Urinary Tract Infection
Conditions
Keywords
Drug Therapy
Brief summary
The purpose of this study is to compare the effectiveness of antibiotic flomoxef with cefepime for the treatment of complicated urinary tract infections (cUTIs) in Russian adults.
Detailed description
The drug being tested in this study is called Flomoxef. Flomoxef is being tested in people with a complicated urinary tract infection (cUTI) including a kidney infection. This study compares Flomoxef to Cefepime, another antibiotic. The study enrolled 13 patients. Participants are randomly assigned by a computer generated number to one of two treatment groups: * Flomoxef - intravenous infusion 2g twice daily (every 12 hours); or * Cefepime - intravenous infusion 1g twice daily (every 12 hours). This multi-center trial is conducted at 4 sites in the Russian Federation. The overall time to participate in this study is 30+/-3 days. Participants make six visits to the clinic. Study was prematurely terminated due to administrative and strategic reasons.
Interventions
DRUGFlomoxef
Flomoxef intravenous infusion
DRUGCefepime
Cefepime intravenous infusion
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Is a man or woman aged 18 to 70 years, inclusive. 2. Has pyuria (a white blood cell \[WBC\] count greater than 10/μL in unspun urine or greater than or equal to 10 per high power field in spun urine). 3. Has clinical signs and/or symptoms of a complicated lower urinary tract infection (UTI) and/or acute pyelonephritis that include one or more of the following: fever (i.e, axillary temperature greater than 37.7°C), chills, malaise, flank pain, back pain, and/or costo-vertebral angle pain or tenderness and/or any symptoms of dysuria (dysuria, urinary urgency, urinary frequency, suprapubic discomfort, new urinary incontinence or worsening of pre-existing incontinence) that occur in the presence of a functional or anatomical abnormality of the urinary tract or in the presence of catheterization. 4. Has a pretreatment baseline urine culture specimen obtained within 24 hours before the administration of the first dose of study drug (NOTE: Participants may be enrolled in this study and start intravenous (IV) study drug therapy before the Investigator knows the results of the baseline urine culture). 5. Requires IV antibacterial therapy for the treatment of the presumed complicated UTI (cUTI). 6. In the opinion of the investigator, is capable of understanding and complying with protocol requirements. 7. Signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures, or has a legally acceptable representative sign the forms. 8. Meets protocol-specified criteria regarding the use of contraception; and 9-Is willing and able to comply with study procedures.
Exclusion criteria
1. Has received any investigational compound within 30 days of screening. 2. Is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in the conduct of this study (eg, spouse, parent, child, or sibling) or may consent under duress. 3. Is a female participant who is pregnant or lactating or intending to become pregnant before, during, or within one month after participating in this study, or intends to donate ova during such time period. 4. Is a male participant who intends to donate sperm during the course of this study or for 12 weeks thereafter. 5. Has participated in another clinical study within the past 30 days. 6. Has a history of allergy to or intolerance of beta-lactams (penicillins, cephalosporins or carbopenems). 7. Has signs, symptoms or history of any condition that, per protocol or in the opinion of the investigator, might compromise: 1) the safety or well-being of the participant or study staff, 2) the safety or well-being of the participant's offspring (such as through pregnancy or breast-feeding), or 3) the analysis of results. 8. Has received any amount of potentially therapeutic antibacterial therapy after collection of the pretreatment baseline urine culture and before administration of the first dose of study drug. 9. Has received any dose of a potentially therapeutic antibacterial agent for the treatment of the current UTI within 48 hours before providing the pretreatment baseline urine culture specimen. 10. Has a current urinary catheter that is not scheduled to be removed before the End-of-Therapy (EOT) visit (intermittent straight catheterization during the IV study drug administration period is acceptable). 11. Has any history of trauma to the pelvis or urinary tract within one year before the screening visit. 