A Pharmacokinetics Study of MK-7655A in Pediatric Participants With Gram-negative Infections (MK-7655A-020)
Sponsor
Merck Sharp & Dohme LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT03230916
Collaborator
(none)
47
33
1
33.1
1.4
0
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
47 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1b, Open-label, Single-dose Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of MK-7655A in Pediatric Subjects From Birth to Less Than 18 Years of Age With Confirmed or Suspected Gram-negative Infections
Actual Study Start Date
:
Nov 6, 2017
Actual Primary Completion Date
:
Jul 28, 2020
Actual Study Completion Date
:
Aug 11, 2020
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: IMI/REL FDC 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). |
Drug: IMI/REL FDC
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).
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Imipenem (IMI) Area Under the Concentration Time Curve From Time 0 to Infinity (AUC0-∞) [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]
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.
- IMI Maximum Concentration (Cmax) [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]
Maximum plasma concentration (Cmax) of IMI was calculated. Cmax is the peak plasma concentration of study drug after administration.
- IMI Central Volume of Distribution (Vc) [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]
Central volume of distribution (Vc) of plasma IMI was calculated.
- IMI Clearance (CL) [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]
Systemic clearance (CL) of plasma IMI was calculated.
- IMI Percentage of Time Above the Minimum Concentration (%TMIC) [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]
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.
- Relebactam (REL) AUC0-∞ [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]
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.
- REL Maximum Concentration (Cmax) [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]
Maximum plasma concentration (Cmax) of REL was calculated. Cmax is the peak plasma concentration of study drug after administration.
- REL Clearance (CL) [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]
Systemic clearance (CL) of plasma REL was calculated.
- REL Central Volume of Distribution (Vc) [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]
Central volume of distribution (Vc) of plasma REL was calculated.
- Cilastatin (CIL) AUC0-∞ [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]
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.
- CIL Time to Maximum Concentration (Tmax) [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]
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.
- CIL Concentration at End of Infusion (Ceoi) [30 min after the start of infusion for Cohort 1; 60 min after the start of infusion for Cohorts 2-5]
Concentration at end of infusion (Ceoi) of plasma CIL was determined.
- CIL Terminal Half-Life (t1/2) [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]
Terminal half-life (t1/2) of plasma CIL was not calculated.
- CIL Clearance (CL) [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]
Systemic clearance (CL) of plasma CIL was not calculated.
- CIL Volume of Distribution (Vss) [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]
Volume of distribution (Vss) of plasma CIL was not calculated.
Secondary Outcome Measures
- Number of Participants Who Experienced an Adverse Event (AE) [Up to 17 days]
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.
- Number of Participants Who Discontinued Study Drug Due to an AE [Day 1]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
1 Day
to 17 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Arkansas Children's Hospital ( Site 1311) | Little Rock | Arkansas | United States | 72202 |
| 2 | Children's Hospital of Orange County ( Site 1301) | Orange | California | United States | 92868 |
| 3 | Rady Children's Hospital-San Diego ( Site 1305) | San Diego | California | United States | 92123 |
| 4 | Our Lady of the Lake Hospital ( Site 1304) | Baton Rouge | Louisiana | United States | 70808 |
| 5 | St. Louis Children's Hospital ( Site 1322) | Saint Louis | Missouri | United States | 63110 |
| 6 | Duke University Medical Center ( Site 1317) | Durham | North Carolina | United States | 27710 |
| 7 | The Children's Hospital of Philadelphia ( Site 1318) | Philadelphia | Pennsylvania | United States | 19104 |
| 8 | Seattle Childrens Hospital ( Site 1321) | Seattle | Washington | United States | 98105 |
| 9 | MHAT Pazardjik AD ( Site 0208) | Pazardjik | Pazardzhik | Bulgaria | 4400 |
| 10 | UMHAT Deva Maria. EOOD ( Site 0209) | Burgas | Bulgaria | 8127 | |
| 11 | UMHAT Dr. Georgi Stranski EAD ( Site 0211) | Pleven | Bulgaria | 5800 | |
| 12 | UMHAT Kanev AD ( Site 0203) | Ruse | Bulgaria | 7002 | |
| 13 | UMHAT Kanev AD ( Site 0212) | Ruse | Bulgaria | 7002 | |
| 14 | Hospital Pablo Tobon Uribe ( Site 0301) | Medellin | Antioquia | Colombia | 050034 |
| 15 | Hospital General de Medellin Luz Castro de Gutierrez ( Site 0303) | Medellin | Antioquia | Colombia | 500515 |
| 16 | Fundacion Valle del Lili ( Site 0300) | Cali | Valle Del Cauca | Colombia | 760032 |
| 17 | General Hospital of Thessaloniki Hippokrateio ( Site 1402) | Thessaloniki | Greece | 546 42 | |
| 18 | Akershus Universitetssykehus HF ( Site 0903) | Loerenskog | Akershus | Norway | 1478 |
| 19 | Stavanger Universitetssykehus, Helse Stavanger ( Site 0901) | Stavanger | Rogaland | Norway | 4011 |
| 20 | St. Olavs Hospital ( Site 0900) | Trondheim | Sor-Trondelag | Norway | 7006 |
| 21 | Haukeland Universitetssjukehus ( Site 0902) | Bergen | Vestfold | Norway | 5021 |
| 22 | Wojewodzki Specjalistyczny Szpital im. Bieganskiego w Lodzi ( Site 1000) | Lodz | Lodzkie | Poland | 91-347 |
| 23 | SPZOZ im. Dzieci Warszawy w Dziekanowie Lesnym ( Site 1002) | Lomianki | Mazowieckie | Poland | 05-092 |
| 24 | SI Dnipropetrovsk Regional Children Clinical Hospital DOR ( Site 1214) | Dnipro | Dnipropetrovska Oblast | Ukraine | 49100 |
| 25 | Kharkiv City Children Hospital 16 ( Site 1200) | Kharkiv | Kharkivska Oblast | Ukraine | 61075 |
| 26 | Institution of Pediatr Obstetr and Gynec NAMS of Ukraine ( Site 1213) | Kyiv | Kyivska Oblast | Ukraine | 04050 |
| 27 | Odessa Regional Children Clinical Hospital ( Site 1203) | Odesa | Odeska Oblast | Ukraine | 65031 |
| 28 | Children City Clinical Hospital ( Site 1215) | Poltava | Poltavska Oblast | Ukraine | 36004 |
| 29 | Zaporizhzhya Regional Clinical Childrens Hospital ( Site 1202) | Zaporizhzhya | Zaporizka Oblast | Ukraine | 69063 |
