Safety and Efficacy of IV CXA-101 and IV Ceftazidime in Patients With Complicated Urinary Tract Infections

ID: NCT00921024
Status: Completed
Phase: Phase 2
Start Date: July 01, 2009
First Submitted: June 12, 2009
Last Updated: January 06, 2016
Results: Available
Success Rate: 94%
Sponsors & Collaborators: Cubist Pharmaceuticals LLC
Location: Germany, Poland, United States
Conditions: Complicated Urinary Tract Infection
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Study Description

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of intravenous CXA 101 and comparator in complicated urinary tract infection

Detailed Description

This is a Phase 2, multicenter, prospective, randomized, double-blind, comparative efficacy and safety study of IV CXA 101 versus IV ceftazidime for 7 to 10 days.

Subjects are followed up 6 to 9 days after the last dose of study drug to assess clinical signs and symptoms of infection. A Late Follow Up evaluation (21 to 28 days after the last dose of study drug) occurs for those subjects who respond to therapy. The primary assessment of effectiveness is the microbiological response (the eradication at post-therapy of the infectious organism identified at the start of study). An additional assessment of efficacy includes the overall clinical response, which is described as cured, improved, or failed. Safety assessments include the incidence of adverse events throughout the study, clinical laboratory tests (hematology, serum chemistry, and urinalysis) and physical examinations at the start of the study and post-therapy.
Condition or disease Intervention/treatment Phase

Complicated Urinary Tract Infection

Drug: CXA-101
Other Names
Drug: Ceftazidime
Other Names
Phase 2

Tracking Information

First Submitted DateJune 12, 2009
Last Update Posted DateJanuary 06, 2016
Start DateJuly 01, 2009
Actual Completion DateApril 01, 2010
Primary Completion DateMarch 01, 2010
Results First Submitted DateJanuary 09, 2015
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • Microbiological Response at the Test of Cure (TOC) Visit in the Microbiological Modified Intent-to-Treat (mMITT) Population [Time Frame: TOC; 6-9 days after last study drug administration]

    Microbiological response is eradication for each baseline pathogen

  • Microbiological Response at the TOC Visit in the Microbiologically Evaluable (ME) Population. [Time Frame: TOC; 6-9 days after last study drug administration]

    Microbiological response is eradication for each baseline pathogen

Original Primary Outcome Measures

  • Microbiological Response at the TOC Visit in the Microbiologically Evaluable (ME) Population.

    Microbiological response is eradication for each baseline pathogen

  • Microbiological Response at the Test of Cure (TOC) Visit in the Microbiological Modified Intent-to-Treat (mMITT) Population

    Microbiological response is eradication for each baseline pathogen

Current Secondary Outcome Measures

Not Available

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleSafety and Efficacy of IV CXA-101 and IV Ceftazidime in Patients With Complicated Urinary Tract Infections
Official TitleA Multicenter, Double-blind, Randomized, Phase 2 Study to Compare the Safety and Efficacy of Intravenous CXA-101 and Intravenous Ceftazidime in Complicated Urinary Tract Infection, Including Pyelonephritis
Brief Summary

The purpose of this study is to evaluate the safety and efficacy of intravenous CXA 101 and comparator in complicated urinary tract infection

Detailed Description

This is a Phase 2, multicenter, prospective, randomized, double-blind, comparative efficacy and safety study of IV CXA 101 versus IV ceftazidime for 7 to 10 days.

Subjects are followed up 6 to 9 days after the last dose of study drug to assess clinical signs and symptoms of infection. A Late Follow Up evaluation (21 to 28 days after the last dose of study drug) occurs for those subjects who respond to therapy. The primary assessment of effectiveness is the microbiological response (the eradication at post-therapy of the infectious organism identified at the start of study). An additional assessment of efficacy includes the overall clinical response, which is described as cured, improved, or failed. Safety assessments include the incidence of adverse events throughout the study, clinical laboratory tests (hematology, serum chemistry, and urinalysis) and physical examinations at the start of the study and post-therapy.

Study TypeInterventional
Study PhasePhase 2
Estimated Enrollment
129
Allocation
Randomized
Interventional Model
Parallel Assignment
Masking
Quadruple
Primary Purpose
Treatment
Conditions
Complicated Urinary Tract Infection
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
Drug: CXA-101

intravenous

Other Names
Drug: Ceftazidime

intravenous

Other Names
Study Groups/Cohorts
1
CXA-101

2
Ceftazidime

Study Arms
Experimental 1
CXA-101
Drug : CXA-101
intravenous

Active Comparator 2
Ceftazidime
Drug : Ceftazidime
intravenous

Arm Intervention/Treatment
Experimental 1
CXA-101
Drug : CXA-101
Active Comparator 2
Ceftazidime
Drug : Ceftazidime

Recruitment Information

Recruitment Status:Completed
Enrollment129
Completion DateApril 01, 2010
Eligibility Criteria: Inclusion Criteria:
1. Males and females 18 to 90 years of age, inclusive.
2. Pyuria (white blood cell [WBC] count > 10/µL in unspun urine or ≥ 10 per high power field in spun urine)
3. Clinical signs and/or symptoms of cUTI, either of:
a. Pyelonephritis, as indicated by both of the following: i. Fever (oral temperature ≥ 37.8°C); ii. Flank pain or costovertebral angle tenderness;
OR
b. Complicated lower UTI, as indicated by both of the following: i. At least one of the following new or worsening symptoms:
- Dysuria;
- Frequency;
- Suprapubic pain;
- Urgency
ii. At least one of the following complicating factors:
- Male gender;
- Current bladder instrumentation or indwelling urinary catheter that is expected to be removed during the course of IV study drug administration;
- Obstructive uropathy that is expected to be medically or surgically treated during the course of IV study drug administration;
- Urogenital surgery within 7 days preceding administration of the first dose of study drug;
- Functional or anatomical abnormality of the urogenital tract including anatomic malformations or neurogenic bladder with voiding disturbance of at least 100 mL residual urine.

Exclusion Criteria
1. Documented history of any hypersensitivity or allergic reaction to any β-lactam antibacterial
2. Concomitant infection requiring systemic antibacterial therapy in addition to IV study drug therapy at the time of randomization. Drugs with only gram-positive activity (e.g. vancomycin, linezolid) are allowed
3. Complete, permanent obstruction of the urinary tract
4. Confirmed (at time of randomization) fungal urinary tract infection (with ≥ 103 fungal CFU/mL)
5. Suspected or confirmed perinephric or intrarenal abscess
6. Suspected or confirmed prostatitis
7. Known ileal loop or vesico-ureteral reflux
8. Women who are pregnant or nursing
GenderAll
Age18 Years to 90 Years
Accepts Healthy VolunteersNo
Contacts
Not Available
Listed Location Countries
Germany
Poland
United States

Administrative Information

NCT Number:NCT00921024
Other Study ID Numbers
7625-001
CXA 101-03
Has Data Monitoring CommitteeNo
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible Party,
Study Sponsor
Cubist Pharmaceuticals LLC
Collaborators
Not Available
Investigators
Principal Investigator
Ahmad Haidar, MD
Mississippi Medical Research, LLC
Principal Investigator
Florian Wagenlehner, MD
Uniklinikum Giessen
Principal Investigator
Ryszard Gellert, MD
Szpital Bielański im.Ks. Jerzego Popiełuszki Samodzielny Publiczny Zakład Opieki Zdrowotnej IV Kliniczny Oddzial Chorób Wewnętrznych i Pododdział Nefrologiczny

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Not Available

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Two subjects, one in each arm, did not receive treatment.

Reporting Groups

TitleDescription
CXA-101
CXA-101: intravenous 1000 mg every 8 hours
Ceftazidime
Ceftazidime: intravenous 1000 mg every 8 hours

Participant Flow: Overall

CXA-101Ceftazidime
Started8542
Completed8139
Not Completed43
Lost to Follow-up20
Received concomittant therapy20
Withdrawal by Subject03

Baseline Characteristics

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Not Available

Reporting Groups

TitleDescription
CXA-101
CXA-101: intravenous 1000 mg every 8 hours
Ceftazidime
Ceftazidime: intravenous 1000 mg every 8 hours
Total
Total of all reporting groups

Baseline Measures

CXA-101CeftazidimeTotal
Overall Participants Analyzed
Units: Participants
Participants Analyzed
8542127
8542127
Age
Units: years - Mean (Standard Deviation)
Participants Analyzed
8542127
56.8 (19.78)62.7 (19.74)58.8 (19.88)
Gender
Units: participants - Number
Participants Analyzed
8542127
Female421658
Male432669

Outcome Measures

1. Primary: Microbiological Response at the Test of Cure (TOC) Visit in the Microbiological Modified Intent-to-Treat (mMITT) Population

Measure Type
Primary
Measure Title
Microbiological Response at the Test of Cure (TOC) Visit in the Microbiological Modified Intent-to-Treat (mMITT) Population
Measure Description
Microbiological response is eradication for each baseline pathogen
Time Frame
TOC; 6-9 days after last study drug administration

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
mMITT: Treated patients, with baseline pathogen.

