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| ID | Type | Description | Link |
|---|---|---|---|
| MK-7665A-020 | Other Identifier | Merck | |
| 2016-004328-43 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| IMI/REL FDC | Experimental | 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). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| IMI/REL FDC | Drug | 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). |
| Measure | Description | Time Frame |
|---|---|---|
| Imipenem (IMI) Area Under the Concentration Time Curve From Time 0 to Infinity (AUC0-∞) | Area under the concentration time curve from time 0 to infinity (AUC0-∞) of plasma imipenem (IMI) was calculated. AUC0-∞ is the area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time. | 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5 |
| IMI Maximum Concentration (Cmax) | Maximum plasma concentration (Cmax) of IMI was calculated. Cmax is the peak plasma concentration of study drug after administration. | 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5 |
| IMI Central Volume of Distribution (Vc) | Central volume of distribution (Vc) of plasma IMI was calculated. | 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5 |
| IMI Clearance (CL) | Systemic clearance (CL) of plasma IMI was calculated. | 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5 |
| IMI Percentage of Time Above the Minimum Concentration (%TMIC) | Percentage of time spent above the minimum inhibitory concentration (%TMIC) of plasma IMI was calculated. %TMIC is defined as the percentage of time (in hours) in which the lowest concentration of a study drug, completely inhibits growth of the specific organism being tested. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Who Experienced an Adverse Event (AE) | Number of participants with one or more AEs was calculated. An AE is defined as any untoward medical occurrence in a participant administered study drug and which may or may not have a causal relationship to the study drug. | Up to 17 days |
| Number of Participants Who Discontinued Study Drug Due to an AE |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Arkansas Children's Hospital ( Site 1311) | Little Rock | Arkansas | 72202 | United States | ||
| Children's Hospital of Orange County ( Site 1301) |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37562063 | Result | Bradley JS, Makieieva N, Tondel C, Roilides E, Kelly MS, Patel M, Vaddady P, Maniar A, Zhang Y, Paschke A, Chen LF. Pharmacokinetics, Safety, and Tolerability of Imipenem/Cilastatin/Relebactam in Children with Confirmed or Suspected Gram-Negative Bacterial Infections: A Phase 1b, Open-Label, Single-Dose Clinical Trial. J Clin Pharmacol. 2023 Dec;63(12):1387-1397. doi: 10.1002/jcph.2334. Epub 2023 Sep 2. |
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Note: Participant information is shown by age cohort and drug dosage to provide clinically-similar groups for analysis of participant baseline characteristics and safety data. Participant information in pharmacokinetic (PK) outcome measures is shown by age cohort, drug dose received and infusion time in order to provide appropriate and clinically discrete groups for PK analysis and modeling.
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1: IMI/REL 15/7.5 mg/kg | Adolescents (age 12 to <18 years) administered with a single intravenous (IV) 30-minute infusion dose of imipenem/cilastatin/relebactam (IMI/REL) at 15/7.5 mg/kg, up to maximum dose of 500/250 mg |
| FG001 | Cohort 2: IMI/REL 15/7.5 mg/kg |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Aug 22, 2019 |
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| 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5 |
| Relebactam (REL) AUC0-∞ | Area under the concentration time curve from time 0 to infinity (AUC0-∞) of plasma relebactam (REL) was calculated. AUC0-∞ is the area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time. | 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5 |
| REL Maximum Concentration (Cmax) | Maximum plasma concentration (Cmax) of REL was calculated. Cmax is the peak plasma concentration of study drug after administration. | 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5 |
| REL Clearance (CL) | Systemic clearance (CL) of plasma REL was calculated. | 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5 |
| REL Central Volume of Distribution (Vc) | Central volume of distribution (Vc) of plasma REL was calculated. | 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5 |
| Cilastatin (CIL) AUC0-∞ | Area under the concentration time curve from time 0 to infinity (AUC0-∞) of plasma cilastatin (CIL) was not calculated. AUC0-∞ is the area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time. | 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5 |
| CIL Time to Maximum Concentration (Tmax) | Time to maximum plasma concentration (Tmax) of CIL was determined. Tmax is defined as the time after drug administration at which peak drug concentration in plasma occurs. | 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5 |
| CIL Concentration at End of Infusion (Ceoi) | Concentration at end of infusion (Ceoi) of plasma CIL was determined. | 30 min after the start of infusion for Cohort 1; 60 min after the start of infusion for Cohorts 2-5 |
| CIL Terminal Half-Life (t1/2) | Terminal half-life (t1/2) of plasma CIL was not calculated. | 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5 |
