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An open-label, non-randomized, multi-centre, Phase I/II trial to assess the efficacy and safety of 2 schedules of PXD101 in combination with idarubicin in patients with AML not suitable for standard intensive therapy.
This trial is an open-label, multi-centre, dose-escalation Phase I/II study to evaluate safety, explore efficacy, pharmacodynamics, and pharmacokinetics of the combination of PXD101 with idarubicin administered in two different schedules in patients with AML. The PXD101 plus idarubicin treatment will be repeated at suitable intervals (target is every 3 weeks for schedule A and every 2 weeks for schedule B) depending upon toxicities or disease progression. Safety and efficacy assessments will be performed at every cycle.
Schedule A uses PXD101 by 30 min infusion daily for 5 days every 3 weeks with escalating doses of idarubicin.
Schedule B uses escalating doses of continuous infusion (48h) of PXD101 alone or in combination with idarubicin.
In both regimens the trial may be expanded at the Maximum Tolerated Dose (MTD).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A | Experimental | PXD101 administered as a 30-minute intravenous (IV) infusion of 1000 mg/m²/d for five consecutive days every 3 weeks. Idarubicin administered on day 5 (first steps) or days 4 and 5 (later steps). Patients will be treated in a 21-day cycle for a minimum of 2 cycles and a maximum of 6 cycles (depending on cumulated idarubicin dose). |
|
| Arm B | Experimental | PXD101 administered by continuous intravenous infusion over 24-48 hours and idarubicin (in the later steps) added after the first 24 hours. The second cycle will start on day 15 but under observation of possible toxicity. Further cycles will be administered q 14 d for up to 6 cycles. The first dose steps will be carried out with PXD101 alone for safety reasons. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PXD101 | Drug |
|
| |
| idarubicin |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Tolerated Dose, Dose Limiting Toxicity | DLT (dose limiting toxicities): patients with any of the toxicities: 1.Haematological toxicity is not included in the definition due to bone marrow involvement by the disease except for following grade 4 ANC (absolute neutrophil count) and PLT (platelet count) for 6 weeks with less than 5% blasts in bone marrow. 2.Drug related non hematological Grade 3 or 4 toxicity except alopecia, brief nausea and vomiting, diarrhea, rash, arthralgias and myalgias. Treatment interventions should palliate toxicity symptoms prior to concluding a DLT has occurred (e.g if nausea and vomiting to Grade 3 have been associated with the drug). If despite standard treatment Grade 3 nausea and or vomiting persisted then a DLT was considered to have occurred. Grade 4 diarrhea in spite of standard therapeutic measures was included in DLT definition. 3.Inability to tolerate full dosing cycle due to toxicity or any drug-related adverse event resulting in more than 14 day treatment delay in the next treatment cycle | First Cycle |
| Overall Response | Efficacy measured as Response rate (complete response ([CR] and Complete remission with incomplete recovery of platelets [CRi]) and partial response ([PR])) using the response criteria of the International Working Group (Cheson et al 2003). CR includes CRi, CRc (Cytogenetic complete remission), and CRm (Molecular complete remission). | Throughout study, after each cycle for the first two cycles, then after every second cycle |
| Measure | Description | Time Frame |
|---|---|---|
| Time to Response (CR and PR) | Time to response: time in weeks from first treatment to obtainment of the particular response status (CR and PR) | Throughout study, after each cycle for the first two cycles, then after every second cycle |
| Duration of Response (CR and PR) |
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Inclusion Criteria: (abbreviated)
Signed consent
AML patients:
Performance status (ECOG) ≤ 2
Age ≥ 18 years
Acceptable liver, renal and bone marrow function as defined
Serum potassium within normal range.
