A Phase 2 interventional study of levofloxacin and plazomicin in Complicated Urinary Tract Infection and Acute Pyelonephritis, sponsored by Achaogen, Inc.. Completed. Open to participants aged 18 Years to 85 Years. Per ClinicalTrials.gov, last updated 2018-08-22.
Sponsored by Achaogen, Inc. · Phase 2, Interventional, and Treatment
This was a multi-center, multi-national, double-blind, randomized, comparator-controlled study of plazomicin administered intravenously compared with levofloxacin, a standard approved intravenous therapy for complicated urinary tract infection (cUTI) and acute pyelonephritis (AP).
779 studies on the registry are indexed under Urinary Tract Infections; 132 are open to participants now.
This study's enrollment of 145 is above the median of 130 across 544 interventional studies indexed under Urinary Tract Infections.
Browse Urinary Tract Infections studies →Achaogen, Inc. is the lead sponsor of 12 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
Key Inclusion Criteria:
Key Exclusion Criteria:
Patients received two intravenous (IV) infusions daily for 5 consecutive days: 10 milligrams per kilogram (mg/kg) plazomicin followed by placebo.
Drug: plazomicin · Drug: placebo
Patients received two IV infusions daily for 5 consecutive days: 15 mg/kg plazomicin followed by placebo.
Drug: plazomicin · Drug: placebo
Patients received two IV infusions daily for 5 consecutive days: placebo followed by 750 milligrams (mg) levofloxacin.
Drug: levofloxacin · Drug: placebo
Percentage of Patients Who Attained Microbiological Eradication (MBE) at the Test of Cure (TOC) Visit in the Microbiological Intent to Treat (MITT) Population
MBE was defined as documented eradication of all isolated pathogens. This was based on a urine culture, taken at the TOC visit that showed that all pathogens isolated at baseline at ≥10\^5 colony forming unit(s) per milliliter (CFU/mL) were reduced to \<10\^4 CFU/mL.
Time frame: Day 1 to TOC (Day 12)
Percentage of Patients Who Attained MBE at the TOC Visit in the Microbiologically Evaluable (ME) Population
MBE was defined as documented eradication of all isolated pathogens. This was based on a urine culture, taken at the TOC visit that showed that all pathogens isolated at baseline at ≥10\^5 CFU/mL were reduced to \<10\^4 CFU/mL.
Time frame: Day 1 to TOC (Day 12)
Percentage of Patients With Treatment-Emergent Adverse Events (TEAE)
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.
Time frame: Day 1 to the end of study (Day 40)
Percentage of Patients Who Attained Clinical Cure Based on Investigator and Sponsor Assessments at TOC Visit in the Intent-to-treat (ITT) Population
Investigator's assessment criteria defined Clinical Cure as resolution of baseline clinical signs and symptoms of infection through the TOC visit. The sponsor's assessment criteria was programmatically based on the investigator's assessment of participant clinical outcome, the number of days and doses of drug received and whether an antibiotic was administered.
Time frame: Day 1 to TOC (Day 12)
Percentage of Patients Who Attained Clinical Cure Based on Investigator and Sponsor Assessments at the TOC Visit in the CE Population
Investigator's assessment criteria defined Clinical Cure as a resolution of baseline clinical signs and symptoms of infection through the TOC visit. The sponsor's assessment criteria was programmatically based on the investigator's assessment of participant clinical outcome, the number of days and doses of drug received and whether an antibiotic was administered.
Time frame: Day 1 to TOC (Day 12)
Percentage of Patients Who Attained Clinical Cure Based on Investigator and Sponsor Assessments at the End of Treatment (EOT) Visit in the CE Population
Investigator's assessment criteria defined Clinical Cure as a resolution of baseline clinical signs and symptoms of infection through the EOT visit. The Sponsor's assessment criteria was programmatically based on the investigator's assessment of participant clinical outcome, the number of days and doses of drug received and whether an antibiotic was administered.
Time frame: Day 1 to EOT (Day 5)
Percentage of Patients Who Attained MBE at the EOT Visit in the ME Population
MBE was defined as documented eradication of all isolated pathogens. This was based on a urine culture, taken at the EOT visit that showed that all pathogens isolated at baseline at ≥10\^5 CFU/mL were reduced to \<10\^4 CFU/mL.
