increase in this public health issue during the opioid epidemic.

Buprenorphine treatment became more prevalent, rising from 3% to 41% of cases, and was associated with an increase in neonatal abstinence syndrome (NAS) treatment, indicating a need for improved prenatal care for affected mothers and their infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prenatal treatment for opioid dependency: observations from a large inner-city clinic. Saia, K., Bagley, SM., Wachman, EM., et al.[2018]

Buprenorphine treatment for pregnant women with opioid use disorder is associated with a lower risk of preterm birth and results in greater birth weight and larger head circumference compared to methadone, based on a review of 18 studies involving 2,146 participants.

There were no significant differences in rates of fetal death or congenital anomalies between the two treatments, suggesting that buprenorphine does not pose greater risks than methadone for these outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buprenorphine compared with methadone to treat pregnant women with opioid use disorder: a systematic review and meta-analysis of safety in the mother, fetus and child. Zedler, BK., Mann, AL., Kim, MM., et al.[2023]

Buprenorphine is increasingly being used as a treatment for pregnant women with opioid use disorder (OUD), rising from 10.1% to 33.2% between 2009 and 2012, and is associated with better neonatal outcomes compared to methadone.

Women using buprenorphine tend to be older, more educated, and employed, while those on methadone are more likely to have a history of severe substance use issues, highlighting disparities in treatment access and the need for improved availability of buprenorphine for pregnant women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Factors associated with buprenorphine versus methadone use in pregnancy. Krans, EE., Bogen, D., Richardson, G., et al.[2018]

The novel subcutaneous depot formulation of buprenorphine (CAM2038 q1w) demonstrated dose-proportional pharmacokinetics, supporting its use for once-weekly dosing in patients with opioid use disorder, with a median time to first use of rescue medication being 10 days.

Patients experienced a significant and sustained reduction in opiate withdrawal symptoms for at least 7 days after a single dose of CAM2038 q1w, indicating its efficacy in maintaining treatment without the need for daily dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and pharmacodynamics of a buprenorphine subcutaneous depot formulation (CAM2038) for once-weekly dosing in patients with opioid use disorder. Haasen, C., Linden, M., Tiberg, F.[2018]

Citations

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Three sources of data illustrate that the use of monthly BUP-XR during pregnancy has demonstrated no increased risk and is consistent with the ...

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Buprenorphine may be associated with more favorable neonatal and maternal outcomes than methadone, but existing data are limited.

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pubmed.ncbi.nlm.nih.gov

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Three sources of data illustrate that the use of monthly BUP-XR during pregnancy has demonstrated no increased risk and is consistent with the ...

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Treatment of Opioid Use Disorder Before, During, and After ...

A treatment plan for opioid use disorder (OUD) can increase the chances of a healthy pregnancy. · Methadone and buprenorphine are recommended ...