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| ID | Type | Description | Link |
|---|---|---|---|
| R01AG058660 | U.S. NIH Grant/Contract | View source | |
| 2022-002326-27 | EudraCT Number |
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| Name | Class |
|---|---|
| National Institute on Aging (NIA) | NIH |
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This is a multi-center, randomized, double-blind, placebo-controlled, parallel group 36 week multicenter Phase 2 study of two doses of CT1812 in adults with mild to moderate Alzheimer's Disease (AD).
This is a multi-center, randomized, double-blind, placebo-controlled, parallel group 36 week multicenter Phase 2 study of two doses of CT1812 in adults with mild to moderate Alzheimer's Disease (AD).
This Phase 2 study is designed to evaluate the safety of two doses of CT1812 administered once daily for 6 months in adults aged 50 to 85 who have been diagnosed with mild to moderate Alzheimer's disease. Randomized participants will receive 100 mg of CT1812, 300 mg of CT1812, or placebo once daily for 182 days. Exploratory endpoints that evaluate the effect of CT1812 on biomarkers are also included.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Active Treatment- CT1812 100 mg | Active Comparator | CT1812 at a dose of 100 mg |
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| Active Treatment- CT1812 300 mg | Active Comparator | CT1812 at a dose of 300mg |
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| Placebo Comparator - Placebo | Placebo Comparator | Placebo |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CT1812 | Drug | Active Study Drug |
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| Measure | Description | Time Frame |
|---|---|---|
| Number of Study Participants With at Least One Mild, Moderate, or Severe Treatment Emergent Adverse Events (TEAEs) | Adverse events were captured from the start of study-related procedures at Visit 1 (including diagnostic assessments or signing of ICF) onward during the course of this study. Adverse events were coded using MedDRA Version 27.0.TEAEs are events that occurred or worsened on or after the first application of study drug. Participants are counted once for each system organ class (SOC) and once for each preferred term (PT). | Up to 210 Days |
| Number of Study Participants With at Least One Treatment Emergent Adverse Events (TEAs) and Serious Adverse Events (SAEs). | Adverse events were captured from the start of study-related procedures at Visit 1 (including diagnostic assessments or signing of ICF) onward during the course of this study. Adverse events were coded using MedDRA Version 27.0.TEAEs are events that occurred or worsened on or after the first application of study drug. Participants are counted once for each system organ class (SOC) and once for each preferred term (PT). | Up to 210 Days |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in the Cerebrospinal Fluid (CSF) Biomarkers | Change from baseline in CSF-Aβ, Tau, phospho-Tau, neurogranin, synaptotagmin, synaptosomal-associated protein-25 (SNAP25), neurofilament light chain (NfL), and Aβ-oligomers.Change from baseline is calculated as the observed value minus the baseline value. | Baseline to Day 182 |
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Inclusion Criteria:
Men, and women of non-childbearing potential, 50-85 years of age inclusively, with a diagnosis of mild to moderate Alzheimer's disease according to the 2011 NIA-AA criteria and at least a 6 month decline in cognitive function documented in the medical record.
i) Non-childbearing potential for women is defined as postmenopausal (last natural menses greater than 24 months) or undergone a documented bilateral tubal ligation or hysterectomy. If last natural menses less than 24 months, a serum FSH value confirming post-menopausal status can be employed.
ii) Male participants who are sexually active with a woman of child-bearing potential must agree to use condoms during the trial and for 3 months after last dose unless the woman is using an acceptable means of birth control. Acceptable forms of birth control include abstinence, birth control pills, or any double combination of: intrauterine device (IUD), male or female condom, diaphragm, sponge, and cervical cap.
