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Compare Ceftazidime-Avibactam and Doripenem Followed by Oral Therapy for Hospitalized Adults With Complicated UTIs (Urinary Tract Infections)

This study is currently recruiting participants.
Verified May 2013 by AstraZeneca
Sponsor:
Collaborator:
Cerexa, Inc.
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01599806
First received: May 15, 2012
Last updated: May 8, 2013
Last verified: May 2013
History of Changes
  Purpose

The purpose of this study is to evaluate the effects of Ceftazidime Avibactam compared to Doripenem for treating hospitalized patients with complicated urinary tract infections, including acute pyelonephritis.


Condition Intervention Phase
cUTI
Complicated Urinary Tract Infection
Acute Pyelonephritis
 Drug: CAZ-AVI
Drug: Doripenem
Drug: Either switch to oral therapy : 500 mg of Ciprofloxacin (oral)
Drug: or switch to oral therapy : 800 mg/160 mg of sulfamethoxazole/trimethoprim
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase III, Randomized, Multicenter, Double-Blind, Double Dummy, Parallel Group, Comparative Study to Determine the Efficacy, Safety, and Tolerability of Ceftazidime Avibactam (CAZ-AVI, Formerly CAZ104) Versus Doripenem Followed by Appropriate Oral Therapy in the Treatment of Complicated Urinary Tract Infections, Including Acute Pyelonephritis, With a Gram Negative Pathogen in Hospitalized Adults

