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    Summary
    EudraCT Number:2011-005722-21
    Sponsor's Protocol Code Number:D4280C00004
    National Competent Authority:Poland - Office for Medicinal Products
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2012-10-09
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedPoland - Office for Medicinal Products
    A.2EudraCT number2011-005722-21
    A.3Full title of the trial
    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
    Wieloośrodkowe, randomizowane, prowadzone w grupach równoległych metodą podwójnie ślepej i podwójnie pozorowanej próby porównawcze badanie fazy III oceniające skuteczność, bezpieczeństwo i tolerancję stosowania ceftazydymu-awibaktamu (CAZ-AVI, poprzednia nazwa: CAZ104) w porównaniu z doripenemem, z następczym leczeniem doustnym powikłanych zakażeń układu moczowego, w tym ostrego odmiedniczkowego zapalenia nerek, wywołanych patogenem Gram ujemnym u dorosłych wymagających hospitalizacji
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Compare Ceftazidime-Avibactam vs Doripenem Followed by Oral Therapy for hospitalized adults with complicated UTIs
    A.4.1Sponsor's protocol code numberD4280C00004
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorAstraZeneca AB
    B.1.3.4CountrySweden
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportAstraZeneca AB
    B.4.2CountrySweden
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAstraZeneca
    B.5.2Functional name of contact pointInformation Centre
    B.5.3 Address:
    B.5.3.1Street AddressRoom Tatnall Bldg, 1800 Concord Pike PO Box 15437
    B.5.3.2Town/ cityWilmington
    B.5.3.3Post codeDE 19850-5437
    B.5.3.4CountryUnited States
    B.5.4Telephone number""""""""
    B.5.5Fax number""""""""
    B.5.6E-mailinformation.center@astrazeneca.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameceftazidime avibactam
    D.3.2Product code CAZ AVI
    D.3.4Pharmaceutical form Powder for concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCEFTAZIDIME PENTAHYDRATE
    D.3.9.1CAS number 78439-06-2
    D.3.9.4EV Substance CodeSUB01134MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2000
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNAVIBACTAM
    D.3.9.1CAS number 1192491-61-4
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number500
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Doribax
    D.2.1.1.2Name of the Marketing Authorisation holderJanssen-Cilag International NV
    D.2.1.2Country which granted the Marketing AuthorisationBelgium
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameDoripenem
    D.3.4Pharmaceutical form Powder for concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNDORIPENEM
    D.3.9.1CAS number 148016-81-3
    D.3.9.4EV Substance CodeSUB22196
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number500
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 3
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Ciproxin
    D.2.1.1.2Name of the Marketing Authorisation holderBayer plc, Bayer Schering Pharma
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameCiprofloxacin
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.1CAS number 85721-33-1
    D.3.9.3Other descriptive nameCIPROFLOXACIN
    D.3.9.4EV Substance CodeSUB07470MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number500
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 4
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Septrin Forte
    D.2.1.1.2Name of the Marketing Authorisation holderAspen Pharma Trading Limited
    D.2.1.2Country which granted the Marketing AuthorisationIreland
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameSulfamethoxazole/Trimethoprim
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNSULFAMETHOXAZOLE
    D.3.9.1CAS number 723-46-6
    D.3.9.4EV Substance CodeSUB10711MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number800
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTRIMETHOPRIM
    D.3.9.1CAS number 738-70-5
    D.3.9.4EV Substance CodeSUB11310MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number160
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for injection/infusion
    D.8.4Route of administration of the placeboIntravenous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Complicated Urinary Tract Infections (cUTIs)
    Powikłane zakażenie układu moczowego (pZUM)
    E.1.1.1Medical condition in easily understood language
    Urinary Tract Infection
    Zakażenie układu moczowego
    E.1.1.2Therapeutic area Diseases [C] - Bacterial Infections and Mycoses [C01]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To assess the noninferiority of ceftazidime-avibactam compared with doripenem with respect to symptomatic resolution of UTI-specific symptoms and resolution of, or improvement in, flank pain based on the patient-reported symptom assessment
    Ocena co najmniej równoważności ceftazydymu-awibaktamu w porównaniu z doripenemem pod względem następujących równorzędnych głównych punktów końcowych w zmodyfikowanym zbiorze do analizy zdefiniowanym w oparciu o zamiar leczenia, dla którego dostępne są dane mikrobiologiczne:
    Ustąpienie objawów (lub powrót do stanu sprzed choroby) w przypadku objawów swoistych dla ZUM, za wyjątkiem bólu w okolicy lędźwiowej (częstość/nagłe parcie/bolesne oddawanie moczu/ból okolicy nadłonowej) oraz ustąpienie lub zmniejszenie objawów dla bólu w okolicy lędźwiowej na podstawie samooceny odpowiedzi objawów przez pacjenta w czasie wizyty Dzień 5.
    Dla każdego pacjenta eradykacja mikrobiologiczna i ustąpienie objawów (lub powrót do stanu sprzed choroby) w przypadku wszystkich objawów swoistych dla ZUM (częstość/nagłe parcie/bolesne oddawanie moczu/ból okolicy nadłonowej/ból w okolicy lędźwiowej) na podstawie samooceny odpowiedzi objawów przez pacjenta w czasie wizyty dotyczącej analizy wyleczeń.
    E.2.2Secondary objectives of the trial
    •To deter. the efficacy(Ef) of CAZ-AVI compared w/ dori wrt the per pt & per-pathogen MR at the EoIVT,ToC,& LFU visits in pts who are in the mmITT,ME,& eME analysis sets(AS)
    •To deter. the Ef of CAZ-AVI compared to dori wrt the symptomatic resolution of UTI-specific symptoms based on pt-reported symptom assessment at ToC, & LFU visits in mmITT AS
    •To deter. the Ef of CAZ-AVI compared w/ dori wrt the investigator-determined CC at the EoIVT,ToC,& LFU visits in pts who are in the mmITT,ME,eME,& CE AS
    •To eval the Ef of CAZ-AVI vs dori in pathogens resistant to ceftazidime
    •To comp the time to 1st defervescence of CAZ-AVI vs dori in pts who are on IV study therapy & who have fever at study entry in the mmITT,ME,eME,& CE AS
    •To eval the safety & toler. profile of CAZ-AVI compared w/ dori in the tx of pts w/ a cUTI in the safety AS
    •To eval the pk of the ind. components of CAZ-AVI(avibactam & ceftazidime)
    •To eval CAZ-AVI exposure & the antimicrobial response relationship
    •Określenie skuteczności produktu CAZ AVI w porównaniu z doripenemem pod względem odpowiedzi mikrobiologicznej dla każdego pacjenta w czasie wizyty dotyczącej zakończenia leczenia dożylnego [EOT (IV)], TOC i późnej wizyty kontrolnej (LFU)
    •Określenie skuteczności preparatu CAZ AVI w porównaniu z doripenemem pod względem ustąpienia objawów (lub powrotu do stanu sprzed choroby) w przypadku wszystkich objawów swoistych dla ZUM (nadmierna częstość/nagłe parcie/bolesne oddawanie moczu/ból okolicy nadłonowej/ból w okolicy lędźwiowej) na podstawie samooceny odpowiedzi objawów przez pacjenta w czasie wizyt TOC i LFU
    •Określenie skuteczności preparatu CAZ AVI w porównaniu z doripenemem pod względem odpowiedzi mikrobiologicznej dla każdego patogenu w czasie wizyty EOT (IV), TOC i LFU u pacjentów w zbiorze do analizy mMITT, ME i poszerzonym zbiorze ME.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1.18 to 90 years of age inclusive
    2.Female patient is authorized to participate in this clinical study if she has been surgically sterilized or postmenopausal for at least 1 year orher sexual partner has had a vasectomy and must be willing, during treatment and for at least 7 days after last dose of IV study therapy, to practice highly effective methods of birth control
    3.Has pyuria with >/= 10 WBCs and has a positive urine culture within 48 hours of enrollment containing >/=10 to the fifth CFU/ml of a recognized uropathogen known to be susceptible to IV study therapy (CAZ-AVI and doripenem)
    4.Demonstrates either acute pyelonephritis or complicated lower UTI without pyelonephritis
    1.Pacjent musi być w wieku od 18 do 90 lat włączenie.
    2.Kobiety mogą wziąć udział w badaniu, jeżeli spełnią następujące kryteria: pacjentka została poddana chirurgicznej sterylizacji lub znajduje się w okresie pomenopauzalnym od przynajmniej 1 roku lub jej partner przeszedł zabieg wasektomii i wyraża zgodę na stosowanie wysoce skutecznych metod kontroli urodzin podczas otrzymywania badanego leczenia IV i przez okres co najmniej 7 dni od zakończenia przyjmowania badanego leczenia IV.
    3.Pacjent choruje na ropomocz określony jako ≥10 białych krwinek w polu widzenia w próbce moczu pobranej ze środkowego strumienia lub z cewnika, w standardowym badaniu osadu moczu, lub ≥10 białych krwinek/ mm3 w nieodwirowanym moczu.
    4.U pacjenta występuje ostre odmiedniczkowe zapalenie nerek lub powikłane zakażenie dolnego odcinka układu moczowego bez odmiedniczkowego zapalenia nerek
    E.4Principal exclusion criteria
    1.Urine pathogen is a Gram-positive pathogen or a uropathogen resistant to CAZ-AVI or doripenem
    2.Patient's urine culture at study entry isolates more than 2 microorganisms regardless of colony count or patient has a confirmed fungal UTI
    3.Patient is receiving hemodialysis or peritoneal dialysis or had a renal transplant
    4.Patient is immunocompromised.
    5.Patient is considered unlikely to survive the 6- to 8-week study period or have a rapidly progressive or terminal illness, including septic shock that is associated with a high risk of mortality
    1.W przypadku, gdy dostępny będzie wynik posiewu moczu, przynajmniej 1 Gram-ujemny uropatogen będzie odporny na preparat CAZ-AVI lub doripenem.
    2.W przypadku, gdy dostępny będzie wynik posiewu moczu, posiew moczu pacjenta przy włączeniu do badania będzie izolował więcej niż 2 mikroorganizmy niezależnie od liczebności kolonii lub u pacjenta zostanie potwierdzone grzybicze zakażenie układu moczowego.
    3.Pacjent otrzymuje hemodializę lub dializę otrzewnową lub u pacjenta wykonano przeszczep nerki.
    4.U pacjenta występuje upośledzenie odporności
    5.Uważa się za mało prawdopodobne, że pacjent przeżyje 6-8 tygodniowy okres badania albo u pacjenta wystąpiła gwałtowna progresja lub nieuleczalna choroba, w tym wstrząs septyczny, który jest związany z wysokim ryzkiem śmiertelności.
    E.5 End points
    E.5.1Primary end point(s)
    •The proportion of patients with resolved (or return to premorbid) UTI symptoms except flank pain and resolution or improvement in flank pain based on patient-reported symptom assessment response at Day 5 visit. Timeframe: Day 5 after study drug start
    •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. Timeframe: 21 to 25 days after study drug start
    •Odsetek pacjentów, u których stwierdzono ustąpienie objawów (lub powrót do stanu sprzed choroby) w przypadku objawów swoistych dla ZUM na podstawie samooceny odpowiedzi objawów przez pacjenta w czasie wizyty w 5. dniu. Rama czasowa: dzień 5 od rozpoczęcia badanego leczenia
    •Odsetek pacjentów, u których stwierdzono eradykację mikrobiologiczną oraz ustąpienie objawów w przypadku wszystkich objawów swoistych dla ZUM na podstawie samooceny odpowiedzi objawów przez pacjenta. Rama czasowa: 21 do 25 dni od rozpoczęcia badanego leczenia.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Primary Outcome measure 1 - Day 5 after start of study drug
    Primary Outcome measure 2 - Day 21-25 after start of study drug
    1. Pomiar wyniku pierwszorzędowego – 5. dzień od rozpoczęcia przyjmowania leku badanego
    2. Pomiar wyniku pierwszorzędowego – 21. do 25. dzień po rozpoczęciu przyjmowania leku badanego
    E.5.2Secondary end point(s)
    •The proportion of pts w/ a favorable per pt MR in the mmITT analysis set. Outcome measured at the following timepoints: w/in 24 hrs after IV completion, 21-25 days & 45-52 days after study drug start(SDS)
    •The proportion of pts w/ a favorable per pt MR in the ME analysis set. Timeframe: w/in 24 hrs after IV completion, 21-25 days & 45-52 days after SDS
    •The proportion of pts w/ a favorable per pt MR in the extended ME analysis set. Timeframe: w/in 24 hrs after IV completion, 21-25 days & 45-52 days after SDS
    •The proportion of pts w/ resolution (or return to premorbid) of all UTI-specific symptoms based on the pt-reported symptom assessment response in the mmITT analysis set. Outcome measured at the following timepoints: 21-25 days & 45-52 days after SDS
    •The proportion of favorable per-pathogen MR in the mmITT analysis set. Outcome measured at the following timepoints: w/in 24 hrs after IV completion, 21-25 days & 45-52 days after study drug start
    •The proportion of favorable per-pathogen MR in the ME analysis set. Timeframe: w/in 24 hrs after IV completion, 21-25 days & 45-52 days after the start of study drug(SoSD)
    •The proportion of favorable per-pathogen MR in the extended ME analysis set. Timeframe: w/in 24 hrs after IV completion, 21-25 days & 45-52 days after the SoSD
    •The proportion of pts w/ an investigator-determined CC in the mmITT analysis set. Outcome measured at the following timepoints: w/in 24 hrs after IV completion, 21-25 days & 45-52 days after the SoSD
    •The proportion of pts w/ an investigator-determined CC in the ME analysis set. Timeframe: w/in 24 hrs after IV completion, 21-25 days & 45-52 days after the SoSD
    •The proportion of pts w/ an investigator-determined CC in the extended ME analysis set. Timeframe: w/in 24 hrs after IV completion, 21 ~ 25 days & 45 ~ 52 days after the SoSD
    •The proportion of pts w/ an investigator-determined CC in the CE analysis set. Timeframe: w/in 24 hrs after IV completion, 21-25 days & 45-52 days after the SoSD
    •The favorable per pathogen MR by categories of minimum inhibitory concentration in the mmITT analysis set. Outcome measured at the following timepoints: w/in 24 hrs after IV completion, 21-25 days & 45-52 days after the SoSD
    •The favorable per pathogen MR by categories of minimum inhibitory concentration in the ME analysis set. Outcome measured at the following timepoints: w/in 24 hrs after IV completion, 21-25days & 45-52 days after the SoSD
    •The favorable per pathogen MR by categories of minimum inhibitory concentration in the extended ME analysis set. Outcome measured at the following timepoints: 24 hrs after completion of study drug, 21-25 days & 45-52 days after the SoSD
    •The proportion of pts w/ favorable investigator clinical response assessment in pts infected w/ a ceftazidime resistant pathogen in the mmITT analysis set. Outcome measured at the following timepoint: 21-25 days after study drug start
    •The proportion of pts w/ an investigator-determined CC in pts infected w/ a ceftazidime resistant pathogen in the ME analysis set. Outcome measured at the following timepoint: 21-25 days after study drug start
    •The proportion of pts w/ an investigator-determined CC in pts infected w/ a ceftazidime resistant pathogen in the extended ME analysis set. Outcome measured at the following timepoint: 21-25 days after study drug start
    •The proportion of pts w/ favorable per-pt MR for pts infected w/ a ceftazidime resistant pathogen in the mmITT analysis set. Outcome measured at the following timepoint: 21-25 days after SDS
    •The proportion of pts w/ favorable per-pt MR for pts infected w/ a ceftazidime resistant pathogen in the ME analysis set. Timeframe: 21-25 days after study drug start
    •The proportion of pts w/ favorable per-pt MR for pts infected w/ a ceftazidime resistant pathogen in the extended ME analysis set. Timeframe: 21-25 days after study drug start
    •The proportion of pts w/ symptomatic resolution (defined in the coprimary variables) for pts infected w/ a ceftazidime resistant pathogen in the mmITT analysis set. Outcome measured at the following timepoint: Day 5 & 21-25 days after study drug start
    •The time to 1st defervescence while on IV study therapy in pts in the mmITT, ME, extended ME, and CE analysis sets who have fever at study entry. Timeframe: any time after start of study drug to end of IV study therapy
    •Evaluation of the pk of the individual components of CAZ-AVI (avibactam & ceftazidime)
    •The safety & tolerability by incidence & severity of adverse events & serious adverse events, vital signs, clinical laboratory tests, ECGs & physical exams. Outcome measured at the following timepoints: study duration (screening visit (Day -1) through last follow up visit (up to 52 days)
