Trial Outcomes & Findings for A Study of Plazomicin Compared With Levofloxacin for the Treatment of Complicated Urinary Tract Infection (cUTI) and Acute Pyelonephritis (AP) (NCT NCT01096849)
NCT ID: NCT01096849
Last Updated: 2018-08-22
Results Overview
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.
COMPLETED
PHASE2
145 participants
Day 1 to TOC (Day 12)
2018-08-22
Participant Flow
Participant milestones
| Measure |
Plazomicin (10 mg/kg)
Patients received two intravenous (IV) infusions daily for 5 consecutive days: 10 milligrams per kilogram (mg/kg) plazomicin followed by placebo.
|
Plazomicin (15 mg/kg)
Patients received two IV infusions daily for 5 consecutive days: 15 mg/kg plazomicin followed by placebo.
|
Levofloxacin
Patients received two IV infusions daily for 5 consecutive days: placebo followed by 750 milligrams (mg) levofloxacin.
|
|---|---|---|---|
|
Overall Study
STARTED
|
22
|
76
|
47
|
|
Overall Study
COMPLETED
|
20
|
64
|
41
|
|
Overall Study
NOT COMPLETED
|
2
|
12
|
6
|
Reasons for withdrawal
| Measure |
Plazomicin (10 mg/kg)
Patients received two intravenous (IV) infusions daily for 5 consecutive days: 10 milligrams per kilogram (mg/kg) plazomicin followed by placebo.
|
Plazomicin (15 mg/kg)
Patients received two IV infusions daily for 5 consecutive days: 15 mg/kg plazomicin followed by placebo.
|
Levofloxacin
Patients received two IV infusions daily for 5 consecutive days: placebo followed by 750 milligrams (mg) levofloxacin.
|
|---|---|---|---|
|
Overall Study
Consent Withdrawn
|
1
|
4
|
2
|
|
Overall Study
Lack of Efficacy
|
0
|
2
|
0
|
|
Overall Study
Unacceptable/ Intolerable AE(s)
|
0
|
1
|
1
|
|
Overall Study
Investigator or Medical Monitor Decision
|
0
|
1
|
0
|
|
Overall Study
Administrative Reasons
|
0
|
1
|
2
|
|
Overall Study
Lost to Follow-up
|
1
|
3
|
1
|
Baseline Characteristics
A Study of Plazomicin Compared With Levofloxacin for the Treatment of Complicated Urinary Tract Infection (cUTI) and Acute Pyelonephritis (AP)
Baseline characteristics by cohort
| Measure |
Plazomicin (10 mg/kg)
n=22 Participants
Patients received two IV infusions daily for 5 consecutive days: 10 mg/kg plazomicin followed by placebo.
|
Plazomicin (15 mg/kg)
n=76 Participants
Patients received two IV infusions daily for 5 consecutive days: 15 mg/kg plazomicin followed by placebo.
|
Levofloxacin
n=47 Participants
Patients received two IV infusions daily for 5 consecutive days: placebo followed by 750 mg levofloxacin.
|
Total
n=145 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
17 Participants
n=5 Participants
|
72 Participants
n=7 Participants
|
42 Participants
n=5 Participants
|
131 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
5 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
14 Participants
n=4 Participants
|
|
Age, Continuous
|
46.5 years
STANDARD_DEVIATION 18.12 • n=5 Participants
|
40.00 years
STANDARD_DEVIATION 15.02 • n=7 Participants
|
44.8 years
STANDARD_DEVIATION 14.61 • n=5 Participants
|
42.6 years
STANDARD_DEVIATION 15.53 • n=4 Participants
|
|
Sex: Female, Male
Female
|
18 Participants
n=5 Participants
|
61 Participants
n=7 Participants
|
37 Participants
n=5 Participants
|
116 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
29 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Day 1 to TOC (Day 12)Population: The MITT population was defined as a subset patients from the ITT population with at least one isolated causative pathogen from an acceptable pretreatment urine specimen.
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.