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • The proportion of patients with resolved (or return to premorbid) UTI (Urinary Tract Infection) symptoms except flank pain and resolution or improvement in flank pain based on patient-reported symptom assessment response [ Time Frame: Day 5 after study drug start ] [ Designated as safety issue: No ]
  • The proportion of patients with a per patient microbiological eradication and resolution (or return to premorbid) of all UTI (Urinary Tract Infection)-specified symptoms based on patient-reported symptom assessment response [ Time Frame: 21 to 25 day after randomization ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The proportion of patients with a favorable per patient microbiological response in the microbiological modified Intent-To-Treat analysis set [ Time Frame: Within 24 hours after IV (intravenous) completion, 21 to 25 days and 45 to 52 days after study drug start ] [ Designated as safety issue: No ]
  • The proportion of patients with a favorable per patient microbiological response in the microbiologically evaluable analysis set [ Time Frame: Within 24 hours after IV (intravenous) completion, 21 to 25 days and 45 to 52 days after study drug start ] [ Designated as safety issue: No ]
  • The proportion of patients with a favorable per patient microbiological response in the extended microbiological evaluable analysis set [ Time Frame: Within 24 hours after IV (intravenous) completion, 21 to 25 days and 45 to 52 days after study drug start ] [ Designated as safety issue: No ]
  • The proportion of patients with resolution (or return to premorbid) of all UTI (Urinary Tract Infection)-specific symptoms based on the patient-reported symptom assessment response in the microbiological modified Intent-To-Treat analysis set [ Time Frame: 21 to 25 days and 45 to 52 days after study drug start ] [ Designated as safety issue: No ]
  • The proportion of favorable per-pathogen microbiological response in the microbiological modified Intent-To-Treat analysis set [ Time Frame: Within 24 hours after IV (intravenous) completion, 21 to 25 days and 45 to 52 days after study drug start ] [ Designated as safety issue: No ]
  • The proportion of favorable per-pathogen microbiological response in the microbiologically evaluable analysis set [ Time Frame: Within 24 hours after IV (intravenous) completion, 21 to 25 days and 45 to 52 days after the start of the study drug ] [ Designated as safety issue: No ]
  • The proportion of favorable per-pathogen microbiological response in the extended microbiologically evaluable analysis set [ Time Frame: Within 24 hours after IV (intravenous) completion, 21 to 25 days and 45 to 52 days after the start of the study drug ] [ Designated as safety issue: No ]
  • The proportion of patients with an investigator-determined clinical cure in the microbiological modified Intent-To-Treat analysis set [ Time Frame: Within 24 hours after IV(intravenous) completion, 21 to 25 days and 45 to 52 days after the start of the study drug ] [ Designated as safety issue: No ]
  • The proportion of patients with an investigator-determined clinical cure in the microbiologically evaluable analysis set [ Time Frame: Within 24 hours after IV (intravenous) completion, 21 to 25 days and 45 to 52 days after the start of the study drug ] [ Designated as safety issue: No ]
  • The proportion of patients with an investigator-determined clinical cure in the extended microbiologically evaluable analysis set [ Time Frame: Within 24 hours after IV (intravenous) completion,anytime between 21 - 25 days and anytime between 45 - 52 days after the start of the study drug ] [ Designated as safety issue: No ]
  • The proportion of patients with an investigator-determined clinical cure in the clinically evaluable analysis set [ Time Frame: Within 24 hours after IV (intravenous) completion, 21 to 25 days and 45 to 52 days after the start of the study drug ] [ Designated as safety issue: No ]
  • The favorable per pathogen microbiologic response by categories of minimum inhibitory concentration in the microbiological modified Intent-To-Treat analysis set [ Time Frame: Within 24 hours after IV(intravenous) completion, 21 to 25 days and 45 to 52 days after the start of the study drug ] [ Designated as safety issue: No ]
  • The favorable per pathogen microbiologic response by categories of minimum inhibitory concentration in the microbiologically evaluable analysis set [ Time Frame: Within 24 hours after IV (intravenous) completion, 21 to 25 days and 45 to 52 days after the start of the study drug ] [ Designated as safety issue: No ]
  • The favorable per pathogen microbiologic response by categories of minimum inhibitory concentration in the extended microbiologically evaluable analysis set [ Time Frame: Within 24 hours after completion of study drug, 21 to 25 days and 45 to 52 days after the start of the study drug ] [ Designated as safety issue: No ]
  • The proportion of patients with favorable investigator clinical response assessment in patients infected with a ceftazidime resistant pathogen in the microbiological modified Intent-To-Treat analysis set [ Time Frame: 21 to 25 days after study drug start ] [ Designated as safety issue: No ]
  • The proportion of patients with an investigator-determined clinical cure in patients infected with a ceftazidime resistant pathogen in the microbiologically evaluable analysis set [ Time Frame: 21 to 25 days after study drug start ] [ Designated as safety issue: No ]
  • The proportion of patients with an investigator-determined clinical cure in patients infected with a ceftazidime resistant pathogen in the extended microbiologically evaluable analysis set [ Time Frame: 21 to 25 days after study drug start ] [ Designated as safety issue: No ]
  • The proportion of patients with favorable per-patient microbiological response for patients infected with a ceftazidime resistant pathogen in the microbiological modified Intent-To-Treat analysis set [ Time Frame: 21 to 25 days after study drug start ] [ Designated as safety issue: No ]
  • The proportion of patients with favorable per-patient microbiological response for patients infected with a ceftazidime resistant pathogen in the microbiologically evaluable analysis set [ Time Frame: 21 to 25 days after study drug start ] [ Designated as safety issue: No ]
  • The proportion of patients with favorable per-patient microbiological response for patients infected with a ceftazidime resistant pathogen in the extended microbiologically evaluable analysis set [ Time Frame: 21 to 25 days after study drug start ] [ Designated as safety issue: No ]
  • The proportion of patients with symptomatic resolution (defined in the primary variables) for patients infected with a ceftazidime resistant pathogen in the microbiological modified Intent-To-Treat analysis set [ Time Frame: Day 5 and 21 to 25 days after study drug start ] [ Designated as safety issue: No ]
  • The time to first defervescence while on IV (intravenous) study therapy in patients in the microbiological modified Intent-To-Treat analysis set who have fever at study entry [ Time Frame: Any time after start of study drug to end of IV (intravenous) study therapy, which is a minimum of 5 days to a maximum of 14 days of IV study therapy ] [ Designated as safety issue: No ]
  • The time to first defervescence while on IV (intravenous) study therapy in patients in the microbiologically evaluable analysis set who have fever at study entry [ Time Frame: Any time after start of study drug to end of IV (intravenous) study therapy, which is a minimum of 5 days to a maximum of 14 days of IV study therapy ] [ Designated as safety issue: No ]
  • The time to first defervescence while on IV (intravenous) study therapy in patients in the extended microbiologically evaluable analysis set who have fever at study entry [ Time Frame: Any time after start of study drug to end of IV (intravenous) study therapy, which is a minimum of 5 days to a maximum of 14 days of IV study therapy ] [ Designated as safety issue: No ]
  • The time to first defervescence while on IV (intravenous) study therapy in patients in the clinically evaluable analysis set who have fever at study entry [ Time Frame: Any time after start of study drug to end of IV (intravenous) study therapy, which is a minimum of 5 days to a maximum of 14 days of IV study therapy ] [ Designated as safety issue: No ]
  • Profile of pharmacokinetic (PK) of the individual components of CAZ-AVI (avibactam and ceftazidime)- maximum plasma concentration (Cmax) [ Time Frame: Anytime within 15 minutes prior to or after stopping study drug, anytime between 30 and 90 minutes after stopping study drug, anytime between 300 minutes and 360 minutes after stopping study drug ] [ Designated as safety issue: No ]
    Cmax - Maximum plasma concentration

  • Profile of pharmacokinetic (PK) of the individual components of CAZ-AVI (avibactam and ceftazidime)- minimum plasma concentration (Cmin) [ Time Frame: Anytime within 15 minutes prior to or after stopping study drug, anytime between 30 and 90 minutes after stopping study drug, anytime between 300 minutes and 360 minutes after stopping study drug ] [ Designated as safety issue: No ]
    Cmin - Minimum plasma concentration

  • Profile of pharmacokinetic (PK) of the individual components of CAZ-AVI (avibactam and ceftazidime)- area under the plasma concentration time curve at steady state (AUCss) [ Time Frame: Anytime within 15 minutes prior to or after stopping study drug, anytime between 30 and 90 minutes after stopping study drug, anytime between 300 minutes and 360 minutes after stopping study drug ] [ Designated as safety issue: No ]
    AUCss - Area under the plasma concentration time curve at steady state

