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    The EU Clinical Trials Register currently displays   36785   clinical trials with a EudraCT protocol, of which   6075   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2007-001117-42
    Sponsor's Protocol Code Number:DORI-NOS-2001
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2007-09-04
    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 ConcernedGermany - BfArM
    A.2EudraCT number2007-001117-42
    A.3Full title of the trial
    A Randomized, Open-Label, Multicenter Study to Assess the Safety and Tolerability of Doripenem Compared With Imipenem in the Treatment of Subjects With Complicated Intra-Abdominal Infections or Ventilator-Associated Pneumonia
    A.4.1Sponsor's protocol code numberDORI-NOS-2001
    A.7Trial is part of a Paediatric Investigation Plan Information not present in EudraCT
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorJanssen Cilag International NV
    B.1.3.4CountryBelgium
    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 support
    B.4.2Country
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation
    B.5.2Functional name of contact point
    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 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 AuthorisationEuropean Union
    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.3.4Pharmaceutical form Powder for solution for infusion
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    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 monohydrate
    D.3.9.1CAS number 364622-82-2
    D.3.9.2Current sponsor codeJNJ-38174942
    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) Information not present in EudraCT
    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 Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    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 Information not present in EudraCT
    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 Tienam IV 500 mg/500 mg Powder for Solution for Infusion
    D.2.1.1.2Name of the Marketing Authorisation holderMSD Polska Sp. Z.o.o.
    D.2.1.2Country which granted the Marketing AuthorisationPoland
    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.3.4Pharmaceutical form Powder for solution for infusion
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    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 INNImipenem
    D.3.9.1CAS number 74431-23-5
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number500
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCilastatin
    D.3.9.1CAS number 82009-34-5
    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) Information not present in EudraCT
    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 Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    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 Information not present in EudraCT
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    ventilator-associated pneumonia

    complicated intra-abdominal infections
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10056570
    E.1.2Term Intra-abdominal infection
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10065153
    E.1.2Term Ventilator associated pneumonia
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective is to assess the safety and tolerability of doripenem 1 g infused over 4 hours at 8-hour intervals.
    E.2.2Secondary objectives of the trial
    ·To compare the clinical cure rate of doripenem compared with imipenem after 7 days of study drug therapy and at the TOC visit in subjects with VAP
    ·To compare the clinical response of doripenem compared with imipenem in subjects with cIAI at the TOC visit
    ·To determine the PK profile of doripenem 1 g infused over 4 hours in subjects with VAP and cIAI
    ·To compare mortality rates in subjects treated with doripenem compared with imipenem. "Thirty-day all-cause mortality" will be assessed for all subjects.
    ·To determine the per-pathogen microbiologic and clinical response of subjects with VAP and cIAI by the MIC of the baseline pathogen
    ·To explore the exposure-response relationships for microbiologic and clinical outcomes using PK/PD modeling
    ·To collect medical resource utilization data to be used in the possible development of an economic model that will be analyzed and reported separately
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    · Men or women 18 years of age or older
    · Women must be postmenopausal , surgically sterile, abstinent, or, if sexually active, be practicing an effective method of birth control before entry and throughout the study; have a negative serum beta-human chorionic gonadotropin or urine pregnancy test at screening (depending on local regulations).
    · Subjects must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study. Consent may be given for unconscious/incapacitated subjects by their next of kin, guardian, or legal representative, according to local regulatory and ethical practice using a subject information sheet and informed consent form approved by the responsible Ethics Committee.

    Subjects with VAP must also:
    · Have been hospitalized (or been in a chronic care facility) for greater than or equal to 5 days.
    · Have received mechanical ventilation for greater than or equal to 48 hours
    · Have a Clinical Pulmonary Infection Score (CPIS) of greater than or equal to 5
    · Have new or progressive radiographic infiltrates (not related to another disease process).
