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| ID | Type | Description | Link |
|---|---|---|---|
| R56AG055416 | U.S. NIH Grant/Contract | View source | |
| R01AG048349 | U.S. NIH Grant/Contract | View source | |
| R01AG061091 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute on Aging (NIA) | NIH |
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The primary objective of the study is to evaluate the efficacy of AGB101 on slowing cognitive and functional impairment as measured by changes in the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score as compared with placebo in participants with mild cognitive impairment due to Alzheimer's Disease (MCI due to AD) also known as prodromal AD. Participants will be randomized to receive placebo or AGB101 (220 mg), once daily for 78 weeks. Secondary objectives are to assess the effect of AGB101 compared with placebo on clinical progression as measured by Mini-Mental State Examination (MMSE) and Functional Activities Questionnaire (FAQ).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo Oral Tablet | Placebo Comparator | Matching placebo to AGB101 tablet once daily, taken orally, for 78 weeks. |
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| AGB101 220 mg tablet | Experimental | Single 220 mg AGB101 tablet once daily, taken orally, for 78 weeks. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo Oral Tablet | Drug | Placebo oral tablet |
| |
| AGB101 220 mg tablet |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) Score From Baseline | CDR-SB scores at baseline were subtracted from CDR-SB scores at week 78 to generate the change score from baseline, with a possible total range of -18 to 18. Positive change scores reflect greater impairment on the CDR-SB at week 78, while negative change scores reflect less impairment on the CDR-SB at week 78. | 78 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Mini Mental Status Exam (MMSE) Score From Baseline | MMSE scores at baseline were subtracted from MMSE scores at week 78 to generate the change score from baseline, with a possible total range of -30 to 30. Positive change scores reflect improved performance on the MMSE at week 78, while negative change scores reflect worsening performance on the MMSE at week 78. | 78 weeks |
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Inclusion Criteria:
Subjects between 55 and 85 years old (inclusive) in good general health:
Have a study partner who has sufficient contact with the subject to be able to provide assessment of memory changes, who can accompany the subject to all the clinic visits for the duration of each visit, and who is able to provide an independent evaluation of the subject's functioning
Have MCI due to AD as defined by all of the following criteria and consistent with the National Institute on Aging-Alzheimer's Association criteria:
Permitted medications:
Willing and able to undergo imaging procedures:
A Positron Emission Tomography (PET) scan with Florbetaben(an 18F isotope diagnostic agent) or documented evidence of an amyloid positive PET scan.
The Florbetaben scan performed at baseline must be read by a qualified physician with experience in reading amyloid PET scans, and it should be consistent with the presence of amyloid plaques.
Repeated MRI scans (3 Tesla) with no contraindications to MRI. MRI scan results are consistent with the diagnosis of amnestic MCI due to Alzheimer's disease with no clinically significant findings of non-AD pathology that could account for the observed cognitive impairment.
Willing to allow collection of blood for apolipoprotein E (ApoE) genotyping.
Exclusion Criteria:
Use of anticonvulsant medications or excluded psychotropic medications within 3 months prior to the baseline visit
Participation in a therapeutic clinical study for any medical or psychiatric indications within 3 months (6 months for biologics) of the screening visit, or at any time during the study.
Subjects must understand that they may only enroll in this clinical study once; they may not enroll in any other clinical study while participating in the current study, and they may not participate in a clinical study of a drug, biologic, therapeutic device, or medical food, in which the last dose/administration was received within 3 months (6 months for biologics) prior to screening.
History of hypersensitivity or lack of tolerability to AGB101 (levetiracetam)
Severe renal impairment (creatinine clearance of <30 mL/minute) or undergoing hemodialysis
Any significant neurological disease other than suspected incipient AD, such as Parkinson's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder (lifetime history; infant febrile seizures are not exclusionary), subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic deficits, or known structural brain abnormalities
Presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments, or foreign objects in the eyes, skin, or body
Diagnosis of major depression or bipolar disorder, as described in the Diagnostic and Statistical Manual of Mental Disorders, 5th Ed (DSM-5), within the past 3 years.
Psychotic features, agitation, or behavioral problems within the last 3 months that could lead to difficulty complying with the protocol. Subjects must not have a major depressive disorder or other types of depression that could confound diagnosis of MCI due to AD, or clinical assessments, in the opinion of the investigator. The geriatric depression scale (long form score >9 suggests depression) results should be reviewed by the investigator to assist in this determination.
Modified Hachinski Ischemic Scale (HIS) score >4
History of schizophrenia (DSM-5 criteria)
History of alcohol or substance abuse or dependence within the past 3 years (DSM-5 criteria)
Any significant systemic illness or unstable medical condition that could lead to difficulty in complying with the protocol requirements.
Clinically significant abnormalities in B12 or thyroid function test that might interfere with the study.
A low B12 (below normative range for elderly) is exclusionary, unless follow-up labs (homocysteine and methylmalonic acid) indicate that it is not physiologically significant. If the B12 deficiency is treated, subjects may become eligible to participate in the study.
Residence in a skilled nursing facility. Individuals in independent living communities, assisted living facilities, residential care facilities, or continuing care communities are eligible provided they engage in a sufficient spectrum of activity to permit assessment of all 6 domains contributing to the CDR-SB. Individuals in these facilities must also have a caregiver who has the ability to observe the subject during the study and can participate in clinical evaluations.
Any use of excluded medications (e.g., antiepileptics, certain antidepressants or antipsychotics, antihistamines with anticholinergic properties, opiates)
Participation in clinical studies using the ISLT, Behavioral Pattern Separation (BPS-O) task, or the trail making test (A, B) within 1 month of screening
Female subjects must not be pregnant, lactating, or of childbearing potential (i.e., they must be 2 years post menopause or surgically sterile)
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| Name | Affiliation | Role |
|---|---|---|
| Richard Mohs, PhD | AgeneBio | Principal Investigator |
| Sharon Rosenzweig-Lipson, PhD | AgeneBio | Study Director |
| Russell Barton, MS | AgeneBio | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Banner Alzheimer's Institute | Phoenix | Arizona | 85006 | United States | ||
| Senior Clinical Trials, Inc. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo Oral Tablet | Matching placebo to AGB101 tablet once daily, taken orally, for 78 weeks. Placebo Oral Tablet: Placebo oral tablet |
| FG001 | AGB101 220 mg Tablet | Single 220 mg AGB101 tablet once daily, taken orally, for 78 weeks. AGB101 220 mg tablet: 220 mg AGB101 active compound |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 19, 2020 |
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| Drug |
220 mg AGB101 active compound |
|
| Change in Functional Activities Questionnaire (FAQ) Score From Baseline | FAQ scores at baseline were subtracted from FAQ scores at week 78 to generate the change score from baseline, with a possible total range of -30 to 30. Positive change scores reflect greater impairment on the FAQ at week 78, while negative change scores reflect less impairment on the FAQ at week 78. | 78 weeks |
| Laguna Hills |
| California |
| 92653 |
| United States |
| Excell Research Inc | Oceanside | California | 92056 | United States |
| The Mile High Research Center | Denver | Colorado | 80218 | United States |
| Boynton Beach Medical Research Institite | Boynton Beach | Florida | 33437 | United States |
| Brain Matters Research | Delray Beach | Florida | 33445 | United States |
| MD Clinical | Hallandale | Florida | 33009 | United States |
| Miami Jewish Health | Miami | Florida | 33137 | United States |
| Bioclinica Research | Orlando | Florida | 32806 | United States |
| IMIC Research | Palmetto Bay | Florida | 33157 | United States |
| The Roskamp Institute, Inc | Sarasota | Florida | 34243 | United States |
| Brain Matters Research | Stuart | Florida | 34997 | United States |
| NeuroStudies.net, LLC | Decatur | Georgia | 30033 | United States |
| Great Lakes Clinical Trials | Chicago | Illinois | 60640 | United States |
| Johns Hopkins University School of Medicine | Baltimore | Maryland | 21205 | United States |
| Memory Center/Hattiesburg Clinic | Hattiesburg | Mississippi | 39401 | United States |
| Clinical Research Professionals | Chesterfield | Missouri | 63005 | United States |
| The NeuroCognitive Institute | Mount Arlington | New Jersey | 07856 | United States |
| Global Medical Institutes LLC; Princeton Medical Institute | Princeton | New Jersey | 08540 | United States |
| Neurology Specialist of Monmouth County, PA | West Long Branch | New Jersey | 07764 | United States |
| Neurological Associates of Albany PC | Albany | New York | 12208 | United States |
| Richmond Behavioral Associates | Staten Island | New York | 10312 | United States |
| Clinical Biotechnology Research Institute at RSFH | Charleston | South Carolina | 29401 | United States |
| Toronto Memory Program | Toronto | Ontario | M3B 2S7 | Canada |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo Oral Tablet | Matching placebo to AGB101 tablet once daily, taken orally, for 78 weeks. Placebo Oral Tablet: Placebo oral tablet |
| BG001 | AGB101 220 mg Tablet | Single 220 mg AGB101 tablet once daily, taken orally, for 78 weeks. AGB101 220 mg tablet: 220 mg AGB101 active compound |
| 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 | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Clinical Dementia Rating-Sum of Boxes (CDR-SB) | The CDR-SB is the sum score of 6 domains of cognitive function (memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care), with the score of each domain ranging from 0 (no impairment) to 3 (severe impairment). The total possible range is 0 to 18 with higher scores indicating greater impairment. | Mean | Standard Deviation | units on a scale |
| ||||||||||||||
| Mini Mental Status Exam (MMSE) | The MMSE is the sum score of an 11 item exam designed to assess five components of cognition: orientation, registration, attention and calculation, recall, and language. The total possible range is 0-30, with lower scores indicating greater impairment. | Mean | Standard Deviation | units on a scale |
| ||||||||||||||
| Functional Activities Questionnaire (FAQ) | The FAQ measures instrumental activities of daily living, such as preparing balanced meals and managing finances. The total possible range is from 0 to 30, with higher scores indicating greater impairment. | Baseline FAQ measure not collected for 7 subjects. | Mean | Standard Deviation | units on a scale |
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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 Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB) Score From Baseline | CDR-SB scores at baseline were subtracted from CDR-SB scores at week 78 to generate the change score from baseline, with a possible total range of -18 to 18. Positive change scores reflect greater impairment on the CDR-SB at week 78, while negative change scores reflect less impairment on the CDR-SB at week 78. | Posted | Mean | Standard Deviation | score on a scale | 78 weeks |
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| Secondary | Change in Mini Mental Status Exam (MMSE) Score From Baseline | MMSE scores at baseline were subtracted from MMSE scores at week 78 to generate the change score from baseline, with a possible total range of -30 to 30. Positive change scores reflect improved performance on the MMSE at week 78, while negative change scores reflect worsening performance on the MMSE at week 78. | Posted | Mean | Standard Deviation | units on a scale | 78 weeks |
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| Secondary | Change in Functional Activities Questionnaire (FAQ) Score From Baseline | FAQ scores at baseline were subtracted from FAQ scores at week 78 to generate the change score from baseline, with a possible total range of -30 to 30. Positive change scores reflect greater impairment on the FAQ at week 78, while negative change scores reflect less impairment on the FAQ at week 78. | Posted | Mean | Standard Deviation | units on a scale | 78 weeks |
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18 months
Three subjects were randomized and assigned to receive AGB101 but were not treated, lowering the total number of at risk participants treated with AGB101 to 78.
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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 | Placebo Oral Tablet | Matching placebo to AGB101 tablet once daily, taken orally, for 78 weeks. Placebo Oral Tablet: Placebo oral tablet | 0 | 83 | 10 | 83 | 49 | 83 |
| EG001 | AGB101 220 mg Tablet | Single 220 mg AGB101 tablet once daily, taken orally, for 78 weeks. AGB101 220 mg tablet: 220 mg AGB101 active compound | 2 | 78 | 13 | 78 | 40 | 78 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute myocardial infarction | Cardiac disorders | MedDRA | Non-systematic Assessment |
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| Atrial fibrillation | Cardiac disorders | MedDRA | Non-systematic Assessment |
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| Atrioventricular block second degree | Cardiac disorders | MedDRA | Non-systematic Assessment |
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| Bradycardia | Cardiac disorders | MedDRA | Non-systematic Assessment |
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| Coronary artery disease | Cardiac disorders | MedDRA | Non-systematic Assessment |
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| Coronary artery occlusion | Cardiac disorders | MedDRA | Non-systematic Assessment |
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| Sinus node dysfunction | Cardiac disorders | MedDRA | Non-systematic Assessment |
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| Appendicitis | Infections and infestations | MedDRA | Non-systematic Assessment |
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| Cystitis | Infections and infestations | MedDRA | Non-systematic Assessment |
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| Pneumonia legionella | Infections and infestations | MedDRA | Non-systematic Assessment |
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| Sepsis | Infections and infestations | MedDRA | Non-systematic Assessment |
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| Hip fracture | Injury, poisoning and procedural complications | MedDRA | Non-systematic Assessment |
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| Joint injury | Injury, poisoning and procedural complications | MedDRA | Non-systematic Assessment |
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| Hypoglycemia | Metabolism and nutrition disorders | MedDRA | Non-systematic Assessment |
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| Pancreatic carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA | Non-systematic Assessment |
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| Plasma cell myeloma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA | Non-systematic Assessment |
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| Seizure | Nervous system disorders | MedDRA | Non-systematic Assessment |
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| Transient ischemic attack | Nervous system disorders | MedDRA | Non-systematic Assessment |
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| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA | Non-systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA | Non-systematic Assessment |
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| Hypertensive crisis | Vascular disorders | MedDRA | Non-systematic Assessment |
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| Hypertensive urgency | Vascular disorders | MedDRA | Non-systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Blood and lymphatic system disorders | Blood and lymphatic system disorders | MedDRA | Non-systematic Assessment |
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| cardiac disorders | Cardiac disorders | MedDRA | Non-systematic Assessment |
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| Ear and labyrinth disorders | Ear and labyrinth disorders | MedDRA | Non-systematic Assessment |
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| Endocrine disorders | Endocrine disorders | MedDRA | Non-systematic Assessment |
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| Eye disorders | Eye disorders | MedDRA | Non-systematic Assessment |
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| Gastrointestinal disorders | Gastrointestinal disorders | MedDRA | Non-systematic Assessment |
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| General disorders and administration site condition | General disorders | MedDRA | Non-systematic Assessment |
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| Hepatobiliary disorders | Hepatobiliary disorders | MedDRA | Non-systematic Assessment |
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| Infections and infestations | Infections and infestations | MedDRA | Non-systematic Assessment |
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| Injury, poisoning and procedural complications | Injury, poisoning and procedural complications | MedDRA | Non-systematic Assessment |
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| Investigations | Investigations | MedDRA | Non-systematic Assessment |
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| Metabolism and nutrition disorders | Metabolism and nutrition disorders | MedDRA | Non-systematic Assessment |
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| Musculoskeletal and connective tissue disorders | Musculoskeletal and connective tissue disorders | MedDRA | Non-systematic Assessment |
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| Neoplasms benign, malignant and unspecified (inc cysts and polyps) | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA | Non-systematic Assessment |
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| Nervous system disorders | Nervous system disorders | MedDRA | Non-systematic Assessment |
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| Product issues | Product Issues | MedDRA | Non-systematic Assessment |
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| Psychiatric disorders | Psychiatric disorders | MedDRA | Non-systematic Assessment |
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| Renal and urinary disorders | Renal and urinary disorders | MedDRA | Non-systematic Assessment |
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| Reproductive system and breast disorders | Reproductive system and breast disorders | MedDRA | Non-systematic Assessment |
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| Respiratory, thoracic and mediastinal disorders | Respiratory, thoracic and mediastinal disorders | MedDRA | Non-systematic Assessment |
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| Skin and subcutaneous tissue disorders | Skin and subcutaneous tissue disorders | MedDRA | Non-systematic Assessment |
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| Social circumstances | Social circumstances | MedDRA | Non-systematic Assessment |
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| Surgical and medical procedures | Surgical and medical procedures | MedDRA | Non-systematic Assessment |
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| Vascular disorders | Vascular disorders | MedDRA | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Richard Mohs | agenebio | 317-997-3241 | richard.mohs@agenebio.com |
| Mar 18, 2024 |
| Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D060825 | Cognitive Dysfunction |
| ID | Term |
|---|---|
| D003072 | Cognition Disorders |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D013607 | Tablets |
| ID | Term |
|---|---|
| D004304 | Dosage Forms |
| D004364 | Pharmaceutical Preparations |
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