Buprenorphine for Opioid Use Disorder in Pregnancy

(MOMs-INO Trial)

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

71 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a sub-study of NIDA CTN Protocol 0080: Medication Treatment for Opioid Use Disorder in Expectant Mothers (MOMs; Unique protocol ID: 2019-0429-1). Caretakers of the infants delivered by MOMs participants will be offered the opportunity to enroll in this sub-study, which is designed to evaluate the impact of extended-release buprenorphine (BUP-XR), relative to sublingual buprenorphine (BUP-SL), on infant neurodevelopment. The additional data collected in this sub-study will be combined with data from the main MOMs trial.

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.

What data supports the idea that Buprenorphine for Opioid Use Disorder in Pregnancy is an effective drug?

The available research shows that Buprenorphine is effective for treating opioid use disorder in pregnant women. One study found that pregnant women who used Buprenorphine had normal birth outcomes and their babies experienced only mild withdrawal symptoms, which did not require additional medication. Another study highlighted that Buprenorphine, when combined with prenatal care, was safe and effective, leading to short hospital stays for newborns. These findings suggest that Buprenorphine is a promising option for managing opioid use disorder during pregnancy. ^{1 2 3 4 5}

What safety data exists for using buprenorphine in pregnant women with opioid use disorder?

Existing safety data indicates that buprenorphine is safe for use in pregnant women with opioid use disorder. Studies show that prenatal exposure to buprenorphine results in normal birth outcomes and a relatively mild neonatal abstinence syndrome, with symptoms peaking by 72 hours and resolving by 120 hours. Infants typically do not require pharmacological treatment. Buprenorphine is considered safe and effective when combined with comprehensive prenatal care. Comparisons with methadone also support its safety for mothers, fetuses, and children. ^{1 2 3 6 7}

Is the drug Buprenorphine Injection, Buprenorphine Sublingual Product a promising treatment for opioid use disorder in pregnancy?

Yes, Buprenorphine is a promising treatment for opioid use disorder in pregnancy. It is considered safe and effective, and it is associated with better outcomes for newborns compared to other treatments like methadone. ^{2 5 8 9 10}

Research Team

T. John Winhusen, PhD

Principal Investigator

University of Cincinnati

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Buprenorphine and Naloxone Versus Buprenorphine for Opioid Use Disorder in Pregnancy: A Cohort Study. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Sublingual buprenorphine for treatment of neonatal abstinence syndrome: a randomized trial. [2021]

3. Ireland pubmed.ncbi.nlm.nih.gov

Buprenorphine treatment of pregnant opioid--dependent women: maternal and neonatal outcomes. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Prenatal treatment for opioid dependency: observations from a large inner-city clinic. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Subcutaneous Extended-Release Buprenorphine Use in Pregnancy. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

The Naloxone Component of Buprenorphine/Naloxone: Discouraging Misuse, but at What Cost? [2023]

7. England 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. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Factors associated with buprenorphine versus methadone use in pregnancy. [2018]

9. United States 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. [2018]

10. United States pubmed.ncbi.nlm.nih.gov

Dose-adjusted plasma concentrations of sublingual buprenorphine are lower during than after pregnancy. [2023]