Outcome measures
| Measure |
Plazomicin (10 mg/kg)
n=12 Participants
Patients received two IV infusions daily for 5 consecutive days: 10 mg/kg plazomicin followed by placebo.
|
Plazomicin (15 mg/kg)
n=51 Participants
Patients received two IV infusions daily for 5 consecutive days: 15 mg/kg plazomicin followed by placebo.
|
Levofloxacin
n=29 Participants
Patients received two IV infusions daily for 5 consecutive days: placebo followed by 750 mg 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 percentage of patients
Interval 21.1 to 78.9
|
60.8 percentage of patients
Interval 46.1 to 74.2
|
58.6 percentage of patients
Interval 38.9 to 76.5
|
PRIMARY outcome
Timeframe: Day 1 to TOC (Day 12)Population: The ME population was defined as clinically evaluable (CE) patients who had a causative pathogen isolated at baseline (ie, patients in both the MITT and CE populations). To be included in the ME population, a patient must also have had results obtained from non-contaminated urine culture at TOC.
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.
Outcome measures
| Measure |
Plazomicin (10 mg/kg)
n=7 Participants
Patients received two IV infusions daily for 5 consecutive days: 10 mg/kg plazomicin followed by placebo.
|
Plazomicin (15 mg/kg)
n=35 Participants
Patients received two IV infusions daily for 5 consecutive days: 15 mg/kg plazomicin followed by placebo.
|
Levofloxacin
n=21 Participants
Patients received two IV infusions daily for 5 consecutive days: placebo followed by 750 mg levofloxacin.
|
|---|---|---|---|
|
Percentage of Patients Who Attained MBE at the TOC Visit in the Microbiologically Evaluable (ME) Population
|
85.7 percentage of patients
Interval 42.1 to 99.6
|
88.6 percentage of patients
Interval 73.3 to 96.8
|
81.0 percentage of patients
Interval 58.1 to 94.6
|
PRIMARY outcome
Timeframe: Day 1 to the end of study (Day 40)Population: The Safety population was defined as 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 (10 mg/kg)
n=22 Participants
Patients received two IV infusions daily for 5 consecutive days: 10 mg/kg plazomicin followed by placebo.
|
Plazomicin (15 mg/kg)
n=74 Participants
Patients received two IV infusions daily for 5 consecutive days: 15 mg/kg plazomicin followed by placebo.
|
Levofloxacin
n=44 Participants
Patients received two IV infusions daily for 5 consecutive days: placebo followed by 750 mg levofloxacin.
|
|---|---|---|---|
|
Percentage of Patients With Treatment-Emergent Adverse Events (TEAE)
|
31.8 percentage of patients
|
35.1 percentage of patients
|
47.7 percentage of patients
|
SECONDARY outcome
Timeframe: Day 1 to TOC (Day 12)Population: The intent-to-treat (ITT) population was defined as all randomized patients.
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.
Outcome measures
| Measure |
Plazomicin (10 mg/kg)
n=22 Participants
Patients received two IV infusions daily for 5 consecutive days: 10 mg/kg plazomicin followed by placebo.
|
Plazomicin (15 mg/kg)
n=76 Participants
Patients received two IV infusions daily for 5 consecutive days: 15 mg/kg plazomicin followed by placebo.
|
Levofloxacin
n=47 Participants
Patients received two IV infusions daily for 5 consecutive days: placebo followed by 750 mg levofloxacin.
|
|---|---|---|---|
|
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: Cured
|
63.6 percentage of patients
Interval 40.7 to 82.8
|
69.7 percentage of patients
Interval 58.1 to 79.8
|
70.2 percentage of patients
Interval 55.1 to 82.7
|
|
Percentage of Patients Who Attained Clinical Cure Based on Investigator and Sponsor Assessments at TOC Visit in the Intent-to-treat (ITT) Population
Sponsor's Assessment: Cured
|
59.1 percentage of patients
Interval 36.4 to 79.3
|
69.7 percentage of patients
Interval 58.1 to 79.8
|
68.1 percentage of patients
Interval 52.9 to 80.9
|
SECONDARY outcome
Timeframe: Day 1 to TOC (Day 12)Population: The CE population was defined as patients who received at least 80% of study drug for clinical successes or 40% for clinical failures and must not have had indeterminate clinical response at TOC.
