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Study of Ceftolozane/Tazobactam (MK-7625A) in Combination With Metronidazole in Japanese Participants With Complicated Intra-abdominal Infection (MK-7625A-013)

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ClinicalTrials.gov Identifier: NCT02739997
Recruitment Status : Completed
First Posted : April 15, 2016
Results First Posted : July 12, 2018
Last Update Posted : August 9, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Intra-abdominal Infection
Complicated Intra-abdominal Infection
Interventions Drug: MK-7625A 1.5 g (ceftolozane 1 g/tazobactam 0.5 g)
Drug: metronidazole 500 mg
Enrollment 100
Recruitment Details Adult participants with complicated intra-abdominal infection (cIAI) were recruited at 37 study sites in Japan.
Pre-assignment Details  
Arm/Group Title MK-7625A + Metronidazole
Hide Arm/Group Description MK-7625A 1.5 g (ceftolozane 1 g + tazobactam 0.5 g) plus metronidazole 500 mg was administered as an IV infusion every 8 hours for 4 to 14 days.
Period Title: Overall Study
Started 100
Completed 98
Not Completed 2
Reason Not Completed
Death             1
Withdrawal by Subject             1
Arm/Group Title MK-7625A + Metronidazole
Hide Arm/Group Description MK-7625A 1.5 g (ceftolozane 1 g + tazobactam 0.5 g) plus metronidazole 500 mg was administered as an IV infusion every 8 hours for 4 to 14 days.
Overall Number of Baseline Participants 100
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 100 participants
61.1  (16.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 100 participants
Female
33
  33.0%
Male
67
  67.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 100 participants
American Indian or Alaska Native
0
   0.0%
Asian
100
 100.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
0
   0.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
1.Primary Outcome
Title Percentage of Participants With Clinical Response (Clinical Cure, Clinical Failure, or Indeterminate) at Test of Cure (TOC)
Hide Description The percentage of participants with clinical responses (cure, failure, or indeterminate) at TOC was determined. Clinical cure was defined as "complete resolution or significant improvement in signs and symptoms of the index infection, such that no additional antibacterial therapy or surgical or drainage procedure is required". Clinical failure was defined as "death related to IAI at any time point; persisting or recurrent infection within the abdomen requiring additional intervention to cure; need for treatment with additional antibiotics for ongoing IAI symptoms; or post-surgical wound infection that requires additional antimicrobial therapy and/or non-routing wound care". Indeterminate was defined as "study data are not available for evaluation for any reason, including death during the study period unrelated to the index infection; or extenuating circumstances that preclude classification as cure or failure".
Time Frame Day 28 (28 days after initiating study therapy)
Hide Outcome Measure Data
Hide Analysis Population Description
Clinically evaluable participants were defined as those who received study therapy for ≥3 days, had 80-120% study therapy compliance, met criteria for cIAI, adhered to study procedures, and had a clinical response at the TOC visit within the specified visit window are included.
Arm/Group Title MK-7625A + Metronidazole
Hide Arm/Group Description:
MK-7625A 1.5 g (ceftolozane 1 g + tazobactam 0.5 g) plus metronidazole 500 mg was administered as an IV infusion every 8 hours for 4 to 14 days.
Overall Number of Participants Analyzed 88
Measure Type: Number
Unit of Measure: Percentage of Participants
Success 92.0
Failure 8.0
Indeterminate 0.0
2.Primary Outcome
Title Percentage of Participants With Adverse Events (AEs)
Hide Description The percentage of participants with ≥1 AEs 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.
Time Frame Up to Day 42 (up to 28 days after completing study therapy)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received ≥1 dose of study therapy are included.
Arm/Group Title MK-7625A + Metronidazole
Hide Arm/Group Description:
MK-7625A 1.5 g (ceftolozane 1 g + tazobactam 0.5 g) plus metronidazole 500 mg was administered as an IV infusion every 8 hours for 4 to 14 days.
