Evaluation of Pharmacokinetics, Safety, and Tolerability of Ceftazidime-avibactam in Neonates and Infants.

NCT04126031 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: C35910242018-002800-16NOOR
• Study Type: interventional
• Target: 48
• Locations: 8 countries
• Sites: 18

Brief Summary

This study will assess the pharmacokinetics, safety, and tolerability of single and multiple doses of intravenous ceftazidime-avibactam in hospitalized infants and neonates from 26 weeks gestation to 3 months of age. In Part A of the study all patients will receive a single dose of ceftazidime-avibactam. In Part B all patients will received multiple doses of ceftazidime-avibactam. Efficacy will be assessed in the infants and neonates receiving multiple doses of ceftazidime-avibactam.

Conditions

Gram-negative Bacterial Infection

Keywords

Gram-negative, ceftazidime-avibactam, neonate, infant

Outcome Measures

Primary Outcomes (7)

• Plasma Concentrations of Ceftazidime and Avibactam 2 Hours Post-dose: Part A

  2 hours post dose on Day 1

• Plasma Concentrations of Ceftazidime and Avibactam 2 Hours and 30 Minutes Post-dose: Part A

  2 hours and 30 minutes post dose on Day 1

• Plasma Concentrations of Ceftazidime and Avibactam of 7 Hours Post-dose: Part A

  7 hours post dose on Day 1

• Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Part B

  An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in participant hospitalization; life-threatening experience (immediate risk of dying) ; persistent or significant disability/incapacity; congenital anomaly.

  Day 1 up to maximum of Day 49

• Number of Participants Who Died: Part B

  Day 1 up to maximum of Day 49

• Number of Participants Who Discontinued Treatment and Study Due to AEs: Part B

  Day 1 up to maximum of Day 49

• Number of Participants With Clinically Significant Laboratory Parameters Occurred in More Than 2 Participants: Part B

  Number of participants in Part B with clinically significant abnormal laboratory parameters that occurred in more than 2 participants from Day 1 up to 35 days after the last dose of CAZ-AVI were reported in this outcome measure. Clinically significant labs were abnormal laboratory results which the investigator reported as being clinically significant. Only parameters with non-zero values are reported.

  Day 1 up to maximum of Day 49

Secondary Outcomes (10)

• Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs): Part A

  Day 1 up to maximum of Day 35

• Number of Participants Who Died: Part A

  Day 1 up to maximum of Day 35

• Number of Participants Who Discontinued Treatment and Study Due to AEs: Part A

  Day 1 up to maximum of Day 35

• Plasma Concentrations of Ceftazidime and Avibactam 2 Hours, 2 Hours and 30 Minutes, 7 Hours Post Doses on Day 1: Part B

  2 hours, 2 hours 30 mins, and 7 hours post dose on Day 1

• Number of Participants According to Clinical Outcome At End of IV Treatment(EOIV), End of Treatment(EOT), Test of Cure(TOC) and Late Follow-Up(LFU): Intent to Treat (ITT) Analysis Population: Part B

  EOIV, EOT, TOC, LFU

Study Arms (2)

Part A, Cohorts 1-3

EXPERIMENTAL

Single dose pharmacokinetics. This arm will include three age cohorts.

Drug: Part A: Single Dose Ceftazidime-Avibactam, Cohorts 1-3

Part B, Cohorts 1-3

EXPERIMENTAL

Multi-dose pharmacokinetics. This arm will include three age cohorts.

Drug: Part B: Multiple-dose Ceftazidime-Avibactam, Cohorts 1-3

Interventions

Part A: Single Dose Ceftazidime-Avibactam, Cohorts 1-3 DRUG

Single intravenous infusion of ceftazidime-avibactam over 2 hours

Part A, Cohorts 1-3

Part B: Multiple-dose Ceftazidime-Avibactam, Cohorts 1-3 DRUG

Multiple intravenous infusions of ceftazidime-avibactam over 2 hours, repeated every 8 hours up to 14 days

Part B, Cohorts 1-3

Eligibility Criteria

• Age: 0 Days - 88 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Evidence of a personally signed and dated informed consent document indicating that the subject's parent(s), legal guardian, or legally acceptable representative has been informed of all pertinent aspects of the study.
• Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
• Male or female neonates and infants with age at Screening:
• Cohort 1: Full term infants (gestational age ≥ 37 weeks) with chronological age \>28 days to \<3 months (\<89 days) or pre-term infants with corrected age \>28 days to \<3 months (\<89 days). A maximum of 3 pre-term corrected age infants may be enrolled in each part (A and B) of Cohort 1. Sites will be notified in writing if this limit is reached.
• Cohort 2: Full term neonates (gestational age ≥ 37 weeks) from birth to ≤ 28 days.
• Cohort 3: Pre-term neonates (gestational age ≥ 26 to \<37 weeks) from birth to ≤ 28 days.
• Corrected age = Subtract the number of weeks born before 40 weeks of gestation from the chronological age.
• \. Hospitalized and receiving intravenous antibacterial therapy for the treatment of a suspected or confirmed bacterial infection.
• Hospitalized with suspected or confirmed aerobic Gram-negative bacterial infection requiring intravenous antibacterial therapy.
• Subjects must meet at least 1 clinical and 1 laboratory criterion or meet at least 2 of the clinical criteria:
• Clinical Criteria:
• Hypothermia (\<36ºC) OR fever (\>38.5ºC);
• Bradycardia OR tachycardia OR rhythm instability;
• Urine output 0.5 to 1 mL/kg/h OR hypotension OR mottled skin OR impaired peripheral perfusion;
• Petechial rash OR sclerema neonatorum;

You may not qualify if:

• Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the Investigator, or subjects who are Pfizer employees, including their family members, directly involved in the conduct of the study.
• Participation in another clinical study involving investigational drug(s) within 30 days prior to study entry and/or during this study participation or have previously participated in the current study or in another study of CAZ-AVI (in which an active agent was received).
• Use of potent inhibitors of organic anion transporters OAT1 and/or OAT3 (eg, probenecid, p-aminohippuric acid (PAH), or teriflunomide) are prohibited. This prohibition of OAT1 and/or OAT3 inhibitors also applies to the mothers of any neonates or infants who are breast feeding during the trial.
• Other acute or chronic medical or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the subject inappropriate for entry into this study.
• Documented history of any hypersensitivity or allergic reaction to any beta-lactam antibiotic.
• Refractory septic shock within 24 hours before screening that does not resolve after 60 minutes of vasopressor therapy.
• Moderate or severe renal impairment defined as serum creatinine ≥ 2 times the upper limit of normal (ULN) for age OR urine output \<0.5 mL/kg/h (measured over at least 8 hours) OR requirement for dialysis. Deterioration of renal function after enrollment during Part B of the study will be handled on a case-by-case basis in discussion with the Medical Monitor.
• Evidence of progressively fatal underlying disease, or life expectancy of ≤ 60 days.
• Documented history of seizure.
• Active acute viral hepatitis or acute hepatic failure.
• Known Clostridium difficile associated diarrhea.
• Requiring or currently taking antiretroviral therapy for human immunodeficiency virus (HIV) or known HIV positive mother.
• Any condition (eg, cystic fibrosis, urea cycle disorders), antepartum/peripartum factors, or procedures that would, in the opinion of the Investigator, make the subject unsuitable for the study, place a subject at risk, or compromise the quality of data.
• Treatment with ceftazidime within 12 hours of CAZ-AVI administration.
• Subject received a blood or a blood component transfusion within 24 hours of the start of CAZ AVI infusion.

Sponsors & Collaborators

• Pfizer: lead
• Allergan: collaborator

Study Sites (18)

Tufts Children's Hospital at Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Duke University Investigational Drug Services

Durham, North Carolina, 27710, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

University of Utah

Salt Lake City, Utah, 84108, United States

Location

Primary Children's Hospital

Salt Lake City, Utah, 84113, United States

Location

Tallinn Children's Hospital

Tallinn, 13419, Estonia

Location

Athens General Children's Hospital "Panagioti and Aglaias Kyriakou"

Athens, Ampelokipi, 11 527, Greece

Location

"ATTIKON" University General Hospital

Chaïdári, Athens, 124 62, Greece

Location

"Hippokration" General Hospital of Thessaloniki

Thessaloniki, 546 42, Greece

Location

Debreceni Egyetem Klinikai Központ

Debrecen, 4032, Hungary

Location

Kanizsai Dorottya Korhaz

Nagykanizsa, 8800, Hungary

Location

Szabolcs-Szatmár-Bereg Megyei Kórházak és Oktatókórház, Jósa András Oktatókórház

Nyíregyháza, 4400, Hungary

Location

Kasturba Medical College and Hospital

Manipal, Karnataka, 576104, India

Location

Ospedale Pediatrico Bambino Gesu

Rome, RM, 00165, Italy

Location

Univerzitna nemocnica Martin

Martin, 036 59, Slovakia

Location

Hsinchu Mackay Memorial Hospital, Department of Pharmacy

Hsinchu, R.o.c, 300, Taiwan

Location

Hsinchu Mackay Memorial Hospital

Hsinchu, 30071, Taiwan

Location

National Taiwan University Hospital

Taipei, 10041, Taiwan

Location

Related Publications (1)

• Bradley J, Roilides E, Tawadrous M, Yan JL, Soto E, Stone GG, Kamat S, Irani P, England R. Pharmacokinetics and Safety of Ceftazidime-Avibactam in Neonates and Young Infants: A Phase 2a, Multicenter Prospective Trial. J Pediatric Infect Dis Soc. 2025 May 13;14(5):piaf028. doi: 10.1093/jpids/piaf028.

  PMID: 40251980 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Gram-Negative Bacterial Infections

Interventions

avibactam, ceftazidime drug combination

Condition Hierarchy (Ancestors)

Bacterial Infections; Bacterial Infections and Mycoses; Infections

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Non-randomized, 2-part with three age cohorts in each part

Study Record Dates

• First Submitted: September 27, 2019
• First Posted: October 14, 2019
• Study Start: January 14, 2020
• Primary Completion: December 30, 2022
• Study Completion: December 30, 2022
• Last Updated: March 26, 2024
• Results First Posted: March 26, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share

Locations

HU (3); US (5); IT (1); SL (1); TW (3); ES (1); GR (3); IN (1)