Clinical trial NCT02486627: A Study of Plazomicin Compared With Meropenem for the Treatment of Complicated Urinary Tract Infection (cUTI) Including Acute Pyelonephritis (AP)
Official title: A Phase 3, Randomized, Multicenter, Double-Blind Study to Evaluate the Efficacy and Safety of Plazomicin Compared With Meropenem Followed by Optional Oral Therapy for the Treatment of Complicated Urinary Tract Infection (cUTI), Including Acute Pyelonephritis (AP), in Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Complicated Urinary Tract Infection
Acute Pyelonephritis
Keywords: cUTI
AP
ACHN-490
anti-infective
anti-bacterial
antibiotic
anti-microbial
UTI
bacterial infection
Gram-negative
Lead sponsor: Achaogen, Inc.
Sponsor class: INDUSTRY
First posted: 2015-07-01
Enrollment: 609
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This was a randomized, multicenter, multinational, double-blind study comparing the efficacy and safety of plazomicin compared with meropenem followed by optional oral (PO) therapy in the treatment of cUTI, including AP, in adults.


Eligibility criteria: Key Inclusion Criteria:

* Pyuria
* Have a pretreatment baseline urine culture obtained within 36 hours before the start of administration of the first dose of study drug
* Clinical signs and/or symptoms of acute pyelonephritis or complicated urinary tract infection
* Normal renal function or moderate renal impairment

Key Exclusion Criteria:

* Confirmed fungal urinary tract infection at the time of randomization
* Known urinary tract infection or colonization with Gram-positive pathogens
* Current cUTI or AP is known to be caused by a pathogen resistant to meropenem
* Female participants of childbearing potential if they are known to be pregnant or have a positive pregnancy test at screening, breastfeeding, or unable or unwilling to use a highly effective method of birth control during the study and for at least 30 days following the last dose of study medication
* Any rapidly progressing disease or immediately life-threatening illness
* Documented presence of immunodeficiency or an immunocompromised condition
* Documented or known history of otologic surgery or disease including use of hearing aid, head injury leading to otologic damage, Ménière's disease, tumor of the head, neck, or auditory system, perilymphatic fistula, or autoimmune disease of the inner ear, or family history of hearing loss (excluding age-related hearing loss \[onset after age of 65 years\])

Primary outcomes:
measure: Percentage of Patients With Composite of Microbiological Eradication and Clinical Cure in the Microbiological Modified ITT (mMITT) Population at Day 5
timeFrame: Day 5
measure: Percentage of Patients With Composite of Microbiological Eradication and Clinical Cure in the mMITT Population at Test of Cure (TOC)
timeFrame: Day 17 TOC Visit
Secondary outcomes:
measure: Percentage of Patients With Composite of Microbiological Eradication and Clinical Cure in the ME Population at Day 5
timeFrame: Day 5
measure: Percentage of Patients With Composite of Microbiological Eradication and Clinical Cure in the ME Population at TOC
timeFrame: Day 17 TOC Visit
measure: Percentage of Patients With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Up to Day 32
measure: Plasma Pharmacokinetics (PK): Area Under the Curve From 0 to 24 Hours (AUC 0-24h)
timeFrame: Day 3
measure: Plasma PK: Maximum Observed Plasma Drug Concentration (Cmax)
timeFrame: Day 3
measure: Plasma PK: Minimum Observed Plasma Drug Concentration (Cmin)
timeFrame: Day 3
Other outcomes:
Locations:
Study officials:
affiliation: Achaogen, Inc.
name: Lynn E Connolly, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Wagenlehner FME, Cloutier DJ, Komirenko AS, Cebrik DS, Krause KM, Keepers TR, Connolly LE, Miller LG, Friedland I, Dwyer JP; EPIC Study Group. Once-Daily Plazomicin for Complicated Urinary Tract Infections. N Engl J Med. 2019 Feb 21;380(8):729-740. doi: 10.1056/NEJMoa1801467.