| 30 | Bristol Royal Hospital for Children ( Site 1101) | Bristol | Bristol, City Of | United Kingdom | BS2 8AF |
| 31 | University Hospital Southampton NHS Foundation Trust ( Site 1100) | Southampton | Hampshire | United Kingdom | SO16 6YD |
| 32 | St. Georges University Hospital NHS Foundation Trust ( Site 1103) | London | London, City Of | United Kingdom | SW17 0QT |
| 33 | Great Northern Children s Hospital ( Site 1102) | Newcastle | Newcastle Upon Tyne | United Kingdom | NE1 4LP |
Sponsors and Collaborators
- Merck Sharp & Dohme LLC
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier:
NCT03230916
Other Study ID Numbers:
- 7655A-020
- 2016-004328-43
- MK-7665A-020
First Posted:
Jul 27, 2017
Last Update Posted:
Dec 13, 2021
Last Verified:
Oct 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | 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. |
| Arm/Group Title | Cohort 1: IMI/REL 15/7.5 mg/kg | Cohort 2: IMI/REL 15/7.5 mg/kg | Cohort 3: IMI/REL 15/7.5 mg/kg | Cohort 4: IMI/REL 10/5 mg/kg | Cohort 4: IMI/REL 15/7.5 mg/kg | Cohort 5: Subcohort 1: IMI/REL 10/5 mg/kg | Cohort 5: Subcohort 2: IMI/REL 10/5 mg/kg | Cohort 5: Subcohort 3: IMI/REL 10/5 mg/kg | Cohort 5: Subcohort 1: IMI/REL 15/7.5 mg/kg | Cohort 5: Subcohort 2: IMI/REL 15/7.5 mg/kg | Cohort 5: Subcohort 3: IMI/REL 15/7.5 mg/kg |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | 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 | 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 | 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 | Infants (3 months to <1 year) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 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 | 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 | 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 | Younger neonates (<1 week of age) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 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 | 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 | Younger neonates (<1 week of age) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| Period Title: Overall Study | |||||||||||
| STARTED | 7 | 6 | 6 | 4 | 4 | 6 | 3 | 2 | 2 | 3 | 4 |
| Treated | 7 | 6 | 6 | 4 | 4 | 5 | 3 | 2 | 2 | 3 | 4 |
| COMPLETED | 7 | 6 | 6 | 4 | 4 | 5 | 3 | 2 | 2 | 3 | 4 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Cohort 1: IMI/REL 15/7.5 mg/kg | Cohort 2: IMI/REL 15/7.5 mg/kg | Cohort 3: IMI/REL 15/7.5 mg/kg | Cohort 4: IMI/REL 10/5 mg/kg | Cohort 4: IMI/REL 15/7.5 mg/kg | Cohort 5: Subcohort 1: IMI/REL 10/5 mg/kg | Cohort 5: Subcohort 2: IMI/REL 10/5 mg/kg | Cohort 5: Subcohort 3: IMI/REL 10/5 mg/kg | Cohort 5: Subcohort 1: IMI/REL 15/7.5 mg/kg | Cohort 5: Subcohort 2: IMI/REL 15/7.5 mg/kg | Cohort 5: Subcohort 3: IMI/REL 15/7.5 mg/kg | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | 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 | 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 | 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 | Infants (3 months to <1 year) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 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 | 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 | 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 | Younger neonates (<1 week of age) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 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 | 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 | Younger neonates (<1 week of age) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg | Total of all reporting groups |
| Overall Participants | 7 | 6 | 6 | 4 | 4 | 6 | 3 | 2 | 2 | 3 | 4 | 47 |
| Age, Customized (Count of Participants) | ||||||||||||
| In utero |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Preterm newborn infants (gestational age < 37 wks) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Newborns (0-27 days) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
3
100%
|
2
100%
|
0
0%
|
3
100%
|
4
100%
|
12
25.5%
|
| Infants and toddlers (28 days-23 months) |
0
0%
|
0
0%
|
0
0%
|
4
100%
|
4
100%
|
6
100%
|
0
0%
|
0
0%
|
2
100%
|
0
0%
|
0
0%
|
16
34%
|
| Children (2-11 years) |
0
0%
|
6
100%
|
6
100%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
12
25.5%
|
| Adolescents (12-17 years) |
7
100%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
7
14.9%
|
| Adults (18-64 years) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| From 65-84 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| 85 years and over |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Sex: Female, Male (Count of Participants) | ||||||||||||
| Female |
5
71.4%
|
5
83.3%
|
4
66.7%
|
4
100%
|
2
50%
|
2
33.3%
|
1
33.3%
|
1
50%
|
2
100%
|
1
33.3%
|
1
25%
|
28
59.6%
|
| Male |
2
28.6%
|
1
16.7%
|
2
33.3%
|
0
0%
|
2
50%
|
4
66.7%
|
2
66.7%
|
1
50%
|
0
0%
|
2
66.7%
|
3
75%
|
19
40.4%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||||||||||
| Hispanic or Latino |
0
0%
|
0
0%
|
2
33.3%
|
1
25%
|
2
50%
|
1
16.7%
|
1
33.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
7
14.9%
|
| Not Hispanic or Latino |
7
100%
|
6
100%
|
4
66.7%
|
3
75%
|
2
50%
|
5
83.3%
|
1
33.3%
|
2
100%
|
2
100%
|
3
100%
|
4
100%
|
39
83%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
33.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
2.1%
|
| Race (NIH/OMB) (Count of Participants) | ||||||||||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
25%
|
1
2.1%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
25%
|
1
16.7%
|
2
66.7%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
4
8.5%
|
| White |
7
100%
|
6
100%
|
4
66.7%
|
3
75%
|
2
50%
|
5
83.3%
|
0
0%
|
2
100%
|
2
100%
|
3
100%
|
3
75%
|
37
78.7%
|
| More than one race |
0
0%
|
0
0%
|
1
16.7%
|
1
25%
|
1
25%
|
0
0%
|
1
33.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
4
8.5%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
2.1%
|
Outcome Measures
| Title | Imipenem (IMI) Area Under the Concentration Time Curve From Time 0 to Infinity (AUC0-∞) |
|---|---|
| Description | 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. |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All allocated participants who were compliant with the protocol and had at least 1 post-dose pharmacokinetic (PK) data point available for IMI AUC0-∞ |
