Main
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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register. |
Register:
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EUCTR |
Last refreshed on:
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29 January 2018 |
Main ID: |
EUCTR2015-002726-39-ES |
Date of registration:
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03/02/2016 |
Prospective Registration:
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Yes |
Primary sponsor: |
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Public title:
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A study to determine how the drug(ATM-AVI) is moved in your body and whether the drug is safe and tolerable for the treatment of complicated Intra-Abdominal Infections (cIAIs) in hospitalized adults
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Scientific title:
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A Phase IIa prospective, open-label, multicenter study to determine the pharmacokinetics (PK) and safety and tolerability of aztreonam-avibactam (ATM-AVI) for the treatment of complicated Intra-Abdominal Infections (cIAIs) in hospitalized adults - REJUVENATE |
Date of first enrolment:
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05/04/2016 |
Target sample size:
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40 |
Recruitment status: |
Not Recruiting |
URL:
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https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-002726-39 |
Study type:
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Interventional clinical trial of medicinal product |
Study design:
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Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1
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Phase:
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Human pharmacology (Phase I): no
Therapeutic exploratory (Phase II): yes
Therapeutic confirmatory - (Phase III): no
Therapeutic use (Phase IV): no
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Countries of recruitment
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Germany
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Spain
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Contacts
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Name:
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Unidad de Investigación Clínica
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Address:
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C/ Serrano Galvache, 56; Parque Norte, Edificio Álamo
28033
Madrid
Spain |
Telephone:
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900200444 |
Email:
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informacionEECC-Spain@astrazeneca.com |
Affiliation:
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AstraZeneca Farmacéutica Spain, S.A. |
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Name:
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Unidad de Investigación Clínica
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Address:
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C/ Serrano Galvache, 56; Parque Norte, Edificio Álamo
28033
Madrid
Spain |
Telephone:
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900200444 |
Email:
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informacionEECC-Spain@astrazeneca.com |
Affiliation:
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AstraZeneca Farmacéutica Spain, S.A. |
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Key inclusion & exclusion criteria
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Inclusion criteria: 1. Provision of informed consent prior to any study-specific procedures. 2. Male or female from 18 to 90 years of age inclusive. 3. Female patients are authorized to participate in this clinical study if criteria concerning pregnancy avoidance stated in the protocol are met 4. Diagnosis of cIAI EITHER: Intra-operative/postoperative enrolment with visual confirmation (presence of pus within the abdominal cavity) of an intra-abdominal infection associated with peritonitis. Surgical intervention includes open laparotomy, percutaneous drainage of an abscess, or laparoscopic surgery. Specimens from the surgical intervention must be sent for culture. Patients who undergo a surgical procedure with complete fascial closure are appropriate for the trial. The skin incision may be left open for purposes of wound management as long as complete fascial closure is accomplished. The patient has at least 1 of the following diagnosed during the surgical intervention: (a) Cholecystitis with gangrenous rupture or perforation or progression of the infection beyond the gallbladder wall (b) Diverticular disease with perforation or abscess (c) Appendiceal perforation or peri-appendiceal abscess (d) Acute gastric or duodenal perforations, only if operated on >24 hours after perforation occurs (e) Traumatic perforation of the intestines, only if operated on >12 hours after perforation occurs (f) Secondary peritonitis (but not spontaneous bacterial peritonitis associated with cirrhosis and chronic ascites) (g) Intra abdominal abscess (including of liver or spleen provided that there is extension beyond the organ with evidence of intraperitoneal involvement) OR Preoperative enrollment where the following clinical criteria are met with confirmation of infection by surgical intervention within 24 hours of entry: (a) Requirement for surgical intervention, defined per protocol as open laparotomy, percutaneous drainage of an abscess, or laparoscopic surgery (b) Evidence of systemic inflammatory response, with at least one of the following: ? Fever (defined as body temperature >38°C) or hypothermia with a core body temperature <35°C ? Elevated white blood cells (>12000 cells/µL) ? Systolic blood pressure <90 mmHg or mean arterial pressure <70 mmHg, or a systolic blood pressure decrease of >40 mmHg? Increased heart rate ( >90 bpm) and respiratory rate (>20 breaths/min) ? Hypoxemia (defined as oxygen saturation < 95% by pulse oximetry) ? Altered mental status. (c) Physical findings consistent with intra-abdominal infection, such as: ? Abdominal pain and/or tenderness, with or without rebound ? Localized or diffuse abdominal wall rigidity ? Abdominal mass. (d) Supportive radiologic imaging findings of intra-abdominal infection such as perforated intraperitoneal abscess detected on computed tomography scan, magnetic resonance image, or ultrasound. (e) Specimens from the surgical intervention will be sent for culture for isolation of both aerobic and anaerobic bacteria.