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.
Outcome measures
| Measure |
Plazomicin (10 mg/kg)
n=18 Participants
Patients received two IV infusions daily for 5 consecutive days: 10 mg/kg plazomicin followed by placebo.
|
Plazomicin (15 mg/kg)
n=64 Participants
Patients received two IV infusions daily for 5 consecutive days: 15 mg/kg plazomicin followed by placebo.
|
Levofloxacin
n=42 Participants
Patients received two IV infusions daily for 5 consecutive days: placebo followed by 750 mg levofloxacin.
|
|---|---|---|---|
|
Percentage of Patients Who Attained Clinical Cure Based on Investigator and Sponsor Assessments at the TOC Visit in the CE Population
Investigator's Assessment: Cured
|
66.7 percentage of patients
Interval 41.0 to 86.7
|
76.6 percentage of patients
Interval 64.3 to 86.2
|
78.6 percentage of patients
Interval 63.2 to 89.7
|
|
Percentage of Patients Who Attained Clinical Cure Based on Investigator and Sponsor Assessments at the TOC Visit in the CE Population
Sponsor's Assessment: Cured
|
66.7 percentage of patients
Interval 41.0 to 86.7
|
76.6 percentage of patients
Interval 64.3 to 86.2
|
76.2 percentage of patients
Interval 60.5 to 87.9
|
SECONDARY outcome
Timeframe: Day 1 to EOT (Day 5)Population: The CE population was defined as patients who received at least 80% of study drug for clinical successes or 40% for clinical failures and must not have had indeterminate clinical response at TOC.
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.
Outcome measures
| Measure |
Plazomicin (10 mg/kg)
n=18 Participants
Patients received two IV infusions daily for 5 consecutive days: 10 mg/kg plazomicin followed by placebo.
|
Plazomicin (15 mg/kg)
n=64 Participants
Patients received two IV infusions daily for 5 consecutive days: 15 mg/kg plazomicin followed by placebo.
|
Levofloxacin
n=42 Participants
Patients received two IV infusions daily for 5 consecutive days: placebo followed by 750 mg levofloxacin.
|
|---|---|---|---|
|
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: Cured
|
94.4 percentage of patients
Interval 72.7 to 99.9
|
82.8 percentage of patients
Interval 71.3 to 91.1
|
88.1 percentage of patients
Interval 74.4 to 96.0
|
|
Percentage of Patients Who Attained Clinical Cure Based on Investigator and Sponsor Assessments at the End of Treatment (EOT) Visit in the CE Population
Sponsor's Assessment: Cured
|
94.4 percentage of patients
Interval 72.7 to 99.9
|
82.8 percentage of patients
Interval 71.3 to 91.1
|
85.7 percentage of patients
Interval 71.5 to 94.6
|
SECONDARY outcome
Timeframe: Day 1 to EOT (Day 5)Population: The ME population was defined as CE patients who had a causative pathogen isolated at baseline (ie, patients in both the MITT and CE populations). To be included in the ME population, a patient must also have had results obtained from non-contaminated urine culture at TOC.
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.
Outcome measures
| Measure |
Plazomicin (10 mg/kg)
n=7 Participants
Patients received two IV infusions daily for 5 consecutive days: 10 mg/kg plazomicin followed by placebo.
|
Plazomicin (15 mg/kg)
n=35 Participants
Patients received two IV infusions daily for 5 consecutive days: 15 mg/kg plazomicin followed by placebo.
|
Levofloxacin
n=21 Participants
Patients received two IV infusions daily for 5 consecutive days: placebo followed by 750 mg levofloxacin.
|
|---|---|---|---|
|
Percentage of Patients Who Attained MBE at the EOT Visit in the ME Population
|
85.7 percentage of patients
Interval 42.1 to 99.6
|
82.9 percentage of patients
Interval 66.4 to 93.4
|
76.2 percentage of patients
Interval 52.8 to 91.8
|
SECONDARY outcome
Timeframe: Day 1 to EOT (Day 5)Population: The MITT population was defined as a subset patients from the ITT population with at least one isolated causative pathogen from an acceptable pretreatment urine specimen.
