Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2009-010866-49 | EudraCT Number |
Not provided
Not provided
Not provided
The trial has been terminated due to an estimated low probability of clinical benefit based on limited anti-leukemic effects observed in safety run-in (Part 1)
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This is an open-label, multi-center, dose-escalation trial of pimasertib (MSC1936369B) in blood and bone marrow cancers. The trial will be conducted in two parts:
Part 1 (safety run-in period): Will determine the maximum tolerated dose (MTD) of the study drug in subjects with advanced hematological malignancies.
Part 2: Will assess the anti-leukemic activity of the study drug in older subjects with newly diagnosed poor prognosis acute myeloid leukemia (AML) who are not candidates for intensive chemotherapy.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Regimen 1 (Part 1) | Experimental |
| |
| Regimen 2 (Part 1) | Experimental |
| |
| Regimen 3 (Part 1) | Experimental |
| |
| Regimen 1 (Part 2) | Experimental |
| |
| Regimen 2 (Part 2) | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pimasertib | Drug | Pimasertib will be administered orally at a dose of 8 mg twice daily (BID) on Days 1 to 5, 8 to 12, 15 to 19, and 22 to 26 of a 28-day cycle. The dose will be escalated to 15 mg BID, 23 mg BID, 30 mg BID, 42 mg BID, 60 mg BID, and 75 mg BID) until Maximum Tolerated Dose (MTD) is reached. The treatment will be continued until disease progression, intolerable toxicity, or Investigator/subject decision. |
| Measure | Description | Time Frame |
|---|---|---|
| Part 1: Number of Subjects With Dose Limiting Toxicities (DLTs) | The DLT was any toxicity that resulted in treatment delay for more than (>) 2 weeks due to treatment-related adverse effects, or any Grade greater than or equal to (>=) 3 non-hematological toxicity excluding Grade 4 asymptomatic increases in liver function tests reversible within 7 days in subjects with liver involvement, and Grade 3 asymptomatic increases in liver function tests reversible within 7 days for subjects without liver involvement, Grade 3 vomiting unless encountered and persistent for more than 3 days despite adequate and optimal therapy, and Grade 3 diarrhea unless encountered and persistent for more than 3 days despite adequate and optimal anti-diarrhea therapy at any DL and judged to be possibly or probably related to the trial treatment by the Investigator and/or the Sponsor. | Baseline Up to Day 29 of Cycle 1 |
| Part 2: Percentage of Subjects With Best Overall Response | The best overall response was to be reported as either of the following: (1) Morphologic complete remission (CR) = normalization of the peripheral blood absolute neutrophil count (PBANC) >1.0x10^9 per liter (/L), platelets >100x10^9 /L, bone marrow aspirate with less than or equal to (<=) 5 percent (%) blasts, no blasts with Auer rods (AML only). (2) Complete remission with incomplete blood count recovery (CRi) = Same as CR without normalization of PBANC and platelet count. (3) Partial remission (PR) = normalization of PBANC >1.0x10^9/L, platelets >100x10^9/L, and at least a 50% decrease in the percentage of marrow aspirate blasts to 5-25%, or marrow blasts less than (<) 5%. (4) Progressive disease (PD) = >50% increase in peripheral blood or bone marrow blasts. (5) Stable disease (SD) = subjects who failed to achieve CR, CRi or PR and without criteria for PD. | Day 29 of every 29-day cycle until progression reported between day of first subject randomized, September 2009, until cut-off date, December 2012 |
| Measure | Description | Time Frame |
|---|---|---|
| Part 1: Number of Subjects With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Permanent Treatment Discontinuation | An adverse event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs include both SAEs and non-SAEs. |
Not provided
Inclusion criteria:
Part 1:
Subjects with one of the following conditions:
Primary or secondary AML, pathologically confirmed according to World Health Organization (WHO) classification who meet at least one of the following conditions:
Subjects with myelodysplastic syndrome (MDS), International Prognostic Scoring System (IPSS) Int-2 or high risk who are resistant or intolerant to standard treatment and not candidates for transplantation
Subjects with relapsed or refractory multiple myeloma (MM), who have failed or are intolerant to at least two prior therapies including thalidomide, lenalidomide and bortezomib
Subjects with advanced myeloproliferative disorders (MPD) for whom no established treatment options are available
Subjects with acute lymphocytic leukemia (ALL), relapsed, refractory or intolerant to standard treatment and for whom no effective treatment options are available
Age greater than or equal to 18 years
Subjects have read and understood the Informed Consent Form and are willing and able to give informed consent. They fully understand requirements of the trial and are willing to comply with all trial visits and assessments
Subjects and their partners must be willing to avoid pregnancy during the trial and until 1 month after the last trial drug administration. Subjects must therefore be willing to use adequate contraception as approved by the Investigator, two barrier methods or one barrier method with spermicide or intrauterine device, 2 weeks before, during the trial and 1 month after. The use of hormonal contraceptives should be avoided due to a possible drug-drug interaction in female subjects of childbearing age
Part 2:
Subjects (male and female) with newly diagnosed primary or secondary AML pathologically confirmed according to WHO classification who have not been exposed to any prior therapy for AML with the exception of:
Subjects meet at least one of the following conditions:
Age greater than or equal to 75 years OR
Age greater than or equal to 60 and less than 75 years with at least one of the following poor prognostic factors:
Subjects have read and understood the Informed Consent Form and are willing and able to give informed consent. They fully understand requirements of the trial and are willing to comply with all trial visits and assessments
Subjects and their partners must be willing to avoid pregnancy during the trial and until 1 month after the last trial drug administration. Subjects must therefore be willing to use adequate contraception as approved by the Investigator such as two barrier methods or one barrier method with spermicide or intrauterine device, 2 weeks before, during the trial and 1 month after. The use of hormonal contraceptives should be avoided due to a possible drug-drug interaction in female subjects of childbearing age
Exclusion Criteria:
Part 1 and Part 2:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Medical responsible | Merck KGaA, Darmstadt, Germany | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Northwestern University | Chicago | Illinois | United States | |||
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins |
Enrolled: 116 screened for eligibility; 35 were excluded (mainly non-fulfillment of inclusion or exclusion). 81 subjects were randomized.
