Study of Ceftolozane/Tazobactam (MK-7625A) in Combination With Metronidazole in Japanese Participants With Complicated Intra-abdominal Infection (MK-7625A-013)
Condition: Intra-abdominal Infection; Complicated Intra-abdominal Infection
MeSH terms: Infections; Communicable Diseases; Intraabdominal Infections
Intervention: MK-7625A 1.5 g (ceftolozane 1 g/tazobactam 0.5 g); metronidazole 500 mg
Intervention description: MK-7625A 1.5 g (ceftolozane 1 g/tazobactam 0.5 g) administered as an intravenous (IV) infusion; metronidazole 500 mg administered as an IV infusion
Intervention MeSH terms: Metronidazole; Tazobactam; Ceftolozane
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 100.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        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.