Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 4 of 9 for:    ACHN-490 OR Plazomicin

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02486627
Recruitment Status : Completed
First Posted : July 1, 2015
Results First Posted : August 23, 2018
Last Update Posted : August 23, 2018
Sponsor:
Information provided by (Responsible Party):
Achaogen, Inc.

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.

Condition or disease Intervention/treatment Phase
Complicated Urinary Tract Infection Acute Pyelonephritis Drug: plazomicin Drug: meropenem Drug: levofloxacin (oral) Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 609 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : January 11, 2016
Actual Primary Completion Date : September 22, 2016
Actual Study Completion Date : September 22, 2016

Resource links provided by the National Library of Medicine

Drug Information available for: Meropenem

Arm Intervention/treatment
Experimental: Plazomicin
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)
Active Comparator: Meropenem
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)



Primary Outcome Measures :
  1. Percentage of Patients With Composite of Microbiological Eradication and Clinical Cure in the Microbiological Modified ITT (mMITT) Population at Day 5 [ Time Frame: 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.

  2. Percentage of Patients With Composite of Microbiological Eradication and Clinical Cure in the mMITT Population at Test of Cure (TOC) [ Time Frame: 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 an evaluation of clinical outcome for any reason.


Secondary Outcome Measures :
  1. Percentage of Patients With Composite of Microbiological Eradication and Clinical Cure in the ME Population at Day 5 [ Time Frame: 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.

  2. Percentage of Patients With Composite of Microbiological Eradication and Clinical Cure in the ME Population at TOC [ Time Frame: 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.

  3. Percentage of Patients With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: 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 newly appeared, increased in frequency, or worsened in severity following initiation of study drug.

  4. Plasma Pharmacokinetics (PK): Area Under the Curve From 0 to 24 Hours (AUC 0-24h) [ Time Frame: 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.

  5. Plasma PK: Maximum Observed Plasma Drug Concentration (Cmax) [ Time Frame: 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.

  6. Plasma PK: Minimum Observed Plasma Drug Concentration (Cmin) [ Time Frame: 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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])

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02486627


Sponsors and Collaborators
Achaogen, Inc.
Investigators
Layout table for investigator information
Study Director: Lynn E Connolly, MD, PhD Achaogen, Inc.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Achaogen, Inc.
ClinicalTrials.gov Identifier: NCT02486627     History of Changes
Other Study ID Numbers: ACHN-490-009
2015-001588-37 ( EudraCT Number )
U1111-1171-1554 ( Other Identifier: WHO )
First Posted: July 1, 2015    Key Record Dates
Results First Posted: August 23, 2018
Last Update Posted: August 23, 2018
Last Verified: July 2018

Keywords provided by Achaogen, Inc.:
cUTI
AP
ACHN-490
anti-infective
anti-bacterial
antibiotic
anti-microbial
UTI
bacterial infection
Gram-negative

Additional relevant MeSH terms:
Layout table for MeSH terms
Infection
Communicable Diseases
Urinary Tract Infections
Pyelonephritis
Urologic Diseases
Nephritis, Interstitial
Nephritis
Kidney Diseases
Pyelitis
Levofloxacin
Ofloxacin
Meropenem
Anti-Infective Agents, Urinary
Anti-Infective Agents
Renal Agents
Anti-Bacterial Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Cytochrome P-450 CYP1A2 Inhibitors
Cytochrome P-450 Enzyme Inhibitors