First/last subject (informed consent): September 2009/12 April 2012. Last subject completed : December 2012; Clinical data cut-off: December 2012.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Regimen 1 (Part 1) | Pimasertib was administered orally at a dose of 8 mg twice daily (BID) on Days 1 to 5, 8 to 12, 15 to 19, and 22 to 26 of a 28-day cycle. The dose was escalated to 15 mg BID, 23 mg BID, 30 mg BID, 42 mg BID, 60 mg BID, and 75 mg BID) until Maximum Tolerated Dose (MTD) was obtained. The treatment was continued until disease progression, intolerable toxicity, or Investigator/subject decision. |
| FG001 | Regimen 2 (Part 1) | Pimasertib was administered orally at a dose of 8 mg BID on Days 1 to 21 of a 28-day cycle. The dose was escalated to 15 mg BID, 23 mg BID, 30 mg BID, 42 mg BID, 45 mg BID, 60 mg BID, 75 mg BID, and 90 mg BID until MTD was obtained. The treatment was continued until disease progression, intolerable toxicity, or Investigator/subject decision. |
| FG002 | Regimen 3 (Part 1) | Pimasertib was administered orally at a dose of 60 mg BID on Days 1-28 of a 28-day cycle. The dose was escalated to 75 mg BID until MTD was obtained. The treatment was continued until disease progression, intolerable toxicity, or Investigator/subject decision. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Baseline analysis population included all the subjects who were treated with at least one administration of pimasertib.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Regimen 1 (Part 1) | Pimasertib was administered orally at a dose of 8 mg twice daily (BID) on Days 1 to 5, 8 to 12, 15 to 19, and 22 to 26 of a 28-day cycle. The dose was escalated to 15 mg BID, 23 mg BID, 30 mg BID, 42 mg BID, 60 mg BID, and 75 mg BID) until Maximum Tolerated Dose (MTD) was obtained. The treatment was continued until disease progression, intolerable toxicity, or Investigator/subject decision. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Number |
| 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 | Part 1: Number of Subjects With Dose Limiting Toxicities (DLTs) | The DLT was any toxicity that resulted in treatment delay for more than (>) 2 weeks due to treatment-related adverse effects, or any Grade greater than or equal to (>=) 3 non-hematological toxicity excluding Grade 4 asymptomatic increases in liver function tests reversible within 7 days in subjects with liver involvement, and Grade 3 asymptomatic increases in liver function tests reversible within 7 days for subjects without liver involvement, Grade 3 vomiting unless encountered and persistent for more than 3 days despite adequate and optimal therapy, and Grade 3 diarrhea unless encountered and persistent for more than 3 days despite adequate and optimal anti-diarrhea therapy at any DL and judged to be possibly or probably related to the trial treatment by the Investigator and/or the Sponsor. | The DLT analysis set included all subjects who received over 90 percent (%) administration of trial medication in Cycle 1 or showed a DLT. | Posted | Number | subjects | Baseline Up to Day 29 of Cycle 1 |
|
Up to 3 years
A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. SAEs and Other AEs (non-SAEs) were reported.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Regimen 1 (Part 1) | Pimasertib was administered orally at a dose of 8 mg twice daily (BID) on Days 1 to 5, 8 to 12, 15 to 19, and 22 to 26 of a 28-day cycle. The dose was escalated to 15 mg BID, 23 mg BID, 30 mg BID, 42 mg BID, 60 mg BID, and 75 mg BID) until Maximum Tolerated Dose (MTD) was obtained. The treatment was continued until disease progression, intolerable toxicity, or Investigator/subject decision. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA Version 15.1 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA Version 15.1 | Non-systematic Assessment |
The trial has been terminated due to an estimated low probability of clinical benefit based on limited anti-leukemic effects observed in safety run-in (Part 1).
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Merck KGaA Communication Center | Merck Serono, a division of Merck KGaA | +49-6151-72-5200 | service@merckgroup.com |
Not provided
| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| D019337 | Hematologic Neoplasms |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
Not provided
Not provided
| ID | Term |
|---|---|
| C550600 | N-(2,3-dihydroxypropyl)-1-((2-fluoro-4-iodophenyl)amino)isonicotinamide |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
|
| Pimasertib | Drug | Pimasertib will be administered orally at a dose of 8 mg BID on Days 1 to 21 of a 28-day cycle. The dose will be escalated to 15 mg BID, 23 mg BID, 30 mg BID, 42 mg BID, 45 mg BID, 60 mg BID, 75 mg BID, and 90 mg BID until MTD is reached. The treatment will be continued until disease progression, intolerable toxicity, or Investigator/subject decision. |
|
|
| Pimasertib | Drug | Pimasertib will be administered orally at a dose of 60 mg BID on Days 1-28 of a 28-day cycle. The dose escalation will proceed to 75 mg BID until MTD is reached. The treatment will be continued until disease progression, intolerable toxicity, or Investigator/subject decision. |
|
|
| Pimasertib | Drug | Pimasertib will be administered orally twice daily on Days 1 to 5, 8 to 12, 15 to 19, and 22 to 26 of a 28-day cycle. Dose will be determined by Part 1 of the trial (could be the MTD or lower dose level). The treatment will be continued until disease progression, intolerable toxicity, or Investigator/subject decision. |
|
|
| Pimasertib | Drug | Pimasertib will be administered orally twice daily on Days 1 to 21 of a 28-day cycle. Dose will be determined by Part 1 of the trial (could be the MTD or lower dose level). The treatment will be continued until disease progression, intolerable toxicity, or Investigator/subject decision. |
|
|
| Baseline up to 3 years |
| Part 1: Maximum Plasma Concentration (Cmax) of Pimasertib Single Dose | Predose 0.5, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, and 10.0 hours post-dose on Day 1 of cycle 1; Regimen 1, 2 and 3 |
| Part 1: Maximum Plasma Concentration (Cmax) of Pimasertib Multiple Dose | Pre dose 0.5, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, and 10.0 hours post dose in Cycle 1 on Day 19 to Day 21 (Regimen 1 and 2) or Day 26 (Regimen 3). |
| Part 1: Time to Reach Maximum Plasma Concentration (Tmax): Single Dose | Predose 0.5, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, and 10.0 hours post-dose on Day 1 of cycle 1; Regimen 1, 2 and 3 |
| Part 1: Time to Reach Maximum Plasma Concentration (Tmax): Multiple Dose | Pre dose 0.5, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, and 10.0 hours post dose in Cycle 1 on Day 19 to Day 21 (Regimen 1 and 2) or Day 26 (Regimen 3) |
| Part 1: Apparent Terminal Half-Life (t1/2) of Pimasertib: Single Dose | The apparent terminal half-life was defined as the time required for the plasma concentration of drug to decrease 50% in the final stage of its elimination. | Predose 0.5, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, and 10.0 hours post-dose on Day 1 of cycle 1; Regimen 1, 2 and 3 |
| Part 1: Apparent Terminal Half-Life (t1/2) of Pimasertib: Multiple Dose | The apparent terminal half-life was defined as the time required for the plasma concentration of drug to decrease 50% in the final stage of its elimination. | Pre dose 0.5, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, and 10.0 hours post dose in Cycle 1 on Day 19 to Day 21 (Regimen 1 and 2) or Day 26 (Regimen 3). |
| Part 1: Area Under Curve From Time Zero to Last Sampling Time at Which the Concentration is at or Above Lower Limit of Quantification (AUC0-t) of Pimasertib: Single Dose | Predose 0.5, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, and 10.0 hours post-dose on Day 1 of cycle 1; Regimen 1, 2 and 3 |
| Part 1: Area Under Curve From Time Zero to Last Sampling Time at Which the Concentration is at or Above Lower Limit of Quantification (AUC0-t) of Pimasertib: Multiple Dose | Pre dose 0.5, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, and 10.0 hours post dose in Cycle 1 on Day 19 to Day 21 (Regimen 1 and 2) or Day 26 (Regimen 3). |
| Part 1: Area Under Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Pimasertib: Single Dose | The AUC0-inf was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity. It is obtained from AUC0-t plus AUCt-infinity. | Predose 0.5, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, and 10.0 hours post-dose on Day 1 of cycle 1; Regimen 1, 2 and 3 |
| Part 1: Area Under Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Pimasertib: Multiple Dose | The AUC0-inf was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity. It is obtained from AUC0-t plus AUCt-infinity. | Pre dose 0.5, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, and 10.0 hours post dose in Cycle 1 on Day 19 to Day 21 (Regimen 1 and 2) or Day 26 (Regimen 3) |
| Part 1: Apparent Oral Clearance (CL/f) of Pimasertib: Single Dose | Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent clearance after oral dose (CL/f) is influenced by the fraction absorbed. Data for Pimasertib 75 mg arm was not available for all the regimens combined, thus reported as separate outcome measure and not included in this outcome. | Predose 0.5, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, and 10.0 hours post-dose on Day 1 of cycle 1; Regimen 1, 2 and 3 |
| Part 1: Apparent Oral Clearance (CL/f) of Pimasertib for Pimasertib 75 mg Reporting Arm: Single Dose | Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent clearance after oral dose (CL/f) is influenced by the fraction absorbed. | Predose 0.5, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, and 10.0 hours post-dose on Day 1 of cycle 1; Regimen 1, 2 and 3 |
| Part 1: Apparent Oral Clearance (CL/f) of Pimasertib: Multiple Dose | Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent clearance after oral dose (CL/f) is influenced by the fraction absorbed. | Pre dose 0.5, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, and 10.0 hours post dose in Cycle 1 on Day 19 to Day 21 (Regimen 1 and 2) or Day 26 (Regimen 3) |
| Part 1: Apparent Oral Volume of Distribution (Vz/f) of Pimasertib:Single Dose | Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. Apparent volume of distribution after oral dose (Vz/f) was influenced by the fraction absorbed. Data for Pimasertib 75 mg arm was not available for all the regimens combined, thus reported as separate outcome measure and not included in this outcome. | Predose 0.5, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, and 10.0 hours post-dose on Day 1 of cycle 1; Regimen 1, 2 and 3 |
| Part 1: Apparent Oral Volume of Distribution (Vz/f) of Pimasertib for Pimasertib 75 mg Reporting Arm:Single Dose | Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. Apparent volume of distribution after oral dose (Vz/f) was influenced by the fraction absorbed. | Predose 0.5, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, and 10.0 hours post-dose on Day 1 of cycle 1; Regimen 1, 2 and 3 |
| Part 1: Apparent Oral Volume of Distribution (Vz/f) of Pimasertib: Multiple Dose | Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. Apparent volume of distribution after oral dose (Vz/f) was influenced by the fraction absorbed. | Pre dose 0.5, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, and 10.0 hours post dose in Cycle 1 on Day 19 to Day 21 (Regimen 1 and 2) or Day 26 (Regimen 3) |
| Part 1: Percentage of Subjects With Best Overall Response | The best overall response was reported as either of the following: (1) Morphologic complete remission (CR) = normalization of the peripheral blood absolute neutrophil count (PBANC) >1.0x10^9 per liter (/L), platelets >100x10^9 /L, bone marrow aspirate with less than or equal to (<=) 5 percent (%) blasts, no blasts with Auer rods (AML only). (2) Complete remission with incomplete blood count recovery (CRi) = Same as CR without normalization of PBANC and platelet count. (3) Partial remission (PR) = normalization of PBANC >1.0x10^9/L, platelets >100x10^9/L, and at least a 50% decrease in the percentage of marrow aspirate blasts to 5-25%, or marrow blasts less than (<) 5%. (4) Progressive disease (PD) = >50% increase in peripheral blood or bone marrow blasts. (5) Stable disease (SD) = Subjects who failed to achieve CR, CRi or PR and without criteria for PD. | Day 29 of every alternate 29-day cycle until progression reported between day of first subject randomized, September 2009, until cut-off date, December 2012 |
| Part 2: Number of Subjects With TEAEs, Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Permanent Treatment Discontinuation | An adverse event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that results in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. | Up to 3 years |
| Baltimore |
| Maryland |
| United States |
| Beth Israel Deaconess Medical Center | Boston | Massachusetts | United States |
| Dana Farber Cancer Institute | Boston | Massachusetts | United States |
| University of Texas - MD Anderson Cancer Center | Houston | Texas | United States |
| Hospital Hotel Dieu, Service D'Hematologie | Nantes | Cedex | France |
| Hospital Edouard Herriot, Service d'Hematologie Clinique | Lyon | France |
| Hospital Saint Louis, Service des Maladies du Sang | Paris | France |
| CHU du Haut-Leveque, Service des Maladies du Sang Unite de Recherche Clinique | Pessac | France |
| BG001 | Regimen 2 (Part 1) | Pimasertib was administered orally at a dose of 8 mg BID on Days 1 to 21 of a 28-day cycle. The dose was escalated to 15 mg BID, 23 mg BID, 30 mg BID, 42 mg BID, 45 mg BID, 60 mg BID, 75 mg BID, and 90 mg BID until MTD was obtained. The treatment was continued until disease progression, intolerable toxicity, or Investigator/subject decision. |
| BG002 | Regimen 3 (Part 1) | Pimasertib was administered orally at a dose of 60 mg BID on Days 1-28 of a 28-day cycle. The dose was escalated to 75 mg BID until MTD was obtained. The treatment was continued until disease progression, intolerable toxicity, or Investigator/subject decision. |
| BG003 | Total | Total of all reporting groups |
| Subjects |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG000 |
| Regimen 1 (Part 1) |
Pimasertib was administered orally at a dose of 8 mg twice daily (BID) on Days 1 to 5, 8 to 12, 15 to 19, and 22 to 26 of a 28-day cycle. The dose was escalated to 15 mg BID, 23 mg BID, 30 mg BID, 42 mg BID, 60 mg BID, and 75 mg BID) until Maximum Tolerated Dose (MTD) was obtained. The treatment was continued until disease progression, intolerable toxicity, or Investigator/subject decision. |
| OG001 | Regimen 2 (Part 1) | Pimasertib was administered orally at a dose of 8 mg BID on Days 1 to 21 of a 28-day cycle. The dose was escalated to 15 mg BID, 23 mg BID, 30 mg BID, 42 mg BID, 45 mg BID, 60 mg BID, 75 mg BID, and 90 mg BID until MTD was obtained. The treatment was continued until disease progression, intolerable toxicity, or Investigator/subject decision. |
| OG002 | Regimen 3 (Part 1) | Pimasertib was administered orally at a dose of 60 mg BID on Days 1-28 of a 28-day cycle. The dose was escalated to 75 mg BID until MTD was obtained. The treatment was continued until disease progression, intolerable toxicity, or Investigator/subject decision. |
|
|
| Primary | Part 2: Percentage of Subjects With Best Overall Response | The best overall response was to be reported as either of the following: (1) Morphologic complete remission (CR) = normalization of the peripheral blood absolute neutrophil count (PBANC) >1.0x10^9 per liter (/L), platelets >100x10^9 /L, bone marrow aspirate with less than or equal to (<=) 5 percent (%) blasts, no blasts with Auer rods (AML only). (2) Complete remission with incomplete blood count recovery (CRi) = Same as CR without normalization of PBANC and platelet count. (3) Partial remission (PR) = normalization of PBANC >1.0x10^9/L, platelets >100x10^9/L, and at least a 50% decrease in the percentage of marrow aspirate blasts to 5-25%, or marrow blasts less than (<) 5%. (4) Progressive disease (PD) = >50% increase in peripheral blood or bone marrow blasts. (5) Stable disease (SD) = subjects who failed to achieve CR, CRi or PR and without criteria for PD. | Due to limited anti-leukemic effects observed in the safety run-in part decision was made not to conduct part 2 hence this outcome measure was not assessed. Effects observed in the safety run-in part decision was made not to conduct part 2 hence this outcome measure was not assessed. | Posted | Day 29 of every 29-day cycle until progression reported between day of first subject randomized, September 2009, until cut-off date, December 2012 |
|
|
| Secondary | Part 1: Number of Subjects With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Permanent Treatment Discontinuation | An adverse event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs include both SAEs and non-SAEs. | The safety analysis set included all the subjects who received at least one administration of the trial medication. | Posted | Number | Subjects | Baseline up to 3 years |
|
|
|
| Secondary | Part 1: Maximum Plasma Concentration (Cmax) of Pimasertib Single Dose | Pharmacokinetic analysis set included all the subjects who received at least 1 dose of trial medication and provided adequate PK samples per protocol. N (number of subject analyzed) signifies subjects evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram/milliliter | Predose 0.5, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, and 10.0 hours post-dose on Day 1 of cycle 1; Regimen 1, 2 and 3 |
|
|
|
| Secondary | Part 1: Maximum Plasma Concentration (Cmax) of Pimasertib Multiple Dose | Pharmacokinetic analysis set included all the subjects who received at least 1 dose of trial medication and provided adequate PK samples per protocol. N (number of subject analyzed) signifies subjects evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram/milliliter | Pre dose 0.5, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, and 10.0 hours post dose in Cycle 1 on Day 19 to Day 21 (Regimen 1 and 2) or Day 26 (Regimen 3). |
|
|
|
| Secondary | Part 1: Time to Reach Maximum Plasma Concentration (Tmax): Single Dose | Pharmacokinetic analysis set included all the subjects who received at least 1 dose of trial medication and provided pharmacokinetic samples per protocol. N (number of subject analyzed) signifies subjects evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour | Predose 0.5, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, and 10.0 hours post-dose on Day 1 of cycle 1; Regimen 1, 2 and 3 |
|
|
|
| Secondary | Part 1: Time to Reach Maximum Plasma Concentration (Tmax): Multiple Dose | Pharmacokinetic analysis set included all the subjects who received at least 1 dose of trial medication and provided pharmacokinetic samples per protocol. Number of subjects analysed refer to the subjects evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour | Pre dose 0.5, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, and 10.0 hours post dose in Cycle 1 on Day 19 to Day 21 (Regimen 1 and 2) or Day 26 (Regimen 3) |
|
|
|
| Secondary | Part 1: Apparent Terminal Half-Life (t1/2) of Pimasertib: Single Dose | The apparent terminal half-life was defined as the time required for the plasma concentration of drug to decrease 50% in the final stage of its elimination. | Pharmacokinetic analysis set included all the subjects who received at least 1 dose of trial medication and provided pharmacokinetic samples. N (number of subject analyzed) signifies subjects evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour | Predose 0.5, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, and 10.0 hours post-dose on Day 1 of cycle 1; Regimen 1, 2 and 3 |
|
|
|
| Secondary | Part 1: Apparent Terminal Half-Life (t1/2) of Pimasertib: Multiple Dose | The apparent terminal half-life was defined as the time required for the plasma concentration of drug to decrease 50% in the final stage of its elimination. | Pharmacokinetic analysis set included all the subjects who received at least 1 dose of trial medication and provided pharmacokinetic samples. N (number of subject analyzed) signifies subjects evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour | Pre dose 0.5, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, and 10.0 hours post dose in Cycle 1 on Day 19 to Day 21 (Regimen 1 and 2) or Day 26 (Regimen 3). |
|
|
|
| Secondary | Part 1: Area Under Curve From Time Zero to Last Sampling Time at Which the Concentration is at or Above Lower Limit of Quantification (AUC0-t) of Pimasertib: Single Dose | Pharmacokinetic analysis set included all the subjects who received at least 1 dose of trial medication and provided pharmacokinetic samples. N (number of subject analyzed) signifies subjects evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour*nanogram/milliliter | Predose 0.5, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, and 10.0 hours post-dose on Day 1 of cycle 1; Regimen 1, 2 and 3 |
|
|
|
| Secondary | Part 1: Area Under Curve From Time Zero to Last Sampling Time at Which the Concentration is at or Above Lower Limit of Quantification (AUC0-t) of Pimasertib: Multiple Dose | Pharmacokinetic analysis set included all the subjects who received at least 1 dose of trial medication and provided pharmacokinetic samples. '"n" =Subjects evaluable for this outcome measure for specified categories for each reporting group, respectively. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour*nanogram/milliliter | Pre dose 0.5, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, and 10.0 hours post dose in Cycle 1 on Day 19 to Day 21 (Regimen 1 and 2) or Day 26 (Regimen 3). |
|
|
|
| Secondary | Part 1: Area Under Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Pimasertib: Single Dose | The AUC0-inf was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity. It is obtained from AUC0-t plus AUCt-infinity. | Pharmacokinetic analysis set included all the subjects who received at least 1 dose of trial medication and provided pharmacokinetic samples. 'N'(number of subjects analyzed)=subjects evaluable for this measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour*nanogram/milliliter | Predose 0.5, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, and 10.0 hours post-dose on Day 1 of cycle 1; Regimen 1, 2 and 3 |
|
|
|
| Secondary | Part 1: Area Under Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Pimasertib: Multiple Dose | The AUC0-inf was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity. It is obtained from AUC0-t plus AUCt-infinity. | Pharmacokinetic analysis set included all the subjects who received at least 1 dose of trial medication and provided pharmacokinetic samples. N (number of subject analyzed) signifies subjects evaluable for this outcome measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour*nanogram/milliliter | Pre dose 0.5, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, and 10.0 hours post dose in Cycle 1 on Day 19 to Day 21 (Regimen 1 and 2) or Day 26 (Regimen 3) |
|
|
|
| Secondary | Part 1: Apparent Oral Clearance (CL/f) of Pimasertib: Single Dose | Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent clearance after oral dose (CL/f) is influenced by the fraction absorbed. Data for Pimasertib 75 mg arm was not available for all the regimens combined, thus reported as separate outcome measure and not included in this outcome. | Pharmacokinetic analysis set included all the subjects who received at least 1 dose of trial medication and provided pharmacokinetic samples. 'N'(number of subjects analyzed)=subjects evaluable for this measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | liter/hour | Predose 0.5, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, and 10.0 hours post-dose on Day 1 of cycle 1; Regimen 1, 2 and 3 |
|
|
|
| Secondary | Part 1: Apparent Oral Clearance (CL/f) of Pimasertib for Pimasertib 75 mg Reporting Arm: Single Dose | Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent clearance after oral dose (CL/f) is influenced by the fraction absorbed. | Pharmacokinetic analysis set included all the subjects who received at least 1 dose of trial medication and provided pharmacokinetic samples. 'N'(number of subjects analyzed)=subjects evaluable for this measure and "n" = subjects evaluable for the specified regimen. | Posted | Mean | Standard Deviation | liter/hour | Predose 0.5, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, and 10.0 hours post-dose on Day 1 of cycle 1; Regimen 1, 2 and 3 |
|
|
|
| Secondary | Part 1: Apparent Oral Clearance (CL/f) of Pimasertib: Multiple Dose | Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent clearance after oral dose (CL/f) is influenced by the fraction absorbed. | Pharmacokinetic analysis set included all the subjects who received at least 1 dose of trial medication and provided pharmacokinetic samples. 'N'(number of subjects analyzed)=subjects evaluable for this measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | liter/hour | Pre dose 0.5, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, and 10.0 hours post dose in Cycle 1 on Day 19 to Day 21 (Regimen 1 and 2) or Day 26 (Regimen 3) |
|
|
|
| Secondary | Part 1: Apparent Oral Volume of Distribution (Vz/f) of Pimasertib:Single Dose | Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. Apparent volume of distribution after oral dose (Vz/f) was influenced by the fraction absorbed. Data for Pimasertib 75 mg arm was not available for all the regimens combined, thus reported as separate outcome measure and not included in this outcome. | Pharmacokinetic analysis set included all the subjects who received at least 1 dose of trial medication and provided pharmacokinetic samples. 'N'(number of subjects analyzed)=subjects evaluable for this measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | liter | Predose 0.5, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, and 10.0 hours post-dose on Day 1 of cycle 1; Regimen 1, 2 and 3 |
|
|
|
| Secondary | Part 1: Apparent Oral Volume of Distribution (Vz/f) of Pimasertib for Pimasertib 75 mg Reporting Arm:Single Dose | Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. Apparent volume of distribution after oral dose (Vz/f) was influenced by the fraction absorbed. | Pharmacokinetic analysis set included all the subjects who received at least 1 dose of trial medication and provided pharmacokinetic samples. 'N'(number of subjects analyzed)=subjects evaluable for this measure and "n" = subjects evaluable for the specified regimen. | Posted | Mean | Standard Deviation | liter | Predose 0.5, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, and 10.0 hours post-dose on Day 1 of cycle 1; Regimen 1, 2 and 3 |
|
|
|
| Secondary | Part 1: Apparent Oral Volume of Distribution (Vz/f) of Pimasertib: Multiple Dose | Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. Apparent volume of distribution after oral dose (Vz/f) was influenced by the fraction absorbed. | Pharmacokinetic analysis set included all the subjects who received at least 1 dose of trial medication and provided pharmacokinetic samples. 'N'(number of subjects analyzed)=subjects evaluable for this measure. | Posted | Geometric Mean | Geometric Coefficient of Variation | liter | Pre dose 0.5, 1.0, 1.5, 2.0, 2.5, 4.0, 6.0, and 10.0 hours post dose in Cycle 1 on Day 19 to Day 21 (Regimen 1 and 2) or Day 26 (Regimen 3) |
|
|
|
| Secondary | Part 1: Percentage of Subjects With Best Overall Response | The best overall response was reported as either of the following: (1) Morphologic complete remission (CR) = normalization of the peripheral blood absolute neutrophil count (PBANC) >1.0x10^9 per liter (/L), platelets >100x10^9 /L, bone marrow aspirate with less than or equal to (<=) 5 percent (%) blasts, no blasts with Auer rods (AML only). (2) Complete remission with incomplete blood count recovery (CRi) = Same as CR without normalization of PBANC and platelet count. (3) Partial remission (PR) = normalization of PBANC >1.0x10^9/L, platelets >100x10^9/L, and at least a 50% decrease in the percentage of marrow aspirate blasts to 5-25%, or marrow blasts less than (<) 5%. (4) Progressive disease (PD) = >50% increase in peripheral blood or bone marrow blasts. (5) Stable disease (SD) = Subjects who failed to achieve CR, CRi or PR and without criteria for PD. | The efficacy analysis set included all subjects who received at least 1 administration of planned dose of pimasertib and had at least 1 efficacy assessment after the first dose. 'N' (number of subjects analyzed)=subjects evaluable for this outcome measure. | Posted | Number | Percentage of Subjects | Day 29 of every alternate 29-day cycle until progression reported between day of first subject randomized, September 2009, until cut-off date, December 2012 |
|
|
|
| Secondary | Part 2: Number of Subjects With TEAEs, Serious TEAEs, TEAEs Leading to Death and TEAEs Leading to Permanent Treatment Discontinuation | An adverse event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that results in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. | This outcome measure was not analyzed as the trial was terminated during safety run-in (Part 1). | Posted | Up to 3 years |
|
|
| 24 |
| 33 |
| 32 |
| 33 |
| EG001 | Regimen 2 (Part 1) | Pimasertib was administered orally at a dose of 8 mg BID on Days 1 to 21 of a 28-day cycle. The dose was escalated to 15 mg BID, 23 mg BID, 30 mg BID, 42 mg BID, 45 mg BID, 60 mg BID, 75 mg BID, and 90 mg BID until MTD was obtained. The treatment was continued until disease progression, intolerable toxicity, or Investigator/subject decision. | 28 | 32 | 30 | 32 |
| EG002 | Regimen 3 (Part 1) | Pimasertib was administered orally at a dose of 60 mg BID on Days 1-28 of a 28-day cycle. The dose was escalated to 75 mg BID until MTD was obtained. The treatment was continued until disease progression, intolerable toxicity, or Investigator/subject decision. | 12 | 15 | 15 | 15 |
| Febrile Neutropenia | Blood and lymphatic system disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Thrombocytosis | Blood and lymphatic system disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Acute coronary syndrome | Cardiac disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Atrial fibrillation | Cardiac disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Cardiac failure congestive | Cardiac disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Sinus bradycardia | Cardiac disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Photopsia | Eye disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Retinal detachment | Eye disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Visual impairment | Eye disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Caecitis | Gastrointestinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Colitis | Gastrointestinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Ileus | Gastrointestinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Large intestinal obstruction | Gastrointestinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Lower gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Mouth haemorrhage | Gastrointestinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Upper gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Asthenia | General disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Disease progression | General disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Face oedema | General disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| General physical health deterioration | General disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Mucosal inflammation | General disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Pyrexia | General disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Bacteraemia | Infections and infestations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Bronchopulmonary aspergillosis | Infections and infestations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Clostridial infection | Infections and infestations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Clostridium difficile colitis | Infections and infestations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Device related infection | Infections and infestations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Diverticulitis | Infections and infestations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Enterococcal bacteraemia | Infections and infestations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Enterocolitis infectious | Infections and infestations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Escherichia bacteraemia | Infections and infestations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Human herpes virus 6 infection | Infections and infestations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Infection | Infections and infestations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Lung Infection | Infections and infestations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Parainfluenzae virus infection | Infections and infestations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Pneumonia fungal | Infections and infestations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Sepsis | Infections and infestations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Septic shock | Infections and infestations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Tonsillitis | Infections and infestations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Urinary tract infection enterococcal | Infections and infestations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Hip fracture | Injury, poisoning and procedural complications | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Overdose | Injury, poisoning and procedural complications | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Subdural haematoma | Injury, poisoning and procedural complications | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Asparatate aminotransferase increased | Investigations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Neutrophil count decreased | Investigations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| White Blood Cell Count Increased | Investigations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Tumor lysis syndrome | Metabolism and nutrition disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Depressed level of consciousness | Nervous system disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Haemorrhage intracranial | Nervous system disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Subdural hygroma | Nervous system disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Delirium | Psychiatric disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Nephritic syndrome | Renal and urinary disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Renal failure | Renal and urinary disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Renal failure acute | Renal and urinary disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Renal tubular necrosis | Renal and urinary disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Cystocele | Reproductive system and breast disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Acute respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Lung disorder | Respiratory, thoracic and mediastinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Pleural Effusion | Respiratory, thoracic and mediastinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Angioedema | Skin and subcutaneous tissue disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Swelling face | Skin and subcutaneous tissue disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Deep vein thrombosis | Vascular disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Shock haemorrhagic | Vascular disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Varicose vein | Vascular disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Febrile bone marrow aplasia | Blood and lymphatic system disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Leukocytosis | Blood and lymphatic system disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Spontaneous haematoma | Blood and lymphatic system disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Atrial fibrillation | Cardiac disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Atrioventricular block second degree | Cardiac disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Bradycardia | Cardiac disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Pericardial effusion | Cardiac disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Pneumopericardium | Cardiac disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Sinus tachycardia | Cardiac disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Ear Pain | Ear and labyrinth disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Hypoacusis | Ear and labyrinth disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Blepharitis | Eye disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Chorioretinopathy | Eye disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Conjunctival hyperaemia | Eye disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Conjunctival oedema | Eye disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Conjunctivitis | Eye disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Detachment of retinal pigment epithelium | Eye disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Dry eye | Eye disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Erythema of eyelid | Eye disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Eyelid disorder | Eye disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Eyelid oedema | Eye disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Lacrimation increased | Eye disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Macular Degeneration | Eye disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Macular oedema | Eye disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Metamorphopsia | Eye disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Ocular hypertension | Eye disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Optic disc haemorrhage | Eye disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Periorbital oedema | Eye disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Photopsia | Eye disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Retinal detachment | Eye disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Retinal haemorrhage | Eye disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Retinal oedema | Eye disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Retinal vein occlusion | Eye disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Scotoma | Eye disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Vision blurred | Eye disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Visual acuity reduced | Eye disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Visual impairment | Eye disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Vitreous floaters | Eye disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Xerophthalmia | Eye disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Anal fissure | Gastrointestinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Aphthous stomatitis | Gastrointestinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Faecal incontinence | Gastrointestinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Gingival bleeding | Gastrointestinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Gingival inflammation | Gastrointestinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Haematemesis | Gastrointestinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Hyperchlorhydria | Gastrointestinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Lip oedema | Gastrointestinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Melaena | Gastrointestinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Mouth haemorrhage | Gastrointestinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Mouth ulceration | Gastrointestinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Oral disorder | Gastrointestinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Oral pain | Gastrointestinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Proctalgia | Gastrointestinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Rectal haemorrhage | Gastrointestinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Stomatitis necrotising | Gastrointestinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Asthenia | General disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Chest pain | General disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Chills | General disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Face oedema | General disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Generalised oedema | General disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Hyperthermia | General disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Localised oedema | General disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Malaise | General disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Mucosal inflammation | General disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Oedema | General disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Pyrexia | General disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Graft versus host disease in intestine | Immune system disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Graft versus host disease in skin | Immune system disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Anal abscess | Infections and infestations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Bacteraemia | Infections and infestations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Clostridial infection | Infections and infestations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Herpes simplex ophthalmic | Infections and infestations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Human herpesvirus 6 virus infection | Infections and infestations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Localised infection | Infections and infestations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Oral candidiasis | Infections and infestations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Oral fungal infection | Infections and infestations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Paronychia | Infections and infestations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Rhinitis | Infections and infestations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Sepsis | Infections and infestations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Staphylococcal sepsis | Infections and infestations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Craniocerebral injury | Injury, poisoning and procedural complications | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Eschar | Injury, poisoning and procedural complications | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Muscle strain | Injury, poisoning and procedural complications | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Overdose | Injury, poisoning and procedural complications | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Procedural pain | Injury, poisoning and procedural complications | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Subdural haematoma | Injury, poisoning and procedural complications | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Transfusion reaction | Injury, poisoning and procedural complications | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Wound | Injury, poisoning and procedural complications | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Activated partial thromboplastin time prolonged | Investigations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Blood albumin decreased | Investigations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Blood bilirubin increased | Investigations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Blood calcium decreased | Investigations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Blood creatine increased | Investigations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Blood creatinine | Investigations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Blood glucose increased | Investigations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Blood magnesium decreased | Investigations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Blood phosphorus increased | Investigations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Blood potassium decreased | Investigations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Blood sodium decreased | Investigations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Blood urea increased | Investigations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Blood uric acid increased | Investigations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Electrocardiogram QT prolonged | Investigations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Gamma-glutamyltransferase | Investigations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Gamma-glutamyltransferase increased | Investigations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Haemoglobin decreased | Investigations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| International normalised ratio increased | Investigations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Neutrophil count decreased | Investigations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Weight decreased | Investigations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Weight increased | Investigations | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Hypermagnesaemia | Metabolism and nutrition disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Hypernatraemia | Metabolism and nutrition disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Hyperphosphataemia | Metabolism and nutrition disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Malnutrition | Metabolism and nutrition disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Metabolic acidosis | Metabolism and nutrition disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Hypercreatinaemia | Musculoskeletal and connective tissue disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Synovial cyst | Musculoskeletal and connective tissue disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Benign neoplasm of skin | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Aphonia | Nervous system disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Cognitive disorder | Nervous system disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Convulsion | Nervous system disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Hypokinesia | Nervous system disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Lethargy | Nervous system disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Neuropathy peripheral | Nervous system disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Sciatica | Nervous system disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Agitation | Psychiatric disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Confusional state | Psychiatric disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Hallucination | Psychiatric disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Hallucination, visual | Psychiatric disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Dysuria | Renal and urinary disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Haematuria | Renal and urinary disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Pollakiuria | Renal and urinary disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Proteinuria | Renal and urinary disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Renal failure acute | Renal and urinary disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Testis discomfort | Reproductive system and breast disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Uterine prolapse | Reproductive system and breast disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Vulvovaginal pain | Reproductive system and breast disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Acute pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Acute respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Tachypnoea | Respiratory, thoracic and mediastinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Acne | Skin and subcutaneous tissue disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Blood blister | Skin and subcutaneous tissue disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Decubitus ulcer | Skin and subcutaneous tissue disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Dermatitis diaper | Skin and subcutaneous tissue disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Exfoliative rash | Skin and subcutaneous tissue disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Petechiae | Skin and subcutaneous tissue disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Purpura | Skin and subcutaneous tissue disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Rash generalised | Skin and subcutaneous tissue disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Rash macular | Skin and subcutaneous tissue disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Skin disorder | Skin and subcutaneous tissue disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Skin lesion | Skin and subcutaneous tissue disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Skin reaction | Skin and subcutaneous tissue disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Swelling face | Skin and subcutaneous tissue disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Deep vein thrombosis | Vascular disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Flushing | Vascular disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Hot flush | Vascular disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Orthostatic hypotension | Vascular disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Infusion site oedema | General disorders | MedDRA Version 15.1 | Non-systematic Assessment |
|
| Hordeolum | Infections and infestations | MedDRA Version 15.1 | Non-systematic Assessment |
|
Not provided
| D006402 |
| Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D009371 | Neoplasms by Site |
| Title | Measurements |
|---|---|
|
| TEAEs Leading to Death |
|
| TEAEs Leading to Treatment Discontinuation |
|
|
|
| Title | Measurements |
|---|---|
|
| PR |
|
| SD |
|
| PD |
|