Trial Outcomes & Findings for A Study of Plazomicin Compared With Meropenem for the Treatment of Complicated Urinary Tract Infection (cUTI) Including Acute Pyelonephritis (AP) (NCT NCT02486627)
NCT ID: NCT02486627
Last Updated: 2018-08-23
Results Overview
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.
COMPLETED
PHASE3
609 participants
Day 5
2018-08-23
Participant Flow
Participant milestones
| Measure |
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).
|
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).
|
|---|---|---|
|
Overall Study
STARTED
|
306
|
303
|
|
Overall Study
COMPLETED
|
299
|
294
|
|
Overall Study
NOT COMPLETED
|
7
|
9
|
Reasons for withdrawal
| Measure |
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).
|
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).
|
|---|---|---|
|
Overall Study
Death
|
1
|
0
|
|
Overall Study
Other Unspecified
|
0
|
2
|
|
Overall Study
Consent Withdrawn by Participant
|
4
|
3
|
|
Overall Study
Significant Participant Noncompliance
|
1
|
1
|
|
Overall Study
Lost to Follow-up
|
1
|
3
|
Baseline Characteristics
A Study of Plazomicin Compared With Meropenem for the Treatment of Complicated Urinary Tract Infection (cUTI) Including Acute Pyelonephritis (AP)
Baseline characteristics by cohort
| Measure |
Plazomicin
n=306 Participants
Patients received up to 15 mg/kg plazomicin as an 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
n=303 Participants
Patients received 1.0 g meropenem as an IV infusion 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).
|
Total
n=609 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
58.2 years
STANDARD_DEVIATION 18.29 • n=99 Participants
|
59 years
STANDARD_DEVIATION 17.62 • n=107 Participants
|
58.6 years
STANDARD_DEVIATION 17.95 • n=206 Participants
|
|
Sex: Female, Male
Female
|
171 Participants
n=99 Participants
|
149 Participants
n=107 Participants
|
320 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
135 Participants
n=99 Participants
|
154 Participants
n=107 Participants
|
289 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
White
|
304 Participants
n=99 Participants
|
302 Participants
n=107 Participants
|
606 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
American Indian or Native American
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiin/Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Other Unspecified
|
1 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Day 5Population: The mMITT Population consisted of all patients in the ITT Population who received any amount of study drug and had at least one qualified baseline pathogen from a study qualifying baseline urine culture against which meropenem and plazomicin have antibacterial activity.
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.
Outcome measures
| Measure |
Plazomicin
n=191 Participants
Patients received up to 15 mg/kg plazomicin as an 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
n=197 Participants
Patients received 1.0 g meropenem as an IV infusion 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).
|
|---|---|---|
|
Percentage of Patients With Composite of Microbiological Eradication and Clinical Cure in the Microbiological Modified ITT (mMITT) Population at Day 5
Composite Cure
|
88 percentage of patients
|
91.4 percentage of patients
|
|
Percentage of Patients With Composite of Microbiological Eradication and Clinical Cure in the Microbiological Modified ITT (mMITT) Population at Day 5
Composite Failure
|
10.5 percentage of patients
|
7.6 percentage of patients
|
|
Percentage of Patients With Composite of Microbiological Eradication and Clinical Cure in the Microbiological Modified ITT (mMITT) Population at Day 5
Indeterminate
|
1.6 percentage of patients
|
1 percentage of patients
|
PRIMARY outcome
Timeframe: Day 17 TOC VisitPopulation: The mMITT Population consisted of all patients in the ITT Population who received any amount of study drug and had at least one qualified baseline pathogen from a study qualifying baseline urine culture against which meropenem and plazomicin have antibacterial activity.
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.
Outcome measures
| Measure |
Plazomicin
n=191 Participants
Patients received up to 15 mg/kg plazomicin as an 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
n=197 Participants
Patients received 1.0 g meropenem as an IV infusion 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).
|
|---|---|---|
|
Percentage of Patients With Composite of Microbiological Eradication and Clinical Cure in the mMITT Population at Test of Cure (TOC)
Composite Cure
|
81.7 percentage of patients
|
70.1 percentage of patients
|
|
Percentage of Patients With Composite of Microbiological Eradication and Clinical Cure in the mMITT Population at Test of Cure (TOC)
Composite Failure
|
15.2 percentage of patients
|
25.9 percentage of patients
|
|
Percentage of Patients With Composite of Microbiological Eradication and Clinical Cure in the mMITT Population at Test of Cure (TOC)
Indeterminate
|
3.1 percentage of patients
|
4.1 percentage of patients
|
SECONDARY outcome
Timeframe: Day 5Population: The ME (Day 5) population consists of clinically evaluable patients with interpretable culture results at Day 5, defined as one that has clearly identified pathogen(s) or one where baseline pathogen(s) could be excluded.
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.
Outcome measures
| Measure |
Plazomicin
n=188 Participants
Patients received up to 15 mg/kg plazomicin as an 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
n=190 Participants
Patients received 1.0 g meropenem as an IV infusion 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).
|
|---|---|---|
|
Percentage of Patients With Composite of Microbiological Eradication and Clinical Cure in the ME Population at Day 5
Day 5: Composite Cure
|
89.4 percentage of patients
|
94.2 percentage of patients
|
|
Percentage of Patients With Composite of Microbiological Eradication and Clinical Cure in the ME Population at Day 5
Day 5: Composite Failure
|
10.6 percentage of patients
|
5.8 percentage of patients
|
SECONDARY outcome
Timeframe: Day 17 TOC VisitPopulation: The ME (TOC) population consists of clinically evaluable patients with interpretable culture results at TOC, defined as one that has clearly identified pathogen(s) or one where baseline pathogen(s) could be excluded.
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.
Outcome measures
| Measure |
Plazomicin
n=179 Participants
Patients received up to 15 mg/kg plazomicin as an 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
n=177 Participants
Patients received 1.0 g meropenem as an IV infusion 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).
|
|---|---|---|
|
Percentage of Patients With Composite of Microbiological Eradication and Clinical Cure in the ME Population at TOC
TOC: Composite Cure
|
84.9 percentage of patients
|
75.1 percentage of patients
|
|
Percentage of Patients With Composite of Microbiological Eradication and Clinical Cure in the ME Population at TOC
TOC: Composite Failure
|
15.1 percentage of patients
|
24.9 percentage of patients
|
SECONDARY outcome
Timeframe: Up to Day 32Population: The safety population included all randomized patients who received any amount of study drug.
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.
Outcome measures
| Measure |
Plazomicin
n=303 Participants
Patients received up to 15 mg/kg plazomicin as an 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
n=301 Participants
Patients received 1.0 g meropenem as an IV infusion 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).
|
|---|---|---|
|
Percentage of Patients With Treatment-Emergent Adverse Events (TEAEs)
|
19.5 percentage of patients
|
21.6 percentage of patients
|
SECONDARY outcome
Timeframe: Day 3Population: The PK Population included patients who received at least one dose of plazomicin and had at least one quantifiable plazomicin plasma concentration available for analysis.
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.
Outcome measures
| Measure |
Plazomicin
n=281 Participants
Patients received up to 15 mg/kg plazomicin as an 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
Patients received 1.0 g meropenem as an IV infusion 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).
|
|---|---|---|
|
Plasma Pharmacokinetics (PK): Area Under the Curve From 0 to 24 Hours (AUC 0-24h)
|
234 mg*h/L (milligrams times hour per liter)
Geometric Coefficient of Variation 38.5
|
—
|
SECONDARY outcome
Timeframe: Day 3Population: The PK Population included patients who received at least one dose of plazomicin and had at least one quantifiable plazomicin plasma concentration available for analysis.
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.
Outcome measures
| Measure |
Plazomicin
n=281 Participants
Patients received up to 15 mg/kg plazomicin as an 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
Patients received 1.0 g meropenem as an IV infusion 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).
|
|---|---|---|
|
Plasma PK: Maximum Observed Plasma Drug Concentration (Cmax)
|
46.6 mg/L
Geometric Coefficient of Variation 43
|
—
|
SECONDARY outcome
Timeframe: Day 3Population: The PK Population included patients who received at least one dose of plazomicin and had at least one quantifiable plazomicin plasma concentration available for analysis.
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.
Outcome measures
| Measure |
Plazomicin
n=281 Participants
Patients received up to 15 mg/kg plazomicin as an 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
Patients received 1.0 g meropenem as an IV infusion 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).
|
|---|---|---|
|
Plasma PK: Minimum Observed Plasma Drug Concentration (Cmin)
|
0.88 mg/L
Geometric Coefficient of Variation 95.4
|
—
|
Adverse Events
Plazomicin
Meropenem
Serious adverse events
| Measure |
Plazomicin
n=303 participants at risk
Patients received up to 15 mg/kg plazomicin as an 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
n=301 participants at risk
Patients received 1.0 g meropenem as an IV infusion 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).
|
|---|---|---|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic neoplasm
|
0.33%
1/303 • Up to Day 32
The AE collection period began with the first dose of study drug and ended at the last follow up visit (LFU). LFU was up to 32 Days after the first dose of study drug.
|
0.00%
0/301 • Up to Day 32
The AE collection period began with the first dose of study drug and ended at the last follow up visit (LFU). LFU was up to 32 Days after the first dose of study drug.
|
|
General disorders
Pyrexia
|
0.00%
0/303 • Up to Day 32
The AE collection period began with the first dose of study drug and ended at the last follow up visit (LFU). LFU was up to 32 Days after the first dose of study drug.
|
0.33%
1/301 • Up to Day 32
The AE collection period began with the first dose of study drug and ended at the last follow up visit (LFU). LFU was up to 32 Days after the first dose of study drug.
|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/303 • Up to Day 32
The AE collection period began with the first dose of study drug and ended at the last follow up visit (LFU). LFU was up to 32 Days after the first dose of study drug.
|
0.33%
1/301 • Up to Day 32
The AE collection period began with the first dose of study drug and ended at the last follow up visit (LFU). LFU was up to 32 Days after the first dose of study drug.
|
|
Renal and urinary disorders
Acute kidney injury
|
0.66%
2/303 • Up to Day 32
The AE collection period began with the first dose of study drug and ended at the last follow up visit (LFU). LFU was up to 32 Days after the first dose of study drug.
|
0.00%
0/301 • Up to Day 32
The AE collection period began with the first dose of study drug and ended at the last follow up visit (LFU). LFU was up to 32 Days after the first dose of study drug.
|
|
Renal and urinary disorders
Calculus urinary
|
0.33%
1/303 • Up to Day 32
The AE collection period began with the first dose of study drug and ended at the last follow up visit (LFU). LFU was up to 32 Days after the first dose of study drug.
|
0.00%
0/301 • Up to Day 32
The AE collection period began with the first dose of study drug and ended at the last follow up visit (LFU). LFU was up to 32 Days after the first dose of study drug.
|
|
Infections and infestations
Clostridium difficile colitis
|
0.00%
0/303 • Up to Day 32
The AE collection period began with the first dose of study drug and ended at the last follow up visit (LFU). LFU was up to 32 Days after the first dose of study drug.
|
0.33%
1/301 • Up to Day 32
The AE collection period began with the first dose of study drug and ended at the last follow up visit (LFU). LFU was up to 32 Days after the first dose of study drug.
|
|
Infections and infestations
Orchitis
|
0.00%
0/303 • Up to Day 32
The AE collection period began with the first dose of study drug and ended at the last follow up visit (LFU). LFU was up to 32 Days after the first dose of study drug.
|
0.33%
1/301 • Up to Day 32
The AE collection period began with the first dose of study drug and ended at the last follow up visit (LFU). LFU was up to 32 Days after the first dose of study drug.
|
|
Infections and infestations
Pneumonia
|
0.33%
1/303 • Up to Day 32
The AE collection period began with the first dose of study drug and ended at the last follow up visit (LFU). LFU was up to 32 Days after the first dose of study drug.
|
0.00%
0/301 • Up to Day 32
The AE collection period began with the first dose of study drug and ended at the last follow up visit (LFU). LFU was up to 32 Days after the first dose of study drug.
|
|
Infections and infestations
Pyelonephritis acute
|
0.00%
0/303 • Up to Day 32
The AE collection period began with the first dose of study drug and ended at the last follow up visit (LFU). LFU was up to 32 Days after the first dose of study drug.
|
0.33%
1/301 • Up to Day 32
The AE collection period began with the first dose of study drug and ended at the last follow up visit (LFU). LFU was up to 32 Days after the first dose of study drug.
|
|
Infections and infestations
Septic shock
|
0.00%
0/303 • Up to Day 32
The AE collection period began with the first dose of study drug and ended at the last follow up visit (LFU). LFU was up to 32 Days after the first dose of study drug.
|
0.33%
1/301 • Up to Day 32
The AE collection period began with the first dose of study drug and ended at the last follow up visit (LFU). LFU was up to 32 Days after the first dose of study drug.
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/303 • Up to Day 32
The AE collection period began with the first dose of study drug and ended at the last follow up visit (LFU). LFU was up to 32 Days after the first dose of study drug.
|
0.33%
1/301 • Up to Day 32
The AE collection period began with the first dose of study drug and ended at the last follow up visit (LFU). LFU was up to 32 Days after the first dose of study drug.
|
|
Infections and infestations
Urosepsis
|
0.33%
1/303 • Up to Day 32
The AE collection period began with the first dose of study drug and ended at the last follow up visit (LFU). LFU was up to 32 Days after the first dose of study drug.
|
0.00%
0/301 • Up to Day 32
The AE collection period began with the first dose of study drug and ended at the last follow up visit (LFU). LFU was up to 32 Days after the first dose of study drug.
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Investigator may publish/present the study results provided all of the following: (i) the primary publication has been published; or, if no such publication has occurred, at least 18m have passed since the completion of the study; (ii) Achaogen is allowed at least 60d to review; (iii) confidential information is deleted as requested; (iv) comments and proposed revisions are considered; and (v) during the 60d review, if requested, the Investigator shall delay the publication or presentation.
- Publication restrictions are in place
Restriction type: OTHER