Dose Escalation Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics of ASP2215 in Patients With Relapsed or Refractory Acute Myeloid Leukemia
Study Details
Study Description
Brief Summary
The objective of this study was to assess the safety and tolerability, including the maximum tolerated dose, of gilteritinib in participants with relapsed or treatment-refractory acute myeloid leukemia (AML). This study also determined the pharmacokinetic (PK) parameters of gilteritinib.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1/Phase 2 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Gilteritinib 20 mg in Escalation Phase Participants received a single dose of 20 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. |
Drug: Gilteritinib
Participants received gilteritinib oral tablets (10 mg, 40 mg or 100 mg, depending on the dose) once daily without food allowed for at least 2 hours before and 1 hour after dosing starting from day -2 and day of cycle 1, for continuous 28-day cycles.
Other Names:
Drug: Voriconazole
Participants received 200 mg voriconazole tablets daily every 12 hours starting from day 16 of cycle 1 through day 1 of cycle 2.
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Experimental: Gilteritinib 40 mg in Escalation Phase Participants received a single dose of 40 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. |
Drug: Gilteritinib
Participants received gilteritinib oral tablets (10 mg, 40 mg or 100 mg, depending on the dose) once daily without food allowed for at least 2 hours before and 1 hour after dosing starting from day -2 and day of cycle 1, for continuous 28-day cycles.
Other Names:
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Experimental: Gilteritinib 80 mg in Escalation Phase Participants received a single dose of 80 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. |
Drug: Gilteritinib
Participants received gilteritinib oral tablets (10 mg, 40 mg or 100 mg, depending on the dose) once daily without food allowed for at least 2 hours before and 1 hour after dosing starting from day -2 and day of cycle 1, for continuous 28-day cycles.
Other Names:
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Experimental: Gilteritinib 120 mg in Escalation Phase Participants received a single dose of 120 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. |
Drug: Gilteritinib
Participants received gilteritinib oral tablets (10 mg, 40 mg or 100 mg, depending on the dose) once daily without food allowed for at least 2 hours before and 1 hour after dosing starting from day -2 and day of cycle 1, for continuous 28-day cycles.
Other Names:
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Experimental: Gilteritinib 200 mg in Escalation Phase Participants received a single dose of 200 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. |
Drug: Gilteritinib
Participants received gilteritinib oral tablets (10 mg, 40 mg or 100 mg, depending on the dose) once daily without food allowed for at least 2 hours before and 1 hour after dosing starting from day -2 and day of cycle 1, for continuous 28-day cycles.
Other Names:
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Experimental: Gilteritinib 300 mg in Escalation Phase Participants received a single dose of 300 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. |
Drug: Gilteritinib
Participants received gilteritinib oral tablets (10 mg, 40 mg or 100 mg, depending on the dose) once daily without food allowed for at least 2 hours before and 1 hour after dosing starting from day -2 and day of cycle 1, for continuous 28-day cycles.
Other Names:
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Experimental: Gilteritinib 450 mg in Escalation Phase Participants received a single dose of 450 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. |
Drug: Gilteritinib
Participants received gilteritinib oral tablets (10 mg, 40 mg or 100 mg, depending on the dose) once daily without food allowed for at least 2 hours before and 1 hour after dosing starting from day -2 and day of cycle 1, for continuous 28-day cycles.
Other Names:
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Experimental: Gilteritinib 20 mg in Expansion Phase Participants received 20 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. Starting on day 16 of cycle 1, participants also received 200 mg voriconazole orally every 12 hours through day 1 of cycle 2. |
Drug: Gilteritinib
Participants received gilteritinib oral tablets (10 mg, 40 mg or 100 mg, depending on the dose) once daily without food allowed for at least 2 hours before and 1 hour after dosing starting from day -2 and day of cycle 1, for continuous 28-day cycles.
Other Names:
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Experimental: Gilteritinib 40 mg in Expansion Phase Participants received 40 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. |
Drug: Gilteritinib
Participants received gilteritinib oral tablets (10 mg, 40 mg or 100 mg, depending on the dose) once daily without food allowed for at least 2 hours before and 1 hour after dosing starting from day -2 and day of cycle 1, for continuous 28-day cycles.
Other Names:
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Experimental: Gilteritinib 80 mg in Expansion Phase Participants received 80 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. |
Drug: Gilteritinib
Participants received gilteritinib oral tablets (10 mg, 40 mg or 100 mg, depending on the dose) once daily without food allowed for at least 2 hours before and 1 hour after dosing starting from day -2 and day of cycle 1, for continuous 28-day cycles.
Other Names:
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Experimental: Gilteritinib 120 mg in Expansion Phase Participants received 120 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. |
Drug: Gilteritinib
Participants received gilteritinib oral tablets (10 mg, 40 mg or 100 mg, depending on the dose) once daily without food allowed for at least 2 hours before and 1 hour after dosing starting from day -2 and day of cycle 1, for continuous 28-day cycles.
Other Names:
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Experimental: Gilteritinib 200 mg in Expansion Phase Participants received 200 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, certain participants also received 500 mg cephalexin as a single oral dose. |
Drug: Gilteritinib
Participants received gilteritinib oral tablets (10 mg, 40 mg or 100 mg, depending on the dose) once daily without food allowed for at least 2 hours before and 1 hour after dosing starting from day -2 and day of cycle 1, for continuous 28-day cycles.
Other Names:
Drug: Cephalexin
Participants received a single oral dose of 500 mg cephalexin tablet or capsule on day -1 and day 15 of cycle 1.
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Experimental: Gilteritinib 300 mg in Expansion Phase Participants received 300 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, participants also received 2 mg midazolam as a single oral dose. |
Drug: Gilteritinib
Participants received gilteritinib oral tablets (10 mg, 40 mg or 100 mg, depending on the dose) once daily without food allowed for at least 2 hours before and 1 hour after dosing starting from day -2 and day of cycle 1, for continuous 28-day cycles.
Other Names:
Drug: Midazolam
Participants received a single oral dose of 2 mg of midazolam syrup on day -1 and day 15 of cycle 1.
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Outcome Measures
Primary Outcome Measures
- Number of Participants With Dose Limiting Toxicities (DLTs) [From first dose up to end of cycle 1 (30 days)]
To determine the maximum tolerated dose, safety was assessed by DLTs, defined as any grade ≥ 3 non-hematologic or extramedullary toxicity that occurred within 30 days starting with the first dose taken on day -2, and included the first treatment cycle in the dose escalation phase and in the first treatment cycle (28 days) in the dose expansion phase, that was considered to be possibly or probably related to study drug. Exceptions to this were the following: (1) Alopecia, anorexia or fatigue, (2) Grade 3 nausea and/or vomiting if not required tube feeding or total parenteral nutrition, or diarrhea if not required or prolonged hospitalization that was managed to grade ≤ 2 with standard antiemetic or antidiarrheal medications used at prescribed dose within 7 days of onset, (3) Grade 3 fever with neutropenia, with or without infection, (4) Grade 3 infection.
- Number of Participants With Adverse Events (AEs) [From first dose of study drug up to 30 days after last dose of study drug (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)]
Safety was assessed by AEs, which included abnormalities identified during a medical test (e.g. laboratory tests, vital signs, electrocardiogram, etc.) if the abnormality induced clinical signs or symptoms, needed active intervention, interruption or discontinuation of study medication or was clinically significant. A treatment-emergent AE (TEAE) was defined as an AE observed after starting administration of the study drug up to 30 days after last dose of study drug (for participants who underwent hematopoietic stem cell transplantation [HSCT]: defined as AEs observed after starting study drug until the last dose before on study HSCT plus 30 days, and AEs that began after resumption of gilteritinib and within 30 days after the last dose of gilteritinib). AEs were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (1-Mild, 2-Moderate, 3-Severe, 4-LifeThreatening, 5-Death).
- Area Under the Concentration-time Curve Over the 24-Hour Dosing Interval (AUC24) After Single and Multiple Doses of Gilteritinib [Day -2 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose]
Plasma samples were used for pharmacokinetic assessments.
- Maximum Concentration (Cmax) After Single and Multiple Doses of Gilteritinib [Day -2 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose]
Plasma samples were used for pharmacokinetic assessments.
- Area Under the Concentration-time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) After Single and Multiple Doses of Gilteritinib [Day -2 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose]
Plasma samples were used for pharmacokinetic assessments.
- Time to Observed Cmax (Tmax) After Single and Multiple Doses of Gilteritinib [Day -2 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose]
Plasma samples were used for pharmacokinetic assessments.
- Terminal Elimination Half-life (t1/2) After Multiple Doses of Gilteritinib [Cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose]
Plasma samples were used for pharmacokinetic assessments.
- Accumulation Ratio After Multiple Doses of Gilteritinib [Cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose]
Plasma samples were used for pharmacokinetic assessments.
Secondary Outcome Measures
- Percentage of Participants With Complete Remission (CR) During the First 2 Cycles [During the first 2 cycles (56 days)]
CR was defined according to modified Cheson criteria (2003), using centrally evaluated myeloblast counts from bone marrow aspirate/biopsy assessments and centrally evaluated hematology results; if neither central bone marrow aspirate nor biopsy was available, myeloblast was imputed with locally evaluated bone marrow aspirate/biopsy assessments (derived response). Participants were classified as being in CR when they had bone marrow regenerating normal hematopoietic cells, achieved a morphologic leukemia-free state, had an absolute neutrophil count (ANC) > 1 x 10^9/L, platelet count ≥ 100 x 10^9/L, normal marrow differential with < 5% blasts, had been red blood cell (RBC) and platelet transfusion independent (defined as 1 week without RBC transfusion and 1 week without platelet transfusion), had no presence of Auer rods and no evidence of extramedullary leukemia, and blast counts in peripheral blood had been ≤ 2%. Exact 95% confidence interval was estimated using binomial distribution.
- Percentage of Participants With CR During Treatment [Up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)]
CR was defined according to modified Cheson criteria (2003), using centrally evaluated myeloblast counts from bone marrow aspirate/biopsy assessments and centrally evaluated hematology results; if neither central bone marrow aspirate nor biopsy was available, myeloblast was imputed with locally evaluated bone marrow aspirate/biopsy assessments (derived response). Participants were classified as being in CR when they had bone marrow regenerating normal hematopoietic cells, achieved a morphologic leukemia-free state, had an absolute neutrophil count (ANC) > 1 x 10^9/L, platelet count ≥ 100 x 10^9/L, normal marrow differential with < 5% blasts, had been red blood cell (RBC) and platelet transfusion independent (defined as 1 week without RBC transfusion and 1 week without platelet transfusion), had no presence of Auer rods and no evidence of extramedullary leukemia, and blast counts in peripheral blood had been ≤ 2%. Exact 95% confidence interval was estimated using binomial distribution.
- Percentage of Participants With CR With Incomplete Platelet Recovery (CRp) [Up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)]
CRp was defined according to modified Cheson criteria (2003), using centrally evaluated myeloblast counts from bone marrow aspirate/biopsy assessments and centrally evaluated hematology results; if neither central bone marrow aspirate nor biopsy was available, myeloblast was imputed with locally evaluated bone marrow aspirate/biopsy assessments (derived response). Participants were classified as being in CRp when they achieved CR except for incomplete platelet recovery (< 100 x 10^9/L). Exact 95% confidence interval was estimated using the binomial distribution.
- Percentage of Participants With CR With Incomplete Hematological Recovery (CRi) [Up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)]
CRi was defined according to modified Cheson criteria (2003), using centrally evaluated myeloblast counts from bone marrow aspirate/biopsy assessments and centrally evaluated hematology results; if neither central bone marrow aspirate nor biopsy was available, myeloblast was imputed with locally evaluated bone marrow aspirate/biopsy assessments (derived response). Participants were classified as being in CRi when they fulfilled all the criteria for CR except for incomplete hematological recovery with residual neutropenia < 1 x 10^9/L with or without complete platelet recovery. RBC and platelet transfusion independence were not required. Exact 95% confidence interval was estimated using the binomial distribution.
- Percentage of Participants With Complete Remission With Partial Hematologic Recovery (CRh) [Up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)]
CRh was defined according to modified Cheson criteria (2003), using centrally evaluated myeloblast counts from bone marrow aspirate/biopsy assessments and centrally evaluated hematology results; if neither central bone marrow aspirate nor biopsy was available, myeloblast was imputed with locally evaluated bone marrow aspirate/biopsy assessments (derived response). Participants were classified as being in CRh when they could not be classified as being in CR and had bone marrow blasts < 5% and partial hematologic recovery ANC >= 0.5 x 10^9/L and platelets >= 50 x 10^9/L. There should not be evidence of extramedullary leukemia. Exact 95% confidence interval was estimated using the binomial distribution. CRh was calculated only for participants who were FLT3 mutation positive.
- Percentage of Participants With Composite CR (CRc) [Up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)]
CRc was defined according to modified Cheson criteria (2003), using centrally evaluated myeloblast counts from bone marrow aspirate/biopsy assessments and centrally evaluated hematology results; if neither central bone marrow aspirate nor biopsy was available, myeloblast was imputed with locally evaluated bone marrow aspirate/biopsy assessments (derived response). Participants were classified as being in CRc when they had achieved either CR, complete remission with incomplete platelet recovery (CRp, defined as had achieved CR except for incomplete platelet recovery (< 100 x 10^9/L) or complete remission with incomplete hematologic recovery (CRi, defined as had fulfilled all the criteria for CR except for incomplete hematological recovery with residual neutropenia < 1 x 10^9/L with or without complete platelet recovery; RBC platelet transfusion independence not required). Exact 95% confidence interval was estimated using the binomial distribution.
- Percentage of Participants With Partial Remission (PR) [Up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)]
PR was defined according to modified Cheson criteria (2003), using centrally evaluated myeloblast counts from bone marrow aspirate/biopsy assessments and centrally evaluated hematology results; if neither central bone marrow aspirate nor biopsy was available, myeloblast was imputed with locally evaluated bone marrow aspirate/biopsy assessments (derived response). Participants were classified as being in PR when they had bone marrow regenerating normal hematopoietic cells with evidence of peripheral recovery with no (or only a few regenerating) circulating blasts and with a decrease of at least 50% in the percentage of blasts in the bone marrow aspirate with the total marrow blasts between 5% and 25%. A value of less or equal than 5% blasts was also considered a PR if Auer rods were present. There should be no evidence of extramedullary leukemia. Exact 95% confidence interval was estimated using the binomial distribution.
- Percentage of Participants With Best Response [Up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)]
Best response was defined according to modified Cheson criteria (2003), using centrally evaluated myeloblast counts from bone marrow aspirate/biopsy assessments and centrally evaluated hematology results; if neither central bone marrow aspirate nor biopsy was available, myeloblast was imputed with locally evaluated bone marrow aspirate/biopsy assessments (derived response). BR was defined as the best measured response for all visits (in the order of CR, CRp, CRi, and PR) post-treatment. Participants who achieved the best response of CR, CRp, CRi or PR were classified as responders. Participants who did not achieve at least PR were considered as non-responders. Exact 95% confidence interval was estimated using the binomial distribution.
- Percentage of Participants With Complete Remission and Complete Remission With Partial Hematologic Recovery (CR/CRh) [Up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)]
Participants with CR/CRh were defined as participants who achieved either CR or CRh. Participants with CR had bone marrow regenerating normal hematopoietic cells, achieved a morphologic leukemia-free state, had an ANC > 1 x 10^9/L, platelet count ≥ 100 x 10^9/L, and normal marrow differential with < 5% blasts, had been RBC and platelet transfusion independent (defined as 1 week without RBC transfusion and 1 week without platelet transfusion). Also, there had been no presence of Auer rods, no evidence of extramedullary leukemia, and blast counts in peripheral blood had been ≤ 2%. Participants with CRh could not be classified as being in CR and had bone marrow blasts < 5%, partial hematologic recovery ANC >= 0.5 x 10^9/L and platelets >= 50 x 10^9/L. There should not be evidence of extramedullary leukemia. Exact 95% confidence interval was estimated using the binomial distribution. CR/CRh was calculated only for participants who were FLT3 mutation positive.
- Duration of CR (DCR) [From date of remission until end of study (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)]
DCR was defined as the time from the date of first CR until the date of documented relapse for participants who achieved CR. Participants who died without report of relapse were considered non-events and censored at their last relapse-free disease assessment date. Other participants who did not relapse on study were considered non-events and censored at the last relapse-free disease assessment date. DCR was calculated using Kaplan-Meier method and therefore data are estimated.
- Duration of CRp (DCRp) [From date of remission until end of study (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)]
DCRp was defined as the time from the date of first CRp until the date of documented relapse for participants who achieved CRp. Participants who died without report of relapse were considered non-events and censored at their last relapse-free disease assessment date. Other participants who did not relapse on study were considered non-events and censored at the last relapse-free disease assessment date. DCRp was calculated using Kaplan-Meier method and therefore data are estimated.
- Duration of CRi (DCRi) [From date of remission until end of study (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)]
DCRi was defined as the time from the date of first CRi until the date of documented relapse for participants who achieved CRi. Participants who died without report of relapse and participants who did not relapse were considered non-events and censored at the last relapse-free disease assessment date. DCRi was calculated using Kaplan-Meier method and therefore data are estimated.
- Duration of CRh (DCRh) [From date of remission until end of study (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)]
DCRh was defined as the time from the date of first CRh until the date of documented relapse for participants who achieved CRh but did not have a best response of CR. Participants who died without report of relapse and participants who did not relapse were considered non-events and censored at the last relapse-free disease assessment date. DCRh was calculated using Kaplan-Meier method and therefore data are estimated. DCRh was calculated only for participants who were FLT3 mutation positive.
- Duration of CRc (DCRc) [From date of remission until end of study (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)]
DCRc was defined as the time from the date of first CRc until the date of documented relapse for participants who achieved CRc. Participants who died without report of relapse and participants who did not relapse were considered non-events and censored at the last relapse-free disease assessment date. DCRc was calculated using Kaplan-Meier method and therefore data are estimated.
- Duration of CR/CRh (DCRCRh) [From date of remission until end of study (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)]
DCRCRh was defined as the time from the date of first DCRCRh until the date of documented relapse for participants who achieved CR or CRh. For participants who achieved both CR and CRh, the first CR date or CRh date, whichever occurred first, was used. Participants who died without report of relapse and participants who did not relapse were considered non-events and censored at the last relapse-free disease assessment date. DCRCRh was calculated using Kaplan-Meier method and therefore data are estimated. DCRCRh was calculated only for participants who were FLT3 mutation positive.
- Duration of Response [From date of remission until end of study (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)]
Duration of response was defined as the time from the date of either first CRc or PR until the date of documented relapse of any type for participants who achieved CRc or PR. Participants who died without report of relapse were considered non-events and censored at their last relapse-free disease assessment date. Other participants who did not relapse on study are considered non-events and censored at the last relapse-free assessment date. Duration of response was calculated using Kaplan-Meier method and therefore data are estimated.
- Time to CR (TTCR) [From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)]
TTCR was defined as the time from the first dose of study drug until the date of first CR.
- Time to CRp (TTCRp) [From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)]
TTCRp was defined as the time from the first dose of study drug until the date of first CRp. TTCRp was evaluated for participants who achieved CRp.
- Time to CRi (TTCRi) [From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)]
TTCRi was defined as the time from the first dose of study drug until the date of first CRi. TTCRi was evaluated for participants who achieved CRi.
- Time to First CR/CRh (TTFCRCRh) [From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)]
TTFCRCRh was defined as the time from the first dose of study drug until the date of first either CR or CRh. TTFCRCRh was evaluated for participants who achieved CR or CRh. For participants who achieve both CR and CRh, the first CR date or CRh date, whichever occurs first was used. TTFCRCRh was calculated only for participants who were FLT3 mutation positive.
- Time to Best CR/CRh (TTBCRCRh) [From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)]
TTBCRCRh was defined as the time from the first dose of study drug until the first date that the best response of CR or CRh was achieved. TTBCRCRh was evaluated for participants who achieved CR or CRh. For participants who achieve both CR and CRh, the first CR date was used. TTBCRCRh was calculated only for participants who were FLT3 mutation positive.
- Time to CRc (TTCRc) [From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)]
TTCRc was defined as the time from the first dose of study drug until the date of first CRc. TTCRc was evaluated for participants who achieved CRc.
- Time to Response (TTR) [From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)]
TTR was defined as the time from the first dose of study drug until the date of either first CRc or PR. TTR was evaluated for participants who achieved CRc or PR.
- Time to Best Response (TTBR) [From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days)]
TTBR was defined as the time from the first dose of study drug until the first disease assessment date when participant achieved best response. TTBR was evaluated in participants who achieved best response of CR, CRp, CRi, or PR.
- Overall Survival (OS) [From first dose of study drug up to end of study (median time on study was 157.0 days, minimum of 5 days and maximum of 1320 days)]
The time from the date of first dose of study drug until the date of death from any cause. For a participant who was not known to have died by the end of study follow-up, OS was censored at the date of last contact. OS was calculated using Kaplan-Meier method and therefore data are estimated.
- Event Free Survival (EFS) [From first dose of study drug up to end of study (median time on study was 157.0 days, minimum of 5 days and maximum of 1320 days)]
EFS was defined as the time from the date of first dose of study drug until the date of documented relapse, treatment failure or death from any cause, whichever occurred first. For a participant with none of these events, EFS was censored at the date of last relapse-free disease assessment. A participant without post-treatment disease assessment was censored at randomization date. Treatment failure included those participants who discontinued the treatment due to "progressive disease" or "lack of efficacy" without a previous response of CR, CRp, CRi or PR. Treatment failure date referred to the start of new anti-leukemia therapy or the last treatment evaluation date when new anti-leukemia therapy date was not available. For participants who were censored, last relapse-free disease assessment date referred to the participant's last disease assessment date. EFS was calculated using Kaplan-Meier method and therefore data are estimated.