Acceptable coagulation status as defined
Precautions for female patients with reproductive potential as defined
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| e-mail contact via enquiries@topotarget.com | Valerio Therapeutics | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CHU Lapeyronie | Montpellier | 34295 | France | |||
| Hôpital St. Louis |
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm A, Step 1 | PXD101 (belinostat) 1000 mg/m²/d for 5 consecutive days every 3 weeks. On day 5, Idarubicin 5 mg/m² |
| FG001 | Arm A, Step 2 | PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On day 5, Idarubicin 10 mg/m² |
| FG002 | Arm A, Step 3 | PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On days 4 and 5, Idarubicin 7.5 mg/m²/d |
| FG003 | Arm A, Step 4 | PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On days 4 and 5, Idarubicin 10 mg/m²/d |
| FG004 | Arm B, Steps 1-6 | PXD101 administered by continuous intravenous infusion over 24-48 hours, doses 25 mg/m²/24 hours to 800 mg/m²/24 hours for 48 hours |
| FG005 | Arm B, Step 7 | PXD101 administered by continuous intravenous infusion over 48 hours, dose 1000 mg/m²/48 hours Idarubicin added at 5 mg/m² after 48 hours. Further cycles will be administered q 14 d for up to 6 cycles |
| FG006 | Arm B, Step 8 | PXD101 administered by continuous intravenous infusion over 48 hours, dose 1000 mg/m²/48 hours Idarubicin added at 5 mg/m² after 24 and 48 hours. Further cycles will be administered q 14 d for up to 6 cycles |
| FG007 | Arm B, Step 9 | PXD101 administered by continuous intravenous infusion over 48 hours, dose 1000 mg/m²/48 hours Idarubicin added at 7.5 mg/m² after 24 and 48 hours. Further cycles will be administered q 14 d for up to 6 cycles |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm A, Step 1 | PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On day 5, Idarubicin 5 mg/m² |
| BG001 | Arm A, Step 2 | PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On day 5, Idarubicin 10 mg/m² |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Maximum Tolerated Dose, Dose Limiting Toxicity | DLT (dose limiting toxicities): patients with any of the toxicities: 1.Haematological toxicity is not included in the definition due to bone marrow involvement by the disease except for following grade 4 ANC (absolute neutrophil count) and PLT (platelet count) for 6 weeks with less than 5% blasts in bone marrow. 2.Drug related non hematological Grade 3 or 4 toxicity except alopecia, brief nausea and vomiting, diarrhea, rash, arthralgias and myalgias. Treatment interventions should palliate toxicity symptoms prior to concluding a DLT has occurred (e.g if nausea and vomiting to Grade 3 have been associated with the drug). If despite standard treatment Grade 3 nausea and or vomiting persisted then a DLT was considered to have occurred. Grade 4 diarrhea in spite of standard therapeutic measures was included in DLT definition. 3.Inability to tolerate full dosing cycle due to toxicity or any drug-related adverse event resulting in more than 14 day treatment delay in the next treatment cycle | Posted | Number | participants | First Cycle |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm A, Step 1 | PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On day 5, Idarubicin 5 mg/m² |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | Meddra | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (10.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| PRS Admnistrator Gunilla Emanuelson | Topotarget A/S | +45 39 17 83 92 | enquiries@topotarget.com |
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| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| C487081 | belinostat |
| D015255 | Idarubicin |
| ID | Term |
|---|---|
| D003630 | Daunorubicin |
| D018943 | Anthracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
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| Drug |
|
|
Duration of Response (CR and PR) in Weeks |
| Throughout study, after each cycle for the first two cycles, then after every second cycle |
| Overall Survival | Overall survival: time in weeks from entry into study until death from any cause. All patients without this endpoint at the time of discontinuation or the end of trial have been censored. | Throughout study, after each cycle for the first two cycles, then after every second cycle |
| Relapse-Free Survival | Relapse-free survival: time (weeks) from leukemia-free state to relapse or death from any cause. | Throughout study, after each cycle for the first two cycles, then after every second cycle |
| Event-Free Survival | Event-free survival: time (weeks) from entry into study until treatment failure, disease relapse or death from any cause. | Throughout study, after each cycle for the first two cycles, then after every second cycle |
| Remission Duration | Remission duration: time (weeks) from date of remission status to disease relapse. | Throughout study, after each cycle for the first two cycles, then after every second cycle |
