AZD9773 Dose Escalation Study
perjantai 19. heinäkuuta 2013 päivittänyt: 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.
Tutkimuksen yleiskatsaus
Opintotyyppi
Interventio
Ilmoittautuminen (Todellinen)
70
Vaihe
- Vaihe 2
Yhteystiedot ja paikat
Tässä osiossa on tutkimuksen suorittajien yhteystiedot ja tiedot siitä, missä tämä tutkimus suoritetaan.
Opiskelupaikat
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Alabama
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Birmingham, Alabama, Yhdysvallat
- Research Site
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Delaware
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Newark, Delaware, Yhdysvallat
- Research Site
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Florida
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Bay Pines, Florida, Yhdysvallat
- Research Site
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Miami, Florida, Yhdysvallat
- Research Site
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Illinois
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Chicago, Illinois, Yhdysvallat
- Research Site
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Oak Park, Illinois, Yhdysvallat
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Peoria, Illinois, Yhdysvallat
- Research Site
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Indiana
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Indianapolis, Indiana, Yhdysvallat
- Research Site
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Iowa
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Iowa City, Iowa, Yhdysvallat
- Research Site
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Kentucky
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Hazard, Kentucky, Yhdysvallat
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Lexington, Kentucky, Yhdysvallat
- Research Site
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Maryland
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Baltimore, Maryland, Yhdysvallat
- Research Site
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Missouri
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Kansas City, Missouri, Yhdysvallat
- Research Site
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New Jersey
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Camden, New Jersey, Yhdysvallat
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Newark, New Jersey, Yhdysvallat
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New York
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Brooklyn, New York, Yhdysvallat
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New York, New York, Yhdysvallat
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Rochester, New York, Yhdysvallat
- Research Site
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North Carolina
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Durham, North Carolina, Yhdysvallat
- Research Site
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Greensboro, North Carolina, Yhdysvallat
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Winston Salem, North Carolina, Yhdysvallat
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Ohio
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Columbus, Ohio, Yhdysvallat
- Research Site
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Oklahoma
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Oklahoma City, Oklahoma, Yhdysvallat
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Tennessee
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Nashville, Tennessee, Yhdysvallat
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Texas
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Galveston, Texas, Yhdysvallat
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Houston, Texas, Yhdysvallat
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Osallistumiskriteerit
Tutkijat etsivät ihmisiä, jotka sopivat tiettyyn kuvaukseen, jota kutsutaan kelpoisuuskriteereiksi. Joitakin esimerkkejä näistä kriteereistä ovat henkilön yleinen terveydentila tai aiemmat hoidot.
Kelpoisuusvaatimukset
Opintokelpoiset iät
18 vuotta ja vanhemmat (Aikuinen, Vanhempi Aikuinen)
Hyväksyy terveitä vapaaehtoisia
Ei
Sukupuolet, jotka voivat opiskella
Kaikki
Kuvaus
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.
Opintosuunnitelma
Tässä osiossa on tietoja tutkimussuunnitelmasta, mukaan lukien kuinka tutkimus on suunniteltu ja mitä tutkimuksella mitataan.
Miten tutkimus on suunniteltu?
Suunnittelun yksityiskohdat
- Ensisijainen käyttötarkoitus: Hoito
- Jako: Satunnaistettu
- Inventiomalli: Yksittäinen ryhmätehtävä
- Naamiointi: Kolminkertaistaa
Aseet ja interventiot
Osallistujaryhmä / Arm |
Interventio / Hoito |
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Placebo Comparator: Plasebo
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Plasebo
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Kokeellinen: AZD9773 cohort 1 (50 units/kg)
AZD9773: single infusion of 50 units/kg
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intravenous infusions
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Kokeellinen: AZD9773 cohort 2 (250 units/kg)
AZD9773: single infusion of 250 units/kg
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intravenous infusions
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Kokeellinen: 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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Kokeellinen: 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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Kokeellinen: 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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Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
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Change From Baseline in Creatinine Values
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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.
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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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Toissijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
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28-Day Mortality
Aikaikkuna: 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
Aikaikkuna: 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)
Aikaikkuna: 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)
Aikaikkuna: 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)
Aikaikkuna: 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)
Aikaikkuna: 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)
Aikaikkuna: 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)
Aikaikkuna: 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)
Aikaikkuna: 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)
Aikaikkuna: 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)
Aikaikkuna: 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)
Aikaikkuna: 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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Yhteistyökumppanit ja tutkijat
Täältä löydät tähän tutkimukseen osallistuvat ihmiset ja organisaatiot.
Sponsori
Tutkijat
- Opintojohtaja: Steven Simonson, MD, AstraZeneca
Julkaisuja ja hyödyllisiä linkkejä
Tutkimusta koskevien tietojen syöttämisestä vastaava henkilö toimittaa nämä julkaisut vapaaehtoisesti. Nämä voivat koskea mitä tahansa tutkimukseen liittyvää.
Opintojen ennätyspäivät
Nämä päivämäärät seuraavat ClinicalTrials.gov-sivustolle lähetettyjen tutkimustietueiden ja yhteenvetojen edistymistä. National Library of Medicine (NLM) tarkistaa tutkimustiedot ja raportoidut tulokset varmistaakseen, että ne täyttävät tietyt laadunvalvontastandardit, ennen kuin ne julkaistaan julkisella verkkosivustolla.
Opi tärkeimmät päivämäärät
Opiskelun aloitus
Tiistai 1. tammikuuta 2008
Ensisijainen valmistuminen (Todellinen)
Keskiviikko 1. heinäkuuta 2009
Opintojen valmistuminen (Todellinen)
Keskiviikko 1. heinäkuuta 2009
Opintoihin ilmoittautumispäivät
Ensimmäinen lähetetty
Torstai 31. tammikuuta 2008
Ensimmäinen toimitettu, joka täytti QC-kriteerit
Perjantai 1. helmikuuta 2008
Ensimmäinen Lähetetty (Arvio)
Torstai 14. helmikuuta 2008
Tutkimustietojen päivitykset
Viimeisin päivitys julkaistu (Arvio)
Torstai 22. elokuuta 2013
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
Perjantai 19. heinäkuuta 2013
Viimeksi vahvistettu
Maanantai 1. heinäkuuta 2013
Lisää tietoa
Tähän tutkimukseen liittyvät termit
Muita asiaankuuluvia MeSH-ehtoja
Muut tutkimustunnusnumerot
- D0620C00004
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