Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| P01NS044233 | U.S. NIH Grant/Contract | View source | |
| U54NS065736 | U.S. NIH Grant/Contract | View source |
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DSMB recommended stopping the study after an interim analysis of the primary endpoint revealed that futility criteria were met.
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| Name | Class |
|---|---|
| National Institute of Neurological Disorders and Stroke (NINDS) | NIH |
| Vanderbilt University | OTHER |
| Rare Disease Research Network Autonomic Consortium | UNKNOWN |
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The purpose of this study was to determine whether Rifampicin was effective in slowing or reversing the progression of multiple system atrophy (MSA). Research studies indicate that there is an abnormality in protein synthesis and structure in parts of the brain responsible for MSA (protein misfolding) and the drug Rifampicin could potentially prevent or reverse this protein alteration. The study was done on participants with early MSA. The study consisted of taking the drug 2 times a day for 12 months. Participants underwent an evaluation of symptoms and function and will underwent a neurologic examination at the beginning of the study, at 6 months and at 12 months. They were also be contacted at 3 and 9 months by telephone. Studies were done at 10 participating sites.
MSA is a progressive, fatal disorder characterized by autonomic failure and parkinsonism and/or cerebellar involvement. Neuropathologically, MSA is characterized by glial cytoplasmic inclusions (GCI) of abnormally aggregated α-synuclein (α-syn). This was a study to test the hypothesis that Rifampicin, because of its ability to inhibit the formation of α-synuclein fibrils and disaggregate fibrils already formed, will delay progression or reverse neurologic and autonomic functions and symptoms in MSA. This approach has been proposed as a potential approach to treat parkinsonism and specifically, MSA. In an experimental model of MSA, it was hypothesized that Rifampicin would improve behavioral abnormalities of MSA and halt or reverse the pathological changes. The primary objective was to undertake a double-blind placebo-controlled clinical trial on the effect of Rifampicin on progression of neurological and autonomic failure in MSA.
The Data Safety Monitoring Board (DSMB) recommended stopping the study after an interim analysis of the primary endpoint revealed that futility criteria were met.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Rifampicin | Active Comparator | Subjects randomized to this arm will receive 300 mg Rifampicin two times a day for 12 months. |
|
| Placebo | Placebo Comparator | Subjects randomized to this arm will receive placebo capsules twice daily for 12 months. The capsules will contain riboflavin (vitamin B2). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Rifampicin | Drug | 300 mg, 2 times daily |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Rate of Change From Baseline to 12 Months in the Total Unified Multiple System Atrophy Rating Scale (UMSARS) Part I Score (Minus Question 11) | UMSARS is a scale measuring disease progression that comprises 4 parts; only Parts I and II were used in this study. Part I scores symptoms of neurological and autonomic dysfunction. Part II is a motor examination. Part I has 12 questions with a rating scale ranging from 0 (normal) to 4 (extreme dysfunction). Therefore the total score for Part I could range from 0 (normal) to 48 (extreme dysfunction). Participant-specific rate of change in points per month was estimated using slope estimate from least square regression where for each participant, their UMSARS I scores were plotted over time measured in months. | baseline, 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline to 12 Months in UMSARS Part I Score (Minus Question 11) | UMSARS is a scale measuring disease progression that comprises 4 parts, only Parts I and II were used in this study. Part I scores symptoms of neurological and autonomic dysfunction. Part II is a motor examination. Part I has 12 questions with a rating scale ranging from 0 (normal) to 4 (extreme dysfunction). Therefore the total score for Part I could range from 0 (normal) to 48 (extreme dysfunction). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Phillip A Low, MD | Mayo Clinic | Principal Investigator |
| David Robertson, MD | Vanderbilt University | Principal Investigator |
| Sid Gilman, retired, MD | University of Michigan | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UCLA Medical Center | Los Angeles | California | 90095 | United States | ||
| University of California, San Diego |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24507091 | Result | Low PA, Robertson D, Gilman S, Kaufmann H, Singer W, Biaggioni I, Freeman R, Perlman S, Hauser RA, Cheshire W, Lessig S, Vernino S, Mandrekar J, Dupont WD, Chelimsky T, Galpern WR. Efficacy and safety of rifampicin for multiple system atrophy: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2014 Mar;13(3):268-75. doi: 10.1016/S1474-4422(13)70301-6. Epub 2014 Feb 5. |
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Subjects were enrolled from 10 specialized tertiary centers in the United States from April 2011 through April 2012.