| Belinostat Cmax | Cmax: Arm A: at Cycle 1 Day 4, Cycle 1 Day 5 Arm B: Cycle 1 Day 1 and Cycle 1 Day 2 | Samples taken in Cycle 1 only, prior to initial dose on days 4 and 5 and at end of infusion, 5, 15, and 30 min, and 1, 2, 3, 4, and 6 hours post infusion |
| Belinostat AUC (Area Under Curve) | Cycle 1, prior to initial dose on days 4 and 5 and at end of infusion, 5, 15, and 30 min, and 1, 2, 3, 4, and 6 hours post infusion |
| Elimination t½ | Cycle 1, Samples taken in Cycle 1 only, prior to initial dose on days 4 and 5 and at end of infusion, 5, 15, and 30 min, and 1, 2, 3, 4, and 6 hours post infusion |
| Paris |
| 75475 |
| France |
| Uniklinik Homburg | Homburg | 66424 | Germany |
| Uni Hospital Marburg | Marburg | 35043 | Germany |
| Universitätsklinikum Ulm | Ulm | 89081 | Germany |
| Christie Hospital NHS Trust | Manchester | M20 4BX | United Kingdom |
| Death |
|
| Adverse Event |
|
| Withdrawal by Subject |
|
| Relapse |
|
| BG002 | Arm A, Step 3 | PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On days 4 and 5, Idarubicin 7.5 mg/m²/d |
| BG003 | Arm A, Step 4 | PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On days 4 and 5, Idarubicin 10 mg/m²/d |
| BG004 | Arm B, Steps 1-6 | PXD101 administered by continuous intravenous infusion over 24-48 hours, doses 25 mg/m²/24 hours to 800 mg/m²/24 hours for 48 hours |
| BG005 | Arm B, Step 7 | PXD101 administered by continuous intravenous infusion over 48 hours, dose 1000 mg/m²/48 hours Idarubicin added at 5 mg/m² after 48 hours. Further cycles will be administered q 14 d for up to 6 cycles |
| BG006 | Arm B, Step 8 | PXD101 administered by continuous intravenous infusion over 48 hours, dose 1000 mg/m²/48 hours Idarubicin added at 5 mg/m² after 24 and 48 hours. Further cycles will be administered q 14 d for up to 6 cycles |
| BG007 | Arm B, Step 9 | PXD101 administered by continuous intravenous infusion over 48 hours, dose 1000 mg/m²/48 hours Idarubicin added at 7.5 mg/m² after 24 and 48 hours. Further cycles will be administered q 14 d for up to 6 cycles |
| BG008 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Arm A, Step 1 |
PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On day 5, Idarubicin 5 mg/m² |
| OG001 | Arm A, Step 2 | PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On day 5, Idarubicin 10 mg/m² |
| OG002 | Arm A, Step 3 | PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On days 4 and 5, Idarubicin 7.5 mg/m²/d |
| OG003 | Arm A, Step 4 | PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On days 4 and 5, Idarubicin 10 mg/m²/d |
| OG004 | Arm B, Steps 1-6 | PXD101 administered by continuous intravenous infusion over 24-48 hours, doses 25 mg/m²/24 hours to 800 mg/m²/24 hours for 48 hours |
| OG005 | Arm B, Step 7 | PXD101 administered by continuous intravenous infusion over 48 hours, dose 1000 mg/m²/48 hours Idarubicin added at 5 mg/m² after 48 hours. Further cycles will be administered q 14 d for up to 6 cycles |
| OG006 | Arm B, Step 8 | PXD101 administered by continuous intravenous infusion over 48 hours, dose 1000 mg/m²/48 hours Idarubicin added at 5 mg/m² after 24 and 48 hours. Further cycles will be administered q 14 d for up to 6 cycles |
| OG007 | Arm B, Step 9 | PXD101 administered by continuous intravenous infusion over 48 hours, dose 1000 mg/m²/48 hours Idarubicin added at 7.5 mg/m² after 24 and 48 hours. Further cycles will be administered q 14 d for up to 6 cycles |
|
|
| Primary | Overall Response | Efficacy measured as Response rate (complete response ([CR] and Complete remission with incomplete recovery of platelets [CRi]) and partial response ([PR])) using the response criteria of the International Working Group (Cheson et al 2003). CR includes CRi, CRc (Cytogenetic complete remission), and CRm (Molecular complete remission). | Posted | Number | participants | Throughout study, after each cycle for the first two cycles, then after every second cycle |
|
|
|
| Secondary | Time to Response (CR and PR) | Time to response: time in weeks from first treatment to obtainment of the particular response status (CR and PR) | Time to response was reported among participants who reported response | Posted | Median | 95% Confidence Interval | Weeks | Throughout study, after each cycle for the first two cycles, then after every second cycle |
|
|
|
| Secondary | Duration of Response (CR and PR) | Duration of Response (CR and PR) in Weeks | All patients who received at least one dose of belinostat and/or idarubicin were included in the full analysis set (FAS). Duration of response was reported among participants who reported response | Posted | Mean | Full Range | weeks | Throughout study, after each cycle for the first two cycles, then after every second cycle |
|
|
|
