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| ID | Type | Description | Link |
|---|---|---|---|
| CDR0000322830 | Registry Identifier | PDQ (Physician Data Query) |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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RATIONALE: Lamotrigine may be effective in reducing pain, numbness, tingling, and other symptoms of peripheral neuropathy. It is not yet known whether lamotrigine is effective in treating peripheral neuropathy caused by chemotherapy.
PURPOSE: This randomized phase III trial is studying how well lamotrigine works in reducing pain, numbness, tingling, and other symptoms of peripheral neuropathy caused by chemotherapy in patients with cancer.
OBJECTIVES:
OUTLINE: This is a randomized, placebo-controlled, double-blind study. Patients are stratified according to neurotoxic chemotherapy received (taxanes vs platinum-based compounds vs vinca alkaloids vs combination vs other), status of neurotoxic chemotherapy (actively receiving therapy vs discontinued or completed), and duration of pain or neuropathy symptoms (1-3 months vs 3-6 months vs more than 6 months). Patients are randomized to 1 of 2 treatment arms.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm I - lamotrigine | Experimental | Patients receive oral lamotrigine once daily for 2 weeks and then twice daily for 8 weeks. Treatment continues for 10 weeks in the absence of unacceptable toxicity. Quality of life, pain, mood states, and symptom distress are assessed at baseline and at 4, 6, 8, and 10 weeks. Patients are followed at 3-7 days. |
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| Arm II - placebo | Other | Patients receive oral placebo once daily for 2 weeks and then twice daily for 8 weeks. Treatment continues for 10 weeks in the absence of unacceptable toxicity. Quality of life, pain, mood states, and symptom distress are assessed at baseline and at 4, 6, 8, and 10 weeks. Patients are followed at 3-7 days. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| lamotrigine | Drug |
| ||
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Average Daily Pain Score as Measured Using a Pain Intensity Rating (NRS) | The change in mean score for average daily pain from baseline to week 10 using the Pain Intensity Rating (NRS) are reported below. The NRS scale ranges from 0 to 10 with higher scores corresponding to having more pain. | From baseline to week 10 |
| Change in Average Pain Score as Measured Using the European Cooperative Oncology Group (ECOG) Neuropathy Scale (ENS) | The change in mean score for average daily pain from baseline to week 10 using the European Cooperative Oncology Group (ECOG) neuropathy scale (ENS) are reported below. The ENS scale goes from 0 to 3 with 0=none, 1=mild paresthesias, 2=mild or moderate sensory loss and/or moderate paresthesias, and 3=severe sensory loss or paresthesias that interfere with function. | From baseline to week 10 |
| Measure | Description | Time Frame |
|---|---|---|
| The Change in Overall Quality of Life as Measured by the Uniscale QOL From Baseline to Week 10 | The change in overall quality of life as measured by the Uniscale QOL (Week 10 minus Baseline) using the Wilcoxon test is reported for each arm below. The Uniscale is a score that ranges from 0 to 100, with 0 being QOL as bad as it can be and 100 being as good as it can be. | From baseline to week 10 |
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DISEASE CHARACTERISTICS:
Diagnosis of cancer
Received, or are currently receiving, neurotoxic chemotherapy, including any of the following:
Experiencing pain or symptoms of peripheral neuropathy for at least 1 month attributed to chemotherapy
PATIENT CHARACTERISTICS:
Age
Life expectancy
Hepatic
Renal
Other
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No prior allergic reaction or intolerance to lamotrigine
No extreme difficulty swallowing pills
No other identified causes of painful paresthesia preceding chemotherapy, including any of the following:
Radiation or malignant plexopathy
Lumbar or cervical radiculopathy
Pre-existing peripheral neuropathy of another etiology, such as any of the following:
No significant psychiatric illness (e.g., mania, psychosis, or schizophrenia) that would preclude study participation
Able to complete questionnaires
PRIOR CONCURRENT THERAPY:
Chemotherapy
Other
More than 7 days since prior, and no concurrent use of any of the following:
Tricyclic antidepressants (e.g., amitriptyline, nortriptyline, or desipramine)
Monoamine oxidase inhibitors
Opioid analgesics
Anticonvulsants (e.g., gabapentin, topiramate, valproic acid, or clonazepam)
Adjuvant analgesics (e.g., mexiletine)
Topical analgesics (e.g., lidocaine gel or patch) to the affected area
Amifostine
More than 30 days since prior investigational agents for pain control
No other concurrent investigational agents for pain control
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| Name | Affiliation | Role |
|---|---|---|
| Ravi D. Rao, MD, MBBS | Mayo Clinic | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mayo Clinic Scottsdale | Scottsdale | Arizona | 85259 | United States | ||
| Mayo Clinic - Jacksonville |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 18428211 | Result | Rao RD, Flynn PJ, Sloan JA, Wong GY, Novotny P, Johnson DB, Gross HM, Renno SI, Nashawaty M, Loprinzi CL. Efficacy of lamotrigine in the management of chemotherapy-induced peripheral neuropathy: a phase 3 randomized, double-blind, placebo-controlled trial, N01C3. Cancer. 2008 Jun 15;112(12):2802-8. doi: 10.1002/cncr.23482. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm I - Lamotrigine | Patients receive oral lamotrigine (25 mg per pill) once daily for 2 weeks and then twice daily for 8 weeks. Treatment continues for 10 weeks total in the absence of unacceptable toxicity. |
| FG001 | Arm II - Placebo |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Randomization |
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|
| Change in Brief Pain Inventory (BPI) Worst Pain Score [Week 10 Minus Baseline] | The average change in Brief Pain Inventory (BPI) Worst Pain scores between baseline and week 10 using Wilcoxon test are reported for each arm below. The BPI scales range from 0 to 10 with 0 meaning no pain and 10 meaning pain as bad as you can imagine. | From baseline to week 10 |
| Change in Brief Pain Inventory (BPI) Least Pain Score [Week 10 Minus Baseline] | The average change in Brief Pain Inventory (BPI) Least Pain scores between baseline and week 10 using Wilcoxon test are reported for each arm below. The BPI scales range from 0 to 10 with 0 meaning no pain and 10 meaning pain as bad as you can imagine. Time Frame: Up to 1 week post-treatment | From baseline to week 10 |
| Change in Brief Pain Inventory (BPI) Average Pain Score [Week 10 Minus Baseline] | The average change in Brief Pain Inventory (BPI) Average Pain scores between baseline and week 10 using Wilcoxon test are reported for each arm below. The BPI scales range from 0 to 10 with 0 meaning no pain and 10 meaning pain as bad as you can imagine. | From baseline to week 10 |
| Change in Brief Pain Inventory (BPI) Pain Now Score [Week 10 Minus Baseline] | The average change in Brief Pain Inventory (BPI) Pain Now scores between baseline and week 10 using Wilcoxon test are reported for each arm below. The BPI scales range from 0 to 10 with 0 meaning no pain and 10 meaning pain as bad as you can imagine. | From baseline to week 10 |
| Change in Brief Pain Inventory (BPI) Pain Relief Score [Week 10 Minus Baseline] | The average change in Brief Pain Inventory (BPI) Pain Relief scores between baseline and week 10 using Wilcoxon test are reported for each arm below. The BPI scales range from 0 to 10 with 0 meaning no pain and 10 meaning pain as bad as you can imagine. | From baseline to week 10 |
| Change in Brief Pain Inventory (BPI) Pain Interference Score [Week 10 Minus Baseline] | The average change in Brief Pain Inventory (BPI) Pain Interference scores between baseline and week 10 using Wilcoxon test are reported for each arm below. The BPI scales range from 0 to 10 with 0 meaning no pain and 10 meaning pain as bad as you can imagine. | From baseline to week 10 |
| Change in POMS Total Score [Week 10 Minus Baseline] | The average change in POMS Total scores between baseline and week 10 using Wilcoxon test are reported for each arm below. The POMS scales are calculated from patient responses on 30 questions asking how they have been feeling during the past week. The scores are all transformed so that 0 is the worst possible value and 100 is the best possible value. | From baseline to week 10 |
| Jacksonville |