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.
Outcome measures
| Measure |
Plazomicin (10 mg/kg)
n=12 Participants
Patients received two IV infusions daily for 5 consecutive days: 10 mg/kg plazomicin followed by placebo.
|
Plazomicin (15 mg/kg)
n=51 Participants
Patients received two IV infusions daily for 5 consecutive days: 15 mg/kg plazomicin followed by placebo.
|
Levofloxacin
n=29 Participants
Patients received two IV infusions daily for 5 consecutive days: placebo followed by 750 mg levofloxacin.
|
|---|---|---|---|
|
Percentage of Patients Who Attained MBE at the EOT Visit in the MITT Population
|
83.3 percentage of patients
Interval 51.6 to 97.9
|
74.5 percentage of patients
Interval 60.4 to 85.7
|
72.4 percentage of patients
Interval 52.8 to 87.3
|
SECONDARY outcome
Timeframe: Day 1 to TOC (Day 12)Population: The ME population was defined as CE patients who had a causative pathogen isolated at baseline (ie, patients in both the MITT and CE populations). To be included in the ME population, a patient must also have had results obtained from non-contaminated urine culture at TOC.
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.
Outcome measures
| Measure |
Plazomicin (10 mg/kg)
n=7 Participants
Patients received two IV infusions daily for 5 consecutive days: 10 mg/kg plazomicin followed by placebo.
|
Plazomicin (15 mg/kg)
n=35 Participants
Patients received two IV infusions daily for 5 consecutive days: 15 mg/kg plazomicin followed by placebo.
|
Levofloxacin
n=21 Participants
Patients received two IV infusions daily for 5 consecutive days: placebo followed by 750 mg levofloxacin.
|
|---|---|---|---|
|
Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population by Baseline Pathogen
Gram-positive bacteria (aerobes), eradication
|
100 percentage of patients
|
100 percentage of patients
|
100 percentage of patients
|
|
Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population by Baseline Pathogen
Gram-negative bacteria (aerobes), eradication
|
83.3 percentage of patients
|
87.5 percentage of patients
|
80.0 percentage of patients
|
SECONDARY outcome
Timeframe: Day 1 to TOC (Day 12)Population: The ME population was defined as CE patients who had a causative pathogen isolated at baseline (ie, patients in both the MITT and CE populations). To be included in the ME population, a patient must also have had results obtained from non-contaminated urine culture at TOC.
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.
Outcome measures
| Measure |
Plazomicin (10 mg/kg)
n=7 Participants
Patients received two IV infusions daily for 5 consecutive days: 10 mg/kg plazomicin followed by placebo.
|
Plazomicin (15 mg/kg)
n=35 Participants
Patients received two IV infusions daily for 5 consecutive days: 15 mg/kg plazomicin followed by placebo.
|
Levofloxacin
n=21 Participants
Patients received two IV infusions daily for 5 consecutive days: placebo followed by 750 mg levofloxacin.
|
|---|---|---|---|
|
Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population Stratified by Infection Category
Acute pyelonephritis, eradication
|
100 percentage of patients
Interval 15.8 to 100.0
|
88.9 percentage of patients
Interval 65.3 to 98.6
|
80 percentage of patients
Interval 51.9 to 95.7
|
|
Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population Stratified by Infection Category
Complicated Lower UTI, eradication
|
80.0 percentage of patients
Interval 28.4 to 99.5
|
88.2 percentage of patients
Interval 63.6 to 98.5
|
83.3 percentage of patients
Interval 35.9 to 99.6
|
|
Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population Stratified by Infection Category
cUTI with indwelling catheter, eradication
|
0 percentage of patients
Interval 0.0 to 97.5
|
75 percentage of patients
Interval 19.4 to 99.4
|
—
|
|
Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population Stratified by Infection Category
cUTI without indwelling catheter, eradication
|
100 percentage of patients
Interval 39.8 to 100.0
|
92.3 percentage of patients
Interval 64.0 to 99.8
|
83.3 percentage of patients
Interval 35.9 to 99.6
|
SECONDARY outcome
Timeframe: Day 1 to TOC (Day 12)Population: The ME population was defined as CE patients who had a causative pathogen isolated at baseline (ie, patients in both the MITT and CE populations). To be included in the ME population, a patient must also have had results obtained from non-contaminated urine culture at TOC.
