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Study was terminated due to Sponsor decision (all except 1 patient were off-treatment and 2 patients were in survival follow-up)
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This is an open-label, multicenter, Phase 2 study to evaluate the efficacy and safety of oral selinexor in participants with recurrent gliomas.
This is an open-label, multicenter, Phase 2 study to evaluate the efficacy and safety of oral selinexor in participants with recurrent gliomas.
Initially, the study included 2 arms: an exploratory Surgical Arm (Arm A) with sequential enrollment for participants who require surgery and a medical arm (Arm B) for participants who are not eligible for surgery.
Enrollment in Arm B was stopped to explore alternative dosing in Protocol Versions ≥ 4.0 to potentially improve tolerability. Four arms (Arms C, D, E, and F) were added to the Medical Arm in Protocol Version 4.0. Arms E and F were eliminated in protocol version 6.0 and no participants were ever enrolled in these arms.
Participants in the primary population enrolled under Protocol Version ≥ 4.0 will be randomized to Arm C and Arm D (approximately 30 participants per arm) to explore alternative dosing to potentially improve tolerability.
After screening and registration/randomization in the study, participants enrolling in Arm A or randomized to Arm C will receive 60 mg selinexor orally twice weekly. Participants randomized to Arm D will receive 80 mg selinexor orally weekly.
Participants will be treated until progression of disease or the development of unacceptable toxicities. All participants will then undergo the End of Treatment (EOT) visit.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A: Selinexor 60 mg and Surgery | Experimental | Participants who required surgery received up to 3 doses of oral selinexor tablets 60 milligrams (mg) twice weekly (BIW) on Day 1, Day 3 and between 2 and 48 hours prior to surgery, subsequently underwent surgery for resection of their tumor and resumed selinexor tablets 60 mg BIW after recovery, during Week 1 to 4 of each 4-week cycle, until progression of disease (PD) or development of unacceptable toxicities. |
|
| Arm B: Selinexor 50 mg/m^2 | Experimental | Participants who were not eligible for surgery received selinexor tablets 50 mg per square meter (mg/m^2) BIW during Week 1 to 4 of each 4-week cycle until PD or development of unacceptable toxicities. |
|
| Arm C: Selinexor 60 mg | Experimental | Participants who were not eligible for surgery received selinexor tablets 60 mg BIW during Week 1 to 4 of each 4-week cycle until PD or development of unacceptable toxicities. |
|
| Arm D: Selinexor 80 mg | Experimental | Participants who were not eligible for surgery received selinexor tablets 80 mg once weekly (QW) during Week 1 to 4 of each 4-week cycle until PD or development of unacceptable toxicities. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Selinexor | Drug | One cycle is 28 days (4 weeks). |
|
| Measure | Description | Time Frame |
|---|---|---|
| 6-Month Progression-Free Survival (PFS) Rate | The analysis of 6mPFS was performed by calculating the estimated survival probability of having PFS ≥ 6 months based on Kaplan-Meier method, where PFS was defined as the time from the start of study treatment until first documented progression based on Response Assessment in Neuro-Oncology (RANO) criteria, or death from any cause. Progressive disease occurs when either of the criteria was present: greater than or equal to (≥) 25 percentage (%) increase in T1 gadolinium enhancing disease, increase in T2/ Fluid-attenuated inversion recovery (FLAIR), detection of new lesions, or decreased clinical status. | From start of study treatment up to disease progression or death, whichever occurred first (assessed up to Month 6) |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Response Rate (ORR) | The ORR was determined as percentage of participants who had either complete response (CR) or partial response (PR) using the RANO criteria. CR: No T1 gadolinium enhancing disease, stable or decreasing T2/FLAIR, no new lesions, no corticosteroid use and stable, or increasing clinical status. PR: ≥50% decrease in T1 gadolinium enhancing disease, stable or decreasing T2/FLAIR, no new lesions, stable or decreased use of corticosteroids, and stable or increased clinical status. |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States | ||
| Dana Farber Cancer Institute, Center for Neuro-Oncology |
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A total of 76 participants were enrolled, randomized and treated in this study.
This study was conducted at 6 sites across the United States of America, Denmark and Netherland between 03 March 2014 and 23 January 2020.
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm A: Selinexor 60 mg and Surgery | Participants who required surgery received up to 3 doses of oral selinexor tablets 60 milligrams (mg) twice weekly (BIW) on Day 1, Day 3 and between 2 and 48 hours prior to surgery, subsequently underwent surgery for resection of their tumor and resumed selinexor tablets 60 mg BIW after recovery, during Week 1 to 4 of each 4-week cycle, until progression of disease (PD) or development of unacceptable toxicities. |
| FG001 | Arm B: Selinexor 50 mg/m^2 | Participants who were not eligible for surgery received selinexor tablets 50 mg per square meter (mg/m^2) BIW during Week 1 to 4 of each 4-week cycle until PD or development of unacceptable toxicities. |
| FG002 | Arm C: Selinexor 60 mg | Participants who were not eligible for surgery received selinexor tablets 60 mg BIW during Week 1 to 4 of each 4-week cycle until PD or development of unacceptable toxicities. |
| FG003 | Arm D: Selinexor 80 mg | Participants who were not eligible for surgery received selinexor tablets 80 mg once weekly (QW) during Week 1 to 4 of each 4-week cycle until PD or development of unacceptable toxicities. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Safety population consisted of all participants who had received any amount of study treatment.
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm A: Selinexor 60 mg and Surgery | Participants who required surgery received up to 3 doses of oral selinexor tablets 60 mg BIW on Day 1, Day 3 and between 2 and 48 hours prior to surgery, subsequently underwent surgery for resection of their tumor and resumed selinexor tablets 60 mg BIW after recovery, during Week 1 to 4 of each 4-week cycle, until PD or development of unacceptable toxicities. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | 6-Month Progression-Free Survival (PFS) Rate | The analysis of 6mPFS was performed by calculating the estimated survival probability of having PFS ≥ 6 months based on Kaplan-Meier method, where PFS was defined as the time from the start of study treatment until first documented progression based on Response Assessment in Neuro-Oncology (RANO) criteria, or death from any cause. Progressive disease occurs when either of the criteria was present: greater than or equal to (≥) 25 percentage (%) increase in T1 gadolinium enhancing disease, increase in T2/ Fluid-attenuated inversion recovery (FLAIR), detection of new lesions, or decreased clinical status. | Modified intent-to-treat (mITT) population consisted of all enrolled participants in Arms B, C and D who had received at least 1 dose of study medication and have at least 1 post-baseline efficacy follow-up assessment, unless the participant discontinued treatment prior to the first post baseline assessment due to death, toxicity, or PD. Data for this outcome measure was not planned to be collected and analyzed for Arm A: Selinexor 60 mg and Surgery. | Posted | Number | 95% Confidence Interval | percentage of participants | From start of study treatment up to disease progression or death, whichever occurred first (assessed up to Month 6) |
From start of study treatment administration up to 71 months
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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: Selinexor 60 mg and Surgery | Participants who required surgery received up to 3 doses of oral selinexor tablets 60 mg BIW on Day 1, Day 3 and between 2 and 48 hours prior to surgery, subsequently underwent surgery for resection of their tumor and resumed selinexor tablets 60 mg BIW after recovery, during Week 1 to 4 of each 4-week cycle, until PD or development of unacceptable toxicities. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA 23.0 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 23.0 | Non-systematic Assessment |
Study was terminated due to Sponsor decision (all except 1 patient were off-treatment and 2 patients were in survival follow-up).
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jatin Shah, MD | Karyopharm Therapeutics Inc. | (617) 658-0600 | jshah@karyopharm.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Nov 13, 2015 | Jun 16, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 5, 2020 | Jun 16, 2021 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D005909 | Glioblastoma |
| D005910 | Glioma |
| D001932 | Brain Neoplasms |
| D001254 | Astrocytoma |
| D009837 | Oligodendroglioma |
| ID | Term |
|---|---|
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
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| ID | Term |
|---|---|
| C585161 | selinexor |
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|
| Up to 71 months |
| Overall Survival (OS) | The OS was calculated from the date of start of study treatment to the date of death. Participants who were still alive prior to the data cut-off for final efficacy analysis, or who dropout prior to study end, were censored on the day they were last known to be alive. The OS was estimated using Kaplan-Meier method. | From date of study treatment up to date of death (assessed up to 71 months) |
| Progression-free Survival (PFS) | The PFS was calculated from the date of start of study treatment to the date of disease progression based on RANO criteria, or date of death should progression not have occurred. Progressive disease occurs when either of the criteria was present: ≥25% increase in T1 gadolinium enhancing disease, increased T2/FLAIR, detection of new lesions, or decreased clinical status. | From start of study treatment up to disease progression (assessed up to 71 months) |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | An adverse event (AE) was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) was defined as an AE that was fatal; life threatening (places the participant at immediate risk of death); requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; was a congenital anomaly/birth defect; and other important medical events. TEAE was defined as any AE with onset or worsening of a pre-existing condition on or after the first administration of study medication through 30 days following last dose or any event considered drug-related by the Investigator through the end of the study. TEAEs included both serious and non-serious TEAEs. | From start of study treatment administration up to 71 months |
| Boston |
| Massachusetts |
| 02215 |
| United States |
| Columbia University, Herbert Irving Comprehensive Cancer Center | New York | New York | 10032 | United States |
| The Phase I Unit, Dept. of Oncology, Rigshospitalet | Copenhagen | DK-2100 | Denmark |
| University of Groningen Faculty of Medical Sciences, Medical Oncology | Groningen | 9713 GZ | Netherlands |
| Erasmus MC-Daniel den Hoed Cancer Center- Neuro-Oncology Unit | Rotterdam | 3008AE | Netherlands |
| Lost to Follow-up |
|
| Physician Decision |
|
| Progressive Disease |
|
| Withdrawal by Participant |
|
| Study Terminated by Sponsor |
|
| Other-unspecified |
|
| BG001 | Arm B: Selinexor 50 mg/m^2 | Participants who were not eligible for surgery received selinexor tablets 50 mg/m^2 BIW during Week 1 to 4 of each 4-week cycle until PD or development of unacceptable toxicities. |
| BG002 | Arm C: Selinexor 60 mg | Participants who were not eligible for surgery received selinexor tablets 60 mg BIW during Week 1 to 4 of each 4-week cycle until PD or development of unacceptable toxicities. |
| BG003 | Arm D: Selinexor 80 mg | Participants who were not eligible for surgery received selinexor tablets 80 mg QW during Week 1 to 4 of each 4-week cycle until PD or development of unacceptable toxicities. |
| BG004 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| ID | Title | Description |
|---|---|---|
| OG000 | Arm B: Selinexor 50 mg/m^2 | Participants who were not eligible for surgery received selinexor tablets 50 mg/m^2 BIW during Week 1 to 4 of each 4-week cycle until PD or development of unacceptable toxicities. |
| OG001 | Arm C: Selinexor 60 mg | Participants who were not eligible for surgery received selinexor tablets 60 mg BIW during Week 1 to 4 of each 4-week cycle until PD or development of unacceptable toxicities. |
| OG002 | Arm D: Selinexor 80 mg | Participants who were not eligible for surgery received selinexor tablets 80 mg QW during Week 1 to 4 of each 4-week cycle until PD or development of unacceptable toxicities. |
|
|
| Secondary | Overall Response Rate (ORR) | The ORR was determined as percentage of participants who had either complete response (CR) or partial response (PR) using the RANO criteria. CR: No T1 gadolinium enhancing disease, stable or decreasing T2/FLAIR, no new lesions, no corticosteroid use and stable, or increasing clinical status. PR: ≥50% decrease in T1 gadolinium enhancing disease, stable or decreasing T2/FLAIR, no new lesions, stable or decreased use of corticosteroids, and stable or increased clinical status. | mITT population consisted of all enrolled participants in Arms B, C and D who had received at least 1 dose of study medication and have at least 1 post-baseline efficacy follow-up assessment, unless the participant discontinued treatment prior to the first post baseline assessment due to death, toxicity, or disease progression. Data for this outcome measure was not planned to be collected and analyzed for Arm A: Selinexor 60 mg and Surgery. | Posted | Number | 95% Confidence Interval | percentage of participants | Up to 71 months |
|
|
|
| Secondary | Overall Survival (OS) | The OS was calculated from the date of start of study treatment to the date of death. Participants who were still alive prior to the data cut-off for final efficacy analysis, or who dropout prior to study end, were censored on the day they were last known to be alive. The OS was estimated using Kaplan-Meier method. | mITT population consisted of all enrolled participants in Arms B, C and D who had received at least 1 dose of study medication and have at least 1 post-baseline efficacy follow-up assessment, unless the participant discontinued treatment prior to the first post baseline assessment due to death, toxicity, or disease progression. Data for this outcome measure was not planned to be collected and analyzed for Arm A: Selinexor 60 mg and Surgery. | Posted | Median | 95% Confidence Interval | months | From date of study treatment up to date of death (assessed up to 71 months) |
|
|
|
| Secondary | Progression-free Survival (PFS) | The PFS was calculated from the date of start of study treatment to the date of disease progression based on RANO criteria, or date of death should progression not have occurred. Progressive disease occurs when either of the criteria was present: ≥25% increase in T1 gadolinium enhancing disease, increased T2/FLAIR, detection of new lesions, or decreased clinical status. | mITT population consisted of all enrolled participants in Arms B, C and D who had received at least 1 dose of study medication and have at least 1 post-baseline efficacy follow-up assessment, unless the participant discontinued treatment prior to the first post baseline assessment due to death, toxicity, or disease progression. Data for this outcome measure was not planned to be collected and analyzed for Arm A: Selinexor 60 mg and Surgery. | Posted | Median | 95% Confidence Interval | months | From start of study treatment up to disease progression (assessed up to 71 months) |
|
|
|
| Secondary | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | An adverse event (AE) was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) was defined as an AE that was fatal; life threatening (places the participant at immediate risk of death); requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; was a congenital anomaly/birth defect; and other important medical events. TEAE was defined as any AE with onset or worsening of a pre-existing condition on or after the first administration of study medication through 30 days following last dose or any event considered drug-related by the Investigator through the end of the study. TEAEs included both serious and non-serious TEAEs. | Safety population consisted of all participants who had received any amount of study treatment. | Posted | Count of Participants | Participants | From start of study treatment administration up to 71 months |
|
|
|
| 8 |
| 8 |
| 5 |
| 8 |
| 8 |
| 8 |
| EG001 | Arm B: Selinexor 50 mg/m^2 | Participants who were not eligible for surgery received selinexor tablets 50 mg/m^2 BIW during Week 1 to 4 of each 4-week cycle until PD or development of unacceptable toxicities. | 22 | 24 | 7 | 24 | 24 | 24 |
| EG002 | Arm C: Selinexor 60 mg | Participants who were not eligible for surgery received selinexor tablets 60 mg BIW during Week 1 to 4 of each 4-week cycle until PD or development of unacceptable toxicities. | 10 | 14 | 7 | 14 | 14 | 14 |
| EG003 | Arm D: Selinexor 80 mg | Participants who were not eligible for surgery received selinexor tablets 80 mg QW during Week 1 to 4 of each 4-week cycle until PD or development of unacceptable toxicities. | 21 | 30 | 7 | 30 | 30 | 30 |
| Fatigue | General disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Asthenia | General disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| General physical health deterioration | General disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
|
| Meningitis bacterial | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
|
| Staphylococcal infection | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
|
| Acetabulum fracture | Injury, poisoning and procedural complications | MedDRA 23.0 | Non-systematic Assessment |
|
| Concussion | Injury, poisoning and procedural complications | MedDRA 23.0 | Non-systematic Assessment |
|
| Shunt malfunction | Injury, poisoning and procedural complications | MedDRA 23.0 | Non-systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Hyperlipasaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Non-systematic Assessment |
|
| Intracranial tumour haemorrhage | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Non-systematic Assessment |
|
| Seizure | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Brain oedema | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Cerebrospinal fluid leakage | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Cerebrovascular accident | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Pneumocephalus | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Confusional state | Psychiatric disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Embolism | Vascular disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Lymphopenia | Blood and lymphatic system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Tinnitus | Ear and labyrinth disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Hypoacusis | Ear and labyrinth disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Cushingoid | Endocrine disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Inappropriate antidiuretic hormone secretion | Endocrine disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Vision blurred | Eye disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Dry eye | Eye disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Eye pain | Eye disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Periorbital oedema | Eye disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Visual acuity reduced | Eye disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Gait disturbance | General disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Malaise | General disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Face oedema | General disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Non-cardiac chest pain | General disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
|
| Cystitis | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 23.0 | Non-systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA 23.0 | Non-systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA 23.0 | Non-systematic Assessment |
|
| Incision site pain | Injury, poisoning and procedural complications | MedDRA 23.0 | Non-systematic Assessment |
|
| Spinal compression fracture | Injury, poisoning and procedural complications | MedDRA 23.0 | Non-systematic Assessment |
|
| Wound dehiscence | Injury, poisoning and procedural complications | MedDRA 23.0 | Non-systematic Assessment |
|
| Weight decreased | Investigations | MedDRA 23.0 | Non-systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 23.0 | Non-systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA 23.0 | Non-systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA 23.0 | Non-systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Hyperlipasaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Hypercreatininaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Hyperamylasaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Osteoporosis | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Memory impairment | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Aphasia | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Balance disorder | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Dysarthria | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Seizure | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Haemorrhage intracranial | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Hemiparesis | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Neuropathy peripheral | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Tremor | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Coordination abnormal | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Depressed level of consciousness | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Disturbance in attention | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Hemianopia homonymous | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| IIIrd nerve disorder | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Lethargy | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Motor dysfunction | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Taste disorder | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Visual field defect | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Ataxia | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Cerebrospinal fluid leakage | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Intracranial pressure increased | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Upper motor neurone lesion | Nervous system disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Confusional state | Psychiatric disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Abnormal behaviour | Psychiatric disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Mood altered | Psychiatric disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Personality change | Psychiatric disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Urinary incontinence | Renal and urinary disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Pollakiuria | Renal and urinary disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Erectile dysfunction | Reproductive system and breast disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Nasal Congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Apnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Purpura | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Flushing | Vascular disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Embolism | Vascular disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 23.0 | Non-systematic Assessment |
|
| Cataract | Eye disorders | MedDRA 23.0 | Non-systematic Assessment |
|
Not provided
Not provided
| D009369 | Neoplasms |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
| D016543 | Central Nervous System Neoplasms |
| D009423 | Nervous System Neoplasms |
| D009371 | Neoplasms by Site |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| Participants with TESAEs |
|