12. Has any other contraindications to the medicines that are to be used in the study (according to the manufacturer's instructions). 13. Is considered unlikely to survive the four-week study period or has any rapidly progressing disease or immediately life-threatening illness (including acute hepatic failure, respiratory failure or septic shock).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved Resolution of All Clinical Symptoms of a Complicated Urinary Tract Infection (cUTI) at the End of Treatment (EOT) Visit | Baseline and Days 7 to 14 | At the EOT visit (Days 7 to 14), the Investigator collected information about each symptom and performed a judgement about the participant's status. Clinical symptoms present at trial entry were considered to be resolved if the participant has no pyuria; no fever; no malaise, flank pain, back pain, and/or costo-vertebral angle pain or tenderness; and no symptoms of dysuria, urinary urgency, urinary frequency, suprapubic discomfort, new urinary incontinence, or worsening of pre-existing incontinence. Resolution of all clinical symptoms of cUTI were assessed relative to baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved Clinical Resolution of Symptoms of a cUTI at Visit 3, TOC and Late Follow-up (LFU) Visits | Baseline, Days 3, 14 to 21 and 30 | At Visit 3 (Day 3) and at the TOC (Days 14 to 21) and LFU visits (Day 30), the Investigator collected information about each symptom and performed a judgement about the participant's status. Clinical symptoms present at trial entry were considered to be resolved if the participant has no pyuria; no fever; no malaise, flank pain, back pain, and/or costo-vertebral angle pain or tenderness; and no symptoms of dysuria, urinary urgency, urinary frequency, suprapubic discomfort, new urinary incontinence, or worsening of pre-existing incontinence. Resolution of all clinical symptoms of cUTI were assessed relative to baseline. |
| Percentage of Participants With Microbiologic Eradication of the Unique Pathogen at the EOT and TOC Visits | Baseline, Days 7 to 14 and 14 to 21 | A urine sample was collected from the participants at the EOT (Days 7 to 14) and TOC (Day 14 to 21) visits to determine the level of uropathogen. Cultures of the urine sample were processed by using a calibrated loop to identify a quantitative count of bacteria, with a lower limit of 10\^4 CFU/mL. Microbiological response at the TOC visit was based on the same grades as for the EOT visit. The infection was considered to be eradicated if all uropathogens isolated at study entry at a level equal to or greater than 10\^4 CFU/mL have decreased to less than 10\^4 CFU/mL. |
| Percentage of Participants With Microbiologic Persistence of the Unique Pathogen at the EOT and TOC Visits | Baseline, Days 7 to 14 and 14 to 21 | A urine sample was collected from the participants at the EOT (Days 7 to 14) and TOC (Days 14 to 21) visits to determine the level of uropathogen. Cultures of the urine sample was processed by using a calibrated loop to identify a quantitative count of bacteria, with a lower limit of 10\^4 CFU/mL. Microbiological response at the TOC visit was be based on the same grades as for the EOT visit. The infection was considered to be persistent if the level of the uropathogen has increased by greater than or equal to 10\^4 CFU/mL from the time of study entry to that of the EOT and TOC visits. |
| Percentage of Participants With a New Infection at the EOT and TOC Visits | Baseline, Days 7 to 14 and 14 to 21 | A urine sample was collected from the participants at the EOT (Days 7 to 14) and TOC (Days 14 to 21) visits to determine the level of uropathogen. Cultures of the urine sample were processed by using a calibrated loop to identify a quantitative count of bacteria, with a lower limit of 10\^4 CFU/mL. A new infection was defined as the isolation and growth of a uropathogen other than the original pathogen. |
| Percentage of Participants With Microbiological Success at the EOT and Test-of-Cure (TOC) Visits | Baseline, Days 7 to 14 and 14 to 21 | A urine sample was collected at EOT (Days 7 to 14) and TOC (Days 14 to 21) visits to determine level of uropathogen. Cultures of urine sample were processed by calibrated loop to identify a quantitative count of bacteria, with a lower limit of 10\^4 colony forming units per milliliter (CFU/mL). Microbiological success was defined as bacterial uropathogen level of \<10\^4 CFU/mL. Microbiological response was categorized as:microbiological eradication/persistence/new infection/superinfection. An infection was eradicated if all uropathogens isolated at study entry at a level ≥10\^4 CFU/mL have decreased to \<10\^4 CFU/mL, persistent if level of uropathogen has increased by ≥10\^4 CFU/Ml. A new infection, if there is isolation and growth of a uropathogen other than original pathogen and superinfection if there is growth of a uropathogen other than original pathogen at a level ≥10\^4 CFU/mL. Microbiological success was assessed relative to baseline. |
| Number of Participants With Serious Adverse Events (SAEs) and Treatment-Emergent-Adverse Events (TEAEs) | Baseline up to Day 30 | An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. A Serious Adverse Event (SAE) A serious is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. |
| Number of Participants With Clinically Significant Abnormal Laboratory Values | Day 21 | The number of participants with any markedly abnormal (above or below normal ranges) standard safety laboratory values was collected throughout study. |
| Number of Participants With Clinically Significant Change in Vital Signs | Day 1 up to Day 21 | Vital signs included body temperature (axillary measurement), diastolic and systolic blood pressure (5 minutes), respiratory rate, and pulse (bpm). |
| Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 1 up to Day 21 | Physical examination consists of examinations of the following body systems: (1) cardiovascular system; (2) dermatologic system (3) ears, nose, throat; (4) extremities; (5) eyes; (6) gastrointestinal system; (7) genitourinary system; (8) lymph nodes; (9) musculoskeletal system; (10) nervous system; (11) respiratory system. |
| Percentage of Participants With a Superinfection at the EOT and TOC Visits | Baseline, Day 7 to 14 and 14 to 21 | A urine sample was collected from the participants at the EOT (Days 7 to 14) and TOC (Days 14 to 21) visits to determine the level of uropathogen. Cultures of the urine sample were processed by using a calibrated loop to identify a quantitative count of bacteria, with a lower limit of 10\^4 CFU/mL. A superinfection was defined as growth of a uropathogen other than the original pathogen at a level greater than or equal to 10\^4 CFU/mL at any time during the course of active therapy. |
Countries
Russia
Participant flow
Recruitment details
Participants took part in the study at 4 investigative sites in Russia from 01 December 2015 to 15 Feb 2016.
Pre-assignment details
Participants with a diagnosis of complicated urinary tract infections were enrolled in 1:1 ratio to flomoxef or cefepime arm groups.
Participants by arm
| Arm | Count |
|---|---|
| Flomoxef Flomoxef, 2g, injection, intravenously, twice daily (every 12 hours) for up to 12 days. | 6 |
| Cefepime Cefepime, 1g, injection, intravenously, twice daily (every 12 hours) for up to 14 days. | 7 |
| Total | 13 |
Baseline characteristics
| Characteristic | Flomoxef | Cefepime | Total |
|---|---|---|---|
| Age, Continuous | 55.0 years STANDARD_DEVIATION 17.1 | 53.3 years STANDARD_DEVIATION 12.9 | 54.1 years STANDARD_DEVIATION 14.3 |
| Body mass index | 25.443 kg/m^2 STANDARD_DEVIATION 4.821 | 31.041 kg/m^2 STANDARD_DEVIATION 8.321 | 28.458 kg/m^2 STANDARD_DEVIATION 7.262 |
| Region of Enrollment Russia | 6 participants | 7 participants | 13 participants |
| Sex: Female, Male Female | 4 Participants | 5 Participants | 9 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 4 Participants |
| Smoking status Non-tobacco user | 4 participants | 6 participants | 10 participants |
| Smoking status Tobacco user | 2 participants | 1 participants | 3 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 6 | 2 / 7 |
| serious Total, serious adverse events | 0 / 6 | 0 / 7 |
Outcome results
Primary
Percentage of Participants Who Achieved Resolution of All Clinical Symptoms of a Complicated Urinary Tract Infection (cUTI) at the End of Treatment (EOT) Visit
At the EOT visit (Days 7 to 14), the Investigator collected information about each symptom and performed a judgement about the participant's status. Clinical symptoms present at trial entry were considered to be resolved if the participant has no pyuria; no fever; no malaise, flank pain, back pain, and/or costo-vertebral angle pain or tenderness; and no symptoms of dysuria, urinary urgency, urinary frequency, suprapubic discomfort, new urinary incontinence, or worsening of pre-existing incontinence. Resolution of all clinical symptoms of cUTI were assessed relative to baseline.
Time frame: Baseline and Days 7 to 14
Population: The micro-intent to treat (ITT) population included all participants who were randomized and had a baseline bacterial pathogen on culture of urine that causes UTI against which the investigational drug has antibacterial activity.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Flomoxef | Percentage of Participants Who Achieved Resolution of All Clinical Symptoms of a Complicated Urinary Tract Infection (cUTI) at the End of Treatment (EOT) Visit | 60.0 percentage of participants |
| Cefepime | Percentage of Participants Who Achieved Resolution of All Clinical Symptoms of a Complicated Urinary Tract Infection (cUTI) at the End of Treatment (EOT) Visit | 42.9 percentage of participants |
Secondary
Number of Participants With Clinically Significant Abnormal Laboratory Values
The number of participants with any markedly abnormal (above or below normal ranges) standard safety laboratory values was collected throughout study.
Time frame: Day 21
Population: The safety population included all participants who received any dose of planned study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Flomoxef | Number of Participants With Clinically Significant Abnormal Laboratory Values | Neutrophil count decreased | 1 participants |
| Flomoxef | Number of Participants With Clinically Significant Abnormal Laboratory Values | White blood cells count increased | 1 participants |
| Flomoxef | Number of Participants With Clinically Significant Abnormal Laboratory Values | C-reactive Protein level increased | 1 participants |
| Flomoxef | Number of Participants With Clinically Significant Abnormal Laboratory Values | C-reactive Protein level decreased | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Abnormal Laboratory Values | C-reactive Protein level decreased | 1 participants |
| Cefepime | Number of Participants With Clinically Significant Abnormal Laboratory Values | Neutrophil count decreased | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Abnormal Laboratory Values | C-reactive Protein level increased | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Abnormal Laboratory Values | White blood cells count increased | 0 participants |
Secondary
Number of Participants With Clinically Significant Change in Physical Examination Findings
Physical examination consists of examinations of the following body systems: (1) cardiovascular system; (2) dermatologic system (3) ears, nose, throat; (4) extremities; (5) eyes; (6) gastrointestinal system; (7) genitourinary system; (8) lymph nodes; (9) musculoskeletal system; (10) nervous system; (11) respiratory system.