5. Patients who failed prior antibacterial treatment for their current cIAI can be enrolled but must: ? Have a documented pathogen causing cIAI that is resistant to the prior therapy while assuming the organism is known to be sensitive to ATM-AVI. ? Require surgical intervention. 6. Patient must have or will have a surgical intervention within 24 hours (before or after) the administration of the first dose of study drug Are the trial subjects under 18? no Number of subjects for th
Exclusion criteria: 1. Involvement in the planning and/or conduct of the study 2. Patient has been previously enrolled in this study, previously treated with ATM-AVI or previously participated in an investigation study containing AVI 3. Patient has participated or intends to participate in any other clinical study that involves the administration of an investigational medication at the time of presentation, during the course of the study, or during the 30 days prior to study start. 4. Patient has a history of serious allergy, hypersensitivity (eg, anaphylaxis), or any serious reaction to aztreonam, carbapenem, monobactam or other ?-lactam antibiotics, avibactam, nitroimidazoles or metronidazole, or any of the excipients of the respective (investigational) medicinal products to be administered during the study 5. Patient has a 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 ulcer with surgery within 24 hours (these are considered situations of peritoneal soiling before infection has become established); another intra-abdominal process in which the primary etiology is not likely to be infectious 6. Patient has a simple cholecystitis, gangrenous cholecystitis without rupture, simple appendicitis, acute suppurative cholangitis, infected necrotizing pancreatitis, pancreatic abscess or ischaemic/necrotic intestine without perforation 7. Patient has a cIAI managed by staged abdominal repair (STAR), open abdomen technique or any situation where infection source control is not likely to be achieved or in whom the abdomen is left open, particularly those for whom re-operation is planned, or those unlikely to solely respond to antimicrobial therapy 8. At screening, if it is known the patient has an infection due to a pathogen that is unlikely to respond to ATM-AVI plus metronidazole treatment 9. Patient has a rapidly progressive (expected to die in <30 days) or terminal illness, including acute hepatic failure, respiratory failure or septic shock with a high risk of mortality due to other causes than cIAI 10. Patient has received systemic antibacterial agents within the 48-hour period prior to study entry, unless either of the following pertains: (a) Patient has a new infection (not considered a treatment failure) and the following is met: ? Patient received no more than 24 hours within the 48 hour period of total prior antibiotic therapy (b) Patient is considered to have failed the previous treatment regimen 11. Patient has a concurrent infection that may interfere with the evaluation of clinical cure for the study therapy 12. Patient needs effective concomitant systemic antibacterials (oral, IV, or intramuscular) or antifungals in addition to the investigational product and metronidazole 13. Patient has creatinine clearance ?50 ml/min. Note: following review of PK and safety data from the first 10 enrolled patients, and the confirmation of a provisional dose schedule, patients with a creatinine clearance of 31 ? 50 mL/min may be included. 14. Patient has had acute hepatitis in the prior 6 months, chronic hepatitis, cirrhosis (any Child-Pugh class), acute hepatic failure, or acute decompensation of chronic hepatic failure 15. Presence of hepatic disease as indicated by aspartate aminotransferase (AST) or alanine transaminase (ALT) >3 × upper limit of normal (ULN) at Screening. Patients with AST and/or ALT >3 × ULN an
Age minimum:
Age maximum:
Gender:
Female: yes Male: yes
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Health Condition(s) or Problem(s) studied
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Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]
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Complicated Intra-Abdominal Infections (cIAIs) in hospitalized adults
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Intervention(s)
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Product Name: AVIBACTAM Product Code: AVI Pharmaceutical Form: Powder for concentrate for solution for infusion INN or Proposed INN: avibactam sodium CAS Number: 1192491-61-4 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 600-
Trade Name: AZACTAM 1 g vial Product Code: J01DF01 Pharmaceutical Form: Powder for concentrate for solution for infusion INN or Proposed INN: aztreonam CAS Number: 827611-49-4 Other descriptive name: AZTREONAM LYSINE Concentration unit: g gram(s) Concentration type: equal Concentration number: 1-
Trade Name: Metronidazole 500 mg/ 100 ml intravenous infusion Product Name: Metronidazole 500 mg/100 ml Intravenous Product Code: SUB08922MIG Pharmaceutical Form: Solution for injection/infusion INN or Proposed INN: Metronidazole CAS Number: 442-48-1 Current Sponsor code: Metronidazole Other descriptive name: Metronidazole Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 5-
Trade Name: AZACTAM 2 g Pharmaceutical Form: Powder for concentrate for solution for infusion INN or Proposed INN: aztreonam CAS Number: 827611-49-4 Other descriptive name: AZTREONAM LYSINE Concentration unit: g gram(s) Concentration type: equal Concentration number: 2-
Trade Name: AZACTAM 2 g Pharmaceutical Form: Powder and solvent for solution for infusion INN or Proposed INN: aztreonam CAS Number: 827611-49-4 Other descriptive name: AZTREONAM LYSINE Concentration unit: g gram(s) Concentration type: equal Concentration number: 2-
Trade Name: AZACTAM 1 g Pharmaceutical Form: Powder and solvent for solution for infusion INN or Proposed INN: aztreonam CAS Number: 827611-49-4 Other descriptive name: AZTREONAM LYSINE Concentration unit: g gram(s) Concentration type: equal Concentration number: 1-
Trade Name: Aztreonam Pharmaceutical Form: Powder and solvent for solution for infusion INN or Proposed INN: aztreonam CAS Number: 827611-49-4 Other descriptive name: AZTREONAM LYSINE Concentration un
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Primary Outcome(s)
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Primary end point(s): 1.Concentrations of ATM and AVI in plasma; concentration-time profile of ATM and AVI The derived PK parameters Cmax, tmax, AUC(0-6), AUC(0-last), tlast, t1/2, Vss, Vz and CL for the patients undergoing intensive sampling on day 4; 2. Safety and tolerability as assessed by adverse events, physical examination, vital signs, ECGs, and laboratory assessments
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Secondary Objective: To assess the treatment outcome per patient at the test of cure (TOC) visit; To assess the relationship between exposure and clinical cure for ATM-AVI
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Main Objective: To determine the PK of ATM-AVI and to assess the safety of ATM-AVI in the patient population
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Timepoint(s) of evaluation of this end point: 1. Sampling take Trough (within 10 min prior to IV infusion start), 0.5h 1, 2, 3 (within 15 minutes before IV infusion stop), 3.25, 3.5. 3.75, 4, 5, and 6 h after start of IV infusion on Day 4
2. AE, Physical exam, vital sign, ECG and laboratory assessments conducted from screening to last visit
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Secondary Outcome(s)
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Secondary end point(s): Proportion of patients with clinical cure at the TOC visit; Correlation of derived PK parameters for ATM-AVI and clinical cure at TOC
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Timepoint(s) of evaluation of this end point: at test of cure visit (Day 25 ± 3)
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Secondary ID(s)
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D4910C00009
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2015-002726-39-DE
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Source(s) of Monetary Support
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AstraZeneca AB
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Results
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Results available:
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Date Posted:
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Date Completed:
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URL:
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