Diagnostic confirmation by amyloid PET with florbetaben or another approved amyloid PET ligand. Previous amyloid imaging study with a positive result will be accepted. If none is available, then amyloid PET will be conducted during screening. Diagnostic confirmation by a CSF sample collected at the screening visit lumbar puncture in place of amyloid PET will also be acceptable
Neuroimaging (MRI) obtained during screening consistent with the clinical diagnosis of Alzheimer's disease and without findings of significant exclusionary abnormalities (see exclusion criteria, number 4). An historical MRI, up to 1 year prior to screening, may be used as long as there is no history of intervening neurologic disease or clinical events (such as a stroke, head trauma etc.) and the subject is without clinical symptoms or signs suggestive of such intervening events.).
MMSE 18-26 inclusive.
Exclusion Criteria:
Screening MRI (or historical MRI, if applicable) of the brain indicative of significant abnormality, including, but not limited to, prior hemorrhage or infarct >1 cm3, >3 lacunar infarcts, cerebral contusion, encephalomalacia, aneurysm, vascular malformation, subdural hematoma, hydrocephalus, space-occupying lesion (e.g. abscess or brain tumor such as meningioma). If a small incidental meningioma is observed, the medical monitor may be contacted to discuss eligibility..
Clinical or laboratory findings consistent with:
A current DSM-V diagnosis of active major depression, schizophrenia or bipolar disorder. Subjects with depressive symptoms successfully managed by a stable dose of an antidepressant are allowed entry.
Clinically significant, advanced or unstable disease that may interfere with outcome evaluations.
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| Name | Affiliation | Role |
|---|---|---|
| Anthony Caggiano, MD | Cognition Therapeutics | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 21st Century Neurology/ Xenoscience Inc. | Phoenix | Arizona | 85004 | United States | ||
| Imaging Endpoints |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41943055 | Derived | Di Caro V, Cho E, Thiel J, Lizama BN, Koel-Simmelink MJA, Pandey K, Duong D, Seyfried NT, Grundman M, Teunissen CE, Zetterberg H, Blennow K, Caggiano AO, Hamby ME. Impact of zervimesine on the neuroinflammatory biomarker GFAP and related proteomic molecular correlates in plasma of participants from a phase 2 clinical trial in Alzheimer's disease. Alzheimers Res Ther. 2026 Apr 6;18(1):112. doi: 10.1186/s13195-026-02025-4. | |
| 41930592 | Derived |
| Label | URL |
|---|---|
| Shine Study Information | View source |
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A total of 372 participants were screened, and 153 were randomized: 51 to CT1812 100 mg, 51 to CT1812 300 mg, and 51 to placebo. Study drug was administered to all participants in the CT1812 groups (100%) and to 50 participants (98.0%) in the placebo group. One participant in the placebo arm was randomized in error and did not receive study drug after informing the site post-randomization and prior to dosing of a prohibited concomitant medication.
The study was conducted in 12 centers in the United States, 3 centers in Australia, 3 centers in the Netherlands, 8 centers in Czech Republic, and 4 centers in Spain.
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| ID | Title | Description |
|---|---|---|
| FG000 | Active Treatment- CT1812 100 mg | CT1812 at a dose of 100 mg CT1812: Active Study Drug |
| FG001 | Active Treatment- CT1812 300 mg | CT1812 at a dose of 300 mg CT1812: Active Study Drug |
| 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 | Yes | No | No | Study Protocol | Jun 12, 2023 | May 21, 2025 |
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This is a multi-center Phase 2, randomized, double-blind, placebo-controlled, parallel-group study.