| CIL Clearance (CL) | Systemic clearance (CL) of plasma CIL was not calculated. | 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5 |
| CIL Volume of Distribution (Vss) | Volume of distribution (Vss) of plasma CIL was not calculated. | 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to12 hrs after start of DI for Cohort 5 |
Number of participants who discontinued study drug due to an AE was calculated. An AE is defined as any untoward medical occurrence in a participant administered study drug and which may or may not have a causal relationship to the study drug. |
| Day 1 |
| Orange |
| California |
| 92868 |
| United States |
| Rady Children's Hospital-San Diego ( Site 1305) | San Diego | California | 92123 | United States |
| Our Lady of the Lake Hospital ( Site 1304) | Baton Rouge | Louisiana | 70808 | United States |
| St. Louis Children's Hospital ( Site 1322) | St Louis | Missouri | 63110 | United States |
| Duke University Medical Center ( Site 1317) | Durham | North Carolina | 27710 | United States |
| The Children's Hospital of Philadelphia ( Site 1318) | Philadelphia | Pennsylvania | 19104 | United States |
| Seattle Childrens Hospital ( Site 1321) | Seattle | Washington | 98105 | United States |
| MHAT Pazardjik AD ( Site 0208) | Pazardzhik | Pazardzhik | 4400 | Bulgaria |
| UMHAT Deva Maria. EOOD ( Site 0209) | Burgas | 8127 | Bulgaria |
| UMHAT Dr. Georgi Stranski EAD ( Site 0211) | Pleven | 5800 | Bulgaria |
| UMHAT Kanev AD ( Site 0203) | Rousse | 7002 | Bulgaria |
| UMHAT Kanev AD ( Site 0212) | Rousse | 7002 | Bulgaria |
| Hospital Pablo Tobon Uribe ( Site 0301) | Medellín | Antioquia | 050034 | Colombia |
| Hospital General de Medellin Luz Castro de Gutierrez ( Site 0303) | Medellín | Antioquia | 500515 | Colombia |
| Fundacion Valle del Lili ( Site 0300) | Cali | Valle del Cauca Department | 760032 | Colombia |
| General Hospital of Thessaloniki Hippokrateio ( Site 1402) | Thessaloniki | 546 42 | Greece |
| Akershus Universitetssykehus HF ( Site 0903) | Loerenskog | Akershus | 1478 | Norway |
| Stavanger Universitetssykehus, Helse Stavanger ( Site 0901) | Stavanger | Rogaland | 4011 | Norway |
| St. Olavs Hospital ( Site 0900) | Trondheim | Sor-Trondelag | 7006 | Norway |
| Haukeland Universitetssjukehus ( Site 0902) | Bergen | Vestfold | 5021 | Norway |
| SPZOZ im. Dzieci Warszawy w Dziekanowie Lesnym ( Site 1002) | Łomianki | Masovian Voivodeship | 05-092 | Poland |
| Wojewodzki Specjalistyczny Szpital im. Bieganskiego w Lodzi ( Site 1000) | Lodz | Łódź Voivodeship | 91-347 | Poland |
| SI Dnipropetrovsk Regional Children Clinical Hospital DOR ( Site 1214) | Dnipro | Dnipropetrovsk Oblast | 49100 | Ukraine |
| Kharkiv City Children Hospital 16 ( Site 1200) | Kharkiv | Kharkiv Oblast | 61075 | Ukraine |
| Institution of Pediatr Obstetr and Gynec NAMS of Ukraine ( Site 1213) | Kyiv | Kyivska Oblast | 04050 | Ukraine |
| Odessa Regional Children Clinical Hospital ( Site 1203) | Odesa | Odesa Oblast | 65031 | Ukraine |
| Children City Clinical Hospital ( Site 1215) | Poltava | Poltava Oblast | 36004 | Ukraine |
| Zaporizhzhya Regional Clinical Childrens Hospital ( Site 1202) | Zaporizhzhya | Zaporizhzhia Oblast | 69063 | Ukraine |
| Bristol Royal Hospital for Children ( Site 1101) | Bristol | Bristol, City of | BS2 8AF | United Kingdom |
| University Hospital Southampton NHS Foundation Trust ( Site 1100) | Southampton | Hampshire | SO16 6YD | United Kingdom |
| St. Georges University Hospital NHS Foundation Trust ( Site 1103) | London | London, City of | SW17 0QT | United Kingdom |
| Great Northern Children s Hospital ( Site 1102) | Newcastle | Newcastle Upon Tyne | NE1 4LP | United Kingdom |
Older children (6 to <12 years) administered with a single IV 30-minute or 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg, up to a maximum dose of 500/250 mg |
| FG002 | Cohort 3: IMI/REL 15/7.5 mg/kg | Younger children (2 to <6 years) administered with a single IV 30-minute or 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| FG003 | Cohort 4: IMI/REL 10/5 mg/kg | Infants (3 months to <1 year) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 mg/kg |
| FG004 | Cohort 4: IMI/REL 15/7.5 mg/kg | Toddlers (1 to <2 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| FG005 | Cohort 5: Subcohort 1: IMI/REL 10/5 mg/kg | Young infants (4 weeks to <3 months of age) administered with a single IV 60-minute dose of IMI/REL at 10/5 mg/kg |
| FG006 | Cohort 5: Subcohort 2: IMI/REL 10/5 mg/kg | Older neonates (1 to <4 weeks of age) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 mg/kg |
| FG007 | Cohort 5: Subcohort 3: IMI/REL 10/5 mg/kg | Younger neonates (<1 week of age) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 mg/kg |
| FG008 | Cohort 5: Subcohort 1: IMI/REL 15/7.5 mg/kg | Young infants (4 weeks to <3 months of age) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| FG009 | Cohort 5: Subcohort 2: IMI/REL 15/7.5 mg/kg | Older neonates (1 to <4 weeks of age) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| FG010 | Cohort 5: Subcohort 3: IMI/REL 15/7.5 mg/kg | Younger neonates (<1 week of age) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| Treated |
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| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1: IMI/REL 15/7.5 mg/kg | Adolescents (age 12 to <18 years) administered with a single intravenous (IV) 30-minute infusion dose of imipenem/cilastatin/relebactam (IMI/REL) at 15/7.5 mg/kg, up to maximum dose of 500/250 mg |
| BG001 | Cohort 2: IMI/REL 15/7.5 mg/kg | Older children (6 to <12 years) administered with a single IV 30-minute or 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg, up to a maximum dose of 500/250 mg |
| BG002 | Cohort 3: IMI/REL 15/7.5 mg/kg | Younger children (2 to <6 years) administered with a single IV 30-minute or 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| BG003 | Cohort 4: IMI/REL 10/5 mg/kg | Infants (3 months to <1 year) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 mg/kg |
| BG004 | Cohort 4: IMI/REL 15/7.5 mg/kg | Toddlers (1 to <2 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| BG005 | Cohort 5: Subcohort 1: IMI/REL 10/5 mg/kg | Young infants (4 weeks to <3 months of age) administered with a single IV 60-minute dose of IMI/REL at 10/5 mg/kg |
| BG006 | Cohort 5: Subcohort 2: IMI/REL 10/5 mg/kg | Older neonates (1 to <4 weeks of age) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 mg/kg |
| BG007 | Cohort 5: Subcohort 3: IMI/REL 10/5 mg/kg | Younger neonates (<1 week of age) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 mg/kg |
| BG008 | Cohort 5: Subcohort 1: IMI/REL 15/7.5 mg/kg | Young infants (4 weeks to <3 months of age) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| BG009 | Cohort 5: Subcohort 2: IMI/REL 15/7.5 mg/kg | Older neonates (1 to <4 weeks of age) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| BG010 | Cohort 5: Subcohort 3: IMI/REL 15/7.5 mg/kg | Younger neonates (<1 week of age) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| BG011 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Imipenem (IMI) Area Under the Concentration Time Curve From Time 0 to Infinity (AUC0-∞) | Area under the concentration time curve from time 0 to infinity (AUC0-∞) of plasma imipenem (IMI) was calculated. AUC0-∞ is the area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time. | All allocated participants who were compliant with the protocol and had at least 1 post-dose pharmacokinetic (PK) data point available for IMI AUC0-∞ | Posted | Geometric Mean | Geometric Coefficient of Variation | μM*hr | 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5 |
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| Primary | IMI Maximum Concentration (Cmax) | Maximum plasma concentration (Cmax) of IMI was calculated. Cmax is the peak plasma concentration of study drug after administration. | All allocated participants who were compliant with the protocol and had at least 1 post-dose pharmacokinetic (PK) data point available for IMI Cmax | Posted | Geometric Mean | Geometric Coefficient of Variation | μM | 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5 |
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| Primary | IMI Central Volume of Distribution (Vc) | Central volume of distribution (Vc) of plasma IMI was calculated. | All allocated participants who were compliant with the protocol and had at least 1 post-dose PK data point available for IMI Vc | Posted | Geometric Mean | Geometric Coefficient of Variation | Liters | 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5 |
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| Primary | IMI Clearance (CL) | Systemic clearance (CL) of plasma IMI was calculated. | All allocated participants who were compliant with the protocol and had at least 1 post-dose PK data point available for IMI CL | Posted | Geometric Mean | Geometric Coefficient of Variation | L/hr | 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5 |
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| Primary | IMI Percentage of Time Above the Minimum Concentration (%TMIC) | Percentage of time spent above the minimum inhibitory concentration (%TMIC) of plasma IMI was calculated. %TMIC is defined as the percentage of time (in hours) in which the lowest concentration of a study drug, completely inhibits growth of the specific organism being tested. | All allocated participants who were compliant with the protocol and had at least 1 post-dose PK data point available for IMI %TMIC | Posted | Geometric Mean | Geometric Coefficient of Variation | Percentage of time | 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5 |
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| Primary | Relebactam (REL) AUC0-∞ | Area under the concentration time curve from time 0 to infinity (AUC0-∞) of plasma relebactam (REL) was calculated. AUC0-∞ is the area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time. | All allocated participants who were compliant with the protocol and had at least 1 post-dose PK data point available for REL AUC0-∞ | Posted | Geometric Mean | Geometric Coefficient of Variation | μM*hr | 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5 |
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| Primary | REL Maximum Concentration (Cmax) | Maximum plasma concentration (Cmax) of REL was calculated. Cmax is the peak plasma concentration of study drug after administration. | All allocated participants who were compliant with the protocol and had at least 1 post-dose PK data point available for REL Cmax | Posted | Geometric Mean | Geometric Coefficient of Variation | μM | 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5 |
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| Primary | REL Clearance (CL) | Systemic clearance (CL) of plasma REL was calculated. | All allocated participants who were compliant with the protocol and had at least 1 post-dose PK data point available for REL CL | Posted | Geometric Mean | Geometric Coefficient of Variation | L/hr | 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5 |
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| Primary | REL Central Volume of Distribution (Vc) | Central volume of distribution (Vc) of plasma REL was calculated. | All allocated participants who were compliant with the protocol and had at least 1 post-dose PK data point available for REL Vc | Posted | Geometric Mean | Geometric Coefficient of Variation | Liters | 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5 |
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| Primary | Cilastatin (CIL) AUC0-∞ | Area under the concentration time curve from time 0 to infinity (AUC0-∞) of plasma cilastatin (CIL) was not calculated. AUC0-∞ is the area under the plasma concentration versus time curve from time zero (pre-dose) to extrapolated infinite time. | Due to sparse PK sampling schedule, per participant data could not be calculated. | Posted | 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5 |
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| Primary | CIL Time to Maximum Concentration (Tmax) | Time to maximum plasma concentration (Tmax) of CIL was determined. Tmax is defined as the time after drug administration at which peak drug concentration in plasma occurs. | All allocated participants who were compliant with the protocol and had at least 1 post-dose PK data point available for CIL Tmax | Posted | Median | Full Range | Hours | 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5 |
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| Primary | CIL Concentration at End of Infusion (Ceoi) | Concentration at end of infusion (Ceoi) of plasma CIL was determined. | All allocated participants who were compliant with the protocol and had at least 1 post-dose PK data point available for CIL Ceoi | Posted | Geometric Mean | Geometric Coefficient of Variation | μM | 30 min after the start of infusion for Cohort 1; 60 min after the start of infusion for Cohorts 2-5 |
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| Primary | CIL Terminal Half-Life (t1/2) | Terminal half-life (t1/2) of plasma CIL was not calculated. | Due to sparse PK sampling schedule, per participant data could not be calculated. | Posted | 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5 |
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| Primary | CIL Clearance (CL) | Systemic clearance (CL) of plasma CIL was not calculated. | Due to sparse PK sampling schedule, per participant data could not be calculated. | Posted | 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to 12 hrs after start of DI for Cohort 5 |
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| Primary | CIL Volume of Distribution (Vss) | Volume of distribution (Vss) of plasma CIL was not calculated. | Due to sparse PK sampling schedule, per participant data could not be calculated. | Posted | 30 minutes (min) before start of drug infusion (DI) and 10 min after the end of DI for all cohorts; 1.5 to 2.5 hours (hrs) and 4.5 to 6 hrs after start of DI for Cohorts 1-4; 2 to 5 hrs and 6 to12 hrs after start of DI for Cohort 5 |
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| Secondary | Number of Participants Who Experienced an Adverse Event (AE) | Number of participants with one or more AEs was calculated. An AE is defined as any untoward medical occurrence in a participant administered study drug and which may or may not have a causal relationship to the study drug. | All allocated participants who received infusion (including partial doses) of study drug | Posted | Count of Participants | Participants | Up to 17 days |
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| Secondary | Number of Participants Who Discontinued Study Drug Due to an AE | Number of participants who discontinued study drug due to an AE was calculated. An AE is defined as any untoward medical occurrence in a participant administered study drug and which may or may not have a causal relationship to the study drug. | All allocated participants who received infusion (including partial doses) of study drug | Posted | Count of Participants | Participants | Day 1 |
|
Up to 17 days (AE reporting), up to 19 days (all-cause mortality)
The analysis population included all allocated participants who received infusion (including partial doses) of study drug. Note: Participant information is shown by age cohort and drug dosage, to provide clinically-similar groups for analysis of safety data.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort 1: IMI/REL 15/7.5 mg/kg | Adolescents (age 12 to <18 years) administered with a single IV 30-minute infusion dose of IMI/REL at 15/7.5 mg/kg, up to maximum dose of 500/250 mg | 0 | 7 | 0 | 7 | 1 | 7 |
| EG001 | Cohort 2: IMI/REL 15/7.5 mg/kg | Older children (6 to <12 years) administered with a single IV 30-minute or 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg, up to a maximum dose of 500/250 mg | 0 | 6 | 0 | 6 | 0 | 6 |
| EG002 | Cohort 3: IMI/REL 15/7.5 mg/kg | Younger children (2 to <6 years) administered with a single IV 30-minute or 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg | 0 | 6 | 0 | 6 | 3 | 6 |
| EG003 | Cohort 4: IMI/REL 10/5 mg/kg | Infants (3 months to <1 year) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 mg/kg | 0 | 4 | 0 | 4 | 1 | 4 |