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.
Outcome measures
| Measure |
Plazomicin (10 mg/kg)
n=7 Participants
Patients received two IV infusions daily for 5 consecutive days: 10 mg/kg plazomicin followed by placebo.
|
Plazomicin (15 mg/kg)
n=35 Participants
Patients received two IV infusions daily for 5 consecutive days: 15 mg/kg plazomicin followed by placebo.
|
Levofloxacin
n=21 Participants
Patients received two IV infusions daily for 5 consecutive days: placebo followed by 750 mg levofloxacin.
|
|---|---|---|---|
|
Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population by Country/Region
India, eradicaton
|
66.7 percentage of patients
Interval 9.4 to 99.2
|
66.7 percentage of patients
Interval 22.3 to 95.7
|
0 percentage of patients
Interval 0.0 to 70.8
|
|
Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population by Country/Region
Latin America, eradication
|
100 percentage of patients
Interval 15.8 to 100.0
|
100 percentage of patients
Interval 71.5 to 100.0
|
100 percentage of patients
Interval 63.1 to 100.0
|
|
Percentage of Patients Who Attained MBE at the TOC Visit in the ME Population by Country/Region
North America, eradication
|
100 percentage of patients
Interval 15.8 to 100.0
|
88.9 percentage of patients
Interval 65.3 to 98.6
|
90 percentage of patients
Interval 55.5 to 99.7
|
SECONDARY outcome
Timeframe: Day 1 to End of Study (Day 40)Population: The MITT population was defined as a subset patients from the ITT population with at least one isolated causative pathogen from an acceptable pretreatment urine specimen.
Resolution of clinical signs and symptoms is defined as absence of all signs and symptoms present at baseline.
Outcome measures
| Measure |
Plazomicin (10 mg/kg)
n=12 Participants
Patients received two IV infusions daily for 5 consecutive days: 10 mg/kg plazomicin followed by placebo.
|
Plazomicin (15 mg/kg)
n=51 Participants
Patients received two IV infusions daily for 5 consecutive days: 15 mg/kg plazomicin followed by placebo.
|
Levofloxacin
n=29 Participants
Patients received two IV infusions daily for 5 consecutive days: placebo followed by 750 mg levofloxacin.
|
|---|---|---|---|
|
Time (Days) to Resolution of Signs and Symptoms of cUTI and AP in the MITT Population
|
11.8 days
Standard Error 2.67
|
10.7 days
Standard Error 1.93
|
13.3 days
Standard Error 3.16
|
SECONDARY outcome
Timeframe: Day 1 to End of Study (Day 40)Population: The MITT population was defined as a subset patients from the ITT population with at least one isolated causative pathogen from an acceptable pretreatment urine specimen.
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.
Outcome measures
| Measure |
Plazomicin (10 mg/kg)
n=12 Participants
Patients received two IV infusions daily for 5 consecutive days: 10 mg/kg plazomicin followed by placebo.
|
Plazomicin (15 mg/kg)
n=51 Participants
Patients received two IV infusions daily for 5 consecutive days: 15 mg/kg plazomicin followed by placebo.
|
Levofloxacin
n=29 Participants
Patients received two IV infusions daily for 5 consecutive days: placebo followed by 750 mg levofloxacin.
|
|---|---|---|---|
|
Time (Days) to Clinical Cure Based on Investigator's and Sponsor's Assessments in the MITT Population
Investigator's Assessment
|
9.5 days
Standard Error 2.43
|
7.0 days
Standard Error 0.71
|
7.6 days
Standard Error 0.82
|
|
Time (Days) to Clinical Cure Based on Investigator's and Sponsor's Assessments in the MITT Population
Sponsor's Assessment
|
9.5 days
Standard Error 2.43
|
7.0 days
Standard Error 0.71
|
7.4 days
Standard Error 0.83
|
SECONDARY outcome
Timeframe: Day 1 to End of Study (Day 40)Population: The MITT population was defined as a subset patients from the ITT population with at least one isolated causative pathogen from an acceptable pretreatment urine specimen.