| Arm/Group Title | Cohort 1: IMI/REL 500/250 mg 30-minute Infusion | Cohort 2: IMI/REL 15/7.5 mg/kg 30-minute Infusion | Cohort 2: IMI/REL 15/7.5 mg/kg mg 60-minute Infusion | Cohort 2: IMI/REL 500/250 mg 30-minute Infusion | Cohort 2: IMI/REL 500/250 mg 60-minute Infusion | Cohort 3: IMI/REL 15/7.5 mg/kg 30-minute Infusion | Cohort 3: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Cohort 4: IMI/REL 10/5 mg/kg 60-minute Infusion | Cohort 4: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Cohort 5: IMI/REL 10/5 mg/kg 60-minute Infusion | Cohort 5: IMI/REL 15/7.5 mg/kg 60-minute Infusion |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Adolescents (age 12 to <18 years) administered with a single IV 30-minute infusion dose of IMI/REL at 500/250 mg | Older children (6 to <12 years) administered with a single IV 30-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 | Older children (6 to <12 years) administered with a single IV 30-minute infusion dose of IMI/REL at 500/250 mg | Older children (6 to <12 years) administered with a single IV 60-minute infusion dose of IMI/REL at 500/250 mg | Younger children (2 to <6 years) administered with a single IV 30-minute infusion dose of IMI/REL at 15/7.5 mg/kg | Younger children (2 to <6 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 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 | Toddlers (1 to 2 years) administered with a single IV 60-minute infusion dose of IMI/REL at 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 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 15/7.5 mg/kg |
| Measure Participants | 6 | 1 | 2 | 2 | 1 | 3 | 3 | 4 | 4 | 6 | 9 |
| Geometric Mean (Geometric Coefficient of Variation) [μM*hr] |
134.7
(19.8)
|
153.2
(NA)
|
219.4
(39.2)
|
139.4
(26.6)
|
140
(NA)
|
156
(18.9)
|
163
(31.2)
|
95.4
(39.3)
|
219.2
(39.6)
|
152.5
(14.1)
|
271.3
(15.4)
|
| Title | IMI Maximum Concentration (Cmax) |
|---|---|
| Description | Maximum plasma concentration (Cmax) of IMI was calculated. Cmax is the peak plasma concentration of study drug after administration. |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All allocated participants who were compliant with the protocol and had at least 1 post-dose pharmacokinetic (PK) data point available for IMI Cmax |
| Arm/Group Title | Cohort 1: IMI/REL 500/250 mg 30-minute Infusion | Cohort 2: IMI/REL 15/7.5 mg/kg 30-minute Infusion | Cohort 2: IMI/REL 15/7.5 mg/kg mg 60-minute Infusion | Cohort 2: IMI/REL 500/250 mg 30-minute Infusion | Cohort 2: IMI/REL 500/250 mg 60-minute Infusion | Cohort 3: IMI/REL 15/7.5 mg/kg 30-minute Infusion | Cohort 3: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Cohort 4: IMI/REL 10/5 mg/kg 60-minute Infusion | Cohort 4: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Cohort 5: IMI/REL 10/5 mg/kg 60-minute Infusion | Cohort 5: IMI/REL 15/7.5 mg/kg 60-minute Infusion |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Adolescents (age 12 to <18 years) administered with a single IV 30-minute infusion dose of IMI/REL at 500/250 mg | Older children (6 to <12 years) administered with a single IV 30-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 | Older children (6 to <12 years) administered with a single IV 30-minute infusion dose of IMI/REL at 500/250 mg | Older children (6 to <12 years) administered with a single IV 60-minute infusion dose of IMI/REL at 500/250 mg | Younger children (2 to <6 years) administered with a single IV 30-minute infusion dose of IMI/REL at 15/7.5 mg/kg | Younger children (2 to <6 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 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 | Toddlers (1 to 2 years) administered with a single IV 60-minute infusion dose of IMI/REL at 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 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 15/7.5 mg/kg |
| Measure Participants | 6 | 1 | 2 | 2 | 1 | 3 | 3 | 4 | 4 | 6 | 9 |
| Geometric Mean (Geometric Coefficient of Variation) [μM] |
107.6
(16.4)
|
126.0
(NA)
|
123.0
(20.6)
|
114.2
(9.2)
|
110.6
(NA)
|
150.3
(6.7)
|
125.1
(25.2)
|
64.9
(29.6)
|
127.7
(36.0)
|
79.4
(26.4)
|
119.8
(16.8)
|
| Title | IMI Central Volume of Distribution (Vc) |
|---|---|
| Description | Central volume of distribution (Vc) of plasma IMI was calculated. |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All allocated participants who were compliant with the protocol and had at least 1 post-dose PK data point available for IMI Vc |
| Arm/Group Title | Cohort 1: IMI/REL 500/250 mg 30-minute Infusion | Cohort 2: IMI/REL 15/7.5 mg/kg 30-minute Infusion | Cohort 2: IMI/REL 15/7.5 mg/kg mg 60-minute Infusion | Cohort 2: IMI/REL 500/250 mg 30-minute Infusion | Cohort 2: IMI/REL 500/250 mg 60-minute Infusion | Cohort 3: IMI/REL 15/7.5 mg/kg 30-minute Infusion | Cohort 3: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Cohort 4: IMI/REL 10/5 mg/kg 60-minute Infusion | Cohort 4: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Cohort 5: IMI/REL 10/5 mg/kg 60-minute Infusion | Cohort 5: IMI/REL 15/7.5 mg/kg 60-minute Infusion |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Adolescents (age 12 to <18 years) administered with a single IV 30-minute infusion dose of IMI/REL at 500/250 mg | Older children (6 to <12 years) administered with a single IV 30-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 | Older children (6 to <12 years) administered with a single IV 30-minute infusion dose of IMI/REL at 500/250 mg | Older children (6 to <12 years) administered with a single IV 60-minute infusion dose of IMI/REL at 500/250 mg | Younger children (2 to <6 years) administered with a single IV 30-minute infusion dose of IMI/REL at 15/7.5 mg/kg | Younger children (2 to <6 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 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 | Toddlers (1 to 2 years) administered with a single IV 60-minute infusion dose of IMI/REL at 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 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 15/7.5 mg/kg |
| Measure Participants | 6 | 1 | 2 | 2 | 1 | 3 | 3 | 4 | 4 | 6 | 9 |
| Geometric Mean (Geometric Coefficient of Variation) [Liters] |
10.27
(16.2)
|
8.00
(NA)
|
4.33
(5.2)
|
9.60
(2.4)
|
8.70
(NA)
|
3.49
(19.6)
|
2.49
(34.6)
|
2.39
(53.2)
|
1.52
(35.0)
|
1.06
(29.6)
|
0.95
(34.2)
|
| Title | IMI Clearance (CL) |
|---|---|
| Description | Systemic clearance (CL) of plasma IMI was calculated. |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All allocated participants who were compliant with the protocol and had at least 1 post-dose PK data point available for IMI CL |