| EG004 | Cohort 4: IMI/REL 15/7.5 mg/kg | Toddlers (1 to <2 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg | 0 | 4 | 0 | 4 | 2 | 4 |
| EG005 | Cohort 5: Subcohort 1: IMI/REL 10/5 mg/kg | Young infants (4 weeks to <3 months of age) administered with a single IV 60-minute dose of IMI/REL at 10/5 mg/kg | 0 | 5 | 0 | 5 | 1 | 5 |
| EG006 | Cohort 5: Subcohort 2: IMI/REL 10/5 mg/kg | Older neonates (1 to <4 weeks of age) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 mg/kg | 0 | 3 | 0 | 3 | 0 | 3 |
| EG007 | Cohort 5: Subcohort 3: IMI/REL 10/5 mg/kg | Younger neonates (<1 week of age) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 mg/kg | 0 | 2 | 0 | 2 | 0 | 2 |
| EG008 | Cohort 5: Subcohort 1: IMI/REL 15/7.5 mg/kg | Young infants (4 weeks to <3 months of age) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg | 0 | 2 | 0 | 2 | 0 | 2 |
| EG009 | Cohort 5: Subcohort 2: IMI/REL 15/7.5 mg/kg | Older neonates (1 to <4 weeks of age) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg | 0 | 3 | 0 | 3 | 0 | 3 |
| EG010 | Cohort 5: Subcohort 3: IMI/REL 15/7.5 mg/kg | Younger neonates (<1 week of age) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg | 0 | 4 | 0 | 4 | 0 | 4 |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Thrombocytoses | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 23.0 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 23.0 | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA 23.0 | Systematic Assessment |
| |
| Miliaria | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Trials Disclosure | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| Jul 21, 2021 |
| Prot_SAP_000.pdf |
| Preterm newborn infants (gestational age < 37 wks) |
|
| Newborns (0-27 days) |
|
| Infants and toddlers (28 days-23 months) |
|
| Children (2-11 years) |
|
| Adolescents (12-17 years) |
|
| Adults (18-64 years) |
|
| From 65-84 years |
|
| 85 years and over |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| OG003 | Cohort 2: IMI/REL 500/250 mg 30-minute Infusion | Older children (6 to <12 years) administered with a single IV 30-minute infusion dose of IMI/REL at 500/250 mg |
| OG004 | Cohort 2: IMI/REL 500/250 mg 60-minute Infusion | Older children (6 to <12 years) administered with a single IV 60-minute infusion dose of IMI/REL at 500/250 mg |
| OG005 | Cohort 3: IMI/REL 15/7.5 mg/kg 30-minute Infusion | Younger children (2 to <6 years) administered with a single IV 30-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| OG006 | Cohort 3: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Younger children (2 to <6 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| OG007 | Cohort 4: IMI/REL 10/5 mg/kg 60-minute Infusion | Infants (3 months to <1 year) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 mg/kg |
| OG008 | Cohort 4: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Toddlers (1 to 2 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| OG009 | Cohort 5: IMI/REL 10/5 mg/kg 60-minute Infusion | Neonates to infants (birth to <3 months of age) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 mg/kg |
| OG010 | Cohort 5: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Neonates to infants (birth to <3 months of age) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
|
|
| Cohort 2: IMI/REL 500/250 mg 30-minute Infusion |
Older children (6 to <12 years) administered with a single IV 30-minute infusion dose of IMI/REL at 500/250 mg |
| OG004 | Cohort 2: IMI/REL 500/250 mg 60-minute Infusion | Older children (6 to <12 years) administered with a single IV 60-minute infusion dose of IMI/REL at 500/250 mg |
| OG005 | Cohort 3: IMI/REL 15/7.5 mg/kg 30-minute Infusion | Younger children (2 to <6 years) administered with a single IV 30-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| OG006 | Cohort 3: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Younger children (2 to <6 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| OG007 | Cohort 4: IMI/REL 10/5 mg/kg 60-minute Infusion | Infants (3 months to <1 year) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 mg/kg |
| OG008 | Cohort 4: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Toddlers (1 to 2 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| OG009 | Cohort 5: IMI/REL 10/5 mg/kg 60-minute Infusion | Neonates to infants (birth to <3 months of age) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 mg/kg |
| OG010 | Cohort 5: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Neonates to Infants (birth to <3 months of age) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
|
|
Older children (6 to <12 years) administered with a single IV 30-minute infusion dose of IMI/REL at 500/250 mg |
| OG004 | Cohort 2: IMI/REL 500/250 mg 60-minute Infusion | Older children (6 to <12 years) administered with a single IV 60-minute infusion dose of IMI/REL at 500/250 mg |
| OG005 | Cohort 3: IMI/REL 15/7.5 mg/kg 30-minute Infusion | Younger children (2 to <6 years) administered with a single IV 30-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| OG006 | Cohort 3: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Younger children (2 to <6 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| OG007 | Cohort 4: IMI/REL 10/5 mg/kg 60-minute Infusion | Infants (3 months to <1 year) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 mg/kg |
| OG008 | Cohort 4: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Toddlers (1 to 2 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| OG009 | Cohort 5: IMI/REL 10/5 mg/kg 60-minute Infusion | Neonates to infants (birth to <3 months of age) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 mg/kg |
| OG010 | Cohort 5: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Neonates to infants (birth to <3 months of age) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
|
|
Older children (6 to <12 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg
| OG003 | Cohort 2: IMI/REL 500/250 mg 30-minute Infusion | Older children (6 to <12 years) administered with a single IV 30-minute infusion dose of IMI/REL at 500/250 mg |
| OG004 | Cohort 2: IMI/REL 500/250 mg 60-minute Infusion | Older children (6 to <12 years) administered with a single IV 60-minute infusion dose of IMI/REL at 500/250 mg |
| OG005 | Cohort 3: IMI/REL 15/7.5 mg/kg 30-minute Infusion | Younger children (2 to <6 years) administered with a single IV 30-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| OG006 | Cohort 3: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Younger children (2 to <6 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| OG007 | Cohort 4: IMI/REL 10/5 mg/kg 60-minute Infusion | Infants (3 months to <1 year) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 mg/kg |
| OG008 | Cohort 4: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Toddlers (1 to 2 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| OG009 | Cohort 5: IMI/REL 10/5 mg/kg 60-minute Infusion | Neonates to infants (birth to <3 months of age) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 mg/kg |
| OG010 | Cohort 5: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Neonates to infants (birth to <3 months of age) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
|
|
| OG003 | Cohort 2: IMI/REL 500/250 mg 30-minute Infusion | Older children (6 to <12 years) administered with a single IV 30-minute infusion dose of IMI/REL at 500/250 mg |
| OG004 | Cohort 2: IMI/REL 500/250 mg 60-minute Infusion | Older children (6 to <12 years) administered with a single IV 60-minute infusion dose of IMI/REL at 500/250 mg |
| OG005 | Cohort 3: IMI/REL 15/7.5 mg/kg 30-minute Infusion | Younger children (2 to <6 years) administered with a single IV 30-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| OG006 | Cohort 3: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Younger children (2 to <6 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| OG007 | Cohort 4: IMI/REL 10/5 mg/kg 60-minute Infusion | Infants (3 months to <1 year) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 mg/kg |
| OG008 | Cohort 4: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Toddlers (1 to 2 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| OG009 | Cohort 5: IMI/REL 10/5 mg/kg 60-minute Infusion | Neonates to infants (birth to <3 months of age) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 mg/kg |
| OG010 | Cohort 5: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Neonates to infants (birth to <3 months of age) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
|
|
| OG003 |
| Cohort 2: IMI/REL 500/250 mg 30-minute Infusion |
Older children (6 to <12 years) administered with a single IV 30-minute infusion dose of IMI/REL at 500/250 mg |
| OG004 | Cohort 2: IMI/REL 500/250 mg 60-minute Infusion | Older children (6 to <12 years) administered with a single IV 60-minute infusion dose of IMI/REL at 500/250 mg |
| OG005 | Cohort 3: IMI/REL 15/7.5 mg/kg 30-minute Infusion | Younger children (2 to <6 years) administered with a single IV 30-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| OG006 | Cohort 3: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Younger children (2 to <6 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| OG007 | Cohort 4: IMI/REL 10/5 mg/kg 60-minute Infusion | Infants (3 months to <1 year) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 mg/kg |
| OG008 | Cohort 4: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Toddlers (1 to 2 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| OG009 | Cohort 5: IMI/REL 10/5 mg/kg 60-minute Infusion | Neonates to infants (birth to <3 months of age) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 mg/kg |
| OG010 | Cohort 5: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Neonates to infants (birth to <3 months of age) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
|
|
Older children (6 to <12 years) administered with a single IV 30-minute infusion dose of IMI/REL at 500/250 mg |
| OG004 | Cohort 2: IMI/REL 500/250 mg 60-minute Infusion | Older children (6 to <12 years) administered with a single IV 60-minute infusion dose of IMI/REL at 500/250 mg |
| OG005 | Cohort 3: IMI/REL 15/7.5 mg/kg 30-minute Infusion | Younger children (2 to <6 years) administered with a single IV 30-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| OG006 | Cohort 3: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Younger children (2 to <6 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| OG007 | Cohort 4: IMI/REL 10/5 mg/kg 60-minute Infusion | Infants (3 months to <1 year) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 mg/kg |
| OG008 | Cohort 4: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Toddlers (1 to 2 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| OG009 | Cohort 5: IMI/REL 10/5 mg/kg 60-minute Infusion | Neonates to infants (birth to <3 months of age) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 mg/kg |
