Buprenorphine Pharmacometric Open Label Research Study of Drug Exposure

NCT03608696 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 18C.272
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Neonatal withdrawal syndrome is a series of signs and symptoms in infants exposed to opioids in utero. Buprenorphine has demonstrated a 40% reduction in length of pharmacologic treatment compared to oral morphine. These results were with an empirically derived dose. This study will use pharmacokinetic modeling-informed dosing to clarify the dose/response relationship and use a rational approach to define an optimal dose regimen. The clinical trial will be open label, single arm design with a goal of initial testing of a new dosing regimen.

Conditions

Neonatal Abstinence Syndrome; Neonatal Opiate Withdrawal Syndrome

Keywords

buprenorphine; pharmacometrics

Outcome Measures

Primary Outcomes (1)

• Buprenorphine Pharmacokinetics

  Goal is to define buprenorphine pharmacokinetic exposure (Area under the plasma concentration versus time curve (AUC)) in infants treated with buprenorphine for neonatal abstinence syndrome (NAS) using a model-based optimized dose.

  Duration of pharmacologic treatment for neonatal abstinence syndrome up to 70 days of age

Other Outcomes (2)

• Number of Participants With Treatment Related Adverse Events

  Duration of pharmacologic treatment for neonatal abstinence syndrome, up to 70 days of age

• Length of Treatment

  Duration of pharmacologic treatment for neonatal abstinence syndrome up to 70 days of age

Study Arms (1)

buprenorphine

EXPERIMENTAL

Buprenorphine 0.075 mg ml sublingual solution Initial daily dose 24 mcg/kg/day Initial unit dose 8 mcg/kg q8 hours Maximum daily dose 75 mcg/kg/day Maximum unit dose 25 mcg/kg q8 hours Up-titration rate 33% Maximum # of up-titrations 4 Weaning rate 15% Cessation (bottom) dose \< Initial dose Dosing interval until bottom dose (hrs) 8 Dose interval extension #1 at bottom dose (hrs) 12 Dose interval extension #2 at bottom dose (hrs) 24

Drug: Buprenorphine

Interventions

Buprenorphine DRUG

buprenorphine 0.075 mg/ml solution

buprenorphine

Eligibility Criteria

• Age: Up to 4 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• ≥ 36 weeks gestation
• Exposure to opioids in utero
• Demonstration of signs and symptoms of neonatal abstinence syndrome requiring pharmacologic treatment

You may not qualify if:

• Major congenital malformations and/or intrauterine growth retardation, defined as birth weight \<2000 gm
• Medical illness requiring intensification of medical therapy. This includes but is not limited to suspected sepsis requiring antibiotic therapy.
• Hypoglycemia requiring treatment with intravenous dextrose
• Inability of mother to give informed consent due to co-morbid psychiatric diagnosis

Sponsors & Collaborators

• Thomas Jefferson University: lead
• Chiesi Farmaceutici S.p.A.: collaborator

Study Sites (1)

Thomas Jefferson University Hosptial

Philadelphia, Pennsylvania, 19107, United States

Location

Related Publications (1)

• Eudy-Byrne R, Zane N, Adeniyi-Jones SC, Gastonguay MR, Ruiz-Garcia A, Kaushal G, Kraft WK. Pharmacometric dose optimization of buprenorphine in neonatal opioid withdrawal syndrome. Clin Transl Sci. 2021 Nov;14(6):2171-2183. doi: 10.1111/cts.13074. Epub 2021 Sep 16.

  PMID: 34080312 RESULT

MeSH Terms

Conditions

Neonatal Abstinence Syndrome

Interventions

Buprenorphine

Condition Hierarchy (Ancestors)

Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Results Point of Contact

• Title: Walter Kraft
• Organization: Thomas Jefferson University

walter.kraft@jefferson.edu

2159559077

Study Officials

• Walter K Kraft, MD

  Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2018
• First Posted: August 1, 2018
• Study Start: August 29, 2018
• Primary Completion: July 11, 2019
• Study Completion: July 11, 2019
• Last Updated: February 11, 2022
• Results First Posted: February 11, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: until 2024
• Access Criteria: Consent of principal investigator or designee, with data use agreement in place

Locations

US (1)