| Arm/Group Title | Cohort 1: IMI/REL 500/250 mg 30-minute Infusion | Cohort 2: IMI/REL 15/7.5 mg/kg 30-minute Infusion | Cohort 2: IMI/REL 15/7.5 mg/kg mg 60-minute Infusion | Cohort 2: IMI/REL 500/250 mg 30-minute Infusion | Cohort 2: IMI/REL 500/250 mg 60-minute Infusion | Cohort 3: IMI/REL 15/7.5 mg/kg 30-minute Infusion | Cohort 3: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Cohort 4: IMI/REL 10/5 mg/kg 60-minute Infusion | Cohort 4: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Cohort 5: IMI/REL 10/5 mg/kg 60-minute Infusion | Cohort 5: IMI/REL 15/7.5 mg/kg 60-minute Infusion |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Adolescents (age 12 to <18 years) administered with a single IV 30-minute infusion dose of IMI/REL at 500/250 mg | Older children (6 to <12 years) administered with a single IV 30-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 | Older children (6 to <12 years) administered with a single IV 30-minute infusion dose of IMI/REL at 500/250 mg | Older children (6 to <12 years) administered with a single IV 60-minute infusion dose of IMI/REL at 500/250 mg | Younger children (2 to <6 years) administered with a single IV 30-minute infusion dose of IMI/REL at 15/7.5 mg/kg | Younger children (2 to <6 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 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 | Toddlers (1 to 2 years) administered with a single IV 60-minute infusion dose of IMI/REL at 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 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 15/7.5 mg/kg |
| Measure Participants | 6 | 1 | 2 | 2 | 1 | 3 | 3 | 4 | 4 | 6 | 9 |
| Geometric Mean (Geometric Coefficient of Variation) [L/hr] |
12.58
(18.4)
|
9.60
(NA)
|
5.25
(9.2)
|
11.67
(27.6)
|
11.74
(NA)
|
5.31
(29.7)
|
4.43
(45.2)
|
3.31
(60.1)
|
1.70
(48.1)
|
1.10
(26.2)
|
0.66
(20.4)
|
| Title | IMI Percentage of Time Above the Minimum Concentration (%TMIC) |
|---|---|
| Description | 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. |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All allocated participants who were compliant with the protocol and had at least 1 post-dose PK data point available for IMI %TMIC |
| Arm/Group Title | Cohort 1: IMI/REL 500/250 mg 30-minute Infusion | Cohort 2: IMI/REL 15/7.5 mg/kg 30-minute Infusion | Cohort 2: IMI/REL 15/7.5 mg/kg mg 60-minute Infusion | Cohort 2: IMI/REL 500/250 mg 30-minute Infusion | Cohort 2: IMI/REL 500/250 mg 60-minute Infusion | Cohort 3: IMI/REL 15/7.5 mg/kg 30-minute Infusion | Cohort 3: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Cohort 4: IMI/REL 10/5 mg/kg 60-minute Infusion | Cohort 4: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Cohort 5: IMI/REL 10/5 mg/kg 60-minute Infusion | Cohort 5: IMI/REL 15/7.5 mg/kg 60-minute Infusion |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Adolescents (age 12 to <18 years) administered with a single IV 30-minute infusion dose of IMI/REL at 500/250 mg | Older children (6 to <12 years) administered with a single IV 30-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 | Older children (6 to <12 years) administered with a single IV 30-minute infusion dose of IMI/REL at 500/250 mg | Older children (6 to <12 years) administered with a single IV 60-minute infusion dose of IMI/REL at 500/250 mg | Younger children (2 to <6 years) administered with a single IV 30-minute infusion dose of IMI/REL at 15/7.5 mg/kg | Younger children (2 to <6 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 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 | Toddlers (1 to 2 years) administered with a single IV 60-minute infusion dose of IMI/REL at 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 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 15/7.5 mg/kg |
| Measure Participants | 6 | 1 | 2 | 2 | 1 | 3 | 3 | 4 | 4 | 6 | 9 |
| Geometric Mean (Geometric Coefficient of Variation) [Percentage of time] |
56.5
(17.1)
|
58.3
(NA)
|
80.3
(26.7)
|
61.6
(25.1)
|
56.7
(NA)
|
50.1
(15.7)
|
57.7
(18.8)
|
50.4
(30.5)
|
73.9
(19.7)
|
70.2
(10.6)
|
93.7
(9.3)
|
| Title | Relebactam (REL) AUC0-∞ |
|---|---|
| Description | 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. |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All allocated participants who were compliant with the protocol and had at least 1 post-dose PK data point available for REL AUC0-∞ |
| Arm/Group Title | Cohort 1: IMI/REL 500/250 mg 30-minute Infusion | Cohort 2: IMI/REL 15/7.5 mg/kg 30-minute Infusion | Cohort 2: IMI/REL 15/7.5 mg/kg mg 60-minute Infusion | Cohort 2: IMI/REL 500/250 mg 30-minute Infusion | Cohort 2: IMI/REL 500/250 mg 60-minute Infusion | Cohort 3: IMI/REL 15/7.5 mg/kg 30-minute Infusion | Cohort 3: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Cohort 4: IMI/REL 10/5 mg/kg 60-minute Infusion | Cohort 4: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Cohort 5: IMI/REL 10/5 mg/kg 60-minute Infusion | Cohort 5: IMI/REL 15/7.5 mg/kg 60-minute Infusion |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Adolescents (age 12 to <18 years) administered with a single IV 30-minute infusion dose of IMI/REL at 500/250 mg | Older children (6 to <12 years) administered with a single IV 30-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 | Older children (6 to <12 years) administered with a single IV 30-minute infusion dose of IMI/REL at 500/250 mg | Older children (6 to <12 years) administered with a single IV 60-minute infusion dose of IMI/REL at 500/250 mg | Younger children (2 to <6 years) administered with a single IV 30-minute infusion dose of IMI/REL at 15/7.5 mg/kg | Younger children (2 to <6 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 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 | Toddlers (1 to 2 years) administered with a single IV 60-minute infusion dose of IMI/REL at 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 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 15/7.5 mg/kg |
| Measure Participants | 6 | 1 | 2 | 2 | 1 | 3 | 3 | 4 | 4 | 6 | 9 |
| Geometric Mean (Geometric Coefficient of Variation) [μM*hr] |
80.1
(20.0)
|
105.6
(NA)
|
123.8
(59.5)
|
90.3
(35.1)
|
80.2
(NA)
|
85.7
(32.4)
|
81.7
(42.0)
|
52.8
(33.6)
|
126.6
(53.7)
|
91.8
(18.3)
|
220.7
(34.1)
|
| Title | REL Maximum Concentration (Cmax) |
|---|---|
| Description | Maximum plasma concentration (Cmax) of REL was calculated. Cmax is the peak plasma concentration of study drug after administration. |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All allocated participants who were compliant with the protocol and had at least 1 post-dose PK data point available for REL Cmax |
| Arm/Group Title | Cohort 1: IMI/REL 500/250 mg 30-minute Infusion | Cohort 2: IMI/REL 15/7.5 mg/kg 30-minute Infusion | Cohort 2: IMI/REL 15/7.5 mg/kg mg 60-minute Infusion | Cohort 2: IMI/REL 500/250 mg 30-minute Infusion | Cohort 2: IMI/REL 500/250 mg 60-minute Infusion | Cohort 3: IMI/REL 15/7.5 mg/kg 30-minute Infusion | Cohort 3: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Cohort 4: IMI/REL 10/5 mg/kg 60-minute Infusion | Cohort 4: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Cohort 5: IMI/REL 10/5 mg/kg 60-minute Infusion | Cohort 5: IMI/REL 15/7.5 mg/kg 60-minute Infusion |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Adolescents (age 12 to <18 years) administered with a single IV 30-minute infusion dose of IMI/REL at 500/250 mg | Older children (6 to <12 years) administered with a single IV 30-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 | Older children (6 to <12 years) administered with a single IV 30-minute infusion dose of IMI/REL at 500/250 mg | Older children (6 to <12 years) administered with a single IV 60-minute infusion dose of IMI/REL at 500/250 mg | Younger children (2 to <6 years) administered with a single IV 30-minute infusion dose of IMI/REL at 15/7.5 mg/kg | Younger children (2 to <6 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 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 | Toddlers (1 to 2 years) administered with a single IV 60-minute infusion dose of IMI/REL at 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 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 15/7.5 mg/kg |
| Measure Participants | 6 | 1 | 2 | 2 | 1 | 3 | 3 | 4 | 4 | 6 | 9 |
| Geometric Mean (Geometric Coefficient of Variation) [μM] |
49.33
(23.0)
|
86.52
(NA)
|
60.32
(30.7)
|
57.44
(26.1)
|
48.73
(NA)
|
59.05
(9.08)
|
48.59
(22.9)
|
32.74
(15.0)
|
59.55
(17.1)
|
34.22
(17.3)
|
61.04
(21.9)
|
| Title | REL Clearance (CL) |
|---|---|
| Description | Systemic clearance (CL) of plasma REL was calculated. |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All allocated participants who were compliant with the protocol and had at least 1 post-dose PK data point available for REL CL |
| Arm/Group Title | Cohort 1: IMI/REL 500/250 mg 30-minute Infusion | Cohort 2: IMI/REL 15/7.5 mg/kg 30-minute Infusion | Cohort 2: IMI/REL 15/7.5 mg/kg mg 60-minute Infusion | Cohort 2: IMI/REL 500/250 mg 30-minute Infusion | Cohort 2: IMI/REL 500/250 mg 60-minute Infusion | Cohort 3: IMI/REL 15/7.5 mg/kg 30-minute Infusion | Cohort 3: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Cohort 4: IMI/REL 10/5 mg/kg 60-minute Infusion | Cohort 4: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Cohort 5: IMI/REL 10/5 mg/kg 60-minute Infusion | Cohort 5: IMI/REL 15/7.5 mg/kg 60-minute Infusion |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Adolescents (age 12 to <18 years) administered with a single IV 30-minute infusion dose of IMI/REL at 500/250 mg | Older children (6 to <12 years) administered with a single IV 30-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 | Older children (6 to <12 years) administered with a single IV 30-minute infusion dose of IMI/REL at 500/250 mg | Older children (6 to <12 years) administered with a single IV 60-minute infusion dose of IMI/REL at 500/250 mg | Younger children (2 to <6 years) administered with a single IV 30-minute infusion dose of IMI/REL at 15/7.5 mg/kg | Younger children (2 to <6 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 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 | Toddlers (1 to 2 years) administered with a single IV 60-minute infusion dose of IMI/REL at 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 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 15/7.5 mg/kg |
| Measure Participants | 6 | 1 | 2 | 2 | 1 | 3 | 3 | 4 | 4 | 6 | 9 |
| Geometric Mean (Geometric Coefficient of Variation) [L/hr] |
8.98
(20.7)
|
6.10
(NA)
|
3.96
(28.9)
|
8.03
(35.7)
|
8.65
(NA)
|
4.20
(40.8)
|
3.65
(54.1)
|
2.56
(54.5)
|
1.27
(62.9)
|
0.74
(27.0)
|
0.35
(30.7)
|
| Title | REL Central Volume of Distribution (Vc) |
|---|---|
| Description | Central volume of distribution (Vc) of plasma REL was calculated. |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All allocated participants who were compliant with the protocol and had at least 1 post-dose PK data point available for REL Vc |
| Arm/Group Title | Cohort 1: IMI/REL 500/250 mg 30-minute Infusion | Cohort 2: IMI/REL 15/7.5 mg/kg 30-minute Infusion | Cohort 2: IMI/REL 15/7.5 mg/kg mg 60-minute Infusion | Cohort 2: IMI/REL 500/250 mg 30-minute Infusion | Cohort 2: IMI/REL 500/250 mg 60-minute Infusion | Cohort 3: IMI/REL 15/7.5 mg/kg 30-minute Infusion | Cohort 3: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Cohort 4: IMI/REL 10/5 mg/kg 60-minute Infusion | Cohort 4: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Cohort 5: IMI/REL 10/5 mg/kg 60-minute Infusion | Cohort 5: IMI/REL 15/7.5 mg/kg 60-minute Infusion |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Adolescents (age 12 to <18 years) administered with a single IV 30-minute infusion dose of IMI/REL at 500/250 mg | Older children (6 to <12 years) administered with a single IV 30-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 | Older children (6 to <12 years) administered with a single IV 30-minute infusion dose of IMI/REL at 500/250 mg | Older children (6 to <12 years) administered with a single IV 60-minute infusion dose of IMI/REL at 500/250 mg | Younger children (2 to <6 years) administered with a single IV 30-minute infusion dose of IMI/REL at 15/7.5 mg/kg | Younger children (2 to <6 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 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 | Toddlers (1 to 2 years) administered with a single IV 60-minute infusion dose of IMI/REL at 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 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 15/7.5 mg/kg |
| Measure Participants | 6 | 1 | 2 | 2 | 1 | 3 | 3 | 4 | 4 | 6 | 9 |
| Geometric Mean (Geometric Coefficient of Variation) [Liters] |
10.58
(17.2)
|
6.76
(NA)
|
4.95
(1.6)
|
9.81
(6.1)
|
9.38
(NA)
|
3.83
(13.8)
|
2.88
(27.4)
|
2.43
(38.8)
|
1.70
(21.1)
|
1.21
(24.6)
|
0.90
(36.7)
|
| Title | Cilastatin (CIL) AUC0-∞ |
|---|---|
| Description | 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. |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Due to sparse PK sampling schedule, per participant data could not be calculated. |
| Arm/Group Title | Cohort 1: IMI/REL 500-250 mg 30-minute Infusion | Cohort 2: IMI/REL 15/7.5 mg/kg 30-minute Infusion | Cohort 2: IMI/REL 15/7.5 mg/kg mg 60-minute Infusion | Cohort 2: IMI/REL 500/250 mg 30-minute Infusion | Cohort 2: IMI/REL 500/250 mg 60-minute Infusion | Cohort 3: IMI/REL 15/7.5 mg/kg 30-minute Infusion | Cohort 3: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Cohort 4: IMI/REL 10/5 mg/kg | Cohort 4: IMI/REL 15/7.5 mg/kg | Cohort 5: IMI/REL 10/5 mg/kg | Cohort 5: IMI/REL 15/7.5 mg/kg |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Cohort 1: IMI/REL 500/250 mg 30-minute infusion Adolescents (age 12 to <18 years) administered with a single IV 30-minute infusion dose of IMI/REL at 500/250 mg | Older children (6 to <12 years) administered with a single IV 30-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 | Older children (6 to <12 years) administered with a single IV 30-minute infusion dose of IMI/REL at 500/250 mg | Older children (6 to <12 years) administered with a single IV 60-minute infusion dose of IMI/REL at 500/250 mg | Younger children (2 to <6 years) administered with a single IV 30-minute infusion dose of IMI/REL at 15/7.5 mg/kg | Younger children (2 to <6 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 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 | Toddlers (1 to 2 years) administered with a single IV 60-minute infusion dose of IMI/REL at 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 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 15/7.5 mg/kg |
| Measure Participants | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Title | CIL Time to Maximum Concentration (Tmax) |
|---|---|
| Description | 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. |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All allocated participants who were compliant with the protocol and had at least 1 post-dose PK data point available for CIL Tmax |
| Arm/Group Title | Cohort 1: IMI/REL 500/250 mg 30-minute Infusion | Cohort 2: IMI/REL 15/7.5 mg/kg 30-minute Infusion | Cohort 2: IMI/REL 15/7.5 mg/kg mg 60-minute Infusion | Cohort 2: IMI/REL 500/250 mg 30-minute Infusion | Cohort 2: IMI/REL 500/250 mg 60-minute Infusion | Cohort 3: IMI/REL 15/7.5 mg/kg 30-minute Infusion | Cohort 3: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Cohort 4: IMI/REL 10/5 mg/kg | Cohort 4: IMI/REL 15/7.5 mg/kg | Cohort 5: IMI/REL 10/5 mg/kg | Cohort 5: IMI/REL 15/7.5 mg/kg |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Adolescents (age 12 to <18 years) administered with a single IV 30-minute infusion dose of IMI/REL at 500/250 mg | Older children (6 to <12 years) administered with a single IV 30-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 | Older children (6 to <12 years) administered with a single IV 30-minute infusion dose of IMI/REL at 500/250 mg | Older children (6 to <12 years) administered with a single IV 60-minute infusion dose of IMI/REL at 500/250 mg | Younger children (2 to <6 years) administered with a single IV 30-minute infusion dose of IMI/REL at 15/7.5 mg/kg | Younger children (2 to <6 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 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 | Toddlers (1 to 2 years) administered with a single IV 60-minute infusion dose of IMI/REL at 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 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 15/7.5 mg/kg |
| Measure Participants | 6 | 1 | 2 | 2 | 1 | 3 | 3 | 4 | 4 | 7 | 9 |
| Median (Full Range) [Hours] |
0.58
|
0.53
|
1.1
|
0.58
|
1.1
|
0.58
|
1.1
|
1.1
|
1.2
|
1.1
|
1.2
|
| Title | CIL Concentration at End of Infusion (Ceoi) |
|---|---|
| Description | Concentration at end of infusion (Ceoi) of plasma CIL was determined. |
| Time Frame | 30 min after the start of infusion for Cohort 1; 60 min after the start of infusion for Cohorts 2-5 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All allocated participants who were compliant with the protocol and had at least 1 post-dose PK data point available for CIL Ceoi |
| Arm/Group Title | Cohort 1: IMI/REL 500/250 mg 30-minute Infusion | Cohort 2: IMI/REL 15/7.5 mg/kg 30-minute Infusion | Cohort 2: IMI/REL 15/7.5 mg/kg mg 60-minute Infusion | Cohort 2: IMI/REL 500/250 mg 30-minute Infusion | Cohort 2: IMI/REL 500/250 mg 60-minute Infusion | Cohort 3: IMI/REL 15/7.5 mg/kg 30-minute Infusion | Cohort 3: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Cohort 4: IMI/REL 10/5 mg/kg | Cohort 4: IMI/REL 15/7.5 mg/kg | Cohort 5: IMI/REL 10/5 mg/kg | Cohort 5: IMI/REL 15/7.5 mg/kg |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Adolescents (age 12 to <18 years) administered with a single IV 30-minute infusion dose of IMI/REL at 500/250 mg | Older children (6 to <12 years) administered with a single IV 30-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 | Older children (6 to <12 years) administered with a single IV 30-minute infusion dose of IMI/REL at 500/250 mg | Older children (6 to <12 years) administered with a single IV 60-minute infusion dose of IMI/REL at 500/250 mg | Younger children (2 to <6 years) administered with a single IV 30-minute infusion dose of IMI/REL at 15/7.5 mg/kg | Younger children (2 to <6 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 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 | Toddlers (1 to 2 years) administered with a single IV 60-minute infusion dose of IMI/REL at 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 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 15/7.5 mg/kg |
| Measure Participants | 6 | 1 | 2 | 2 | 1 | 3 | 3 | 3 | 4 | 7 | 9 |
| Geometric Mean (Geometric Coefficient of Variation) [μM] |
86.9
(41.0)
|
122
(NA)
|
111
(51)
|
80.5
(22)
|
74.8
(NA)
|
102
(32)
|
80.9
(62)
|
37.0
(64.0)
|
94.5
(42.0)
|
63.6
(28.0)
|
107.0
(20.0)
|
| Title | CIL Terminal Half-Life (t1/2) |
|---|---|
| Description | Terminal half-life (t1/2) of plasma CIL was not calculated. |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Due to sparse PK sampling schedule, per participant data could not be calculated. |
| Arm/Group Title | Cohort 1: IMI/REL 500/250 mg 30-minute Infusion | Cohort 2: IMI/REL 15/7.5 mg/kg 30-minute Infusion | Cohort 2: IMI/REL 15/7.5 mg/kg mg 60-minute Infusion | Cohort 2: IMI/REL 500/250 mg 30-minute Infusion | Cohort 2: IMI/REL 500/250 mg 60-minute Infusion | Cohort 3: IMI/REL 15/7.5 mg/kg 30-minute Infusion | Cohort 3: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Cohort 4: IMI/REL 10/5 mg/kg | Cohort 4: IMI/REL 15/7.5 mg/kg | Cohort 5: IMI/REL 10/5 mg/kg | Cohort 5: IMI/REL 15/7.5 mg/kg |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Adolescents (age 12 to <18 years) administered with a single IV 30-minute infusion dose of IMI/REL at 500/250 mg | Older children (6 to <12 years) administered with a single IV 30-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 | Older children (6 to <12 years) administered with a single IV 30-minute infusion dose of IMI/REL at 500/250 mg | Older children (6 to <12 years) administered with a single IV 60-minute infusion dose of IMI/REL at 500/250 mg | Younger children (2 to <6 years) administered with a single IV 30-minute infusion dose of IMI/REL at 15/7.5 mg/kg | Younger children (2 to <6 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 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 | Toddlers (1 to 2 years) administered with a single IV 60-minute infusion dose of IMI/REL at 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 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 15/7.5 mg/kg |
| Measure Participants | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Title | CIL Clearance (CL) |
|---|---|
| Description | Systemic clearance (CL) of plasma CIL was not calculated. |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Due to sparse PK sampling schedule, per participant data could not be calculated. |
| Arm/Group Title | Cohort 1: IMI/REL 500/250 mg 30-minute Infusion | Cohort 2: IMI/REL 15/7.5 mg/kg 30-minute Infusion | Cohort 2: IMI/REL 15/7.5 mg/kg mg 60-minute Infusion | Cohort 2: IMI/REL 500/250 mg 30-minute Infusion | Cohort 2: IMI/REL 500/250 mg 60-minute Infusion | Cohort 3: IMI/REL 15/7.5 mg/kg 30-minute Infusion | Cohort 3: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Cohort 4: IMI/REL 10/5 mg/kg | Cohort 4: IMI/REL 15/7.5 mg/kg | Cohort 5: IMI/REL 10/5 mg/kg | Cohort 5: IMI/REL 15/7.5 mg/kg |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Adolescents (age 12 to <18 years) administered with a single IV 30-minute infusion dose of IMI/REL at 500/250 mg | Older children (6 to <12 years) administered with a single IV 30-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 | Older children (6 to <12 years) administered with a single IV 30-minute infusion dose of IMI/REL at 500/250 mg | Older children (6 to <12 years) administered with a single IV 60-minute infusion dose of IMI/REL at 500/250 mg | Younger children (2 to <6 years) administered with a single IV 30-minute infusion dose of IMI/REL at 15/7.5 mg/kg | Younger children (2 to <6 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 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 | Toddlers (1 to 2 years) administered with a single IV 60-minute infusion dose of IMI/REL at 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 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 15/7.5 mg/kg |
| Measure Participants | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Title | CIL Volume of Distribution (Vss) |
|---|---|
| Description | Volume of distribution (Vss) of plasma CIL was not calculated. |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Due to sparse PK sampling schedule, per participant data could not be calculated. |
| Arm/Group Title | Cohort 1: IMI/REL 500/250 mg 30-minute Infusion | Cohort 2: IMI/REL 15/7.5 mg/kg 30-minute Infusion | Cohort 2: IMI/REL 15/7.5 mg/kg mg 60-minute Infusion | Cohort 2: IMI/REL 500/250 mg 30-minute Infusion | Cohort 2: IMI/REL 500/250 mg 60-minute Infusion | Cohort 3: IMI/REL 15/7.5 mg/kg 30-minute Infusion | Cohort 3: IMI/REL 15/7.5 mg/kg 60-minute Infusion | Cohort 4: IMI/REL 10/5 mg/kg | Cohort 4: IMI/REL 15/7.5 mg/kg | Cohort 5: IMI/REL 10/5 mg/kg | Cohort 5: IMI/REL 15/7.5 mg/kg |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Adolescents (age 12 to <18 years) administered with a single IV 30-minute infusion dose of IMI/REL at 500/250 mg | Older children (6 to <12 years) administered with a single IV 30-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 | Older children (6 to <12 years) administered with a single IV 30-minute infusion dose of IMI/REL at 500/250 mg | Older children (6 to <12 years) administered with a single IV 60-minute infusion dose of IMI/REL at 500/250 mg | Younger children (2 to <6 years) administered with a single IV 30-minute infusion dose of IMI/REL at 15/7.5 mg/kg | Younger children (2 to <6 years) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 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 | Toddlers (1 to 2 years) administered with a single IV 60-minute infusion dose of IMI/REL at 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 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 15/7.5 mg/kg |
| Measure Participants | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Title | Number of Participants Who Experienced an Adverse Event (AE) |
|---|---|
| Description | 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. |
| Time Frame | Up to 17 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| All allocated participants who received infusion (including partial doses) of study drug |
| Arm/Group Title | Cohort 1: IMI/REL 15/7.5 mg/kg | Cohort 2: IMI/REL 15/7.5 mg/kg | Cohort 3: IMI/REL 15/7.5 mg/kg | Cohort 4: IMI/REL 10/5 mg/kg | Cohort 4: IMI/REL 15/7.5 mg/kg | Cohort 5: Subcohort 1: IMI/REL 10/5 mg/kg | Cohort 5: Subcohort 2: IMI/REL 10/5 mg/kg | Cohort 5: Subcohort 3: IMI/REL 10/5 mg/kg | Cohort 5: Subcohort 1: IMI/REL 15/7.5 mg/kg | Cohort 5: Subcohort 2: IMI/REL 15/7.5 mg/kg | Cohort 5: Subcohort 3: IMI/REL 15/7.5 mg/kg |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | 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 | 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 maximum dose of 500/250 mg | 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 | Infants (3 months to <1 year) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 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 | 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 | 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 | Younger neonates (<1 week of age) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 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 | 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 | Younger neonates (<1 week of age) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| Measure Participants | 7 | 6 | 6 | 4 | 4 | 5 | 3 | 2 | 2 | 3 | 4 |
| Count of Participants [Participants] |
1
14.3%
|
0
0%
|
3
50%
|
1
25%
|
2
50%
|
1
16.7%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants Who Discontinued Study Drug Due to an AE |
|---|---|
| Description | 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. |
| Time Frame | Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All allocated participants who received infusion (including partial doses) of study drug |
| Arm/Group Title | Cohort 1: IMI/REL 15/7.5 mg/kg | Cohort 2: IMI/REL 15/7.5 mg/kg | Cohort 3: IMI/REL 15/7.5 mg/kg | Cohort 4: IMI/REL 10/5 mg/kg | Cohort 4: IMI/REL 15/7.5 mg/kg | Cohort 5: Subcohort 1: IMI/REL 10/5 mg/kg | Cohort 5: Subcohort 2: IMI/REL 10/5 mg/kg | Cohort 5: Subcohort 3: IMI/REL 10/5 mg/kg | Cohort 5: Subcohort 1: IMI/REL 15/7.5 mg/kg | Cohort 5: Subcohort 2: IMI/REL 15/7.5 mg/kg | Cohort 5: Subcohort 3: IMI/REL 15/7.5 mg/kg |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | 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 | 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 maximum dose of 500/250 mg | 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 | Infants (3 months to <1 year) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 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 | 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 | 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 | Younger neonates (<1 week of age) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 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 | 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 | Younger neonates (<1 week of age) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg |
| Measure Participants | 7 | 6 | 6 | 4 | 4 | 5 | 3 | 2 | 2 | 3 | 4 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Adverse Events
| Time Frame | Up to 17 days (AE reporting), up to 19 days (all-cause mortality) | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | 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. | |||||||||||||||||||||
| Arm/Group Title | Cohort 1: IMI/REL 15/7.5 mg/kg | Cohort 2: IMI/REL 15/7.5 mg/kg | Cohort 3: IMI/REL 15/7.5 mg/kg | Cohort 4: IMI/REL 10/5 mg/kg | Cohort 4: IMI/REL 15/7.5 mg/kg | Cohort 5: Subcohort 1: IMI/REL 10/5 mg/kg | Cohort 5: Subcohort 2: IMI/REL 10/5 mg/kg | Cohort 5: Subcohort 3: IMI/REL 10/5 mg/kg | Cohort 5: Subcohort 1: IMI/REL 15/7.5 mg/kg | Cohort 5: Subcohort 2: IMI/REL 15/7.5 mg/kg | Cohort 5: Subcohort 3: IMI/REL 15/7.5 mg/kg | |||||||||||
| Arm/Group Description | 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 | 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 | 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 | Infants (3 months to <1 year) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 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 | 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 | 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 | Younger neonates (<1 week of age) administered with a single IV 60-minute infusion dose of IMI/REL at 10/5 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 | 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 | Younger neonates (<1 week of age) administered with a single IV 60-minute infusion dose of IMI/REL at 15/7.5 mg/kg | |||||||||||
All Cause Mortality |
||||||||||||||||||||||
| Cohort 1: IMI/REL 15/7.5 mg/kg | Cohort 2: IMI/REL 15/7.5 mg/kg | Cohort 3: IMI/REL 15/7.5 mg/kg | Cohort 4: IMI/REL 10/5 mg/kg | Cohort 4: IMI/REL 15/7.5 mg/kg | Cohort 5: Subcohort 1: IMI/REL 10/5 mg/kg | Cohort 5: Subcohort 2: IMI/REL 10/5 mg/kg | Cohort 5: Subcohort 3: IMI/REL 10/5 mg/kg | Cohort 5: Subcohort 1: IMI/REL 15/7.5 mg/kg | Cohort 5: Subcohort 2: IMI/REL 15/7.5 mg/kg | Cohort 5: Subcohort 3: IMI/REL 15/7.5 mg/kg | ||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/7 (0%) | 0/6 (0%) | 0/6 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 0/3 (0%) | 0/2 (0%) | 0/2 (0%) | 0/3 (0%) | 0/4 (0%) | |||||||||||
Serious Adverse Events |
||||||||||||||||||||||
| Cohort 1: IMI/REL 15/7.5 mg/kg | Cohort 2: IMI/REL 15/7.5 mg/kg | Cohort 3: IMI/REL 15/7.5 mg/kg | Cohort 4: IMI/REL 10/5 mg/kg | Cohort 4: IMI/REL 15/7.5 mg/kg | Cohort 5: Subcohort 1: IMI/REL 10/5 mg/kg | Cohort 5: Subcohort 2: IMI/REL 10/5 mg/kg | Cohort 5: Subcohort 3: IMI/REL 10/5 mg/kg | Cohort 5: Subcohort 1: IMI/REL 15/7.5 mg/kg | Cohort 5: Subcohort 2: IMI/REL 15/7.5 mg/kg | Cohort 5: Subcohort 3: IMI/REL 15/7.5 mg/kg | ||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/7 (0%) | 0/6 (0%) | 0/6 (0%) | 0/4 (0%) | 0/4 (0%) | 0/5 (0%) | 0/3 (0%) | 0/2 (0%) | 0/2 (0%) | 0/3 (0%) | 0/4 (0%) | |||||||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||||||||||
| Cohort 1: IMI/REL 15/7.5 mg/kg | Cohort 2: IMI/REL 15/7.5 mg/kg | Cohort 3: IMI/REL 15/7.5 mg/kg | Cohort 4: IMI/REL 10/5 mg/kg | Cohort 4: IMI/REL 15/7.5 mg/kg | Cohort 5: Subcohort 1: IMI/REL 10/5 mg/kg | Cohort 5: Subcohort 2: IMI/REL 10/5 mg/kg | Cohort 5: Subcohort 3: IMI/REL 10/5 mg/kg | Cohort 5: Subcohort 1: IMI/REL 15/7.5 mg/kg | Cohort 5: Subcohort 2: IMI/REL 15/7.5 mg/kg | Cohort 5: Subcohort 3: IMI/REL 15/7.5 mg/kg | ||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/7 (14.3%) | 0/6 (0%) | 3/6 (50%) | 1/4 (25%) | 2/4 (50%) | 1/5 (20%) | 0/3 (0%) | 0/2 (0%) | 0/2 (0%) | 0/3 (0%) | 0/4 (0%) | |||||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||||||
| Anaemia | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 2/6 (33.3%) | 2 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/2 (0%) | 0 | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 |
| Thrombocytoses | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/2 (0%) | 0 | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||||||||||||
| Diarrhoea | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 1/6 (16.7%) | 1 | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/2 (0%) | 0 | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 |
| Infections and infestations | ||||||||||||||||||||||
| Nasopharyngitis | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/2 (0%) | 0 | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 |
| Investigations | ||||||||||||||||||||||
| Aspartate aminotransferase increased | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/2 (0%) | 0 | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 |
| Alanine aminotransferase increased | 1/7 (14.3%) | 1 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/2 (0%) | 0 | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 |
| Neutrophil count decreased | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/2 (0%) | 0 | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||||||||||||||
| Miliaria | 0/7 (0%) | 0 | 0/6 (0%) | 0 | 0/6 (0%) | 0 | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/2 (0%) | 0 | 0/2 (0%) | 0 | 0/3 (0%) | 0 | 0/4 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
| Name/Title | Clinical Trials Disclosure |
|---|---|
| Organization | Merck Sharp & Dohme Corp. |
| Phone | 1-800-672-6372 |
| ClinicalTrialsDisclosure@merck.com |
Responsible Party:
Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier:
NCT03230916
Other Study ID Numbers:
- 7655A-020
- 2016-004328-43
- MK-7665A-020
First Posted:
Jul 27, 2017
Last Update Posted:
Dec 13, 2021
Last Verified:
Oct 1, 2021