A Study to Assess Sulbactam-durlobactam in Pediatric Patients With Acinetobacter Baumannii-calcoaceticus Complex Infection

Официальное название

A Multicenter, Open-label, Phase 1b Study to Assess the Pharmacokinetics, Safety, and Tolerability of Sulbactam-Durlobactam in Hospitalized Pediatric Patients From Birth to <18 Years Who Are Receiving Systemic Antibiotic Therapy for Suspected or Confirmed Acinetobacter Baumannii-calcoaceticus Complex Infection

Обзор

The goal of this clinical trial is to investigate the use of Sulbactam-Durlobactam (SUL-DUR) in pediatric patients and is being conducted to collect pharmacokinetic (PK) and safety data to enable the identification of appropriate pediatric dosing regimens for patients with Acinetobacter baumannii-calcoaceticus complex (ABC) infections

Вмешательства

• Препарат Sulbactam 25mg/kg -Durlobactam 25mg/kg (Every 6 hours)
  25mg/kg SUL and 25mg/kg DUR
• Препарат Sulbactam 20mg/kg-Durlobactam 20mg/kg (Every 8 hours)
  20mg/kg SUL and 20mg/kg DUR
• Препарат Sulbactam 25mg/kg -Durlobactam 25mg/kg (Every 8 hours)
  25mg/kg SUL and 25mg/kg DUR
• Препарат Sulbactam 20mg/kg-Durlobactam 20mg/kg (Every 12 hours)
  20mg/kg SUL and 20mg/kg DUR

Первичные конечные точки

• Assess the pharmacokinetic (PK) parameters for maximum concentration (Cmax) of sulbactam and durlobactam [Срок оценки: Day 1 and Day 3]
• Assess the PK parameters for area under the plasma concentration-time curve from 0 to 24 hours (AUC 0-24) of sulbactam and durlobactam [Срок оценки: Day 1 and Day 3]

Вторичные конечные точки (12)

• Percentage of participants experiencing Treatment Emergent Adverse Events (TEAEs) [Срок оценки: 28 days]
• Percentage of TEAEs leading to study drug discontinuation [Срок оценки: 28 days]
• Incidence of related TEAEs [Срок оценки: 28 days]
• Incidence of serious TEAEs [Срок оценки: 28 days]
• Change from baseline values of liver function measured by Comprehensive Metabolic Panel (CMP) [Срок оценки: Baseline and Day 28]
• Change from baseline values of kidney function measured by CMP [Срок оценки: Baseline and Day 28]
• Change from baseline values of hemoglobin [Срок оценки: Baseline and Day 28]
• Change from baseline value of white blood cell count [Срок оценки: Baseline and Day 28]
• Change from baseline value of platelets [Срок оценки: Baseline and Day 28]
• Change from baseline value of diastolic blood pressure [Срок оценки: Baseline and Day 28]
• Change from baseline value of systolic blood pressure [Срок оценки: Baseline and Day 28]
• Change from baseline values of heart rate [Срок оценки: Baseline and Day 28]

Критерии участия

Критерии включения

• Patient from birth (defined as post-natal age of 7 days) to <18 years of age at the time of written informed consent (and assent, if applicable) and is hospitalized.
• Patient and/or parent(s) or legal guardian(s) have provided the written informed consent and/or assent.
• Patient has confirmed or suspected diagnosis of ABC infection and requires IV antibiotics for treatment.
• Patient has expected survival of 30 days after enrollment in the study.
• If patient is an individual of childbearing potential or reproductive potential, then the patient must remain abstinent OR must utilize one of the highly effective methods of contraception (ie, condom, combined oral contraceptive, implant, or injectable) from at least 30 days prior to screening until at least 30 days after administration of the last dose of study drug.

Критерии исключения

• Patient is a preterm infant, born at <28 weeks gestational age.
• Patient has history of significant hypersensitivity or allergic reaction to any β-lactam, any contraindication to the excipients used in the formulation, or any contraindication to the use of β-lactam antibiotics. Note: For β-lactams, a history of a mild rash followed by uneventful re-exposure is not a contraindication to enrollment.
• Patient is in refractory septic shock at the time of enrollment, defined as persistent hypotension despite adequate fluid resuscitation or vasopressive therapy.
• Patient is pregnant, breastfeeding, or intends to become pregnant.
• Patient is receiving peritoneal dialysis or cardiopulmonary bypass.
• Patient has received blood transfusion within 24 hours of study drug administration.
• Patient is a newborn with clinically significant anemia who, in the opinion of the investigator, will not be able to tolerate the necessary blood draws to complete the study activities.
• Patient (or patient's mother, if the patient is being breastfed) is using or will need to use any medications known to inhibit organic anion transporter 1 (OAT1) (eg, probenecid).
• Patient has clinically significant renal, hepatic, or hemodynamic instability.
• For Cohorts 1 through 3 only: patient has weight outside of the 5th to 95th percentile based on age.
• Patient has an age-appropriate estimated creatinine clearance that indicates renal impairment.
• Patient has the following laboratory results at Screening:

• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3×upper limit of normal (ULN) and,
• Total bilirubin >2×ULN for age with conjugated/direct bilirubin >20% of the total. Note: Patients with AST or ALT up to 5×ULN are eligible if these elevations are acute and are documented as being directly related to the infectious process being treated.
• Patient has clinically significant abnormal laboratory test results not related to the underlying infection that might expose the patient to risk by participating in the trial, confound the results of the trial, or interfere with the patient's participation for the full duration of the trial.
• Patient (or patient's mother, if the patient is being breastfed) has participated in a clinical study involving investigational medication or an investigational device within the last 30 days or 5 half-lives, whichever is longer, prior to first dose of the study drug.
• Patient has any condition that, in the opinion of the investigator, would compromise the safety of the patient or the quality of the data.
• Patient is unable or unwilling, in the opinion of the investigator, to comply with the protocol.
• Patient (or patient's mother, if the patient is being breastfed) has previously received durlobactam.
• Patient (or patient's mother, if the patient is being breastfed) has received sulbactam and/or sulbactam-containing regimens (eg, Unasyn) within 72 hours of first dose of the study drug.
• Patient (or patient's mother, if the patient is being breastfed) has received amphotericin B within 7 days of first dose of the study drug.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 4 центра

• UCLA Medical Center — Los Angeles
• Rady Children's Hospital — San Diego
• ECU Brody School of Medicine — Greenville
• University of Texas Medical Branch at Galveston — Galveston

Идентификаторы

NCT: NCT06801223 · CS2514-2023-002

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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