Treatment of bacterial infections in pediatric populations MedDRA version: 20.0 Level: LLT Classification code 10071097 Term: Beta-lactam antibiotic resistance System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Trade Name: Recarbio
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: IMIPENEM
CAS Number: 64221-86-9
Concentration unit: mg milligram(s)
Concentration type: equal
Concentra
Sponsors
Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Require hospitalization and treatment with IV antibacterial therapy for confirmed or suspected gram-negative bacterial infection (in the absence of meningitis), and is expected to require hospitalization through completion of IV study intervention, with at least 1 of the following primary infection types, based on the specific criteria required to be met for the respective infection type: - Hospital-acquired bacterial pneumonia (HABP) or ventilator-associated bacterial pneumonia (VABP) - Complicated intra-abdominal infection (cIAI) - Complicated urinary tract infection (cUTI) 2. Participants is male or female and is from birth to less than 18 years of age inclusive, at the time of providing documented informed consent/assent. For Age Cohorts 4 and 5, participant is at least 37 weeks postmenstrual age at the time of providing documented informed consent/assent. Postmenstrual age is calculated by adding the gestational age at the time of birth to the chronological age at the time of providing documented informed consent/assent. 3. Not be pregnant or breastfeeding, and at least 1 of the following conditions applies: a. Not be a woman of childbearing potential (WOCBP) OR b. A WOCBP must agree to follow the contraceptive guidance during the intervention period and for at least 24 hours after the last dose of study intervention 4. The participant (or legally acceptable representative if applicable) has provided documented informed consent/assent for the study 5. Have sufficient intravascular access to receive study intervention through an existing peripheral or central line Are the trial subjects under 18? yes Number of subjects for this age range: 140 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Is expected to survive less than 72 hours 2. Has a concurrent infection that would interfere with evaluation of response to the study antibacterials (IMI/REL or Active Control) 3. Has HABP/VABP caused by an obstructive process, including lung cancer (or other malignancy metastatic to the lungs resulting in pulmonary obstruction) or other known obstruction 4. Has a cUTI that meets any of the following: - Complete obstruction of any portion of the urinary tract (ie, requiring a permanent indwelling urinary catheter or instrumentation) - Documented reflux of ileal loop urinary diversion - Suspected or confirmed perinephric or intrarenal abscess - Suspected or confirmed prostatitis, urethritis, or epididymitis - Trauma to pelvis/urinary tract - Presence of indwelling urinary catheter which cannot be removed at study entry 5. Has any of the following medical conditions at screening: - A history of a seizure disorder (requiring ongoing treatment with anticonvulsive therapy or prior treatment with anticonvulsive therapy within the last 3 years) - Cystic fibrosis 6. Has a history of serious allergy, hypersensitivity (eg, anaphylaxis), or any serious reaction to IMI or to any of the following: - Any carbapenem, cephalosporin, penicillin, or other ß-lactam agent - Other BLIs (eg, tazobactam, sulbactam, clavulanic acid, avibactam) 7. Has a history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might expose the participant to risk by participating in the study, confound the results of the study, or interfere with the participant’s participation for the full duration of the study 8. If less than 3 months of age, has received more than 72 hours of empiric antibacterial treatment for suspect meningitis has been ruled out prior to initiation of IV study intervention 9. If 3 months of age or older, or less than 3 months without suspected meningitis, has received potentially therapeutic antibacterial therapy (eg, with gram-negative activity), including bladder infusions with topical urinary antiseptics or antibacterial agents, for a duration of more than 24 hours during the 48 hours preceding the first dose of study intervention 10. Is anticipated to be treated with any of the following medications: - Valproic acid or divalproex sodium (or has used valproic acid or divalproex sodium in the 2 weeks prior to screening) through 24 hours after completion of the final dose of IV study intervention for participants who receive IMI/REL or carbapenem - Concomitant IV, oral, or inhaled antimicrobial agents with gram-negative activity, in addition to those designated in the study intervention groups, during the course of all (IV/oral) study intervention - Planned receipt of suppressive/prophylactic antibiotics with gram-negative activity after completion of study intervention 11. Is currently participating in or has participated in an interventional clinical study with an investigational compound or device within 30 days prior to screening 12. Has enrolled previously in the current study and been discontinued, or has received REL for any other reason 13. Has an estimated CrCl (based on the Cockcroft-Gault equation, for participants =12 years of age) or estimated glomerular filtration rate (eGFR, based on the modified Schwartz equation, for participants <12 years of age) below that specified for the appropriate age range; or requires peritoneal dialysis, hemodialysis, or hemofiltration 14. Has alanine amino
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and tolerability of IMI/REL (imipenem/cilastatin/relebactam) from the first dose of intravenous (IV) study intervention through 14 days after the end of therapy (EOT);Secondary Objective: A) To evaluate the efficacy of IMI/REL by assessing all-cause mortality at Day 28 post-randomization and clinical and microbiological response at the EOT, Early Follow-up (EFU, 7 to 14 days after EOT), and Late Follow-up (LFU, 7 to 14 days after EFU) visits B) To characterize the PK profile of imipenem and relebactam following administration of IMI/REL;Primary end point(s): 1. Percentage of participants with one or more adverse event (AE) 2. Percentage of participants who discontinued study medication due to an AE;Timepoint(s) of evaluation of this end point: 1. Up to 28 days 2. Up to 14 days | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Number of deaths by all causes through Day 28 2. Percentage of participants with a favorable clinical response at EOT 3. Percentage of participants with a favorable clinical response at EFU 4. Percentage of participants with a favorable clinical response at LFU 5. Percentage of participants with a favorable microbiological response at EOT 6. Percentage of participants with a favorable microbiological response at EFU 7. Percentage of participants with a favorable microbiological response at LFU 8. Area under the curve from time 0 to 24 hours (AUC0-24) of imipenem following administration of IMI/REL 9. AUC0-24 of relebactam following administration of IMI/RE 10. Concentration at end of infusion (Ceoi) of imipenem following administration of IMI/REL 11. Ceoi of relabactam following administration of IMI/REL 12 %T>MIC of imipenem (percentage of time imipenem concentration is above IMI/REL minimum inhibitory concentration) following administration of IMI/REL;Timepoint(s) of evaluation of this end point: 1. Up to Day 28 2. Day 5 up to Day 14 3. Day 12 up to Day 28 4. Day 19 up to Day 42 5. Day 5 up to Day 14 6. Day 12 up to Day 28 7. Day 19 up to Day 42 8. Day 5 up to Day 14 9. Day 5 up to Day 14 10. Day 5 up to Day 14 11. Day 5 up to Day 14 12. Day 5 up to Day 14 | — |
Countries
Bulgaria, Colombia, Estonia, France, Germany, Greece, Israel, Mexico, Norway, Philippines, Poland, Russian Federation, South Africa, Spain, Türkiye, Ukraine, United States
Outcome results
None listed