Clinical trial NCT06801223: A Study to Assess Sulbactam-durlobactam in Pediatric Patients With Acinetobacter Baumannii-calcoaceticus Complex Infection
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Acinetobacter Baumannii-calcoaceticus Complex Infection (ABC)
Keywords: Acinetobacter baumannii-calcoaceticus complex infection
Sulbactam-durlobactam
Hospital-acquired bacteria pneumonia
Ventilator-associated bacterial pneumonia
Acinetobacter
ABC infection
Lead sponsor: Innoviva Specialty Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: Entasis Therapeutics
First posted: 2025-01-30
Enrollment: 48
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: Inclusion Criteria:

1. 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.
2. Patient and/or parent(s) or legal guardian(s) have provided the written informed consent and/or assent.
3. Patient has confirmed or suspected diagnosis of ABC infection and requires IV antibiotics for treatment.
4. Patient has expected survival of 30 days after enrollment in the study.
5. 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.

Exclusion Criteria:

1. Patient is a preterm infant, born at \<28 weeks gestational age.
2. 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.
3. Patient is in refractory septic shock at the time of enrollment, defined as persistent hypotension despite adequate fluid resuscitation or vasopressive therapy.
4. Patient is pregnant, breastfeeding, or intends to become pregnant.
5. Patient is receiving peritoneal dialysis or cardiopulmonary bypass.
6. Patient has planned blood transfusion within 24 hours of study drug administration and for the duration of the trial.
7. 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.
8. 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).
9. Patient has clinically significant renal, hepatic, or hemodynamic instability.
10. For Cohorts 1 through 3 only: patient has weight outside of the 5th to 95th percentile based on age.
11. Patient has an age-appropriate estimated creatinine clearance that indicates renal impairment.
12. Patient has the following laboratory results at Screening:

    1. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>3×upper limit of normal (ULN) and,
    2. 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.
13. 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.
14. 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.
15. Patient has any condition that, in the opinion of the investigator, would compromise the safety of the patient or the quality of the data.
16. Patient is unable or unwilling, in the opinion of the investigator, to comply with the protocol.
17. Patient (or patient's mother, if the patient is being breastfed) has previously received durlobactam.
18. 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.
19. 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.

Primary outcomes:
measure: Assess the pharmacokinetic (PK) parameters for maximum concentration (Cmax) of sulbactam and durlobactam
timeFrame: Day 1 and Day 3
measure: Assess the PK parameters for area under the plasma concentration-time curve from 0 to 24 hours (AUC 0-24) of sulbactam and durlobactam
timeFrame: Day 1 and Day 3
Secondary outcomes:
measure: Percentage of participants experiencing Treatment Emergent Adverse Events (TEAEs)
timeFrame: 28 days
measure: Percentage of TEAEs leading to study drug discontinuation
timeFrame: 28 days
measure: Incidence of related TEAEs
timeFrame: 28 days
measure: Incidence of serious TEAEs
timeFrame: 28 days
measure: Change from baseline values of liver function measured by Comprehensive Metabolic Panel (CMP)
timeFrame: Baseline and Day 28
measure: Change from baseline values of kidney function measured by CMP
timeFrame: Baseline and Day 28
measure: Change from baseline values of hemoglobin
timeFrame: Baseline and Day 28
measure: Change from baseline value of white blood cell count
timeFrame: Baseline and Day 28
measure: Change from baseline value of platelets
timeFrame: Baseline and Day 28
measure: Change from baseline value of diastolic blood pressure
timeFrame: Baseline and Day 28
measure: Change from baseline value of systolic blood pressure
timeFrame: Baseline and Day 28
measure: Change from baseline values of heart rate
timeFrame: Baseline and Day 28
measure: Change from baseline value of respiration rate
timeFrame: Baseline through Day 28
measure: Change from baseline value of temperature
timeFrame: Baseline and Day 28
Other outcomes:
Locations:
city: Galveston
country: United States
facility: University of Texas Medical Branch at Galveston
state: Texas
Study officials:
References: