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

This study has been completed.
Sponsor:
Collaborator:
Cerexa, Inc.
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01595438
First received: April 27, 2012
Last updated: October 20, 2014
Last verified: October 2014
  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
Complicated Urinary Tract Infection (cUTI) Including 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 (oral)
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:


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-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-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 study drug start ] [ 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 study drug start ] [ 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 study drug start ] [ 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 study drug start ] [ 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 study drug start ] [ 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 study drug start ] [ 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 study drug start ] [ 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: 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 co-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 ]

Enrollment: 563
Study Start Date: October 2012
Study Completion Date: August 2014
Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AZ drug
IV treatment
Drug: CAZ-AVI
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 (oral)
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 (oral)

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01595438

  Show 84 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: NCT01595438     History of Changes
Other Study ID Numbers: D4280C00002, 2011-005721-43
Study First Received: April 27, 2012
Last Updated: October 20, 2014
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Belgium: Federal Agency for Medicinal Products and Health Products
Brazil: National Health Surveillance Agency
Bulgaria: Bulgarian Drug Agency
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
India: Ministry of Health
Israel: Ministry of Health
Japan: Pharmaceuticals and Medical Devices Agency
Mexico: Federal Commission for Sanitary Risks Protection
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)
Taiwan : Food and Drug Administration
Ukraine: 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:
Communicable Diseases
Infection
Pyelonephritis
Urinary Tract Infections
Kidney Diseases
Nephritis
Nephritis, Interstitial
Pyelitis
Urologic Diseases
Ceftazidime
Ciprofloxacin
Sulfamethoxazole
Trimethoprim
Trimethoprim-Sulfamethoxazole Combination
Anti-Bacterial Agents
Anti-Infective Agents
Anti-Infective Agents, Urinary
Antimalarials
Antineoplastic Agents
Antiparasitic Agents
Antiprotozoal Agents
Enzyme Inhibitors
Folic Acid Antagonists
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Renal Agents
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on November 24, 2014