Time frame: Day 1 to EOT (Day 5)
Percentage of Patients Who Attained MBE at the EOT Visit in the MITT Population
MBE was defined as documented eradication of all isolated pathogens. This was based on a urine culture, taken at the EOT visit that showed that all pathogens isolated at baseline at ≥10\^5 CFU/mL were reduced to \<10\^4 CFU/mL.
Time frame: Day 1 to EOT (Day 5)
Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population by Baseline Pathogen
MBE was defined as documented eradication of all isolated pathogens. This was based on a urine culture, taken at the TOC visit that showed that all pathogens isolated at baseline at ≥10\^5 CFU/mL were reduced to \<10\^4 CFU/mL.
Time frame: Day 1 to TOC (Day 12)
Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population Stratified by Infection Category
MBE was defined as documented eradication of all isolated pathogens. This was based on a urine culture, taken at the TOC visit that showed that all pathogens isolated at baseline at ≥10\^5 CFU/mL were reduced to \<10\^4 CFU/mL.
Time frame: Day 1 to TOC (Day 12)
Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population by Country/Region
MBE was defined as documented eradication of all isolated pathogens. This was based on a urine culture, taken at the TOC visit that showed that all pathogens isolated at baseline at ≥10\^5 CFU/mL were reduced to \<10\^4 CFU/mL.
Time frame: Day 1 to TOC (Day 12)
Time (Days) to Resolution of Signs and Symptoms of cUTI and AP in the MITT Population
Resolution of clinical signs and symptoms is defined as absence of all signs and symptoms present at baseline.
Time frame: Day 1 to End of Study (Day 40)
Time (Days) to Clinical Cure Based on Investigator's and Sponsor's Assessments in the MITT Population
Investigator's assessment criteria defined Clinical Cure as a resolution of baseline clinical signs and symptoms of infection through the TOC visit. The Sponsor's assessment criteria was programmatically based on the investigator's assessment of participant clinical outcome, the number of days and doses of drug received and whether an antibiotic was administered.
Time frame: Day 1 to End of Study (Day 40)
Time (Days) to Defervescense in the MITT Population
Defervescence is defined as the absence of fever \<37.7 degrees Celsius and is assessed in patients who were afebrile at baseline.
Time frame: Day 1 to End of Study (Day 40)
Percentage of Patients Experiencing a Clinical Relapse or Microbiological Recurrence in the ME Population
Patients who had a clinical relapse (defined as the return of clinical signs and symptoms requiring antibiotic therapy) or microbiological recurrence (defined as eradication of the original pathogen\[s\] at the TOC visit but regrowth at the level \>10\^5 CFU/mL by the LTFU \[long term follow up\] visit).
Time frame: Day 1 to LTFU (Day 40)
Percentage of Patients With a Superinfection or New Infection in the ME Population
Superinfections are defined as a pathogen other than the one at baseline found in urine at ≥10\^5 CFU/mL any time after the first infusion through EOT. New infections are defined as a pathogen other than the one at baseline found in urine at ≥10\^5 CFU/mL any time after EOT.
Time frame: Day 1 to to End of Study (Day 40)
| Milestone | Plazomicin (10 mg/kg) | Plazomicin (15 mg/kg) | Levofloxacin |
|---|---|---|---|
| Started | 22 | 76 | 47 |
| Completed | 20 | 64 | 41 |
| Not completed | 2 | 12 | 6 |
| Withdrew: Consent withdrawn | 1 | 4 | 2 |
| Withdrew: Lack of efficacy | 0 | 2 | 0 |
| Withdrew: Unacceptable/ intolerable ae(s) | 0 | 1 | 1 |
| Withdrew: Investigator or medical monitor decision | 0 | 1 | 0 |
| Withdrew: Administrative reasons | 0 | 1 | 2 |
| Withdrew: Lost to follow-up | 1 | 3 | 1 |
MBE was defined as documented eradication of all isolated pathogens. This was based on a urine culture, taken at the TOC visit that showed that all pathogens isolated at baseline at ≥10\^5 colony forming unit(s) per milliliter (CFU/mL) were reduced to \<10\^4 CFU/mL.