| Secondary | Overall Survival | Overall survival: time in weeks from entry into study until death from any cause. All patients without this endpoint at the time of discontinuation or the end of trial have been censored. | Posted | Median | 95% Confidence Interval | Weeks | Throughout study, after each cycle for the first two cycles, then after every second cycle |
|
|
|
| Secondary | Relapse-Free Survival | Relapse-free survival: time (weeks) from leukemia-free state to relapse or death from any cause. | Relapse free survival was reported among participants who reported response | Posted | Number | Weeks | Throughout study, after each cycle for the first two cycles, then after every second cycle |
|
|
|
| Secondary | Event-Free Survival | Event-free survival: time (weeks) from entry into study until treatment failure, disease relapse or death from any cause. | Posted | Median | 95% Confidence Interval | Weeks | Throughout study, after each cycle for the first two cycles, then after every second cycle |
|
|
|
| Secondary | Remission Duration | Remission duration: time (weeks) from date of remission status to disease relapse. | Remission duration was reported among participants who reported response | Posted | Mean | 95% Confidence Interval | Weeks | Throughout study, after each cycle for the first two cycles, then after every second cycle |
|
|
|
| Secondary | Belinostat Cmax | Cmax: Arm A: at Cycle 1 Day 4, Cycle 1 Day 5 Arm B: Cycle 1 Day 1 and Cycle 1 Day 2 | Results shown for dose level 1000 mg/m2/d | Posted | Mean | Standard Deviation | ng/mL | Samples taken in Cycle 1 only, prior to initial dose on days 4 and 5 and at end of infusion, 5, 15, and 30 min, and 1, 2, 3, 4, and 6 hours post infusion |
|
|
|
| Secondary | Belinostat AUC (Area Under Curve) | Results shown for dose level 1000 mg/m2/d | Posted | Mean | Standard Deviation | ng*hrs/mL | Cycle 1, prior to initial dose on days 4 and 5 and at end of infusion, 5, 15, and 30 min, and 1, 2, 3, 4, and 6 hours post infusion |
|
|
|
| Secondary | Elimination t½ | Results shown for dose level 1000 mg/m2/d | Posted | Mean | Standard Deviation | Hours | Cycle 1, Samples taken in Cycle 1 only, prior to initial dose on days 4 and 5 and at end of infusion, 5, 15, and 30 min, and 1, 2, 3, 4, and 6 hours post infusion |
|
|
|
| 2 |
| 3 |
| 3 |
| 3 |
| EG001 | Arm A, Step 2 | PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On day 5, Idarubicin 10 mg/m² | 2 | 3 | 3 | 3 |
| EG002 | Arm A, Step 3 | PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On days 4 and 5, Idarubicin 7.5 mg/m²/d | 2 | 3 | 3 | 3 |
| EG003 | Arm A, Step 4 | PXD101 1000 mg/m²/d for 5 consecutive days every 3 weeks. On days 4 and 5, Idarubicin 10 mg/m²/d | 7 | 9 | 9 | 9 |
| EG004 | Arm B, Steps 1-6 | PXD101 administered by continuous intravenous infusion over 24-48 hours, doses 25 mg/m²/24 hours to 800 mg/m²/24 hours for 48 hours | 2 | 7 | 6 | 7 |
| EG005 | Arm B, Step 7 | PXD101 administered by continuous intravenous infusion over 48 hours, dose 1000 mg/m²/48 hours Idarubicin added at 5 mg/m² after 48 hours. Further cycles will be administered q 14 d for up to 6 cycles | 2 | 3 | 3 | 3 |
| EG006 | Arm B, Step 8 | PXD101 administered by continuous intravenous infusion over 48 hours, dose 1000 mg/m²/48 hours Idarubicin added at 5 mg/m² after 24 and 48 hours. Further cycles will be administered q 14 d for up to 6 cycles | 6 | 6 | 6 | 6 |
| EG007 | Arm B, Step 9 | PXD101 administered by continuous intravenous infusion over 48 hours, dose 1000 mg/m²/48 hours Idarubicin added at 7.5 mg/m² after 24 and 48 hours. Further cycles will be administered q 14 d for up to 6 cycles | 6 | 7 | 7 | 7 |
| Febrile bone marrow aplasia | Blood and lymphatic system disorders | Meddra | Systematic Assessment |
|
| Febrile neutropenia | Blood and lymphatic system disorders | Meddra | Systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | Meddra | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | Meddra | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | Meddra | Systematic Assessment |
|
| Ascites | Gastrointestinal disorders | Meddra | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | Meddra | Systematic Assessment |
|
| Pyrexia | General disorders | Meddra | Systematic Assessment |
|
| Anal infection | Infections and infestations | Meddra | Systematic Assessment |
|
| Bacterial infection | Infections and infestations | Meddra | Systematic Assessment |
|
| Central line infection | Infections and infestations | Meddra | Systematic Assessment |
|
| Clostridium bacteraemia | Infections and infestations | Meddra | Systematic Assessment |
|
| Clostridium difficile colitis | Infections and infestations | Meddra | Systematic Assessment |
|
| Enteritis infectious | Infections and infestations | Meddra | Systematic Assessment |
|
| Enterobacter bacteraemia | Infections and infestations | Meddra | Systematic Assessment |
|
| Enterococcal bacteriaemia | Infections and infestations | Meddra | Systematic Assessment |
|
| Fungal infection | Infections and infestations | Meddra | Systematic Assessment |
|
| Paronychia | Infections and infestations | Meddra | Systematic Assessment |
|
| Pneumonia | Infections and infestations | Meddra | Systematic Assessment |
|
| Pseudomonas infection | Infections and infestations | Meddra | Systematic Assessment |
|
| Pulmonary mycosis | Infections and infestations | Meddra | Systematic Assessment |
|
| Sepsis | Infections and infestations | Meddra | Systematic Assessment |
|
| Soft tissue infection | Infections and infestations | Meddra | Systematic Assessment |
|
| Lumbar vertebral fracture | Injury, poisoning and procedural complications | Meddra | Systematic Assessment |
|
| Splenic rupture | Injury, poisoning and procedural complications | Meddra | Systematic Assessment |
|
| Blood creatinine increased | Investigations | Meddra | Systematic Assessment |
|
| Electrocardiogram QT prolonged | Investigations | Meddra | Systematic Assessment |
|
| Hypocalcaemia | Metabolism and nutrition disorders | Meddra | Systematic Assessment |
|
| Tumor lysis syndrome | Metabolism and nutrition disorders | Meddra | Systematic Assessment |
|
| Polyneuropathy | Nervous system disorders | Meddra | Systematic Assessment |
|
| Renal failure | Renal and urinary disorders | Meddra | Systematic Assessment |
|
| Lung disorder | Respiratory, thoracic and mediastinal disorders | Meddra | Systematic Assessment |
|
| Lung infiltration | Respiratory, thoracic and mediastinal disorders | Meddra | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | Meddra | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | Meddra | Systematic Assessment |
|
| Coagulopathy | Blood and lymphatic system disorders | Meddra | Systematic Assessment |
|
| Erythropenia | Blood and lymphatic system disorders | Meddra | Systematic Assessment |
|
| Febrile Bone Marrow Aplasia | Blood and lymphatic system disorders | Meddra | Systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | Meddra | Systematic Assessment |
|
| Lymphadenopathy | Blood and lymphatic system disorders | Meddra | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | Meddra | Systematic Assessment |
|
| Splenomegaly | Blood and lymphatic system disorders | Meddra | Systematic Assessment |
|
| Spontaneous Hematoma | Blood and lymphatic system disorders | Meddra | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | Meddra | Systematic Assessment |
|
| Thrombotic Microangiopathy | Blood and lymphatic system disorders | Meddra | Systematic Assessment |
|
| Cardiac Disorder | Cardiac disorders | Meddra | Systematic Assessment |
|
| Conduction Disorder | Cardiac disorders | Meddra | Systematic Assessment |
|
| Extrasystoles | Cardiac disorders | Meddra | Systematic Assessment |
|
| Left ventricular dysfunction | Cardiac disorders | Meddra | Systematic Assessment |
|
| Myocardial Ischaemia | Cardiac disorders | Meddra | Systematic Assessment |
|
| Supraventricular extrasystoles | Cardiac disorders | Meddra | Systematic Assessment |
|
| Antithrombin Iii Deficiency | Congenital, familial and genetic disorders | Meddra | Systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | Meddra | Systematic Assessment |
|
| Diplopia | Eye disorders | Meddra | Systematic Assessment |
|
| Dry eye | Eye disorders | Meddra | Systematic Assessment |
|
| Lacrimation increased | Eye disorders | Meddra | Systematic Assessment |
|
| Macular Degeneration | Eye disorders | Meddra | Systematic Assessment |
|
| Retinal Haemorrhage | Eye disorders | Meddra | Systematic Assessment |
|
| Vision Blurred | Eye disorders | Meddra | Systematic Assessment |
|
| Visual Impairment | Eye disorders | Meddra | Systematic Assessment |
|
| Vitreous Detachment | Eye disorders | Meddra | Systematic Assessment |
|
| Abdominal Pain | Gastrointestinal disorders | Meddra | Systematic Assessment |
|
| Abdominal Pain Upper | Gastrointestinal disorders | Meddra | Systematic Assessment |
|
| Anal Fissure | Gastrointestinal disorders | Meddra | Systematic Assessment |
|
| Anal Haemorrhage | Gastrointestinal disorders | Meddra | Systematic Assessment |
|
| Aphthous Stomatitis | Gastrointestinal disorders | Meddra | Systematic Assessment |
|
| Ascites | Gastrointestinal disorders | Meddra | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | Meddra | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | Meddra | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | Meddra | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | Meddra | Systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | Meddra | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | Meddra | Systematic Assessment |
|
| Gastrooesophageal Reflux Disease | Gastrointestinal disorders | Meddra | Systematic Assessment |
|
| Haemorrhoids | Gastrointestinal disorders | MedDRA (10.0) | Systematic Assessment |
|
| Inguinal Hernia | Gastrointestinal disorders | Meddra | Systematic Assessment |
|
| Intestinal Haemorrhage | Gastrointestinal disorders | Meddra | Systematic Assessment |
|
| Mouth Haemorrhage | Gastrointestinal disorders | Meddra | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Meddra | Systematic Assessment |
|
| Proctalgia | Gastrointestinal disorders | Meddra | Systematic Assessment |
|
| Tongue Blistering | Gastrointestinal disorders | Meddra | Systematic Assessment |
|
| Tongue Discolouration | Gastrointestinal disorders | Meddra | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | Meddra | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | Meddra | Systematic Assessment |
|
| Asthenia | General disorders | Meddra | Systematic Assessment |
|
| Catheter Site Erythema | General disorders | Meddra | Systematic Assessment |
|
| Catheter Site Inflammation | General disorders | Meddra | Systematic Assessment |
|
| Catheter Site Related Reaction | General disorders | Meddra | Systematic Assessment |
|
| Chest Pain | General disorders | Meddra | Systematic Assessment |
|
| Chills | General disorders | Meddra | Systematic Assessment |
|
| Face Oedema | General disorders | Meddra | Systematic Assessment |
|
| Fatigue | General disorders | Meddra | Systematic Assessment |
|
| Feeling Cold | General disorders | Meddra | Systematic Assessment |
|
| General Physical Health Deterioration | General disorders | Meddra | Systematic Assessment |
|
| Generalised Oedema | General disorders | Meddra | Systematic Assessment |
|
| Inflammation | General disorders | Meddra | Systematic Assessment |
|
| Influenza Like Illness | General disorders | Meddra | Systematic Assessment |
|
| Infusion Site Pain | General disorders | Meddra | Systematic Assessment |
|
| Injection Site Reaction | General disorders | Meddra | Systematic Assessment |
|
| Localised Oedema | General disorders | Meddra | Systematic Assessment |
|
| Malaise | General disorders | Meddra | Systematic Assessment |
|
| Mucosal Inflammation | General disorders | Meddra | Systematic Assessment |
|
| Nodule | General disorders | Meddra | Systematic Assessment |
|
| Oedema Peripheral | General disorders | Meddra | Systematic Assessment |
|
| Pyrexia | General disorders | Meddra | Systematic Assessment |
|
| Visceral Oedema | General disorders | Meddra | Systematic Assessment |
|
| Jaundice | Hepatobiliary disorders | Meddra | Systematic Assessment |
|
| Anal Infection | Infections and infestations | Meddra | Systematic Assessment |
|
| Bacterial Infection | Infections and infestations | Meddra | Systematic Assessment |
|
| Bronchopulmonary Aspergillosis | Infections and infestations | Meddra | Systematic Assessment |
|
| Central Line Infection | Infections and infestations | Meddra | Systematic Assessment |
|
| Clostridium Bacteriaemia | Infections and infestations | Meddra | Systematic Assessment |
|
| Clostridium Difficilie Colitis | Infections and infestations | Meddra | Systematic Assessment |
|
| Enteritis Infectious | Infections and infestations | Meddra | Systematic Assessment |
|
| Enterobacter Bacteriaemia | Infections and infestations | MedDRA (10.0) | Systematic Assessment |
|
| Enterococcal Bacteriaemia | Infections and infestations | Meddra | Systematic Assessment |
|
| Enterocolitis Infectious | Infections and infestations | Meddra | Systematic Assessment |
|
| Fungal Infection | Infections and infestations | Meddra | Systematic Assessment |
|
| Fungal Skin Infection | Infections and infestations | Meddra | Systematic Assessment |
|
| Herpes Simplex | Infections and infestations | Meddra | Systematic Assessment |
|
| Impetigo | Infections and infestations | Meddra | Systematic Assessment |
|
| Infection | Infections and infestations | Meddra | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | Meddra | Systematic Assessment |
|
| Oral Fungal Infection | Infections and infestations | Meddra | Systematic Assessment |
|
| Oral Herpes | Infections and infestations | Meddra | Systematic Assessment |
|
| Paronychia | Infections and infestations | Meddra | Systematic Assessment |
|
| Pneumonia | Infections and infestations | Meddra | Systematic Assessment |
|
| Pseudomonas Infection | Infections and infestations | Meddra | Systematic Assessment |
|
| Pulmonary Mycosis | Infections and infestations | Meddra | Systematic Assessment |
|
| Puncture Site Infection | Infections and infestations | Meddra | Systematic Assessment |
|
| Sepsis | Infections and infestations | Meddra | Systematic Assessment |
|
| Soft Tissue Infection | Infections and infestations | Meddra | Systematic Assessment |
|
| Tonsillitis | Infections and infestations | Meddra | Systematic Assessment |
|
| Upper Respiratory Tract Infection | Infections and infestations | Meddra | Systematic Assessment |
|
| Allergic Transfusion Reaction | Injury, poisoning and procedural complications | Meddra | Systematic Assessment |
|
| Lumbar Vertebral Fracture | Injury, poisoning and procedural complications | Meddra | Systematic Assessment |
|
| Muscle Rupture | Injury, poisoning and procedural complications | Meddra | Systematic Assessment |
|
| Postoperative thrombosis | Injury, poisoning and procedural complications | Meddra | Systematic Assessment |
|
| Procedural Pain | Injury, poisoning and procedural complications | Meddra | Systematic Assessment |
|
| Splenic Rupture | Injury, poisoning and procedural complications | Meddra | Systematic Assessment |
|
| Traumatic Haematoma | Injury, poisoning and procedural complications | Meddra | Systematic Assessment |
|
| Wound Complication | Injury, poisoning and procedural complications | Meddra | Systematic Assessment |
|
| Alanine Aminotransferase Increased | Investigations | Meddra | Systematic Assessment |
|
| Aspartate Aminotransferase Increased | Investigations | Meddra | Systematic Assessment |
|
| Blood Bilirubin Increased | Investigations | Meddra | Systematic Assessment |
|
| Blood Cholesterol Increased | Investigations | Meddra | Systematic Assessment |
|
| Blood Creatinine Increased | Investigations | Meddra | Systematic Assessment |
|
| Blood Potassium Decreased | Investigations | Meddra | Systematic Assessment |
|
| Body Temperature Increased | Investigations | Meddra | Systematic Assessment |
|
| Central Venous Pressure Increased | Investigations | Meddra | Systematic Assessment |
|
| Electrocardiogram Qt Prolonged | Investigations | Meddra | Systematic Assessment |
|
| Gamma-Glutamyltransferase Increased | Investigations | Meddra | Systematic Assessment |
|
| Haemoglobin Decreased | Investigations | Meddra | Systematic Assessment |
|
| Heart Rate Increased | Investigations | Meddra | Systematic Assessment |
|
| International Normalised Ratio Increased | Investigations | MedDRA (10.0) | Systematic Assessment |
|
| Ph Urine Deacreased | Investigations | Meddra | Systematic Assessment |
|
| Platelet Count Decreased | Investigations | Meddra | Systematic Assessment |
|
| Troponin T | Investigations | Meddra | Systematic Assessment |
|
| Weight Decreased | Investigations | Meddra | Systematic Assessment |
|
| Weight Increased | Investigations | Meddra | Systematic Assessment |
|
| White Blood Cell Count Decreased | Investigations | Meddra | Systematic Assessment |
|
| Decreased Appetite | Metabolism and nutrition disorders | Meddra | Systematic Assessment |
|
| Hyperkalaemia | Metabolism and nutrition disorders | Meddra | Systematic Assessment |
|
| Hypernatraemia | Metabolism and nutrition disorders | Meddra | Systematic Assessment |
|
| Hyperuricaemia | Metabolism and nutrition disorders | Meddra | Systematic Assessment |
|
| Hypoalbuminaemia | Metabolism and nutrition disorders | Meddra | Systematic Assessment |
|
| Hypocalcaemia | Metabolism and nutrition disorders | Meddra | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | Meddra | Systematic Assessment |
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| Hypomagnesaemia | Metabolism and nutrition disorders | Meddra | Systematic Assessment |
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| Hyponatraemia | Metabolism and nutrition disorders | Meddra | Systematic Assessment |
|
| Hypophosphataemia | Metabolism and nutrition disorders | Meddra | Systematic Assessment |
|
| Malnutrition | Metabolism and nutrition disorders | Meddra | Systematic Assessment |
|
| Tumour Lysis Syndrome | Metabolism and nutrition disorders | Meddra | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | Meddra | Systematic Assessment |
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| Back Pain | Musculoskeletal and connective tissue disorders | Meddra | Systematic Assessment |
|
| Bone Pain | Musculoskeletal and connective tissue disorders | Meddra | Systematic Assessment |
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| Joint Swelling | Musculoskeletal and connective tissue disorders | Meddra | Systematic Assessment |
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| Muscle Spasms | Musculoskeletal and connective tissue disorders | Meddra | Systematic Assessment |
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| Muscular Weakness | Musculoskeletal and connective tissue disorders | Meddra | Systematic Assessment |
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| Musculoskeletal Chest Pain | Musculoskeletal and connective tissue disorders | Meddra | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | Meddra | Systematic Assessment |
|
| Neck Pain | Musculoskeletal and connective tissue disorders | Meddra | Systematic Assessment |
|
| Pain In Extremity | Musculoskeletal and connective tissue disorders | Meddra | Systematic Assessment |
|
| Dizziness | Nervous system disorders | Meddra | Systematic Assessment |
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| Dysgeusia | Nervous system disorders | Meddra | Systematic Assessment |
|
| Headache | Nervous system disorders | Meddra | Systematic Assessment |
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| Lethargy | Nervous system disorders | Meddra | Systematic Assessment |
|
| Movement Disorder | Nervous system disorders | Meddra | Systematic Assessment |
|
| Nystagmus | Nervous system disorders | Meddra | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | Meddra | Systematic Assessment |
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| Peripheral Sensory Neuropathy | Nervous system disorders | Meddra | Systematic Assessment |
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| Polyneuropathy | Nervous system disorders | Meddra | Systematic Assessment |
|
| Somnolence | Nervous system disorders | Meddra | Systematic Assessment |
|
| Syncope | Nervous system disorders | Meddra | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA (10.0) | Systematic Assessment |
|
| Confusional State | Psychiatric disorders | Meddra | Systematic Assessment |
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| Depression | Psychiatric disorders | Meddra | Systematic Assessment |
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| Insomnia | Psychiatric disorders | Meddra | Systematic Assessment |
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| Sleep Disorder | Psychiatric disorders | Meddra | Systematic Assessment |
|
| Chromaturia | Renal and urinary disorders | MedDRA (10.0) | Systematic Assessment |
|
| Nocturia | Renal and urinary disorders | Meddra | Systematic Assessment |
|
| Renal Failure | Renal and urinary disorders | Meddra | Systematic Assessment |
|
| Urethral Pain | Renal and urinary disorders | Meddra | Systematic Assessment |
|
| Urinary Retention | Renal and urinary disorders | Meddra | Systematic Assessment |
|
| Benign Prostatic Hyperplasia | Reproductive system and breast disorders | MedDRA (10.0) | Systematic Assessment |
|
| Acute Pulmonary Oedema | Respiratory, thoracic and mediastinal disorders | Meddra | Systematic Assessment |
|
| Bronchitis Chronic | Respiratory, thoracic and mediastinal disorders | Meddra | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | Meddra | Systematic Assessment |
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| Dysphonia | Respiratory, thoracic and mediastinal disorders | Meddra | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | Meddra | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | Meddra | Systematic Assessment |
|
| Hiccups | Respiratory, thoracic and mediastinal disorders | Meddra | Systematic Assessment |
|
| Lung Disorder | Respiratory, thoracic and mediastinal disorders | Meddra | Systematic Assessment |
|
| Lung Infiltration | Respiratory, thoracic and mediastinal disorders | Meddra | Systematic Assessment |
|
| Oropharyngeal Blistering | Respiratory, thoracic and mediastinal disorders | Meddra | Systematic Assessment |
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| Pleural Effusion | Respiratory, thoracic and mediastinal disorders | Meddra | Systematic Assessment |
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| Pulmonary Congestion | Respiratory, thoracic and mediastinal disorders | Meddra | Systematic Assessment |
|
| Pulmonary Oedema | Respiratory, thoracic and mediastinal disorders | Meddra | Systematic Assessment |
|
| Rhinitis Allergic | Respiratory, thoracic and mediastinal disorders | Meddra | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (10.0) | Systematic Assessment |
|
| Blood Blister | Skin and subcutaneous tissue disorders | Meddra | Systematic Assessment |
|
| Dry Skin | Skin and subcutaneous tissue disorders | Meddra | Systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | Meddra | Systematic Assessment |
|
| Night Sweats | Skin and subcutaneous tissue disorders | Meddra | Systematic Assessment |
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| Petechiae | Skin and subcutaneous tissue disorders | Meddra | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | Meddra | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | Meddra | Systematic Assessment |
|
| Denture Wearer | Social circumstances | Meddra | Systematic Assessment |
|
| Flushing | Vascular disorders | MedDRA (10.0) | Systematic Assessment |
|
| Hot Flush | Vascular disorders | Meddra | Systematic Assessment |
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| Hypertension | Vascular disorders | Meddra | Systematic Assessment |
|
| Hypotension | Vascular disorders | Meddra | Systematic Assessment |
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| Pallor | Vascular disorders | Meddra | Systematic Assessment |
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| Phlebitis | Vascular disorders | Meddra | Systematic Assessment |
|
| Thrombophlebitis | Vascular disorders | MedDRA (10.0) | Systematic Assessment |
|
| Febrile neutropenia | Blood and lymphatic system disorders | Meddra | Systematic Assessment |
|
| Sinus tachycardia | Cardiac disorders | Meddra | Systematic Assessment |
|
| Cystitis haemorrhagic | Renal and urinary disorders | Meddra | Systematic Assessment |
|
Not provided
| D006402 |
| Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006841 |
| Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |