Complicated Urinary Tract InfectionPhase 3EPICNCT02486627
A Study of Plazomicin Compared With Meropenem for the Treatment of Complicated Urinary Tract Infection (cUTI) Including Acute Pyelonephritis (AP)
A Phase 3 study testing plazomicin, meropenem and levofloxacin (oral) in people with Complicated Urinary Tract Infection and Acute Pyelonephritis, run by Achaogen, Inc..
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Complicated Urinary Tract Infection, Acute Pyelonephritis
- What is being tested?
- plazomicin, meropenem and levofloxacin (oral)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 609 participants
- Where
- No sites listed yet
- Study dates
- 11 Jan 2016to 22 Sep 2016
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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])
About this study
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
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.
- Being tested
- plazomicin, meropenem, levofloxacin (oral)
- Keywords
- cUTI, AP, ACHN-490, anti-infective, anti-bacterial, antibiotic, anti-microbial, UTI, bacterial infection, Gram-negative
- Medical subject headings
- Bacterial Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
plazomicinDrug
meropenemDrug
levofloxacin (oral)Drug
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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). Receives: Drug: meropenem; Drug: levofloxacin (oral) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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
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.
Measured: Day 5
Percentage of Patients With Composite of Microbiological Eradication and Clinical Cure in the ME Population at TOC
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.
Measured: Day 17 TOC Visit
Percentage of Patients With Treatment-Emergent Adverse Events (TEAEs)
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.
Measured: Up to Day 32
Plasma Pharmacokinetics (PK): Area Under the Curve From 0 to 24 Hours (AUC 0-24h)
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.
Measured: Day 3
Plasma PK: Maximum Observed Plasma Drug Concentration (Cmax)
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.
Measured: Day 3
Plasma PK: Minimum Observed Plasma Drug Concentration (Cmin)
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.
Measured: Day 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2015 (estimated)
- Study start11 Jan 2016
- Primary completion22 Sep 2016
- Study completion22 Sep 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Complicated Urinary Tract InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 609 participants (actual)
Sponsor and investigators
- Lead sponsor
- Achaogen, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Lynn E Connolly, MD, PhD, Study director, Achaogen, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02486627
- Sponsor's protocol ID
- ACHN-490-009
- Other IDs
- 2015-001588-37, U1111-1171-1554, 2015
- Acronym
- EPIC
- Status last verified
- Jul 2018
- First submitted
- 25 Jun 2015
- Last updated
- 23 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 30786187
Study at a glance
From the registry record, last updated by the sponsor on 23 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02486627
- Acronym / sponsor ID
- EPIC / ACHN-490-009
- Keywords
- cUTI, AP, ACHN-490, anti-infective, anti-bacterial, antibiotic, anti-microbial, UTI
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 609 participants (actual)
- Lead sponsor
- Achaogen, Inc.Industry (pharma, biotech, devices)
- Study start
- 11 Jan 2016 (actual)
- Primary completion
- 22 Sep 2016 (actual)
- Study completion
- 22 Sep 2016 (actual)
- First posted
- 1 Jul 2015 (estimated)
- Results
- Posted 23 Aug 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Plazomicin | Experimental | Drug: plazomicin, Drug: levofloxacin (oral)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). |
| Meropenem | Active comparator | Drug: meropenem, Drug: levofloxacin (oral)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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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 (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| plazomicin | Drug | Plazomicin |
| meropenem | Drug | Meropenem |
| levofloxacin (oral) | Drug | Meropenem, Plazomicin |
Primary outcome
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.
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.
6 secondary outcomes
Percentage of Patients With Composite of Microbiological Eradication and Clinical Cure in the ME Population at Day 5
Time frame: Day 5
Percentage of Patients With Composite of Microbiological Eradication and Clinical Cure in the ME Population at TOC
Time frame: Day 17 TOC Visit
Percentage of Patients With Treatment-Emergent Adverse Events (TEAEs)
Time frame: Up to Day 32
Plasma Pharmacokinetics (PK): Area Under the Curve From 0 to 24 Hours (AUC 0-24h)
Time frame: Day 3
Plasma PK: Maximum Observed Plasma Drug Concentration (Cmax)
Time frame: Day 3
Plasma PK: Minimum Observed Plasma Drug Concentration (Cmin)
Time frame: Day 3
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30786187Wagenlehner 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lynn E Connolly, MD, PhD study director
Achaogen, Inc.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing plazomicin, meropenem and levofloxacin (oral) in people with Complicated Urinary Tract Infection and Acute Pyelonephritis, run by Achaogen, Inc..
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Aug 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02486627, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Aug 2018.