| Florida |
| 32224 |
| United States |
| CCOP - Atlanta Regional | Atlanta | Georgia | 30342-1701 | United States |
| MBCCOP - Hawaii | Honolulu | Hawaii | 96813 | United States |
| CCOP - Illinois Oncology Research Association | Peoria | Illinois | 61615-7828 | United States |
| CCOP - Carle Cancer Center | Urbana | Illinois | 61801 | United States |
| CCOP - Cedar Rapids Oncology Project | Cedar Rapids | Iowa | 52403-1206 | United States |
| CCOP - Iowa Oncology Research Association | Des Moines | Iowa | 50309-1854 | United States |
| Siouxland Hematology-Oncology Associates at June E. Nylen Cancer Center | Sioux City | Iowa | 51101-1733 | United States |
| CCOP - Wichita | Wichita | Kansas | 67214-3882 | United States |
| CCOP - Michigan Cancer Research Consortium | Ann Arbor | Michigan | 48106 | United States |
| CCOP - Duluth | Duluth | Minnesota | 55805 | United States |
| Mayo Clinic Cancer Center | Rochester | Minnesota | 55905 | United States |
| Coborn Cancer Center | Saint Cloud | Minnesota | 56303 | United States |
| CCOP - Metro-Minnesota | Saint Louis Park | Minnesota | 55416 | United States |
| CCOP - Missouri Valley Cancer Consortium | Omaha | Nebraska | 68106 | United States |
| Cancer Care Center at Medcenter One Hospital | Bismarck | North Dakota | 58501-5505 | United States |
| CCOP - Dayton | Dayton | Ohio | 45429 | United States |
| CCOP - Toledo Community Hospital | Toledo | Ohio | 43623-3456 | United States |
| CCOP - Upstate Carolina | Spartanburg | South Carolina | 29303 | United States |
| Rapid City Regional Hospital | Rapid City | South Dakota | 57709 | United States |
| CCOP - Sioux Community Cancer Consortium | Sioux Falls | South Dakota | 57104 | United States |
| CCOP - St. Vincent Hospital Cancer Center, Green Bay | Green Bay | Wisconsin | 54301 | United States |
Patients receive oral placebo once daily for 2 weeks and then twice daily for 8 weeks. Treatment continues for 10 weeks total in the absence of unacceptable toxicity. |
| COMPLETED |
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| NOT COMPLETED |
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| Treatment |
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm I - Lamotrigine | Patients receive oral lamotrigine (25 mg per pill) once daily for 2 weeks and then twice daily for 8 weeks. Treatment continues for 10 weeks total in the absence of unacceptable toxicity. |
| BG001 | Arm II - Placebo | Patients receive oral placebo once daily for 2 weeks and then twice daily for 8 weeks. Treatment continues for 10 weeks total in the absence of unacceptable toxicity. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Full Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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| 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 | Change in Average Daily Pain Score as Measured Using a Pain Intensity Rating (NRS) | The change in mean score for average daily pain from baseline to week 10 using the Pain Intensity Rating (NRS) are reported below. The NRS scale ranges from 0 to 10 with higher scores corresponding to having more pain. | Posted | Mean | Standard Deviation | units on a scale | From baseline to week 10 |
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| Primary | Change in Average Pain Score as Measured Using the European Cooperative Oncology Group (ECOG) Neuropathy Scale (ENS) | The change in mean score for average daily pain from baseline to week 10 using the European Cooperative Oncology Group (ECOG) neuropathy scale (ENS) are reported below. The ENS scale goes from 0 to 3 with 0=none, 1=mild paresthesias, 2=mild or moderate sensory loss and/or moderate paresthesias, and 3=severe sensory loss or paresthesias that interfere with function. | Posted | Mean | Standard Deviation | units on a scale | From baseline to week 10 |
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| Secondary | The Change in Overall Quality of Life as Measured by the Uniscale QOL From Baseline to Week 10 | The change in overall quality of life as measured by the Uniscale QOL (Week 10 minus Baseline) using the Wilcoxon test is reported for each arm below. The Uniscale is a score that ranges from 0 to 100, with 0 being QOL as bad as it can be and 100 being as good as it can be. | Participants with Uniscale QOL data at both time points available were assessed. | Posted | Mean | Standard Deviation | units on a scale | From baseline to week 10 |
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| Secondary | Change in Brief Pain Inventory (BPI) Worst Pain Score [Week 10 Minus Baseline] | The average change in Brief Pain Inventory (BPI) Worst Pain scores between baseline and week 10 using Wilcoxon test are reported for each arm below. The BPI scales range from 0 to 10 with 0 meaning no pain and 10 meaning pain as bad as you can imagine. | Participants with BPI Worst Pain data at both time points available were assessed. | Posted | Mean | Standard Deviation | units on a scale | From baseline to week 10 |
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| Secondary | Change in Brief Pain Inventory (BPI) Least Pain Score [Week 10 Minus Baseline] | The average change in Brief Pain Inventory (BPI) Least Pain scores between baseline and week 10 using Wilcoxon test are reported for each arm below. The BPI scales range from 0 to 10 with 0 meaning no pain and 10 meaning pain as bad as you can imagine. Time Frame: Up to 1 week post-treatment | Participants with BPI Least Pain data at both time points available were assessed. | Posted | Mean | Standard Deviation | units on a scale | From baseline to week 10 |
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| Secondary | Change in Brief Pain Inventory (BPI) Average Pain Score [Week 10 Minus Baseline] | The average change in Brief Pain Inventory (BPI) Average Pain scores between baseline and week 10 using Wilcoxon test are reported for each arm below. The BPI scales range from 0 to 10 with 0 meaning no pain and 10 meaning pain as bad as you can imagine. | Participants with BPI Average Pain data at both time points available were assessed. | Posted | Mean | Standard Deviation | units on a scale | From baseline to week 10 |
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| Secondary | Change in Brief Pain Inventory (BPI) Pain Now Score [Week 10 Minus Baseline] | The average change in Brief Pain Inventory (BPI) Pain Now scores between baseline and week 10 using Wilcoxon test are reported for each arm below. The BPI scales range from 0 to 10 with 0 meaning no pain and 10 meaning pain as bad as you can imagine. | Participants with BPI Pain Now data at both time points available were assessed. | Posted | Mean | Standard Deviation | units on a scale | From baseline to week 10 |
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| Secondary | Change in Brief Pain Inventory (BPI) Pain Relief Score [Week 10 Minus Baseline] | The average change in Brief Pain Inventory (BPI) Pain Relief scores between baseline and week 10 using Wilcoxon test are reported for each arm below. The BPI scales range from 0 to 10 with 0 meaning no pain and 10 meaning pain as bad as you can imagine. | Participants with BPI Pain Relief data at both time points available were assessed. | Posted | Mean | Standard Deviation | units on a scale | From baseline to week 10 |
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| Secondary | Change in Brief Pain Inventory (BPI) Pain Interference Score [Week 10 Minus Baseline] | The average change in Brief Pain Inventory (BPI) Pain Interference scores between baseline and week 10 using Wilcoxon test are reported for each arm below. The BPI scales range from 0 to 10 with 0 meaning no pain and 10 meaning pain as bad as you can imagine. | Participants with BPI Pain Interference data at both time points available were assessed. | Posted | Mean | Standard Deviation | units on a scale | From baseline to week 10 |
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| Secondary | Change in POMS Total Score [Week 10 Minus Baseline] | The average change in POMS Total scores between baseline and week 10 using Wilcoxon test are reported for each arm below. The POMS scales are calculated from patient responses on 30 questions asking how they have been feeling during the past week. The scores are all transformed so that 0 is the worst possible value and 100 is the best possible value. | Participants with POMS scales data at both time points available were assessed. | Posted | Mean | Standard Deviation | units on a scale | From baseline to week 10 |
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Adverse events were collected over the 10 weeks of the study.
Each CTCAE term is a unique representation of a specific event used for medical documentation/scientific analysis and is a single MedDRA Lowest Level Term (LLT). All AEs are reported below for patients who reported AEs for cycle >0 and grade >0.Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, and appear in the SAE table.
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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 I - Lamotrigine | Patients receive oral lamotrigine (25 mg per pill) once daily for 2 weeks and then twice daily for 8 weeks. Treatment continues for 10 weeks total in the absence of unacceptable toxicity. | 0 | 61 | 0 | 61 | 26 | 61 |
| EG001 | Arm II - Placebo | Patients receive oral placebo once daily for 2 weeks and then twice daily for 8 weeks. Treatment continues for 10 weeks total in the absence of unacceptable toxicity. | 0 | 63 | 0 | 63 | 24 | 63 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Arrhythmia supraventricular | Cardiac disorders | MedDRA 6 | Systematic Assessment |
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| Vision blurred | Eye disorders | MedDRA 6 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA 6 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 6 | Systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | MedDRA 6 | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA 6 | Systematic Assessment |
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| Flatulence | Gastrointestinal disorders | MedDRA 6 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 6 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 6 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 6 | Systematic Assessment |
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| General symptom | General disorders | MedDRA 6 | Systematic Assessment |
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| Pain | General disorders | MedDRA 6 | Systematic Assessment |
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| Pain due to radiation | General disorders | MedDRA 6 | Systematic Assessment |
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| Infection without neutropenia | Infections and infestations | MedDRA 6 | Systematic Assessment |
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| Blood glucose increased | Metabolism and nutrition disorders | MedDRA 6 | Systematic Assessment |
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| Dehydration | Metabolism and nutrition disorders | MedDRA 6 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 6 | Systematic Assessment |
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| Muscle weakness | Musculoskeletal and connective tissue disorders | MedDRA 6 | Systematic Assessment |
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| Ataxia | Nervous system disorders | MedDRA 6 | Systematic Assessment |
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| Depressed level of consciousness | Nervous system disorders | MedDRA 6 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 6 | Systematic Assessment |
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| Extrapyramidal disorder | Nervous system disorders | MedDRA 6 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 6 | Systematic Assessment |
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| Nystagmus | Nervous system disorders | MedDRA 6 | Systematic Assessment |
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| Peripheral sensory neuropathy | Nervous system disorders | MedDRA 6 | Systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA 6 | Systematic Assessment |
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| Dysuria (painful urination) | Renal and urinary disorders | MedDRA 6 | Systematic Assessment |
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| Dyspnea (shortness of breath) | Respiratory, thoracic and mediastinal disorders | MedDRA 6 | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 6 | Systematic Assessment |
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| Rash desquamating | Skin and subcutaneous tissue disorders | MedDRA 6 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Charles L. Loprinzi, M.D. | Mayo Clinic | 507-284-3731 | cloprinzi@mayo.edu |
| ID | Term |
|---|---|
| D020258 | Neurotoxicity Syndromes |
| D010146 | Pain |
| ID | Term |
|---|---|
| D009422 | Nervous System Diseases |
| D011041 | Poisoning |
| D064419 | Chemically-Induced Disorders |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D000077213 | Lamotrigine |
| ID | Term |
|---|---|
| D014227 | Triazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Other (Specifics not available) |
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| Male |
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