Reporting Groups

TitleDescription
CXA-101
CXA-101: intravenous 1000 mg every 8 hours
Ceftazidime
Ceftazidime: intravenous 1000 mg every 8 hours

Outcome Measures

CXA-101Ceftazidime
Participants Analyzed
Units: Participants
6538
Microbiological Response at the Test of Cure (TOC) Visit in the Microbiological Modified Intent-to-Treat (mMITT) Population
Units: percentage of patients - Number (95% Confidence Interval)
83.176.3

Statistical Analysis

Groups
All Groups
Statistical Test Type
Superiority or Other
Statistical Method
Not Available
P Value
Not Available
Risk Difference (RD)
6.80000
to
  1. Additional details about the analysis, such as null hypothesis and power calculation
    Not Available
  2. Details of power calculation, definition of non-inferiority margin, and other key parameters
    Not Available
  3. Other relevant method information, such as adjustments or degrees of freedom
    Not Available
  4. Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance
    Not Available
  5. Other relevant estimation information
    Not Available

2. Primary: Microbiological Response at the TOC Visit in the Microbiologically Evaluable (ME) Population.

Measure Type
Primary
Measure Title
Microbiological Response at the TOC Visit in the Microbiologically Evaluable (ME) Population.
Measure Description
Microbiological response is eradication for each baseline pathogen
Time Frame
TOC; 6-9 days after last study drug administration

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ME: Treated patients, with baseline pathogen, complied with protocol.

Reporting Groups

TitleDescription
CXA-101
CXA-101: intravenous 1000 mg every 8 hours
Ceftazidime
Ceftazidime: intravenous 1000 mg every 8 hours

Outcome Measures

CXA-101Ceftazidime
Participants Analyzed
Units: Participants
5527
Microbiological Response at the TOC Visit in the Microbiologically Evaluable (ME) Population.
Units: percentage of patients - Number (95% Confidence Interval)
85.592.6

Statistical Analysis

Groups
All Groups
Statistical Test Type
Superiority or Other
Statistical Method
Not Available
P Value
Not Available
Risk Difference (RD)
-7.10000
to
  1. Additional details about the analysis, such as null hypothesis and power calculation
    Not Available
  2. Details of power calculation, definition of non-inferiority margin, and other key parameters
    Not Available
  3. Other relevant method information, such as adjustments or degrees of freedom
    Not Available
  4. Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance
    Not Available
  5. Other relevant estimation information
    Not Available

Serious Adverse Events

Time Frame
Not Available
Additional Description
Not Available
Frequency Threshold0% (Threshold above which other adverse events are reported)

Reporting Groups

TitleDescription
CXA-101
CXA-101: intravenous 1000 mg every 8 hours
Ceftazidime
Ceftazidime: intravenous 1000 mg every 8 hours

Serious Adverse Events

CXA-101Ceftazidime
Total, serious adverse events
No. of participants affected / at risk1/85 (0.00%)0/42 (0.00%)
Pyelonephritis
No. of participants affected / at risk1/85 (0.00%)0/42 (0.00%)

Other Adverse Events

Time Frame
Not Available
Additional Description
Not Available
Frequency Threshold2% (Threshold above which other adverse events are reported)

Reporting Groups

TitleDescription
CXA-101
CXA-101: intravenous 1000 mg every 8 hours
Ceftazidime
Ceftazidime: intravenous 1000 mg every 8 hours

Other Adverse Events

CXA-101Ceftazidime
Total, other adverse events
No. of participants affected / at risk33/85 (0.00%)16/42 (0.00%)
Anaemia
No. of participants affected / at risk1/85 (0.00%)1/42 (0.00%)
Vertigo
No. of participants affected / at risk0/85 (0.00%)1/42 (0.00%)
Arteriosclerotic retinopathy
No. of participants affected / at risk0/85 (0.00%)1/42 (0.00%)
Retinal degeneration
No. of participants affected / at risk0/85 (0.00%)1/42 (0.00%)
Vision blurred
No. of participants affected / at risk0/85 (0.00%)1/42 (0.00%)
Visual impairment
No. of participants affected / at risk0/85 (0.00%)1/42 (0.00%)
Abdominal pain
No. of participants affected / at risk2/85 (0.00%)1/42 (0.00%)
Abdominal pain upper
No. of participants affected / at risk1/85 (0.00%)1/42 (0.00%)
Constipation
No. of participants affected / at risk8/85 (0.00%)2/42 (0.00%)
Diarrhoea
No. of participants affected / at risk3/85 (0.00%)3/42 (0.00%)
Gingival pain
No. of participants affected / at risk0/85 (0.00%)1/42 (0.00%)
Mouth ulceration
No. of participants affected / at risk0/85 (0.00%)1/42 (0.00%)
Nausea
No. of participants affected / at risk5/85 (0.00%)0/42 (0.00%)
Oral pain
No. of participants affected / at risk0/85 (0.00%)1/42 (0.00%)
Vomiting
No. of participants affected / at risk1/85 (0.00%)1/42 (0.00%)
Chest pain
No. of participants affected / at risk0/85 (0.00%)1/42 (0.00%)
Chills
No. of participants affected / at risk0/85 (0.00%)1/42 (0.00%)
Feeling abnormal
No. of participants affected / at risk0/85 (0.00%)1/42 (0.00%)
Infusion site erythema
No. of participants affected / at risk2/85 (0.00%)0/42 (0.00%)
Infusion site extravasation
No. of participants affected / at risk2/85 (0.00%)0/42 (0.00%)
Infustion site irritation
No. of participants affected / at risk3/85 (0.00%)0/42 (0.00%)
Infusion site reaction
No. of participants affected / at risk1/85 (0.00%)1/42 (0.00%)
Infustion site swelling
No. of participants affected / at risk2/85 (0.00%)0/42 (0.00%)
Pyrexia
No. of participants affected / at risk3/85 (0.00%)1/42 (0.00%)
Urinary tract infection
No. of participants affected / at risk2/85 (0.00%)0/42 (0.00%)
Hypokalaemia
No. of participants affected / at risk1/85 (0.00%)1/42 (0.00%)
Back pain
No. of participants affected / at risk2/85 (0.00%)1/42 (0.00%)
Flank pain
No. of participants affected / at risk2/85 (0.00%)0/42 (0.00%)
Headache
No. of participants affected / at risk5/85 (0.00%)0/42 (0.00%)
Agression
No. of participants affected / at risk0/85 (0.00%)1/42 (0.00%)
Depression
No. of participants affected / at risk0/85 (0.00%)1/42 (0.00%)
Insomnia
No. of participants affected / at risk4/85 (0.00%)0/42 (0.00%)
Sleep disorder
No. of participants affected / at risk6/85 (0.00%)2/42 (0.00%)
Haematuria
No. of participants affected / at risk0/85 (0.00%)1/42 (0.00%)
Renal cyst
No. of participants affected / at risk1/85 (0.00%)1/42 (0.00%)
Cough
No. of participants affected / at risk2/85 (0.00%)0/42 (0.00%)
Dyspnoea
No. of participants affected / at risk1/85 (0.00%)1/42 (0.00%)
Blister
No. of participants affected / at risk1/85 (0.00%)1/42 (0.00%)
Hypertension
No. of participants affected / at risk2/85 (0.00%)0/42 (0.00%)
Hypotension
No. of participants affected / at risk1/85 (0.00%)1/42 (0.00%)
Phlebitis
No. of participants affected / at risk2/85 (0.00%)0/42 (0.00%)

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.
The data generated in this clinical study are the exclusive property of the Sponsor and are confidential. Authorship on any primary publication of the results from this study will be based on contributions to study design, enrollment, data analysis, and interpretation of results.

Results Point of Contact

Name/TitleOrganizationPhoneEmail
Dr. Obi Umeh, Vice President Global Medical Sciences
Cubist Pharmaceuticals, Inc.
781-860-8415