Imipenem/Cilastatin/Relebactam Pharmacokinetics, Safety, and Outcomes in Adults and Adolescents With Cystic Fibrosis

Summary

There is established evidence that patients with Cystic Fibrosis (CF) may have altered antibiotic pharmacokinetics compared with non-CF patients. Imipenem/cilastatin/relebactam is a novel broad spectrum intravenous beta-lactam/beta-lactamase inhibitor combination antibiotic with potent activity against multidrug resistant Gram-negative bacteria, including imipenem non-susceptible Pseudomonas aeruginosa. Relebactam has also been shown to restore imipenem activity in Burkholderia cepacia complex, a group of opportunistic multidrug resistant pathogens that commonly infect patients with CF. This study will determine the pharmacokinetics and tolerability of imipenem/cilastatin/relebactam in 16 adolescent and adult patients with CF acute pulmonary exacerbations at one of seven participating hospitals in the US, with exploratory aim of reporting relative percent increase in FEV1 from pre- to post-treatment and return to baseline FEV1 after treatment with imipenem/cilastatin/relebactam for acute pulmonary exacerbations due to P. aeruginosa in patients with CF. Patients will receive a 10-14 day course of imipenem/cilastatin/relebactam, dosed according to renal function every 6 hours over 30 mins, with or without adjunctive aminoglycoside or fluoroquinolone therapy per local hospital guidelines. Blood will be sampled during one dosing interval at steady-state (i.e. after at least 3 doses) to determine concentrations and pharmacokinetics of imipenem and relebactam. Relative change in pulmonary function will be assessed two weeks after end of therapy. Safety and tolerability will be assessed throughout the duration of the study.

Conditions

• Cystic Fibrosis
• Pneumonia, Bacterial

Interventions

DRUG

Imipenem/Cilastatin/Relebactam

Patients will receive intravenous imipenem/cilastatin/relebactam every 6 hours for 10-14 days.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC

  collaborator INDUSTRY

• Q2 Solutions

  collaborator INDUSTRY

• Connecticut Children's Medical Center

  collaborator OTHER

• St. Christopher's Hospital for Children

  collaborator OTHER

• University of Texas Southwestern Medical Center

  collaborator OTHER

• University of Pittsburgh Medical Center

  collaborator OTHER

• Indiana University Health Methodist Hospital

  collaborator OTHER

• James Whitcomb Riley Hospital for Children

  collaborator OTHER

• Hartford Hospital

  lead OTHER

Principal Investigators

• Joseph L. Kuti, PharmD · Hartford Hospital

Study Design

Allocation

NA

Purpose

OTHER

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

12 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-01-03

Primary Completion

2024-10-14

Completion

2024-12-11

FDA Drug

Yes

Countries

• United States

Study Locations