  • Profile of pharmacokinetic (PK) of the individual components of CAZ-AVI (avibactam and ceftazidime)- terminal half-life (t½ ) [ Time Frame: Anytime within 15 minutes prior to or after stopping study drug, anytime between 30 and 90 minutes after stopping study drug, anytime between 300 minutes and 360 minutes after stopping study drug ] [ Designated as safety issue: No ]
    t½ - terminal half-life

  • The safety and tolerability profile by incidence and severity of adverse events and serious adverse events, vital signs, clinical laboratory tests, ECGs and physical exams [ Time Frame: study duration (from screening visit (Day -1) through last follow up visit (up to 52 days) ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 964
Study Start Date: October 2012
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AZ Drug
IV treatment
 Drug: CAZ-AVI
Drug: Ceftazidime 2000 mg and 500 mg of avibactam
Drug: Either switch to oral therapy : 500 mg of Ciprofloxacin (oral) Drug: or switch to oral therapy : 800 mg/160 mg of sulfamethoxazole/trimethoprim
Active Comparator: Comparator
IV treatment
 Drug: Doripenem
500 mg of Doripenem
Drug: Either switch to oral therapy : 500 mg of Ciprofloxacin (oral) Drug: or switch to oral therapy : 800 mg/160 mg of sulfamethoxazole/trimethoprim

Detailed Description:

A Phase III, Randomized, Multicenter, Double-Blind, Double Dummy, Parallel Group, Comparative Study to Determine the Efficacy, Safety, and Tolerability of Ceftazidime Avibactam (CAZ-AVI, formerly CAZ104) Versus Doripenem Followed by Appropriate Oral Therapy in the Treatment of Complicated Urinary Tract Infections, Including Acute Pyelonephritis, With a Gram Negative Pathogen in Hospitalized Adults

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 18 to 90 years of age inclusive
  • Female patients can participate if they are surgically sterile or completed menopause or females capable of having children and agree not to attempt pregnancy while receiving IV study therapy and for a period of 7 days after
  • Has pyuria with >/= 10 WBCs (white blood cell) and has a positive urine culture within 48 hours of enrollment containing >/=10 to the fifth CFU (colony forming unit ) /ml of a recognized uropathogen known to be susceptible to IV study therapy (CAZ-AVI and doripenem)
  • Demonstrates either acute pyelonephritis or complicated lower UTI without pyelonephritis

Exclusion Criteria:

  • Urine pathogen is a Gram-positive pathogen or a uropathogen resistant to CAZ-AVI or doripenem
  • Patient's urine culture at study entry isolates more than 2 microorganisms regardless of colony count or patient has a confirmed fungal UTI
  • Patient is receiving hemodialysis or peritoneal dialysis or had a renal transplant
  • Patient is immunocompromised
  • Patient is considered unlikely to survive the 6- to 8-week study period or has a rapidly progressive or terminal illness including septic shock which is associated with a high risk of mortality
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01599806

Contacts
Contact: AstraZeneca Clinical Study Information 800-236-9933 information.center@astrazeneca.com
Contact: Arvil Stephens 1-910-558-7573 Arvil.Stephens@ppdi.com

  Show 96 Study Locations
Sponsors and Collaborators
AstraZeneca
Cerexa, Inc.
Investigators
Study Director: Paul Newell, MBBS, MRCP AstraZeneca
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01599806     History of Changes
Other Study ID Numbers: D4280C00004, 2011-005722-21
Study First Received: May 15, 2012
Last Updated: May 8, 2013
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Brazil: National Health Surveillance Agency
Bulgaria: Bulgarian Drug Agency
Canada: Health Canada
Croatia: Ministry of Health and Social Care
Czech Republic: State Institute for Drug Control
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Greece: National Organization of Medicines
Israel: Ministry of Health
India: Drugs Controller General of India
Italy: National Institute of Health
Mexico: Federal Commission for Sanitary Risks Protection
Peru: Ministry of Health
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romania: National Medicines Agency
Russia: Ministry of Health of the Russian Federation
South Korea: Korea Food and Drug Administration (KFDA)
Spain: Spanish Agency of Medicines
Taiwan : Food and Drug Administration
Ukraine: State Pharmacological Center - Ministry of Health
United States: Food and Drug Administration

Keywords provided by AstraZeneca:
Ceftazidime
Doripenem
Ciprofloxacin
sulfamethoxazole/trimethoprim
 Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

Additional relevant MeSH terms:
Pyelonephritis
Urinary Tract Infections
Nephritis, Interstitial
Nephritis
Kidney Diseases
Urologic Diseases
Pyelitis
Infection
Anti-Infective Agents
Ceftazidime
Ciprofloxacin
Sulfamethoxazole
Trimethoprim
 Trimethoprim-Sulfamethoxazole Combination
Therapeutic Uses
Pharmacologic Actions
Anti-Bacterial Agents
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Infective Agents, Urinary
Renal Agents
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Folic Acid Antagonists

ClinicalTrials.gov processed this record on June 17, 2013