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

• Sponsor: Cubist Pharmaceuticals LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00921024
• Collaborator: (none)
• Enrollment: 129
• Locations: 21
• Arms: 2
• Actual Duration (Months): 8.3
• Patients Per Site: 6.1
• Patients Per Site Per Month: 0.7

Study Details

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

Condition or Disease	Intervention/Treatment	Phase
Complicated Urinary Tract Infection	Drug: CXA-101; Drug: Ceftazidime	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 129 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A 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
• Actual Study Start Date: Jun 30, 2009
• Actual Primary Completion Date: Feb 25, 2010
• Actual Study Completion Date: Mar 11, 2010

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

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

   Microbiological response is eradication for each baseline pathogen

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

   Microbiological response is eradication for each baseline pathogen

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

1. Pyelonephritis, as indicated by both of the following: i. Fever (oral temperature ≥ 37.8°C); ii. Flank pain or costovertebral angle tenderness;

OR

1. 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

1. 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Healthcare Partners Medical Group	Los Angeles	California	United States	90015
2	Compass Research, LLC	Orlando	Florida	United States	32806
3	Atlanta Institute for Medical Research, Inc.	Decatur	Georgia	United States	30030
4	Infectious Disease of Indiana, PSC	Indianapolis	Indiana	United States	46280
5	Mississippi Medical Research, LLC	Picayune	Mississippi	United States	39466
6	Great Falls Clinic, LLP	Butte	Montana	United States	59701
7	Remington-Davis, Inc. Clinical Research	Columbus	Ohio	United States	43215
8	Kreiskrankenhaus Backnang	Backnang		Germany	71522
9	URO Forschungs GmbH	Berlin		Germany	10115
10	Uniklinikum Giessen	Giessen		Germany	35392
11	Evangelisches Krankenhaus Giessen Urologie	Giessen		Germany	35398
12	Universitätsklinikum Schleswig Holstein Campus Lübeck	Lübeck		Germany	23538
13	Brüderkrankenhaus St. Josef Paderborn	Paderborn		Germany	33098
14	Urologische Klinik Dr. Castringius München-Planegg	Planegg		Germany	82152
15	Samodzielny Publiczny Szpital Kliniczny nr 4 Katedra i Klinika Nefrologii	Lublin		Poland	20-954
16	Wojewódźki Szpital Specjalistyczny nr 1 Oddział Chorób Wewnętrznych	Tychy		Poland	43-100
17	Szpital Bielański im.Ks. Jerzego Popiełuszki Samodzielny Publiczny Zakład Opieki Zdrowotnej IV Kliniczny Oddzial Chorób Wewnętrznych	Warszawa		Poland	01-809
18	Szpital Kliniczny Dzieciątka Jezus-Centrum Leczenia Obrażeń Klinika Urologii Ogólnej, Onkologicznej Czynnościowej	Warszawa		Poland	02-005
19	Szpital Praski p.w. Przemienienia Pańskiego Samodzielny Publiczny Zakład Opieki Zdrowotnej ll Oddział Wewnętrznych	Warszawa		Poland	03-401
20	Wojewódźki Szpital Specjalistyczny Oddział Nefrologiczny	Wrocław		Poland	51-124
21	Samodzielny Publiczny Szpital Wojewódźki im. Papieża Jana Pawła ll Oddział Wewnętrznych Nefrologiczno-Endokrynologiczny ze Stacją Dializ	Zamość		Poland	22-400

Sponsors and Collaborators

• Cubist Pharmaceuticals LLC

Investigators

• Principal Investigator: Ahmad Haidar, MD, Mississippi Medical Research, LLC
• Principal Investigator: Ryszard Gellert, MD, Szpital Bielański im.Ks. Jerzego Popiełuszki Samodzielny Publiczny Zakład Opieki Zdrowotnej IV Kliniczny Oddzial Chorób Wewnętrznych i Pododdział Nefrologiczny
• Principal Investigator: Florian Wagenlehner, MD, Uniklinikum Giessen

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Cubist Pharmaceuticals LLC
• ClinicalTrials.gov Identifier: NCT00921024
• Other Study ID Numbers: 7625-001; CXA 101-03
• First Posted: Jun 16, 2009
• Last Update Posted: Oct 18, 2018
• Last Verified: Sep 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Cubist Pharmaceuticals LLC: Complicated Urinary Tract Infection; Pyelonephritis; Antimicrobial; Cephalosporin; Intravenous
• Additional relevant MeSH terms: Infections; Communicable Diseases; Urinary Tract Infections; Pyelonephritis; Ceftazidime; Ceftolozane

Study Results

Participant Flow

Pre-assignment Detail	Two subjects, one in each arm, did not receive treatment.

