A Multicenter, Open-label, Noncomparative, Japanese Phase III Study to Assess the Efficacy and Safety of Ceftolozane/Tazobactam (MK-7625A) in Japanese Patients With Uncomplicated Pyelonephritis and Complicated Urinary Tract Infection
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 115
- Primary Endpoint
- Percentage of Participants With Microbiological Response of Eradication at Test of Cure (TOC)
Study Overview
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) for the treatment of complicated urinary tract infection (cUTI) including pyelonephritis (uncomplicated or complicated pyelonephritis and complicated lower urinary tract infection) in Japanese participants. Efficacy will be primarily assessed by microbiological response defined as eradication of the baseline pathogen or pathogens.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Japanese males or females who need hospitalization
- •Clinical signs and/or symptoms of urinary tract infection (UTI) at screening visit, either one of the following:
- •Pyelonephritis (uncomplicated or complicated)
- •Complicated lower UTI (cUTI)
- •Has a pretreatment baseline urine culture specimen obtained within 24 hours of start of study drug
- •Requires IV antibacterial therapy for the treatment of the presumed UTI
- •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 a history of recent or recurrent Gram-positive organism UTI suggesting colonization, or participant with UTI that shows or suspects the presence of a Gram-positive organism only
- •Has a history of any moderate or severe hypersensitivity or allergic reaction to any Beta-lactam antibacterial including cephalosporins, carbapenems and penicillins, or tazobactam
- •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, linezolid, daptomycin and teicoplanin)
- •Is receiving probenecid
- •Is currently receiving bladder infusions with topical urinary antiseptics or antibacterial agents
- •Has received any amount of potentially therapeutic antibacterial therapy after collection of the pretreatment baseline urine culture and before administration of the first dose of study drug.
- •Has received any dose of a potentially therapeutic antibacterial agent for the treatment of the current UTI within 48 hours before the pretreatment baseline urine is obtained
- •Intractable urinary infection at baseline that would require more than 7 days of study drug
- •Has complete, permanent obstruction of the urinary tract.
- •Has confirmed fungal urinary tract infection at time of randomization (with ≥ 10^3 fungal colony forming units /mL)
- •Has permanent indwelling bladder catheter or urinary stent including nephrostomy
- •Has suspected or confirmed perinephric or intrarenal abscess
- •Has suspected or confirmed prostatitis, urethritis, or epididymitis
- •Has ileal loop or known vesico-ureteral reflux
- •Severe impairment of renal function including an estimated CrCl < 30 mL/min, requirement for peritoneal dialysis, hemodialysis or hemofiltration, or oliguria (< 20 mL/hr urine output over 24 hours)
- •Has urinary catheter that is not scheduled to be removed before the end of therapy
- •Has any rapidly progressing disease or immediately life-threatening illness including acute hepatic failure, respiratory failure, and septic shock
- •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 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.
Arms & Interventions
MK-7625A
MK-7625A 1.5 g (ceftolozane 1 g/tazobactam 0.5 g) administered as an intravenous (IV) infusion every 8 hours for 7 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.
Intervention: MK-7625A 1.5 g (ceftolozane 1 g/tazobactam 0.5 g) (Drug)
Outcomes
Primary Outcomes
Percentage of Participants With Microbiological Response of Eradication at Test of Cure (TOC)
Time Frame: Day 14 (14 days post first dose of study drug)
The per-pathogen microbiological outcome was determined for each uropathogen isolated at baseline at TOC (14 days post first dose). Microbiological outcome was classified as "eradication", "persistence" or "indeterminate." A successful microbiological response was "eradication" which was defined as urine culture showed all uropathogens found at baseline at ≥10\^5 colony-forming unit (CFU)/mL were reduced to \<10\^4 CFU/mL. If the outcome for any uropathogen was" persistence" (CFU/mL not reduced the result was classified as unsuccessful. Participants with responses reported as "indeterminate" were excluded.
Percentage of Participants Who Report 1 or More Adverse Event (AE)
Time Frame: Up to 42 days post first dose of study drug
An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not it was considered related to the medicinal product. The percentage of participants that reported at least 1 AE was summarized.
Percentage of Participants Discontinuing Study Drug Due to an AE
Time Frame: Up to 7 days after the first dose of study drug
An AE was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, regardless of whether or not considered related to the medicinal product. The percentage of participants that had study drug discontinued during the study due to an AE was summarized.
Secondary Outcomes
- Percentage of Participants With Microbiological Response of Eradication at End Of Therapy (EOT)(Day 7 (7 days post first dose of study drug))
- Percentage of Participants With Microbiological Response of Eradication at Late Follow-up (LFU)(Day 42 (42 days post first dose of study drug))
- Percentage of Participants With Clinical Response of Clinical Cure at TOC(Day 14 (14 days post first dose of study drug))
- Percentage of Participants With Clinical Response of Clinical Cure at EOT(Day 7 (7 days post first dose of study drug))
- Percentage of Participants With Clinical Response of Clinical Cure at LFU(Day 42 (42 days post first dose of study drug))
- Percentage of Participants With a Composite Response of Both Eradication and Clinical Cure at TOC(Day 14 (14 days post first dose of study drug))
- Percentage of Participants With Microbiological Response of Eradication, by Pathogen at EOT(Day 7 (7 days post first dose of study drug))
- Percentage of Participants With Microbiological Response of Eradication by Pathogen at TOC(Day 14 (14 days post first dose of study drug))
- Percentage of Participants With Microbiological Response of Eradication by Pathogen at LFU(Day 42 (42 days post first dose of study drug))