Time frame: Day 1 up to Day 21
Population: The safety population included all participants who received any dose of planned study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Flomoxef | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 1: Eyes | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 1: Gastrointestinal system | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 1: Cardiovascular system | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 3: Cardiovascular system | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 7-14: Cardiovascular system | 1 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 14-21: Cardiovascular system | 1 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 1: Dermatologic system | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 3: Dermatologic system | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 7-14: Dermatologic system | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 14-21: Dermatologic system | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 1: Ear/Nose/Tongue | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 3: Ear/Nose/Tongue | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 7-14: Ear/Nose/Tongue | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 14-21: Ear/Nose/Tongue | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 1: Extremities | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 3: Extremities | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 7-14: Extremities | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 14-21: Extremities | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 3: Eyes | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 7-14: Eyes | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 4-21: Eyes | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 3: Gastrointestinal system | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 7-14: Gastrointestinal system | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 14-21: Gastrointestinal system | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 1: Genitourinary system | 6 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 3: Genitourinary system | 3 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 7-14: Genitourinary system | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 14-21: Genitourinary system | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 1: Lymph nodes | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 3: Lymph nodes | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 7-14: Lymph nodes | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 14-21: Lymph nodes | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 1: Musculoskeletal system | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 3: Musculoskeletal system | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 7-14: Musculoskeletal system | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 14-21: Musculoskeletal system | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 1: Nervous system | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 3: Nervous system | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 7-14: Nervous system | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 14-21: Nervous system | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 1: Respiratory system | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 3: Respiratory system | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 7-14: Respiratory system | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 14-21: Respiratory system | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 1: Musculoskeletal system | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 4-21: Eyes | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 3: Gastrointestinal system | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 7-14: Gastrointestinal system | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 1: Genitourinary system | 7 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 7-14: Nervous system | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 1: Cardiovascular system | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 3: Musculoskeletal system | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 3: Cardiovascular system | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 14-21: Gastrointestinal system | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 7-14: Cardiovascular system | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 3: Respiratory system | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 14-21: Cardiovascular system | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 7-14: Musculoskeletal system | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 1: Dermatologic system | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 3: Genitourinary system | 6 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 3: Dermatologic system | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 14-21: Nervous system | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 7-14: Dermatologic system | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 7-14: Genitourinary system | 1 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 14-21: Dermatologic system | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 14-21: Musculoskeletal system | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 1: Ear/Nose/Tongue | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 14-21: Genitourinary system | 1 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 3: Ear/Nose/Tongue | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 14-21: Respiratory system | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 7-14: Ear/Nose/Tongue | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 1: Lymph nodes | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 14-21: Ear/Nose/Tongue | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 1: Nervous system | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 1: Extremities | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 3: Lymph nodes | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 3: Extremities | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 1: Respiratory system | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 7-14: Extremities | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 7-14: Lymph nodes | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 14-21: Extremities | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 1: Eyes | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 3: Nervous system | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 3: Eyes | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 14-21: Lymph nodes | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 7-14: Eyes | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 7-14: Respiratory system | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Physical Examination Findings | Day 1: Gastrointestinal system | 0 participants |
Secondary
Number of Participants With Clinically Significant Change in Vital Signs
Vital signs included body temperature (axillary measurement), diastolic and systolic blood pressure (5 minutes), respiratory rate, and pulse (bpm).
Time frame: Day 1 up to Day 21
Population: The safety population included all participants who received any dose of planned study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Flomoxef | Number of Participants With Clinically Significant Change in Vital Signs | Day 1: Systolic Blood Pressure | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Vital Signs | Day 3: Body Temperature | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Vital Signs | Day 3: Systolic Blood Pressure | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Vital Signs | Day 7-14: Systolic Blood Pressure | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Vital Signs | Day 14-21: Systolic Blood Pressure | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Vital Signs | Day 1: Diastolic Blood Pressure | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Vital Signs | Day 3: Diastolic Blood Pressure | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Vital Signs | Day 7-14: Diastolic Blood Pressure | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Vital Signs | Day 14-21: Diastolic Blood Pressure | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Vital Signs | Day 1: Pulse Rate | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Vital Signs | Day 3: Pulse Rate | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Vital Signs | Day 7-14: Pulse Rate | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Vital Signs | Day 14-21: Pulse Rate | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Vital Signs | Day 1: Respiration Rate | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Vital Signs | Day 3: Respiration Rate | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Vital Signs | Day 7-14: Respiration Rate | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Vital Signs | Day 14-21: Respiration Rate | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Vital Signs | Day 1: Body Temperature | 2 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Vital Signs | Day 7-14: Body Temperature | 0 participants |
| Flomoxef | Number of Participants With Clinically Significant Change in Vital Signs | Day 14-21: Body Temperature | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Vital Signs | Day 1: Body Temperature | 2 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Vital Signs | Day 1: Systolic Blood Pressure | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Vital Signs | Day 3: Pulse Rate | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Vital Signs | Day 3: Body Temperature | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Vital Signs | Day 7-14: Respiration Rate | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Vital Signs | Day 3: Systolic Blood Pressure | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Vital Signs | Day 7-14: Pulse Rate | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Vital Signs | Day 7-14: Systolic Blood Pressure | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Vital Signs | Day 14-21: Body Temperature | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Vital Signs | Day 14-21: Systolic Blood Pressure | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Vital Signs | Day 14-21: Pulse Rate | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Vital Signs | Day 1: Diastolic Blood Pressure | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Vital Signs | Day 14-21: Respiration Rate | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Vital Signs | Day 3: Diastolic Blood Pressure | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Vital Signs | Day 1: Respiration Rate | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Vital Signs | Day 7-14: Diastolic Blood Pressure | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Vital Signs | Day 7-14: Body Temperature | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Vital Signs | Day 14-21: Diastolic Blood Pressure | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Vital Signs | Day 3: Respiration Rate | 0 participants |
| Cefepime | Number of Participants With Clinically Significant Change in Vital Signs | Day 1: Pulse Rate | 0 participants |
Secondary
Number of Participants With Serious Adverse Events (SAEs) and Treatment-Emergent-Adverse Events (TEAEs)
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. A Serious Adverse Event (SAE) A serious is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.
Time frame: Baseline up to Day 30
Population: The safety population included all participants who received any dose of planned study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Flomoxef | Number of Participants With Serious Adverse Events (SAEs) and Treatment-Emergent-Adverse Events (TEAEs) | SAEs | 0 participants |
| Flomoxef | Number of Participants With Serious Adverse Events (SAEs) and Treatment-Emergent-Adverse Events (TEAEs) | TEAEs | 2 participants |
| Cefepime | Number of Participants With Serious Adverse Events (SAEs) and Treatment-Emergent-Adverse Events (TEAEs) | SAEs | 0 participants |
| Cefepime | Number of Participants With Serious Adverse Events (SAEs) and Treatment-Emergent-Adverse Events (TEAEs) | TEAEs | 2 participants |
Secondary
Percentage of Participants Who Achieved Clinical Resolution of Symptoms of a cUTI at Visit 3, TOC and Late Follow-up (LFU) Visits
At Visit 3 (Day 3) and at the TOC (Days 14 to 21) and LFU visits (Day 30), the Investigator collected information about each symptom and performed a judgement about the participant's status. Clinical symptoms present at trial entry were considered to be resolved if the participant has no pyuria; no fever; no malaise, flank pain, back pain, and/or costo-vertebral angle pain or tenderness; and no symptoms of dysuria, urinary urgency, urinary frequency, suprapubic discomfort, new urinary incontinence, or worsening of pre-existing incontinence. Resolution of all clinical symptoms of cUTI were assessed relative to baseline.
Time frame: Baseline, Days 3, 14 to 21 and 30
Population: The micro-ITT population included all participants who were randomized and had a baseline bacterial pathogen on culture of urine that causes UTI against which the investigational drug has antibacterial activity.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Flomoxef | Percentage of Participants Who Achieved Clinical Resolution of Symptoms of a cUTI at Visit 3, TOC and Late Follow-up (LFU) Visits | Day 3 | 0.0 percentage of participants |
| Flomoxef | Percentage of Participants Who Achieved Clinical Resolution of Symptoms of a cUTI at Visit 3, TOC and Late Follow-up (LFU) Visits | Days 14 to 21 | 60.0 percentage of participants |
| Flomoxef | Percentage of Participants Who Achieved Clinical Resolution of Symptoms of a cUTI at Visit 3, TOC and Late Follow-up (LFU) Visits | Day 30 | 60.0 percentage of participants |
| Cefepime | Percentage of Participants Who Achieved Clinical Resolution of Symptoms of a cUTI at Visit 3, TOC and Late Follow-up (LFU) Visits | Day 30 | 57.1 percentage of participants |
| Cefepime | Percentage of Participants Who Achieved Clinical Resolution of Symptoms of a cUTI at Visit 3, TOC and Late Follow-up (LFU) Visits | Day 3 | 14.3 percentage of participants |
| Cefepime | Percentage of Participants Who Achieved Clinical Resolution of Symptoms of a cUTI at Visit 3, TOC and Late Follow-up (LFU) Visits | Days 14 to 21 | 28.6 percentage of participants |
Secondary
Percentage of Participants With a New Infection at the EOT and TOC Visits
A urine sample was collected from the participants at the EOT (Days 7 to 14) and TOC (Days 14 to 21) visits to determine the level of uropathogen. Cultures of the urine sample were processed by using a calibrated loop to identify a quantitative count of bacteria, with a lower limit of 10\^4 CFU/mL. A new infection was defined as the isolation and growth of a uropathogen other than the original pathogen.
Time frame: Baseline, Days 7 to 14 and 14 to 21
Population: Due to premature trial termination and small sample size, data for new infection due to particular pathogen numbers in different time periods was not determined.
Secondary
Percentage of Participants With a Superinfection at the EOT and TOC Visits
A urine sample was collected from the participants at the EOT (Days 7 to 14) and TOC (Days 14 to 21) visits to determine the level of uropathogen. Cultures of the urine sample were processed by using a calibrated loop to identify a quantitative count of bacteria, with a lower limit of 10\^4 CFU/mL. A superinfection was defined as growth of a uropathogen other than the original pathogen at a level greater than or equal to 10\^4 CFU/mL at any time during the course of active therapy.
Time frame: Baseline, Day 7 to 14 and 14 to 21
Population: Due to premature trial termination and small sample size, data for superinfection due to particular pathogen numbers in different time periods was not determined.
Secondary
Percentage of Participants With Microbiological Success at the EOT and Test-of-Cure (TOC) Visits
A urine sample was collected at EOT (Days 7 to 14) and TOC (Days 14 to 21) visits to determine level of uropathogen. Cultures of urine sample were processed by calibrated loop to identify a quantitative count of bacteria, with a lower limit of 10\^4 colony forming units per milliliter (CFU/mL). Microbiological success was defined as bacterial uropathogen level of \<10\^4 CFU/mL. Microbiological response was categorized as:microbiological eradication/persistence/new infection/superinfection. An infection was eradicated if all uropathogens isolated at study entry at a level ≥10\^4 CFU/mL have decreased to \<10\^4 CFU/mL, persistent if level of uropathogen has increased by ≥10\^4 CFU/Ml. A new infection, if there is isolation and growth of a uropathogen other than original pathogen and superinfection if there is growth of a uropathogen other than original pathogen at a level ≥10\^4 CFU/mL. Microbiological success was assessed relative to baseline.
Time frame: Baseline, Days 7 to 14 and 14 to 21
Population: The micro-ITT population included all participants who were randomized and had a baseline bacterial pathogen on culture of urine that causes UTI against which the investigational drug has antibacterial activity.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Flomoxef | Percentage of Participants With Microbiological Success at the EOT and Test-of-Cure (TOC) Visits | Days 7 to 14: Persistence | 20.0 percentage of participants |
| Flomoxef | Percentage of Participants With Microbiological Success at the EOT and Test-of-Cure (TOC) Visits | Days 14 to 21: Superinfection | 40.0 percentage of participants |
| Flomoxef | Percentage of Participants With Microbiological Success at the EOT and Test-of-Cure (TOC) Visits | Days 7 to 14: Superinfection | 0.0 percentage of participants |
| Flomoxef | Percentage of Participants With Microbiological Success at the EOT and Test-of-Cure (TOC) Visits | Days 14 to 21: Eradication | 80.0 percentage of participants |
| Flomoxef | Percentage of Participants With Microbiological Success at the EOT and Test-of-Cure (TOC) Visits | Days 14 to 21: New infection | 20.0 percentage of participants |
| Flomoxef | Percentage of Participants With Microbiological Success at the EOT and Test-of-Cure (TOC) Visits | Days 14 to 21: Persistence | 0.0 percentage of participants |
| Flomoxef | Percentage of Participants With Microbiological Success at the EOT and Test-of-Cure (TOC) Visits | Days 7 to 14: New infection | 0.0 percentage of participants |
| Flomoxef | Percentage of Participants With Microbiological Success at the EOT and Test-of-Cure (TOC) Visits | Days 7 to 14: Eradication | 80.0 percentage of participants |
| Cefepime | Percentage of Participants With Microbiological Success at the EOT and Test-of-Cure (TOC) Visits | Days 14 to 21: Superinfection | 28.6 percentage of participants |
| Cefepime | Percentage of Participants With Microbiological Success at the EOT and Test-of-Cure (TOC) Visits | Days 14 to 21: Eradication | 85.7 percentage of participants |
| Cefepime | Percentage of Participants With Microbiological Success at the EOT and Test-of-Cure (TOC) Visits | Days 14 to 21: New infection | 14.3 percentage of participants |
| Cefepime | Percentage of Participants With Microbiological Success at the EOT and Test-of-Cure (TOC) Visits | Days 7 to 14: Eradication | 85.7 percentage of participants |
| Cefepime | Percentage of Participants With Microbiological Success at the EOT and Test-of-Cure (TOC) Visits | Days 7 to 14: New infection | 14.3 percentage of participants |
| Cefepime | Percentage of Participants With Microbiological Success at the EOT and Test-of-Cure (TOC) Visits | Days 7 to 14: Persistence | 14.3 percentage of participants |
| Cefepime | Percentage of Participants With Microbiological Success at the EOT and Test-of-Cure (TOC) Visits | Days 14 to 21: Persistence | 14.3 percentage of participants |
| Cefepime | Percentage of Participants With Microbiological Success at the EOT and Test-of-Cure (TOC) Visits | Days 7 to 14: Superinfection | 14.3 percentage of participants |
Secondary
Percentage of Participants With Microbiologic Eradication of the Unique Pathogen at the EOT and TOC Visits
A urine sample was collected from the participants at the EOT (Days 7 to 14) and TOC (Day 14 to 21) visits to determine the level of uropathogen. Cultures of the urine sample were processed by using a calibrated loop to identify a quantitative count of bacteria, with a lower limit of 10\^4 CFU/mL. Microbiological response at the TOC visit was based on the same grades as for the EOT visit. The infection was considered to be eradicated if all uropathogens isolated at study entry at a level equal to or greater than 10\^4 CFU/mL have decreased to less than 10\^4 CFU/mL.
Time frame: Baseline, Days 7 to 14 and 14 to 21
Population: Due to premature trial termination and small sample size, data for eradication for particular pathogen numbers in different time periods was not determined.
Secondary
Percentage of Participants With Microbiologic Persistence of the Unique Pathogen at the EOT and TOC Visits
A urine sample was collected from the participants at the EOT (Days 7 to 14) and TOC (Days 14 to 21) visits to determine the level of uropathogen. Cultures of the urine sample was processed by using a calibrated loop to identify a quantitative count of bacteria, with a lower limit of 10\^4 CFU/mL. Microbiological response at the TOC visit was be based on the same grades as for the EOT visit. The infection was considered to be persistent if the level of the uropathogen has increased by greater than or equal to 10\^4 CFU/mL from the time of study entry to that of the EOT and TOC visits.
Time frame: Baseline, Days 7 to 14 and 14 to 21
Population: Due to premature trial termination and small sample size, data for persistence of particular pathogen numbers in different time periods was not determined.