Arm/Group Title	CXA-101	Ceftazidime
Arm/Group Description	CXA-101: intravenous 1000 mg every 8 hours	Ceftazidime: intravenous 1000 mg every 8 hours
Period Title: Overall Study
STARTED	85	42
COMPLETED	81	39
NOT COMPLETED	4	3

Baseline Characteristics

Arm/Group Title	CXA-101	Ceftazidime	Total
Arm/Group Description	CXA-101: intravenous 1000 mg every 8 hours	Ceftazidime: intravenous 1000 mg every 8 hours	Total of all reporting groups
Overall Participants	85	42	127
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.8 (19.78)	62.7 (19.74)	58.8 (19.88)
Sex: Female, Male (Count of Participants)
Female	42 49.4%	16 38.1%	58 45.7%
Male	43 50.6%	26 61.9%	69 54.3%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

mMITT: Treated patients, with baseline pathogen.

Arm/Group Title	CXA-101	Ceftazidime
Arm/Group Description	CXA-101: intravenous 1000 mg every 8 hours	Ceftazidime: intravenous 1000 mg every 8 hours
Measure Participants	65	38
Number (95% Confidence Interval) [percentage of patients]	83.1	76.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CXA-101, Ceftazidime
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	6.8
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

ME: Treated patients, with baseline pathogen, complied with protocol.

Arm/Group Title	CXA-101	Ceftazidime
Arm/Group Description	CXA-101: intravenous 1000 mg every 8 hours	Ceftazidime: intravenous 1000 mg every 8 hours
Measure Participants	55	27
Number (95% Confidence Interval) [percentage of patients]	85.5	92.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CXA-101, Ceftazidime
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-7.1
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	CXA-101		Ceftazidime
Arm/Group Description	CXA-101: intravenous 1000 mg every 8 hours		Ceftazidime: intravenous 1000 mg every 8 hours
All Cause Mortality
	CXA-101		Ceftazidime
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	CXA-101		Ceftazidime
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/85 (1.2%)		0/42 (0%)
Infections and infestations
Pyelonephritis	1/85 (1.2%)	1	0/42 (0%)	0
Other (Not Including Serious) Adverse Events
	CXA-101		Ceftazidime
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	33/85 (38.8%)		16/42 (38.1%)
Blood and lymphatic system disorders
Anaemia	1/85 (1.2%)		1/42 (2.4%)
Ear and labyrinth disorders
Vertigo	0/85 (0%)		1/42 (2.4%)
Eye disorders
Arteriosclerotic retinopathy	0/85 (0%)		1/42 (2.4%)
Retinal degeneration	0/85 (0%)		1/42 (2.4%)
Vision blurred	0/85 (0%)		1/42 (2.4%)
Visual impairment	0/85 (0%)		1/42 (2.4%)
Gastrointestinal disorders
Abdominal pain	2/85 (2.4%)		1/42 (2.4%)
Abdominal pain upper	1/85 (1.2%)		1/42 (2.4%)
Constipation	8/85 (9.4%)		2/42 (4.8%)
Diarrhoea	3/85 (3.5%)		3/42 (7.1%)
Gingival pain	0/85 (0%)		1/42 (2.4%)
Mouth ulceration	0/85 (0%)		1/42 (2.4%)
Nausea	5/85 (5.9%)		0/42 (0%)
Oral pain	0/85 (0%)		1/42 (2.4%)
Vomiting	1/85 (1.2%)		1/42 (2.4%)
General disorders
Chest pain	0/85 (0%)		1/42 (2.4%)
Chills	0/85 (0%)		1/42 (2.4%)
Feeling abnormal	0/85 (0%)		1/42 (2.4%)
Infusion site erythema	2/85 (2.4%)		0/42 (0%)
Infusion site extravasation	2/85 (2.4%)		0/42 (0%)
Infustion site irritation	3/85 (3.5%)		0/42 (0%)
Infusion site reaction	1/85 (1.2%)		1/42 (2.4%)
Infustion site swelling	2/85 (2.4%)		0/42 (0%)
Pyrexia	3/85 (3.5%)		1/42 (2.4%)
Infections and infestations
Urinary tract infection	2/85 (2.4%)		0/42 (0%)
Metabolism and nutrition disorders
Hypokalaemia	1/85 (1.2%)		1/42 (2.4%)
Musculoskeletal and connective tissue disorders
Back pain	2/85 (2.4%)		1/42 (2.4%)
Flank pain	2/85 (2.4%)		0/42 (0%)
Nervous system disorders
Headache	5/85 (5.9%)		0/42 (0%)
Psychiatric disorders
Agression	0/85 (0%)		1/42 (2.4%)
Depression	0/85 (0%)		1/42 (2.4%)
Insomnia	4/85 (4.7%)		0/42 (0%)
Sleep disorder	6/85 (7.1%)		2/42 (4.8%)
Renal and urinary disorders
Haematuria	0/85 (0%)		1/42 (2.4%)
Renal cyst	1/85 (1.2%)		1/42 (2.4%)
Respiratory, thoracic and mediastinal disorders
Cough	2/85 (2.4%)		0/42 (0%)
Dyspnoea	1/85 (1.2%)		1/42 (2.4%)
Skin and subcutaneous tissue disorders
Blister	1/85 (1.2%)		1/42 (2.4%)
Vascular disorders
Hypertension	2/85 (2.4%)		0/42 (0%)
Hypotension	1/85 (1.2%)		1/42 (2.4%)
Phlebitis	2/85 (2.4%)		0/42 (0%)

Limitations/Caveats

[Not Specified]

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.