| OG010 | Cohort 5: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Neonates to infants (birth to <3 months of age) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
|
|
| Cohort 2: IMI/REL 500/250 mg 30-minute Infusion |
Older children (6 to <12 years) administered with a single IV 30-minute infusion dose of IMI/REL at 500/250 mg |
| OG004 | Cohort 2: IMI/REL 500/250 mg 60-minute Infusion | Older children (6 to <12 years) administered with a single IV 60-minute infusion dose of IMI/REL at 500/250 mg |
| OG005 | Cohort 3: IMI/REL 15/7.5 mg/kg 30-minute Infusion | Younger children (2 to <6 years) administered with a single IV 30-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| OG006 | Cohort 3: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Younger children (2 to <6 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| OG007 | Cohort 4: IMI/REL 10/5 mg/kg 60-minute Infusion | Infants (3 months to <1 year) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 mg/kg |
| OG008 | Cohort 4: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Toddlers (1 to 2 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| OG009 | Cohort 5: IMI/REL 10/5 mg/kg 60-minute Infusion | Neonates to infants (birth to <3 months of age) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 mg/kg |
| OG010 | Cohort 5: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Neonates to infants (birth to <3 months of age) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
|
|
| OG003 | Cohort 2: IMI/REL 500/250 mg 30-minute Infusion | Older children (6 to <12 years) administered with a single IV 30-minute infusion dose of IMI/REL at 500/250 mg |
| OG004 | Cohort 2: IMI/REL 500/250 mg 60-minute Infusion | Older children (6 to <12 years) administered with a single IV 60-minute infusion dose of IMI/REL at 500/250 mg |
| OG005 | Cohort 3: IMI/REL 15/7.5 mg/kg 30-minute Infusion | Younger children (2 to <6 years) administered with a single IV 30-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| OG006 | Cohort 3: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Younger children (2 to <6 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| OG007 | Cohort 4: IMI/REL 10/5 mg/kg | Infants (3 months to <1 year) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 mg/kg |
| OG008 | Cohort 4: IMI/REL 15/7.5 mg/kg | Toddlers (1 to 2 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| OG009 | Cohort 5: IMI/REL 10/5 mg/kg | Neonates to infants (birth to <3 months of age) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 mg/kg |
| OG010 | Cohort 5: IMI/REL 15/7.5 mg/kg | Neonates to infants (birth to <3 months of age) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
|
| OG003 | Cohort 2: IMI/REL 500/250 mg 30-minute Infusion | Older children (6 to <12 years) administered with a single IV 30-minute infusion dose of IMI/REL at 500/250 mg |
| OG004 | Cohort 2: IMI/REL 500/250 mg 60-minute Infusion | Older children (6 to <12 years) administered with a single IV 60-minute infusion dose of IMI/REL at 500/250 mg |
| OG005 | Cohort 3: IMI/REL 15/7.5 mg/kg 30-minute Infusion | Younger children (2 to <6 years) administered with a single IV 30-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| OG006 | Cohort 3: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Younger children (2 to <6 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| OG007 | Cohort 4: IMI/REL 10/5 mg/kg | Infants (3 months to <1 year) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 mg/kg |
| OG008 | Cohort 4: IMI/REL 15/7.5 mg/kg | Toddlers (1 to 2 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| OG009 | Cohort 5: IMI/REL 10/5 mg/kg | Neonates to infants (birth to <3 months of age) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 mg/kg |
| OG010 | Cohort 5: IMI/REL 15/7.5 mg/kg | Neonates to infants (birth to <3 months of age) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
|
|
Older children (6 to <12 years) administered with a single IV 30-minute infusion dose of IMI/REL at 500/250 mg |
| OG004 | Cohort 2: IMI/REL 500/250 mg 60-minute Infusion | Older children (6 to <12 years) administered with a single IV 60-minute infusion dose of IMI/REL at 500/250 mg |
| OG005 | Cohort 3: IMI/REL 15/7.5 mg/kg 30-minute Infusion | Younger children (2 to <6 years) administered with a single IV 30-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| OG006 | Cohort 3: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Younger children (2 to <6 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| OG007 | Cohort 4: IMI/REL 10/5 mg/kg | Infants (3 months to <1 year) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 mg/kg |
| OG008 | Cohort 4: IMI/REL 15/7.5 mg/kg | Toddlers (1 to 2 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| OG009 | Cohort 5: IMI/REL 10/5 mg/kg | Neonates to infants (birth to <3 months of age) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 mg/kg |
| OG010 | Cohort 5: IMI/REL 15/7.5 mg/kg | Neonates to infants (birth to <3 months of age) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
|
|
Older children (6 to <12 years) administered with a single IV 30-minute infusion dose of IMI/REL at 500/250 mg
| OG004 | Cohort 2: IMI/REL 500/250 mg 60-minute Infusion | Older children (6 to <12 years) administered with a single IV 60-minute infusion dose of IMI/REL at 500/250 mg |