Defervescence is defined as the absence of fever \<37.7 degrees Celsius and is assessed in patients who were afebrile at baseline.
Outcome measures
| Measure |
Plazomicin (10 mg/kg)
n=1 Participants
Patients received two IV infusions daily for 5 consecutive days: 10 mg/kg plazomicin followed by placebo.
|
Plazomicin (15 mg/kg)
n=9 Participants
Patients received two IV infusions daily for 5 consecutive days: 15 mg/kg plazomicin followed by placebo.
|
Levofloxacin
n=3 Participants
Patients received two IV infusions daily for 5 consecutive days: placebo followed by 750 mg levofloxacin.
|
|---|---|---|---|
|
Time (Days) to Defervescense in the MITT Population
|
1.0 days
|
2.1 days
Standard Error 0.26
|
2.0 days
Standard Error 0.58
|
SECONDARY outcome
Timeframe: Day 1 to LTFU (Day 40)Population: The ME population was defined as CE patients who had a causative pathogen isolated at baseline (ie, patients in both the MITT and CE populations). To be included in the ME population, a patient must also have had results obtained from non-contaminated urine culture at TOC.
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).
Outcome measures
| Measure |
Plazomicin (10 mg/kg)
n=7 Participants
Patients received two IV infusions daily for 5 consecutive days: 10 mg/kg plazomicin followed by placebo.
|
Plazomicin (15 mg/kg)
n=35 Participants
Patients received two IV infusions daily for 5 consecutive days: 15 mg/kg plazomicin followed by placebo.
|
Levofloxacin
n=21 Participants
Patients received two IV infusions daily for 5 consecutive days: placebo followed by 750 mg levofloxacin.
|
|---|---|---|---|
|
Percentage of Patients Experiencing a Clinical Relapse or Microbiological Recurrence in the ME Population
Clinical Relapse
|
0 percentage of patients
|
14.3 percentage of patients
|
6.3 percentage of patients
|
|
Percentage of Patients Experiencing a Clinical Relapse or Microbiological Recurrence in the ME Population
Microbiological Recurrence
|
0 percentage of patients
|
6.5 percentage of patients
|
23.5 percentage of patients
|
SECONDARY outcome
Timeframe: Day 1 to to End of Study (Day 40)Population: The ME population was defined as CE patients who had a causative pathogen isolated at baseline (ie, patients in both the MITT and CE populations). To be included in the ME population, a patient must also have had results obtained from non-contaminated urine culture at TOC.
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.
Outcome measures
| Measure |
Plazomicin (10 mg/kg)
n=7 Participants
Patients received two IV infusions daily for 5 consecutive days: 10 mg/kg plazomicin followed by placebo.
|
Plazomicin (15 mg/kg)
n=35 Participants
Patients received two IV infusions daily for 5 consecutive days: 15 mg/kg plazomicin followed by placebo.
|
Levofloxacin
n=21 Participants
Patients received two IV infusions daily for 5 consecutive days: placebo followed by 750 mg levofloxacin.
|
|---|---|---|---|
|
Percentage of Patients With a Superinfection or New Infection in the ME Population
Superinfection
|
28.6 percentage of patients
|
8.6 percentage of patients
|
0 percentage of patients
|
|
Percentage of Patients With a Superinfection or New Infection in the ME Population
New infection
|
0 percentage of patients
|
2.9 percentage of patients
|
4.8 percentage of patients
|
Adverse Events
Plazomicin (10 mg/kg)
Plazomicin (15 mg/kg)
Levofloxacin
Serious adverse events
| Measure |
Plazomicin (10 mg/kg)
n=22 participants at risk
Patients received two IV infusions daily for 5 consecutive days: 10 mg/kg plazomicin followed by placebo.
|
Plazomicin (15 mg/kg)
n=74 participants at risk
Patients received two IV infusions daily for 5 consecutive days: 15 mg/kg plazomicin followed by placebo.
|
Levofloxacin
n=44 participants at risk
Patients received two IV infusions daily for 5 consecutive days: placebo followed by 750 mg levofloxacin.
|
|---|---|---|---|
|
Infections and infestations
Pyelonephritis acute
|
0.00%
0/22 • Day 1 to the end of the study (Day 40)
The safety population, all randomized patients who received any amount of study drug.
|
0.00%
0/74 • Day 1 to the end of the study (Day 40)
The safety population, all randomized patients who received any amount of study drug.
|
2.3%
1/44 • Day 1 to the end of the study (Day 40)
The safety population, all randomized patients who received any amount of study drug.
|
|
Nervous system disorders
Convulsion
|
0.00%
0/22 • Day 1 to the end of the study (Day 40)
The safety population, all randomized patients who received any amount of study drug.
|
0.00%
0/74 • Day 1 to the end of the study (Day 40)
The safety population, all randomized patients who received any amount of study drug.
|
2.3%
1/44 • Day 1 to the end of the study (Day 40)
The safety population, all randomized patients who received any amount of study drug.
|
|
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
|
0.00%
0/22 • Day 1 to the end of the study (Day 40)
The safety population, all randomized patients who received any amount of study drug.
|
1.4%
1/74 • Day 1 to the end of the study (Day 40)
The safety population, all randomized patients who received any amount of study drug.
|
0.00%
0/44 • Day 1 to the end of the study (Day 40)
The safety population, all randomized patients who received any amount of study drug.
|
Other adverse events
| Measure |
Plazomicin (10 mg/kg)
n=22 participants at risk
Patients received two IV infusions daily for 5 consecutive days: 10 mg/kg plazomicin followed by placebo.
|
Plazomicin (15 mg/kg)
n=74 participants at risk
Patients received two IV infusions daily for 5 consecutive days: 15 mg/kg plazomicin followed by placebo.
|
Levofloxacin
n=44 participants at risk
Patients received two IV infusions daily for 5 consecutive days: placebo followed by 750 mg levofloxacin.
|
|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/22 • Day 1 to the end of the study (Day 40)
The safety population, all randomized patients who received any amount of study drug.
|
5.4%
4/74 • Day 1 to the end of the study (Day 40)
The safety population, all randomized patients who received any amount of study drug.
|
4.5%
2/44 • Day 1 to the end of the study (Day 40)
The safety population, all randomized patients who received any amount of study drug.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/22 • Day 1 to the end of the study (Day 40)
The safety population, all randomized patients who received any amount of study drug.
|
5.4%
4/74 • Day 1 to the end of the study (Day 40)
The safety population, all randomized patients who received any amount of study drug.
|
0.00%
0/44 • Day 1 to the end of the study (Day 40)
The safety population, all randomized patients who received any amount of study drug.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/22 • Day 1 to the end of the study (Day 40)
The safety population, all randomized patients who received any amount of study drug.
|
5.4%
4/74 • Day 1 to the end of the study (Day 40)
The safety population, all randomized patients who received any amount of study drug.
|
2.3%
1/44 • Day 1 to the end of the study (Day 40)
The safety population, all randomized patients who received any amount of study drug.
|
|
Nervous system disorders
Headache
|
9.1%
2/22 • Day 1 to the end of the study (Day 40)
The safety population, all randomized patients who received any amount of study drug.
|
8.1%
6/74 • Day 1 to the end of the study (Day 40)
The safety population, all randomized patients who received any amount of study drug.
|
6.8%
3/44 • Day 1 to the end of the study (Day 40)
The safety population, all randomized patients who received any amount of study drug.
|
|
Nervous system disorders
Dizziness
|
0.00%
0/22 • Day 1 to the end of the study (Day 40)
The safety population, all randomized patients who received any amount of study drug.
|
5.4%
4/74 • Day 1 to the end of the study (Day 40)
The safety population, all randomized patients who received any amount of study drug.
|
0.00%
0/44 • Day 1 to the end of the study (Day 40)
The safety population, all randomized patients who received any amount of study drug.
|
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