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| Placebo | Drug | Non-active study drug |
|
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| Amyloid Beta 1-42/Amyloid Beta 1-40 (Aβ42/40) in the Cerebrospinal Fluid (CSF) Biomarkers |
Ratio of Amyloid Beta 1-42 (Aβ42) to Amyloid Beta 1-40 (Aβ40) Concentration from Baseline to Day 182. |
| Baseline to Day 182 |
| Scottsdale |
| Arizona |
| 85258 |
| United States |
| Ki Health Partners, LLC dba New England Institute for Clinical Research | Stamford | Connecticut | 06905 | United States |
| JEM Research Institute | Atlantis | Florida | 33462 | United States |
| Charter Research | Lady Lake | Florida | 32159 | United States |
| ClinCloud, LLC | Maitland | Florida | 32751 | United States |
| Allied Biomedical Research Institute | Miami | Florida | 33155 | United States |
| Compass Research LLC- Bioclinica Research | The Villages | Florida | 32162 | United States |
| ClinCloud | Viera | Florida | 32940 | United States |
| Alzheimer's Memory Center | Charlotte | North Carolina | 28270 | United States |
| The Ohio State University - Wexner | Columbus | Ohio | 43221-3502 | United States |
| Neuro Behavirol Clinical Research C | North Canton | Ohio | 44720 | United States |
| St Vincent's Hospital Sydney | Ivanhoe | Victoria | 3079 | Australia |
| Alfred Health | Melbourne | Victoria | 3004 | Australia |
| Melbourne Health | Parkville | Victoria | 3050 | Australia |
| Australian Alzheimer's Research Foundation | Nedlands | Western Australia | 6009 | Australia |
| Neuro Health Centrum ltd | Brno | 628 00 | Czechia |
| NeuropsychiatrieHK S.R.O | Hradec Králové | 503 41 | Czechia |
| A-Shine S.R.O | Pilsen | 30100 | Czechia |
| Clintrial S.R.O | Prague | 100 00 | Czechia |
| Neuropsychiatrie s.r.o. | Prague | 16 000 | Czechia |
| Forbeli S.R.O | Prague | 160 00 | Czechia |
| INEP | Prague | 18600 | Czechia |
| Vestra Clinics | Rychnov nad Kněžnou | 51601 | Czechia |
| Brain Research Den Bosch | 's-Hertogenbosch | 5223 LA | Netherlands |
| Brain Research Center Amsterdam | Amsterdam | 1081 GN | Netherlands |
| Brain Research Center Zwolle | Zwolle | 8025 AZ | Netherlands |
| Fundación ACE | Barcelona | 08028 | Spain |
| Hospital Clinico Universitario Virgen De La Arrixaca | El Palmar | 30120 | Spain |
| Centro de Salud San Juan | Salamanca | 37005 | Spain |
| Hospital Victoria EUGENIA. Unidad de Neurociencias. | Seville | 41009 | Spain |
| Fundación Neuropolis - Hospital Viamed Montecanal | Zaragoza | 5000 | Spain |
| Vijverberg EGB, Scharre DW, Woodward M, Catalano S, Hamby ME, Grundman M, Morgan RE, Iaci J, Devins T, Caggiano AO. Randomized, double-blind study of zervimesine in mild to moderate Alzheimer's disease. J Alzheimers Dis. 2026 May;111(2):897-908. doi: 10.1177/13872877261437145. Epub 2026 Apr 3. |
| 39166791 | Derived | Lizama BN, Williams C, North HA, Pandey K, Duong D, Di Caro V, Mecca AP, Blennow K, Zetterberg H, Levey AI, Grundman M, van Dyck CH, Caggiano AO, Seyfried NT, Hamby ME. CT1812 biomarker signature from a meta-analysis of CSF proteomic findings from two Phase 2 clinical trials in Alzheimer's disease. Alzheimers Dement. 2024 Oct;20(10):6860-6880. doi: 10.1002/alz.14152. Epub 2024 Aug 21. |
| 38914170 | Derived | Lizama BN, North HA, Pandey K, Williams C, Duong D, Cho E, Di Caro V, Ping L, Blennow K, Zetterberg H, Lah J, Levey AI, Grundman M, Caggiano AO, Seyfried NT, Hamby ME. An interim exploratory proteomics biomarker analysis of a phase 2 clinical trial to assess the impact of CT1812 in Alzheimer's disease. Neurobiol Dis. 2024 Sep;199:106575. doi: 10.1016/j.nbd.2024.106575. Epub 2024 Jun 22. |
| FG002 | Placebo Comparator - Placebo | Placebo Placebo: Non-active study drug |
| COMPLETED |
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| NOT COMPLETED |
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One participant in the placebo arm was randomized in error and did not receive the study drug after informing the site, post-randomization and prior to dosing, about a prohibited concomitant medication. Therefore, the number of participants in the placebo arm is 50, not 51.
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| ID | Title | Description |
|---|---|---|
| BG000 | Active Treatment- CT1812 100 mg | CT1812 at a dose of 100 mg CT1812: Active Study Drug |
| BG001 | Active Treatment- CT1812 300 mg | CT1812 at a dose of 300 mg CT1812: Active Study Drug |
| BG002 | Placebo Comparator - Placebo | Placebo Placebo: Non-active study drug |
| BG003 | 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 | Data are based on the safety population, which is defined as all participants who received one or more doses of the study drug. | Mean | Standard Deviation | years |
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| Sex: Female, Male | Data are based on the safety population, which is defined as all participants who received one or more doses of the study drug. | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Data are based on the safety population, which is defined as all participants who received one or more doses of the study drug. | Count of Participants | Participants |
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| Race (NIH/OMB) | Data are based on the safety population, which is defined as all participants who received one or more doses of the study drug. | Count of Participants | Participants |
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| Height | Data are based on the safety population, which is defined as all participants who received one or more doses of the study drug. | Two subjects-one in the CT1812 100 mg arm and one in the CT1812 300 mg arm-missed the baseline height measurement. | Mean | Standard Deviation | cm |
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| Weight | Data are based on the safety population, which is defined as all participants who received one or more doses of the study drug. | Mean | Standard Deviation | Kg |
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| BMI | Data are based on the safety population, which is defined as all participants who received one or more doses of the study drug. | Two subjects-one in the CT1812 100 mg arm and one in the CT1812 300 mg arm-missed the baseline BMI measurement. | Mean | Standard Deviation | kg/m^2 |
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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 | Number of Study Participants With at Least One Mild, Moderate, or Severe Treatment Emergent Adverse Events (TEAEs) | Adverse events were captured from the start of study-related procedures at Visit 1 (including diagnostic assessments or signing of ICF) onward during the course of this study. Adverse events were coded using MedDRA Version 27.0.TEAEs are events that occurred or worsened on or after the first application of study drug. Participants are counted once for each system organ class (SOC) and once for each preferred term (PT). | Data are based on the safety population, which is defined as all participants who received one or more doses of the study drug. | Posted | Count of Participants | Participants | Up to 210 Days |
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| Primary | Number of Study Participants With at Least One Treatment Emergent Adverse Events (TEAs) and Serious Adverse Events (SAEs). | Adverse events were captured from the start of study-related procedures at Visit 1 (including diagnostic assessments or signing of ICF) onward during the course of this study. Adverse events were coded using MedDRA Version 27.0.TEAEs are events that occurred or worsened on or after the first application of study drug. Participants are counted once for each system organ class (SOC) and once for each preferred term (PT). | Data are based on the safety population, which is defined as all participants who received one or more doses of the study drug. | Posted | Count of Participants | Participants | Up to 210 Days |
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| Secondary | Change From Baseline in the Cerebrospinal Fluid (CSF) Biomarkers | Change from baseline in CSF-Aβ, Tau, phospho-Tau, neurogranin, synaptotagmin, synaptosomal-associated protein-25 (SNAP25), neurofilament light chain (NfL), and Aβ-oligomers.Change from baseline is calculated as the observed value minus the baseline value. | The analyzed population represents the number of subjects in the Efficacy modified intent-to-treat (mITT) population and participants who had both baseline and Day 182 CSF samples collected. | Posted | Mean | Standard Deviation | ng/L | Baseline to Day 182 |
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| Secondary | Amyloid Beta 1-42/Amyloid Beta 1-40 (Aβ42/40) in the Cerebrospinal Fluid (CSF) Biomarkers | Ratio of Amyloid Beta 1-42 (Aβ42) to Amyloid Beta 1-40 (Aβ40) Concentration from Baseline to Day 182. | The analyzed population represents the number of subjects in the Efficacy modified intent-to-treat (mITT) population and participants who had both baseline and Day 182 CSF samples collected. | Posted | Mean | Standard Deviation | ratio | Baseline to Day 182 |
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Adverse events were captured from the start of study-related procedures at Visit 1 (- 60 to -1 days) until the safety follow up visit V15 (study day 210 (±2) days). Important medical events and conditions occurring prior to this period were not recorded as AEs; they were captured within the medical chart and in the medical history section of the CRF.