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| ID | Title | Description |
|---|---|---|
| FG000 | Rifampicin | Subjects randomized to this arm will receive 300 mg Rifampicin two times a day for 12 months. |
| FG001 | Placebo | Subjects randomized to this arm will receive placebo capsules twice daily for 12 months. The capsules will contain riboflavin (vitamin B2). |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
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| ID | Title | Description |
|---|---|---|
| BG000 | Rifampicin | Subjects randomized to this arm will receive 300 mg Rifampicin two times a day for 12 months. |
| BG001 | Placebo | Subjects randomized to this arm will receive placebo capsules twice daily for 12 months. The capsules will contain riboflavin (vitamin B2). |
| 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 | Rate of Change From Baseline to 12 Months in the Total Unified Multiple System Atrophy Rating Scale (UMSARS) Part I Score (Minus Question 11) | UMSARS is a scale measuring disease progression that comprises 4 parts; only Parts I and II were used in this study. Part I scores symptoms of neurological and autonomic dysfunction. Part II is a motor examination. Part I has 12 questions with a rating scale ranging from 0 (normal) to 4 (extreme dysfunction). Therefore the total score for Part I could range from 0 (normal) to 48 (extreme dysfunction). Participant-specific rate of change in points per month was estimated using slope estimate from least square regression where for each participant, their UMSARS I scores were plotted over time measured in months. | Analysis was done using intention to treat principles and no imputations were done for any missing values or slope estimates. All randomized participants who took at least two doses of the study drug were included in the principal efficacy analysis. One subject on the Rifampicin arm did not return after the baseline visit. | Posted | Mean | Standard Deviation | units on a scale per month | baseline, 12 months |
Adverse events were to be recorded from the time a participant signed the informed consent form and throughout the 12 months of the study, even if they prematurely discontinued the study drug.
The attribution of serious adverse events was determined by the Medical Review Officer, whereas the attribution of non-serious adverse events was determined by the reporter.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Rifampicin | Subjects randomized to this arm will receive 300 mg Rifampicin two times a day for 12 months. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Joint Function | Musculoskeletal and connective tissue disorders | CTCAE (Unspecified) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Speech impairment | General disorders | CTCAE (Unspecified) | Systematic Assessment |
The study was terminated early; the Data Safety and Monitoring Board recommended stopping the study after an interim analysis of the primary endpoint revealed that futility criteria were met.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Phillip A. Low | Mayo Clinic | 507-284-3375 | low@mayo.edu |
Not provided
| ID | Term |
|---|---|
| D019578 | Multiple System Atrophy |
| ID | Term |
|---|---|
| D054969 | Primary Dysautonomias |
| D001342 | Autonomic Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D001480 | Basal Ganglia Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D012293 | Rifampin |
| C087181 | isoniazid, pyrazinamide, rifampin drug combination |
| D012256 | Riboflavin |
| ID | Term |
|---|---|
| D012294 | Rifamycins |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
Not provided
Not provided
Not provided
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| placebo | Drug | placebo |
|
|
| baseline, 12 months |
| Change From Baseline to 12 Months in UMSARS Part II | UMSARS is a scale measuring disease progression that comprises 4 parts; only Parts I and II were used in this study. Part I scores symptoms of neurological and autonomic dysfunction. Part II is a motor examination. Part II has 14 items with a rating scale ranging from 0 (normal) to 4 (extreme dysfunction). Therefore the total score for Part II could range from 0 (normal) to 56 (extreme dysfunction). | baseline, 12 months |
| Change From Baseline to 12 Months in Total UMSARS (i.e., UMSARS Part I Minus Question 11 + UMSARS Part II) | UMSARS is a scale measuring disease progression that comprises 4 parts; only Parts I and II were used in this study. Part I scores symptoms of neurological and autonomic dysfunction. Part II is a motor examination. Part I has 12 questions with a rating scale ranging from 0 (normal) to 4 (extreme dysfunction). Part II has 14 items with a rating scale ranging from 0 (normal) to 4 (extreme dysfunction). Therefore the total score for total UMSARS Parts I minus Question 11 + Part II could range from 0 (normal) to 104 (extreme dysfunction). | baseline, 12 months |
| Rate of Change From Baseline to 12 Months in Total UMSARS (i.e., UMSARS Part I Minus Question 11 + UMSARS Part II) Using Slope Estimate | UMSARS is a scale measuring disease progression that comprises 4 parts; only Parts I and II were used in this study. Part I scores symptoms of neurological and autonomic dysfunction. Part II is a motor examination. Part I has 12 questions with a rating scale ranging from 0 (normal) to 4 (extreme dysfunction). Part II has 14 items with a rating scale ranging from 0 (normal) to 4 (extreme dysfunction). Therefore the total score for total UMSARS Parts I minus Question 11 + Part II could range from 0 (normal) to 104 (extreme dysfunction). Participant-specific rate of change in points per month was estimated using slope estimate from least square regression where for each participant, their total UMSARS scores were plotted over time measured in months. | baseline, 12 months |
| Change From Baseline to 12 Months in the COMPASS-Select Scale | The composite autonomic symptoms score (COMPASS) provides a score of autonomic symptom severity with appropriate weighting. In the COMPASS_select, symptoms are confined to 6 select domains of symptoms. The version of the COMPASS-Select used (06-09-2009 v1) has 46 questions, with multiple parts, scores ranging from "much worse" to "no such symptoms." Scores could range from 0 (no such symptoms) to 85 (much worse). | baseline, 12 months |
| Change in the COMPASS-Select-Change Scale From Baseline to 12 Months | The change in COMPASS is a derivative of COMPASS and evaluates the change in symptoms over time on selected domains of symptoms as a function of natural history or intervention therapy. The focus is on 7 selected domains. The version of the COMPASS-Change -Select Scale used (06-09-2009 Ver. 1) has 16 questions, with multiple parts, scores ranging from "much worse" to "no such symptoms." The score could range from 0 (no such symptoms) to 94 (much worse). | baseline, 12 months |
| San Diego |
| California |
| 92103 |
| United States |
| Mayo Clinic | Jacksonville | Florida | 32224 | United States |
| University of South Florida | Tampa | Florida | 33606 | United States |
| Harvard Medical School | Boston | Massachusetts | 02215 | United States |
| University of Michigan | Ann Arbor | Michigan | 48109 | United States |
| Mayo Clinic | Rochester | Minnesota | 55905 | United States |
| New York University | New York | New York | 10016 | United States |
| Vanderbilt University | Nashville | Tennessee | 37232 | United States |
| University of Texas Southwestern Medical Center | Dallas | Texas | 75390 | United States |
| Withdrawal by Subject |
|
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Multiple System Atrophy (MSA) Type | Number | participants |
|
| Certainty of Multiple System Atrophy (MSA) Diagnosis | Criteria for probable MSA:1)Autonomic failure involving urinary incontinence or an orthostatic decrease of blood pressure within 3 min of standing by at least 30 mm Hg systolic or 15 mm Hg diastolic and 2)Poorly levodopa-responsive parkinsonism, or 3) cerebellar syndrome (gait ataxia with cerebellar dysarthria, limb ataxia, or cerebellar oculomotor dysfunction). Criteria for possible MSA:1)Parkinsonism or 2)cerebellar syndrome and 3)at least one feature suggesting autonomic dysfunction (unexplained urinary urgency, frequent bladder emptying, erectile dysfunction, orthostatic hypotension.) | Number | participants |
|
| ID |
|---|
| Title |
|---|
| Description |
|---|
| OG000 | Rifampicin | Subjects randomized to this arm will receive 300 mg Rifampicin two times a day for 12 months. |
| OG001 | Placebo | Subjects randomized to this arm will receive placebo capsules twice daily for 12 months. The capsules will contain riboflavin (vitamin B2). |
|
|
|
| Secondary | Change From Baseline to 12 Months in UMSARS Part I Score (Minus Question 11) | UMSARS is a scale measuring disease progression that comprises 4 parts, only Parts I and II were used in this study. Part I scores symptoms of neurological and autonomic dysfunction. Part II is a motor examination. Part I has 12 questions with a rating scale ranging from 0 (normal) to 4 (extreme dysfunction). Therefore the total score for Part I could range from 0 (normal) to 48 (extreme dysfunction). | Analysis was done using intention to treat principles. Not all patients reached the 12 month time point due to missed visits or the early termination of the study. | Posted | Mean | Standard Deviation | units on a scale | baseline, 12 months |
|
|
|
|
| Secondary | Change From Baseline to 12 Months in UMSARS Part II | UMSARS is a scale measuring disease progression that comprises 4 parts; only Parts I and II were used in this study. Part I scores symptoms of neurological and autonomic dysfunction. Part II is a motor examination. Part II has 14 items with a rating scale ranging from 0 (normal) to 4 (extreme dysfunction). Therefore the total score for Part II could range from 0 (normal) to 56 (extreme dysfunction). | Analysis was done using intention to treat principles. Not all patients reached the 12 month time point due to missed visits or the early termination of the study. | Posted | Mean | Standard Deviation | units on a scale | baseline, 12 months |
|
|
|
|
| Secondary | Change From Baseline to 12 Months in Total UMSARS (i.e., UMSARS Part I Minus Question 11 + UMSARS Part II) | UMSARS is a scale measuring disease progression that comprises 4 parts; only Parts I and II were used in this study. Part I scores symptoms of neurological and autonomic dysfunction. Part II is a motor examination. Part I has 12 questions with a rating scale ranging from 0 (normal) to 4 (extreme dysfunction). Part II has 14 items with a rating scale ranging from 0 (normal) to 4 (extreme dysfunction). Therefore the total score for total UMSARS Parts I minus Question 11 + Part II could range from 0 (normal) to 104 (extreme dysfunction). | Analysis was done using intention to treat principles. Not all patients reached the 12 month time point due to missed visits or the early termination of the study. | Posted | Mean | Standard Deviation | units on a scale | baseline, 12 months |
|
|
|
|
| Secondary | Rate of Change From Baseline to 12 Months in Total UMSARS (i.e., UMSARS Part I Minus Question 11 + UMSARS Part II) Using Slope Estimate | UMSARS is a scale measuring disease progression that comprises 4 parts; only Parts I and II were used in this study. Part I scores symptoms of neurological and autonomic dysfunction. Part II is a motor examination. Part I has 12 questions with a rating scale ranging from 0 (normal) to 4 (extreme dysfunction). Part II has 14 items with a rating scale ranging from 0 (normal) to 4 (extreme dysfunction). Therefore the total score for total UMSARS Parts I minus Question 11 + Part II could range from 0 (normal) to 104 (extreme dysfunction). Participant-specific rate of change in points per month was estimated using slope estimate from least square regression where for each participant, their total UMSARS scores were plotted over time measured in months. | Analysis was done using intention to treat principles. Not all patients reached the 12 month time point due to missed visits or the early termination of the study. | Posted | Mean | Standard Deviation | units on a scale per month | baseline, 12 months |
|
|
|
|
| Secondary | Change From Baseline to 12 Months in the COMPASS-Select Scale | The composite autonomic symptoms score (COMPASS) provides a score of autonomic symptom severity with appropriate weighting. In the COMPASS_select, symptoms are confined to 6 select domains of symptoms. The version of the COMPASS-Select used (06-09-2009 v1) has 46 questions, with multiple parts, scores ranging from "much worse" to "no such symptoms." Scores could range from 0 (no such symptoms) to 85 (much worse). | Analysis was done using intention to treat principles. Not all patients reached the 12 month time point due to missed visits or the early termination of the study. | Posted | Mean | Standard Deviation | units on a scale | baseline, 12 months |
|
|
|
|
| Secondary | Change in the COMPASS-Select-Change Scale From Baseline to 12 Months | The change in COMPASS is a derivative of COMPASS and evaluates the change in symptoms over time on selected domains of symptoms as a function of natural history or intervention therapy. The focus is on 7 selected domains. The version of the COMPASS-Change -Select Scale used (06-09-2009 Ver. 1) has 16 questions, with multiple parts, scores ranging from "much worse" to "no such symptoms." The score could range from 0 (no such symptoms) to 94 (much worse). | Analysis was done using intention to treat principles. Not all patients reached the 12 month time point due to missed visits or the early termination of the study. | Posted | Mean | Standard Deviation | units on a scale | baseline, 12 months |
|
|
|
|
| 3 |
| 50 |
| 31 |
| 50 |
| EG001 | Placebo | Subjects randomized to this arm will receive placebo capsules twice daily for 12 months. The capsules will contain riboflavin (vitamin B2). | 12 | 50 | 26 | 50 |
| Infection with unknown ANC | Infections and infestations | CTCAE (Unspecified) | Systematic Assessment |
|