    · Have at least one of the following:
    – Fever (in the absence of antipyretics), increase in core temperature of greater than 1°C OR an oral temperature greater than 38°C, a tympanic temperature of 38.5°C, a rectal/core temperature greater than 39°C, a temporal temperature greater than 38.5°C
    – Hypothermia, defined as a rectal/core body temperature of less than 35°C (axillary temperature measurements are not acceptable)
    – Leukocytosis (a total white blood cell [WBC] count greater than or equal to 10 x 109/L or greater than or equal to 15% immature neutrophils [bands], regardless of total peripheral white count; or leukopenia with total WBC less than 4.5 x 109/L)
    · Have microbiologic samples (quantitative BAL and tracheal aspirate) suitable for culture
    · Have an Acute Physiology and Chronic Health Evaluation (APACHE) II score of 8 to 29, inclusive

    Subjects with cIAI must also:
    · Have clinical evidence of intra-abdominal infection
    – If enrolled preoperatively, must have evidence of a systemic infection, with at least 1 of the following:
    · Fever (oral temperature greater than 38°C) or hypothermia (core body temperature less than 35°C)
    · Elevated WBC count (greater than 10,500 cells/mm3)
    · Decrease in blood pressure relative to baseline of greater than 15 mmHg systolic (however systolic blood pressure should not be less than 90 mmHg and subject should not have required continued pressor support)
    · Increased pulse (greater than 100 beats per minute [bpm]) and respiratory rates (greater than 20 bpm)
    · Hypoxemia (partial pressure of oxygen [PaO2] less than 60 mmHg or pulse oximetry less than 90% on room air)
    – In addition, if preoperative, must have at least one of the following physical signs consistent with IAI:
    · Abdominal pain or tenderness
    · Localized or diffuse abdominal wall rigidity
    · Mass
    · Ileus
    · Have a requirement for surgical intervention (e.g., laparotomy, laparoscopic surgery, or percutaneous draining of an abscess) within 24 hours of study entry
    · Require antibacterial therapy, in addition to surgical intervention
    · Have one of the following eligible diagnoses:
    – Cholecystitis (including gangrenous cholecystitis) with rupture, perforation, or progression of the infection beyond the gallbladder wall
    – Diverticular disease with perforation or abscess
    – Appendiceal perforation only if associated with generalized peritonitis
    – Acute gastric and duodenal perforations, only if operated upon more than 24 hours after perforation occurred
    – Traumatic perforation of the intestines, only if operated upon more than 12 hours after perforation occurred
    – Peritonitis; due to perforated viscus, that is postoperative or due to other focus of infection (but not spontaneous bacterial peritonitis associated with cirrhosis and chronic ascites). Subjects with inflammatory bowel disease or ischemic bowel disease are eligible, provided there is bowel perforation.
    – Intra-abdominal abscess (including liver and spleen) not due to appendiceal perforation
    A subject enrolled as a failure of a prior antibacterial treatment must:
    · Have a positive culture (from an intra-abdominal site)
    · Require surgical intervention
    Such subjects can be enrolled before the results of the culture are known. However, if the culture is negative, the subject must be removed from study therapy, but remain in the safety population.
    E.4Principal exclusion criteria
    •· History of subjects with acute hepatic failure or acute decompensation of chronic hepatic failure
    · History of severe impairment of renal function requiring peritoneal dialysis, hemodialysis, hemofiltration, or oliguria
    · History of immunocompromising illness, acquired immunodeficiency syndrome, or human immunodeficiency virus with a CD4 count less than 200 cells/mL within the past 6 months, organ (including bone marrow) transplant recipients, hematologic malignancy, and use of immunosuppressive therapy at screening, including use of high-dose corticosteroids (e.g., greater than 40 mg prednisone or equivalent per day for greater than 2 weeks)
    · History of any rapidly progressing disease or immediately life-threatening illness (including acute hepatic failure and septic shock. Sustained shock is defined as a systolic blood pressure less than 90 mmHg for greater than 2 hours, despite adequate fluid resuscitation, with evidence of hypoperfusion or need for sympathomimetic agents.)
    · History of hypersensitivity reactions to carbapenems, penicillins, other b lactam antibiotics, or b-lactamase inhibitors (subjects with a history of mild skin rash, documented not to have been caused by previous b-lactam use are permitted to enroll)
    · Have previously received doripenem
    · Have previously received imipenem or meropenem in the past week
    · Have any other known or suspected condition that may jeopardize adherence to protocol requirements
    · Active seizure disorder or brain injury such that imipenem would not be administered to the subject in usual practice
    · Hematocrit of less than 25% or hemoglobin of less that 8 g/dL
    · Neutropenia with absolute neutrophil count of less than 1,000 cell/mm3. Subjects with neutrophil counts as low as 500 cells/mm3 are permitted if the reduction is due to the acute infection process.
    · Platelet count of less than 50,000 cells/mm3
    · Is unlikely to survive the 6- to 8-week study period
    · Current use of probenecid or valproic acid
    · Have received an experimental drug or used an experimental medical device within 1 month before the planned start of treatment.
    · Is breast-feeding
    ·
    Additional exclusion criteria for subjects with VAP:
    · Subjects with either:
    – Known bronchial obstruction or a history of postobstructive pneumonia
    – Primary lung cancer or another metastatic malignancy to the lungs
    – Cystic fibrosis
    – Lung abscess
    – Empyema
    – Acute respiratory distress syndrome (diffuse radiographic infiltrates and PaO2 to fraction of inspired oxygen [FiO2] ratio less than 200)
    – Active pulmonary tuberculosis
    – Subjects requiring antibiotic cover for aspiration pneumonia, atypical pneumonia (including known Legionella pneumophila), or Pneumocystis jiroveci (carinii) pneumonia, fungal pneumonia, or known or suspected gastric aspiration (i.e., chemical pneumonitis)
    · Subjects with prior antibiotic therapy (active against likely causative pathogens of respiratory infection) will be excluded if the prior antibiotic:
    – Was started or added for the current infection
    AND
    – This new antibiotic has been given for more than 24 hours before the first dose of i.v. study drug therapy.
    Note that subjects will not be excluded if their prior antibiotic therapy has been given for more than 48 hours and remains unchanged before the first dose of i.v. study therapy.

    Additional exclusion criteria for subjects with cIAI:
    · Diagnosis of abdominal wall abscess, small bowel obstruction or ischemic bowel disease without perforation, traumatic bowel perforation with surgery within 12 hours, perforation of gastroduodenal ulcers with surgery within 24 hours (these are considered situations of peritoneal soiling before infection has become established)
    · Appendicitis in the absence of generalized peritonitis, or any intra abdominal processes in which the primary etiology is not likely to be infectious
    · History of uncomplicated intra-abdominal infection, (e.g., simple cholecystitis, i.e., gangrenous or suppurative cholecystitis without rupture or extension beyond the gallbladder wall), or acute suppurative cholangitis
    . Have an APACHE score > 30
    · Necrotizing pancreatitis or pancreatic abscess
    · Intra-abdominal infection where planned management is by staged abdominal repair or an open abdomen technique
    · The need for concomitant systemic antibacterial agents (other than vancomycin) in addition to study drug(s)
    · Use of systemic antibiotic therapy for cIAI for 24 or more hours immediately preceding the first dose of i.v. study drug therapy (unless there is a documented lack of response to such therapy)
    · No more than 1 dose of an active nonstudy antibacterial regimen was given postoperatively. For subjects enrolled preoperatively, including those enrolled as failures of previous antibacterial therapy, no postoperative nonstudy antibacterial therapy is allowed.
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint of this study is the assessment of safety as
    measured by the overall incidence of treatment-emergent adverse events.
    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 No
    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) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    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 Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    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.8.3 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 concerned8
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA12
    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 Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    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
    Last visit of the last subject undergoing the trial.
    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 months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years1
    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.1.3Elderly (>=65 years) Yes
    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 Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Ventilator associated pneumonia may have altered states of consciousness.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state30
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 60
    F.4.2.2In the whole clinical trial 250
    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 Decision2008-01-30
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2007-12-03
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2008-11-05
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
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