A Pharmacokinetics Study of MK-7655A in Pediatric Participants With Gram-negative Infections (MK-7655A-020)
Condition: Suspected or Documented Gram-negative Bacterial Infection
MeSH terms: Infections; Communicable Diseases; Bacterial Infections; Gram-Negative Bacterial Infections
Intervention: IMI/REL FDC
Intervention description: IMI/REL is supplied as a single fixed dose combination (FDC) vial; which is administered at a maximum dose of 15 mg/kg IMI and 15 mg/kg CIL (up to 500 mg IMI and 500 mg CIL) and 7.5 mg/kg REL (up to 250 mg REL).
Intervention MeSH terms: Relebactam
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 47.0
Sex: All
Minimum age: 1 Day
Maximum age: 17 Years
Healthy volunteers: No

Summary:

      This study aims to obtain plasma pharmacokinetic (PK) data and characterize the PK profile of
      imipenem (IMI), cilastatin (CIL), and relebactam (REL) following administration of a single
      intravenous (IV) dose of MK-7655A (a fixed ratio combination of
      imipenem/cilastatin/relebactam), hereafter referred to as IMI/REL.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Has a parent or legally acceptable representative (LAR) who provides written informed
             consent for the trial on the participant's behalf.

          -  Aged from birth to <18 years old.

          -  Is hospitalized, currently receiving antibacterial treatment for confirmed or
             suspected Gram-negative bacterial infection, and expected to require hospitalization
             until at least 24 hours after completion of study drug administration.

          -  Is not of reproductive potential; but if of reproductive potential, agrees to avoid
             becoming pregnant or impregnating a partner from the time of consent through 24 hours
             after completion of study drug administration.

          -  Has clinically stable renal function at the time of screening that is judged to be
             within acceptable ranges.

          -  Has sufficient intravascular access to receive study drug through an existing
             peripheral or central line.

        Exclusion Criteria:

          -  Has a personal history of hypersensitivity to imipenem/cilastatin (IMI) or to any of
             the following: any carbapenem, cephalosporin, penicillin, or other β-lactam agent; or
             other β-lactamase inhibitors (BLIs) e.g. tazobactam, sulbactam, clavulanic acid,
             avibactam.

          -  Female is currently pregnant or breast feeding or has a positive serum β-human
             chorionic gonadotropin (β-hCG) pregnancy test.

          -  Has a history of a seizure disorder requiring ongoing treatment with anti-convulsive
             therapy or prior treatment with anti-convulsive therapy within the last 3 years.

          -  Has used or plans to use valproic acid or divalproex sodium within 2 weeks prior to
             screening or at any point between screening and 24 hours after the completion of study
             drug infusion.

          -  Has received treatment or plans to receive treatment with any carbapenem antibiotic
             within 48 hours prior to initiation of study drug infusion or at any point between
             administration of study drug and the last PK sample collection.

          -  Has used or plans to use any of the following medications, which are organic anion
             transporter (OAT) 1 or OAT3 inhibitors, within 1 week prior to screening or at any
             point between screening and the last PK sample collection: cimetidine, probenecid,
             indomethacin, mefenamic acid, furosemide or other loop diuretics (eg, bumetanide,
             torsemide, ethacrynic acid), angiotensin receptor blockers (eg, valsartan), and
             ketorolac.

          -  Is currently participating in or has participated in an interventional clinical trial
             with an investigational compound or device within 30 days prior to screening.

          -  Has enrolled previously in the current trial and been discontinued, or has received
             REL for any other reason.

          -  Has a current diagnosis of cystic fibrosis, meningitis, or severe sepsis.

          -  Is expected to survive less than 72 hours after completion of study drug
             administration.

          -  Has a history of clinically significant renal, hepatic, or hemodynamic instability.

          -  Plans to use cardiopulmonary bypass, extracorporeal membrane oxygenation,
             hemodialysis, or peritoneal dialysis during the study.

          -  For participants that are 2 to 17 years of age only: weighs outside of the 5th to 95th
             percentile based on age.

          -  Is, at the time of signing informed consent, a user of recreational or illicit drugs
             or has had a recent history (within the last year) of drug or alcohol abuse or
             dependence.

          -  Has a planned blood transfusion within 24 hours of study drug administration or
             expected before the end of the PK sampling.

          -  Has had significant blood loss (≥5% of total blood volume) within 4 weeks before the
             screening visit.