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NCT02486627: EPIC

A Study of Plazomicin Compared With Meropenem for the Treatment of Complicated Urinary Tract Infection (cUTI) Including Acute Pyelonephritis (AP)

Completed Phase 3 Results posted Last updated 23 August 2018
What this trial tests

Phase 3 trial testing plazomicin in Complicated Urinary Tract Infection in 609 participants. Completed in 22 September 2016.

Timeline
11 January 2016
Primary endpoint
22 September 2016
22 September 2016

Quick facts

Lead sponsorAchaogen, Inc.
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment609
Start date11 January 2016
Primary completion22 September 2016
Estimated completion22 September 2016

Drugs / interventions tested

Conditions studied

Sponsor

Achaogen, Inc. — full company profile →

Who can join

18 and older, any sex, with Complicated Urinary Tract Infection or Acute Pyelonephritis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Patients With Composite of Microbiological Eradication and Clinical Cure in the Microbiological Modified ITT (mMITT) Population at Day 5 Primary · Day 5

Microbiological eradication was defined as a urine culture that showed the pathogen found at baseline at ≥10\^5 colony forming units per milliliter (CFU/mL) was reduced to \<10\^4 CFU/mL. Clinical Cure at Day 5: marked improvement evidenced by complete resolution or return to premorbid levels or reduction in severity of all core baseline symptoms with worsening of none, and no new symptoms developed. Failure: Lack of improvement in core baseline symptoms of cUTI or development of new core symptoms of cUTI; adverse event (AE) requiring the discontinuation of study drug and the patient required

Composite Cure
GroupValue95% CI
Plazomicin88
Meropenem91.4
Composite Failure
GroupValue95% CI
Plazomicin10.5
Meropenem7.6
Indeterminate
GroupValue95% CI
Plazomicin1.6
Meropenem1
Percentage of Patients With Composite of Microbiological Eradication and Clinical Cure in the mMITT Population at Test of Cure (TOC) Primary · Day 17 TOC Visit

Microbiological eradication was defined as a urine culture that showed the pathogen found at baseline at ≥10\^5 CFU/mL was reduced to \<10\^4 CFU/mL. Clinical Cure at TOC Visit: the complete resolution or return to premorbid levels of core symptoms of cUTI and no new symptoms develop, and no use of non-study antibiotic therapy for the current cUTI. Failure: Persistence of one or more core symptom of infection or reappearance of or development of new core symptoms that require alternative non-study antibiotic therapy for the current cUTI. Indeterminate: Insufficient data are available to allow

Composite Cure
GroupValue95% CI
Plazomicin81.7
Meropenem70.1
Composite Failure
GroupValue95% CI
Plazomicin15.2
Meropenem25.9
Indeterminate
GroupValue95% CI
Plazomicin3.1
Meropenem4.1
Percentage of Patients With Composite of Microbiological Eradication and Clinical Cure in the ME Population at Day 5 Secondary · Day 5

Microbiological eradication: urine culture showed the pathogen found at baseline at ≥10\^5 CFU/mL was reduced to \<10\^4 CFU/mL. Clinical Cure Day 5: Marked improvement defined as complete resolution or return to premorbid levels or reduction in severity of all core baseline symptoms with worsening of none, and no new symptoms develop. Failure Day 5: Lack of improvement in core baseline symptoms of cUTI or development of new core symptoms of cUTI; AE requiring the discontinuation of study drug and the patient required alternative non-study antibiotic therapy for the current cUTI.

Day 5: Composite Cure
GroupValue95% CI
Plazomicin89.4
Meropenem94.2
Day 5: Composite Failure
GroupValue95% CI
Plazomicin10.6
Meropenem5.8
Percentage of Patients With Composite of Microbiological Eradication and Clinical Cure in the ME Population at TOC Secondary · Day 17 TOC Visit

Microbiological eradication: urine culture showed the pathogen found at baseline at ≥10\^5 CFU/mL was reduced to \<10\^4 CFU/mL. Clinical Cure TOC: Complete resolution or return to premorbid levels of core symptoms of cUTI and no new symptoms develop, and no use of non-study antibiotic therapy for the current cUTI. Failure TOC: Persistence of one or more core symptom of infection or reappearance of or development of new core symptoms that require alternative non-study antibiotic therapy for the current cUTI.

TOC: Composite Cure
GroupValue95% CI
Plazomicin84.9
Meropenem75.1
TOC: Composite Failure
GroupValue95% CI
Plazomicin15.1
Meropenem24.9
Percentage of Patients With Treatment-Emergent Adverse Events (TEAEs) Secondary · Up to Day 32

An adverse event (AE) is any untoward medical occurrence associated with the use of a drug in humans, whether or not it is considered to be drug related. An AE (also referred to as an adverse experience) can be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, and it does not imply any judgment about causality. Adverse events also include the exacerbation or worsening of a condition present at screening other than the index infection for which the patient was enrolled in the study. A TEAE is any AE that n

GroupValue95% CI
Plazomicin19.5
Meropenem21.6
Plasma Pharmacokinetics (PK): Area Under the Curve From 0 to 24 Hours (AUC 0-24h) Secondary · Day 3

PK blood samples were collected on Day 3 (plus or minus 1 day) of study drug administration for the determination of plazomicin concentrations in plazomicin-treated patients.

GroupValue95% CI
Plazomicin234± 38.5
Plasma PK: Maximum Observed Plasma Drug Concentration (Cmax) Secondary · Day 3

PK blood samples were collected on Day 3 (plus or minus 1 day) of study drug administration for the determination of plazomicin concentrations in plazomicin-treated patients.

GroupValue95% CI
Plazomicin46.6± 43
Plasma PK: Minimum Observed Plasma Drug Concentration (Cmin) Secondary · Day 3

PK blood samples were collected on Day 3 (plus or minus 1 day) of study drug administration for the determination of plazomicin concentrations in plazomicin-treated patients.

GroupValue95% CI
Plazomicin0.88± 95.4

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to Day 32. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Plazomicin
Serious: 5/303 (2%)
Deaths: 1/303
Meropenem
Serious: 5/301 (2%)
Deaths: 0/301

Serious adverse events (12 terms)

ReactionSystemPlazomicinMeropenem
Acute kidney injuryRenal and urinary disorders
Metastatic neoplasmNeoplasms benign, malignant and unspecified (incl cysts and polyps)
PyrexiaGeneral disorders
PancreatitisGastrointestinal disorders
Calculus urinaryRenal and urinary disorders
Clostridium difficile colitisInfections and infestations
OrchitisInfections and infestations
PneumoniaInfections and infestations
Pyelonephritis acuteInfections and infestations
Septic shockInfections and infestations
Urinary tract infectionInfections and infestations
UrosepsisInfections and infestations

Most-reported serious reactions: Acute kidney injury, Metastatic neoplasm, Pyrexia, Pancreatitis, Calculus urinary, Clostridium difficile colitis, Orchitis, Pneumonia.

Data from ClinicalTrials.gov NCT02486627 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Infections Caused by Carbapenem-Resistant <i>Enterobacteriaceae</i>: An Update on Therapeutic Options.
    Sheu CC, Chang YT, Lin SY, Chen YH, et al · · 2019 · cited 334× · PMID 30761114 · DOI 10.3389/fmicb.2019.00080
  2. The "Old" and the "New" Antibiotics for MDR Gram-Negative Pathogens: For Whom, When, and How.
    Karaiskos I, Lagou S, Pontikis K, Rapti V, et al · · 2019 · cited 185× · PMID 31245348 · DOI 10.3389/fpubh.2019.00151
  3. Once-Daily Plazomicin for Complicated Urinary Tract Infections.
    Wagenlehner FME, Cloutier DJ, Komirenko AS, Cebrik DS, et al · · 2019 · cited 139× · PMID 30786187 · DOI 10.1056/nejmoa1801467
  4. Aminoglycoside Revival: Review of a Historically Important Class of Antimicrobials Undergoing Rejuvenation.
    Serio AW, Keepers T, Andrews L, Krause KM. · · 2018 · cited 107× · PMID 30447062 · DOI 10.1128/ecosalplus.esp-0002-2018
  5. Towards the Prevention of Aminoglycoside-Related Hearing Loss.
    O'Sullivan ME, Perez A, Lin R, Sajjadi A, et al · · 2017 · cited 68× · PMID 29093664 · DOI 10.3389/fncel.2017.00325
  6. <i>In Vitro</i> Activity of Plazomicin against Gram-Negative and Gram-Positive Isolates Collected from U.S. Hospitals and Comparative Activities of Aminoglycosides against Carbapenem-Resistant Enterobacteriaceae and Isolates Carrying Carbapenemase Genes.
    Castanheira M, Davis AP, Mendes RE, Serio AW, et al · · 2018 · cited 54× · PMID 29866862 · DOI 10.1128/aac.00313-18
  7. Association between the Presence of Aminoglycoside-Modifying Enzymes and In Vitro Activity of Gentamicin, Tobramycin, Amikacin, and Plazomicin against Klebsiella pneumoniae Carbapenemase- and Extended-Spectrum-β-Lactamase-Producing Enterobacter Species.
    Haidar G, Alkroud A, Cheng S, Churilla TM, et al · · 2016 · cited 35× · PMID 27297487 · DOI 10.1128/aac.00869-16
  8. Plazomicin against Multidrug-Resistant Bacteria: A Scoping Review.
    Alfieri A, Di Franco S, Donatiello V, Maffei V, et al · · 2022 · cited 21× · PMID 36556314 · DOI 10.3390/life12121949

Verify or expand the search:

Other trials of plazomicin

Trials testing the same drug.

Other recruiting trials for Complicated Urinary Tract Infection

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Other Achaogen, Inc. trials

Trials by the same sponsor.

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