The safety of CT1812 was evaluated by the incidence and severity of adverse events (AEs) and changes in the usage of concomitant medications, vital signs, physical examination findings, electrocardiogram (ECG) findings, clinical laboratory testing (serum chemistry, hematology, and urinalysis), and Columbia-Suicide Severity Rating Scale (C-SSRS).
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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 | Active Treatment- CT1812 100 mg | CT1812 at a dose of 100 mg CT1812: Active Study Drug | 0 | 51 | 2 | 51 | 25 | 51 |
| EG001 | Active Treatment- CT1812 300 mg | CT1812 at a dose of 300 mg CT1812: Active Study Drug | 0 | 51 | 3 | 51 | 25 | 51 |
| EG002 | Placebo Comparator - Placebo | Placebo Placebo: Non-active study drug | 1 | 50 | 5 | 50 | 33 | 50 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Stomatitis | Gastrointestinal disorders | MedDRA version 27.0 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA version 27.0 | Systematic Assessment |
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| HIP FRACTURE | Injury, poisoning and procedural complications | MedDRA version 27.0 | Systematic Assessment |
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| Hematuria | Renal and urinary disorders | MedDRA version 27.0 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA version 27.0 | Systematic Assessment |
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| Infection unknown etiology | Infections and infestations | MedDRA version 27.0 | Systematic Assessment |
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| Recurrent Presyncope | Nervous system disorders | MedDRA version 27.0 | Systematic Assessment |
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| Syncope x2 | Nervous system disorders | MedDRA version 27.0 | Systematic Assessment |
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| Bradycardia (intermittent) | Cardiac disorders | MedDRA version 27.0 | Systematic Assessment |
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| Renal Oncocytosis (left kidney) | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 27.0 | Systematic Assessment |
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| Papillary Renal Cell Carcinoma (left kidney) | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 27.0 | Systematic Assessment |
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| Retinal Detachment Right Side | Eye disorders | MedDRA version 27.0 | Systematic Assessment |
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| Delirium | Psychiatric disorders | MedDRA version 27.0 | Systematic Assessment |
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| Acute Renal Failure | Renal and urinary disorders | MedDRA version 27.0 | Systematic Assessment |
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| Lung Neoplasia Inferior Right with Metastasis in Liver and Bones | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 27.0 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Alanine aminotransferase increased | Investigations | MedDRA version 27.0 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA version 27.0 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA version 27.0 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA version 27.0 | Systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | MedDRA version 27.0 | Systematic Assessment |
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| Post lumbar puncture syndrome | Injury, poisoning and procedural complications | MedDRA version 27.0 | Systematic Assessment |
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| Skin laceration | Injury, poisoning and procedural complications | MedDRA version 27.0 | Systematic Assessment |
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| Hepatic enzyme increased | Investigations | MedDRA version 27. | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA version 27.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA version 27.0 | Systematic Assessment |
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| Anxiety | Psychiatric disorders | MedDRA version 27.0 | Systematic Assessment |
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| Blood potassium increased | Investigations | MedDRA version 27.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Anthony Caggiano | Cogntion Therapeutics Inc | 914-221-6730 | acaggiano@cogrx.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 23, 2024 | May 21, 2025 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D024801 | Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D004341 | Drug Evaluation |
| ID | Term |
|---|---|
| D000076722 | Drug Development |
| D008919 | Investigative Techniques |
| D005069 | Evaluation Studies as Topic |
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| Title | Measurements |
|---|---|
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| Moderate TEAEs |
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| Severe TEAEs |
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| Units | Counts |
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| Participants |
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| Participants |
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