Study of Ceftolozane/Tazobactam (MK-7625A) in Japanese Participants With Uncomplicated Pyelonephritis and Complicated Urinary Tract Infection (MK-7625A-014)

NCT02728089 | Completed Phase 3 Results

• 3 other identifiers: 7625A-014MK-7625A-014163276
• Study Type: interventional
• Target: 115
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Urinary Tract Infection (UTI); Complicated Urinary Tract Infection; Pyelonephritis; Uncomplicated Pyelonephritis

Outcome Measures

Primary Outcomes (3)

• Percentage of Participants With Microbiological Response of Eradication at Test of Cure (TOC)

  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.

  Day 14 (14 days post first dose of study drug)

• Percentage of Participants Who Report 1 or More Adverse Event (AE)

  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.

  Up to 42 days post first dose of study drug

• Percentage of Participants Discontinuing Study Drug Due to an AE

  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.

  Up to 7 days after the first dose of study drug

Secondary Outcomes (9)

• 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)

Study Arms (1)

MK-7625A

EXPERIMENTAL

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.

Drug: MK-7625A 1.5 g (ceftolozane 1 g/tazobactam 0.5 g)

Interventions

MK-7625A 1.5 g (ceftolozane 1 g/tazobactam 0.5 g) DRUG

MK-7625A 1.5 g (ceftolozane 1 g/tazobactam 0.5 g) administered as an intravenous (IV) infusion

MK-7625A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• Arakawa S, Kawahara K, Kawahara M, Yasuda M, Fujimoto G, Sato A, Yokokawa R, Yoshinari T, Rhee EG, Aoyama N. The efficacy and safety of tazobactam/ceftolozane in Japanese patients with uncomplicated pyelonephritis and complicated urinary tract infection. J Infect Chemother. 2019 Feb;25(2):104-110. doi: 10.1016/j.jiac.2018.10.009. Epub 2018 Nov 9.

  PMID: 30420153 BACKGROUND

MeSH Terms

Conditions

Urinary Tract Infections; Pyelonephritis

Interventions

ceftolozane; Tazobactam

Condition Hierarchy (Ancestors)

Infections; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Nephritis, Interstitial; Nephritis; Kidney Diseases; Pyelitis

Intervention Hierarchy (Ancestors)

Penicillanic Acid; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Sulfones; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2016
• First Posted: April 5, 2016
• Study Start: April 14, 2016
• Primary Completion: September 5, 2017
• Study Completion: September 5, 2017
• Last Updated: February 5, 2019
• Results First Posted: September 19, 2018

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will share