Overall Number of Participants Analyzed 100
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
62.0
(51.7 to 71.5)
3.Primary Outcome
Title Percentage of Participants Discontinuing Study Drug Due to AEs
Hide Description The percentage of participants withdrawing from study therapy due to an AE was determined.
Time Frame Up to Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received ≥1 dose of study therapy are included.
Arm/Group Title MK-7625A + Metronidazole
Hide Arm/Group Description:
MK-7625A 1.5 g (ceftolozane 1 g + tazobactam 0.5 g) plus metronidazole 500 mg was administered as an IV infusion every 8 hours for 4 to 14 days.
Overall Number of Participants Analyzed 100
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
0.0
(0.0 to 3.6)
4.Secondary Outcome
Title Percentage of Participants With Clinical Response (Clinical Cure, Clinical Failure, or Indeterminate) at End Of Therapy (EOT)
Hide Description The percentage of participants with clinical responses (cure, failure, or indeterminate) at EOT was determined. Clinical cure was defined as "complete resolution or significant improvement in signs and symptoms of the index infection, such that no additional antibacterial therapy or surgical or drainage procedure is required". Clinical failure was defined as "death related to IAI at any time point; persisting or recurrent infection within the abdomen requiring additional intervention to cure; need for treatment with additional antibiotics for ongoing IAI symptoms; or post-surgical wound infection that requires additional antimicrobial therapy and/or non-routing wound care". Indeterminate was defined as "study data are not available for evaluation for any reason, including death during the study period unrelated to the index infection; or extenuating circumstances that preclude classification as cure or failure".
Time Frame Up to Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Clinically evaluable participants were defined as those who received study therapy for ≥3 days, had 80-120% study therapy compliance, met criteria for cIAI, adhered to study procedures, and had a clinical response at EOT visit within the specified visit window are included.
Arm/Group Title MK-7625A + Metronidazole
Hide Arm/Group Description:
MK-7625A 1.5 g (ceftolozane 1 g + tazobactam 0.5 g) plus metronidazole 500 mg was administered as an IV infusion every 8 hours for 4 to 14 days.
Overall Number of Participants Analyzed 92
Measure Type: Number
Unit of Measure: Percentage of Participants
Success 94.6
Failure 5.4
Indeterminate 0.0
5.Secondary Outcome
Title Percentage of Participants With Clinical Response (Clinical Cure, Clinical Failure, or Indeterminate) at Late Follow-Up (LFU)
Hide Description The percentage of participants with clinical responses (cure, failure, or indeterminate) at LFU was determined. Clinical cure was defined as "complete resolution or significant improvement in signs and symptoms of the index infection, such that no additional antibacterial therapy or surgical or drainage procedure is required". Clinical failure was defined as "death related to IAI at any time point; persisting or recurrent infection within the abdomen requiring additional intervention to cure; need for treatment with additional antibiotics for ongoing IAI symptoms; or post-surgical wound infection that requires additional antimicrobial therapy and/or non-routing wound care". Indeterminate was defined as "study data are not available for evaluation for any reason, including death during the study period unrelated to the index infection; or extenuating circumstances that preclude classification as cure or failure".
Time Frame Up to Day 42 (28 days after completing study therapy)
Hide Outcome Measure Data
Hide Analysis Population Description
Clinically evaluable participants were defined as those who received study therapy for ≥3 days, had 80-120% study therapy compliance, met criteria for cIAI, adhered to study procedures, and had a clinical response at LFU visit within the specified visit window are included.
Arm/Group Title MK-7625A + Metronidazole
Hide Arm/Group Description:
MK-7625A 1.5 g (ceftolozane 1 g + tazobactam 0.5 g) plus metronidazole 500 mg was administered as an IV infusion every 8 hours for 4 to 14 days.
Overall Number of Participants Analyzed 85
Measure Type: Number
Unit of Measure: Percentage of Participants
Success 90.6
Failure 9.4
Indeterminate 0.0
6.Secondary Outcome
Title Percentage of Participants With Microbiological Response (Eradication, Persistence, or Indeterminate) at EOT
Hide Description The percentage of participants with microbiological responses (eradication, persistence, or indeterminate) at EOT was determined. Eradication was defined as "absence of the baseline pathogen in a specimen". Persistence was defined as "presence of the baseline pathogen in a specimen". Indeterminate was defined as "Baseline culture either not obtained or has an assessment of no growth, or any other circumstance that makes it impossible to define the microbiological response".
Time Frame Up to Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Expanded microbiologically evaluable participants were defined as those who received study therapy for ≥3 days, had 80-120% study therapy compliance, met criteria for cIAI, adhered to study procedures, had a microbiological response at the EOT visit within the specified visit window, and have ≥1 identified intra-abdominal pathogen are included.
Arm/Group Title MK-7625A + Metronidazole
Hide Arm/Group Description:
MK-7625A 1.5 g (ceftolozane 1 g + tazobactam 0.5 g) plus metronidazole 500 mg was administered as an IV infusion every 8 hours for 4 to 14 days.
Overall Number of Participants Analyzed 65
Measure Type: Number
Unit of Measure: Percentage of Participants
Eradication 93.8
Persistence 6.2
Indeterminate 0.0
7.Secondary Outcome
Title Percentage of Participants With Microbiological Response (Eradication, Persistence, or Indeterminate) at TOC
Hide Description The percentage of participants with microbiological response (eradication, persistence, or indeterminate) at TOC was determined. Eradication was defined as "absence of the baseline pathogen in a specimen". Persistence was defined as "presence of the baseline pathogen in a specimen". Indeterminate was defined as "Baseline culture either not obtained or has an assessment of no growth, or any other circumstance that makes it impossible to define the microbiological response".
Time Frame Day 28 (28 days after initiating study therapy)
Hide Outcome Measure Data
Hide Analysis Population Description
Expanded microbiologically evaluable participants were defined as those who received study therapy for ≥3 days, had 80-120% study therapy compliance, met criteria for cIAI, adhered to study procedures, had a microbiological response at the TOC visit within the specified visit window, and have ≥1 identified intra-abdominal pathogen are included.
Arm/Group Title MK-7625A + Metronidazole
Hide Arm/Group Description:
MK-7625A 1.5 g (ceftolozane 1 g + tazobactam 0.5 g) plus metronidazole 500 mg was administered as an IV infusion every 8 hours for 4 to 14 days.
Overall Number of Participants Analyzed 61
Measure Type: Number
Unit of Measure: Percentage of Participants
Eradication 90.2
Persistence 9.8
Indeterminate 0.0
8.Secondary Outcome
Title Percentage of Participants With Microbiological Response (Eradication, Persistence, or Indeterminate) by Pathogen at EOT
Hide Description The percentage of participants with per-pathogen microbiological responses at EOT was determined. Individual pathogens were identified at baseline, and the overall percentage of participants with eradication or presumed eradication within each pathogen category are shown.
Time Frame Up to Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Expanded microbiologically evaluable participants were defined as those who received study therapy for ≥3 days, had 80-120% study therapy compliance, met criteria for cIAI, adhered to study procedures, had a microbiological response at the EOT visit within the specified visit window, and have ≥1 identified intra-abdominal pathogen are included.
Arm/Group Title MK-7625A + Metronidazole
Hide Arm/Group Description:
MK-7625A 1.5 g (ceftolozane 1 g + tazobactam 0.5 g) plus metronidazole 500 mg was administered as an IV infusion every 8 hours for 4 to 14 days.
