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

NCT02486627 | Completed Phase 3 Results DMC

• 3 other identifiers: ACHN-490-0092015-001588-37U1111-1171-1554
• Study Type: interventional
• Target: 609
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Complicated Urinary Tract Infection; Acute Pyelonephritis

Keywords

cUTI; AP; ACHN-490; anti-infective; anti-bacterial; antibiotic; anti-microbial; UTI; bacterial infection; Gram-negative

Outcome Measures

Primary Outcomes (2)

• Percentage of Patients With Composite of Microbiological Eradication and Clinical Cure in the Microbiological Modified ITT (mMITT) Population at 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 alternative non-study antibiotic therapy for the current cUTI. Indeterminate: Insufficient data are available to allow an evaluation of clinical outcome for any reason.

  Day 5

• Percentage of Patients With Composite of Microbiological Eradication and Clinical Cure in the mMITT Population at Test of Cure (TOC)

  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 an evaluation of clinical outcome for any reason.

  Day 17 TOC Visit

Secondary Outcomes (6)

• Percentage of Patients With Composite of Microbiological Eradication and Clinical Cure in the ME Population at Day 5

  Day 5

• Percentage of Patients With Composite of Microbiological Eradication and Clinical Cure in the ME Population at TOC

  Day 17 TOC Visit

• Percentage of Patients With Treatment-Emergent Adverse Events (TEAEs)

  Up to Day 32

• Plasma Pharmacokinetics (PK): Area Under the Curve From 0 to 24 Hours (AUC 0-24h)

  Day 3

• Plasma PK: Maximum Observed Plasma Drug Concentration (Cmax)

  Day 3

Study Arms (2)

Plazomicin

EXPERIMENTAL

Patients received 15 milligrams per kilogram (mg/kg) plazomicin as an intravenous (IV) infusion once daily followed by matching placebo infusions 8 and 16 hours later. After a minimum of 4 days of IV plazomicin, patients could switch to 250 or 500 mg oral levofloxacin for a total duration of 7 to 10 days (IV plus oral).

Drug: plazomicin; Drug: levofloxacin (oral)

Meropenem

ACTIVE COMPARATOR

Patients received 1.0 g meropenem as an IV infusion every 8 hours (q8h). After a minimum of 4 days of IV meropenem, patients could switch to 250 or 500 mg oral levofloxacin for a total duration of 7 to 10 days (IV plus oral).

Drug: meropenem; Drug: levofloxacin (oral)

Interventions

plazomicin DRUG

Plazomicin

meropenem DRUG

Meropenem

levofloxacin (oral) DRUG

Meropenem; Plazomicin

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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 \[onset after age of 65 years\])

Sponsors & Collaborators

• Achaogen, Inc.: lead

Related Publications (1)

• 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.

  PMID: 30786187 DERIVED

MeSH Terms

Conditions

Bacterial Infections

Interventions

plazomicin; Meropenem; Levofloxacin

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Thienamycins; Carbapenems; beta-Lactams; Lactams; Amides; Organic Chemicals; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Ofloxacin; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines

Results Point of Contact

• Title: Clinical Trials Registration Group
• Organization: Achaogen, Inc.

clinical-trials@achaogen.com

Study Officials

• Lynn E Connolly, MD, PhD

  Achaogen, Inc.

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2015
• First Posted: July 1, 2015
• Study Start: January 11, 2016
• Primary Completion: September 22, 2016
• Study Completion: September 22, 2016
• Last Updated: August 23, 2018
• Results First Posted: August 23, 2018

Record last verified: 2018-07