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Efficacy and Safety of Imipenem+Cilastatin/Relebactam (MK-7655A) Versus Colistimethate Sodium+Imipenem+Cilastatin in Imipenem-Resistant Bacterial Infection (MK-7655A-013) (RESTORE-IMI 1)

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ClinicalTrials.gov Identifier: NCT02452047
Recruitment Status : Completed
First Posted : May 22, 2015
Results First Posted : October 19, 2018
Last Update Posted : October 19, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Bacterial Infections
Interventions Drug: Imipenem+Cilastatin/Relebactam
Drug: Colistimethate sodium (CMS)
Drug: Imipenem+Cilastatin
Drug: Placebo to CMS
Enrollment 50
Recruitment Details Adult participants with hospital-acquired bacterial pneumonia (HABP), ventilator-associated bacterial pneumonia (VABP), complicated intra-abdominal infection (cIAI), or complicated urinary tract infection (cUTI) were recruited at 35 study centers in 17 countries.
Pre-assignment Details  
Arm/Group Title Group 1: Imipenem+Cilastatin/Relebactam Group 2: Colistimethate Sodium + Imipenem+Cilastatin Group 3: Open-Label Imipenem+Cilastatin/Relebactam
Hide Arm/Group Description Participants with HABP, VABP, cIAI, or cUTI caused by imipenem-nonsusceptible but imipenem/relebactam- and colistin-susceptible pathogens were randomized to receive imipenem+cilastatin/relebactam IV infusion once every 6 hours and placebo for colistimethate sodium IV infusion once every 12 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP). Participants with HABP, VABP, cIAI, or cUTI caused by imipenem-nonsusceptible but imipenem/relebactam- and colistin-susceptible pathogens were randomized to receive colistimethate sodium IV infusion once every 12 hours and imipenem+cilastatin IV infusion once every 6 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP). Participants with HABP, VABP, cIAI, or cUTI caused by imipenem- and colistin-nonsusceptible pathogens received open-label imipenem+cilastatin/relebactam IV infusion once every 6 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Period Title: Overall Study
Started 31 16 3
Completed 27 11 1
Not Completed 4 5 2
Reason Not Completed
Adverse Event             0             1             1
Death             1             3             1
Physician Decision             1             0             0
Lost to Follow-up             1             1             0
Withdrawal by Subject             1             0             0
Arm/Group Title Group 1: Imipenem+Cilastatin/Relebactam Group 2: Colistimethate Sodium + Imipenem+Cilastatin Group 3: Open-Label Imipenem+Cilastatin/Relebactam Total
Hide Arm/Group Description Participants with HABP, VABP, cIAI, or cUTI caused by imipenem-nonsusceptible but imipenem/relebactam- and colistin-susceptible pathogens were randomized to receive imipenem+cilastatin/relebactam IV infusion once every 6 hours and placebo for colistimethate sodium IV infusion once every 12 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP). Participants with HABP, VABP, cIAI, or cUTI caused by imipenem-nonsusceptible but imipenem/relebactam- and colistin-susceptible pathogens were randomized to receive colistimethate sodium IV infusion once every 12 hours and imipenem+cilastatin IV infusion once every 6 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP). Participants with HABP, VABP, cIAI, or cUTI caused by imipenem- and colistin-nonsusceptible pathogens received open-label imipenem+cilastatin/relebactam IV infusion once every 6 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP). Total of all reporting groups
Overall Number of Baseline Participants 31 16 3 50
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 31 participants 16 participants 3 participants 50 participants
56.1  (16.5) 62.8  (14.9) 50.0  (23.1) 57.9  (16.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 31 participants 16 participants 3 participants 50 participants
Female
11
  35.5%
6
  37.5%
2
  66.7%
19
  38.0%
Male
20
  64.5%
10
  62.5%
1
  33.3%
31
  62.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 31 participants 16 participants 3 participants 50 participants
American Indian or Alaska Native
1
   3.2%
0
   0.0%
0
   0.0%
1
   2.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
1
   6.3%
0
   0.0%
1
   2.0%
White
26
  83.9%
15
  93.8%
3
 100.0%
44
  88.0%
More than one race
4
  12.9%
0
   0.0%
0
   0.0%
4
   8.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Percentage of Participants With Favorable Overall Response (FOR)
Hide Description The percentage of participants with FOR was determined for Groups 1 and 2. FOR was determined based on clinically relevant outcomes for the primary site of infection as follows: HABP/VABP: survival through Day 28; cIAI: favorable clinical response (all pretherapy symptoms of index infection resolved with no evidence of resurgence, no additional antibiotic therapy required, and no unplanned surgical or percutaneous drainage procedures) at Day 28; cUTI: favorable composite clinical response (all pretherapy symptoms of index infection resolved with no evidence of resurgence, no additional antibiotic therapy required) and microbiological response (urine culture shows sustained eradication of the baseline uropathogen [e.g., ≥10^5 CFU/mL at study entry is reduced to <10^4 CFU/mL]) at Early Follow-up (EFU).
Time Frame Up to Day 30 (up to 9 days after completing study treatment)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Groups 1 and 2 who received ≥1 dose of each trial drug within a given IV treatment regimen, and who had a baseline bacterial pathogen that met inclusion criteria, are included. As per protocol, efficacy data from open-label Group 3 was considered exploratory and not included in the comparative analysis.
Arm/Group Title Group 1: Imipenem+Cilastatin/Relebactam Group 2: Colistimethate Sodium + Imipenem+Cilastatin Group 3: Open-Label Imipenem+Cilastatin/Relebactam
Hide Arm/Group Description:
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem-nonsusceptible but imipenem/relebactam- and colistin-susceptible pathogens were randomized to receive imipenem+cilastatin/relebactam IV infusion once every 6 hours and placebo for colistimethate sodium IV infusion once every 12 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem-nonsusceptible but imipenem/relebactam- and colistin-susceptible pathogens were randomized to receive colistimethate sodium IV infusion once every 12 hours and imipenem+cilastatin IV infusion once every 6 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem- and colistin-nonsusceptible pathogens received open-label imipenem+cilastatin/relebactam IV infusion once every 6 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Overall Number of Participants Analyzed 21 10 0
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
71.4
(49.8 to 86.4)
70.0
(39.2 to 89.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1: Imipenem+Cilastatin/Relebactam, Group 2: Colistimethate Sodium + Imipenem+Cilastatin
Comments [Not Specified]
Type of Statistical Test Other
Comments Difference in percentages
Method of Estimation Estimation Parameter Difference in FOR %
Estimated Value -7.3
Confidence Interval (2-Sided) 90%
-27.5 to 21.4
Estimation Comments Stratified Miettinen & Nurminen method by infection type
2.Primary Outcome
Title Percentage of Participants With ≥1 Adverse Events (AEs)
Hide Description The percentage of participants in Groups 1, 2, and 3 experiencing ≥1 AEs during treatment and 14-day follow-up was determined. An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Statistical analysis included only Groups 1 and 2 as indicated by the protocol.
Time Frame Up to Day 35 (up to 14 days after completing study treatment)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in Groups 1, 2, and 3 who received ≥1 dose of study drug are included.