- Leukemia Free Survival (LFS) [From first dose of study drug up to end of study (median time on study was 157.0 days, minimum of 5 days and maximum of 1320 days)]
LFS was defined as the time from the date of first CRc until the date of documented relapse or death for participants who achieved CRc. For a participant who was not known to have relapsed or died, LFS was censored on the date of last relapse-free disease assessment date. LFS was calculated using Kaplan-Meier method and therefore data are estimated.
- Percentage of Participants Who Achieved Transfusion Conversion [Baseline (28 days prior to first dose until 28 days after the first dose) and postbaseline (from 29 days after first dose date until last dose date); median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days]
Participants who achieved transfusion conversion were defined as the number of participants who were transfusion dependent at baseline period but became transfusion independent at post-baseline period divided by the total number of participants who were transfusion dependent at baseline period. Participants were considered baseline transfusion dependent if there were RBC or platelet transfusions within the baseline period. Participants were considered post-baseline transfusion independent if they were on treatment >=84 days, and if there was one consecutive 56 days without any RBC or platelet transfusion within post-baseline period. If participants were on treatment >28 days but <84 days, and there was no RBC or platelet transfusion within post-baseline period, or on treatment <=28 days, post-baseline transfusion status was not evaluable. Exact 95% confidence interval was estimated using the binomial distribution.
- Percentage of Participants Who Achieved Transfusion Maintenance [Baseline (28 days prior to first dose until 28 days after the first dose) and postbaseline (from 29 days after first dose date until last dose date); median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days]
Participants who achieved transfusion maintenance were defined as the number of participants who were transfusion independent at baseline period and still maintained transfusion independent at post-baseline period divided by the total number of participants who were transfusion independent at baseline period.
- AUC24 of Gilteritinib in Co-administration With Voriconazole [Cycle 1 Day 15 and Cycle 2 Day 1: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (gilteritinib)]
Plasma samples were used for pharmacokinetic assessments.
- Cmax of Gilteritinib in Co-administration With Voriconazole [Cycle 1 Day 15 and Cycle 2 Day 1: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (gilteritinib)]
Plasma samples were used for pharmacokinetic assessments.
- AUClast of Gilteritinib in Co-administration With Voriconazole [Cycle 1 Day 15 and Cycle 2 Day 1: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (gilteritinib)]
Plasma samples were used for pharmacokinetic assessments.
- Tmax of Gilteritinib in Co-administration With Voriconazole [Cycle 1 Day 15 and Cycle 2 Day 1: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (gilteritinib)]
Plasma samples were used for pharmacokinetic assessments.
- AUC24 of Midazolam Administered With and Without Gilteritinib [Day -1 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (midazolam)]
Plasma samples were used for pharmacokinetic assessments.
- AUC24 of Metabolite 1-Hydroxymidazolam After Administration of Midazolam With and Without Gilteritinib [Day -1 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (midazolam)]
Plasma samples were used for pharmacokinetic assessments.
- Cmax of Midazolam Administered With and Without Gilteritinib [Day -1 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (midazolam)]
Plasma samples were used for pharmacokinetic assessments.
- Cmax of 1-Hydroxymidazolam After Administration of Midazolam With and Without Gilteritinib [Day -1 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (midazolam)]
Plasma samples were used for pharmacokinetic assessments.
- AUClast of Midazolam Administered With and Without Gilteritinib [Day -1 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (midazolam)]
Plasma samples were used for pharmacokinetic assessments.
- AUClast of 1-Hydroxymidazolam After Administration of Midazolam With and Without Gilteritinib [Day -1 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (midazolam)]
Plasma samples were used for pharmacokinetic assessments.
- Tmax of Midazolam Administered With and Without Gilteritinib [Day -1 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (midazolam)]
Plasma samples were used for pharmacokinetic assessments.
- Tmax of 1-Hydroxymidazolam After Administration of Midazolam With and Without Gilteritinib [Day -1 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (midazolam)]
Plasma samples were used for pharmacokinetic assessments.
- Area Under the Concentration-time Curve From the Time of Dosing Extrapolated to Time Infinity (AUCinf) of Cephalexin Administered With and Without Gilteritinib [Day -1 and cycle 1 day 15: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 24 hours postdose (cephalexin)]
Plasma samples were used for pharmacokinetic assessments.
- Cmax of Cephalexin Administered With and Without Gilteritinib [Day -1 and cycle 1 day 15: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 24 hours postdose (cephalexin)]
Plasma samples were used for pharmacokinetic assessments.
- AUClast of Cephalexin Administered With and Without Gilteritinib [Day -1 and cycle 1 day 15: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 24 hours postdose (cephalexin)]
Plasma samples were used for pharmacokinetic assessments.
- Tmax of Cephalexin Administered With and Without Gilteritinib [Day -1 and cycle 1 day 15: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 24 hours postdose (cephalexin)]
Plasma samples were used for pharmacokinetic assessments.
- T1/2 of Cephalexin Administered With and Without Gilteritinib [Day -1 and cycle 1 day 15: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 24 hours postdose (cephalexin)]
Plasma samples were used for pharmacokinetic assessments.
- Apparent Total Systemic Clearance After Single or Multiple Extravascular Dosing (CL/F) of Cephalexin Administered With and Without Gilteritinib [Day -1 and cycle 1 day 15: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 24 hours postdose (cephalexin)]
Plasma samples were used for pharmacokinetic assessments.
- Apparent Volume of Distribution During the Terminal Elimination Phase After Single Extravascular Dosing (Vz/F) of Cephalexin Administered With and Without Gilteritinib [Day -1 and cycle 1 day 15: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 24 hours postdose (cephalexin)]
Plasma samples were used for pharmacokinetic assessments.
- Amount of Drug Excreted in Urine (Aelast) of Cephalexin Administered With and Without Gilteritinib [Day -1 and cycle 1 day 15: 0-3 hours, 3-6 hours, 6-24 hours postdose (cephalexin)]
Urine samples were used for pharmacokinetic assessments.
- Fraction of Drug Excreted Into Urine in Percentage (%Ae) of Cephalexin Administered With and Without Gilteritinib [Day -1 and cycle 1 day 15: 0-3 hours, 3-6 hours, 6-24 hours postdose (cephalexin)]
Urine samples were used for pharmacokinetic assessments.
- Renal Clearance (CLr) of Cephalexin in Administered With and Without Gilteritinib [Day -1 and cycle 1 day 15: 0-3 hours, 3-6 hours, 6-24 hours postdose (cephalexin)]
Urine samples were used for pharmacokinetic assessments.
Eligibility Criteria
Criteria
Inclusion Criteria:
- Subject is defined as morphologically documented primary or secondary AML by the World
Health Organization (WHO) criteria (2008) and fulfills one of the following:
-
Refractory to at least 1 cycle of induction chemotherapy
-
Relapsed after achieving remission with a prior therapy
-
Subject has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
-
Subject's interval from prior treatment to time of study drug administration is at least 2 weeks for cytotoxic agents (except hydroxyurea given for controlling blast cells), or at least 5 half-lives for prior experimental agents or noncytotoxic agents.
-
Subject must meet the following criteria as indicated on the clinical laboratory tests*:
-
Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <2.5 x institutional upper limit normal (ULN)
-
Total serum bilirubin < 1.5x institutional ULN
-
Serum creatinine < 1.5 x institutional ULN or an estimated glomerular filtration rate (eGFR) of > 50 ml/min as calculated by the Modification of Diet in Renal Disease (MDRD) equation.
-
Subject agrees not to participate in another interventional study while on treatment.
Exclusion Criteria:
-
Subject was diagnosed as acute promyelocytic leukemia (APL).
-
Subject has BCR-ABL-positive leukemia (chronic myelogenous leukemia in blast crisis).
-
Subject has active malignant tumors other than AML or Myelodysplastic syndrome (MDS).
-
Subject has persistent nonhematological toxicities of >= Grade 2 (Common Terminology Criteria for Adverse Events v4), with symptoms and objective findings, from prior AML treatment (including chemotherapy, kinase inhibitors, immunotherapy, experimental agents, radiation, or surgery).
-
Subject has had hematopoietic stem cell transplant (HSCT) and meets any of the following:
-
Is within 2 months of transplant from C1D1
-
Has clinically significant graft-versus-host disease requiring treatment
-
Has >= Grade 2 persistent non-hematological toxicity related to the transplant. Donor lymphocytes infusion (DLI) is not permitted <= 30 days prior to study registration or during the first cycle of treatment on the study in Cohort 1 and first two cycles of the treatment in Cohort 2
-
Subject has clinically active central nervous system leukemia
-
Subject has disseminated intravascular coagulation abnormality (DIC)
-
Subject has had major surgery within 4 weeks prior to the first study dose.
-
Subject has had radiation therapy within 4 weeks prior to the first study dose
-
Subject has congestive heart failure New York Heart Association (NYHA) class 3 or 4, or subject with a history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram performed within 3 months prior to study entry results in a left ventricular ejection fraction that is ≥ 45%
-
Subject requires treatment with concomitant drugs that are strong inhibitors or inducers of Cytochrome P450-isozyme3A4 (CYP3A4) with the exception of antibiotics, antifungals, and antivirals that are used as standard of care post-transplant or to prevent or treat infections and other such drugs that are considered absolutely essential for the care of the subject
-
Subject required treatment with concomitant drugs that target serotonin 5HT1R or 5HT2BR receptors or sigma nonspecific receptor with the exception of drugs that are considered absolutely essential for the care of the subject.
-
Subject has an active uncontrolled infection
-
Subject is known to have human immunodeficiency virus infection
-
Subject has active hepatitis B or C, or other active hepatic disorder
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Site US10021 | Birmingham | Alabama | United States | 35294 |
2 | Site US10023 | Scottsdale | Arizona | United States | 85259 |
3 | Site US10022 | Duarte | California | United States | 91010 |
4 | Site US10008 | Los Angeles | California | United States | 90095-1678 |
5 | Site US10005 | San Francisco | California | United States | 94143 |
6 | Site US10001 | Chicago | Illinois | United States | 60611 |
7 | Site US10015 | Chicago | Illinois | United States | 60637 |
8 | Site US10012 | Baltimore | Maryland | United States | 21201 |
9 | Site US10003 | Baltimore | Maryland | United States | 21287 |
10 | Site US10006 | Minneapolis | Minnesota | United States | 55455 |
11 | Site US10011 | Rochester | Minnesota | United States | 55905 |
12 | Site US10020 | Hackensack | New Jersey | United States | 07601 |
13 | Site US10010 | Buffalo | New York | United States | 14263 |
14 | Site US10009 | New York | New York | United States | 10022 |
15 | Site US10013 | New York | New York | United States | 10032 |
16 | Site US10019 | New York | New York | United States | 10065 |
17 | Site US10014 | Cleveland | Ohio | United States | 44195 |
18 | Site US10018 | Hershey | Pennsylvania | United States | 17033 |
19 | Site US10004 | Philadelphia | Pennsylvania | United States | 19104 |
20 | Site US10017 | Charleston | South Carolina | United States | 29425-8900 |
21 | Site US10007 | Nashville | Tennessee | United States | 37232 |
22 | Site US10002 | Houston | Texas | United States | 77030 |
23 | Site US10026 | Fairfax | Virginia | United States | 22031 |
24 | Site DE49002 | Berlin | Germany | 12203 | |
25 | Site DE49004 | Dresden | Germany | 01307 | |
26 | Site IT39001 | Bologna | Italy | 40138 |
Sponsors and Collaborators
- Astellas Pharma Global Development, Inc.
Investigators
- Study Director: Executive Medical Director, Astellas Pharma Global Development
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.- 2215-CL-0101
Study Results
Participant Flow
Recruitment Details | This dose-escalation/dose-expansion study was conducted in sites in the United States, France, Germany and Italy. The study had 7 dose-escalation cohorts with ≥3 participants enrolled at each dose level. Following escalation to the next dose cohort, additional participants were enrolled to the dose-expansion cohorts per protocol-specified criteria. |
---|---|
Pre-assignment Detail | Participants with acute myeloid leukemia (AML) who relapsed after or were refractory to induction or salvage treatment were selected for this study. Five participants were re-enrolled into the dose-expansion cohorts as they discontinued treatment for reasons other than toxicity or disease progression, as long as they met the eligibility criteria. |
Arm/Group Title | Gilteritinib 20 mg in Escalation Phase | Gilteritinib 40 mg in Escalation Phase | Gilteritinib 80 mg in Escalation Phase | Gilteritinib 120 mg in Escalation Phase | Gilteritinib 200 mg in Escalation Phase | Gilteritinib 300 mg in Escalation Phase | Gilteritinib 450 mg in Escalation Phase | Gilteritinib 20 mg in Expansion Phase | Gilteritinib 40 mg in Expansion Phase | Gilteritinib 80 mg in Expansion Phase | Gilteritinib 120 mg in Expansion Phase | Gilteritinib 200 mg in Expansion Phase | Gilteritinib 300 mg in Expansion Phase |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Arm/Group Description | Participants received a single dose of 20 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 40 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 80 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 120 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 200 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 300 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 450 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received 20 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. Starting on day 16 of cycle 1, participants also received 200 mg voriconazole orally every 12 hours through day 1 of cycle 2. | Participants received 40 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. | Participants received 80 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. | Participants received 120 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. | Participants received 200 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, certain participants also received 500 mg cephalexin as a single oral dose. | Participants received 300 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, participants also received 2 mg midazolam as a single oral dose. |
Period Title: Overall Study | |||||||||||||
STARTED | 5 | 3 | 3 | 3 | 4 | 3 | 4 | 11 | 15 | 21 | 69 | 102 | 17 |
Treated | 5 | 3 | 3 | 3 | 3 | 3 | 3 | 12 | 13 | 21 | 66 | 100 | 17 |
COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
NOT COMPLETED | 5 | 3 | 3 | 3 | 4 | 3 | 4 | 11 | 15 | 21 | 69 | 102 | 17 |
Baseline Characteristics
Arm/Group Title | Gilteritinib 20 mg in Escalation Phase | Gilteritinib 40 mg in Escalation Phase | Gilteritinib 80 mg in Escalation Phase | Gilteritinib 120 mg in Escalation Phase | Gilteritinib 200 mg in Escalation Phase | Gilteritinib 300 mg in Escalation Phase | Gilteritinib 450 mg in Escalation Phase | Gilteritinib 20 mg in Expansion Phase | Gilteritinib 40 mg in Expansion Phase | Gilteritinib 80 mg in Expansion Phase | Gilteritinib 120 mg in Expansion Phase | Gilteritinib 200 mg in Expansion Phase | Gilteritinib 300 mg in Expansion Phase | Total |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Arm/Group Description | Participants received a single dose of 20 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 40 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 80 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 120 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 200 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 300 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 450 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received 20 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. Starting on day 16 of cycle 1, participants also received 200 mg voriconazole orally every 12 hours through day 1 of cycle 2. | Participants received 40 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. | Participants received 80 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. | Participants received 120 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. | Participants received 200 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, certain participants also received 500 mg cephalexin as a single oral dose. | Participants received 300 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, participants also received 2 mg midazolam as a single oral dose. | Total of all reporting groups |
Overall Participants | 5 | 3 | 3 | 3 | 3 | 3 | 3 | 12 | 13 | 21 | 66 | 100 | 17 | 252 |
Age (years) [Mean (Standard Deviation) ] | ||||||||||||||
Mean (Standard Deviation) [years] |
65.8
(6.8)
|
56.7
(6.7)
|
61
(8.7)
|
61.7
(6)
|
64
(1)
|
55.3
(25)
|
61.7
(10.7)
|
59.3
(15.6)
|
59.6
(14)
|
56.3
(18.1)
|
58.3
(16.7)
|
59.8
(14.6)
|
57.7
(15.9)
|
59
(15.1)
|
Sex: Female, Male (Count of Participants) | ||||||||||||||
Female |
2
40%
|
1
33.3%
|
1
33.3%
|
1
33.3%
|
2
66.7%
|
1
33.3%
|
0
0%
|
8
66.7%
|
4
30.8%
|
12
57.1%
|
37
56.1%
|
49
49%
|
5
29.4%
|
123
48.8%
|
Male |
3
60%
|
2
66.7%
|
2
66.7%
|
2
66.7%
|
1
33.3%
|
2
66.7%
|
3
100%
|
4
33.3%
|
9
69.2%
|
9
42.9%
|
29
43.9%
|
51
51%
|
12
70.6%
|
129
51.2%
|
Race/Ethnicity, Customized (Count of Participants) | ||||||||||||||
Black or African American |
0
0%
|
0
0%
|
0
0%
|
1
33.3%
|
1
33.3%
|
0
0%
|
0
0%
|
1
8.3%
|
0
0%
|
4
19%
|
2
3%
|
4
4%
|
3
17.6%
|
16
6.3%
|
White |
5
100%
|
2
66.7%
|
3
100%
|
2
66.7%
|
1
33.3%
|
3
100%
|
3
100%
|
10
83.3%
|
9
69.2%
|
14
66.7%
|
57
86.4%
|
91
91%
|
13
76.5%
|
213
84.5%
|
Asian |
0
0%
|
1
33.3%
|
0
0%
|
0
0%
|
1
33.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
1.5%
|
4
4%
|
0
0%
|
7
2.8%
|
Other |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
8.3%
|
4
30.8%
|
3
14.3%
|
6
9.1%
|
1
1%
|
1
5.9%
|
16
6.3%
|
Ethnicity (Count of Participants) | ||||||||||||||
Not Hispanic or Latino |
5
100%
|
3
100%
|
2
66.7%
|
3
100%
|
3
100%
|
3
100%
|
3
100%
|
11
91.7%
|
12
92.3%
|
20
95.2%
|
62
93.9%
|
97
97%
|
17
100%
|
241
95.6%
|
Hispanic or Latino |
0
0%
|
0
0%
|
1
33.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
8.3%
|
1
7.7%
|
1
4.8%
|
4
6.1%
|
3
3%
|
0
0%
|
11
4.4%
|
Duration of Disease (AML) (months) [Mean (Standard Deviation) ] | ||||||||||||||
Mean (Standard Deviation) [months] |
19.70
(24.62)
|
10.81
(8.58)
|
62.46
(6.97)
|
49.53
(72.17)
|
9.46
(2.23)
|
19.75
(NA)
|
7.21
(4.27)
|
11.3
(6.61)
|
10.53
(11.22)
|
16.3
(9.85)
|
12.65
(11.33)
|
10.9
(9.94)
|
12.09
(17.76)
|
13.16
(14.97)
|
Local FLT3 Mutation Status (Count of Participants) | ||||||||||||||
Negative |
1
20%
|
0
0%
|
0
0%
|
1
33.3%
|
1
33.3%
|
1
33.3%
|
1
33.3%
|
1
8.3%
|
8
61.5%
|
12
57.1%
|
13
19.7%
|
10
10%
|
9
52.9%
|
58
23%
|
Positive |
4
80%
|
3
100%
|
3
100%
|
2
66.7%
|
2
66.7%
|
2
66.7%
|
2
66.7%
|
11
91.7%
|
5
38.5%
|
9
42.9%
|
53
80.3%
|
90
90%
|
8
47.1%
|
194
77%
|
Outcome Measures
Title | Number of Participants With Dose Limiting Toxicities (DLTs) |
---|---|
Description | To determine the maximum tolerated dose, safety was assessed by DLTs, defined as any grade ≥ 3 non-hematologic or extramedullary toxicity that occurred within 30 days starting with the first dose taken on day -2, and included the first treatment cycle in the dose escalation phase and in the first treatment cycle (28 days) in the dose expansion phase, that was considered to be possibly or probably related to study drug. Exceptions to this were the following: (1) Alopecia, anorexia or fatigue, (2) Grade 3 nausea and/or vomiting if not required tube feeding or total parenteral nutrition, or diarrhea if not required or prolonged hospitalization that was managed to grade ≤ 2 with standard antiemetic or antidiarrheal medications used at prescribed dose within 7 days of onset, (3) Grade 3 fever with neutropenia, with or without infection, (4) Grade 3 infection. |
Time Frame | From first dose up to end of cycle 1 (30 days) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the SAF. Only evaluable participants (defined as participants who received at least 80% of the intended dose during cycle 1 [received at least 23 daily doses in escalation phase or 22 daily doses in expansion phase during cycle 1] or participants who developed DLT within cycle 1) were included. |
Arm/Group Title | Gilteritinib 20 mg in Escalation Phase | Gilteritinib 40 mg in Escalation Phase | Gilteritinib 80 mg in Escalation Phase | Gilteritinib 120 mg in Escalation Phase | Gilteritinib 200 mg in Escalation Phase | Gilteritinib 300 mg in Escalation Phase | Gilteritinib 450 mg in Escalation Phase | Gilteritinib 20 mg in Expansion Phase | Gilteritinib 40 mg in Expansion Phase | Gilteritinib 80 mg in Expansion Phase | Gilteritinib 120 mg in Expansion Phase | Gilteritinib 200 mg in Expansion Phase | Gilteritinib 300 mg in Expansion Phase |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Arm/Group Description | Participants received a single dose of 20 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 40 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 80 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 120 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received a single dose of 200 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 300 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 450 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received 20 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. Starting on day 16 of cycle 1, participants also received 200 mg voriconazole orally every 12 hours through day 1 of cycle 2. | Participants received 40 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. | Participants received 80 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. | Participants received 120 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. | Participants received 200 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, certain participants also received 500 mg cephalexin as a single oral dose. | Participants received 300 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, participants also received 2 mg midazolam as a single oral dose. |
