A Pharmacokinetics Study of MK-7655A in Pediatric Participants With Gram-negative Infections (MK-7655A-020)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Suspected or Documented Gram-negative Bacterial Infection

Treatments: Drug: IMI/REL FDC

Study type: Interventional

Funder types: Industry

Identifiers

NCT03230916

MK-7665A-020 (Other Identifier)

7655A-020

2016-004328-43 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 47 patients

Sex: All

Ages: 1 day to 17 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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47 participants in 1 patient group

IMI/REL FDC

Experimental group

Description:

Imipenem/Cilastatin/Relebactam (IMI/REL) administered as a single fixed 2:1 ratio of imipenem/cilastatin to relebactam, with 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).

Treatment:

Drug: IMI/REL FDC