| OG005 | Cohort 3: IMI/REL 15/7.5 mg/kg 30-minute Infusion | Younger children (2 to <6 years) administered with a single IV 30-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| OG006 | Cohort 3: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Younger children (2 to <6 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| OG007 | Cohort 4: IMI/REL 10/5 mg/kg | Infants (3 months to <1 year) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 mg/kg |
| OG008 | Cohort 4: IMI/REL 15/7.5 mg/kg | Toddlers (1 to 2 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| OG009 | Cohort 5: IMI/REL 10/5 mg/kg | Neonates to infants (birth to <3 months of age) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 mg/kg |
| OG010 | Cohort 5: IMI/REL 15/7.5 mg/kg | Neonates to infants (birth to <3 months of age) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
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Older children (6 to <12 years) administered with a single IV 30-minute infusion dose of IMI/REL at 500/250 mg
| OG004 | Cohort 2: IMI/REL 500/250 mg 60-minute Infusion | Older children (6 to <12 years) administered with a single IV 60-minute infusion dose of IMI/REL at 500/250 mg |
| OG005 | Cohort 3: IMI/REL 15/7.5 mg/kg 30-minute Infusion | Younger children (2 to <6 years) administered with a single IV 30-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| OG006 | Cohort 3: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Younger children (2 to <6 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| OG007 | Cohort 4: IMI/REL 10/5 mg/kg | Infants (3 months to <1 year) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 mg/kg |
| OG008 | Cohort 4: IMI/REL 15/7.5 mg/kg | Toddlers (1 to 2 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| OG009 | Cohort 5: IMI/REL 10/5 mg/kg | Neonates to infants (birth to <3 months of age) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 mg/kg |
| OG010 | Cohort 5: IMI/REL 15/7.5 mg/kg | Neonates to infants (birth to <3 months of age) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
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Older children (6 to <12 years) administered with a single IV 30-minute infusion dose of IMI/REL at 500/250 mg
| OG004 | Cohort 2: IMI/REL 500/250 mg 60-minute Infusion | Older children (6 to <12 years) administered with a single IV 60-minute infusion dose of IMI/REL at 500/250 mg |
| OG005 | Cohort 3: IMI/REL 15/7.5 mg/kg 30-minute Infusion | Younger children (2 to <6 years) administered with a single IV 30-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| OG006 | Cohort 3: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Younger children (2 to <6 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| OG007 | Cohort 4: IMI/REL 10/5 mg/kg | Infants (3 months to <1 year) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 mg/kg |
| OG008 | Cohort 4: IMI/REL 15/7.5 mg/kg | Toddlers (1 to 2 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| OG009 | Cohort 5: IMI/REL 10/5 mg/kg | Neonates to infants (birth to <3 months of age) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 mg/kg |
| OG010 | Cohort 5: IMI/REL 15/7.5 mg/kg | Neonates to infants (birth to <3 months of age) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
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Infants (3 months to <1 year) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 mg/kg |
| OG004 | Cohort 4: IMI/REL 15/7.5 mg/kg | Toddlers (1 to <2 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| OG005 | Cohort 5: Subcohort 1: IMI/REL 10/5 mg/kg | Young infants (4 weeks to <3 months of age) administered with a single IV 60-minute dose of IMI/REL at 10/5 mg/kg |
| OG006 | Cohort 5: Subcohort 2: IMI/REL 10/5 mg/kg | Older neonates (1 to <4 weeks of age) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 mg/kg |
| OG007 | Cohort 5: Subcohort 3: IMI/REL 10/5 mg/kg | Younger neonates (<1 week of age) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 mg/kg |
| OG008 | Cohort 5: Subcohort 1: IMI/REL 15/7.5 mg/kg | Young infants (4 weeks to <3 months of age) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| OG009 | Cohort 5: Subcohort 2: IMI/REL 15/7.5 mg/kg | Older neonates (1 to <4 weeks of age) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| OG010 | Cohort 5: Subcohort 3: IMI/REL 15/7.5 mg/kg | Younger neonates (<1 week of age) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
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Infants (3 months to <1 year) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 mg/kg |
| OG004 | Cohort 4: IMI/REL 15/7.5 mg/kg | Toddlers (1 to <2 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| OG005 | Cohort 5: Subcohort 1: IMI/REL 10/5 mg/kg | Young infants (4 weeks to <3 months of age) administered with a single IV 60-minute dose of IMI/REL at 10/5 mg/kg |
| OG006 | Cohort 5: Subcohort 2: IMI/REL 10/5 mg/kg | Older neonates (1 to <4 weeks of age) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 mg/kg |
| OG007 | Cohort 5: Subcohort 3: IMI/REL 10/5 mg/kg | Younger neonates (<1 week of age) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 mg/kg |
| OG008 | Cohort 5: Subcohort 1: IMI/REL 15/7.5 mg/kg | Young infants (4 weeks to <3 months of age) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| OG009 | Cohort 5: Subcohort 2: IMI/REL 15/7.5 mg/kg | Older neonates (1 to <4 weeks of age) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| OG010 | Cohort 5: Subcohort 3: IMI/REL 15/7.5 mg/kg | Younger neonates (<1 week of age) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
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