    -Odsetek pacjentów z korzystną odpowiedzią mikrobiologiczną dla każdego pacjenta w zbiorze do analizy mMITT. Ramy czasowe: w ciągu 24 godzin od ostatniego dnia przyjmowania leku badanego, 21-25 oraz 45-52 dni po rozpoczęciu przyjmowania leku badanego
    -Odsetek pacjentów, u których stwierdzono ustąpienie objawów w przypadku wszystkich objawów swoistych dla ZUM na podstawie samooceny odpowiedzi objawów przez pacjenta. Ramy czasowe: 21-25 oraz 45-52 dni po rozpoczęciu przyjmowania leku badanego
    -Odsetek pacjentów z korzystną odpowiedzią mikrobiologiczną dla każdego patogenu w zbiorze do analizy mMITT, ME i poszerzonym zbiorze ME. Ramy czasowe: w ciągu 24 godzin od ostatniego dnia przyjmowania leku badanego, 21-25 oraz 45-52 dni po rozpoczęciu przyjmowania leku badanego
    -Odsetek pacjentów ze wskaźnikiem wyleczeń klinicznych określanym przez badacza w zbiorze do analizy mMITT. Ramy czasowe: w ciągu 24 godzin od ostatniego dnia przyjmowania leku badanego, 21-25 oraz 45-52 dni po rozpoczęciu przyjmowania leku badanego
    -Odsetek pacjentów z korzystną odpowiedzią mikrobiologiczną dla każdego patogenu względem kategorii najniższego stężenia hamującego (MIC) w zbiorze do analizy mMITT. Ramy czasowe: w ciągu 24 godzin od ostatniego dnia przyjmowania leku badanego, 21-25 oraz 45-52 dni po rozpoczęciu przyjmowania leku badanego
    -Odsetek pacjentów z korzystną oceną odpowiedzi klinicznej przez badacza w zbiorze do analizy mMITT. Ramy czasowe: w ciągu 21 do 25 od rozpoczęcia przyjmowania leku badanego.
    -Czas do stwierdzenia pierwszego ustąpienia gorączki w czasie przyjmowania leków stosowanych w badaniu podawanych dożylnie u pacjentów w zbiorze do analizy mMITT, u których stwierdzano gorączkę w czasie włączenia do badania. Ramy czasowe: w każdym momencie od rozpoczęcia przyjmowania leku badanego do zakończenia przyjmowania leków badanych podawanych dożylnie.
    -Bezpieczeństwo i tolerancja będą oceniane na podstawie częstości i ciężkości zdarzeń niepożądanych (AE) i ciężkich zdarzeń niepożądanych (SAE), pomiaru parametrów życiowych, laboratoryjnych badań klinicznych, EKG oraz badania fizykalnego. Ramy czasowe: w okresie trwania badania (od wizyty przesiewowej do czasu ostatniej wizyty kontrolnej (do 50 dni))
    -PK: stężenie minimalne/maksymalne / obszar pod krzywą stężenia leku w stanie równowagi oraz w okresie półtrwania. Ramy czasowe: 15 minut przed rozpoczęciem lub po zakończeniu podawania leku badanego, w okresie pomiędzy 30 a 90 minut oraz 300 i 360 minut po zakończeniu podawania leku badanego.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Listed in E.5.2
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic Yes
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Microbiology cultures
    kultury mikrobiologiczne
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned5
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA38
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Argentina
    Brazil
    Bulgaria
    Canada
    Croatia
    Czech Republic
    France
    Germany
    Greece
    India
    Israel
    Italy
    Korea, Republic of
    Mexico
    Peru
    Poland
    Romania
    Russian Federation
    Spain
    Taiwan
    Ukraine
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The end of the study is defined as the last visit of the last patient participating in the study.
    Ostatnia wizyta ostatniego pacjenta uczestniczącego w badaniu
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months5
    E.8.9.1In the Member State concerned days28
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months5
    E.8.9.2In all countries concerned by the trial days28
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 328
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 176
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state29
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 250
    F.4.2.2In the whole clinical trial 504
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Standard of care
    Zgodnie ze standardami opieki medycznej
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2012-12-11
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2012-09-12
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2014-08-18
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