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- Sperimentazione clinica NCT00615017
AZD9773 Dose Escalation Study
19 luglio 2013 aggiornato da: AstraZeneca
A Placebo-controlled, Double-blind, Dose-escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics and Pharmacodynamics of Single and Multiple Intravenous Infusions of CytoFab (AZD9773) in Patients With Severe Sepsis
This is a double-blind, placebo-controlled, multi-center, dose-escalation study to assess the safety, tolerability, Pharmacokinetics and Pharmacodynamics of single and multiple ascending intravenous infusions of CytoFab (AZD9773) in adult patients with severe sepsis.
Panoramica dello studio
Stato
Completato
Condizioni
Intervento / Trattamento
Tipo di studio
Interventistico
Iscrizione (Effettivo)
70
Fase
- Fase 2
Contatti e Sedi
Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.
Luoghi di studio
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Alabama
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Birmingham, Alabama, Stati Uniti
- Research Site
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Delaware
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Newark, Delaware, Stati Uniti
- Research Site
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Florida
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Bay Pines, Florida, Stati Uniti
- Research Site
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Miami, Florida, Stati Uniti
- Research Site
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Illinois
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Chicago, Illinois, Stati Uniti
- Research Site
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Oak Park, Illinois, Stati Uniti
- Research Site
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Peoria, Illinois, Stati Uniti
- Research Site
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Indiana
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Indianapolis, Indiana, Stati Uniti
- Research Site
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Iowa
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Iowa City, Iowa, Stati Uniti
- Research Site
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Kentucky
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Hazard, Kentucky, Stati Uniti
- Research Site
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Lexington, Kentucky, Stati Uniti
- Research Site
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Maryland
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Baltimore, Maryland, Stati Uniti
- Research Site
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Missouri
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Kansas City, Missouri, Stati Uniti
- Research Site
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New Jersey
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Camden, New Jersey, Stati Uniti
- Research Site
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Newark, New Jersey, Stati Uniti
- Research Site
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New York
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Brooklyn, New York, Stati Uniti
- Research Site
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New York, New York, Stati Uniti
- Research Site
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Rochester, New York, Stati Uniti
- Research Site
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North Carolina
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Durham, North Carolina, Stati Uniti
- Research Site
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Greensboro, North Carolina, Stati Uniti
- Research Site
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Winston Salem, North Carolina, Stati Uniti
- Research Site
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Ohio
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Columbus, Ohio, Stati Uniti
- Research Site
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Oklahoma
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Oklahoma City, Oklahoma, Stati Uniti
- Research Site
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Tennessee
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Nashville, Tennessee, Stati Uniti
- Research Site
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Texas
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Galveston, Texas, Stati Uniti
- Research Site
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Houston, Texas, Stati Uniti
- Research Site
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Criteri di partecipazione
I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.
Criteri di ammissibilità
Età idonea allo studio
18 anni e precedenti (Adulto, Adulto più anziano)
Accetta volontari sani
No
Sessi ammissibili allo studio
Tutto
Descrizione
Inclusion Criteria:
- Clinical evidence of infection requiring treatment with parenteral antibiotics
- Patients must meet multiple Systemic Inflammatory Response Syndrome (SIRS) criteria
- Patients must meet criteria for cardiovascular and/or respiratory dysfunction
- Sepsis (infection plus SIRS criteria) must be present prior to organ dysfunction
Exclusion Criteria:
- Moribund and death is considered imminent, or patient not expected to survive 90 days because of underlying medical condition, or classified as Do Not Resuscitate or Do Not Treat
- Patient cannot attain a MAP >60 mmHg when measured via an arterial line and/or a Systolic Blood Pressure (SBP) >80 mmHg in the presence of vasopressors and iv fluids for a period of ≥2 hours
- Receiving immunosuppressants, or high dose steroids within 2 months of provision of informed consent
- Any history of hypersensitivity reaction to sheep products, latex, papain or papaya, or chymopapain or previously administered antivenom manufactured using ovine serum, digoxin immune fab (DigiFab™ , DIGIBIND® ), crotalidae polyvalent immune fab (ovine) (CroFab™ ), or other sheep derived product.
- Treatment with anti Tumor-Necrosis-Factor (anti-TNF) antibodies within 8 weeks before provision of written informed consent.