Arm/Group Title Group 1: Imipenem+Cilastatin/Relebactam Group 2: Colistimethate Sodium + Imipenem+Cilastatin Group 3: Open-Label Imipenem+Cilastatin/Relebactam
Hide Arm/Group Description:
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem-nonsusceptible but imipenem/relebactam- and colistin-susceptible pathogens were randomized to receive imipenem+cilastatin/relebactam IV infusion once every 6 hours and placebo for colistimethate sodium IV infusion once every 12 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem-nonsusceptible but imipenem/relebactam- and colistin-susceptible pathogens were randomized to receive colistimethate sodium IV infusion once every 12 hours and imipenem+cilastatin IV infusion once every 6 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem- and colistin-nonsusceptible pathogens received open-label imipenem+cilastatin/relebactam IV infusion once every 6 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Overall Number of Participants Analyzed 31 16 3
Measure Type: Number
Unit of Measure: Percentage of Participants
71.0 81.3 100.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1: Imipenem+Cilastatin/Relebactam, Group 2: Colistimethate Sodium + Imipenem+Cilastatin
Comments [Not Specified]
Type of Statistical Test Other
Comments Difference in percentages
Method of Estimation Estimation Parameter Difference in AE %
Estimated Value -10.3
Confidence Interval (2-Sided) 95%
-33.1 to 18.0
Estimation Comments Miettinen & Nurminen method
3.Primary Outcome
Title Percentage of Participants With ≥1 Serious Adverse Events (SAEs)
Hide Description The percentage of participants in Groups 1, 2, and 3 experiencing ≥1 SAEs during treatment and 14-day follow-up was determined. An SAE is any untoward medical occurrence that, at any dose, results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant injury/incapacity; is a congenital anomaly/birth defect; or is an other important medical event. Statistical analysis included only Groups 1 and 2 as indicated by the protocol.
Time Frame Up to Day 35 (up to 14 days after completing study treatment)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in Groups 1, 2, and 3 who received ≥1 dose of study drug are included.
Arm/Group Title Group 1: Imipenem+Cilastatin/Relebactam Group 2: Colistimethate Sodium + Imipenem+Cilastatin Group 3: Open-Label Imipenem+Cilastatin/Relebactam
Hide Arm/Group Description:
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem-nonsusceptible but imipenem/relebactam- and colistin-susceptible pathogens were randomized to receive imipenem+cilastatin/relebactam IV infusion once every 6 hours and placebo for colistimethate sodium IV infusion once every 12 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem-nonsusceptible but imipenem/relebactam- and colistin-susceptible pathogens were randomized to receive colistimethate sodium IV infusion once every 12 hours and imipenem+cilastatin IV infusion once every 6 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem- and colistin-nonsusceptible pathogens received open-label imipenem+cilastatin/relebactam IV infusion once every 6 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Overall Number of Participants Analyzed 31 16 3
Measure Type: Number
Unit of Measure: Percentage of Participants
9.7 31.3 100.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1: Imipenem+Cilastatin/Relebactam, Group 2: Colistimethate Sodium + Imipenem+Cilastatin
Comments [Not Specified]
Type of Statistical Test Other
Comments Difference in percentages
Method of Estimation Estimation Parameter Difference in SAE %
Estimated Value -21.6
Confidence Interval (2-Sided) 95%
-47.8 to 1.3
Estimation Comments Miettinen & Nurminen method
4.Primary Outcome
Title Percentage of Participants With ≥1 Drug-Related AEs
Hide Description The percentage of participants in Groups 1, 2, and 3 experiencing ≥1 drug-related AEs during treatment and 14-day follow-up was determined. A drug-related AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, and considered by the investigator to be related to the study intervention. Statistical analysis included only Groups 1 and 2 as indicated by the protocol.
Time Frame Up to Day 35 (up to 14 days after completing study treatment)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in Groups 1, 2, and 3 who received ≥1 dose of study drug are included.
Arm/Group Title Group 1: Imipenem+Cilastatin/Relebactam Group 2: Colistimethate Sodium + Imipenem+Cilastatin Group 3: Open-Label Imipenem+Cilastatin/Relebactam
Hide Arm/Group Description:
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem-nonsusceptible but imipenem/relebactam- and colistin-susceptible pathogens were randomized to receive imipenem+cilastatin/relebactam IV infusion once every 6 hours and placebo for colistimethate sodium IV infusion once every 12 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem-nonsusceptible but imipenem/relebactam- and colistin-susceptible pathogens were randomized to receive colistimethate sodium IV infusion once every 12 hours and imipenem+cilastatin IV infusion once every 6 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem- and colistin-nonsusceptible pathogens received open-label imipenem+cilastatin/relebactam IV infusion once every 6 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Overall Number of Participants Analyzed 31 16 3
Measure Type: Number
Unit of Measure: Percentage of Participants
16.1 31.3 33.3
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1: Imipenem+Cilastatin/Relebactam, Group 2: Colistimethate Sodium + Imipenem+Cilastatin
Comments [Not Specified]
Type of Statistical Test Other
Comments Difference in percentages
Method of Estimation Estimation Parameter Difference in drug-related AE %
Estimated Value -15.1
Confidence Interval (2-Sided) 95%
-42.3 to 9.2
Estimation Comments Miettinen & Nurminen method
5.Primary Outcome
Title Percentage of Participants With ≥1 Drug-Related SAEs
Hide Description The percentage of participants in Groups 1, 2, and 3 experiencing ≥1 drug-related SAEs during treatment and 14-day follow-up was determined. A drug-related SAE is any untoward medical occurrence that, at any dose, results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant injury/incapacity; is a congenital anomaly/birth defect; or is an other important medical event, that is considered by the investigator to be related to the study intervention. Statistical analysis included only Groups 1 and 2 as indicated by the protocol.
Time Frame Up to Day 35 (up to 14 days after completing study treatment)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in Groups 1, 2, and 3 who received ≥1 dose of study drug are included.
Arm/Group Title Group 1: Imipenem+Cilastatin/Relebactam Group 2: Colistimethate Sodium + Imipenem+Cilastatin Group 3: Open-Label Imipenem+Cilastatin/Relebactam
Hide Arm/Group Description:
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem-nonsusceptible but imipenem/relebactam- and colistin-susceptible pathogens were randomized to receive imipenem+cilastatin/relebactam IV infusion once every 6 hours and placebo for colistimethate sodium IV infusion once every 12 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem-nonsusceptible but imipenem/relebactam- and colistin-susceptible pathogens were randomized to receive colistimethate sodium IV infusion once every 12 hours and imipenem+cilastatin IV infusion once every 6 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem- and colistin-nonsusceptible pathogens received open-label imipenem+cilastatin/relebactam IV infusion once every 6 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Overall Number of Participants Analyzed 31 16 3
Measure Type: Number
Unit of Measure: Percentage of Participants
0.0 0.0 33.3
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1: Imipenem+Cilastatin/Relebactam, Group 2: Colistimethate Sodium + Imipenem+Cilastatin
Comments [Not Specified]
Type of Statistical Test Other
Comments Difference in percentages
Method of Estimation Estimation Parameter Difference in drug-related SAE %
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-19.7 to 11.2
Estimation Comments Miettinen & Nurminen method
6.Primary Outcome
Title Percentage of Participants Discontinuing From Study Therapy Due to ≥1 AEs
Hide Description The percentage of participants in Group 1, 2, and 3 discontinuing from study drug due to ≥1 AEs during the treatment period was determined. An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Statistical analysis included only Groups 1 and 2 as indicated by the protocol.
Time Frame Up to Day 21
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in Groups 1, 2, and 3 who received ≥1 dose of study drug are included.
Arm/Group Title Group 1: Imipenem+Cilastatin/Relebactam Group 2: Colistimethate Sodium + Imipenem+Cilastatin Group 3: Open-Label Imipenem+Cilastatin/Relebactam
Hide Arm/Group Description:
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem-nonsusceptible but imipenem/relebactam- and colistin-susceptible pathogens were randomized to receive imipenem+cilastatin/relebactam IV infusion once every 6 hours and placebo for colistimethate sodium IV infusion once every 12 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem-nonsusceptible but imipenem/relebactam- and colistin-susceptible pathogens were randomized to receive colistimethate sodium IV infusion once every 12 hours and imipenem+cilastatin IV infusion once every 6 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem- and colistin-nonsusceptible pathogens received open-label imipenem+cilastatin/relebactam IV infusion once every 6 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Overall Number of Participants Analyzed 31 16 3
Measure Type: Number
Unit of Measure: Percentage of Participants
0.0 18.8 33.3
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1: Imipenem+Cilastatin/Relebactam, Group 2: Colistimethate Sodium + Imipenem+Cilastatin
Comments [Not Specified]
Type of Statistical Test Other
Comments Difference in percentages
Method of Estimation Estimation Parameter Difference in discontinuation %
Estimated Value -18.8
Confidence Interval (2-Sided) 95%
-43.3 to -6.2
Estimation Comments Miettinen & Nurminen method
7.Primary Outcome
Title Percentage of Participants Discontinuing From Study Therapy Due to ≥1 Drug-Related AEs
Hide Description The percentage of participants in Groups 1, 2, and 3 discontinuing from study drug due to ≥1 drug-related AEs during the treatment period was determined. A drug-related AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, and considered by the investigator to be related to the study intervention. Statistical analysis included only Groups 1 and 2 as indicated by the protocol.
Time Frame Up to Day 21
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in Groups 1, 2, and 3 who received ≥1 dose of study drug are included.
Arm/Group Title Group 1: Imipenem+Cilastatin/Relebactam Group 2: Colistimethate Sodium + Imipenem+Cilastatin Group 3: Open-Label Imipenem+Cilastatin/Relebactam
Hide Arm/Group Description:
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem-nonsusceptible but imipenem/relebactam- and colistin-susceptible pathogens were randomized to receive imipenem+cilastatin/relebactam IV infusion once every 6 hours and placebo for colistimethate sodium IV infusion once every 12 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem-nonsusceptible but imipenem/relebactam- and colistin-susceptible pathogens were randomized to receive colistimethate sodium IV infusion once every 12 hours and imipenem+cilastatin IV infusion once every 6 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem- and colistin-nonsusceptible pathogens received open-label imipenem+cilastatin/relebactam IV infusion once every 6 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Overall Number of Participants Analyzed 31 16 3
Measure Type: Number
Unit of Measure: Percentage of Participants
0.0 12.5 33.3
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1: Imipenem+Cilastatin/Relebactam, Group 2: Colistimethate Sodium + Imipenem+Cilastatin
Comments [Not Specified]
Type of Statistical Test Other
Comments Difference in percentages
Method of Estimation Estimation Parameter Difference in drug-related discon %
Estimated Value -12.5
Confidence Interval (2-Sided) 95%
-36.3 to -0.3
Estimation Comments Miettinen & Nurminen method
8.Primary Outcome
Title Analysis of Specific AEs With an Incidence of ≥4 Participants in a Treatment Group
Hide Description The percentage of participants experiencing AEs that occurred in ≥4 participants within either Group 1 or Group 2 was assessed. An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Statistical analysis included only Groups 1 and 2 as indicated by the protocol; Group 3 had <4 participants and therefore no data are presented.
Time Frame Up to Day 35 (up to 14 days after completing study treatment)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in Groups 1 and 2 who received ≥1 dose of study drug are included. Group 3 data is not shown for this measure because there are only 3 participants.
Arm/Group Title Group 1: Imipenem+Cilastatin/Relebactam Group 2: Colistimethate Sodium + Imipenem+Cilastatin Group 3: Open-Label Imipenem+Cilastatin/Relebactam
Hide Arm/Group Description:
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem-nonsusceptible but imipenem/relebactam- and colistin-susceptible pathogens were randomized to receive imipenem+cilastatin/relebactam IV infusion once every 6 hours and placebo for colistimethate sodium IV infusion once every 12 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem-nonsusceptible but imipenem/relebactam- and colistin-susceptible pathogens were randomized to receive colistimethate sodium IV infusion once every 12 hours and imipenem+cilastatin IV infusion once every 6 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem- and colistin-nonsusceptible pathogens received open-label imipenem+cilastatin/relebactam IV infusion once every 6 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Overall Number of Participants Analyzed 31 16 0
Measure Type: Number
Unit of Measure: Percentage of Participants
Pyrexia 12.9 12.5
Blood creatinine increased 0.0 25.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1: Imipenem+Cilastatin/Relebactam, Group 2: Colistimethate Sodium + Imipenem+Cilastatin
Comments [Not Specified]
Type of Statistical Test Other
Comments Difference in percentages
Method of Estimation Estimation Parameter Difference in pyrexia %
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-25.2 to 19.7
Estimation Comments Miettinen & Nurminen method
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Group 1: Imipenem+Cilastatin/Relebactam, Group 2: Colistimethate Sodium + Imipenem+Cilastatin
Comments [Not Specified]
Type of Statistical Test Other
Comments Difference in percentages
Method of Estimation Estimation Parameter Difference blood creatinine inc %
Estimated Value -25.0
Confidence Interval (2-Sided) 95%
-49.8 to -10.1
Estimation Comments Miettinen & Nurminen method
9.Primary Outcome
Title Percentage of Participants With ≥1 Events of Clinical Interest (ECI)
Hide Description The percentage of participants in Groups 1, 2, and 3 having ECIs within 2 categories was determined. Category 1 ECIs included post-baseline laboratory values of an elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) value that is ≥3x upper limit of normal (ULN) and an elevated total bilirubin value that is ≥2x ULN and (at the same time) an alkaline phosphatase value that is ≤2x ULN. Category 2 ECIs included a confirmed elevated AST or ALT value that is ≥5x ULN. Statistical analysis included only Groups 1 and 2 as indicated by the protocol.
Time Frame Up to Day 35 (up to 14 days after completing study treatment)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in Groups 1, 2, and 3 who received ≥1 dose of study drug are included.
Arm/Group Title Group 1: Imipenem+Cilastatin/Relebactam Group 2: Colistimethate Sodium + Imipenem+Cilastatin Group 3: Open-Label Imipenem+Cilastatin/Relebactam
Hide Arm/Group Description:
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem-nonsusceptible but imipenem/relebactam- and colistin-susceptible pathogens were randomized to receive imipenem+cilastatin/relebactam IV infusion once every 6 hours and placebo for colistimethate sodium IV infusion once every 12 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem-nonsusceptible but imipenem/relebactam- and colistin-susceptible pathogens were randomized to receive colistimethate sodium IV infusion once every 12 hours and imipenem+cilastatin IV infusion once every 6 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem- and colistin-nonsusceptible pathogens received open-label imipenem+cilastatin/relebactam IV infusion once every 6 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Overall Number of Participants Analyzed 31 16 3
Measure Type: Number
Unit of Measure: Percentage of Participants
Category 1 ECI Number Analyzed 31 participants 16 participants 0 participants
0.0 12.5
Category 2 ECI Number Analyzed 31 participants 16 participants 0 participants
0.0 12.5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1: Imipenem+Cilastatin/Relebactam, Group 2: Colistimethate Sodium + Imipenem+Cilastatin
Comments [Not Specified]
Type of Statistical Test Other
Comments Difference in Category 1 ECI %
Statistical Test of Hypothesis P-Value 0.047
Comments [Not Specified]
Method Miettinen and Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Category 1 ECI %
Estimated Value -12.5
Confidence Interval (2-Sided) 95%
-36.3 to -0.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Group 1: Imipenem+Cilastatin/Relebactam, Group 2: Colistimethate Sodium + Imipenem+Cilastatin
Comments [Not Specified]
Type of Statistical Test Other
Comments Difference in Category 2 ECI %
Statistical Test of Hypothesis P-Value 0.047
Comments [Not Specified]
Method Miettinen and Nurminen method
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Category 2 ECI %
Estimated Value -12.5
Confidence Interval 95%
-36.3 to -0.3
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Percentage of Participants With ≥1 Events of Treatment-Emergent Nephrotoxicity
Hide Description Treatment-emergent nephrotoxity was assessed in Groups 1 and 2 as indicated by the protocol (Group 3 was not included). Nephrotoxicity for participants with normal baseline serum creatinine levels (<1.2 mg/dL) was defined as "doubling of serum creatinine to >1.2 mg/dL or reduction in creatinine clearance (ClCR) of ≥50%". Nephrotoxicity for participants with pre-existing renal dysfunction (baseline serum creatinine level ≥1.2 mg/dL) was defined as "increase in serum creatinine by ≥1 mg/dL or reduction from baseline ClCR of ≥20% or need for renal replacement therapy (RRT)".
Time Frame Up to Day 35 (up to 14 days after completing study treatment)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in Groups 1 and 2 who received ≥1 dose of study drug are included. Per protocol, Group 3 was not included in the nephrotoxicity analysis.
Arm/Group Title Group 1: Imipenem+Cilastatin/Relebactam Group 2: Colistimethate Sodium + Imipenem+Cilastatin Group 3: Open-Label Imipenem+Cilastatin/Relebactam
Hide Arm/Group Description:
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem-nonsusceptible but imipenem/relebactam- and colistin-susceptible pathogens were randomized to receive imipenem+cilastatin/relebactam IV infusion once every 6 hours and placebo for colistimethate sodium IV infusion once every 12 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem-nonsusceptible but imipenem/relebactam- and colistin-susceptible pathogens were randomized to receive colistimethate sodium IV infusion once every 12 hours and imipenem+cilastatin IV infusion once every 6 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem- and colistin-nonsusceptible pathogens received open-label imipenem+cilastatin/relebactam IV infusion once every 6 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Overall Number of Participants Analyzed 31 16 0
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
10.3
(2.8 to 27.2)
56.3
(33.2 to 76.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1: Imipenem+Cilastatin/Relebactam, Group 2: Colistimethate Sodium + Imipenem+Cilastatin
Comments [Not Specified]
Type of Statistical Test Other
Comments Difference in percentages
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in nephrotoxicity %
Estimated Value -45.9
Confidence Interval 95%
-69.1 to -18.4
Estimation Comments Miettinen & Nurminen method
11.Secondary Outcome
Title Percentage of Participants With Favorable Clinical Response (FCR) at Day 28
Hide Description The percentage of participants with FCR at Day 28 was determined for Groups 1 and 2. FCR at Day 28 was defined as "sustained cure" or "cure". Sustained cure (for participants with "cure" response at the prior visit) was defined as "all pretherapy signs and symptoms of index infection resolved with no evidence of resurgence and no additional antibiotic therapy required, and (for cIAI participants) no unplanned surgical procedures or percutaneous drainage procedures have been performed". Cure (for participants with "improved" response at EOT visit) was defined as "all pretherapy signs and symptoms of index infection resolved or returned to preinfection status, and no additional IV antibiotic therapy required, and (for cIAI participants) no unplanned surgical procedures or percutaneous drainage procedures performed".
Time Frame Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Groups 1 and 2 who received ≥1 dose of each trial drug within a given IV treatment regimen, and who had a baseline bacterial pathogen that met inclusion criteria, are included. As per protocol, efficacy data from open-label Group 3 was considered exploratory and not included in the comparative analysis.
Arm/Group Title Group 1: Imipenem+Cilastatin/Relebactam Group 2: Colistimethate Sodium + Imipenem+Cilastatin Group 3: Open-Label Imipenem+Cilastatin/Relebactam
Hide Arm/Group Description:
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem-nonsusceptible but imipenem/relebactam- and colistin-susceptible pathogens were randomized to receive imipenem+cilastatin/relebactam IV infusion once every 6 hours and placebo for colistimethate sodium IV infusion once every 12 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem-nonsusceptible but imipenem/relebactam- and colistin-susceptible pathogens were randomized to receive colistimethate sodium IV infusion once every 12 hours and imipenem+cilastatin IV infusion once every 6 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem- and colistin-nonsusceptible pathogens received open-label imipenem+cilastatin/relebactam IV infusion once every 6 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Overall Number of Participants Analyzed 21 10 0
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
71.4
(49.8 to 86.4)
40.0
(16.7 to 68.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1: Imipenem+Cilastatin/Relebactam, Group 2: Colistimethate Sodium + Imipenem+Cilastatin
Comments [Not Specified]
Type of Statistical Test Other
Comments Difference in Day 28 FCR %
Method of Estimation Estimation Parameter Difference in Day 28 FCR %
Estimated Value 26.3
Confidence Interval (2-Sided) 90%
1.3 to 51.5
Estimation Comments Miettinen and Nurminen method stratified by infection-site stratum
12.Secondary Outcome
Title Percentage of Participants With All-cause Mortality Up to Day 28
Hide Description The percentage of participants with all-cause mortality up to Day 28 was determined for Groups 1 and 2.
Time Frame Up to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Group 1 and Group 2 who received ≥1 dose of each trial drug within a given IV treatment regimen, and who had a baseline bacterial pathogen that met inclusion criteria, are included. As per protocol, efficacy data from open-label Group 3 was considered exploratory and not included in the comparative analysis.
Arm/Group Title Group 1: Imipenem+Cilastatin/Relebactam Group 2: Colistimethate Sodium + Imipenem+Cilastatin Group 3: Open-Label Imipenem+Cilastatin/Relebactam
Hide Arm/Group Description:
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem-nonsusceptible but imipenem/relebactam- and colistin-susceptible pathogens were randomized to receive imipenem+cilastatin/relebactam IV infusion once every 6 hours and placebo for colistimethate sodium IV infusion once every 12 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem-nonsusceptible but imipenem/relebactam- and colistin-susceptible pathogens were randomized to receive colistimethate sodium IV infusion once every 12 hours and imipenem+cilastatin IV infusion once every 6 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem- and colistin-nonsusceptible pathogens received open-label imipenem+cilastatin/relebactam IV infusion once every 6 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Overall Number of Participants Analyzed 21 10 0
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
9.5
(1.4 to 30.1)
30.0
(10.3 to 60.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1: Imipenem+Cilastatin/Relebactam, Group 2: Colistimethate Sodium + Imipenem+Cilastatin
Comments [Not Specified]
Type of Statistical Test Other
Comments Difference in mortality %
Method of Estimation Estimation Parameter Difference in mortality %
Estimated Value -17.3
Confidence Interval (2-Sided) 90%
-46.4 to 6.7
Estimation Comments Miettinen and Nurminen method stratified by infection-site stratum
13.Secondary Outcome
Title Percentage of Participants With FCR on Therapy (OTX)
Hide Description The percentage of participants with a FCR at OTX was determined for Groups 1 and 2. FCR at OTX was defined as "improved". Improved was defined as "all or most pretherapy signs and symptoms of index infection have improved or resolved, and (for cIAI participants) no unplanned surgical procedures or percutaneous drainage procedures have been performed.
Time Frame OTX (Day 3)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Group 1 and Group 2 who received ≥1 dose of each trial drug within a given IV treatment regimen, and who had a baseline bacterial pathogen that met inclusion criteria, are included. As per protocol, efficacy data from open-label Group 3 was considered exploratory and not included in the comparative analysis.
Arm/Group Title Group 1: Imipenem+Cilastatin/Relebactam Group 2: Colistimethate Sodium + Imipenem+Cilastatin Group 3: Open-Label Imipenem+Cilastatin/Relebactam
Hide Arm/Group Description:
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem-nonsusceptible but imipenem/relebactam- and colistin-susceptible pathogens were randomized to receive imipenem+cilastatin/relebactam IV infusion once every 6 hours and placebo for colistimethate sodium IV infusion once every 12 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem-nonsusceptible but imipenem/relebactam- and colistin-susceptible pathogens were randomized to receive colistimethate sodium IV infusion once every 12 hours and imipenem+cilastatin IV infusion once every 6 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem- and colistin-nonsusceptible pathogens received open-label imipenem+cilastatin/relebactam IV infusion once every 6 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Overall Number of Participants Analyzed 21 10 0
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
81.0
(59.4 to 92.9)
40.0
(16.7 to 68.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1: Imipenem+Cilastatin/Relebactam, Group 2: Colistimethate Sodium + Imipenem+Cilastatin
Comments [Not Specified]
Type of Statistical Test Other
Comments Adjusted difference in OTX FCR %
Method of Estimation Estimation Parameter Adjusted difference in OTX FCR %
Estimated Value 33.9
Confidence Interval (2-Sided) 90%
7.4 to 61.1
Estimation Comments Miettinen and Nurminen method stratified by infection-site stratum
14.Secondary Outcome
Title Percentage of Participants With FCR at End of Therapy (EOT)
Hide Description The percentage of participants with FCR at EOT was determined for Groups 1 and 2. FCR at EOT was defined as "cure" or "improved". Cure was defined as "all pretherapy signs and symptoms of index infection resolved or returned to preinfection status, and no additional IV antibiotic therapy required, and (for cIAI participants) no unplanned surgical procedures or percutaneous drainage procedures performed". Improved was defined as "all or most pretherapy signs and symptoms of index infection have improved or resolved, and (for cIAI participants) no unplanned surgical procedures or percutaneous drainage procedures have been performed.
Time Frame At EOT (up to Day 21)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Group 1 and Group 2 who received ≥1 dose of each trial drug within a given IV treatment regimen, and who had a baseline bacterial pathogen that met inclusion criteria, are included. As per protocol, efficacy data from open-label Group 3 was considered exploratory and not included in the comparative analysis.
Arm/Group Title Group 1: Imipenem+Cilastatin/Relebactam Group 2: Colistimethate Sodium + Imipenem+Cilastatin Group 3: Open-Label Imipenem+Cilastatin/Relebactam
Hide Arm/Group Description:
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem-nonsusceptible but imipenem/relebactam- and colistin-susceptible pathogens were randomized to receive imipenem+cilastatin/relebactam IV infusion once every 6 hours and placebo for colistimethate sodium IV infusion once every 12 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem-nonsusceptible but imipenem/relebactam- and colistin-susceptible pathogens were randomized to receive colistimethate sodium IV infusion once every 12 hours and imipenem+cilastatin IV infusion once every 6 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem- and colistin-nonsusceptible pathogens received open-label imipenem+cilastatin/relebactam IV infusion once every 6 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Overall Number of Participants Analyzed 21 10 0
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
90.5
(69.9 to 98.6)
60.0
(31.2 to 83.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1: Imipenem+Cilastatin/Relebactam, Group 2: Colistimethate Sodium + Imipenem+Cilastatin
Comments [Not Specified]
Type of Statistical Test Other
Comments Adjusted difference in EOT FCR %
Method of Estimation Estimation Parameter Adjusted difference in EOT FCR %
Estimated Value 25.4
Confidence Interval (2-Sided) 90%
3.1 to 53.6
Estimation Comments Miettinen and Nurminen method stratified by infection-site stratum
15.Secondary Outcome
Title Percentage of Participants With FCR at EFU
Hide Description The percentage of participants with FCR at EFU was determined for Groups 1 and 2. FCR at EFU was defined as "sustained cure" or "cure". Sustained cure (for participants with "cure" response at the prior visit) was defined as "all pretherapy signs and symptoms of index infection resolved with no evidence of resurgence and no additional antibiotic therapy required, and (for cIAI participants) no unplanned surgical procedures or percutaneous drainage procedures have been performed". Cure (for participants with "improved" response at EOT visit) was defined as "all pretherapy signs and symptoms of index infection resolved or returned to preinfection status, and no additional IV antibiotic therapy required, and (for cIAI participants) no unplanned surgical procedures or percutaneous drainage procedures performed".
Time Frame EFU (Between Day 10 and Day 30 [5 to 9 Days after EOT])
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Group 1 and Group 2 who received ≥1 dose of each trial drug within a given IV treatment regimen, and who had a baseline bacterial pathogen that met inclusion criteria, are included. As per protocol, efficacy data from open-label Group 3 was considered exploratory and not included in the comparative analysis.
Arm/Group Title Group 1: Imipenem+Cilastatin/Relebactam Group 2: Colistimethate Sodium + Imipenem+Cilastatin Group 3: Open-Label Imipenem+Cilastatin/Relebactam
Hide Arm/Group Description:
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem-nonsusceptible but imipenem/relebactam- and colistin-susceptible pathogens were randomized to receive imipenem+cilastatin/relebactam IV infusion once every 6 hours and placebo for colistimethate sodium IV infusion once every 12 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem-nonsusceptible but imipenem/relebactam- and colistin-susceptible pathogens were randomized to receive colistimethate sodium IV infusion once every 12 hours and imipenem+cilastatin IV infusion once every 6 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem- and colistin-nonsusceptible pathogens received open-label imipenem+cilastatin/relebactam IV infusion once every 6 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Overall Number of Participants Analyzed 21 10 0
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
81.0
(59.4 to 92.9)
50.0
(23.7 to 76.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1: Imipenem+Cilastatin/Relebactam, Group 2: Colistimethate Sodium + Imipenem+Cilastatin
Comments [Not Specified]
Type of Statistical Test Other
Comments Adjusted difference in EFU FCR %
Method of Estimation Estimation Parameter Difference in EFU FCR %
Estimated Value 24.7
Confidence Interval (2-Sided) 90%
3.8 to 51.4
Estimation Comments Miettinen and Nurminen method stratified by infection-site stratum
16.Secondary Outcome
Title Percentage of cUTI Participants With Favorable Microbiological Response (FMR) at OTX
Hide Description The percentage of participants with FMR at OTX was determined for participants with cUTI in Groups 1 and 2. FMR was defined as "urine culture results at OTX showing eradication (i.e., ≥10^5 colony forming units [CFU]/mL at baseline was reduced to <10^4 CFU/mL at OTX) of the uropathogen".
Time Frame OTX (Day 3)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Group 1 and Group 2 with cUTI who received ≥1 dose of each trial drug within a given IV treatment regimen, and who had a baseline bacterial pathogen that met inclusion criteria, are included. As per protocol, efficacy data from open-label Group 3 was considered exploratory and not included in the comparative analysis.
Arm/Group Title Group 1: Imipenem+Cilastatin/Relebactam Group 2: Colistimethate Sodium + Imipenem+Cilastatin Group 3: Open-Label Imipenem+Cilastatin/Relebactam
Hide Arm/Group Description:
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem-nonsusceptible but imipenem/relebactam- and colistin-susceptible pathogens were randomized to receive imipenem+cilastatin/relebactam IV infusion once every 6 hours and placebo for colistimethate sodium IV infusion once every 12 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem-nonsusceptible but imipenem/relebactam- and colistin-susceptible pathogens were randomized to receive colistimethate sodium IV infusion once every 12 hours and imipenem+cilastatin IV infusion once every 6 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem- and colistin-nonsusceptible pathogens received open-label imipenem+cilastatin/relebactam IV infusion once every 6 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Overall Number of Participants Analyzed 11 5 0
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
100.0
(70.0 to 100.0)
100.0
(51.1 to 100.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1: Imipenem+Cilastatin/Relebactam, Group 2: Colistimethate Sodium + Imipenem+Cilastatin
Comments [Not Specified]
Type of Statistical Test Other
Comments Difference in percentages
Method of Estimation Estimation Parameter Difference in FMR %
Estimated Value 0.0
Confidence Interval (2-Sided) 90%
-20.8 to 36.6
Estimation Comments Miettinen & Nurminen method
17.Secondary Outcome
Title Percentage of cUTI Participants With FMR at EOT
Hide Description The percentage of participants with FMR at EOT was determined for participants with cUTI in Groups 1 and 2. FMR was defined as "urine culture results at EOT showing eradication (i.e., ≥10^5 CFU/mL at baseline was reduced to <10^4 CFU/mL at EOT) or sustained eradication (i.e., ≥10^5 CFU/mL at baseline that was reduced to <10^4 CFU/mL previously remained <10^4 CFU/mL at EOT) of the uropathogen".
Time Frame At EOT (up to Day 21)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Group 1 and Group 2 with cUTI who received ≥1 dose of each trial drug within a given IV treatment regimen, and who had a baseline bacterial pathogen that met inclusion criteria, are included. As per protocol, efficacy data from open-label Group 3 was considered exploratory and not included in the comparative analysis.
Arm/Group Title Group 1: Imipenem+Cilastatin/Relebactam Group 2: Colistimethate Sodium + Imipenem+Cilastatin Group 3: Open-Label Imipenem+Cilastatin/Relebactam
Hide Arm/Group Description:
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem-nonsusceptible but imipenem/relebactam- and colistin-susceptible pathogens were randomized to receive imipenem+cilastatin/relebactam IV infusion once every 6 hours and placebo for colistimethate sodium IV infusion once every 12 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem-nonsusceptible but imipenem/relebactam- and colistin-susceptible pathogens were randomized to receive colistimethate sodium IV infusion once every 12 hours and imipenem+cilastatin IV infusion once every 6 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem- and colistin-nonsusceptible pathogens received open-label imipenem+cilastatin/relebactam IV infusion once every 6 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Overall Number of Participants Analyzed 11 5 0
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
100.0
(70.0 to 100.0)
100.0
(51.1 to 100.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1: Imipenem+Cilastatin/Relebactam, Group 2: Colistimethate Sodium + Imipenem+Cilastatin
Comments [Not Specified]
Type of Statistical Test Other
Comments Difference in percentages
Method of Estimation Estimation Parameter Difference in FMR %
Estimated Value 0.0
Confidence Interval (2-Sided) 90%
-20.8 to 36.6
Estimation Comments Miettinen & Nurminen method
18.Secondary Outcome
Title Percentage of cUTI Participants With FMR at EFU
Hide Description The percentage of participants with FMR at EFU was determined for participants with cUTI in Groups 1 and 2. FMR was defined as "urine culture results at EFU showing sustained eradication (i.e., ≥10^5 CFU/mL at baseline that was reduced to <10^4 CFU/mL previously remained <10^4 CFU/mL at EFU) of the uropathogen".
Time Frame EFU (Between Day 10 and Day 30 [5 to 9 Days after EOT])
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in Group 1 and Group 2 with cUTI who received ≥1 dose of each trial drug within a given IV treatment regimen, and who had a baseline bacterial pathogen that met inclusion criteria, are included. As per protocol, efficacy data from open-label Group 3 was considered exploratory and not included in the comparative analysis.
Arm/Group Title Group 1: Imipenem+Cilastatin/Relebactam Group 2: Colistimethate Sodium + Imipenem+Cilastatin Group 3: Open-Label Imipenem+Cilastatin/Relebactam
Hide Arm/Group Description:
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem-nonsusceptible but imipenem/relebactam- and colistin-susceptible pathogens were randomized to receive imipenem+cilastatin/relebactam IV infusion once every 6 hours and placebo for colistimethate sodium IV infusion once every 12 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem-nonsusceptible but imipenem/relebactam- and colistin-susceptible pathogens were randomized to receive colistimethate sodium IV infusion once every 12 hours and imipenem+cilastatin IV infusion once every 6 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Participants with HABP, VABP, cIAI, or cUTI caused by imipenem- and colistin-nonsusceptible pathogens received open-label imipenem+cilastatin/relebactam IV infusion once every 6 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
Overall Number of Participants Analyzed 11 5 0
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
72.7
(42.9 to 90.8)
100.0
(51.1 to 100.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group 1: Imipenem+Cilastatin/Relebactam, Group 2: Colistimethate Sodium + Imipenem+Cilastatin
Comments [Not Specified]
Type of Statistical Test Other
Comments Difference in percentages
Method of Estimation Estimation Parameter Difference in FMR %
Estimated Value -27.3
Confidence Interval (2-Sided) 90%
-52.8 to 12.8
Estimation Comments Miettinen & Nurminen method
Time Frame Up to Day 35 (up to 14 days after EOT)
Adverse Event Reporting Description An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. All participants in Groups 1, 2, and 3 who received ≥1 dose of study drug are included. Any event(s) reported to the investigator outside the AE monitoring period are also included.
 
Arm/Group Title Group 1: Imipenem+Cilastatin/Relebactam Group 2: Colistimethate Sodium + Imipenem+Cilastatin Group 3: Open-Label Imipenem+Cilastatin/Relebactam
Hide Arm/Group Description Participants with HABP, VABP, cIAI, or cUTI caused by imipenem-nonsusceptible but imipenem/relebactam- and colistin-susceptible pathogens were randomized to receive imipenem+cilastatin/relebactam IV infusion once every 6 hours and placebo for colistimethate sodium IV infusion once every 12 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP). Participants with HABP, VABP, cIAI, or cUTI caused by imipenem-nonsusceptible but imipenem/relebactam- and colistin-susceptible pathogens were randomized to receive colistimethate sodium IV infusion once every 12 hours and imipenem+cilastatin IV infusion once every 6 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP). Participants with HABP, VABP, cIAI, or cUTI caused by imipenem- and colistin-nonsusceptible pathogens received open-label imipenem+cilastatin/relebactam IV infusion once every 6 hours for 5 to 21 days (cIAI and cUTI) or for 7 to 21 days (HABP or VABP).
All-Cause Mortality
Group 1: Imipenem+Cilastatin/Relebactam Group 2: Colistimethate Sodium + Imipenem+Cilastatin Group 3: Open-Label Imipenem+Cilastatin/Relebactam
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/31 (6.45%)      3/16 (18.75%)      1/3 (33.33%)    
Hide Serious Adverse Events
Group 1: Imipenem+Cilastatin/Relebactam Group 2: Colistimethate Sodium + Imipenem+Cilastatin Group 3: Open-Label Imipenem+Cilastatin/Relebactam
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/31 (12.90%)      5/16 (31.25%)      3/3 (100.00%)    
Cardiac disorders       
Cardiac arrest  1  1/31 (3.23%)  1 0/16 (0.00%)  0 0/3 (0.00%)  0
Ventricular tachycardia  1  0/31 (0.00%)  0 1/16 (6.25%)  1 0/3 (0.00%)  0
Gastrointestinal disorders       
Acute abdomen  1  0/31 (0.00%)  0 0/16 (0.00%)  0 1/3 (33.33%)  1
Duodenal perforation  1  0/31 (0.00%)  0 0/16 (0.00%)  0 1/3 (33.33%)  2
Upper gastrointestinal haemorrhage  1  0/31 (0.00%)  0 1/16 (6.25%)  1 0/3 (0.00%)  0
General disorders       
Systemic inflammatory response syndrome  1  1/31 (3.23%)  1 0/16 (0.00%)  0 0/3 (0.00%)  0
Hepatobiliary disorders       
Hepatic haematoma  1  0/31 (0.00%)  0 0/16 (0.00%)  0 1/3 (33.33%)  1
Infections and infestations       
Escherichia urinary tract infection  1  0/31 (0.00%)  0 0/16 (0.00%)  0 1/3 (33.33%)  1
Lung infection  1  1/31 (3.23%)  1 0/16 (0.00%)  0 0/3 (0.00%)  0
Pneumonia  1  0/31 (0.00%)  0 0/16 (0.00%)  0 2/3 (66.67%)  2
Septic shock  1  0/31 (0.00%)  0 1/16 (6.25%)  1 1/3 (33.33%)  1
Injury, poisoning and procedural complications       
Abdominal wound dehiscence  1  0/31 (0.00%)  0 0/16 (0.00%)  0 1/3 (33.33%)  1
Subarachnoid haemorrhage  1  0/31 (0.00%)  0 1/16 (6.25%)  1 0/3 (0.00%)  0
Investigations       
Alanine aminotransferase increased  1  0/31 (0.00%)  0 1/16 (6.25%)  1 0/3 (0.00%)  0
Aspartate aminotransferase increased  1  0/31 (0.00%)  0 1/16 (6.25%)  1 0/3 (0.00%)  0
Blood alkaline phosphatase increased  1  0/31 (0.00%)  0 1/16 (6.25%)  1 0/3 (0.00%)  0
Nervous system disorders       
Generalised tonic-clonic seizure  1  0/31 (0.00%)  0 0/16 (0.00%)  0 1/3 (33.33%)  1
Psychiatric disorders       
Mental status changes  1  0/31 (0.00%)  0 0/16 (0.00%)  0 1/3 (33.33%)  1
Renal and urinary disorders       
Acute kidney injury  1  1/31 (3.23%)  1 0/16 (0.00%)  0 0/3 (0.00%)  0
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Group 1: Imipenem+Cilastatin/Relebactam Group 2: Colistimethate Sodium + Imipenem+Cilastatin Group 3: Open-Label Imipenem+Cilastatin/Relebactam
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   15/31 (48.39%)      13/16 (81.25%)      3/3 (100.00%)    
Blood and lymphatic system disorders       
Anaemia  1  2/31 (6.45%)  2 1/16 (6.25%)  1 1/3 (33.33%)  1
Leukopenia  1  0/31 (0.00%)  0 1/16 (6.25%)  1 0/3 (0.00%)  0
Cardiac disorders       
Arteriosclerosis coronary artery  1  0/31 (0.00%)  0 1/16 (6.25%)  1 0/3 (0.00%)  0
Atrial flutter  1  0/31 (0.00%)  0 0/16 (0.00%)  0 1/3 (33.33%)  1
Tachyarrhythmia  1  0/31 (0.00%)  0 1/16 (6.25%)  1 0/3 (0.00%)  0
Tachycardia  1  1/31 (3.23%)  1 1/16 (6.25%)  1 0/3 (0.00%)  0
Ear and labyrinth disorders       
Hypoacusis  1  0/31 (0.00%)  0 1/16 (6.25%)  1 0/3 (0.00%)  0
Eye disorders       
Visual acuity reduced  1  0/31 (0.00%)  0 1/16 (6.25%)  1 0/3 (0.00%)  0
Gastrointestinal disorders       
Constipation  1  1/31 (3.23%)  1 0/16 (0.00%)  0 1/3 (33.33%)  1
Diarrhoea  1  1/31 (3.23%)  1 0/16 (0.00%)  0 1/3 (33.33%)  1
Gastritis  1  0/31 (0.00%)  0 1/16 (6.25%)  1 0/3 (0.00%)  0
Gastrooesophageal reflux disease  1  0/31 (0.00%)  0 1/16 (6.25%)  1 1/3 (33.33%)  1
Haematemesis  1  0/31 (0.00%)  0 1/16 (6.25%)  1 0/3 (0.00%)  0
Hypoaesthesia oral  1  0/31 (0.00%)  0 2/16 (12.50%)  2 0/3 (0.00%)  0
Ileus  1  0/31 (0.00%)  0 0/16 (0.00%)  0 1/3 (33.33%)  1
Large intestinal haemorrhage  1  0/31 (0.00%)  0 1/16 (6.25%)  1 0/3 (0.00%)  0
Large intestinal ulcer  1  0/31 (0.00%)  0 1/16 (6.25%)  1 0/3 (0.00%)  0
Large intestine perforation  1  0/31 (0.00%)  0 1/16 (6.25%)  1 0/3 (0.00%)  0
Nausea  1  2/31 (6.45%)  2 3/16 (18.75%)  3 0/3 (0.00%)  0
Retching  1  0/31 (0.00%)  0 0/16 (0.00%)  0 1/3 (33.33%)  1
Vomiting  1  1/31 (3.23%)  1 1/16 (6.25%)  1 0/3 (0.00%)  0
General disorders       
Infusion site phlebitis  1  1/31 (3.23%)  1 2/16 (12.50%)  2 0/3 (0.00%)  0
Oedema  1  2/31 (6.45%)  2 0/16 (0.00%)  0 0/3 (0.00%)  0
Oedema peripheral  1  2/31 (6.45%)  2 0/16 (0.00%)  0 0/3 (0.00%)  0
Peripheral swelling  1  0/31 (0.00%)  0 0/16 (0.00%)  0 1/3 (33.33%)  1
Pyrexia  1  4/31 (12.90%)  5 2/16 (12.50%)  2 0/3 (0.00%)  0
Hepatobiliary disorders       
Hepatic artery stenosis  1  0/31 (0.00%)  0 1/16 (6.25%)  1 0/3 (0.00%)  0
Hepatic failure  1  0/31 (0.00%)  0 1/16 (6.25%)  1 0/3 (0.00%)  0
Periportal oedema  1  0/31 (0.00%)  0 1/16 (6.25%)  1 0/3 (0.00%)  0
Immune system disorders       
Chronic graft versus host disease in liver  1  0/31 (0.00%)  0 1/16 (6.25%)  1 0/3 (0.00%)  0
Infections and infestations       
Abdominal infection  1  2/31 (6.45%)  2 0/16 (0.00%)  0 0/3 (0.00%)  0
Anorectal infection bacterial  1  1/31 (3.23%)  1 0/16 (0.00%)  0 1/3 (33.33%)  1
Bacteraemia  1  0/31 (0.00%)  0 1/16 (6.25%)  1 0/3 (0.00%)  0
Bacterial abdominal infection  1  1/31 (3.23%)  2 1/16 (6.25%)  1 0/3 (0.00%)  0
Biliary tract infection bacterial  1  0/31 (0.00%)  0 1/16 (6.25%)  3 0/3 (0.00%)  0
Biliary tract infection fungal  1  0/31 (0.00%)  0 1/16 (6.25%)  1 0/3 (0.00%)  0
Conjunctivitis  1  0/31 (0.00%)  0 1/16 (6.25%)  1 0/3 (0.00%)  0
Device related infection  1  0/31 (0.00%)  0 0/16 (0.00%)  0 1/3 (33.33%)  1
Ear infection bacterial  1  0/31 (0.00%)  0 0/16 (0.00%)  0 1/3 (33.33%)  1
Ear infection staphylococcal  1  0/31 (0.00%)  0 0/16 (0.00%)  0 1/3 (33.33%)  1
Enterococcal infection  1  0/31 (0.00%)  0 1/16 (6.25%)  1 0/3 (0.00%)  0
Lower respiratory tract infection bacterial  1  1/31 (3.23%)  1 1/16 (6.25%)  1 0/3 (0.00%)  0
Peritoneal candidiasis  1  0/31 (0.00%)  0 1/16 (6.25%)  1 0/3 (0.00%)  0
Peritonitis  1  0/31 (0.00%)  0 1/16 (6.25%)  1 0/3 (0.00%)  0
Respiratory moniliasis  1  1/31 (3.23%)  1 1/16 (6.25%)  1 0/3 (0.00%)  0
Serratia infection  1  0/31 (0.00%)  0 1/16 (6.25%)  1 0/3 (0.00%)  0
Staphylococcal bacteraemia  1  0/31 (0.00%)  0 1/16 (6.25%)  2 1/3 (33.33%)  1
Stenotrophomonas infection  1  0/31 (0.00%)  0 1/16 (6.25%)  1 0/3 (0.00%)  0
Streptococcal urinary tract infection  1  0/31 (0.00%)  0 1/16 (6.25%)  1 0/3 (0.00%)  0
Urinary tract infection  1  2/31 (6.45%)  2 0/16 (0.00%)  0 0/3 (0.00%)  0
Injury, poisoning and procedural complications       
Biliary anastomosis complication  1  0/31 (0.00%)  0 1/16 (6.25%)  1 0/3 (0.00%)  0
Gastrointestinal stoma complication  1  0/31 (0.00%)  0 1/16 (6.25%)  1 0/3 (0.00%)  0
Incision site haemorrhage  1  0/31 (0.00%)  0 1/16 (6.25%)  2 0/3 (0.00%)  0
Laceration  1  0/31 (0.00%)  0 0/16 (0.00%)  0 1/3 (33.33%)  1
Investigations       
Activated partial thromboplastin time prolonged  1  0/31 (0.00%)  0 1/16 (6.25%)  1 0/3 (0.00%)  0
Alanine aminotransferase increased  1  2/31 (6.45%)  2 2/16 (12.50%)  2 0/3 (0.00%)  0
Aspartate aminotransferase increased  1  3/31 (9.68%)  3 2/16 (12.50%)  2 0/3 (0.00%)  0
Blood alkaline phosphatase increased  1  1/31 (3.23%)  1 1/16 (6.25%)  1 0/3 (0.00%)  0
Blood bilirubin increased  1  0/31 (0.00%)  0 2/16 (12.50%)  2 0/3 (0.00%)  0
Blood creatinine increased  1  0/31 (0.00%)  0 4/16 (25.00%)  4 0/3 (0.00%)  0
Blood potassium decreased  1  0/31 (0.00%)  0 1/16 (6.25%)  1 0/3 (0.00%)  0
Blood urea increased  1  0/31 (0.00%)  0 1/16 (6.25%)  1 0/3 (0.00%)  0
C-reactive protein increased  1  2/31 (6.45%)  2 0/16 (0.00%)  0 0/3 (0.00%)  0
Creatinine renal clearance decreased  1  2/31 (6.45%)  2 2/16 (12.50%)  2 0/3 (0.00%)  0
Gamma-glutamyltransferase increased  1  1/31 (3.23%)  1 2/16 (12.50%)  2 0/3 (0.00%)  0
Glomerular filtration rate decreased  1  0/31 (0.00%)  0 1/16 (6.25%)  1 0/3 (0.00%)  0
Haemoglobin decreased  1  1/31 (3.23%)  1 1/16 (6.25%)  1 0/3 (0.00%)  0
Liver function test increased  1  0/31 (0.00%)  0 1/16 (6.25%)  1 0/3 (0.00%)  0
Metabolism and nutrition disorders       
Decreased appetite  1  0/31 (0.00%)  0 0/16 (0.00%)  0 1/3 (33.33%)  1
Hyperkalaemia  1  0/31 (0.00%)  0 0/16 (0.00%)  0 1/3 (33.33%)  1
Hypomagnesaemia  1  0/31 (0.00%)  0 0/16 (0.00%)  0 1/3 (33.33%)  1
Musculoskeletal and connective tissue disorders       
Gouty arthritis  1  0/31 (0.00%)  0 1/16 (6.25%)  1 0/3 (0.00%)  0
Nervous system disorders       
Dizziness  1  0/31 (0.00%)  0 2/16 (12.50%)  2 0/3 (0.00%)  0
Product Issues       
Device dislocation  1  1/31 (3.23%)  1 1/16 (6.25%)  1 0/3 (0.00%)  0
Device occlusion  1  0/31 (0.00%)  0 1/16 (6.25%)  1 0/3 (0.00%)  0
Psychiatric disorders       
Agitation  1  0/31 (0.00%)  0 1/16 (6.25%)  2 0/3 (0.00%)  0
Depression  1  0/31 (0.00%)  0 1/16 (6.25%)  1 0/3 (0.00%)  0
Restlessness  1  0/31 (0.00%)  0 1/16 (6.25%)  1 0/3 (0.00%)  0
Renal and urinary disorders       
Acute kidney injury  1  0/31 (0.00%)  0 0/16 (0.00%)  0 1/3 (33.33%)  1
Renal cyst  1  0/31 (0.00%)  0 1/16 (6.25%)  1 0/3 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Dyspnoea  1  3/31 (9.68%)  3 0/16 (0.00%)  0 0/3 (0.00%)  0
Epistaxis  1  0/31 (0.00%)  0 1/16 (6.25%)  1 0/3 (0.00%)  0
Haemoptysis  1  0/31 (0.00%)  0 1/16 (6.25%)  1 0/3 (0.00%)  0
Hydrothorax  1  0/31 (0.00%)  0 1/16 (6.25%)  1 0/3 (0.00%)  0
Tachypnoea  1  1/31 (3.23%)  1 1/16 (6.25%)  1 0/3 (0.00%)  0
Tracheal mass  1  0/31 (0.00%)  0 1/16 (6.25%)  1 0/3 (0.00%)  0
Skin and subcutaneous tissue disorders       
Decubitus ulcer  1  1/31 (3.23%)  1 1/16 (6.25%)  1 0/3 (0.00%)  0
Vascular disorders       
Hypotension  1  0/31 (0.00%)  0 1/16 (6.25%)  1 1/3 (33.33%)  1
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
Phone: 1-800-672-6372
EMail: ClinicalTrialsDisclosure@merck.com
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02452047    
Other Study ID Numbers: 7655A-013
2015-000066-62 ( EudraCT Number )
163367 ( Registry Identifier: JAPIC-CTI )
First Submitted: May 20, 2015
First Posted: May 22, 2015
Results First Submitted: July 24, 2018
Results First Posted: October 19, 2018
Last Update Posted: October 19, 2018