| Musculoskeletal/soft tissue - other | Musculoskeletal and connective tissue disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Thrombosis/thrombus/embolism | Cardiac disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Cardiac ischemia/infarction | Cardiac disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Vessel injury - artery | Cardiac disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Death not associated with CTCAE Term | Cardiac disorders | CTCAE (Unspecified) | Systematic Assessment | 2 subjects died post-study, unrelated to study drug or placebo. |
|
| Mood Alteration | Psychiatric disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Cardiac general - other | Cardiac disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Renal/genitourinary - other | Renal and urinary disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Adult Respiratory Distress Syndrome (ARDS) | Respiratory, thoracic and mediastinal disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Liver Dysfunction/failure | Hepatobiliary disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Renal Failure | Renal and urinary disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Obstruction/stenosis of airway | Respiratory, thoracic and mediastinal disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Neurology - other | Nervous system disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Vomiting - aspirated/stroke | Vascular disorders | CTCAE (Unspecified) | Systematic Assessment | Subject hospitalized for hernia repair surgery, and surgery went well. Subject was being cleaned by family and vomited, aspirated, and stroked. Subject experienced multiple system failure and was declared dead. |
|
| Prolonged QTc Interval | Cardiac disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Leukocytes | Immune system disorders | CTCAE (Unspecified) | Systematic Assessment | Total White Blood Count (WBC) |
|
| Nausea | Gastrointestinal disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Neutrophils/granulocytes | Immune system disorders | CTCAE (Unspecified) | Systematic Assessment | Absolute neutrophil count (ANC)/Absolute granulocyte count (AGC) |
|
| Wound complication, non-infectious | Infections and infestations | CTCAE (Unspecified) | Systematic Assessment |
|
| Renal/Genitourinary - Other | Renal and urinary disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Urinary frequency/urgency | Renal and urinary disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Heartburn/dyspepsia | Gastrointestinal disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Pain | General disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Fatigue | General disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Petechiae/purpura | Vascular disorders | CTCAE (Unspecified) | Systematic Assessment | hemorrhage/bleeding into skin or mucosa |
|
| Edema: limb | Blood and lymphatic system disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Encephalopathy | Nervous system disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Infection with unknown | Infections and infestations | CTCAE (Unspecified) | Systematic Assessment | ANC |
|
| Lymphopenia | Blood and lymphatic system disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Eyelid dysfunction | Eye disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Glucose, serum-low | Endocrine disorders | CTCAE (Unspecified) | Systematic Assessment | hypoglycemia |
|
| Constitutional Symptoms - other | General disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Creatinine | Renal and urinary disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Neurology - other | Nervous system disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Ataxia | Nervous system disorders | CTCAE (Unspecified) | Systematic Assessment | lack of voluntary coordination of muscle movements |
|
| Nasal Cavity/paranasal sinus reactions | Respiratory, thoracic and mediastinal disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Cystitis | Renal and urinary disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Gastrointestinal - other | Gastrointestinal disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Musculoskeletal/soft tissue - other | Musculoskeletal and connective tissue disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Pneumonitis/pulmonary infiltrates | Respiratory, thoracic and mediastinal disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Taste Alteration (dysgeusia) | General disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Tremor | Musculoskeletal and connective tissue disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Neuropathy: sensory | Nervous system disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Vision - photophobia | Eye disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Dizziness | General disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Hypotension | Vascular disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Urinary retention | Renal and urinary disorders | CTCAE (Unspecified) | Systematic Assessment | (including neurogenic bladder) |
|
| Bruising (in absence of Grade 3 or 4 thrombocytopenia) | General disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Urine color change | Renal and urinary disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Hemorrhage/bleeding - other | Vascular disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Hyperpigmentation | Skin and subcutaneous tissue disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Metabolic/Laboratory - other | General disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Syncope (fainting) | General disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Endocrine - other | Endocrine disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Allergic reaction/hypersensitivity | General disorders | CTCAE (Unspecified) | Systematic Assessment | (including drug fever) |
|
| Blood/Bone marrow - other | Vascular disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Dysphagia (difficulty swallowing) | General disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Glucose, serum-high | Endocrine disorders | CTCAE (Unspecified) | Systematic Assessment | (hyperglycemia) |
|
| Hemoglobin | Blood and lymphatic system disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Hepatobiliary/Pancreas - other | Endocrine disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Joint Function | Musculoskeletal and connective tissue disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Rigors/chills | General disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Adult Respiratory Distress Syndrome (ARDS) | Respiratory, thoracic and mediastinal disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Pulmonary/Upper Respiratory - other | Respiratory, thoracic and mediastinal disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Sweating (diasporesis) | Skin and subcutaneous tissue disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Mood alteration | Psychiatric disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Weight loss | General disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Vision - blurred vision | Eye disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Bone: spine - scoliosis | Musculoskeletal and connective tissue disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Somnolence/depressed level of consciousness | General disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Dermatology/Skin - other | Skin and subcutaneous tissue disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Ophthalmoplegia/diplopia (double vision) | Eye disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Obstruction/stenosis of airway | Respiratory, thoracic and mediastinal disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Fracture | Musculoskeletal and connective tissue disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| International Normalized Ratio (INR) of prothrombin time | Vascular disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| ALT, serum glutamic pyruvic transaminase (SGPT) | Hepatobiliary disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| AST, serum glutamic oxaloacetic transaminase (SGOT) | Hepatobiliary disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Dyspnea (shortness of breath) | Respiratory, thoracic and mediastinal disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Dry mouth/salivary gland (xerostomia) | General disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Memory Impairment | Psychiatric disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Liver dysfunction/failure (clinical) | Hepatobiliary disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| Muscle weakness, generalized or specific area (not due to neuropathy) | Musculoskeletal and connective tissue disorders | CTCAE (Unspecified) | Systematic Assessment |
|
| CNS cerebrovascular ischemia | Nervous system disorders | CTCAE (Unspecified) | Systematic Assessment |
|
Not provided
Not provided
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009069 | Movement Disorders |
| D000080874 | Synucleinopathies |
| D019636 | Neurodegenerative Diseases |
| D047029 | Lactams, Macrocyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |
| D005415 | Flavins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D006575 | Heterocyclic Compounds, 3-Ring |
| D003067 | Coenzymes |
| D045762 | Enzymes and Coenzymes |
| D010860 | Pigments, Biological |
| D001685 | Biological Factors |