Piano di studio
Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione di gruppo singolo
- Mascheramento: Triplicare
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
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Comparatore placebo: Placebo
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Placebo
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Sperimentale: AZD9773 cohort 1 (50 units/kg)
AZD9773: single infusion of 50 units/kg
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intravenous infusions
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Sperimentale: AZD9773 cohort 2 (250 units/kg)
AZD9773: single infusion of 250 units/kg
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intravenous infusions
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Sperimentale: AZD9773 cohort 3 (250/50 units/kg)
AZD9773: loading infusion of 250 units/kg then 9 maintenance doses of 50 units/kg q12hrs
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intravenous infusions
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Sperimentale: AZD9773 cohort 4 (500/100 units/kg)
AZD9773: loading infusion of 500 units/kg then 9 maintenance doses of 100 units/kg q12hrs
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intravenous infusions
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Sperimentale: AZD9773 cohort 5 (750/250 units/kg)
AZD9773: loading infusion of 750 units/kg then 9 maintenance doses of 250 units/kg q12hrs
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intravenous infusions
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
---|---|---|
Change From Baseline in Creatinine Values
Lasso di tempo: End of study (Day 28)
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Change in creatinine values from baseline (pre-infusion) to follow-up (28 days after the start of study drug administration) [calculated as Day 28 mean minus baseline mean].
Safety analysis set (ie all patients who started study drug infusion).
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End of study (Day 28)
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Change From Baseline in Alanine Aminotransferase Values
Lasso di tempo: End of study (Day 28)
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Change in alanine aminotransferase values from baseline (pre-infusion) to follow-up (28 days after the start of study drug administration) [calculated as Day 28 mean minus baseline mean].
Safety analysis set (ie all patients who started study drug infusion).
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End of study (Day 28)
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Change From Baseline in Aspartate Aminotransferase Values
Lasso di tempo: End of study (Day 28)
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Change in aspartate aminotransferase values from baseline (pre-infusion) to follow-up (28 days after the start of study drug administration) [calculated as Day 28 mean minus baseline mean].
Safety analysis set (ie all patients who started study drug infusion).
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End of study (Day 28)
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Change From Baseline in Bilirubin Values
Lasso di tempo: End of study (Day 28)
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Change in bilirubin values from baseline (pre-infusion) to follow-up (28 days after the start of study drug administration) [calculated as Day 28 mean minus baseline mean].
Safety analysis set (ie all patients who started study drug infusion).
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End of study (Day 28)
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Change From Baseline in Haemoglobin Values
Lasso di tempo: End of study (Day 28)
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Change in haemoglobin values from baseline (pre-infusion) to follow-up (28 days after the start of study drug administration) [calculated as Day 28 mean minus baseline mean].
Safety analysis set (ie all patients who started study drug infusion).
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End of study (Day 28)
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Change From Baseline in White Blood Cell Values
Lasso di tempo: End of study (Day 28)
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Change in white blood cell values from baseline (pre-infusion) to follow-up (28 days after the start of study drug administration) [calculated as Day 28 mean minus baseline mean].
Safety analysis set (ie all patients who started study drug infusion).
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End of study (Day 28)
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Change From Baseline in Platelet Count Values
Lasso di tempo: End of study (Day 28)
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Change in platelet count values from baseline (pre-infusion) to follow-up (28 days after the start of study drug administration) [calculated as Day 28 mean minus baseline mean].
Safety analysis set (ie all patients who started study drug infusion).
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End of study (Day 28)
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Change From Baseline in Prothrombin Time Values
Lasso di tempo: Day 7
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Change in prothrombin time values from baseline (pre-infusion) to Day 7 [calculated as Day 7 mean minus baseline mean].
Safety analysis set (ie all patients who started study drug infusion).
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Day 7
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Change From Baseline in Troponin I
Lasso di tempo: Day 6
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Change in troponin I values from baseline (pre-infusion) to Day 6 [calculated as Day 6 mean minus baseline mean].
Safety analysis set (ie all patients who started study drug infusion).
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Day 6
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Change From Baseline in QT With Fridericia Correction (QTcF), Where QT is Measured by ECG, and is the Time Interval Between the Start of the Q Wave and the End of the T Wave in the Heart's Electrical Cycle.
Lasso di tempo: Day 1 (end of infusion) for Cohorts 1 and 2; Day 5 (end of infusion) for Cohorts 3 to 5 and placebo
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Change in QTcF from baseline (pre-infusion) to Day 1 (end of infusion) for Cohorts 1 and 2 [calculated as Day 1 mean minus baseline mean] and Day 5 (end of infusion) for Cohorts 3 to 5 and placebo [calculated as Day 5 mean minus baseline mean].