| percentage of patients | Plazomicin (10 mg/kg) | Plazomicin (15 mg/kg) | Levofloxacin |
|---|---|---|---|
| Percentage of Patients Who Attained Microbiological Eradication (MBE) at the Test of Cure (TOC) Visit in the Microbiological Intent to Treat (MITT) Population | 50 (21.1 to 78.9) | 60.8 (46.1 to 74.2) | 58.6 (38.9 to 76.5) |
MBE was defined as documented eradication of all isolated pathogens. This was based on a urine culture, taken at the TOC visit that showed that all pathogens isolated at baseline at ≥10\^5 CFU/mL were reduced to \<10\^4 CFU/mL.
| percentage of patients | Plazomicin (10 mg/kg) | Plazomicin (15 mg/kg) | Levofloxacin |
|---|---|---|---|
| Percentage of Patients Who Attained MBE at the TOC Visit in the Microbiologically Evaluable (ME) Population | 85.7 (42.1 to 99.6) | 88.6 (73.3 to 96.8) | 81.0 (58.1 to 94.6) |
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.
| percentage of patients | Plazomicin (10 mg/kg) | Plazomicin (15 mg/kg) | Levofloxacin |
|---|---|---|---|
| Percentage of Patients With Treatment-Emergent Adverse Events (TEAE) | 31.8 | 35.1 | 47.7 |
Investigator's assessment criteria defined Clinical Cure as resolution of baseline clinical signs and symptoms of infection through the TOC visit. The sponsor's assessment criteria was programmatically based on the investigator's assessment of participant clinical outcome, the number of days and doses of drug received and whether an antibiotic was administered.
| percentage of patients | Plazomicin (10 mg/kg) | Plazomicin (15 mg/kg) | Levofloxacin |
|---|---|---|---|
| Investigator's Assessment: Cured | 63.6 (40.7 to 82.8) | 69.7 (58.1 to 79.8) | 70.2 (55.1 to 82.7) |
| Sponsor's Assessment: Cured | 59.1 (36.4 to 79.3) | 69.7 (58.1 to 79.8) | 68.1 (52.9 to 80.9) |
Investigator's assessment criteria defined Clinical Cure as a resolution of baseline clinical signs and symptoms of infection through the TOC visit. The sponsor's assessment criteria was programmatically based on the investigator's assessment of participant clinical outcome, the number of days and doses of drug received and whether an antibiotic was administered.
| percentage of patients | Plazomicin (10 mg/kg) | Plazomicin (15 mg/kg) | Levofloxacin |
|---|---|---|---|
| Investigator's Assessment: Cured | 66.7 (41.0 to 86.7) | 76.6 (64.3 to 86.2) | 78.6 (63.2 to 89.7) |
| Sponsor's Assessment: Cured | 66.7 (41.0 to 86.7) | 76.6 (64.3 to 86.2) | 76.2 (60.5 to 87.9) |
Investigator's assessment criteria defined Clinical Cure as a resolution of baseline clinical signs and symptoms of infection through the EOT visit. The Sponsor's assessment criteria was programmatically based on the investigator's assessment of participant clinical outcome, the number of days and doses of drug received and whether an antibiotic was administered.
| percentage of patients | Plazomicin (10 mg/kg) | Plazomicin (15 mg/kg) | Levofloxacin |
|---|---|---|---|
| Investigator's Assessment: Cured | 94.4 (72.7 to 99.9) | 82.8 (71.3 to 91.1) | 88.1 (74.4 to 96.0) |
| Sponsor's Assessment: Cured | 94.4 (72.7 to 99.9) | 82.8 (71.3 to 91.1) | 85.7 (71.5 to 94.6) |
MBE was defined as documented eradication of all isolated pathogens. This was based on a urine culture, taken at the EOT visit that showed that all pathogens isolated at baseline at ≥10\^5 CFU/mL were reduced to \<10\^4 CFU/mL.
| percentage of patients | Plazomicin (10 mg/kg) | Plazomicin (15 mg/kg) | Levofloxacin |
|---|---|---|---|
| Percentage of Patients Who Attained MBE at the EOT Visit in the ME Population | 85.7 (42.1 to 99.6) | 82.9 (66.4 to 93.4) | 76.2 (52.8 to 91.8) |
MBE was defined as documented eradication of all isolated pathogens. This was based on a urine culture, taken at the EOT visit that showed that all pathogens isolated at baseline at ≥10\^5 CFU/mL were reduced to \<10\^4 CFU/mL.
| percentage of patients | Plazomicin (10 mg/kg) | Plazomicin (15 mg/kg) | Levofloxacin |
|---|---|---|---|
| Percentage of Patients Who Attained MBE at the EOT Visit in the MITT Population | 83.3 (51.6 to 97.9) | 74.5 (60.4 to 85.7) | 72.4 (52.8 to 87.3) |
MBE was defined as documented eradication of all isolated pathogens. This was based on a urine culture, taken at the TOC visit that showed that all pathogens isolated at baseline at ≥10\^5 CFU/mL were reduced to \<10\^4 CFU/mL.
| percentage of patients | Plazomicin (10 mg/kg) | Plazomicin (15 mg/kg) | Levofloxacin |
|---|---|---|---|
| Gram-positive bacteria (aerobes), eradication | 100 | 100 | 100 |
| Gram-negative bacteria (aerobes), eradication | 83.3 | 87.5 | 80.0 |
MBE was defined as documented eradication of all isolated pathogens. This was based on a urine culture, taken at the TOC visit that showed that all pathogens isolated at baseline at ≥10\^5 CFU/mL were reduced to \<10\^4 CFU/mL.
| percentage of patients | Plazomicin (10 mg/kg) | Plazomicin (15 mg/kg) | Levofloxacin |
|---|---|---|---|
| Acute pyelonephritis, eradication | 100 (15.8 to 100.0) | 88.9 (65.3 to 98.6) | 80 (51.9 to 95.7) |
| Complicated Lower UTI, eradication | 80.0 (28.4 to 99.5) | 88.2 (63.6 to 98.5) | 83.3 (35.9 to 99.6) |
| cUTI with indwelling catheter, eradication | 0 (0 to 97.5) | 75 (19.4 to 99.4) | — |
| cUTI without indwelling catheter, eradication | 100 (39.8 to 100.0) | 92.3 (64.0 to 99.8) | 83.3 (35.9 to 99.6) |
MBE was defined as documented eradication of all isolated pathogens. This was based on a urine culture, taken at the TOC visit that showed that all pathogens isolated at baseline at ≥10\^5 CFU/mL were reduced to \<10\^4 CFU/mL.
| percentage of patients | Plazomicin (10 mg/kg) | Plazomicin (15 mg/kg) | Levofloxacin |
|---|---|---|---|
| India, eradicaton | 66.7 (9.4 to 99.2) | 66.7 (22.3 to 95.7) | 0 (0 to 70.8) |
| Latin America, eradication | 100 (15.8 to 100) | 100 (71.5 to 100) | 100 (63.1 to 100) |
| North America, eradication | 100 (15.8 to 100) | 88.9 (65.3 to 98.6) | 90 (55.5 to 99.7) |
Resolution of clinical signs and symptoms is defined as absence of all signs and symptoms present at baseline.
| days | Plazomicin (10 mg/kg) | Plazomicin (15 mg/kg) | Levofloxacin |
|---|---|---|---|
| Time (Days) to Resolution of Signs and Symptoms of cUTI and AP in the MITT Population | 11.8 ± 2.67 | 10.7 ± 1.93 | 13.3 ± 3.16 |
Investigator's assessment criteria defined Clinical Cure as a resolution of baseline clinical signs and symptoms of infection through the TOC visit. The Sponsor's assessment criteria was programmatically based on the investigator's assessment of participant clinical outcome, the number of days and doses of drug received and whether an antibiotic was administered.
| days | Plazomicin (10 mg/kg) | Plazomicin (15 mg/kg) | Levofloxacin |
|---|---|---|---|
| Investigator's Assessment | 9.5 ± 2.43 | 7.0 ± 0.71 | 7.6 ± 0.82 |
| Sponsor's Assessment | 9.5 ± 2.43 | 7.0 ± 0.71 | 7.4 ± 0.83 |
Defervescence is defined as the absence of fever \<37.7 degrees Celsius and is assessed in patients who were afebrile at baseline.
| days | Plazomicin (10 mg/kg) | Plazomicin (15 mg/kg) | Levofloxacin |
|---|---|---|---|
| Time (Days) to Defervescense in the MITT Population | 1.0 | 2.1 ± 0.26 | 2.0 ± 0.58 |
Patients who had a clinical relapse (defined as the return of clinical signs and symptoms requiring antibiotic therapy) or microbiological recurrence (defined as eradication of the original pathogen\[s\] at the TOC visit but regrowth at the level \>10\^5 CFU/mL by the LTFU \[long term follow up\] visit).
| percentage of patients | Plazomicin (10 mg/kg) | Plazomicin (15 mg/kg) | Levofloxacin |
|---|---|---|---|
| Clinical Relapse | 0 | 14.3 | 6.3 |
| Microbiological Recurrence | 0 | 6.5 | 23.5 |
Superinfections are defined as a pathogen other than the one at baseline found in urine at ≥10\^5 CFU/mL any time after the first infusion through EOT. New infections are defined as a pathogen other than the one at baseline found in urine at ≥10\^5 CFU/mL any time after EOT.
| percentage of patients | Plazomicin (10 mg/kg) | Plazomicin (15 mg/kg) | Levofloxacin |
|---|---|---|---|
| Superinfection | 28.6 | 8.6 | 0 |
| New infection | 0 | 2.9 | 4.8 |
Collected over Day 1 to the end of the study (Day 40). Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Plazomicin (10 mg/kg) | 0/22 (0%) | 0/22 (0%) | 2/22 (9.1%) |
| Plazomicin (15 mg/kg) | 0/74 (0%) | 1/74 (1.4%) | 22/74 (29.7%) |
| Levofloxacin | 0/44 (0%) | 2/44 (4.5%) | 3/44 (6.8%) |
| Event | Plazomicin (10 mg/kg) | Plazomicin (15 mg/kg) | Levofloxacin |
|---|---|---|---|
| Pyelonephritis acuteInfections and infestations | 0/22 | 0/74 | 1/44 |
| ConvulsionNervous system disorders | 0/22 | 0/74 | 1/44 |
| Abortion spontaneousPregnancy, puerperium and perinatal conditions | 0/22 | 1/74 | 0/44 |
| Event | Plazomicin (10 mg/kg) | Plazomicin (15 mg/kg) | Levofloxacin |
|---|---|---|---|
| HeadacheNervous system disorders | 2/22 | 6/74 | 3/44 |
| DiarrhoeaGastrointestinal disorders | 0/22 | 4/74 | 2/44 |
| NauseaGastrointestinal disorders | 0/22 | 4/74 | 0/44 |
| VomitingGastrointestinal disorders | 0/22 | 4/74 | 1/44 |
| DizzinessNervous system disorders | 0/22 | 4/74 | 0/44 |
The intent-to-treat (ITT) population was defined as all randomized patients.
| Age, Categorical(Participants) | Plazomicin (10 mg/kg) | Plazomicin (15 mg/kg) | Levofloxacin | Total |
|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 17 | 72 | 42 | 131 |
| >=65 years | 5 | 4 | 5 | 14 |
| Age, Continuous(years) | Plazomicin (10 mg/kg) | Plazomicin (15 mg/kg) | Levofloxacin | Total |
|---|---|---|---|---|
| Mean | 46.5 ± 18.12 | 40.00 ± 15.02 | 44.8 ± 14.61 | 42.6 ± 15.53 |
| Sex: Female, Male(Participants) | Plazomicin (10 mg/kg) | Plazomicin (15 mg/kg) | Levofloxacin | Total |
|---|---|---|---|---|
| Female | 18 | 61 | 37 | 116 |
| Male | 4 | 15 | 10 | 29 |
No study locations are listed for this record.
This study is completed, as verified in Aug 2018. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: Plazomicin
Achaogen, Inc.