Overall Number of Participants Analyzed 65
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
Gram-Negative Aerobes Number Analyzed 55 participants
94.5
(84.9 to 98.9)
Gram-Positive Aerobes Number Analyzed 40 participants
95.0
(83.1 to 99.4)
Gram-Negative Anaerobes Number Analyzed 44 participants
97.7
(88.0 to 99.9)
Gram-Positive Anaerobes Number Analyzed 21 participants
90.5
(69.6 to 98.8)
9.Secondary Outcome
Title Percentage of Participants With Microbiological Response (Eradication, Persistence, or Indeterminate) by Pathogen at TOC
Hide Description The percentage of participants with per-pathogen microbiological responses at TOC was determined. Individual pathogens were identified at baseline, and the overall percentage of participants with eradication or presumed eradication within each pathogen category are shown.
Time Frame Day 28 (28 days after initiating study therapy)
Hide Outcome Measure Data
Hide Analysis Population Description
Expanded microbiologically evaluable participants were defined as those who received study therapy for ≥3 days, had 80-120% study therapy compliance, met criteria for cIAI, adhered to study procedures, had a microbiological response at the TOC visit within the specified visit window, and have ≥1 identified intra-abdominal pathogen are included.
Arm/Group Title MK-7625A + Metronidazole
Hide Arm/Group Description:
MK-7625A 1.5 g (ceftolozane 1 g + tazobactam 0.5 g) plus metronidazole 500 mg was administered as an IV infusion every 8 hours for 4 to 14 days.
Overall Number of Participants Analyzed 61
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
Gram-Negative Aerobes Number Analyzed 53 participants
90.6
(79.3 to 96.9)
Gram-Positive Aerobes Number Analyzed 38 participants
89.5
(75.2 to 97.1)
Gram-Negative Anaerobes Number Analyzed 42 participants
95.2
(83.8 to 99.4)
Gram-Positive Anaerobes Number Analyzed 20 participants
85.0
(62.1 to 96.8)
Time Frame Up to Day 42
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 who received ≥1 dose of study drug are included.
 
Arm/Group Title MK-7625A + Metronidazole
Hide Arm/Group Description MK-7625A 1.5 g (ceftolozane 1 g + tazobactam 0.5 g) plus metronidazole 500 mg was administered as an IV infusion every 8 hours for 4 to 14 days.
All-Cause Mortality
MK-7625A + Metronidazole
Affected / at Risk (%)
Total   1/100 (1.00%)    
Hide Serious Adverse Events
MK-7625A + Metronidazole
Affected / at Risk (%) # Events
Total   10/100 (10.00%)    
Gastrointestinal disorders   
Gastrooesophageal reflux disease  1  1/100 (1.00%)  1
Ileus  1  2/100 (2.00%)  2
Hepatobiliary disorders   
Cholecystitis  1  1/100 (1.00%)  1
Infections and infestations   
Pneumonia  1  1/100 (1.00%)  1
Sepsis  1  1/100 (1.00%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Adenocarcinoma of colon  1  1/100 (1.00%)  1
Breast cancer  1  1/100 (1.00%)  1
Diffuse large B-cell lymphoma  1  1/100 (1.00%)  1
Psychiatric disorders   
Eating disorder  1  1/100 (1.00%)  1
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%
MK-7625A + Metronidazole
Affected / at Risk (%) # Events
Total   32/100 (32.00%)    
Gastrointestinal disorders   
Constipation  1  6/100 (6.00%)  6
Diarrhoea  1  7/100 (7.00%)  7
Investigations   
Alanine aminotransferase increased  1  11/100 (11.00%)  11
Aspartate aminotransferase increased  1  13/100 (13.00%)  13
Psychiatric disorders   
Insomnia  1  11/100 (11.00%)  11
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: NCT02739997    
Other Study ID Numbers: 7625A-013
MK-7625A-013 ( Other Identifier: Merck Registration Number )
163275 ( Registry Identifier: JAPIC-CTI )
First Submitted: March 30, 2016
First Posted: April 15, 2016
Results First Submitted: June 14, 2018
Results First Posted: July 12, 2018
Last Update Posted: August 9, 2018