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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.

Tracking Information
First Submitted Date  ICMJE March 30, 2016
First Posted Date  ICMJE April 15, 2016
Results First Submitted Date  ICMJE June 14, 2018
Results First Posted Date  ICMJE July 12, 2018
Last Update Posted Date August 9, 2018
Actual Study Start Date  ICMJE April 8, 2016
Actual Primary Completion Date July 28, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 11, 2018)
  • Percentage of Participants With Clinical Response (Clinical Cure, Clinical Failure, or Indeterminate) at Test of Cure (TOC) [ Time Frame: Day 28 (28 days after initiating study therapy) ]
    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".
  • Percentage of Participants With Adverse Events (AEs) [ Time Frame: Up to Day 42 (up to 28 days after completing study therapy) ]
    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.
  • Percentage of Participants Discontinuing Study Drug Due to AEs [ Time Frame: Up to Day 14 ]
    The percentage of participants withdrawing from study therapy due to an AE was determined.
Original Primary Outcome Measures  ICMJE
 (submitted: April 11, 2016)
  • Percentage of Participants With Clinical Response (Clinical Cure, Clinical Failure, or Indeterminate) at Test of Cure (TOC) [ Time Frame: up to 28 days after first dose of study drug (up to 28 days) ]
  • Percentage of Participants With Adverse Events (AEs) [ Time Frame: From time of first dose until the end of follow-up (up to 42 days) ]
  • Percentage of Participants Discontinuing Study Drug Due to AEs [ Time Frame: up to 14 days after the first dose of study drug (up to 14 days) ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 11, 2018)
  • Percentage of Participants With Clinical Response (Clinical Cure, Clinical Failure, or Indeterminate) at End Of Therapy (EOT) [ Time Frame: Up to Day 14 ]
    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".
  • Percentage of Participants With Clinical Response (Clinical Cure, Clinical Failure, or Indeterminate) at Late Follow-Up (LFU) [ Time Frame: Up to Day 42 (28 days after completing study therapy) ]
    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".
  • Percentage of Participants With Microbiological Response (Eradication, Persistence, or Indeterminate) at EOT [ Time Frame: Up to Day 14 ]
    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".
  • Percentage of Participants With Microbiological Response (Eradication, Persistence, or Indeterminate) at TOC [ Time Frame: Day 28 (28 days after initiating study therapy) ]
    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".
  • Percentage of Participants With Microbiological Response (Eradication, Persistence, or Indeterminate) by Pathogen at EOT [ Time Frame: Up to Day 14 ]
    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.
  • Percentage of Participants With Microbiological Response (Eradication, Persistence, or Indeterminate) by Pathogen at TOC [ Time Frame: Day 28 (28 days after initiating study therapy) ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 11, 2016)
  • Percentage of Participants With Clinical Response (Clinical Cure, Clinical Failure, or Indeterminate) at End Of Therapy (EOT) and Late Follow-Up (LFU) [ Time Frame: up to 42 days after first dose of study drug (up to 42 days) ]
  • Percentage of Participants With Microbiological Response (Eradication, Persistence, or Indeterminate) at EOT and TOC [ Time Frame: up to 28 days after first dose of study drug (up to 28 days) ]
  • Percentage of Participants with Microbiological Response (Eradication, Persistence, or Indeterminate) by Pathogen at EOT and TOC [ Time Frame: up to 28 days after first dose of study drug (up to 28 days) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Ceftolozane/Tazobactam (MK-7625A) in Combination With Metronidazole in Japanese Participants With Complicated Intra-abdominal Infection (MK-7625A-013)
Official Title  ICMJE A Multicenter, Open-label, Noncomparative, Japanese Phase III Study to Assess the Efficacy and Safety of Ceftolozane/Tazobactam (MK-7625A) Used in Combination With Metronidazole in Japanese Patients With Complicated Intra-abdominal Infection.
Brief Summary This is a Phase 3, multi-site, non-randomized, open-label study evaluating the safety and efficacy of MK-7625A 1.5 g (ceftolozane 1 g/tazobactam 0.5 g) plus metronidazole 500 mg for the treatment of Complicated Intra-abdominal Infections (cIAI) in Japanese participants. Efficacy will be primarily assessed by clinical response defined as complete resolution or significant improvement in signs and symptoms of the index infection.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Intra-abdominal Infection
  • Complicated Intra-abdominal Infection
Intervention  ICMJE
  • Drug: MK-7625A 1.5 g (ceftolozane 1 g/tazobactam 0.5 g)
    MK-7625A 1.5 g (ceftolozane 1 g/tazobactam 0.5 g) administered as an intravenous (IV) infusion
  • Drug: metronidazole 500 mg
    metronidazole 500 mg administered as an IV infusion
Study Arms  ICMJE Experimental: MK-7625A + metronidazole
MK-7625A 1.5 g (ceftolozane 1 g/tazobactam 0.5 g) plus metronidazole 500 mg administered as an intravenous (IV) infusion every 8 hours for 4 to 14 days. The dose may be reduced to 750 mg (ceftolozane 500 mg/tazobactam 250 mg) for participants with a creatinine clearance (CrCl) of 30-50 mL/min.
Interventions:
  • Drug: MK-7625A 1.5 g (ceftolozane 1 g/tazobactam 0.5 g)
  • Drug: metronidazole 500 mg
Publications * Mikamo H, Monden K, Miyasaka Y, Horiuchi T, Fujimoto G, Fukuhara T, Yoshinari T, Rhee EG, Shizuya T. The efficacy and safety of tazobactam/ceftolozane in combination with metronidazole in Japanese patients with complicated intra-abdominal infections. J Infect Chemother. 2019 Feb;25(2):111-116. doi: 10.1016/j.jiac.2018.10.012. Epub 2018 Dec 6.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 11, 2016)
100
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE July 28, 2017
Actual Primary Completion Date July 28, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Has one of the following diagnoses with evidence of intra-peritoneal infection: cholecystitis (including gangrenous cholecystitis) with rupture, perforation, or progression of the infection beyond the gallbladder wall; diverticular disease with perforation or abscess; appendiceal perforation or periappendiceal abscess; acute gastric or duodenal perforation, traumatic perforation of the intestine; peritonitis due to perforated viscus or following a prior operative procedure; or Intra-abdominal abscess (including liver and spleen).
  • Has evidence of systemic infection
  • Had or has plans to have surgical intervention within 24 hours of the first dose of study drug
  • Has radiographic evidence of perforation or abscess if enrolled preoperatively
  • Is able to have intra-abdominal specimen taken at baseline for the microbiological assessment
  • Female participants of child bearing potential must not be pregnant (negative human chorionic gonadotropin test) or breastfeeding and must agree to use adequate contraception for the duration of the study and up to 35 days after the last dose of study drug
  • Male participants must agree to use adequate contraception for the duration of the study and up to 75 days after the last dose of study drug

Exclusion Criteria:

  • Has simple appendicitis; abdominal wall abscess; small bowel obstruction or ischemic bowel disease without perforation; spontaneous bacterial peritonitis associated with cirrhosis and chronic ascites; acute suppurative cholangitis; infected necrotizing pancreatitis; pancreatic abscess; infectious mononucleosis; cystic fibrosis; or pelvic infections
  • Has complicated intra-abdominal infection managed by staged abdominal repair (STAR) or open abdomen drainage
  • Has had acute gastric or duodenal perforation (≤ 24 hours after) or traumatic perforation of the intestine (≤ 12 hours after) operated on after the perforation occurred
  • Is expected to be cured by only surgical intervention without use of systemic antibacterial therapy
  • Has used systemic antibacterial therapy for intra-abdominal infection for more than 24 hours prior to the first dose of study drug, unless there is a documented treatment failure with such therapy
  • Has severe impairment of renal function (estimated CrCl < 30 mL/minute), or requirement for peritoneal dialysis, hemodialysis or hemofiltration, or oliguria (< 20 mL/hour urine output over 24 hours)
  • Has a concomitant infection at the time of randomization, which requires non-study systemic antibacterial therapy in addition to study drug with the exception of an antibacterial with Gram-positive activity only (vancomycin, teicoplanin, linezolid and daptomycin)
  • Has used any postoperative non-study antibacterial therapy if enrolled preoperatively
  • Has used more than 1 dose of non-study antibacterial therapy following surgery if enrolled postoperatively
  • Has hepatic disease
  • Is unlikely to survive the 4 to 5 week study period
  • Has organic brain or spinal cord disease
  • Has any rapidly-progressing disease or immediately life-threatening illness
  • Has an immunocompromising condition (i.e., AIDS, hematological malignancy, or bone marrow transplantation, or immunosuppressive therapy) or is receiving ≥ 40 mg of prednisone per day administered continuously for > 14 days prior to study start
  • Has a history of any moderate or severe hypersensitivity or allergic reaction to any beta-lactam (β-lactam) antibacterial, including cephalosporins, carbapenems, penicillins, or β-lactamase inhibitors, or metronidazole, or nitroimidazole derivatives
  • Is receiving or has received disulfiram within 14 days before receiving study drug or who is currently receiving probenecid
  • Has participated in any clinical study of an investigational product within 30 days prior to the first dose of study drug
  • Has previously participated in any study of ceftolozane or MK-7625A.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries Japan
 
Administrative Information
NCT Number  ICMJE NCT02739997
Other Study ID Numbers  ICMJE 7625A-013
MK-7625A-013 ( Other Identifier: Merck Registration Number )
163275 ( Registry Identifier: JAPIC-CTI )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme Corp.
PRS Account Merck Sharp & Dohme Corp.
Verification Date July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP