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The purpose of this research study is to find out more information such as: to determine the effects of high and low fat foods on the pharmacokinetics (PK) of oral KPT-330 tablets and to compare PK of capsules and tablets in Arms 1 and 2; to evaluate tumor response in sarcoma participants in Arm 3; to compare the PK of 60 milligrams (mg) of the new, 2nd generation tablet formulation and 60 mg of the selinexor suspension formula to the current, 1st generation tablets.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1 | Experimental | Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received Selinexor 30 milligrams per meter square (mg/m^2) orally twice weekly in treatment sequence ABCD (Treatment A: fasted, tablet formulation on Day 1 of Week 1; Treatment B: high-fat meal, tablet formulation on Day 1 of Week 2; Treatment C: low-fat meal, tablet formulation on Day 1 of Week 3; Treatment D: low-fat meal, capsule formulation on Day 1 of Week 4 in Cycle 1 (Weeks 1 to 4). |
|
| Arm 2 | Experimental | Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received selinexor 30 mg/m^2 orally twice weekly in treatment sequence BADC (Treatment B: high-fat meal, tablet formulation on Day 1 of Week 1; Treatment A: fasted, tablet formulation on Day 1 of Week 2; Treatment D: low fat meal, capsule formulation on Day 1 of Week 3; Treatment C: low-fat meal, tablet formulation on Day 1 of Week 4 in Cycle 1 (Weeks 1 to 4).All participants received the current (1st generation) tablet formula at a dose of 60 mg on Day 3 of Weeks 1-3 of Cycle 1. |
|
| Arm 3 | Experimental | Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received Selinexor 50 mg/m^2 first generation tablets twice weekly on Days 1 and 3 of each week within 30 minutes of solid food consumption. |
|
| Arm 4 | Experimental | Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received Selinexor 60 mg/m^2 orally in treatment sequence ABC (Treatment A: current [1st generation] tablets on Day 1 of Week 1; Treatment B: new [2nd generation] tablets on Day 1 of Week 2; Treatment C: suspension dose of current [1st generation] tablets on Day 1 of Week 3 in Cycle 1 (Weeks 1 to 3). All participants received the current (1st generation) tablet formula at a dose of 60 mg on Day 3 of Weeks 1-3 of Cycle 1. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| KCP-330 | Drug |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Concentration-time Curve From the Time Zero to the Last Non-zero Concentration (AUC0-t) of Selinexor | AUC0-t was defined as area under the concentration-time curve from time zero to the last non-zero concentration. | Day 1 of weeks 1-3 in Cycle 1: Pre-dose (within 10 minutes before swallowing study drug), 15, 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10,18, 24, and 48 hours post-dose |
| Area Under the Concentration Time Curve From the Time Zero to Extrapolated to Infinity (AUC0-inf) of Selinexor | AUC0-inf was defined as area under the concentration-time curve from time zero to infinity (extrapolated), AUC0-inf was calculated as AUC0-t + Ct/ elimination rate constant (kel), where: Ct = the last observed non- zero concentration. | Day 1 of weeks 1-3 in Cycle 1: Pre-dose (within 10 minutes before swallowing study drug), 15, 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 18, 24, and 48 hours post-dose |
| Maximum Observed Plasma Concentration (Cmax) of Selinexor | Cmax was defined as maximum observed concentration, taken directly from the plasma concentration data. | Day 1 of weeks 1-3 in Cycle 1: Pre-dose (within 10 minutes before swallowing study drug), 15, 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 18, 24, and 48 hours post-dose |
| Time of First Maximum Observed Concentration (Tmax) of Selinexor | Tmax was defined as time of first observation of Cmax, taken directly from the plasma concentration data. | Day 1 of weeks 1-3 in Cycle 1: Pre-dose (within 10 minutes before swallowing study drug), 15, 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 18, 24, and 48 hours post-dose |
| Terminal Phase Half-Life (t1/2) of Selinexor | t1/2 was the terminal phase half-life, it was calculated as ln(2)/kel. |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Best Overall Response According to Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 Criteria | Best overall response rate was defined as the percentage of participants who achieved complete response (CR), and partial response (PR), as assessed by the RECIST v1.1 criteria. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non target) must have reduction in the short axis to less than (<) 10 millimeter (mm). PR was defined as At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum longest diameter (LD). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Michael Kauffman, MD, Ph.D | Karyopharm Therapeutics Inc | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Memorial Sloan Kettering Cancer Centre | New York | New York | 10065 | United States | ||
| Princess Margaret Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27458288 | Derived | Gounder MM, Zer A, Tap WD, Salah S, Dickson MA, Gupta AA, Keohan ML, Loong HH, D'Angelo SP, Baker S, Condy M, Nyquist-Schultz K, Tanner L, Erinjeri JP, Jasmine FH, Friedlander S, Carlson R, Unger TJ, Saint-Martin JR, Rashal T, Ellis J, Kauffman M, Shacham S, Schwartz GK, Abdul Razak AR. Phase IB Study of Selinexor, a First-in-Class Inhibitor of Nuclear Export, in Patients With Advanced Refractory Bone or Soft Tissue Sarcoma. J Clin Oncol. 2016 Sep 10;34(26):3166-74. doi: 10.1200/JCO.2016.67.6346. Epub 2016 Jul 25. |
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A total of 54 participants were enrolled and randomized to study treatment.
This study was conducted at 2 sites in United States and Canada from 30 July 2013 to 21 October 2016.
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm 1: | Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received selinexor 30 milligrams per meter square (mg/m^2) orally twice weekly in treatment sequence ABCD (Treatment A: fasted, tablet formulation on Day 1 of Week 1; Treatment B: high-fat meal, tablet formulation on Day 1 of Week 2; Treatment C: low-fat meal, tablet formulation on Day 1 of Week 3; Treatment D: low-fat meal, capsule formulation on Day 1 of Week 4 in Cycle 1 (Weeks 1 to 4). |
| FG001 | Arm 2: | Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received selinexor 30 mg/m^2 orally twice weekly in treatment sequence BADC (Treatment B: high-fat meal, tablet formulation on Day 1 of Week 1; Treatment A: fasted, tablet formulation on Day 1 of Week 2; Treatment D: low-fat meal, capsule formulation on Day 1 of Week 3; Treatment C: low-fat meal, tablet formulation on Day 1 of Week 4 in Cycle 1 (Weeks 1 to 4). |
| FG002 | Arm 3: | Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received selinexor 50 mg/m^2 first generation tablets twice weekly on Days 1 and 3 of each week within 30 minutes of solid food consumption. |
| FG003 | Arm 4: | Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received selinexor 60 mg/m^2 orally in treatment sequence ABC (Treatment A: current [1st generation] tablets on Day 1 of Week 1; Treatment B: new [2nd generation] tablets on Day 1 of Week 2; Treatment C: suspension dose of current [1st generation] tablets on Day 1 of Week 3 in Cycle 1 (Weeks 1 to 3). All participants received the current (1st generation) tablet formula at a dose of 60 mg on Day 3 of Weeks 1-3 of Cycle 1. |
| FG004 | Arm 5: | Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received selinexor 60 mg/m^2 orally in treatment sequence CAB (Treatment C: suspension dose of current [1st generation] tablets on Day 1 of Week 1; Treatment A: current [1st generation] tablets on Day 1 of Week 2; Treatment B: new [2nd generation] tablets on Day 1 of Week 3 in Cycle 1 (Weeks 1 to 3). All participants received the current (1st generation) tablet formula at a dose of 60 mg on Day 3 of Weeks 1-3 of Cycle 1. |
| FG005 | Arm 6: | Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received selinexor 60 mg/m^2 orally in treatment sequence BCA (Treatment B: new [2nd generation] tablets on Day 1 of Week 1; Treatment C: suspension dose of current [1st generation] tablets on Day 1 of Week 2; Treatment A: current [1st generation] tablets on Day 1 of Week 3 in Cycle 1 (Weeks 1 to 3). All participants received the current (1st generation) tablet formula at a dose of 60 mg on Day 3 of Weeks 1-3 of Cycle 1. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Safety population consisted of all participants who received at least one dose of selinexor.
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm 1: | Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received selinexor 30 mg/m^2 orally twice weekly in treatment sequence ABCD (Treatment A: fasted, tablet formulation on Day 1 of Week 1; Treatment B: high-fat meal, tablet formulation on Day 1 of Week 2; Treatment C: low-fat meal, tablet formulation on Day 1 of Week 3; Treatment D: low-fat meal, capsule formulation on Day 1 of Week 4 in Cycle 1 (Weeks 1 to 4). |
| 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 | Area Under the Concentration-time Curve From the Time Zero to the Last Non-zero Concentration (AUC0-t) of Selinexor | AUC0-t was defined as area under the concentration-time curve from time zero to the last non-zero concentration. | Pharmacokinetic (PK) population included all participants in Arms 1, 2 and Arms 4, 5, and 6 who received selinexor, and for whom the PK profile for all treatments could be adequately characterized. Here 'overall number of participants analyzed' signifies number of participants evaluable for this outcome measure. As pre-specified in SAP and protocol Arm 3 was a non-PK group assessment, so data was not collected and analyzed for this PK outcome. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanograms*hour per milliliter (ng*h/mL) | Day 1 of weeks 1-3 in Cycle 1: Pre-dose (within 10 minutes before swallowing study drug), 15, 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10,18, 24, and 48 hours post-dose |
|
From screening up to 30 days post last study drug dose (up to 39 months)
Safety population consisted of all participants who received at least one dose of selinexor. As pre-specified in SAP, safety data was collected and analyzed as per the individual arms with specified treatment sequences only.
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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 1: | Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received Selinexor 30 milligrams per meter square (mg/m^2) orally twice weekly in treatment sequence ABCD (Treatment A: fasted, tablet formulation on Day 1 of Week 1; Treatment B: high-fat meal, tablet formulation on Day 1 of Week 2; Treatment C: low-fat meal, tablet formulation on Day 1 of Week 3; Treatment D: low-fat meal, capsule formulation on Day 1 of Week 4 in Cycle 1 (Weeks 1 to 4). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 20.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 20.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jatin Shah, MD | Karyopharm Therapeutics Inc | (617) 658-0600 | jshah@karyopharm.com |
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| ID | Term |
|---|---|
| D012509 | Sarcoma |
| D001859 | Bone Neoplasms |
| ID | Term |
|---|---|
| D018204 | Neoplasms, Connective and Soft Tissue |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009371 | Neoplasms by Site |
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| ID | Term |
|---|---|
| C585161 | selinexor |
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|
| Arm 5 | Experimental | Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received Selinexor 60 mg/m^2 orally in treatment sequence CAB (Treatment C: suspension dose of current [1st generation] tablets on Day 1 of Week 1; Treatment A: current [1st generation] tablets on Day 1 of Week 2; Treatment B: new [2nd generation] tablets on Day 1 of Week 3 in Cycle 1 (Weeks 1 to 3). All participants received the current (1st generation) tablet formula at a dose of 60 mg on Day 3 of Weeks 1-3 of Cycle 1. |
|
| Arm 6 | Experimental | Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received Selinexor 60 mg/m^2 orally in treatment sequence BCA (Treatment B: new [2nd generation] tablets on Day 1 of Week 1; Treatment C: suspension dose of current [1st generation] tablets on Day 1 of Week 2; Treatment A: current [1st generation] tablets on Day 1 of Week 3 in Cycle 1 (Weeks 1 to 3). All participants received the current (1st generation) tablet formula at a dose of 60 mg on Day 3 of Weeks 1-3 of Cycle 1. |
|
| Day 1 of weeks 1-3 in Cycle 1: Pre-dose (within 10 minutes before swallowing study drug), 15, 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 18, 24, and 48 hours post-dose |
| Apparent Total Body Clearance (CL/F) of Selinexor | Apparent total body clearance was calculated as Dose/AUC0-inf, uncorrected for fraction absorbed; reported normalized by participant body weight (kilogram [kg]). | Day 1 of weeks 1-3 in Cycle 1: Pre-dose (within 10 minutes before swallowing study drug), 15, 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 18, 24, and 48 hours post-dose |
| Apparent Volume of Distribution (Vd/F) of Selinexor | Vd/F was calculated as Dose/ (kel *AUC0-inf), uncorrected for fraction absorbed; reported normalized by participant body weight (kg). | Day 1 of weeks 1-3 in Cycle 1: Pre-dose (within 10 minutes before swallowing study drug), 15, 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 18, 24, and 48 hours post-dose |
| From the date of first documented response until the date of documented progression or last disease assessment (up to 39 months) |
| Duration of Stable Disease as Per RECIST v1.1 Criteria | Duration of at least stable disease was defined as the time from the date of first dose of study treatment to first documented radiologic evidence of disease recurrence or progression as per RECIST v1.1 Criteria. Participants without evidence of progression were censored at time of last disease assessment. Progressive Disease (PD) was defined as at least a 20% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded since the treatment started. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Appearance of one or more new lesions also constituted progressive disease. | From the date of first dose of study treatment to first documented radiologic evidence of disease recurrence or progression, censored date (up to 39 months) |
| Progression Free Survival (PFS) as Per RECIST v1.1 Criteria | PFS was defined as the time from the date of randomization until the first date of Independent Review Committee (IRC)-confirmed PD per RECIST v1.1, or death due to any cause. PD was defined as at least a 20% increase in the sum of the longest diameter (SLD), taking as reference the smallest sum of the longest diameter (SLD) recorded from baseline or the appearance of 1 or more new lesions. Participants who were last known to be alive and without evidence of progression were censored at time of last disease assessment. If date of progression or death occurred after more than 1 missed disease assessment interval, or 30 days after end of treatment, participants were censored at the time of last evaluable disease assessment prior to the missed assessment. | From first dose of study treatment to time of disease progression or death, censored date (up to 39 months) |
| Overall Survival (OS) | OS was defined as the time from date first dose of study treatment to the date of death. Participants who were still alive prior to the data cutoff for final efficacy analysis, or who dropped out prior to study end, were censored at the day they were last known to be alive. | From first dose of study treatment to death, censored date (up to 39 months) |
| Time to Progression (TTP) | TTP was defined as the time from date of first dose of study treatment to first documented evidence of disease recurrence or progression, or death due to disease progression, whichever occurred first. Participants without evidence of progression were censored at time of last evaluable disease assessment. | From first dose of study treatment to first documented evidence of disease recurrence or progression, or death, censored date (up to 39 months) |
| Number of Participants With Growth Modulation Index (GMI) Less Than or Equal to (<=) 1.33 and Greater Than (>) 1.33 | GMI was defined as the ratio between the TTP with selinexor and the TTP with the most recent prior treatment. GMI was calculated, using a previously described threshold of 1.3 or greater as a sign of potential drug activity and improved overall survival. | Up to 39 months |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | An AE was any untoward medical occurrence in a participant administered a pharmaceutical product during the course of a study and which does not necessarily have to have a causal relationship with this treatment. SAE defined as any AE, occurring at any dose (including after the informed consent form was signed and prior to dosing) that and regardless of causality that: results in death, is life-threatening (participant was at immediate risk of death from event as it occurred), requires in-patient hospitalization (formal admission to a hospital for medical reasons) or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect. TEAE was defined as any AE with onset or worsening of a pre-existing condition on or after the first administration of study treatment through 30 days following last dose or any event considered drug-related by the investigator through the end of the study. | From screening up to 30 days post last study drug dose (up to 39 months) |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign, symptom, or medical condition that occur after participant's signed informed consent obtained. TEAE was defined as any AE with onset or worsening of a pre-existing condition on or after the first administration of study treatment through 28 days following last dose or any event considered drug-related by the investigator through the end of the study. Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life-threatening, and Grade 5: death. | From screening up to 30 days post last study drug dose (up to 39 months) |
| Number of Participants With Clinically Significant Laboratory Abnormalities | Number of participants with clinically significant laboratory abnormalities including clinical chemistry, hematology, coagulation and urinalysis. Number of participants with clinically significant laboratory abnormalities which were deemed clinically significant by the investigator were reported. | From screening up to 30 days post last study drug dose (up to 39 months) |
| Number of Participants With Clinically Significant Changes in Vital Signs | Vital signs included blood pressure (systolic blood pressure and diastolic blood pressure). Measurements were made after the participant had been resting supine for a minimum of 5 minutes. Clinically significant findings were defined as such in the opinion of the investigator occurring at any time on treatment from normal pre-dose based on the condition met (Yes/No). Number of participants with clinically significant changes in vital signs with condition (Yes) were only reported. | From screening up to 30 days post last study drug dose (up to 39 months) |
| Number of Participants With Clinically Significant Changes in Electrocardiogram (ECGs) | Twelve lead ECGs were obtained after the participant has rested in a supine position for at least 5 minutes. Clinically significant findings were defined as such in the opinion of the investigator or designated physician occurring at any time on treatment from normal pre-dose. | From screening up to 30 days post last study drug dose |
| Toronto |
| Ontario |
| M5T 2M9 |
| Canada |
| Physician Decision |
|
| Withdrawal by Subject |
|
| Disease Progression |
|
| Need of treatment not allowed per protocol |
|
| Intercurrent illness |
|
| Death |
|
| BG001 | Arm 2: | Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received selinexor 30 mg/m^2 orally twice weekly in treatment sequence BADC (Treatment B: high-fat meal, tablet formulation on Day 1 of Week 1; Treatment A: fasted, tablet formulation on Day 1 of Week 2; Treatment D: low-fat meal, capsule formulation on Day 1 of Week 3; Treatment C: low-fat meal, tablet formulation on Day 1 of Week 4 in Cycle 1 (Weeks 1 to 4). |
| BG002 | Arm 3: | Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received selinexor 50 mg/m^2 first generation tablets twice weekly on Days 1 and 3 of each week within 30 minutes of solid food consumption. |
| BG003 | Arm 4: | Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received selinexor 60 mg/m^2 orally in treatment sequence ABC (Treatment A: current [1st generation] tablets on Day 1 of Week 1; Treatment B: new [2nd generation] tablets on Day 1 of Week 2; Treatment C: suspension dose of current [1st generation] tablets on Day 1 of Week 3 in Cycle 1 (Weeks 1 to 3). All participants received the current (1st generation) tablet formula at a dose of 60 mg on Day 3 of Weeks 1-3 of Cycle 1. |
| BG004 | Arm 5: | Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received selinexor 60 mg/m^2 orally in treatment sequence CAB (Treatment C: suspension dose of current [1st generation] tablets on Day 1 of Week 1; Treatment A: current [1st generation] tablets on Day 1 of Week 2; Treatment B: new [2nd generation] tablets on Day 1 of Week 3 in Cycle 1 (Weeks 1 to 3). All participants received the current (1st generation) tablet formula at a dose of 60 mg on Day 3 of Weeks 1-3 of Cycle 1. |
| BG005 | Arm 6: | Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received selinexor 60 mg/m^2 orally in treatment sequence BCA (Treatment B: new [2nd generation] tablets on Day 1 of Week 1; Treatment C: suspension dose of current [1st generation] tablets on Day 1 of Week 2; Treatment A: current [1st generation] tablets on Day 1 of Week 3 in Cycle 1 (Weeks 1 to 3). All participants received the current (1st generation) tablet formula at a dose of 60 mg on Day 3 of Weeks 1-3 of Cycle 1. |
| BG006 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants | No |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants | No |
|
| Race/Ethnicity, Customized | Count of Participants | Participants | No |
|
Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received selinexor 30 mg/m^2 orally twice weekly in randomized treatment sequence (i.e. Treatment A: fasted, tablet formulation on Day 1 [Week 1] in Arm 1 and Day 1 [Week 2] in Arm 2). |
| OG001 | Arms 1 and 2: Treatment B: High-Fat Meal, Tablet Formulation | Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received selinexor 30 mg/m^2 orally twice weekly in randomized treatment sequence (i.e. Treatment B: high-fat meal, tablet formulation on Day 1 [Week 2] in Arm 1 and Day 1 [Week 1] in Arm 2). |
| OG002 | Arms 1 and 2: Treatment C: Low-Fat Meal, Tablet Formulation | Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received selinexor 30 mg/m^2 orally twice weekly in randomized treatment sequence (i.e. Treatment C: low-fat meal, tablet formulation on Day 1 [Week 3] in Arm 1 and Day 1 [Week 4] in Arm 2). |
| OG003 | Arms 1 and 2: Treatment D: Low-Fat Meal, Capsule Formulation | Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received selinexor 30 mg/m^2 orally twice weekly in randomized treatment sequence (i.e. Treatment D: low-fat meal, capsule formulation on Day 1 [Week 4] in Arm 1 and Day 1 [Week 3] in Arm 2). |
| OG004 | Arms 4, 5, and 6: Treatment A: First Generation Tablet | Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received Selinexor 60 mg/m^2 orally in randomized treatment sequence (i.e. Treatment A: current [1st generation] tablets on Day 1 and 3 in Arm 4, 5 and 6 for Cycle 1 (Weeks 1 to 3). |
| OG005 | Arms 4, 5, and 6: Treatment B: Second Generation Tablet | Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received Selinexor 60 mg/m^2 orally in randomized treatment sequence (i.e. Treatment B: new [2nd generation] tablets on Day 1 in Arm 4, 5 and 6 for (Weeks 1 to 3). |
| OG006 | Arms 4, 5, and 6: Treatment C: Oral Suspension | Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received selinexor 60 mg/m^2 orally in randomized treatment sequence (i.e. Treatment C: suspension dose of current [1st generation] tablets on Day 1 and 3 in Arm 4, 5 and 6 for (Weeks 1 to 3). |
|
|
| Primary | Area Under the Concentration Time Curve From the Time Zero to Extrapolated to Infinity (AUC0-inf) of Selinexor | AUC0-inf was defined as area under the concentration-time curve from time zero to infinity (extrapolated), AUC0-inf was calculated as AUC0-t + Ct/ elimination rate constant (kel), where: Ct = the last observed non- zero concentration. | PK population included all participants in Arms 1, 2 and Arms 4, 5, and 6 who received selinexor, and for whom the PK profile for all treatments could be adequately characterized. Here 'overall number of participants analyzed' signifies participants who are evaluable for this outcome measure. As pre-specified in SAP and protocol Arm 3 was a non-PK group assessment, so data was not collected and analyzed for this PK outcome. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | Day 1 of weeks 1-3 in Cycle 1: Pre-dose (within 10 minutes before swallowing study drug), 15, 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 18, 24, and 48 hours post-dose |
|
|
|
| Primary | Maximum Observed Plasma Concentration (Cmax) of Selinexor | Cmax was defined as maximum observed concentration, taken directly from the plasma concentration data. | PK population included all participants in Arms 1, 2 and Arms 4, 5, and 6 who received selinexor, and for whom the PK profile for all treatments could be adequately characterized. Here 'overall number of participants analyzed' signifies participants who are evaluable for this outcome measure. As pre-specified in SAP and protocol Arm 3 was a non-PK group assessment, so data was not collected and analyzed for this PK outcome. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram per milliliter (ng/mL) | Day 1 of weeks 1-3 in Cycle 1: Pre-dose (within 10 minutes before swallowing study drug), 15, 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 18, 24, and 48 hours post-dose |
|
|
|
| Primary | Time of First Maximum Observed Concentration (Tmax) of Selinexor | Tmax was defined as time of first observation of Cmax, taken directly from the plasma concentration data. | PK population included all participants in Arms 1, 2 and Arms 4, 5, and 6 who received selinexor, and for whom the PK profile for all treatments could be adequately characterized. Here 'overall number of participants analyzed' signifies participants who are evaluable for this outcome measure. As pre-specified in SAP and protocol Arm 3 was a non-PK group assessment, so data was not collected and analyzed for this PK outcome. | Posted | Median | Full Range | Hour | Day 1 of weeks 1-3 in Cycle 1: Pre-dose (within 10 minutes before swallowing study drug), 15, 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 18, 24, and 48 hours post-dose |
|
|
|
| Primary | Terminal Phase Half-Life (t1/2) of Selinexor | t1/2 was the terminal phase half-life, it was calculated as ln(2)/kel. | PK population included all participants in Arms 1, 2 and Arms 4, 5, and 6 who received selinexor, and for whom the PK profile for all treatments could be adequately characterized. Here 'overall number of participants analyzed' signifies participants who are evaluable for this outcome measure. As pre-specified in SAP and protocol Arm 3 was a non-PK group assessment, so data was not collected and analyzed for this PK outcome. | Posted | Mean | Standard Deviation | Hour | Day 1 of weeks 1-3 in Cycle 1: Pre-dose (within 10 minutes before swallowing study drug), 15, 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 18, 24, and 48 hours post-dose |
|
|
|
| Primary | Apparent Total Body Clearance (CL/F) of Selinexor | Apparent total body clearance was calculated as Dose/AUC0-inf, uncorrected for fraction absorbed; reported normalized by participant body weight (kilogram [kg]). | PK population included all participants in Arms 1, 2 and Arms 4, 5, and 6 who received selinexor, and for whom the PK profile for all treatments could be adequately characterized. Here 'overall number of participants analyzed' signifies participants who are evaluable for this outcome measure. As pre-specified in SAP and protocol Arm 3 was a non-PK group assessment, so data was not collected and analyzed for this PK outcome. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liter per hour per kilogram (L/h/kg) | Day 1 of weeks 1-3 in Cycle 1: Pre-dose (within 10 minutes before swallowing study drug), 15, 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 18, 24, and 48 hours post-dose |
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| Primary | Apparent Volume of Distribution (Vd/F) of Selinexor | Vd/F was calculated as Dose/ (kel *AUC0-inf), uncorrected for fraction absorbed; reported normalized by participant body weight (kg). | PK population included all participants in Arms 1, 2 and Arms 4, 5, and 6 who received selinexor, and for whom the PK profile for all treatments could be adequately characterized. Here 'overall number of participants analyzed' signifies participants who are evaluable for this outcome measure. As pre-specified in SAP and protocol Arm 3 was a non-PK group assessment, so data was not collected and analyzed for this PK outcome. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liter per kilogram (L/kg) | Day 1 of weeks 1-3 in Cycle 1: Pre-dose (within 10 minutes before swallowing study drug), 15, 30 minutes, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 18, 24, and 48 hours post-dose |
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| Secondary | Percentage of Participants With Best Overall Response According to Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 Criteria | Best overall response rate was defined as the percentage of participants who achieved complete response (CR), and partial response (PR), as assessed by the RECIST v1.1 criteria. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non target) must have reduction in the short axis to less than (<) 10 millimeter (mm). PR was defined as At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum longest diameter (LD). | Safety population consisted of all participants who received at least one dose of selinexor. Data for this outcome measure analysis was planned to be analyzed as per disease specific sarcoma. | Posted | Number | Percentage of participants | From the date of first documented response until the date of documented progression or last disease assessment (up to 39 months) |
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|
|
| Secondary | Duration of Stable Disease as Per RECIST v1.1 Criteria | Duration of at least stable disease was defined as the time from the date of first dose of study treatment to first documented radiologic evidence of disease recurrence or progression as per RECIST v1.1 Criteria. Participants without evidence of progression were censored at time of last disease assessment. Progressive Disease (PD) was defined as at least a 20% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded since the treatment started. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Appearance of one or more new lesions also constituted progressive disease. | Safety population consisted of all participants who received at least one dose of selinexor. Data for this outcome measure was planned to be analyzed as per disease specific sarcoma. | Posted | Median | 95% Confidence Interval | Months | From the date of first dose of study treatment to first documented radiologic evidence of disease recurrence or progression, censored date (up to 39 months) |
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|
| Secondary | Progression Free Survival (PFS) as Per RECIST v1.1 Criteria | PFS was defined as the time from the date of randomization until the first date of Independent Review Committee (IRC)-confirmed PD per RECIST v1.1, or death due to any cause. PD was defined as at least a 20% increase in the sum of the longest diameter (SLD), taking as reference the smallest sum of the longest diameter (SLD) recorded from baseline or the appearance of 1 or more new lesions. Participants who were last known to be alive and without evidence of progression were censored at time of last disease assessment. If date of progression or death occurred after more than 1 missed disease assessment interval, or 30 days after end of treatment, participants were censored at the time of last evaluable disease assessment prior to the missed assessment. | Safety population consisted of all participants who received at least one dose of selinexor. Data for this outcome measure was planned to be analyzed as per disease specific sarcoma. | Posted | Median | 95% Confidence Interval | Months | From first dose of study treatment to time of disease progression or death, censored date (up to 39 months) |
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|
| Secondary | Overall Survival (OS) | OS was defined as the time from date first dose of study treatment to the date of death. Participants who were still alive prior to the data cutoff for final efficacy analysis, or who dropped out prior to study end, were censored at the day they were last known to be alive. | Safety population consisted of all participants who received at least one dose of selinexor. Data for this outcome measure was planned to be analyzed as per disease specific sarcoma. | Posted | Median | 95% Confidence Interval | Months | From first dose of study treatment to death, censored date (up to 39 months) |
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|
| Secondary | Time to Progression (TTP) | TTP was defined as the time from date of first dose of study treatment to first documented evidence of disease recurrence or progression, or death due to disease progression, whichever occurred first. Participants without evidence of progression were censored at time of last evaluable disease assessment. | Safety population consisted of all participants who received at least one dose of selinexor. Data for this outcome measure was planned to be analyzed as per disease specific sarcoma. | Posted | Median | 95% Confidence Interval | Months | From first dose of study treatment to first documented evidence of disease recurrence or progression, or death, censored date (up to 39 months) |
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| Secondary | Number of Participants With Growth Modulation Index (GMI) Less Than or Equal to (<=) 1.33 and Greater Than (>) 1.33 | GMI was defined as the ratio between the TTP with selinexor and the TTP with the most recent prior treatment. GMI was calculated, using a previously described threshold of 1.3 or greater as a sign of potential drug activity and improved overall survival. | Safety population consisted of all participants who received at least one dose of selinexor. Data for this outcome measure was planned to be analyzed as per disease specific sarcoma. Here 'overall number of participants analyzed' signifies participants who were evaluable for this outcome measure. | Posted | Count of Participants | Participants | No | Up to 39 months |
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| Secondary | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | An AE was any untoward medical occurrence in a participant administered a pharmaceutical product during the course of a study and which does not necessarily have to have a causal relationship with this treatment. SAE defined as any AE, occurring at any dose (including after the informed consent form was signed and prior to dosing) that and regardless of causality that: results in death, is life-threatening (participant was at immediate risk of death from event as it occurred), requires in-patient hospitalization (formal admission to a hospital for medical reasons) or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, results in a congenital anomaly/birth defect. TEAE was defined as any AE with onset or worsening of a pre-existing condition on or after the first administration of study treatment through 30 days following last dose or any event considered drug-related by the investigator through the end of the study. | Safety population consisted of all participants who received at least one dose of selinexor. As pre-specified in SAP, safety data was collected and analyzed as per the individual arms with specified treatment sequences only. | Posted | Count of Participants | Participants | From screening up to 30 days post last study drug dose (up to 39 months) |
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| Secondary | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign, symptom, or medical condition that occur after participant's signed informed consent obtained. TEAE was defined as any AE with onset or worsening of a pre-existing condition on or after the first administration of study treatment through 28 days following last dose or any event considered drug-related by the investigator through the end of the study. Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life-threatening, and Grade 5: death. | Safety population consisted of all participants who received at least one dose of selinexor. As pre-specified in SAP, safety data was collected and analyzed as per the individual arms with specified treatment sequences only. | Posted | Count of Participants | Participants | From screening up to 30 days post last study drug dose (up to 39 months) |
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| Secondary | Number of Participants With Clinically Significant Laboratory Abnormalities | Number of participants with clinically significant laboratory abnormalities including clinical chemistry, hematology, coagulation and urinalysis. Number of participants with clinically significant laboratory abnormalities which were deemed clinically significant by the investigator were reported. | Safety population consisted of all participants who received at least one dose of selinexor. As pre-specified in SAP, safety data was collected and analyzed as per the individual arms with specified treatment sequences only. | Posted | Count of Participants | Participants | From screening up to 30 days post last study drug dose (up to 39 months) |
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| Secondary | Number of Participants With Clinically Significant Changes in Vital Signs | Vital signs included blood pressure (systolic blood pressure and diastolic blood pressure). Measurements were made after the participant had been resting supine for a minimum of 5 minutes. Clinically significant findings were defined as such in the opinion of the investigator occurring at any time on treatment from normal pre-dose based on the condition met (Yes/No). Number of participants with clinically significant changes in vital signs with condition (Yes) were only reported. | Safety population consisted of all participants who received at least one dose of selinexor. As pre-specified in SAP, safety data was collected and analyzed as per the individual arms with specified treatment sequences only. | Posted | Count of Participants | Participants | From screening up to 30 days post last study drug dose (up to 39 months) |
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| Secondary | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECGs) | Twelve lead ECGs were obtained after the participant has rested in a supine position for at least 5 minutes. Clinically significant findings were defined as such in the opinion of the investigator or designated physician occurring at any time on treatment from normal pre-dose. | Safety population consisted of all participants who received at least one dose of selinexor. As pre-specified in SAP, safety data was collected and analyzed as per the individual arms with specified treatment sequences only. | Posted | Count of Participants | Participants | From screening up to 30 days post last study drug dose |
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|
| 2 |
| 10 |
| 4 |
| 10 |
| 10 |
| 10 |
| EG001 | Arm 2: | Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received selinexor 30 mg/m^2 orally twice weekly in treatment sequence BADC (Treatment B: high-fat meal, tablet formulation on Day 1 of Week 1; Treatment A: fasted, tablet formulation on Day 1 of Week 2; Treatment D: low fat meal, capsule formulation on Day 1 of Week 3; Treatment C: low-fat meal, tablet formulation on Day 1 of Week 4 in Cycle 1 (Weeks 1 to 4).All participants received the current (1st generation) tablet formula at a dose of 60 mg on Day 3 of Weeks 1-3 of Cycle 1. | 2 | 9 | 5 | 9 | 9 | 9 |
| EG002 | Arm 3: | Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received Selinexor 50 mg/m^2 first generation tablets twice weekly on Days 1 and 3 of each week within 30 minutes of solid food consumption. | 1 | 17 | 5 | 17 | 17 | 17 |
| EG003 | Arm 4: | Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received Selinexor 60 mg/m^2 orally in treatment sequence ABC (Treatment A: current [1st generation] tablets on Day 1 of Week 1; Treatment B: new [2nd generation] tablets on Day 1 of Week 2; Treatment C: suspension dose of current [1st generation] tablets on Day 1 of Week 3 in Cycle 1 (Weeks 1 to 3). All participants received the current (1st generation) tablet formula at a dose of 60 mg on Day 3 of Weeks 1-3 of Cycle 1. | 3 | 7 | 2 | 7 | 7 | 7 |
| EG004 | Arm 5: | Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received Selinexor 60 mg/m^2 orally in treatment sequence CAB (Treatment C: suspension dose of current [1st generation] tablets on Day 1 of Week 1; Treatment A: current [1st generation] tablets on Day 1 of Week 2; Treatment B: new [2nd generation] tablets on Day 1 of Week 3 in Cycle 1 (Weeks 1 to 3). All participants received the current (1st generation) tablet formula at a dose of 60 mg on Day 3 of Weeks 1-3 of Cycle 1. | 3 | 5 | 2 | 5 | 5 | 5 |
| EG005 | Arm 6: | Participants with advanced sarcomas (Liposarcoma, Leiomyosarcoma, and Other sarcoma) received Selinexor 60 mg/m^2 orally in treatment sequence BCA (Treatment B: new [2nd generation] tablets on Day 1 of Week 1; Treatment C: suspension dose of current [1st generation] tablets on Day 1 of Week 2; Treatment A: current [1st generation] tablets on Day 1 of Week 3 in Cycle 1 (Weeks 1 to 3). All participants received the current (1st generation) tablet formula at a dose of 60 mg on Day 3 of Weeks 1-3 of Cycle 1. | 2 | 6 | 4 | 6 | 6 | 6 |
| Anaemia | Blood and lymphatic system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Cataract | Eye disorders | MedDRA 20.1 | Systematic Assessment |
|
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Large intestinal obstruction | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Pneumatosis intestinalis | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Death | General disorders | MedDRA 20.1 | Systematic Assessment |
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| Sepsis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Lung infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
|
| Wound complication | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
|
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Myelodysplastic syndrome | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.1 | Systematic Assessment |
|
| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.1 | Systematic Assessment |
|
| Autonomic nervous system imbalance | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Confusional state | Psychiatric disorders | MedDRA 20.1 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Pulmonary haemorrhage | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
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| Embolism | Vascular disorders | MedDRA 20.1 | Systematic Assessment |
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| Hypotension | Vascular disorders | MedDRA 20.1 | Systematic Assessment |
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| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 20.1 | Systematic Assessment |
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| Leukopenia | Blood and lymphatic system disorders | MedDRA 20.1 | Systematic Assessment |
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| Neutropenia | Blood and lymphatic system disorders | MedDRA 20.1 | Systematic Assessment |
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| Sinus tachycardia | Cardiac disorders | MedDRA 20.1 | Systematic Assessment |
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| Bradycardia | Cardiac disorders | MedDRA 20.1 | Systematic Assessment |
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| Tachycardia | Cardiac disorders | MedDRA 20.1 | Systematic Assessment |
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| Angina pectoris | Cardiac disorders | MedDRA 20.1 | Systematic Assessment |
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| Atrial fibrillation | Cardiac disorders | MedDRA 20.1 | Systematic Assessment |
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| Left atrial enlargement | Cardiac disorders | MedDRA 20.1 | Systematic Assessment |
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| Palpitations | Cardiac disorders | MedDRA 20.1 | Systematic Assessment |
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| Sinus bradycardia | Cardiac disorders | MedDRA 20.1 | Systematic Assessment |
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| Ventricular arrhythmia | Cardiac disorders | MedDRA 20.1 | Systematic Assessment |
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| Ear discomfort | Ear and labyrinth disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hypoacusis | Ear and labyrinth disorders | MedDRA 20.1 | Systematic Assessment |
|
| Tinnitus | Ear and labyrinth disorders | MedDRA 20.1 | Systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | MedDRA 20.1 | Systematic Assessment |
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| Vision blurred | Eye disorders | MedDRA 20.1 | Systematic Assessment |
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| Vitreous floaters | Eye disorders | MedDRA 20.1 | Systematic Assessment |
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| Cataract | Eye disorders | MedDRA 20.1 | Systematic Assessment |
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| Dry eye | Eye disorders | MedDRA 20.1 | Systematic Assessment |
|
| Lacrimation increased | Eye disorders | MedDRA 20.1 | Systematic Assessment |
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| Periorbital oedema | Eye disorders | MedDRA 20.1 | Systematic Assessment |
|
| Blepharospasm | Eye disorders | MedDRA 20.1 | Systematic Assessment |
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| Eye irritation | Eye disorders | MedDRA 20.1 | Systematic Assessment |
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| Eye pain | Eye disorders | MedDRA 20.1 | Systematic Assessment |
|
| Photopsia | Eye disorders | MedDRA 20.1 | Systematic Assessment |
|
| Visual impairment | Eye disorders | MedDRA 20.1 | Systematic Assessment |
|
| Vitreous detachment | Eye disorders | MedDRA 20.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
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| Abdominal hernia | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Cheilitis | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Gingival pain | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Lip dry | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Oral dysaesthesia | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Oral pain | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Retroperitoneal haematoma | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Chills | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Mucosal inflammation | General disorders | MedDRA 20.1 | Systematic Assessment |
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| Face oedema | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Peripheral swelling | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Thirst | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Catheter site pain | General disorders | MedDRA 20.1 | Systematic Assessment |
|
| Chest discomfort | General disorders | MedDRA 20.1 | Systematic Assessment |
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| Gait disturbance | General disorders | MedDRA 20.1 | Systematic Assessment |
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| Generalised oedema | General disorders | MedDRA 20.1 | Systematic Assessment |
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| Pain | General disorders | MedDRA 20.1 | Systematic Assessment |
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| Tenderness | General disorders | MedDRA 20.1 | Systematic Assessment |
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| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA 20.1 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
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| Oral candidiasis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
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| Angular cheilitis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
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| Conjunctivitis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
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| Cystitis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
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| Eye infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
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| Fungal skin infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
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| Herpes virus infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
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| Herpes zoster | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
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| Post procedural infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Respiratory tract infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Sepsis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
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| Skin infection | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Urosepsis | Infections and infestations | MedDRA 20.1 | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
|
| Wound secretion | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
|
| Cement embolism | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
|
| Gastrointestinal anastomotic leak | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
|
| Skin abrasion | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
|
| Spinal fracture | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
|
| Tooth fracture | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
|
| Wound complication | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Electrocardiogram QT prolonged | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Activated partial thromboplastin time prolonged | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Blood creatine phosphokinase increased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| International normalised ratio increased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Weight increased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Body temperature increased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Heart rate increased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Pulmonary function test decreased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Blood pressure increased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Carbon dioxide decreased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Electrocardiogram ST-T segment abnormal | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Urine output decreased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hypercreatininaemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hyperamylasaemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hyperlipasaemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
|
| Polydipsia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
|
| Glucose tolerance impaired | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Muscle tightness | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Joint swelling | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Musculoskeletal discomfort | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Neoplasm skin | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.1 | Systematic Assessment |
|
| Neoplasm swelling | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.1 | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Memory impairment | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Balance disorder | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Lethargy | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Cognitive disorder | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Depressed level of consciousness | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Disturbance in attention | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Dizziness postural | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Migraine | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Neuralgia | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Presyncope | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Visual field defect | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA 20.1 | Systematic Assessment |
|
| Agitation | Psychiatric disorders | MedDRA 20.1 | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA 20.1 | Systematic Assessment |
|
| Confusional state | Psychiatric disorders | MedDRA 20.1 | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA 20.1 | Systematic Assessment |
|
| Emotional disorder | Psychiatric disorders | MedDRA 20.1 | Systematic Assessment |
|
| Irritability | Psychiatric disorders | MedDRA 20.1 | Systematic Assessment |
|
| Restlessness | Psychiatric disorders | MedDRA 20.1 | Systematic Assessment |
|
| Haematuria | Renal and urinary disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hydronephrosis | Renal and urinary disorders | MedDRA 20.1 | Systematic Assessment |
|
| Pollakiuria | Renal and urinary disorders | MedDRA 20.1 | Systematic Assessment |
|
| Proteinuria | Renal and urinary disorders | MedDRA 20.1 | Systematic Assessment |
|
| Chromaturia | Renal and urinary disorders | MedDRA 20.1 | Systematic Assessment |
|
| Micturition urgency | Renal and urinary disorders | MedDRA 20.1 | Systematic Assessment |
|
| Urinary tract obstruction | Renal and urinary disorders | MedDRA 20.1 | Systematic Assessment |
|
| Pelvic pain | Reproductive system and breast disorders | MedDRA 20.1 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Atelectasis | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Nasal dryness | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Pleuritic pain | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Sneezing | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Stridor | Respiratory, thoracic and mediastinal disorders | MedDRA 20.1 | Systematic Assessment |
|
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Skin lesion | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Nail cuticle fissure | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Onychoclasis | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Photosensitivity reaction | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Skin hyperpigmentation | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Swelling face | Skin and subcutaneous tissue disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA 20.1 | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 20.1 | Systematic Assessment |
|
| Deep vein thrombosis | Vascular disorders | MedDRA 20.1 | Systematic Assessment |
|
| Embolism | Vascular disorders | MedDRA 20.1 | Systematic Assessment |
|
| Flushing | Vascular disorders | MedDRA 20.1 | Systematic Assessment |
|
| Orthostatic hypotension | Vascular disorders | MedDRA 20.1 | Systematic Assessment |
|
| Thrombosis | Vascular disorders | MedDRA 20.1 | Systematic Assessment |
|
| Lymphopenia | Blood and lymphatic system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA 20.1 | Systematic Assessment |
|
Not provided
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |
|
| Title | Measurements |
|---|---|
|
| Participants with Serious TEAEs |
|
| Grade 2: Moderate |
|
| Grade 3: Severe |
|
| Grade 4: Life Threatening |
|
| Grade 5: Fatal |
|
| Clinical Chemistry |
|
| Coagulation: Prothrombin intl. normalized ratio |
|
| Urinalysis |
|
| Systolic Blood Pressure: > 10 mmHg decrease from baseline (Yes) |
|
| Systolic Blood Pressure: > 20 mmHg decrease from baseline (Yes) |
|
| Systolic Blood Pressure: < 100 mmHg and > 10 mmHg decrease from baseline (Yes) |
|
| Systolic Blood Pressure: < 100 mmHg and > 20 mmHg decrease from baseline (Yes) |
|
| Diastolic Blood Pressure: < 60 mmHg (Yes) |
|
| Diastolic Blood Pressure: > 5 mmHg decrease from baseline (Yes) |
|
| Diastolic Blood Pressure: > 10 mmHg decrease from baseline (Yes) |
|
| Diastolic Blood Pressure: < 60 mmHg and > 5 mmHg decrease from baseline (Yes) |
|
| Diastolic Blood Pressure: < 60 mmHg and > 10 mmHg decrease from baseline (Yes) |
|
| Systolic Blood Pressure : > 140 mmHg (Yes) |
|
| Systolic Blood Pressure: > 160 mmHg (Yes) |
|
| Systolic Blood Pressure: > 10 mmHg increase from baseline (Yes) |
|
| Systolic Blood Pressure: > 20 mmHg increase from baseline (Yes) |
|
| Systolic Blood Pressure: > 160 mmHg and > 10 mmHg increase from baseline (Yes) |
|
| Systolic Blood Pressure: > 160 mmHg and > 20 mmHg increase from baseline (Yes) |
|
| Diastolic Blood Pressure: > 90 mmHg (Yes) |
|
| Diastolic Blood Pressure: > 100 mmHg (Yes) |
|
| Diastolic Blood Pressure: > 5 mmHg increase from baseline (Yes) |
|
| Diastolic Blood Pressure: > 10 mmHg increase from baseline (Yes) |
|
| Diastolic Blood Pressure: > 100 mmHg and > 5 mmHg increase from baseline (Yes) |
|
| Diastolic Blood Pressure: > 100 mmHg and > 10 mmHg increase from baseline (Yes) |
|