Safety analysis set (ie all patients who started study drug infusion).
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Day 1 (end of infusion) for Cohorts 1 and 2; Day 5 (end of infusion) for Cohorts 3 to 5 and placebo
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Change From Baseline in Calculated Mean Arterial Blood Pressure
Lasso di tempo: Day 14
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Change in calculated mean arterial pressure from baseline (pre-infusion) to Day 14 [calculated as Day 14 mean minus baseline mean].
Safety analysis set (ie all patients who started study drug infusion).
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Day 14
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Change From Baseline in Body Weight
Lasso di tempo: Day 6
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Change in body weight from baseline (pre-infusion) to Day 6 [calculated as Day 6 mean minus baseline mean].
Safety analysis set (ie all patients who started study drug infusion).
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Day 6
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Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
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28-Day Mortality
Lasso di tempo: End of study (Day 28)
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The number of patients who had died at Day 28.
Safety analysis set (ie all patients who started study drug infusion).
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End of study (Day 28)
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Change From Baseline in Sequential Organ Failure Assessment (SOFA) Scores
Lasso di tempo: Day 6
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Change in SOFA (Sequential Organ Failure Assessment) scores from baseline (pre-infusion) to Day 6 [calculated as Day 6 mean minus baseline mean].
The SOFA score is out of a maximum of 24 (units on a scale 0 to 24).
The higher the score, the worse the organ system functioning.
Safety analysis set (ie all patients who started study drug infusion).
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Day 6
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Area Under the Serum Concentration-time Curve From 0 to 12 Hours (AUC(0-12)) of Single Dose AZD9773 Serum Total Fabs (Cohorts 1 and 2)
Lasso di tempo: Day 1 [PK samples taken pre-dose, the end of each infusion rate and then at 0.5, 1, 2, 8, and 12h post-(last) infusion]
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AUC(0-12) for single dose AZD9773 serum total Fabs (cohorts 1 and 2).
PK analysis set (ie a subset of the safety analysis set including only those patients without important deviations that could affect the PK).
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Day 1 [PK samples taken pre-dose, the end of each infusion rate and then at 0.5, 1, 2, 8, and 12h post-(last) infusion]
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Terminal Half-life (t1/2) of Single Dose AZD9773 Serum Total Fabs (Cohorts 1 and 2)
Lasso di tempo: Day 1 [PK samples taken pre-dose, the end of each infusion rate and then at 0.5, 1, 2, 8, 12, 24, 48, and 72 h post-(last) infusion]
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t1/2 of single dose AZD9773 serum total Fabs (cohorts 1 and 2).
PK analysis set (ie a subset of the safety analysis set including only those patients without important deviations that could affect the PK).
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Day 1 [PK samples taken pre-dose, the end of each infusion rate and then at 0.5, 1, 2, 8, 12, 24, 48, and 72 h post-(last) infusion]
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Total Apparent Clearance (CL) of Single Dose AZD9773 Serum Total Fabs (Cohorts 1 and 2)
Lasso di tempo: Day 1 [PK samples taken pre-dose, the end of each infusion rate and then at 0.5, 1, 2, 8, 12, 24, 48, and 72 h post-(last) infusion]
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CL of single dose AZD9773 serum total Fabs (cohorts 1 and 2).
PK analysis set (ie a subset of the safety analysis set including only those patients without important deviations that could affect the PK).
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Day 1 [PK samples taken pre-dose, the end of each infusion rate and then at 0.5, 1, 2, 8, 12, 24, 48, and 72 h post-(last) infusion]
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AUC(0-12) of Loading Dose AZD9773 Serum Total Fabs (Cohorts 3, 4 and 5)
Lasso di tempo: Day 1 [PK samples taken pre-dose, the end of each infusion rate and then at 0.5, 1, 2, 8 and 12 h post-(last) infusion]
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AUC(0-12) of loading dose AZD9773 serum total Fabs (cohorts 3, 4 and 5).
PK analysis set (ie a subset of the safety analysis set including only those patients without important deviations that could affect the PK).
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Day 1 [PK samples taken pre-dose, the end of each infusion rate and then at 0.5, 1, 2, 8 and 12 h post-(last) infusion]
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Maximum (End of Infusion) Serum Concentration (Cinf) of Loading Dose AZD9773 Serum Total Fabs (Cohorts 3,4 and 5)
Lasso di tempo: Day 1 [PK samples taken pre-dose, the end of each infusion rate and then at 0.5, 1, 2, 8 and 12 h post-(last)infusion]
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Cinf of loading dose AZD9773 serum total Fabs (cohorts 3, 4 and 5).
PK analysis set (ie a subset of the safety analysis set including only those patients without important deviations that could affect the PK).
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Day 1 [PK samples taken pre-dose, the end of each infusion rate and then at 0.5, 1, 2, 8 and 12 h post-(last)infusion]
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Time to Reach Cinf (Tmax) of Loading Dose AZD9773 Serum Total Fabs (Cohorts 3, 4 and 5)
Lasso di tempo: Day 1 [PK samples taken pre-dose, the end of each infusion rate and then at 0.5, 1, 2, 8 and 12 h post-(last)infusion]
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tmax of loading dose AZD9773 serum total Fabs (cohorts 3, 4 and 5).
PK analysis set (ie a subset of the safety analysis set including only those patients without important deviations that could affect the PK).
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Day 1 [PK samples taken pre-dose, the end of each infusion rate and then at 0.5, 1, 2, 8 and 12 h post-(last)infusion]
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AUC(0-12) of Maintenance Dose AZD9773 Serum Total Fabs (Cohorts 3, 4 and 5)
Lasso di tempo: PK samples taken pre-dose of Doses 5,7 and 9, then at 0, 0.5, 1, 2, 8 and 12 h post dose 9 infusion
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AUC(0-12) of maintenance dose AZD9773 serum total Fabs (cohorts 3, 4 and 5).
PK analysis set (ie a subset of the safety analysis set including only those patients without important deviations that could affect the PK).
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PK samples taken pre-dose of Doses 5,7 and 9, then at 0, 0.5, 1, 2, 8 and 12 h post dose 9 infusion
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Cinf of Maintenance Dose AZD9773 Serum Total Fabs (Cohorts 3, 4 and 5)
Lasso di tempo: PK samples taken pre-dose of Doses 5,7 and 9, then at 0, 0.5, 1, 2, 8 and 12 h post dose 9 infusion
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Cinf of maintenance dose AZD9773 serum total Fabs (cohorts 3, 4 and 5).
PK analysis set (ie a subset of the safety analysis set including only those patients without important deviations that could affect the PK).
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PK samples taken pre-dose of Doses 5,7 and 9, then at 0, 0.5, 1, 2, 8 and 12 h post dose 9 infusion
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Tmax of Maintenance Dose AZD9773 Serum Total Fabs (Cohorts 3, 4 and 5)
Lasso di tempo: PK samples taken pre-dose of Doses 5,7 and 9, then at 0, 0.5, 1, 2, 8 and 12 h post dose 9 infusion
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tmax of maintenance dose AZD9773 serum total Fabs (cohorts 3, 4 and 5).
PK analysis set (ie a subset of the safety analysis set including only those patients without important deviations that could affect the PK).
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PK samples taken pre-dose of Doses 5,7 and 9, then at 0, 0.5, 1, 2, 8 and 12 h post dose 9 infusion
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Number of Patients Below Tumour Necrosis Factor (TNF)-Alpha Limit of Quantification (LOQ) at 24 Hours (n< LOQ)
Lasso di tempo: 24 hours
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Number of patients below tumour necrosis factor (TNF)-alpha limit of quantification (LOQ) at 24 hours (n< LOQ) measured by ELISA (LOQ = 1.3 pg/mL).
Safety analysis set (ie all patients who started study drug infusion).
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24 hours
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Collaboratori e investigatori
Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.
Sponsor
Investigatori
- Direttore dello studio: Steven Simonson, MD, AstraZeneca
Pubblicazioni e link utili
La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.
Studiare le date dei record
Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.
Studia le date principali
Inizio studio
1 gennaio 2008
Completamento primario (Effettivo)
1 luglio 2009
Completamento dello studio (Effettivo)
1 luglio 2009
Date di iscrizione allo studio
Primo inviato
31 gennaio 2008
Primo inviato che soddisfa i criteri di controllo qualità
1 febbraio 2008
Primo Inserito (Stima)
14 febbraio 2008
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Stima)
22 agosto 2013
Ultimo aggiornamento inviato che soddisfa i criteri QC
19 luglio 2013
Ultimo verificato
1 luglio 2013
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
Altri numeri di identificazione dello studio
- D0620C00004
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .
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