Measure Participants | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 9 | 11 | 18 | 62 | 87 | 13 |
Any DLT |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
66.7%
|
1
8.3%
|
1
7.7%
|
2
9.5%
|
7
10.6%
|
15
15%
|
3
17.6%
|
Blood and lymphatic system disorders |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
5.9%
|
Cardiac disorders |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
1.5%
|
0
0%
|
0
0%
|
Eye disorders |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
4.8%
|
0
0%
|
0
0%
|
0
0%
|
Gastrointestinal disorders |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
33.3%
|
0
0%
|
0
0%
|
0
0%
|
1
1.5%
|
4
4%
|
1
5.9%
|
General disorders & administration site conditions |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
1%
|
0
0%
|
Hepatobiliary disorders |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
1.5%
|
0
0%
|
0
0%
|
Infections and infestations |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
7.7%
|
1
4.8%
|
0
0%
|
0
0%
|
0
0%
|
Investigations |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
33.3%
|
0
0%
|
0
0%
|
0
0%
|
2
3%
|
6
6%
|
2
11.8%
|
Metabolism and nutrition disorders |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
2%
|
0
0%
|
Musculoskeletal and connective tissue disorders |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
1%
|
1
5.9%
|
Nervous system disorders |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
8.3%
|
0
0%
|
0
0%
|
0
0%
|
3
3%
|
0
0%
|
Renal and urinary disorders |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
1.5%
|
0
0%
|
0
0%
|
Reproductive system and breast disorders |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
1%
|
0
0%
|
Respiratory, thoracic and mediastinal disorders |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
1.5%
|
2
2%
|
1
5.9%
|
Vascular disorders |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
2%
|
1
5.9%
|
Title | Number of Participants With Adverse Events (AEs) |
---|---|
Description | Safety was assessed by AEs, which included abnormalities identified during a medical test (e.g. laboratory tests, vital signs, electrocardiogram, etc.) if the abnormality induced clinical signs or symptoms, needed active intervention, interruption or discontinuation of study medication or was clinically significant. A treatment-emergent AE (TEAE) was defined as an AE observed after starting administration of the study drug up to 30 days after last dose of study drug (for participants who underwent hematopoietic stem cell transplantation [HSCT]: defined as AEs observed after starting study drug until the last dose before on study HSCT plus 30 days, and AEs that began after resumption of gilteritinib and within 30 days after the last dose of gilteritinib). AEs were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (1-Mild, 2-Moderate, 3-Severe, 4-LifeThreatening, 5-Death). |
Time Frame | From first dose of study drug up to 30 days after last dose of study drug (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the SAF. |
Arm/Group Title | Gilteritinib 20 mg in Escalation Phase | Gilteritinib 40 mg in Escalation Phase | Gilteritinib 80 mg in Escalation Phase | Gilteritinib 120 mg in Escalation Phase | Gilteritinib 200 mg in Escalation Phase | Gilteritinib 300 mg in Escalation Phase | Gilteritinib 450 mg in Escalation Phase | Gilteritinib 20 mg in Expansion Phase | Gilteritinib 40 mg in Expansion Phase | Gilteritinib 80 mg in Expansion Phase | Gilteritinib 120 mg in Expansion Phase | Gilteritinib 200 mg in Expansion Phase | Gilteritinib 300 mg in Expansion Phase |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Arm/Group Description | Participants received a single dose of 20 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 40 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 80 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 120 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 200 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 300 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 450 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received 20 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. Starting on day 16 of cycle 1, participants also received 200 mg voriconazole orally every 12 hours through day 1 of cycle 2. | Participants received 40 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. | Participants received 80 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. | Participants received 120 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. | Participants received 200 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, certain participants also received 500 mg cephalexin as a single oral dose. | Participants received 300 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, participants also received 2 mg midazolam as a single oral dose. |
Measure Participants | 5 | 3 | 3 | 3 | 3 | 3 | 3 | 12 | 13 | 21 | 66 | 100 | 17 |
AEs |
5
100%
|
3
100%
|
3
100%
|
3
100%
|
3
100%
|
3
100%
|
3
100%
|
12
100%
|
13
100%
|
20
95.2%
|
64
97%
|
100
100%
|
17
100%
|
Drug-Related AEs |
3
60%
|
2
66.7%
|
1
33.3%
|
3
100%
|
3
100%
|
2
66.7%
|
3
100%
|
7
58.3%
|
6
46.2%
|
17
81%
|
52
78.8%
|
77
77%
|
13
76.5%
|
Deaths |
2
40%
|
2
66.7%
|
0
0%
|
1
33.3%
|
1
33.3%
|
1
33.3%
|
1
33.3%
|
3
25%
|
4
30.8%
|
11
52.4%
|
23
34.8%
|
49
49%
|
7
41.2%
|
Serious AEs |
2
40%
|
2
66.7%
|
2
66.7%
|
1
33.3%
|
2
66.7%
|
2
66.7%
|
2
66.7%
|
8
66.7%
|
12
92.3%
|
19
90.5%
|
52
78.8%
|
92
92%
|
14
82.4%
|
Drug-Related Serious AEs |
0
0%
|
0
0%
|
0
0%
|
1
33.3%
|
1
33.3%
|
0
0%
|
2
66.7%
|
2
16.7%
|
1
7.7%
|
10
47.6%
|
19
28.8%
|
36
36%
|
4
23.5%
|
AEs Leading to Discontinuation of Study Drug |
2
40%
|
0
0%
|
1
33.3%
|
0
0%
|
1
33.3%
|
0
0%
|
1
33.3%
|
2
16.7%
|
5
38.5%
|
11
52.4%
|
12
18.2%
|
46
46%
|
6
35.3%
|
Drug-Related AEs Leading to Discont. of Study Drug |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
8.3%
|
1
7.7%
|
4
19%
|
5
7.6%
|
10
10%
|
3
17.6%
|
Grade 3 or Higher TEAEs |
3
60%
|
2
66.7%
|
2
66.7%
|
1
33.3%
|
2
66.7%
|
2
66.7%
|
3
100%
|
9
75%
|
13
100%
|
20
95.2%
|
59
89.4%
|
99
99%
|
14
82.4%
|
AEs During On-Study HSCT Period |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
3
4.5%
|
7
7%
|
0
0%
|
Serious AEs During On-Study HSCT |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
3
3%
|
0
0%
|
Title | Area Under the Concentration-time Curve Over the 24-Hour Dosing Interval (AUC24) After Single and Multiple Doses of Gilteritinib |
---|---|
Description | Plasma samples were used for pharmacokinetic assessments. |
Time Frame | Day -2 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetics analysis set (PKAS) - consisted of the subset of the SAF for which sufficient plasma concentration data were available to facilitate derivation of at least 1 pharmacokinetic parameter and for whom the time of dosing on the day of sampling was known. Participants with available data were included in the analysis. |
Arm/Group Title | Gilteritinib 20 mg in Escalation Phase | Gilteritinib 40 mg in Escalation Phase | Gilteritinib 80 mg in Escalation Phase | Gilteritinib 120 mg in Escalation Phase | Gilteritinib 200 mg in Escalation Phase | Gilteritinib 300 mg in Escalation Phase | Gilteritinib 450 mg in Escalation Phase |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants received a single dose of 20 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 40 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 80 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 120 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 200 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 300 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 450 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. |
Measure Participants | 5 | 3 | 3 | 3 | 3 | 3 | 3 |
Day -2 |
302.1
(207.0)
|
360.0
(223.5)
|
1216
(472.6)
|
2480
(1972)
|
3022
(843.6)
|
4163
(3178)
|
3324
(221.1)
|
Cycle 1 Day 15 |
1299
(1006)
|
2482
(33.28)
|
6958
(3273)
|
6943
(3221)
|
31428
(21412)
|
31005
(10068)
|
34768
(NA)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Gilteritinib 20 mg in Escalation Phase, Gilteritinib 40 mg in Escalation Phase, Gilteritinib 80 mg in Escalation Phase, Gilteritinib 120 mg in Escalation Phase, Gilteritinib 200 mg in Escalation Phase, Gilteritinib 300 mg in Escalation Phase, Gilteritinib 450 mg in Escalation Phase |
---|---|---|
Comments | Dose Proportionality (Single Dose / Day -2) was evaluated using the power model. | |
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Slope |
Estimated Value | 0.990 | |
Confidence Interval |
(2-Sided) 90% 0.788 to 1.19 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Gilteritinib 20 mg in Escalation Phase, Gilteritinib 40 mg in Escalation Phase, Gilteritinib 80 mg in Escalation Phase, Gilteritinib 120 mg in Escalation Phase, Gilteritinib 200 mg in Escalation Phase, Gilteritinib 300 mg in Escalation Phase, Gilteritinib 450 mg in Escalation Phase |
---|---|---|
Comments | Dose Proportionality (Multiple Dose / Cycle 1 Day 15) was evaluated using the power model. | |
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Slope |
Estimated Value | 1.22 | |
Confidence Interval |
(2-Sided) 90% 1.00 to 1.43 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Maximum Concentration (Cmax) After Single and Multiple Doses of Gilteritinib |
---|---|
Description | Plasma samples were used for pharmacokinetic assessments. |
Time Frame | Day -2 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the PKAS with available data. |
Arm/Group Title | Gilteritinib 20 mg in Escalation Phase | Gilteritinib 40 mg in Escalation Phase | Gilteritinib 80 mg in Escalation Phase | Gilteritinib 120 mg in Escalation Phase | Gilteritinib 200 mg in Escalation Phase | Gilteritinib 300 mg in Escalation Phase | Gilteritinib 450 mg in Escalation Phase |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants received a single dose of 20 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.. | Participants received a single dose of 40 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study.. | Participants received a single dose of 80 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 120 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 200 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 300 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 450 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. |
Measure Participants | 5 | 3 | 3 | 3 | 3 | 3 | 3 |
Day -2 |
28.13
(21.49)
|
24.98
(14.58)
|
75.29
(25.22)
|
136.7
(94.37)
|
168.2
(45.34)
|
204.3
(136.4)
|
207.6
(51.81)
|
Cycle 1 day 15 |
64.64
(48.77)
|
107.6
(31.92)
|
376.4
(150.5)
|
374.2
(190.1)
|
1462
(815.1)
|
1525
(664.6)
|
1528
(NA)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Gilteritinib 20 mg in Escalation Phase, Gilteritinib 40 mg in Escalation Phase, Gilteritinib 80 mg in Escalation Phase, Gilteritinib 120 mg in Escalation Phase, Gilteritinib 200 mg in Escalation Phase, Gilteritinib 300 mg in Escalation Phase, Gilteritinib 450 mg in Escalation Phase |
---|---|---|
Comments | Dose Proportionality (Single Dose / Day -2) was evaluated using the power model. | |
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Slope |
Estimated Value | 0.808 | |
Confidence Interval |
(2-Sided) 90% 0.629 to 0.988 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Gilteritinib 20 mg in Escalation Phase, Gilteritinib 40 mg in Escalation Phase, Gilteritinib 80 mg in Escalation Phase, Gilteritinib 120 mg in Escalation Phase, Gilteritinib 200 mg in Escalation Phase, Gilteritinib 300 mg in Escalation Phase, Gilteritinib 450 mg in Escalation Phase |
---|---|---|
Comments | Dose Proportionality (Multiple Dose / Cycle 1 Day 15) was evaluated using the power model. | |
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Slope |
Estimated Value | 1.21 | |
Confidence Interval |
(2-Sided) 90% 1.02 to 1.41 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Area Under the Concentration-time Curve From the Time of Dosing to the Last Measurable Concentration (AUClast) After Single and Multiple Doses of Gilteritinib |
---|---|
Description | Plasma samples were used for pharmacokinetic assessments. |
Time Frame | Day -2 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the PKAS with available data. |
Arm/Group Title | Gilteritinib 20 mg in Escalation Phase | Gilteritinib 40 mg in Escalation Phase | Gilteritinib 80 mg in Escalation Phase | Gilteritinib 120 mg in Escalation Phase | Gilteritinib 200 mg in Escalation Phase | Gilteritinib 300 mg in Escalation Phase | Gilteritinib 450 mg in Escalation Phase |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants received a single dose of 20 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 40 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 80 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 120 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 200 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 300 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 450 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. |
Measure Participants | 5 | 3 | 3 | 3 | 3 | 3 | 3 |
Day -2 |
303.0
(207.1)
|
360.4
(224.1)
|
1216
(472.6)
|
2480
(1972)
|
3024
(846.2)
|
4181
(3189)
|
2544
(1427)
|
Cycle 1 day -15 |
1030
(984.2)
|
1990
(1422)
|
7111
(3525)
|
6943
(3221)
|
32248
(22571)
|
31749
(10090)
|
35506
(NA)
|
Title | Time to Observed Cmax (Tmax) After Single and Multiple Doses of Gilteritinib |
---|---|
Description | Plasma samples were used for pharmacokinetic assessments. |
Time Frame | Day -2 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the PKAS with available data. |
Arm/Group Title | Gilteritinib 20 mg in Escalation Phase | Gilteritinib 40 mg in Escalation Phase | Gilteritinib 80 mg in Escalation Phase | Gilteritinib 120 mg in Escalation Phase | Gilteritinib 200 mg in Escalation Phase | Gilteritinib 300 mg in Escalation Phase | Gilteritinib 450 mg in Escalation Phase |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants received a single dose of 20 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 40 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 80 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 120 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 200 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 300 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 450 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. |
Measure Participants | 5 | 3 | 3 | 3 | 3 | 3 | 3 |
Day -2 |
2.00
|
5.983
|
4.000
|
2.083
|
5.233
|
6.067
|
5.783
|
Cycle 1 day 15 |
4.008
|
3.867
|
4.333
|
2.167
|
6.033
|
6.050
|
5.933
|
Title | Terminal Elimination Half-life (t1/2) After Multiple Doses of Gilteritinib |
---|---|
Description | Plasma samples were used for pharmacokinetic assessments. |
Time Frame | Cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the PKAS with available data. |
Arm/Group Title | Gilteritinib 20 mg in Escalation Phase | Gilteritinib 40 mg in Escalation Phase | Gilteritinib 80 mg in Escalation Phase | Gilteritinib 120 mg in Escalation Phase | Gilteritinib 200 mg in Escalation Phase | Gilteritinib 300 mg in Escalation Phase | Gilteritinib 450 mg in Escalation Phase |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants received a single dose of 20 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 40 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 80 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 120 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 200 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 300 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 450 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. |
Measure Participants | 3 | 2 | 3 | 3 | 2 | 3 | 0 |
Mean (Standard Deviation) [hours] |
62.14
(17.88)
|
151.8
(129.2)
|
86.11
(24.08)
|
45.85
(18.83)
|
141.9
(61.51)
|
142.2
(55.04)
|
Title | Accumulation Ratio After Multiple Doses of Gilteritinib |
---|---|
Description | Plasma samples were used for pharmacokinetic assessments. |
Time Frame | Cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the PKAS with available data. |
Arm/Group Title | Gilteritinib 20 mg in Escalation Phase | Gilteritinib 40 mg in Escalation Phase | Gilteritinib 80 mg in Escalation Phase | Gilteritinib 120 mg in Escalation Phase | Gilteritinib 200 mg in Escalation Phase | Gilteritinib 300 mg in Escalation Phase | Gilteritinib 450 mg in Escalation Phase |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants received a single dose of 20 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 40 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 80 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 120 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 200 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 300 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 450 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in in the escalation phase of the study.28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. |
Measure Participants | 3 | 2 | 3 | 3 | 2 | 3 | 0 |
Mean (Standard Deviation) [ratio] |
4.259
(1.069)
|
9.640
(7.754)
|
5.693
(1.442)
|
3.290
(1.118)
|
9.041
(3.693)
|
9.057
(3.303)
|
Title | Percentage of Participants With Complete Remission (CR) During the First 2 Cycles |
---|---|
Description | CR was defined according to modified Cheson criteria (2003), using centrally evaluated myeloblast counts from bone marrow aspirate/biopsy assessments and centrally evaluated hematology results; if neither central bone marrow aspirate nor biopsy was available, myeloblast was imputed with locally evaluated bone marrow aspirate/biopsy assessments (derived response). Participants were classified as being in CR when they had bone marrow regenerating normal hematopoietic cells, achieved a morphologic leukemia-free state, had an absolute neutrophil count (ANC) > 1 x 10^9/L, platelet count ≥ 100 x 10^9/L, normal marrow differential with < 5% blasts, had been red blood cell (RBC) and platelet transfusion independent (defined as 1 week without RBC transfusion and 1 week without platelet transfusion), had no presence of Auer rods and no evidence of extramedullary leukemia, and blast counts in peripheral blood had been ≤ 2%. Exact 95% confidence interval was estimated using binomial distribution. |
Time Frame | During the first 2 cycles (56 days) |
Outcome Measure Data
Analysis Population Description |
---|
Full analysis set (FAS) - consisted of all participants who were enrolled, took at least 1 dose of study drug and who had at least 1 posttreatment data point. Re-enrolled participants and participants from one site due to concerns with this site's GCP compliance were excluded. Participants were summarized under planned reporting groups in the FAS. |
Arm/Group Title | Gilteritinib 20 mg | Gilteritinib 40 mg | Gilteritinib 80 mg | Gilteritinib 120 mg | Gilteritinib 200 mg | Gilteritinib 300 mg | Gilteritinib 450 mg |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. |
Measure Participants | 16 | 16 | 24 | 70 | 100 | 20 | 3 |
FLT3 Mutation Positive |
0
0%
|
0
0%
|
8.3
276.7%
|
3.6
120%
|
3.4
113.3%
|
10
333.3%
|
0
0%
|
FLT3 Mutation Negative |
50.0
1000%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
All Participants |
6.3
126%
|
0
0%
|
4.2
140%
|
2.9
96.7%
|
3.0
100%
|
5.0
166.7%
|
0
0%
|
Title | Percentage of Participants With CR During Treatment |
---|---|
Description | CR was defined according to modified Cheson criteria (2003), using centrally evaluated myeloblast counts from bone marrow aspirate/biopsy assessments and centrally evaluated hematology results; if neither central bone marrow aspirate nor biopsy was available, myeloblast was imputed with locally evaluated bone marrow aspirate/biopsy assessments (derived response). Participants were classified as being in CR when they had bone marrow regenerating normal hematopoietic cells, achieved a morphologic leukemia-free state, had an absolute neutrophil count (ANC) > 1 x 10^9/L, platelet count ≥ 100 x 10^9/L, normal marrow differential with < 5% blasts, had been red blood cell (RBC) and platelet transfusion independent (defined as 1 week without RBC transfusion and 1 week without platelet transfusion), had no presence of Auer rods and no evidence of extramedullary leukemia, and blast counts in peripheral blood had been ≤ 2%. Exact 95% confidence interval was estimated using binomial distribution. |
Time Frame | Up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the FAS. |
Arm/Group Title | Gilteritinib 20 mg | Gilteritinib 40 mg | Gilteritinib 80 mg | Gilteritinib 120 mg | Gilteritinib 200 mg | Gilteritinib 300 mg | Gilteritinib 450 mg |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. |
Measure Participants | 16 | 16 | 24 | 70 | 100 | 20 | 3 |
FLT3 Mutation Positive |
0
0%
|
0
0%
|
16.7
556.7%
|
12.5
416.7%
|
11.2
373.3%
|
10.0
333.3%
|
0
0%
|
FLT3 Mutation Negative |
50.0
1000%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
All Participants |
6.3
126%
|
0
0%
|
8.3
276.7%
|
10.0
333.3%
|
10.0
333.3%
|
5.0
166.7%
|
0
0%
|
Title | Percentage of Participants With CR With Incomplete Platelet Recovery (CRp) |
---|---|
Description | CRp was defined according to modified Cheson criteria (2003), using centrally evaluated myeloblast counts from bone marrow aspirate/biopsy assessments and centrally evaluated hematology results; if neither central bone marrow aspirate nor biopsy was available, myeloblast was imputed with locally evaluated bone marrow aspirate/biopsy assessments (derived response). Participants were classified as being in CRp when they achieved CR except for incomplete platelet recovery (< 100 x 10^9/L). Exact 95% confidence interval was estimated using the binomial distribution. |
Time Frame | Up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the FAS. |
Arm/Group Title | Gilteritinib 20 mg | Gilteritinib 40 mg | Gilteritinib 80 mg | Gilteritinib 120 mg | Gilteritinib 200 mg | Gilteritinib 300 mg | Gilteritinib 450 mg |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. |
Measure Participants | 16 | 16 | 24 | 70 | 100 | 20 | 3 |
FLT3 Mutation Positive |
0
0%
|
0
0%
|
0
0%
|
3.6
120%
|
9.0
300%
|
10.0
333.3%
|
0
0%
|
FLT3 Mutation Negative |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
All Participants |
0
0%
|
0
0%
|
0
0%
|
2.9
96.7%
|
8.0
266.7%
|
5.0
166.7%
|
0
0%
|
Title | Percentage of Participants With CR With Incomplete Hematological Recovery (CRi) |
---|---|
Description | CRi was defined according to modified Cheson criteria (2003), using centrally evaluated myeloblast counts from bone marrow aspirate/biopsy assessments and centrally evaluated hematology results; if neither central bone marrow aspirate nor biopsy was available, myeloblast was imputed with locally evaluated bone marrow aspirate/biopsy assessments (derived response). Participants were classified as being in CRi when they fulfilled all the criteria for CR except for incomplete hematological recovery with residual neutropenia < 1 x 10^9/L with or without complete platelet recovery. RBC and platelet transfusion independence were not required. Exact 95% confidence interval was estimated using the binomial distribution. |
Time Frame | Up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the FAS. |
Arm/Group Title | Gilteritinib 20 mg | Gilteritinib 40 mg | Gilteritinib 80 mg | Gilteritinib 120 mg | Gilteritinib 200 mg | Gilteritinib 300 mg | Gilteritinib 450 mg |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. |
Measure Participants | 16 | 16 | 24 | 70 | 100 | 20 | 3 |
FLT3 Mutation Positive |
7.1
142%
|
0
0%
|
25.0
833.3%
|
30.4
1013.3%
|
20.2
673.3%
|
10.0
333.3%
|
0
0%
|
FLT3 Mutation Negative |
0
0%
|
0
0%
|
16.7
556.7%
|
7.1
236.7%
|
9.1
303.3%
|
0
0%
|
0
0%
|
All Participants |
6.3
126%
|
0
0%
|
20.8
693.3%
|
25.7
856.7%
|
19.0
633.3%
|
5.0
166.7%
|
0
0%
|
Title | Percentage of Participants With Complete Remission With Partial Hematologic Recovery (CRh) |
---|---|
Description | CRh was defined according to modified Cheson criteria (2003), using centrally evaluated myeloblast counts from bone marrow aspirate/biopsy assessments and centrally evaluated hematology results; if neither central bone marrow aspirate nor biopsy was available, myeloblast was imputed with locally evaluated bone marrow aspirate/biopsy assessments (derived response). Participants were classified as being in CRh when they could not be classified as being in CR and had bone marrow blasts < 5% and partial hematologic recovery ANC >= 0.5 x 10^9/L and platelets >= 50 x 10^9/L. There should not be evidence of extramedullary leukemia. Exact 95% confidence interval was estimated using the binomial distribution. CRh was calculated only for participants who were FLT3 mutation positive. |
Time Frame | Up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the FAS, with participants who were FLT3 mutation positive. |
Arm/Group Title | Gilteritinib 20 mg | Gilteritinib 40 mg | Gilteritinib 80 mg | Gilteritinib 120 mg | Gilteritinib 200 mg | Gilteritinib 300 mg | Gilteritinib 450 mg |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. |
Measure Participants | 14 | 8 | 12 | 56 | 89 | 10 | 2 |
Number (95% Confidence Interval) [percentage of participants] |
7.1
142%
|
0
0%
|
8.3
276.7%
|
10.7
356.7%
|
7.9
263.3%
|
20.0
666.7%
|
0
0%
|
Title | Percentage of Participants With Composite CR (CRc) |
---|---|
Description | CRc was defined according to modified Cheson criteria (2003), using centrally evaluated myeloblast counts from bone marrow aspirate/biopsy assessments and centrally evaluated hematology results; if neither central bone marrow aspirate nor biopsy was available, myeloblast was imputed with locally evaluated bone marrow aspirate/biopsy assessments (derived response). Participants were classified as being in CRc when they had achieved either CR, complete remission with incomplete platelet recovery (CRp, defined as had achieved CR except for incomplete platelet recovery (< 100 x 10^9/L) or complete remission with incomplete hematologic recovery (CRi, defined as had fulfilled all the criteria for CR except for incomplete hematological recovery with residual neutropenia < 1 x 10^9/L with or without complete platelet recovery; RBC platelet transfusion independence not required). Exact 95% confidence interval was estimated using the binomial distribution. |
Time Frame | Up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the FAS. |
Arm/Group Title | Gilteritinib 20 mg | Gilteritinib 40 mg | Gilteritinib 80 mg | Gilteritinib 120 mg | Gilteritinib 200 mg | Gilteritinib 300 mg | Gilteritinib 450 mg |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. |
Measure Participants | 16 | 16 | 24 | 70 | 100 | 20 | 3 |
FLT3 Mutation Positive |
7.1
142%
|
0
0%
|
41.7
1390%
|
46.4
1546.7%
|
40.4
1346.7%
|
30.0
1000%
|
0
0%
|
FLT3 Mutation Negative |
50.0
1000%
|
0
0%
|
16.7
556.7%
|
7.1
236.7%
|
9.1
303.3%
|
0
0%
|
0
0%
|
All Participants |
12.5
250%
|
0
0%
|
29.2
973.3%
|
38.6
1286.7%
|
37.0
1233.3%
|
15.0
500%
|
0
0%
|
Title | Percentage of Participants With Partial Remission (PR) |
---|---|
Description | PR was defined according to modified Cheson criteria (2003), using centrally evaluated myeloblast counts from bone marrow aspirate/biopsy assessments and centrally evaluated hematology results; if neither central bone marrow aspirate nor biopsy was available, myeloblast was imputed with locally evaluated bone marrow aspirate/biopsy assessments (derived response). Participants were classified as being in PR when they had bone marrow regenerating normal hematopoietic cells with evidence of peripheral recovery with no (or only a few regenerating) circulating blasts and with a decrease of at least 50% in the percentage of blasts in the bone marrow aspirate with the total marrow blasts between 5% and 25%. A value of less or equal than 5% blasts was also considered a PR if Auer rods were present. There should be no evidence of extramedullary leukemia. Exact 95% confidence interval was estimated using the binomial distribution. |
Time Frame | Up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the FAS. |
Arm/Group Title | Gilteritinib 20 mg | Gilteritinib 40 mg | Gilteritinib 80 mg | Gilteritinib 120 mg | Gilteritinib 200 mg | Gilteritinib 300 mg | Gilteritinib 450 mg |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. |
Measure Participants | 16 | 16 | 24 | 70 | 100 | 20 | 3 |
FLT3 Mutation Positive |
7.1
142%
|
37.5
1250%
|
25.0
833.3%
|
7.1
236.7%
|
7.9
263.3%
|
30.0
1000%
|
50.0
1666.7%
|
FLT3 Mutation Negative |
0
0%
|
0
0%
|
0
0%
|
7.1
236.7%
|
9.1
303.3%
|
0
0%
|
0
0%
|
All Participants |
6.3
126%
|
18.8
626.7%
|
12.5
416.7%
|
7.1
236.7%
|
8.0
266.7%
|
15.0
500%
|
33.3
1110%
|
Title | Percentage of Participants With Best Response |
---|---|
Description | Best response was defined according to modified Cheson criteria (2003), using centrally evaluated myeloblast counts from bone marrow aspirate/biopsy assessments and centrally evaluated hematology results; if neither central bone marrow aspirate nor biopsy was available, myeloblast was imputed with locally evaluated bone marrow aspirate/biopsy assessments (derived response). BR was defined as the best measured response for all visits (in the order of CR, CRp, CRi, and PR) post-treatment. Participants who achieved the best response of CR, CRp, CRi or PR were classified as responders. Participants who did not achieve at least PR were considered as non-responders. Exact 95% confidence interval was estimated using the binomial distribution. |
Time Frame | Up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the FAS. |
Arm/Group Title | Gilteritinib 20 mg | Gilteritinib 40 mg | Gilteritinib 80 mg | Gilteritinib 120 mg | Gilteritinib 200 mg | Gilteritinib 300 mg | Gilteritinib 450 mg |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. |
Measure Participants | 16 | 16 | 24 | 70 | 100 | 20 | 3 |
FLT3 Mutation Positive |
14.3
286%
|
37.5
1250%
|
66.7
2223.3%
|
53.6
1786.7%
|
48.3
1610%
|
60.0
2000%
|
50.0
1666.7%
|
FLT3 Mutation Negative |
50.0
1000%
|
0
0%
|
16.7
556.7%
|
14.3
476.7%
|
18.2
606.7%
|
0
0%
|
0
0%
|
All Participants |
18.8
376%
|
18.8
626.7%
|
41.7
1390%
|
45.7
1523.3%
|
45.0
1500%
|
30.0
1000%
|
33.3
1110%
|
Title | Percentage of Participants With Complete Remission and Complete Remission With Partial Hematologic Recovery (CR/CRh) |
---|---|
Description | Participants with CR/CRh were defined as participants who achieved either CR or CRh. Participants with CR had bone marrow regenerating normal hematopoietic cells, achieved a morphologic leukemia-free state, had an ANC > 1 x 10^9/L, platelet count ≥ 100 x 10^9/L, and normal marrow differential with < 5% blasts, had been RBC and platelet transfusion independent (defined as 1 week without RBC transfusion and 1 week without platelet transfusion). Also, there had been no presence of Auer rods, no evidence of extramedullary leukemia, and blast counts in peripheral blood had been ≤ 2%. Participants with CRh could not be classified as being in CR and had bone marrow blasts < 5%, partial hematologic recovery ANC >= 0.5 x 10^9/L and platelets >= 50 x 10^9/L. There should not be evidence of extramedullary leukemia. Exact 95% confidence interval was estimated using the binomial distribution. CR/CRh was calculated only for participants who were FLT3 mutation positive. |
Time Frame | Up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the FAS, with participants who were FLT3 mutation positive. |
Arm/Group Title | Gilteritinib 20 mg | Gilteritinib 40 mg | Gilteritinib 80 mg | Gilteritinib 120 mg | Gilteritinib 200 mg | Gilteritinib 300 mg | Gilteritinib 450 mg |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. |
Measure Participants | 14 | 8 | 12 | 56 | 89 | 10 | 2 |
Number (95% Confidence Interval) [percentage of participants] |
7.1
142%
|
0
0%
|
25.0
833.3%
|
23.2
773.3%
|
19.1
636.7%
|
30.0
1000%
|
0
0%
|
Title | Duration of CR (DCR) |
---|---|
Description | DCR was defined as the time from the date of first CR until the date of documented relapse for participants who achieved CR. Participants who died without report of relapse were considered non-events and censored at their last relapse-free disease assessment date. Other participants who did not relapse on study were considered non-events and censored at the last relapse-free disease assessment date. DCR was calculated using Kaplan-Meier method and therefore data are estimated. |
Time Frame | From date of remission until end of study (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the FAS. Only participants who achieved CR were included in the analysis. |
Arm/Group Title | Gilteritinib 20 mg | Gilteritinib 40 mg | Gilteritinib 80 mg | Gilteritinib 120 mg | Gilteritinib 200 mg | Gilteritinib 300 mg | Gilteritinib 450 mg |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. |
Measure Participants | 1 | 0 | 2 | 7 | 10 | 1 | 0 |
FLT3 Mutation Positive |
NA
|
NA
|
419.0
|
NA
|
|||
FLT3 Mutation Negative |
NA
|
||||||
All Participants |
NA
|
NA
|
NA
|
419.0
|
NA
|
Title | Duration of CRp (DCRp) |
---|---|
Description | DCRp was defined as the time from the date of first CRp until the date of documented relapse for participants who achieved CRp. Participants who died without report of relapse were considered non-events and censored at their last relapse-free disease assessment date. Other participants who did not relapse on study were considered non-events and censored at the last relapse-free disease assessment date. DCRp was calculated using Kaplan-Meier method and therefore data are estimated. |
Time Frame | From date of remission until end of study (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the FAS. Only participants who achieved CRp were included in the analysis. |
Arm/Group Title | Gilteritinib 20 mg | Gilteritinib 40 mg | Gilteritinib 80 mg | Gilteritinib 120 mg | Gilteritinib 200 mg | Gilteritinib 300 mg | Gilteritinib 450 mg |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. |
Measure Participants | 0 | 0 | 1 | 6 | 12 | 2 | 0 |
FLT3 Mutation Positive |
NA
|
NA
|
450.0
|
NA
|
|||
All Participants |
NA
|
NA
|
450.0
|
NA
|
Title | Duration of CRi (DCRi) |
---|---|
Description | DCRi was defined as the time from the date of first CRi until the date of documented relapse for participants who achieved CRi. Participants who died without report of relapse and participants who did not relapse were considered non-events and censored at the last relapse-free disease assessment date. DCRi was calculated using Kaplan-Meier method and therefore data are estimated. |
Time Frame | From date of remission until end of study (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the FAS. Only participants who achieved CRi were included in the analysis. |
Arm/Group Title | Gilteritinib 20 mg | Gilteritinib 40 mg | Gilteritinib 80 mg | Gilteritinib 120 mg | Gilteritinib 200 mg | Gilteritinib 300 mg | Gilteritinib 450 mg |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. |
Measure Participants | 1 | 0 | 7 | 24 | 31 | 1 | 0 |
FLT3 Mutation Positive |
NA
|
NA
|
120.0
|
191.0
|
NA
|
||
FLT3 Mutation Negative |
41.0
|
99.0
|
|||||
All Participants |
NA
|
79.0
|
120.0
|
191.0
|
NA
|
Title | Duration of CRh (DCRh) |
---|---|
Description | DCRh was defined as the time from the date of first CRh until the date of documented relapse for participants who achieved CRh but did not have a best response of CR. Participants who died without report of relapse and participants who did not relapse were considered non-events and censored at the last relapse-free disease assessment date. DCRh was calculated using Kaplan-Meier method and therefore data are estimated. DCRh was calculated only for participants who were FLT3 mutation positive. |
Time Frame | From date of remission until end of study (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the FAS. Only participants who achieved CRh were included in the analysis. |
Arm/Group Title | Gilteritinib 20 mg | Gilteritinib 40 mg | Gilteritinib 80 mg | Gilteritinib 120 mg | Gilteritinib 200 mg | Gilteritinib 300 mg | Gilteritinib 450 mg |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. |
Measure Participants | 1 | 0 | 1 | 6 | 7 | 2 | 0 |
Median (95% Confidence Interval) [days] |
NA
|
NA
|
64.0
|
101.0
|
NA
|
Title | Duration of CRc (DCRc) |
---|---|
Description | DCRc was defined as the time from the date of first CRc until the date of documented relapse for participants who achieved CRc. Participants who died without report of relapse and participants who did not relapse were considered non-events and censored at the last relapse-free disease assessment date. DCRc was calculated using Kaplan-Meier method and therefore data are estimated. |
Time Frame | From date of remission until end of study (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the FAS. Only participants who achieved CRc were included in the analysis. |
Arm/Group Title | Gilteritinib 20 mg | Gilteritinib 40 mg | Gilteritinib 80 mg | Gilteritinib 120 mg | Gilteritinib 200 mg | Gilteritinib 300 mg | Gilteritinib 450 mg |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. |
Measure Participants | 2 | 0 | 7 | 27 | 37 | 3 | 0 |
FLT3 Mutation Positive |
NA
|
NA
|
98.0
|
191.0
|
NA
|
||
FLT3 Mutation Negative |
NA
|
41.0
|
99.0
|
NA
|
|||
All Participants |
NA
|
79.0
|
99.0
|
191.0
|
NA
|
Title | Duration of CR/CRh (DCRCRh) |
---|---|
Description | DCRCRh was defined as the time from the date of first DCRCRh until the date of documented relapse for participants who achieved CR or CRh. For participants who achieved both CR and CRh, the first CR date or CRh date, whichever occurred first, was used. Participants who died without report of relapse and participants who did not relapse were considered non-events and censored at the last relapse-free disease assessment date. DCRCRh was calculated using Kaplan-Meier method and therefore data are estimated. DCRCRh was calculated only for participants who were FLT3 mutation positive. |
Time Frame | From date of remission until end of study (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the FAS. Only participants who achieved CR or CRh were included in the analysis. |
Arm/Group Title | Gilteritinib 20 mg | Gilteritinib 40 mg | Gilteritinib 80 mg | Gilteritinib 120 mg | Gilteritinib 200 mg | Gilteritinib 300 mg | Gilteritinib 450 mg |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. |
Measure Participants | 1 | 0 | 3 | 13 | 17 | 3 | 0 |
Median (95% Confidence Interval) [days] |
NA
|
NA
|
307.0
|
308.0
|
NA
|
Title | Duration of Response |
---|---|
Description | Duration of response was defined as the time from the date of either first CRc or PR until the date of documented relapse of any type for participants who achieved CRc or PR. Participants who died without report of relapse were considered non-events and censored at their last relapse-free disease assessment date. Other participants who did not relapse on study are considered non-events and censored at the last relapse-free assessment date. Duration of response was calculated using Kaplan-Meier method and therefore data are estimated. |
Time Frame | From date of remission until end of study (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the FAS. Only participants who achieved CRc or PR were included in the analysis. |
Arm/Group Title | Gilteritinib 20 mg | Gilteritinib 40 mg | Gilteritinib 80 mg | Gilteritinib 120 mg | Gilteritinib 200 mg | Gilteritinib 300 mg | Gilteritinib 450 mg |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. |
Measure Participants | 3 | 3 | 10 | 32 | 45 | 6 | 1 |
FLT3 Mutation Positive |
NA
|
NA
|
88.0
|
141.0
|
220.0
|
59.0
|
NA
|
FLT3 Mutation Negative |
NA
|
41.0
|
109.5
|
85.0
|
|||
All Participants |
NA
|
NA
|
79.0
|
126.0
|
220.0
|
59.0
|
NA
|
Title | Time to CR (TTCR) |
---|---|
Description | TTCR was defined as the time from the first dose of study drug until the date of first CR. |
Time Frame | From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the FAS. Only participants who achieved CR were included in the analysis. |
Arm/Group Title | Gilteritinib 20 mg | Gilteritinib 40 mg | Gilteritinib 80 mg | Gilteritinib 120 mg | Gilteritinib 200 mg | Gilteritinib 300 mg | Gilteritinib 450 mg |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. |
Measure Participants | 1 | 0 | 2 | 7 | 10 | 1 | 0 |
FLT3 Mutation Positive |
171.5
|
141.0
|
93.0
|
56.0
|
|||
FLT3 Mutation Negative |
30.0
|
||||||
All Participants |
30.0
|
171.5
|
141.0
|
93.0
|
56.0
|
Title | Time to CRp (TTCRp) |
---|---|
Description | TTCRp was defined as the time from the first dose of study drug until the date of first CRp. TTCRp was evaluated for participants who achieved CRp. |
Time Frame | From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the FAS. Only participants who achieved CRp were included in the analysis. |
Arm/Group Title | Gilteritinib 20 mg | Gilteritinib 40 mg | Gilteritinib 80 mg | Gilteritinib 120 mg | Gilteritinib 200 mg | Gilteritinib 300 mg | Gilteritinib 450 mg |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. |
Measure Participants | 0 | 0 | 1 | 6 | 12 | 2 | 0 |
FLT3 Mutation Positive |
140.0
|
195.0
|
84.5
|
29.0
|
|||
All Participants |
140.0
|
195.0
|
84.5
|
29.0
|
Title | Time to CRi (TTCRi) |
---|---|
Description | TTCRi was defined as the time from the first dose of study drug until the date of first CRi. TTCRi was evaluated for participants who achieved CRi. |
Time Frame | From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the FAS. Only participants who achieved CRi were included in the analysis. |
Arm/Group Title | Gilteritinib 20 mg | Gilteritinib 40 mg | Gilteritinib 80 mg | Gilteritinib 120 mg | Gilteritinib 200 mg | Gilteritinib 300 mg | Gilteritinib 450 mg |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. |
Measure Participants | 1 | 0 | 7 | 24 | 31 | 1 | 0 |
FLT3 Mutation Positive |
57.0
|
57.0
|
57.0
|
39.5
|
28.0
|
||
FLT3 Mutation Negative |
71.5
|
30.0
|
30.0
|
||||
All Participants |
57.0
|
64.0
|
43.5
|
35.0
|
28.0
|
Title | Time to First CR/CRh (TTFCRCRh) |
---|---|
Description | TTFCRCRh was defined as the time from the first dose of study drug until the date of first either CR or CRh. TTFCRCRh was evaluated for participants who achieved CR or CRh. For participants who achieve both CR and CRh, the first CR date or CRh date, whichever occurs first was used. TTFCRCRh was calculated only for participants who were FLT3 mutation positive. |
Time Frame | From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the FAS. Only participants who achieved CR or CRh were included in the analysis. |
Arm/Group Title | Gilteritinib 20 mg | Gilteritinib 40 mg | Gilteritinib 80 mg | Gilteritinib 120 mg | Gilteritinib 200 mg | Gilteritinib 300 mg | Gilteritinib 450 mg |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. |
Measure Participants | 1 | 0 | 3 | 13 | 17 | 3 | 0 |
Median (Full Range) [days] |
57.0
|
57.0
|
59.0
|
57.0
|
28.0
|
Title | Time to Best CR/CRh (TTBCRCRh) |
---|---|
Description | TTBCRCRh was defined as the time from the first dose of study drug until the first date that the best response of CR or CRh was achieved. TTBCRCRh was evaluated for participants who achieved CR or CRh. For participants who achieve both CR and CRh, the first CR date was used. TTBCRCRh was calculated only for participants who were FLT3 mutation positive. |
Time Frame | From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the FAS. Participants who achieved CR or CRh were included in the analysis. |
Arm/Group Title | Gilteritinib 20 mg | Gilteritinib 40 mg | Gilteritinib 80 mg | Gilteritinib 120 mg | Gilteritinib 200 mg | Gilteritinib 300 mg | Gilteritinib 450 mg |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. |
Measure Participants | 1 | 0 | 3 | 13 | 17 | 3 | 0 |
Median (Full Range) [days] |
57.0
|
57.0
|
63.0
|
88.0
|
30.0
|
Title | Time to CRc (TTCRc) |
---|---|
Description | TTCRc was defined as the time from the first dose of study drug until the date of first CRc. TTCRc was evaluated for participants who achieved CRc. |
Time Frame | From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the FAS. Only participants who achieved CRc were included in the analysis. |
Arm/Group Title | Gilteritinib 20 mg | Gilteritinib 40 mg | Gilteritinib 80 mg | Gilteritinib 120 mg | Gilteritinib 200 mg | Gilteritinib 300 mg | Gilteritinib 450 mg |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. |
Measure Participants | 2 | 0 | 7 | 27 | 37 | 3 | 0 |
FLT3 Mutation Positive |
57.0
|
56.0
|
30.0
|
31.5
|
28.0
|
||
FLT3 Mutation Negative |
30.0
|
71.5
|
30.0
|
30.0
|
|||
All Participants |
43.5
|
57.0
|
30.0
|
31.0
|
28.0
|
Title | Time to Response (TTR) |
---|---|
Description | TTR was defined as the time from the first dose of study drug until the date of either first CRc or PR. TTR was evaluated for participants who achieved CRc or PR. |
Time Frame | From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the FAS. Only participants who achieved CRc or PR were included in the analysis. |
Arm/Group Title | Gilteritinib 20 mg | Gilteritinib 40 mg | Gilteritinib 80 mg | Gilteritinib 120 mg | Gilteritinib 200 mg | Gilteritinib 300 mg | Gilteritinib 450 mg |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. |
Measure Participants | 3 | 3 | 10 | 32 | 45 | 6 | 1 |
FLT3 Mutation Positive |
61.5
|
57.0
|
31.0
|
29.0
|
29.0
|
28.0
|
31.0
|
FLT3 Mutation Negative |
30.0
|
71.5
|
29.5
|
29.5
|
|||
All Participants |
30.0
|
57.0
|
43.5
|
29.0
|
29.0
|
28.0
|
31.0
|
Title | Time to Best Response (TTBR) |
---|---|
Description | TTBR was defined as the time from the first dose of study drug until the first disease assessment date when participant achieved best response. TTBR was evaluated in participants who achieved best response of CR, CRp, CRi, or PR. |
Time Frame | From first dose of study drug up to end of treatment (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the FAS. Only participants who achieved CR, CRp, CRi, or PR were included in the analysis. |
Arm/Group Title | Gilteritinib 20 mg | Gilteritinib 40 mg | Gilteritinib 80 mg | Gilteritinib 120 mg | Gilteritinib 200 mg | Gilteritinib 300 mg | Gilteritinib 450 mg |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. |
Measure Participants | 3 | 3 | 10 | 32 | 45 | 6 | 1 |
FLT3 Mutation Positive |
75.5
|
57.0
|
44.0
|
43.5
|
57.0
|
29.0
|
31.0
|
FLT3 Mutation Negative |
30.0
|
71.5
|
29.5
|
29.5
|
|||
All Participants |
57.0
|
57.0
|
58.0
|
30.0
|
56.0
|
29.0
|
31.0
|
Title | Overall Survival (OS) |
---|---|
Description | The time from the date of first dose of study drug until the date of death from any cause. For a participant who was not known to have died by the end of study follow-up, OS was censored at the date of last contact. OS was calculated using Kaplan-Meier method and therefore data are estimated. |
Time Frame | From first dose of study drug up to end of study (median time on study was 157.0 days, minimum of 5 days and maximum of 1320 days) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the FAS. |
Arm/Group Title | Gilteritinib 20 mg | Gilteritinib 40 mg | Gilteritinib 80 mg | Gilteritinib 120 mg | Gilteritinib 200 mg | Gilteritinib 300 mg | Gilteritinib 450 mg |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. |
Measure Participants | 16 | 16 | 24 | 70 | 100 | 20 | 3 |
FLT3 Mutation Positive |
123.0
|
199.5
|
197.5
|
246.0
|
214.0
|
157.0
|
204.0
|
FLT3 Mutation Negative |
NA
|
71.5
|
136.0
|
144.0
|
67.0
|
68.0
|
89.0
|
All Participants |
149.5
|
95.0
|
154.0
|
216.0
|
176.0
|
128.5
|
89.0
|
Title | Event Free Survival (EFS) |
---|---|
Description | EFS was defined as the time from the date of first dose of study drug until the date of documented relapse, treatment failure or death from any cause, whichever occurred first. For a participant with none of these events, EFS was censored at the date of last relapse-free disease assessment. A participant without post-treatment disease assessment was censored at randomization date. Treatment failure included those participants who discontinued the treatment due to "progressive disease" or "lack of efficacy" without a previous response of CR, CRp, CRi or PR. Treatment failure date referred to the start of new anti-leukemia therapy or the last treatment evaluation date when new anti-leukemia therapy date was not available. For participants who were censored, last relapse-free disease assessment date referred to the participant's last disease assessment date. EFS was calculated using Kaplan-Meier method and therefore data are estimated. |
Time Frame | From first dose of study drug up to end of study (median time on study was 157.0 days, minimum of 5 days and maximum of 1320 days) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the FAS. |
Arm/Group Title | Gilteritinib 20 mg | Gilteritinib 40 mg | Gilteritinib 80 mg | Gilteritinib 120 mg | Gilteritinib 200 mg | Gilteritinib 300 mg | Gilteritinib 450 mg |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. |
Measure Participants | 16 | 16 | 24 | 70 | 100 | 20 | 3 |
FLT3 Mutation Positive |
52.0
|
109.0
|
93.5
|
112.0
|
121.0
|
85.0
|
86.0
|
FLT3 Mutation Negative |
58.0
|
39.0
|
74.0
|
85.5
|
45.0
|
43.0
|
71.0
|
All Participants |
58.0
|
55.5
|
76.0
|
108.0
|
118.0
|
65.0
|
71.0
|
Title | Leukemia Free Survival (LFS) |
---|---|
Description | LFS was defined as the time from the date of first CRc until the date of documented relapse or death for participants who achieved CRc. For a participant who was not known to have relapsed or died, LFS was censored on the date of last relapse-free disease assessment date. LFS was calculated using Kaplan-Meier method and therefore data are estimated. |
Time Frame | From first dose of study drug up to end of study (median time on study was 157.0 days, minimum of 5 days and maximum of 1320 days) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the FAS. Only participants who achieved CRc were included in the analysis. |
Arm/Group Title | Gilteritinib 20 mg | Gilteritinib 40 mg | Gilteritinib 80 mg | Gilteritinib 120 mg | Gilteritinib 200 mg | Gilteritinib 300 mg | Gilteritinib 450 mg |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. |
Measure Participants | 2 | 0 | 7 | 27 | 37 | 3 | 0 |
FLT3 Mutation Positive |
242.0
|
98.0
|
98.0
|
146.0
|
296.0
|
||
FLT3 Mutation Negative |
NA
|
41.0
|
99.0
|
38.0
|
|||
All Participants |
242.0
|
79.0
|
98.0
|
146.0
|
296.0
|
Title | Percentage of Participants Who Achieved Transfusion Conversion |
---|---|
Description | Participants who achieved transfusion conversion were defined as the number of participants who were transfusion dependent at baseline period but became transfusion independent at post-baseline period divided by the total number of participants who were transfusion dependent at baseline period. Participants were considered baseline transfusion dependent if there were RBC or platelet transfusions within the baseline period. Participants were considered post-baseline transfusion independent if they were on treatment >=84 days, and if there was one consecutive 56 days without any RBC or platelet transfusion within post-baseline period. If participants were on treatment >28 days but <84 days, and there was no RBC or platelet transfusion within post-baseline period, or on treatment <=28 days, post-baseline transfusion status was not evaluable. Exact 95% confidence interval was estimated using the binomial distribution. |
Time Frame | Baseline (28 days prior to first dose until 28 days after the first dose) and postbaseline (from 29 days after first dose date until last dose date); median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the FAS. Participants who were transfusion dependent at baseline and had evaluable post-baseline transfusion status were included in the analysis. |
Arm/Group Title | Gilteritinib 20 mg | Gilteritinib 40 mg | Gilteritinib 80 mg | Gilteritinib 120 mg | Gilteritinib 200 mg | Gilteritinib 300 mg | Gilteritinib 450 mg |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. |
Measure Participants | 7 | 8 | 16 | 49 | 63 | 8 | 2 |
FLT3 Mutation Positive |
0
0%
|
0
0%
|
37.5
1250%
|
27.5
916.7%
|
40.4
1346.7%
|
NA
NaN
|
NA
NaN
|
FLT3 Mutation Negative |
NA
NaN
|
NA
NaN
|
12.5
416.7%
|
22.2
740%
|
33.3
1110%
|
NA
NaN
|
NA
NaN
|
All Participants |
NA
NaN
|
NA
NaN
|
25.0
833.3%
|
26.5
883.3%
|
39.7
1323.3%
|
NA
NaN
|
NA
NaN
|
Title | Percentage of Participants Who Achieved Transfusion Maintenance |
---|---|
Description | Participants who achieved transfusion maintenance were defined as the number of participants who were transfusion independent at baseline period and still maintained transfusion independent at post-baseline period divided by the total number of participants who were transfusion independent at baseline period. |
Time Frame | Baseline (28 days prior to first dose until 28 days after the first dose) and postbaseline (from 29 days after first dose date until last dose date); median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the FAS. Participants who were transfusion independent at baseline and had evaluable post-baseline transfusion status were included in the analysis. |
Arm/Group Title | Gilteritinib 20 mg | Gilteritinib 40 mg | Gilteritinib 80 mg | Gilteritinib 120 mg | Gilteritinib 200 mg | Gilteritinib 300 mg | Gilteritinib 450 mg |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants received 20 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 40 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 80 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 120 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 200 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 300 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. | Participants received 450 mg gilteritinib orally once on day -2, and starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation. |
Measure Participants | 0 | 0 | 1 | 7 | 10 | 0 | 1 |
FLT3 Mutation Positive |
100.0
2000%
|
75.0
2500%
|
80.0
2666.7%
|
100.0
3333.3%
|
|||
FLT3 Mutation Negative |
33.3
666%
|
||||||
All Participants |
100.0
2000%
|
57.1
1903.3%
|
80.0
2666.7%
|
100.0
3333.3%
|
Title | AUC24 of Gilteritinib in Co-administration With Voriconazole |
---|---|
Description | Plasma samples were used for pharmacokinetic assessments. |
Time Frame | Cycle 1 Day 15 and Cycle 2 Day 1: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (gilteritinib) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the PKAS, with participants administered 20 mg gilteritinib and voriconazole. |
Arm/Group Title | Gilteritinib 20 mg in Expansion Phase |
---|---|
Arm/Group Description | Participants received 20 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. Starting on day 16 of cycle 1, participants also received 200 mg voriconazole orally every 12 hours through day 1 of cycle 2. |
Measure Participants | 1 |
Mean (Standard Deviation) [ng*h/mL] |
919.3
(NA)
|
Title | Cmax of Gilteritinib in Co-administration With Voriconazole |
---|---|
Description | Plasma samples were used for pharmacokinetic assessments. |
Time Frame | Cycle 1 Day 15 and Cycle 2 Day 1: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (gilteritinib) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the PKAS, with participants administered 20 mg gilteritinib and voriconazole. |
Arm/Group Title | Gilteritinib 20 mg in Expansion Phase |
---|---|
Arm/Group Description | Participants received 20 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. Starting on day 16 of cycle 1, participants also received 200 mg voriconazole orally every 12 hours through day 1 of cycle 2. |
Measure Participants | 1 |
Mean (Standard Deviation) [ng/mL] |
63.79
(NA)
|
Title | AUClast of Gilteritinib in Co-administration With Voriconazole |
---|---|
Description | Plasma samples were used for pharmacokinetic assessments. |
Time Frame | Cycle 1 Day 15 and Cycle 2 Day 1: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (gilteritinib) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the PKAS, with participants administered 20 mg gilteritinib and voriconazole. |
Arm/Group Title | Gilteritinib 20 mg in Expansion Phase |
---|---|
Arm/Group Description | Participants received 20 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. Starting on day 16 of cycle 1, participants also received 200 mg voriconazole orally every 12 hours through day 1 of cycle 2. |
Measure Participants | 1 |
Mean (Standard Deviation) [ng*h/mL] |
919.3
(NA)
|
Title | Tmax of Gilteritinib in Co-administration With Voriconazole |
---|---|
Description | Plasma samples were used for pharmacokinetic assessments. |
Time Frame | Cycle 1 Day 15 and Cycle 2 Day 1: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (gilteritinib) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the PKAS, with participants administered 20 mg gilteritinib and voriconazole. |
Arm/Group Title | Gilteritinib 20 mg in Expansion Phase |
---|---|
Arm/Group Description | Participants received 20 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. Starting on day 16 of cycle 1, participants also received 200 mg voriconazole orally every 12 hours through day 1 of cycle 2. |
Measure Participants | 1 |
Median (Full Range) [hours] |
2.08
|
Title | AUC24 of Midazolam Administered With and Without Gilteritinib |
---|---|
Description | Plasma samples were used for pharmacokinetic assessments. |
Time Frame | Day -1 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (midazolam) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the PKAS, with participants administered 300 mg gilteritinib and midazolam. |
Arm/Group Title | Gilteritinib 300 mg in Expansion Phase |
---|---|
Arm/Group Description | Participants received 300 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, participants also received 2 mg midazolam as a single oral dose. |
Measure Participants | 17 |
Midazolam Alone (Day -1) |
66.55
(57.70)
|
Midazolam + Gilteritinib (Cycle 1 Day 15) |
81.56
(65.84)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Gilteritinib 20 mg in Escalation Phase |
---|---|---|
Comments | Statistical Comparison of Midazolam Exposure after Administration of Midazolam Alone or Coadministered with Gilteritinib: The difference of least squares (LS) means of log-transformed pharmacokinetic parameters between midazolam alone and midazolam + gilteritinib and its 90% CI are backtransformed to the raw scale and are expressed as percent. | |
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Geometric LS Mean Ratio |
Estimated Value | 109.46 | |
Confidence Interval |
(2-Sided) 90% 49.82 to 240.48 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | AUC24 of Metabolite 1-Hydroxymidazolam After Administration of Midazolam With and Without Gilteritinib |
---|---|
Description | Plasma samples were used for pharmacokinetic assessments. |
Time Frame | Day -1 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (midazolam) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the PKAS, with participants administered 300 mg gilteritinib and midazolam. |
Arm/Group Title | Gilteritinib 300 mg in Expansion Phase |
---|---|
Arm/Group Description | Participants received 300 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, participants also received 2 mg midazolam as a single oral dose. |
Measure Participants | 17 |
Midazolam Alone (Day -1) |
20.44
(24.80)
|
Midazolam + Gilteritinib (Cycle 1 Day 15) |
23.10
(21.64)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Gilteritinib 20 mg in Escalation Phase |
---|---|---|
Comments | Statistical Comparison of Midazolam Exposure after Administration of Midazolam Alone or Coadministered with Gilteritinib: The difference of LS means of log-transformed pharmacokinetic parameters between 1-hydroxymidazolam alone and 1-hydroxymidazolam + gilteritinib and its 90% CI are backtransformed to the raw scale and are expressed as percent. | |
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Geometric LS Mean Ratio |
Estimated Value | 149.90 | |
Confidence Interval |
() 90% 74.88 to 300.06 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Cmax of Midazolam Administered With and Without Gilteritinib |
---|---|
Description | Plasma samples were used for pharmacokinetic assessments. |
Time Frame | Day -1 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (midazolam) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the PKAS, with participants administered 300 mg gilteritinib and midazolam. |
Arm/Group Title | Gilteritinib 300 mg in Expansion Phase |
---|---|
Arm/Group Description | Participants received 300 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, participants also received 2 mg midazolam as a single oral dose. |
Measure Participants | 17 |
Midazolam Alone (Day -1) |
14.68
(8.923)
|
Midazolam + Gilteritinib (Cycle 1 Day 15) |
18.45
(9.452)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Gilteritinib 20 mg in Escalation Phase |
---|---|---|
Comments | Statistical Comparison of Midazolam Exposure after Administration of Midazolam Alone or Coadministered with Gilteritinib: The difference of LS means of log-transformed pharmacokinetic parameters between midazolam alone and midazolam + gilteritinib and its 90% CI are backtransformed to the raw scale and are expressed as percent. | |
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Geometric LS Mean Ratio |
Estimated Value | 111.64 | |
Confidence Interval |
(2-Sided) 90% 69.54 to 179.25 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Cmax of 1-Hydroxymidazolam After Administration of Midazolam With and Without Gilteritinib |
---|---|
Description | Plasma samples were used for pharmacokinetic assessments. |
Time Frame | Day -1 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (midazolam) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the PKAS, with participants administered 300 mg gilteritinib and midazolam. |
Arm/Group Title | Gilteritinib 300 mg in Expansion Phase |
---|---|
Arm/Group Description | Participants received 300 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, participants also received 2 mg midazolam as a single oral dose. |
Measure Participants | 17 |
Midazolam Alone (Day -1) |
4.562
(2.858)
|
Midazolam + Gilteritinib (Cycle 1 Day 15) |
5.053
(3.158)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Gilteritinib 20 mg in Escalation Phase |
---|---|---|
Comments | Statistical Comparison of Midazolam Exposure after Administration of Midazolam Alone or Coadministered with Gilteritinib: The difference of LS means of log-transformed pharmacokinetic parameters between 1-hydroxymidazolam/midazolam alone and 1-hydroxymidazolam/midazolam + gilteritinib and its 90% CI are backtransformed to the raw scale and are expressed as percent. | |
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Geometric LS Mean Ratio |
Estimated Value | 123.47 | |
Confidence Interval |
(2-Sided) 90% 72.41 to 210.52 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | AUClast of Midazolam Administered With and Without Gilteritinib |
---|---|
Description | Plasma samples were used for pharmacokinetic assessments. |
Time Frame | Day -1 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (midazolam) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the PKAS, with participants administered 300 mg gilteritinib and midazolam. |
Arm/Group Title | Gilteritinib 300 mg in Expansion Phase |
---|---|
Arm/Group Description | Participants received 300 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, participants also received 2 mg midazolam as a single oral dose. |
Measure Participants | 17 |
Midazolam Alone (Day -1) |
59.48
(59.49)
|
Midazolam + Gilteritinib (Cycle 1 Day 15) |
82.44
(64.25)
|
Title | AUClast of 1-Hydroxymidazolam After Administration of Midazolam With and Without Gilteritinib |
---|---|
Description | Plasma samples were used for pharmacokinetic assessments. |
Time Frame | Day -1 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (midazolam) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the PKAS, with participants administered 300 mg gilteritinib and midazolam. |
Arm/Group Title | Gilteritinib 300 mg in Expansion Phase |
---|---|
Arm/Group Description | Participants received 300 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, participants also received 2 mg midazolam as a single oral dose. |
Measure Participants | 17 |
Midazolam Alone (Day -1) |
17.05
(24.70)
|
Midazolam + Gilteritinib (Cycle 1 Day 15) |
23.58
(22.07)
|
Title | Tmax of Midazolam Administered With and Without Gilteritinib |
---|---|
Description | Plasma samples were used for pharmacokinetic assessments. |
Time Frame | Day -1 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (midazolam) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the PKAS, with participants administered 300 mg gilteritinib and midazolam. |
Arm/Group Title | Gilteritinib 300 mg in Expansion Phase |
---|---|
Arm/Group Description | Participants received 300 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, participants also received 2 mg midazolam as a single oral dose. |
Measure Participants | 17 |
Midazolam Alone (Day -1) |
0.5000
|
Midazolam + Gilteritinib (Cycle 1 Day 15) |
1.00
|
Title | Tmax of 1-Hydroxymidazolam After Administration of Midazolam With and Without Gilteritinib |
---|---|
Description | Plasma samples were used for pharmacokinetic assessments. |
Time Frame | Day -1 and cycle 1 day 15: predose, 0.5, 1, 2, 4, 6, 24 hours postdose (midazolam) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the PKAS, with participants administered 300 mg gilteritinib and midazolam. |
Arm/Group Title | Gilteritinib 300 mg in Expansion Phase |
---|---|
Arm/Group Description | Participants received 300 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, participants also received 2 mg midazolam as a single oral dose. |
Measure Participants | 17 |
Midazolam Alone (Day -1) |
0.5583
|
Midazolam + Gilteritinib (Cycle 1 Day 15) |
1.00
|
Title | Area Under the Concentration-time Curve From the Time of Dosing Extrapolated to Time Infinity (AUCinf) of Cephalexin Administered With and Without Gilteritinib |
---|---|
Description | Plasma samples were used for pharmacokinetic assessments. |
Time Frame | Day -1 and cycle 1 day 15: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 24 hours postdose (cephalexin) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the PKAS, with participants administered 200 mg gilteritinib and cephalexin. |
Arm/Group Title | Gilteritinib 200 mg in Expansion Phase |
---|---|
Arm/Group Description | Participants received 200 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, certain participants also received 500 mg cephalexin as a single oral dose. |
Measure Participants | 100 |
Cephalexin Alone (Day -1) |
57650
(20386)
|
Cephalexin + Gilteritinib (Cycle 1 Day 15) |
51873
(18819)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Gilteritinib 20 mg in Escalation Phase |
---|---|---|
Comments | Statistical Assessment of the Effect of Gilteritinib on Cephalexin Pharmacokinetics after Administration of Cephalexin Alone or Coadministered with Gilteritinib: The difference of LS means of log-transformed pharmacokinetic parameters between cephalexin alone and cephalexin + gilteritinib and its 90% CI are backtransformed to the raw scale and are expressed as percent. | |
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Geometric LS Mean Ratio |
Estimated Value | 93.96 | |
Confidence Interval |
(2-Sided) 90% 75.29 to 117.26 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Cmax of Cephalexin Administered With and Without Gilteritinib |
---|---|
Description | Plasma samples were used for pharmacokinetic assessments. |
Time Frame | Day -1 and cycle 1 day 15: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 24 hours postdose (cephalexin) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the PKAS, with participants administered 200 mg gilteritinib and cephalexin. |
Arm/Group Title | Gilteritinib 200 mg in Expansion Phase |
---|---|
Arm/Group Description | Participants received 200 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, certain participants also received 500 mg cephalexin as a single oral dose. |
Measure Participants | 100 |
Cephalexin Alone (Day -1) |
17688
(6680)
|
Cephalexin + Gilteritinib (Cycle 1 day 15) |
16075
(4606)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Gilteritinib 20 mg in Escalation Phase |
---|---|---|
Comments | Statistical Assessment of the Effect of Gilteritinib on Cephalexin Pharmacokinetics after Administration of Cephalexin Alone or Coadministered with Gilteritinib: The difference of LS means of log-transformed pharmacokinetic parameters between cephalexin alone and cephalexin + gilteritinib and its 90% CI are backtransformed to the raw scale and are expressed as percent. | |
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Geometric LS Mean Ratio |
Estimated Value | 91.46 | |
Confidence Interval |
(2-Sided) 90% 74.60 to 112.12 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | AUClast of Cephalexin Administered With and Without Gilteritinib |
---|---|
Description | Plasma samples were used for pharmacokinetic assessments. |
Time Frame | Day -1 and cycle 1 day 15: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 24 hours postdose (cephalexin) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the PKAS, with participants administered 200 mg gilteritinib and cephalexin. |
Arm/Group Title | Gilteritinib 200 mg in Expansion Phase |
---|---|
Arm/Group Description | Participants received 200 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, certain participants also received 500 mg cephalexin as a single oral dose. |
Measure Participants | 100 |
Cephalexin Alone (Day -1) |
53183
(26877)
|
Cephalexin + Gilteritinib (Cycle 1 Day 15) |
54963
(29531)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Gilteritinib 20 mg in Escalation Phase |
---|---|---|
Comments | Statistical Assessment of the Effect of Gilteritinib on Cephalexin Pharmacokinetics after Administration of Cephalexin Alone or Coadministered with Gilteritinib: The difference of LS means of log-transformed pharmacokinetic parameters between cephalexin alone and cephalexin + gilteritinib and its 90% CI are backtransformed to the raw scale and are expressed as percent. | |
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Geometric LS Mean Ratio |
Estimated Value | 97.71 | |
Confidence Interval |
(2-Sided) 90% 74.19 to 128.70 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Tmax of Cephalexin Administered With and Without Gilteritinib |
---|---|
Description | Plasma samples were used for pharmacokinetic assessments. |
Time Frame | Day -1 and cycle 1 day 15: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 24 hours postdose (cephalexin) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the PKAS, with participants administered 200 mg gilteritinib and cephalexin. |
Arm/Group Title | Gilteritinib 200 mg in Expansion Phase |
---|---|
Arm/Group Description | Participants received 200 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, certain participants also received 500 mg cephalexin as a single oral dose. |
Measure Participants | 100 |
Cephalexin Alone (Day -1) |
1.500
|
Cephalexin + Gilteritinib (Cycle 1 Day 15) |
1.483
|
Title | T1/2 of Cephalexin Administered With and Without Gilteritinib |
---|---|
Description | Plasma samples were used for pharmacokinetic assessments. |
Time Frame | Day -1 and cycle 1 day 15: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 24 hours postdose (cephalexin) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the PKAS, with participants administered 200 mg gilteritinib and cephalexin. |
Arm/Group Title | Gilteritinib 200 mg in Expansion Phase |
---|---|
Arm/Group Description | Participants received 200 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, certain participants also received 500 mg cephalexin as a single oral dose. |
Measure Participants | 100 |
Cephalexin Alone (Day -1) |
1.822
(0.5914)
|
Cephalexin + Gilteritinib (Cycle 1 Day 15) |
1.827
(0.7175)
|
Title | Apparent Total Systemic Clearance After Single or Multiple Extravascular Dosing (CL/F) of Cephalexin Administered With and Without Gilteritinib |
---|---|
Description | Plasma samples were used for pharmacokinetic assessments. |
Time Frame | Day -1 and cycle 1 day 15: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 24 hours postdose (cephalexin) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the PKAS, with participants administered 200 mg gilteritinib and cephalexin. |
Arm/Group Title | Gilteritinib 200 mg in Expansion Phase |
---|---|
Arm/Group Description | Participants received 200 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, certain participants also received 500 mg cephalexin as a single oral dose. |
Measure Participants | 100 |
Cephalexin Alone (Day -1) |
9.713
(3.319)
|
Cephalexin + Gilteritinib (Cycle 1 Day 15) |
10.58
(2.977)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Gilteritinib 20 mg in Escalation Phase |
---|---|---|
Comments | Statistical Assessment of the Effect of Gilteritinib on Cephalexin Pharmacokinetics after Administration of Cephalexin Alone or Coadministered with Gilteritinib: The difference of LS means of log-transformed pharmacokinetic parameters between cephalexin alone and cephalexin + gilteritinib and its 90% CI are backtransformed to the raw scale and are expressed as percent. | |
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Geometric LS Mean Ratio |
Estimated Value | 106.42 | |
Confidence Interval |
(2-Sided) 90% 85.28 to 132.81 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Apparent Volume of Distribution During the Terminal Elimination Phase After Single Extravascular Dosing (Vz/F) of Cephalexin Administered With and Without Gilteritinib |
---|---|
Description | Plasma samples were used for pharmacokinetic assessments. |
Time Frame | Day -1 and cycle 1 day 15: predose, 0.5, 1, 1.5, 2, 3, 4, 6, 24 hours postdose (cephalexin) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the PKAS, with participants administered 200 mg gilteritinib and cephalexin. |
Arm/Group Title | Gilteritinib 200 mg in Expansion Phase |
---|---|
Arm/Group Description | Participants received 200 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, certain participants also received 500 mg cephalexin as a single oral dose. |
Measure Participants | 100 |
Cephalexin Alone (Day -1) |
24.07
(7.173)
|
Cephalexin + Gilteritinib (Cycle 1 Day 15) |
25.86
(5.346)
|
Title | Amount of Drug Excreted in Urine (Aelast) of Cephalexin Administered With and Without Gilteritinib |
---|---|
Description | Urine samples were used for pharmacokinetic assessments. |
Time Frame | Day -1 and cycle 1 day 15: 0-3 hours, 3-6 hours, 6-24 hours postdose (cephalexin) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the PKAS, with participants administered 200 mg gilteritinib and cephalexin. |
Arm/Group Title | Gilteritinib 200 mg in Expansion Phase |
---|---|
Arm/Group Description | Participants received 200 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, certain participants also received 500 mg cephalexin as a single oral dose. |
Measure Participants | 100 |
Cephalexin Alone (Day -1) |
548.9
(523.7)
|
Cephalexin + Gilteritinib (Cycle 1 Day 15) |
448.8
(306.1)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Gilteritinib 20 mg in Escalation Phase |
---|---|---|
Comments | Statistical Assessment of the Effect of Gilteritinib on Cephalexin Pharmacokinetics after Administration of Cephalexin Alone or Coadministered with Gilteritinib: The difference of LS means of log-transformed pharmacokinetic parameters between cephalexin alone and cephalexin + gilteritinib and its 90% CI are backtransformed to the raw scale and are expressed as percent. | |
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Geometric LS Mean Ratio |
Estimated Value | 83.93 | |
Confidence Interval |
(2-Sided) 90% 46.53 to 151.39 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Fraction of Drug Excreted Into Urine in Percentage (%Ae) of Cephalexin Administered With and Without Gilteritinib |
---|---|
Description | Urine samples were used for pharmacokinetic assessments. |
Time Frame | Day -1 and cycle 1 day 15: 0-3 hours, 3-6 hours, 6-24 hours postdose (cephalexin) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the PKAS, with participants administered 200 mg gilteritinib and cephalexin. |
Arm/Group Title | Gilteritinib 200 mg in Expansion Phase |
---|---|
Arm/Group Description | Participants received 200 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, certain participants also received 500 mg cephalexin as a single oral dose. |
Measure Participants | 100 |
Cephalexin Alone (Day -1) |
109.8
(104.7)
|
Cephalexin + Gilteritinib (Cycle 1 Day 15) |
89.75
(61.21)
|
Title | Renal Clearance (CLr) of Cephalexin in Administered With and Without Gilteritinib |
---|---|
Description | Urine samples were used for pharmacokinetic assessments. |
Time Frame | Day -1 and cycle 1 day 15: 0-3 hours, 3-6 hours, 6-24 hours postdose (cephalexin) |
Outcome Measure Data
Analysis Population Description |
---|
The analysis population was the PKAS, with participants administered 200 mg gilteritinib and cephalexin. |
Arm/Group Title | Gilteritinib 200 mg in Expansion Phase |
---|---|
Arm/Group Description | Participants received 200 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, certain participants also received 500 mg cephalexin as a single oral dose. |
Measure Participants | 100 |
Cephalexin Alone (Day -1) |
8.784
(8.727)
|
Cephalexin + Gilteritinib (Cycle 1 Day 15) |
11.04
(8.430)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Gilteritinib 20 mg in Escalation Phase |
---|---|---|
Comments | Statistical Assessment of the Effect of Gilteritinib on Cephalexin Pharmacokinetics after Administration of Cephalexin Alone or Coadministered with Gilteritinib: The difference of LS means of log-transformed pharmacokinetic parameters between cephalexin alone and cephalexin + gilteritinib and its 90% CI are backtransformed to the raw scale and are expressed as percent. | |
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Geometric LS Mean Ratio |
Estimated Value | 82.84 | |
Confidence Interval |
(2-Sided) 90% 40.25 to 170.48 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Adverse Events
Time Frame | From first dose of study drug up to 30 days after last dose of study drug (median treatment duration was 69.5 days, minimum of 3 days and maximum of 1320 days) | |||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Adverse Event Reporting Description | The total number of deaths (all causes) includes deaths reported after the time frame above. | |||||||||||||||||||||||||
Arm/Group Title | Gilterinib 20 mg in Escalation Phase | Gilterinib 40 mg in Escalation Phase | Gilterinib 80 mg in Escalation Phase | Gilterinib 120 mg in Escalation Phase | Gilterinib 200 mg in Escalation Phase | Gilterinib 300 mg in Escalation Phase | Gilterinib 450 mg in Escalation Phase | Gilterinib 20 mg in Expansion Phase | Gilterinib 40 mg in Expansion Phase | Gilterinib 80 mg in Expansion Phase | Gilterinib 120 mg in Expansion Phase | Gilterinib 200 mg in Expansion Phase | Gilterinib 300 mg in Expansion Phase | |||||||||||||
Arm/Group Description | Participants received a single dose of 20 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 20 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 40 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 40 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 80 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 80 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 120 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 120 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 200 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 200 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 300 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 300 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received a single dose of 450 mg gilteritinib orally on day -2 to evaluate pharmacokinetics of gilteritinib. Then starting on day 1 of cycle 1, participants received 450 mg gilteritinib orally once daily in 28-day cycles until disease progression or participant discontinuation in the escalation phase of the study. | Participants received 20 mg gilteritinib orally once daily stating on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. Starting on day 16 of cycle 1, participants also received 200 mg voriconazole orally every 12 hours through day 1 of cycle 2. | Participants received 40 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. | Participants received 80 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. | Participants received 120 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. | Participants received 200 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, certain participants also received 500 mg cephalexin as a single oral dose. | Participants received 300 mg gilteritinib orally once daily starting on day 1 of cycle 1 and continued in 28-day cycles until disease progression or participant discontinuation in the expansion phase of the study. On day -1 and day 15 of cycle 1, participants also received 2 mg midazolam as a single oral dose. | |||||||||||||
All Cause Mortality |
||||||||||||||||||||||||||
Gilterinib 20 mg in Escalation Phase | Gilterinib 40 mg in Escalation Phase | Gilterinib 80 mg in Escalation Phase | Gilterinib 120 mg in Escalation Phase | Gilterinib 200 mg in Escalation Phase | Gilterinib 300 mg in Escalation Phase | Gilterinib 450 mg in Escalation Phase | Gilterinib 20 mg in Expansion Phase | Gilterinib 40 mg in Expansion Phase | Gilterinib 80 mg in Expansion Phase | Gilterinib 120 mg in Expansion Phase | Gilterinib 200 mg in Expansion Phase | Gilterinib 300 mg in Expansion Phase | ||||||||||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 4/5 (80%) | 2/3 (66.7%) | 3/3 (100%) | 3/3 (100%) | 2/3 (66.7%) | 3/3 (100%) | 3/3 (100%) | 10/12 (83.3%) | 13/13 (100%) | 21/21 (100%) | 53/66 (80.3%) | 82/100 (82%) | 16/17 (94.1%) | |||||||||||||
Serious Adverse Events |
||||||||||||||||||||||||||
Gilterinib 20 mg in Escalation Phase | Gilterinib 40 mg in Escalation Phase | Gilterinib 80 mg in Escalation Phase | Gilterinib 120 mg in Escalation Phase | Gilterinib 200 mg in Escalation Phase | Gilterinib 300 mg in Escalation Phase | Gilterinib 450 mg in Escalation Phase | Gilterinib 20 mg in Expansion Phase | Gilterinib 40 mg in Expansion Phase | Gilterinib 80 mg in Expansion Phase | Gilterinib 120 mg in Expansion Phase | Gilterinib 200 mg in Expansion Phase | Gilterinib 300 mg in Expansion Phase | ||||||||||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 2/5 (40%) | 2/3 (66.7%) | 2/3 (66.7%) | 1/3 (33.3%) | 2/3 (66.7%) | 2/3 (66.7%) | 2/3 (66.7%) | 8/12 (66.7%) | 12/13 (92.3%) | 19/21 (90.5%) | 52/66 (78.8%) | 92/100 (92%) | 14/17 (82.4%) | |||||||||||||
Blood and lymphatic system disorders | ||||||||||||||||||||||||||
Anaemia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 0/66 (0%) | 0 | 4/100 (4%) | 6 | 0/17 (0%) | 0 |
Disseminated intravascular coagulation | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 1/17 (5.9%) | 1 |
Febrile neutropenia | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 2/3 (66.7%) | 6 | 2/3 (66.7%) | 5 | 0/3 (0%) | 0 | 4/12 (33.3%) | 6 | 7/13 (53.8%) | 7 | 5/21 (23.8%) | 11 | 18/66 (27.3%) | 28 | 35/100 (35%) | 58 | 4/17 (23.5%) | 4 |
Haemolytic anaemia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Leukocytosis | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 2/66 (3%) | 2 | 3/100 (3%) | 3 | 1/17 (5.9%) | 1 |
Neutropenia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 2 | 2/100 (2%) | 2 | 0/17 (0%) | 0 |
Pancytopenia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 2/100 (2%) | 2 | 0/17 (0%) | 0 |
Thrombocytopenia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 2/100 (2%) | 2 | 0/17 (0%) | 0 |
Cardiac disorders | ||||||||||||||||||||||||||
Acute myocardial infarction | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Atrial fibrillation | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 3/66 (4.5%) | 3 | 3/100 (3%) | 4 | 0/17 (0%) | 0 |
Atrial thrombosis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Atrioventricular block second degree | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Cardiac arrest | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Cardiac failure | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Cardiac failure congestive | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 0/66 (0%) | 0 | 2/100 (2%) | 4 | 0/17 (0%) | 0 |
Myocardial infarction | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Myocarditis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 2/100 (2%) | 2 | 0/17 (0%) | 0 |
Pericardial effusion | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Pericarditis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Supraventricular tachycardia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 2/100 (2%) | 2 | 0/17 (0%) | 0 |
Tachycardia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Ventricular fibrillation | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 2 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Ventricular tachycardia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Endocrine disorders | ||||||||||||||||||||||||||
Diabetes insipidus | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Eye disorders | ||||||||||||||||||||||||||
Conjunctival oedema | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Papilloedema | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Gastrointestinal disorders | ||||||||||||||||||||||||||
Colitis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 2 | 0/17 (0%) | 0 |
Diarrhoea | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 5/66 (7.6%) | 5 | 5/100 (5%) | 5 | 0/17 (0%) | 0 |
Dysphagia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 1/17 (5.9%) | 1 |
Enteritis | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Enterocolitis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Gastric haemorrhage | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Gastrointestinal haemorrhage | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 2/66 (3%) | 4 | 2/100 (2%) | 4 | 1/17 (5.9%) | 1 |
Haematemesis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Haematochezia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Intestinal obstruction | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Intestinal perforation | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Large intestinal ulcer | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Lower gastrointestinal haemorrhage | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 2/66 (3%) | 3 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Malabsorption | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Nausea | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 3/100 (3%) | 3 | 0/17 (0%) | 0 |
Neutropenic colitis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 2/66 (3%) | 3 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Pancreatitis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Pancreatitis acute | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Rectal haemorrhage | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Rectal tenesmus | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Small intestinal obstruction | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 1/17 (5.9%) | 1 |
Stomatitis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Swollen tongue | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Upper gastrointestinal haemorrhage | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 1/17 (5.9%) | 1 |
Vomiting | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 2/66 (3%) | 2 | 2/100 (2%) | 2 | 0/17 (0%) | 0 |
General disorders | ||||||||||||||||||||||||||
Asthenia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Chills | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Death | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 2/66 (3%) | 2 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Fatigue | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 2/66 (3%) | 2 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Mucosal inflammation | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 1/17 (5.9%) | 1 |
Multiple organ dysfunction syndrome | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 | 0/21 (0%) | 0 | 1/66 (1.5%) | 2 | 4/100 (4%) | 6 | 0/17 (0%) | 0 |
Oedema peripheral | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Pyrexia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 9/66 (13.6%) | 10 | 9/100 (9%) | 13 | 1/17 (5.9%) | 1 |
Sudden death | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Systemic inflammatory response syndrome | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Hepatobiliary disorders | ||||||||||||||||||||||||||
Cholecystitis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Hepatic failure | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Hyperbilirubinaemia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 2/100 (2%) | 2 | 0/17 (0%) | 0 |
Immune system disorders | ||||||||||||||||||||||||||
Acute graft versus host disease | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Acute graft versus host disease in intestine | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Acute graft versus host disease in skin | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 3/100 (3%) | 4 | 0/17 (0%) | 0 |
Anaphylactic reaction | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Chronic graft versus host disease in skin | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Graft versus host disease in skin | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Infections and infestations | ||||||||||||||||||||||||||
Abscess limb | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 2 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Arthritis bacterial | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 2 | 1/66 (1.5%) | 1 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Bacteraemia | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 5/21 (23.8%) | 9 | 2/66 (3%) | 2 | 5/100 (5%) | 7 | 0/17 (0%) | 0 |
Bacterial infection | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 2 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Bronchopulmonary aspergillosis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 2 | 3/100 (3%) | 4 | 0/17 (0%) | 0 |
Cellulitis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 4/66 (6.1%) | 4 | 4/100 (4%) | 4 | 0/17 (0%) | 0 |
Clostridial infection | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 1/17 (5.9%) | 1 |
Clostridium bacteraemia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 2/100 (2%) | 3 | 0/17 (0%) | 0 |
Clostridium difficile colitis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 6/100 (6%) | 6 | 0/17 (0%) | 0 |
Clostridium difficile infection | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 2/100 (2%) | 2 | 1/17 (5.9%) | 1 |
Corona virus infection | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 1/17 (5.9%) | 1 |
Device related infection | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Diverticulitis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Encephalitis viral | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Enterococcal bacteraemia | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 2/100 (2%) | 2 | 0/17 (0%) | 0 |
Enterococcal infection | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 1/17 (5.9%) | 1 |
Enterocolitis infectious | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Epiglottitis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Escherichia bacteraemia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Escherichia sepsis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Escherichia urinary tract infection | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Fungaemia | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Gastroenteritis viral | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Hepatic infection | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 2 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Herpes zoster | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Infection | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 2/100 (2%) | 2 | 0/17 (0%) | 0 |
Influenza | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 0/100 (0%) | 0 | 1/17 (5.9%) | 1 |
Klebsiella bacteraemia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 2/100 (2%) | 2 | 0/17 (0%) | 0 |
Lung infection | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 2/66 (3%) | 2 | 7/100 (7%) | 10 | 0/17 (0%) | 0 |
Oral infection | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Osteomyelitis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Otitis externa | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Parainfluenzae virus infection | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Periodontitis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Periorbital infection | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Pneumonia | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/3 (66.7%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 2 | 1/13 (7.7%) | 1 | 2/21 (9.5%) | 2 | 13/66 (19.7%) | 15 | 12/100 (12%) | 15 | 1/17 (5.9%) | 1 |
Pneumonia fungal | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 5/66 (7.6%) | 5 | 5/100 (5%) | 5 | 0/17 (0%) | 0 |
Pneumonia haemophilus | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Pneumonia parainfluenzae viral | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Pneumonia viral | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Post procedural cellulitis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Pseudomonas infection | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Pyelonephritis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Respiratory syncytial virus infection | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 2/66 (3%) | 2 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Sepsis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 2/13 (15.4%) | 2 | 7/21 (33.3%) | 8 | 10/66 (15.2%) | 10 | 19/100 (19%) | 25 | 0/17 (0%) | 0 |
Septic shock | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 3/21 (14.3%) | 4 | 0/66 (0%) | 0 | 4/100 (4%) | 6 | 0/17 (0%) | 0 |
Sinusitis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 1/66 (1.5%) | 1 | 0/100 (0%) | 0 | 1/17 (5.9%) | 1 |
Sinusitis fungal | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Skin bacterial infection | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Skin infection | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 1/66 (1.5%) | 1 | 2/100 (2%) | 2 | 0/17 (0%) | 0 |
Soft tissue infection | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 2/66 (3%) | 2 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Staphylococcal bacteraemia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Staphylococcal sepsis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 2/100 (2%) | 4 | 0/17 (0%) | 0 |
Streptococcal bacteraemia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 2/66 (3%) | 3 | 1/100 (1%) | 1 | 1/17 (5.9%) | 1 |
Streptococcal sepsis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Systemic candida | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 1/17 (5.9%) | 1 |
Systemic mycosis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Tooth abscess | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Tooth infection | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Toxic shock syndrome | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Upper respiratory tract infection | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 3/66 (4.5%) | 3 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Urinary tract infection | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 2/21 (9.5%) | 2 | 3/66 (4.5%) | 4 | 2/100 (2%) | 4 | 0/17 (0%) | 0 |
Urinary tract infection bacterial | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 2 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Urinary tract infection enterococcal | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Urosepsis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Injury, poisoning and procedural complications | ||||||||||||||||||||||||||
Facial bones fracture | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Fall | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 2/66 (3%) | 2 | 2/100 (2%) | 2 | 0/17 (0%) | 0 |
Hip fracture | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 1/17 (5.9%) | 1 |
Pelvic fracture | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Post procedural haemorrhage | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Road traffic accident | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Subdural haematoma | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 1/66 (1.5%) | 1 | 2/100 (2%) | 2 | 1/17 (5.9%) | 1 |
Tendon rupture | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Wound complication | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Investigations | ||||||||||||||||||||||||||
Alanine aminotransferase increased | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 2/100 (2%) | 2 | 0/17 (0%) | 0 |
Aspartate aminotransferase increased | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 2/100 (2%) | 2 | 1/17 (5.9%) | 1 |
Blood bilirubin increased | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 2/66 (3%) | 3 | 2/100 (2%) | 3 | 0/17 (0%) | 0 |
Blood creatine phosphokinase increased | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 2/66 (3%) | 2 | 3/100 (3%) | 3 | 0/17 (0%) | 0 |
Blood creatinine increased | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 2/100 (2%) | 4 | 0/17 (0%) | 0 |
Blood lactate dehydrogenase increased | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Blood uric acid increased | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Ejection fraction decreased | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 1/13 (7.7%) | 1 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Electrocardiogram QT prolonged | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Liver function test increased | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Platelet count decreased | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 2/100 (2%) | 2 | 0/17 (0%) | 0 |
Transaminases increased | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Troponin I increased | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
White blood cell count increased | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Metabolism and nutrition disorders | ||||||||||||||||||||||||||
Dehydration | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 1/100 (1%) | 1 | 1/17 (5.9%) | 1 |
Diabetic ketoacidosis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Failure to thrive | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Hyperkalaemia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Hyperuricaemia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Hypocalcaemia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Hyponatraemia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 2/66 (3%) | 4 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Tumour lysis syndrome | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Musculoskeletal and connective tissue disorders | ||||||||||||||||||||||||||
Arthralgia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Back pain | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Joint effusion | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 1/17 (5.9%) | 1 |
Muscular weakness | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 2/66 (3%) | 2 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Musculoskeletal chest pain | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Myalgia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Myositis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Neck pain | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Necrotising myositis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Osteonecrosis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Pain in extremity | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 2 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Rhabdomyolysis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 1/17 (5.9%) | 1 |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||||||||||
Acute myeloid leukaemia | 1/5 (20%) | 1 | 2/3 (66.7%) | 2 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 2/12 (16.7%) | 2 | 3/13 (23.1%) | 3 | 5/21 (23.8%) | 8 | 9/66 (13.6%) | 10 | 20/100 (20%) | 25 | 4/17 (23.5%) | 5 |
Acute myeloid leukaemia recurrent | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Basal cell carcinoma | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Central nervous system leukaemia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Leukaemia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Squamous cell carcinoma | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 2/66 (3%) | 2 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Squamous cell carcinoma of skin | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 2/100 (2%) | 2 | 0/17 (0%) | 0 |
Nervous system disorders | ||||||||||||||||||||||||||
Aphasia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Cerebral ischaemia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 2 | 0/17 (0%) | 0 |
Cerebrovascular accident | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Coordination abnormal | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Encephalopathy | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Haemorrhage intracranial | 1/5 (20%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Headache | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 1/17 (5.9%) | 1 |
Intracranial pressure increased | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Lethargy | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Loss of consciousness | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Neuralgia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Posterior reversible encephalopathy syndrome | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Presyncope | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 2 | 0/17 (0%) | 0 |
Radicular pain | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Seizure | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 2/100 (2%) | 2 | 0/17 (0%) | 0 |
Syncope | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 5/100 (5%) | 6 | 0/17 (0%) | 0 |
Psychiatric disorders | ||||||||||||||||||||||||||
Confusional state | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 2 | 0/17 (0%) | 0 |
Mental status changes | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Renal and urinary disorders | ||||||||||||||||||||||||||
Acute kidney injury | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 3/13 (23.1%) | 3 | 3/21 (14.3%) | 4 | 5/66 (7.6%) | 5 | 14/100 (14%) | 16 | 1/17 (5.9%) | 1 |
Renal failure | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 1/100 (1%) | 1 | 1/17 (5.9%) | 2 |
Renal injury | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Renal tubular necrosis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 1/66 (1.5%) | 1 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Urinary retention | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||||||||
Acute promyelocytic leukaemia differentiation syndrome | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Acute respiratory distress syndrome | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Acute respiratory failure | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 3/100 (3%) | 4 | 0/17 (0%) | 0 |
Aspiration | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Dyspnoea | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 2/100 (2%) | 2 | 0/17 (0%) | 0 |
Epistaxis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Haemoptysis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 2 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Hypoxia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 | 1/21 (4.8%) | 1 | 2/66 (3%) | 2 | 3/100 (3%) | 4 | 0/17 (0%) | 0 |
Laryngeal mass | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Lung infiltration | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Pleural effusion | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 2/66 (3%) | 2 | 2/100 (2%) | 3 | 0/17 (0%) | 0 |
Pneumonitis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Pulmonary embolism | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 0/100 (0%) | 0 | 1/17 (5.9%) | 1 |
Pulmonary haemorrhage | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Respiratory distress | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 2/66 (3%) | 2 | 2/100 (2%) | 2 | 0/17 (0%) | 0 |
Respiratory failure | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 2 | 1/66 (1.5%) | 1 | 11/100 (11%) | 13 | 1/17 (5.9%) | 1 |
Skin and subcutaneous tissue disorders | ||||||||||||||||||||||||||
Acute febrile neutrophilic dermatosis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 2/66 (3%) | 2 | 2/100 (2%) | 2 | 0/17 (0%) | 0 |
Angioedema | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Rash papular | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Skin lesion | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Vascular disorders | ||||||||||||||||||||||||||
Deep vein thrombosis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Embolism | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Haematoma | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Haemorrhage | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Hypertension | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 1/17 (5.9%) | 1 |
Hypotension | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 3/66 (4.5%) | 4 | 4/100 (4%) | 4 | 0/17 (0%) | 0 |
Orthostatic hypotension | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Phlebitis deep | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||||||||||||||||||||
Gilterinib 20 mg in Escalation Phase | Gilterinib 40 mg in Escalation Phase | Gilterinib 80 mg in Escalation Phase | Gilterinib 120 mg in Escalation Phase | Gilterinib 200 mg in Escalation Phase | Gilterinib 300 mg in Escalation Phase | Gilterinib 450 mg in Escalation Phase | Gilterinib 20 mg in Expansion Phase | Gilterinib 40 mg in Expansion Phase | Gilterinib 80 mg in Expansion Phase | Gilterinib 120 mg in Expansion Phase | Gilterinib 200 mg in Expansion Phase | Gilterinib 300 mg in Expansion Phase | ||||||||||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 5/5 (100%) | 2/3 (66.7%) | 3/3 (100%) | 3/3 (100%) | 3/3 (100%) | 3/3 (100%) | 3/3 (100%) | 12/12 (100%) | 12/13 (92.3%) | 20/21 (95.2%) | 62/66 (93.9%) | 97/100 (97%) | 16/17 (94.1%) | |||||||||||||
Blood and lymphatic system disorders | ||||||||||||||||||||||||||
Anaemia | 2/5 (40%) | 2 | 0/3 (0%) | 0 | 1/3 (33.3%) | 3 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 2/12 (16.7%) | 4 | 4/13 (30.8%) | 4 | 7/21 (33.3%) | 10 | 27/66 (40.9%) | 84 | 33/100 (33%) | 65 | 6/17 (35.3%) | 6 |
Febrile neutropenia | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/12 (16.7%) | 2 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 7/66 (10.6%) | 8 | 15/100 (15%) | 20 | 3/17 (17.6%) | 3 |
Hyperfibrinogenaemia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 1/17 (5.9%) | 1 |
Leukocytosis | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 | 1/21 (4.8%) | 1 | 4/66 (6.1%) | 4 | 4/100 (4%) | 6 | 2/17 (11.8%) | 2 |
Lymphadenopathy | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 0/100 (0%) | 0 | 1/17 (5.9%) | 1 |
Neutropenia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 5/66 (7.6%) | 28 | 12/100 (12%) | 29 | 2/17 (11.8%) | 2 |
Thrombocytopenia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 | 3/21 (14.3%) | 6 | 12/66 (18.2%) | 27 | 19/100 (19%) | 44 | 2/17 (11.8%) | 2 |
Cardiac disorders | ||||||||||||||||||||||||||
Angina pectoris | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/12 (16.7%) | 3 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 2/100 (2%) | 2 | 0/17 (0%) | 0 |
Atrial fibrillation | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 3/66 (4.5%) | 3 | 5/100 (5%) | 5 | 0/17 (0%) | 0 |
Atrial flutter | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Palpitations | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 2/21 (9.5%) | 2 | 0/66 (0%) | 0 | 3/100 (3%) | 3 | 0/17 (0%) | 0 |
Pericardial effusion | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 1/66 (1.5%) | 1 | 3/100 (3%) | 3 | 0/17 (0%) | 0 |
Sinus bradycardia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 0/66 (0%) | 0 | 2/100 (2%) | 2 | 0/17 (0%) | 0 |
Sinus tachycardia | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 2/13 (15.4%) | 2 | 1/21 (4.8%) | 2 | 2/66 (3%) | 2 | 6/100 (6%) | 7 | 0/17 (0%) | 0 |
Tachycardia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 1/66 (1.5%) | 1 | 12/100 (12%) | 13 | 0/17 (0%) | 0 |
Ear and labyrinth disorders | ||||||||||||||||||||||||||
Ear discomfort | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Ear pain | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/12 (16.7%) | 2 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 3/100 (3%) | 3 | 0/17 (0%) | 0 |
Endocrine disorders | ||||||||||||||||||||||||||
Hypothyroidism | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 3/100 (3%) | 3 | 0/17 (0%) | 0 |
Eye disorders | ||||||||||||||||||||||||||
Blepharitis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 4/66 (6.1%) | 4 | 2/100 (2%) | 2 | 0/17 (0%) | 0 |
Cataract | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 4/66 (6.1%) | 6 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Cataract nuclear | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Conjunctival haemorrhage | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 | 4/21 (19%) | 4 | 0/66 (0%) | 0 | 3/100 (3%) | 3 | 0/17 (0%) | 0 |
Dry eye | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 8/66 (12.1%) | 10 | 6/100 (6%) | 7 | 0/17 (0%) | 0 |
Eye oedema | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Eye pruritus | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 1/100 (1%) | 1 | 1/17 (5.9%) | 1 |
Glaucoma | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Lacrimation increased | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 2/66 (3%) | 3 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Periorbital oedema | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 2/21 (9.5%) | 2 | 3/66 (4.5%) | 3 | 5/100 (5%) | 9 | 0/17 (0%) | 0 |
Retinal exudates | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Retinal haemorrhage | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 3/66 (4.5%) | 3 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Vision blurred | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 5/66 (7.6%) | 8 | 6/100 (6%) | 6 | 0/17 (0%) | 0 |
Vitreous detachment | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Vitreous floaters | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 4/66 (6.1%) | 4 | 3/100 (3%) | 3 | 0/17 (0%) | 0 |
Gastrointestinal disorders | ||||||||||||||||||||||||||
Abdominal distension | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 7/100 (7%) | 8 | 1/17 (5.9%) | 1 |
Abdominal pain | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/12 (8.3%) | 1 | 1/13 (7.7%) | 1 | 1/21 (4.8%) | 1 | 5/66 (7.6%) | 6 | 15/100 (15%) | 19 | 0/17 (0%) | 0 |
Abdominal pain lower | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Abdominal pain upper | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 3/66 (4.5%) | 3 | 1/100 (1%) | 1 | 1/17 (5.9%) | 1 |
Abdominal tenderness | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Aphthous ulcer | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 1/17 (5.9%) | 1 |
Colitis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 2/66 (3%) | 2 | 2/100 (2%) | 2 | 0/17 (0%) | 0 |
Constipation | 1/5 (20%) | 1 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 2/3 (66.7%) | 2 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/12 (8.3%) | 2 | 1/13 (7.7%) | 1 | 5/21 (23.8%) | 5 | 12/66 (18.2%) | 14 | 32/100 (32%) | 36 | 1/17 (5.9%) | 1 |
Diarrhoea | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/3 (33.3%) | 2 | 1/3 (33.3%) | 2 | 1/12 (8.3%) | 1 | 2/13 (15.4%) | 2 | 5/21 (23.8%) | 12 | 27/66 (40.9%) | 44 | 45/100 (45%) | 71 | 5/17 (29.4%) | 6 |
Dry mouth | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 1/13 (7.7%) | 1 | 2/21 (9.5%) | 2 | 4/66 (6.1%) | 4 | 10/100 (10%) | 10 | 1/17 (5.9%) | 1 |
Dyspepsia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 3/66 (4.5%) | 3 | 3/100 (3%) | 3 | 0/17 (0%) | 0 |
Dysphagia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 2/66 (3%) | 2 | 7/100 (7%) | 8 | 2/17 (11.8%) | 2 |
Gastrointestinal haemorrhage | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 0/66 (0%) | 0 | 4/100 (4%) | 5 | 0/17 (0%) | 0 |
Gingival bleeding | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 2 | 1/21 (4.8%) | 1 | 2/66 (3%) | 2 | 2/100 (2%) | 2 | 0/17 (0%) | 0 |
Gingival pain | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Haemorrhoids | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 1/13 (7.7%) | 1 | 1/21 (4.8%) | 1 | 1/66 (1.5%) | 1 | 6/100 (6%) | 8 | 0/17 (0%) | 0 |
Melaena | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Mouth haemorrhage | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 2/66 (3%) | 2 | 8/100 (8%) | 9 | 0/17 (0%) | 0 |
Mouth ulceration | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 4/66 (6.1%) | 5 | 4/100 (4%) | 5 | 1/17 (5.9%) | 1 |
Nausea | 2/5 (40%) | 3 | 0/3 (0%) | 0 | 2/3 (66.7%) | 3 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 3/13 (23.1%) | 3 | 4/21 (19%) | 5 | 15/66 (22.7%) | 22 | 28/100 (28%) | 37 | 1/17 (5.9%) | 1 |
Oesophagitis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 1/100 (1%) | 1 | 1/17 (5.9%) | 1 |
Oral mucosal blistering | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 2/21 (9.5%) | 2 | 2/66 (3%) | 2 | 1/100 (1%) | 3 | 1/17 (5.9%) | 1 |
Oral pain | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 2/100 (2%) | 3 | 0/17 (0%) | 0 |
Proctalgia | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Rectal haemorrhage | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 4/100 (4%) | 4 | 0/17 (0%) | 0 |
Salivary hypersecretion | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Stomatitis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 1/12 (8.3%) | 1 | 1/13 (7.7%) | 1 | 0/21 (0%) | 0 | 8/66 (12.1%) | 9 | 14/100 (14%) | 15 | 1/17 (5.9%) | 1 |
Tongue coated | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 2 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Vomiting | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 2/3 (66.7%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/12 (16.7%) | 3 | 1/13 (7.7%) | 1 | 5/21 (23.8%) | 6 | 13/66 (19.7%) | 16 | 22/100 (22%) | 31 | 1/17 (5.9%) | 1 |
General disorders | ||||||||||||||||||||||||||
Asthenia | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 2 | 0/3 (0%) | 0 | 2/12 (16.7%) | 2 | 0/13 (0%) | 0 | 3/21 (14.3%) | 3 | 6/66 (9.1%) | 8 | 19/100 (19%) | 20 | 0/17 (0%) | 0 |
Chills | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 5/66 (7.6%) | 5 | 12/100 (12%) | 15 | 0/17 (0%) | 0 |
Face oedema | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 | 2/21 (9.5%) | 3 | 2/66 (3%) | 2 | 2/100 (2%) | 2 | 0/17 (0%) | 0 |
Fatigue | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 1/3 (33.3%) | 2 | 0/3 (0%) | 0 | 3/3 (100%) | 6 | 1/3 (33.3%) | 2 | 1/3 (33.3%) | 3 | 4/12 (33.3%) | 5 | 5/13 (38.5%) | 6 | 8/21 (38.1%) | 11 | 27/66 (40.9%) | 38 | 32/100 (32%) | 47 | 4/17 (23.5%) | 4 |
Gait disturbance | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Generalised oedema | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 2/100 (2%) | 2 | 1/17 (5.9%) | 1 |
Local swelling | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 1/17 (5.9%) | 1 |
Localised oedema | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 1/66 (1.5%) | 2 | 5/100 (5%) | 5 | 0/17 (0%) | 0 |
Malaise | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 2/66 (3%) | 3 | 5/100 (5%) | 5 | 0/17 (0%) | 0 |
Mucosal inflammation | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 7/66 (10.6%) | 9 | 11/100 (11%) | 13 | 0/17 (0%) | 0 |
Nodule | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 1/66 (1.5%) | 2 | 0/100 (0%) | 0 | 1/17 (5.9%) | 1 |
Oedema | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 | 3/21 (14.3%) | 5 | 3/66 (4.5%) | 5 | 6/100 (6%) | 7 | 0/17 (0%) | 0 |
Oedema peripheral | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 4/12 (33.3%) | 4 | 2/13 (15.4%) | 2 | 5/21 (23.8%) | 11 | 17/66 (25.8%) | 22 | 31/100 (31%) | 48 | 1/17 (5.9%) | 2 |
Pain | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 6/66 (9.1%) | 7 | 6/100 (6%) | 9 | 0/17 (0%) | 0 |
Peripheral swelling | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 | 1/21 (4.8%) | 2 | 3/66 (4.5%) | 4 | 4/100 (4%) | 6 | 0/17 (0%) | 0 |
Pyrexia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 3/13 (23.1%) | 3 | 3/21 (14.3%) | 3 | 18/66 (27.3%) | 25 | 24/100 (24%) | 33 | 3/17 (17.6%) | 3 |
Serositis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Hepatobiliary disorders | ||||||||||||||||||||||||||
Hyperbilirubinaemia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 2/21 (9.5%) | 2 | 2/66 (3%) | 2 | 6/100 (6%) | 12 | 0/17 (0%) | 0 |
Immune system disorders | ||||||||||||||||||||||||||
Graft versus host disease | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 3/66 (4.5%) | 4 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Seasonal allergy | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 1/66 (1.5%) | 1 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Infections and infestations | ||||||||||||||||||||||||||
Abscess limb | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Bacteraemia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 2/21 (9.5%) | 2 | 3/66 (4.5%) | 3 | 2/100 (2%) | 2 | 0/17 (0%) | 0 |
Candida infection | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 4/66 (6.1%) | 4 | 2/100 (2%) | 2 | 0/17 (0%) | 0 |
Cellulitis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 2/21 (9.5%) | 3 | 5/66 (7.6%) | 6 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Clostridium difficile infection | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 | 1/21 (4.8%) | 1 | 4/66 (6.1%) | 4 | 2/100 (2%) | 2 | 0/17 (0%) | 0 |
Enterococcal bacteraemia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 2/100 (2%) | 2 | 1/17 (5.9%) | 1 |
Gingivitis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Herpes virus infection | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Herpes zoster | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Influenza | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 5/100 (5%) | 5 | 0/17 (0%) | 0 |
Laryngitis fungal | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Lip infection | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Lung infection | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 | 0/21 (0%) | 0 | 2/66 (3%) | 2 | 5/100 (5%) | 5 | 0/17 (0%) | 0 |
Oral candidiasis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 0/66 (0%) | 0 | 2/100 (2%) | 2 | 0/17 (0%) | 0 |
Oral herpes | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 2 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Pharyngitis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 2 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Pneumonia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 2 | 5/66 (7.6%) | 6 | 5/100 (5%) | 6 | 0/17 (0%) | 0 |
Sinusitis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 2/66 (3%) | 2 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Skin infection | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 | 1/21 (4.8%) | 1 | 3/66 (4.5%) | 3 | 3/100 (3%) | 3 | 0/17 (0%) | 0 |
Upper respiratory tract infection | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 2/13 (15.4%) | 2 | 1/21 (4.8%) | 1 | 7/66 (10.6%) | 9 | 5/100 (5%) | 11 | 0/17 (0%) | 0 |
Urinary tract infection | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 2/21 (9.5%) | 2 | 9/66 (13.6%) | 9 | 5/100 (5%) | 7 | 0/17 (0%) | 0 |
Urinary tract infection bacterial | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 4/66 (6.1%) | 7 | 3/100 (3%) | 4 | 0/17 (0%) | 0 |
Urinary tract infection enterococcal | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/12 (16.7%) | 2 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Injury, poisoning and procedural complications | ||||||||||||||||||||||||||
Contusion | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/12 (8.3%) | 1 | 1/13 (7.7%) | 1 | 3/21 (14.3%) | 3 | 3/66 (4.5%) | 3 | 10/100 (10%) | 11 | 0/17 (0%) | 0 |
Fall | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 | 2/21 (9.5%) | 2 | 11/66 (16.7%) | 15 | 18/100 (18%) | 22 | 0/17 (0%) | 0 |
Incision site pain | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Infusion related reaction | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 3/100 (3%) | 5 | 0/17 (0%) | 0 |
Periorbital haemorrhage | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 1/17 (5.9%) | 1 |
Post procedural haemorrhage | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Procedural pain | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 1/100 (1%) | 1 | 1/17 (5.9%) | 1 |
Stoma site pain | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 2 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Transfusion reaction | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 2 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 3/66 (4.5%) | 3 | 1/100 (1%) | 1 | 1/17 (5.9%) | 1 |
Investigations | ||||||||||||||||||||||||||
Activated partial thromboplastin time prolonged | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/12 (8.3%) | 2 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 4/100 (4%) | 5 | 0/17 (0%) | 0 |
Alanine aminotransferase increased | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 1/12 (8.3%) | 2 | 1/13 (7.7%) | 1 | 3/21 (14.3%) | 9 | 16/66 (24.2%) | 26 | 25/100 (25%) | 46 | 2/17 (11.8%) | 3 |
Aspartate aminotransferase increased | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 2/3 (66.7%) | 4 | 1/12 (8.3%) | 3 | 1/13 (7.7%) | 1 | 3/21 (14.3%) | 9 | 20/66 (30.3%) | 33 | 35/100 (35%) | 61 | 1/17 (5.9%) | 2 |
Blood alkaline phosphatase increased | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 | 3/21 (14.3%) | 12 | 10/66 (15.2%) | 12 | 15/100 (15%) | 19 | 0/17 (0%) | 0 |
Blood bilirubin increased | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 2 | 2/13 (15.4%) | 3 | 3/21 (14.3%) | 3 | 1/66 (1.5%) | 1 | 12/100 (12%) | 22 | 0/17 (0%) | 0 |
Blood creatine phosphokinase increased | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 5/66 (7.6%) | 9 | 15/100 (15%) | 27 | 1/17 (5.9%) | 1 |
Blood creatinine increased | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 2/13 (15.4%) | 2 | 4/21 (19%) | 9 | 13/66 (19.7%) | 23 | 19/100 (19%) | 40 | 1/17 (5.9%) | 1 |
Blood lactate dehydrogenase increased | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 | 0/21 (0%) | 0 | 3/66 (4.5%) | 4 | 7/100 (7%) | 9 | 0/17 (0%) | 0 |
Blood phosphorus decreased | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Blood thyroid stimulating hormone increased | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Blood urea increased | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 2/100 (2%) | 2 | 1/17 (5.9%) | 1 |
Cardiac murmur | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 2/21 (9.5%) | 2 | 1/66 (1.5%) | 1 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Chest X-ray abnormal | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Electrocardiogram QT prolonged | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 9/66 (13.6%) | 13 | 9/100 (9%) | 11 | 0/17 (0%) | 0 |
International normalised ratio increased | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 1/13 (7.7%) | 2 | 1/21 (4.8%) | 1 | 4/66 (6.1%) | 7 | 5/100 (5%) | 7 | 1/17 (5.9%) | 1 |
Liver function test increased | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 2 | 1/66 (1.5%) | 1 | 3/100 (3%) | 4 | 1/17 (5.9%) | 1 |
Neutrophil count decreased | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 2 | 0/3 (0%) | 0 | 2/12 (16.7%) | 4 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 8/66 (12.1%) | 16 | 14/100 (14%) | 29 | 0/17 (0%) | 0 |
Platelet count decreased | 1/5 (20%) | 3 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 2 | 1/3 (33.3%) | 1 | 2/12 (16.7%) | 8 | 3/13 (23.1%) | 4 | 1/21 (4.8%) | 1 | 12/66 (18.2%) | 26 | 17/100 (17%) | 37 | 1/17 (5.9%) | 1 |
Transaminases increased | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 5/66 (7.6%) | 5 | 5/100 (5%) | 6 | 1/17 (5.9%) | 1 |
Ultrasound liver abnormal | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 1/17 (5.9%) | 1 |
Volume blood increased | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Weight decreased | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 1/13 (7.7%) | 1 | 0/21 (0%) | 0 | 3/66 (4.5%) | 3 | 6/100 (6%) | 7 | 0/17 (0%) | 0 |
Weight increased | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 2/66 (3%) | 5 | 12/100 (12%) | 18 | 0/17 (0%) | 0 |
White blood cell count decreased | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 4/66 (6.1%) | 14 | 13/100 (13%) | 30 | 0/17 (0%) | 0 |
Metabolism and nutrition disorders | ||||||||||||||||||||||||||
Decreased appetite | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 2/3 (66.7%) | 3 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 1/13 (7.7%) | 1 | 3/21 (14.3%) | 4 | 11/66 (16.7%) | 13 | 19/100 (19%) | 21 | 1/17 (5.9%) | 1 |
Dehydration | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 2 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 10/100 (10%) | 10 | 0/17 (0%) | 0 |
Fluid overload | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 2/66 (3%) | 2 | 2/100 (2%) | 2 | 0/17 (0%) | 0 |
Fluid retention | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 2/100 (2%) | 2 | 0/17 (0%) | 0 |
Hypercalcaemia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Hyperglycaemia | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/3 (66.7%) | 2 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 5/66 (7.6%) | 7 | 14/100 (14%) | 16 | 0/17 (0%) | 0 |
Hyperkalaemia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 | 1/21 (4.8%) | 2 | 5/66 (7.6%) | 6 | 9/100 (9%) | 10 | 0/17 (0%) | 0 |
Hyperphosphataemia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 | 1/21 (4.8%) | 2 | 2/66 (3%) | 2 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Hyperuricaemia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 2/13 (15.4%) | 2 | 0/21 (0%) | 0 | 4/66 (6.1%) | 4 | 10/100 (10%) | 11 | 0/17 (0%) | 0 |
Hypoalbuminaemia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/12 (8.3%) | 2 | 1/13 (7.7%) | 1 | 4/21 (19%) | 15 | 7/66 (10.6%) | 15 | 18/100 (18%) | 28 | 1/17 (5.9%) | 2 |
Hypocalcaemia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/12 (8.3%) | 1 | 2/13 (15.4%) | 2 | 3/21 (14.3%) | 17 | 11/66 (16.7%) | 23 | 23/100 (23%) | 50 | 1/17 (5.9%) | 1 |
Hypochloraemia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 1/17 (5.9%) | 1 |
Hypoglycaemia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 2/66 (3%) | 2 | 3/100 (3%) | 4 | 0/17 (0%) | 0 |
Hypokalaemia | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 5/12 (41.7%) | 9 | 2/13 (15.4%) | 3 | 2/21 (9.5%) | 11 | 10/66 (15.2%) | 20 | 25/100 (25%) | 33 | 0/17 (0%) | 0 |
Hypomagnesaemia | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 2 | 1/13 (7.7%) | 1 | 3/21 (14.3%) | 3 | 13/66 (19.7%) | 19 | 17/100 (17%) | 25 | 0/17 (0%) | 0 |
Hyponatraemia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 | 2/21 (9.5%) | 8 | 8/66 (12.1%) | 16 | 20/100 (20%) | 26 | 1/17 (5.9%) | 1 |
Hypophosphataemia | 1/5 (20%) | 2 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 6/66 (9.1%) | 10 | 11/100 (11%) | 13 | 2/17 (11.8%) | 2 |
Hypoproteinaemia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 2/100 (2%) | 2 | 0/17 (0%) | 0 |
Hypovolaemia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 2/100 (2%) | 2 | 0/17 (0%) | 0 |
Iron overload | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 4/66 (6.1%) | 4 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Musculoskeletal and connective tissue disorders | ||||||||||||||||||||||||||
Arthralgia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 4/21 (19%) | 4 | 12/66 (18.2%) | 15 | 16/100 (16%) | 23 | 1/17 (5.9%) | 1 |
Back pain | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 2 | 0/13 (0%) | 0 | 2/21 (9.5%) | 2 | 8/66 (12.1%) | 9 | 9/100 (9%) | 11 | 0/17 (0%) | 0 |
Bone pain | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 1/66 (1.5%) | 1 | 7/100 (7%) | 7 | 0/17 (0%) | 0 |
Flank pain | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Muscle spasms | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 3/66 (4.5%) | 4 | 4/100 (4%) | 4 | 0/17 (0%) | 0 |
Muscular weakness | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 | 0/21 (0%) | 0 | 7/66 (10.6%) | 7 | 4/100 (4%) | 4 | 0/17 (0%) | 0 |
Musculoskeletal chest pain | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Musculoskeletal pain | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 2/66 (3%) | 2 | 7/100 (7%) | 7 | 0/17 (0%) | 0 |
Myalgia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 1/13 (7.7%) | 1 | 0/21 (0%) | 0 | 5/66 (7.6%) | 5 | 12/100 (12%) | 14 | 0/17 (0%) | 0 |
Myopathy | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 1/17 (5.9%) | 1 |
Neck pain | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 | 0/21 (0%) | 0 | 4/66 (6.1%) | 5 | 3/100 (3%) | 3 | 0/17 (0%) | 0 |
Pain in extremity | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 | 2/21 (9.5%) | 3 | 10/66 (15.2%) | 13 | 11/100 (11%) | 15 | 0/17 (0%) | 0 |
Pain in jaw | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/12 (16.7%) | 2 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 1/66 (1.5%) | 1 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Nervous system disorders | ||||||||||||||||||||||||||
Cognitive disorder | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 2/100 (2%) | 2 | 0/17 (0%) | 0 |
Dizziness | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 1/13 (7.7%) | 1 | 5/21 (23.8%) | 6 | 17/66 (25.8%) | 19 | 26/100 (26%) | 34 | 0/17 (0%) | 0 |
Dysaesthesia | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 4/66 (6.1%) | 6 | 9/100 (9%) | 10 | 0/17 (0%) | 0 |
Dysgeusia | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/12 (16.7%) | 2 | 1/13 (7.7%) | 1 | 1/21 (4.8%) | 1 | 9/66 (13.6%) | 9 | 11/100 (11%) | 12 | 2/17 (11.8%) | 2 |
Headache | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 2 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 2/12 (16.7%) | 2 | 1/13 (7.7%) | 1 | 3/21 (14.3%) | 4 | 10/66 (15.2%) | 14 | 14/100 (14%) | 20 | 0/17 (0%) | 0 |
Hyperaesthesia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 2/66 (3%) | 2 | 4/100 (4%) | 4 | 0/17 (0%) | 0 |
Lethargy | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 2/21 (9.5%) | 2 | 1/66 (1.5%) | 1 | 3/100 (3%) | 3 | 1/17 (5.9%) | 1 |
Memory impairment | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Neuropathy peripheral | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 2 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 7/66 (10.6%) | 9 | 5/100 (5%) | 6 | 2/17 (11.8%) | 2 |
Paraesthesia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 6/66 (9.1%) | 7 | 7/100 (7%) | 12 | 1/17 (5.9%) | 1 |
Peripheral sensory neuropathy | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Presyncope | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 3/66 (4.5%) | 3 | 7/100 (7%) | 8 | 0/17 (0%) | 0 |
Sciatica | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Somnolence | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 | 1/21 (4.8%) | 1 | 1/66 (1.5%) | 1 | 2/100 (2%) | 2 | 0/17 (0%) | 0 |
Syncope | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 2/66 (3%) | 3 | 6/100 (6%) | 6 | 0/17 (0%) | 0 |
Tremor | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 2 | 6/100 (6%) | 7 | 0/17 (0%) | 0 |
Product Issues | ||||||||||||||||||||||||||
Device occlusion | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 1/17 (5.9%) | 1 |
Psychiatric disorders | ||||||||||||||||||||||||||
Agitation | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 | 1/21 (4.8%) | 1 | 0/66 (0%) | 0 | 3/100 (3%) | 3 | 0/17 (0%) | 0 |
Anxiety | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 1/13 (7.7%) | 1 | 1/21 (4.8%) | 1 | 5/66 (7.6%) | 5 | 6/100 (6%) | 6 | 0/17 (0%) | 0 |
Confusional state | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 2 | 3/21 (14.3%) | 3 | 4/66 (6.1%) | 4 | 10/100 (10%) | 12 | 1/17 (5.9%) | 1 |
Depression | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 3/66 (4.5%) | 3 | 6/100 (6%) | 6 | 0/17 (0%) | 0 |
Disorientation | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Insomnia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 2/12 (16.7%) | 2 | 1/13 (7.7%) | 1 | 3/21 (14.3%) | 3 | 8/66 (12.1%) | 9 | 13/100 (13%) | 14 | 1/17 (5.9%) | 1 |
Mental status changes | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 | 2/21 (9.5%) | 2 | 0/66 (0%) | 0 | 2/100 (2%) | 2 | 1/17 (5.9%) | 1 |
Sleep disorder | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 2/21 (9.5%) | 2 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Renal and urinary disorders | ||||||||||||||||||||||||||
Dysuria | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 3/66 (4.5%) | 3 | 7/100 (7%) | 8 | 0/17 (0%) | 0 |
Haematuria | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 2 | 3/66 (4.5%) | 4 | 6/100 (6%) | 6 | 0/17 (0%) | 0 |
Pollakiuria | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/3 (66.7%) | 2 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 7/100 (7%) | 7 | 0/17 (0%) | 0 |
Urinary incontinence | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 5/66 (7.6%) | 6 | 4/100 (4%) | 5 | 0/17 (0%) | 0 |
Urinary retention | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 2 | 0/66 (0%) | 0 | 7/100 (7%) | 8 | 0/17 (0%) | 0 |
Reproductive system and breast disorders | ||||||||||||||||||||||||||
Nipple pain | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||||||||
Atelectasis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Cough | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/12 (16.7%) | 3 | 1/13 (7.7%) | 1 | 7/21 (33.3%) | 7 | 18/66 (27.3%) | 27 | 26/100 (26%) | 29 | 3/17 (17.6%) | 3 |
Dysphonia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 2 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 2/100 (2%) | 2 | 1/17 (5.9%) | 1 |
Dyspnoea | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 3/12 (25%) | 4 | 5/13 (38.5%) | 5 | 4/21 (19%) | 5 | 19/66 (28.8%) | 23 | 28/100 (28%) | 38 | 2/17 (11.8%) | 2 |
Dyspnoea exertional | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 6/66 (9.1%) | 7 | 3/100 (3%) | 3 | 1/17 (5.9%) | 1 |
Epistaxis | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 3/12 (25%) | 3 | 3/13 (23.1%) | 3 | 3/21 (14.3%) | 3 | 16/66 (24.2%) | 18 | 20/100 (20%) | 24 | 4/17 (23.5%) | 4 |
Haemoptysis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 2/66 (3%) | 2 | 2/100 (2%) | 2 | 0/17 (0%) | 0 |
Hypoxia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 1/13 (7.7%) | 1 | 2/21 (9.5%) | 2 | 5/66 (7.6%) | 8 | 11/100 (11%) | 14 | 0/17 (0%) | 0 |
Nasal congestion | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 3/21 (14.3%) | 4 | 3/66 (4.5%) | 4 | 9/100 (9%) | 9 | 0/17 (0%) | 0 |
Oropharyngeal pain | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/12 (16.7%) | 2 | 2/13 (15.4%) | 2 | 0/21 (0%) | 0 | 5/66 (7.6%) | 6 | 8/100 (8%) | 11 | 0/17 (0%) | 0 |
Pharyngeal disorder | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Pleural effusion | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 2/66 (3%) | 2 | 10/100 (10%) | 14 | 0/17 (0%) | 0 |
Rales | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Rhinorrhoea | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Sinus pain | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Tachypnoea | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 2 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Upper-airway cough syndrome | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 4/66 (6.1%) | 4 | 2/100 (2%) | 3 | 0/17 (0%) | 0 |
Wheezing | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 2/66 (3%) | 2 | 5/100 (5%) | 6 | 0/17 (0%) | 0 |
Skin and subcutaneous tissue disorders | ||||||||||||||||||||||||||
Alopecia | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 5/66 (7.6%) | 6 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Blood blister | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 2/100 (2%) | 2 | 1/17 (5.9%) | 1 |
Decubitus ulcer | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 1/66 (1.5%) | 1 | 2/100 (2%) | 3 | 0/17 (0%) | 0 |
Dermatitis acneiform | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Drug eruption | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 5/66 (7.6%) | 5 | 4/100 (4%) | 4 | 0/17 (0%) | 0 |
Dry skin | 1/5 (20%) | 1 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 2/21 (9.5%) | 4 | 3/66 (4.5%) | 3 | 3/100 (3%) | 5 | 0/17 (0%) | 0 |
Ecchymosis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 | 2/21 (9.5%) | 3 | 3/66 (4.5%) | 3 | 8/100 (8%) | 8 | 1/17 (5.9%) | 1 |
Eccrine squamous syringometaplasia | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Erythema | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 2/21 (9.5%) | 2 | 3/66 (4.5%) | 4 | 4/100 (4%) | 4 | 1/17 (5.9%) | 1 |
Erythema multiforme | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Hyperhidrosis | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 3/21 (14.3%) | 4 | 1/66 (1.5%) | 1 | 4/100 (4%) | 4 | 0/17 (0%) | 0 |
Pain of skin | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 5/100 (5%) | 5 | 1/17 (5.9%) | 1 |
Petechiae | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/12 (16.7%) | 4 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 14/100 (14%) | 14 | 1/17 (5.9%) | 1 |
Photosensitivity reaction | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 | 0/21 (0%) | 0 | 1/66 (1.5%) | 1 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Pigmentation disorder | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 0/17 (0%) | 0 |
Pruritus | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 | 2/21 (9.5%) | 2 | 0/66 (0%) | 0 | 7/100 (7%) | 12 | 0/17 (0%) | 0 |
Rash | 0/5 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/12 (0%) | 0 | 1/13 (7.7%) | 1 | 0/21 (0%) | 0 | 11/66 (16.7%) | 11 | 11/100 (11%) | 13 | 0/17 (0%) | 0 |
Rash maculo-papular | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/12 (16.7%) | 2 | 1/13 (7.7%) | 1 | 1/21 (4.8%) | 1 | 3/66 (4.5%) | 3 | 7/100 (7%) | 9 | 0/17 (0%) | 0 |
Rash papular | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 1/13 (7.7%) | 2 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 0/100 (0%) | 0 | 1/17 (5.9%) | 1 |
Skin lesion | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 1/66 (1.5%) | 1 | 5/100 (5%) | 5 | 2/17 (11.8%) | 4 |
Swelling face | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 2/66 (3%) | 2 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Vascular disorders | ||||||||||||||||||||||||||
Flushing | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 0/66 (0%) | 0 | 1/100 (1%) | 1 | 1/17 (5.9%) | 1 |
Haematoma | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 | 1/21 (4.8%) | 1 | 2/66 (3%) | 2 | 6/100 (6%) | 8 | 0/17 (0%) | 0 |
Hot flush | 1/5 (20%) | 1 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 0/21 (0%) | 0 | 2/66 (3%) | 2 | 2/100 (2%) | 2 | 0/17 (0%) | 0 |
Hypertension | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 1/13 (7.7%) | 1 | 1/21 (4.8%) | 1 | 7/66 (10.6%) | 7 | 16/100 (16%) | 34 | 1/17 (5.9%) | 2 |
Hypotension | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/12 (8.3%) | 1 | 0/13 (0%) | 0 | 3/21 (14.3%) | 4 | 10/66 (15.2%) | 11 | 25/100 (25%) | 32 | 1/17 (5.9%) | 1 |
Orthostatic hypotension | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 1/21 (4.8%) | 2 | 3/66 (4.5%) | 3 | 8/100 (8%) | 8 | 0/17 (0%) | 0 |
Pallor | 0/5 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/12 (0%) | 0 | 0/13 (0%) | 0 | 2/21 (9.5%) | 2 | 1/66 (1.5%) | 1 | 0/100 (0%) | 0 | 0/17 (0%) | 0 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Institute and/or Principal Investigator may publish trial data generated at their specific study site after Sponsor publication of the multi-center data. Sponsor must receive a site's manuscript prior to publication for review and comment as specified in the Investigator Agreement.
Results Point of Contact
Name/Title | Clinical Trial Disclosure |
---|---|
Organization | Astellas Pharma Global Development, Inc. |
Phone | 800-888-7704 |
astellas.resultsdisclosure@astellas.com |
- 2215-CL-0101