AZD9773 Dose Escalation Study
19 de julho de 2013 atualizado por: 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.
Visão geral do estudo
Status
Concluído
Condições
Intervenção / Tratamento
Tipo de estudo
Intervencional
Inscrição (Real)
70
Estágio
- Fase 2
Contactos e Locais
Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.
Locais de estudo
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Alabama
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Birmingham, Alabama, Estados Unidos
- Research Site
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Delaware
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Newark, Delaware, Estados Unidos
- Research Site
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Florida
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Bay Pines, Florida, Estados Unidos
- Research Site
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Miami, Florida, Estados Unidos
- Research Site
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Illinois
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Chicago, Illinois, Estados Unidos
- Research Site
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Oak Park, Illinois, Estados Unidos
- Research Site
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Peoria, Illinois, Estados Unidos
- Research Site
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Indiana
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Indianapolis, Indiana, Estados Unidos
- Research Site
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Iowa
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Iowa City, Iowa, Estados Unidos
- Research Site
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Kentucky
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Hazard, Kentucky, Estados Unidos
- Research Site
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Lexington, Kentucky, Estados Unidos
- Research Site
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Maryland
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Baltimore, Maryland, Estados Unidos
- Research Site
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Missouri
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Kansas City, Missouri, Estados Unidos
- Research Site
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New Jersey
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Camden, New Jersey, Estados Unidos
- Research Site
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Newark, New Jersey, Estados Unidos
- Research Site
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New York
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Brooklyn, New York, Estados Unidos
- Research Site
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New York, New York, Estados Unidos
- Research Site
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Rochester, New York, Estados Unidos
- Research Site
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North Carolina
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Durham, North Carolina, Estados Unidos
- Research Site
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Greensboro, North Carolina, Estados Unidos
- Research Site
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Winston Salem, North Carolina, Estados Unidos
- Research Site
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Ohio
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Columbus, Ohio, Estados Unidos
- Research Site
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Oklahoma
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Oklahoma City, Oklahoma, Estados Unidos
- Research Site
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Tennessee
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Nashville, Tennessee, Estados Unidos
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Texas
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Galveston, Texas, Estados Unidos
- Research Site
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Houston, Texas, Estados Unidos
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Critérios de participação
Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.
Critérios de elegibilidade
Idades elegíveis para estudo
18 anos e mais velhos (Adulto, Adulto mais velho)
Aceita Voluntários Saudáveis
Não
Gêneros Elegíveis para o Estudo
Tudo
Descrição
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.
Plano de estudo
Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição de grupo único
- Mascaramento: Triplo
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
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Comparador de Placebo: Placebo
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Placebo
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Experimental: AZD9773 cohort 1 (50 units/kg)
AZD9773: single infusion of 50 units/kg
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intravenous infusions
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Experimental: AZD9773 cohort 2 (250 units/kg)
AZD9773: single infusion of 250 units/kg
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intravenous infusions
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Experimental: 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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Experimental: 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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Experimental: 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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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Change From Baseline in Creatinine Values
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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.
Prazo: 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
Prazo: 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
Prazo: 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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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
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28-Day Mortality
Prazo: 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
Prazo: 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)
Prazo: 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)
Prazo: 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)
Prazo: 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)
Prazo: 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)
Prazo: 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)
Prazo: 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)
Prazo: 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)
Prazo: 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)
Prazo: 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)
Prazo: 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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Colaboradores e Investigadores
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Patrocinador
Investigadores
- Diretor de estudo: Steven Simonson, MD, AstraZeneca
Publicações e links úteis
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Datas de registro do estudo
Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.
Datas Principais do Estudo
Início do estudo
1 de janeiro de 2008
Conclusão Primária (Real)
1 de julho de 2009
Conclusão do estudo (Real)
1 de julho de 2009
Datas de inscrição no estudo
Enviado pela primeira vez
31 de janeiro de 2008
Enviado pela primeira vez que atendeu aos critérios de CQ
1 de fevereiro de 2008
Primeira postagem (Estimativa)
14 de fevereiro de 2008
Atualizações de registro de estudo
Última Atualização Postada (Estimativa)
22 de agosto de 2013
Última atualização enviada que atendeu aos critérios de controle de qualidade
19 de julho de 2013
Última verificação
1 de julho de 2013
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- D0620C00004
Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .