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The purpose of this research study is to test whether nicotinamide, also known as vitamin B3 or niacinamide, taken in high doses, can reduce phosphorylation of tau (the protein that accumulates in neurofibrillary tangles) in people with Mild Cognitive Impairment or mild Alzheimer's disease (AD) dementia.
Nicotinamide, the amide of nicotinic acid (vitamin B3/niacin), is an oral therapy with a wealth of clinical data in a variety of therapeutic areas, including preliminary data supporting its safety in Alzheimer's disease (AD). Preclinical work in a mouse model that develops both plaques and tangles supports the hypothesis that nicotinamide can act as a histone deacetylase (HDAC) inhibitor to reduce phosphorylation of tau.
The study will implement a group sequential design, incorporating a futility analysis with a go/no-go decision conditional on cerebral spinal fluid CSF biomarker outcomes at 12-months. The primary outcome for the trial is change in p-tau231.
This study timeline includes a screening phase of up to 60 days and treatment phase which is expected to last about 48 weeks and will include 4 study visits.
An additional 12-month treatment and follow-up period is planned, contingent upon a "go" decision based on the primary outcome (CSF p-tau231) or one planned secondary outcome (CSF p-tau181)
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Nicotinamide | Experimental | 1500mg twice daily: 2, 750mg tablets taken orally twice daily |
|
| Placebo | Placebo Comparator | 1500mg twice daily: 2, 750mg tablets taken orally twice daily |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Nicotinamide | Drug | Niacinamide (nicotinamide; 99%) is produced in a 750 mg sustained release tablet. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in P-tau 231 | Change in key peptide in cerebrospinal fluid (CSF) from baseline to 48 weeks. Higher phosphorylated tau (p-tau) is associated with a severity of Alzheimer's disease pathology. | Baseline to 48 weeks |
| Vital Signs - Weight | Weight in kg was recorded at every study visit (screening, baseline, week 12, week 24, and week 48) | Screening through end of study (week 48) |
| Vital Signs - BMI | Body Mass Index (BMI) was recorded at every study visit (screening, baseline, week 12, week 24, and week 48) | Screening through end of study (week 48) |
| Vital Signs - Systolic Blood Pressure | Systolic blood pressure was recorded at every study visit (screening, baseline, week 12, week 24, and week 48) | Screening through end of study (week 48) |
| Vital Signs - Diastolic Blood Pressure | Diastolic blood pressure was recorded at every study visit (screening, baseline, week 12, week 24, and week 48) | Screening through end of study (week 48) |
| Vital Signs - Pulse | Pulse rate was recorded at every study visit (screening, baseline, week 12, week 24, and week 48) | Screening through end of study (week 48) |
| Count of Treatment Emergent Adverse Events | Count of treatment emergent adverse events (TEAEs) over the duration of the study period (baseline to 48 weeks). |
| Measure | Description | Time Frame |
|---|---|---|
| Change in ab40 | Change in key peptide in cerebrospinal fluid (CSF) from baseline to 48 weeks. Lower ab40 is associated with a greater probability of fibrillar amyloid burden in the brain. | Baseline to 48 weeks |
| Change in ab42 |
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Inclusion Criteria:
Mild Cognitive Impairment (MCI) or dementia due to Alzheimer's disease (AD)
Biomarker criteria:
Cerebral Spinal Fluid (CSF) Amyloid Beta 1-42 (Aβ42) <= 600 pg/mL, or A ratio of total tau to Aβ42 ≥ 0.39.
Mini-Mental State Exam (MMSE) ≥ 20
Blood laboratories, urinalysis, and electrocardiogram are within normal limits or deemed clinically not significant by the site investigator
Stable medications (including approved AD therapies) for at least 4 weeks
At least 6 years of education
Able to swallow oral tablets
Speaks English fluently
Available qualified study partner (≥3 times per week in-person communication with the participant)
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Joshua Grill, Ph.D. | Associate Professor of Psychiatry and Human Behavior | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California, Irvine | Irvine | California | 92697 | United States | ||
| University of California, Los Angeles |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 18987186 | Background | Green KN, Steffan JS, Martinez-Coria H, Sun X, Schreiber SS, Thompson LM, LaFerla FM. Nicotinamide restores cognition in Alzheimer's disease transgenic mice via a mechanism involving sirtuin inhibition and selective reduction of Thr231-phosphotau. J Neurosci. 2008 Nov 5;28(45):11500-10. doi: 10.1523/JNEUROSCI.3203-08.2008. | |
| 23273573 |
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Data sharing is integral to the ADCS's mission to develop and execute innovative clinical trials focused on interventions that may prevent, delay, or treat the expression of Alzheimer's disease and related dementias. The ADCS is committed to sharing resources and tools, including data, biospecimens, trial designs, outcome and analysis measures following NIH guidelines.
DATA Sharing: The ADCS Data and Sample Sharing Committee (DSSC) grants access to de-identified data to individuals who complete the request process and agree to the conditions in an ADCS/UCSD Data Us Agreement (DUA). After approval and receipt of the fully executed DUA, applicants are authorized to acquire data. Non-compliance with the DUA, including the requirement to provide requested updates will jeopardize further access to data.
6 months after publication
Data requestors must complete ADCS data and sample sharing request form. Upon approval, requestors must complete a data use agreement prior to accessing data.
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46 participants received at least 1 dose of study drug.
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| ID | Title | Description |
|---|---|---|
| FG000 | Nicotinamide | 1500mg twice daily: 2, 750mg tablets taken orally twice daily Nicotinamide: Niacinamide (nicotinamide; 99%) is produced in a 750 mg sustained release tablet. |
| FG001 | Placebo | 1500mg twice daily: 2, 750mg tablets taken orally twice daily Placebo Comparator: Oral Tablet |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Nicotinamide | 1500mg twice daily: 2, 750mg tablets taken orally twice daily Nicotinamide: Niacinamide (nicotinamide; 99%) is produced in a 750 mg sustained release tablet. |
| BG001 | Placebo |
| 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 | Change in P-tau 231 | Change in key peptide in cerebrospinal fluid (CSF) from baseline to 48 weeks. Higher phosphorylated tau (p-tau) is associated with a severity of Alzheimer's disease pathology. | Posted | Mean | Standard Deviation | pg/ml | Baseline to 48 weeks |
|
Adverse event data were collected from signed consent through the participant duration in the study. The specific time period is from consent through the end of the 48 week double-blind trial. Adverse event information will be collected at every planned and unplanned in-person and telephone visit until 7 (for non-serious AEs) or 30 days (for SAEs) after the last day of study participation.
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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 | Nicotinamide | 1500mg twice daily: 2, 750mg tablets taken orally twice daily Nicotinamide: Niacinamide (nicotinamide; 99%) is produced in a 750 mg sustained release tablet. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Leukocytosis | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 20.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Joshua Grill | University of California, Irvine | (949) 824-5905 | jgrill@uci.edu |
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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 | Dec 28, 2017 | Jul 24, 2023 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 30, 2022 | Jul 13, 2023 | SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jun 11, 2021 | Jul 24, 2023 | ICF_002.pdf |
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| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| D060825 | Cognitive Dysfunction |
| D019636 | Neurodegenerative Diseases |
| D024801 | Tauopathies |
| D003704 | Dementia |
| ID | Term |
|---|---|
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D019965 | Neurocognitive Disorders |
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| ID | Term |
|---|---|
| D009536 | Niacinamide |
| ID | Term |
|---|---|
| D009539 | Nicotinic Acids |
| D000147 | Acids, Heterocyclic |
| D006571 | Heterocyclic Compounds |
| D011725 | Pyridines |
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Double-Blind-Randomized
| Placebo Comparator | Drug | Oral Tablet |
|
| Baseline to 48 weeks |
| Count of Adverse Events by Severity | Count of treatment emergent adverse events (TEAEs) over the duration of the study period (baseline to 48 weeks). | Baseline to 48 weeks |
| Columbia-Suicide Severity Rating Scale | The Columbia-Suicide Severity Rating Scale (C-SSRS) captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors during the corresponding assessment period. The scale includes suggested questions to elicit the type of information needed to determine if a suicide-related thought or behavior occurred. The number and proportion of subjects with treatment emergent Suicidal ideation or behavior during the study period of (baseline to week 48) will be reported overall and by study arm. Treatment emergent suicidal ideation or behavior is defined as a "yes" answer at any time during treatment to any one of the questions in the ten suicidal ideation and behavior categories (Categories 1- 10) on the C-SSRS. Self-injurious behavior without suicidal intent, while assessed on the C-SSRS, does not form part of this outcome. | Baseline to 48 weeks |
| ECG Abnormalities | Count of participants experiencing at least one electrocardiogram (ECG) abnormality. | Baseline to 48 weeks |
| QTC Abnormalities | Count of participants experiencing at least one electrocardiogram (ECG) QT interval abnormality. Abnormal defined as above 460 for men and above 470 for women. | Baseline to 48 weeks |
| Change in QTC | Average within-subject change in electrocardiogram QT interval. | Baseline to 48 weeks |
Change in key peptide in cerebrospinal fluid (CSF) from baseline to 48 weeks. Lower ab42 is associated with a greater probability of fibrillar amyloid burden in the brain.
| Baseline to 48 weeks |
| Change in P-tau 181 | Change in key peptide in cerebrospinal fluid (CSF) from baseline to 48 weeks. Higher total value is associated with greater severity of Alzheimer's disease pathology. | Baseline to 48 weeks |
| Change in Total Tau | Change in CSF total tau in individuals with mild Alzheimer's disease (AD) dementia or Mild Cognitive Impairment due to AD. | Baseline to 48 weeks |
| Change in Ratio of Total Tau/ab40 | Change in ratio of key peptides in cerebrospinal fluid (CSF) from baseline to 48 weeks. A lower ab40/tau ratio is associated with a higher risk of dementia. | Baseline to 48 weeks |
| Change in Ratio of Total Tau/ab42 | Change in ratio of key peptides in cerebrospinal fluid (CSF) from baseline to 48 weeks. A lower ab42/tau ratio is associated with a higher risk of dementia. | Baseline to 48 weeks |
| ADASCog-13 | ADAS-Cog13 is a structured scale that evaluates memory (immediate and delayed word recall; immediate word recognition), receptive and expressive language, orientation, ideational praxis (preparing a letter for mailing), constructional praxis (copying figures), and attention (number cancellation). Ratings of spoken language, language comprehension, word finding difficulty, and ability to remember test instructions also are obtained. Range: 0-85; higher scores indicate greater impairment. | Baseline to 48 weeks |
| Activities of Daily Living - Mild Cognitive Impairment | The ADCS-ADL-MCI is a measure of patient functional performance in Alzheimer's Disease and Mild Cognitive Impairment trials. The informant-based questionnaire assesses conduct of basic and instrumental Activities of Daily Living (ADLs). A total of 24 ADLs are evaluated. Scores range from 0 to 53, with higher scores representing more maintained function. | Baseline to 48 weeks |
| CDR Sum of Boxes | CDR-SB is a composite rating of cognition and everyday function which incorporates both informant input and direct assessment of performance. It assesses through semi-structured interview three cognitive domains (memory, orientation, and judgement/problem solving) and three everyday functional domains (community affairs, home and hobbies, personal care). Level of impairment in each of the six domains is rated from none (score=0) to severe (score=3). The six domain scores are then summed to create the CDR-SB. Range 0-18; higher scores indicate greater impairment. | Baseline to 48 weeks |
| Los Angeles |
| California |
| 90095 |
| United States |
| Liu D, Pitta M, Jiang H, Lee JH, Zhang G, Chen X, Kawamoto EM, Mattson MP. Nicotinamide forestalls pathology and cognitive decline in Alzheimer mice: evidence for improved neuronal bioenergetics and autophagy procession. Neurobiol Aging. 2013 Jun;34(6):1564-80. doi: 10.1016/j.neurobiolaging.2012.11.020. Epub 2012 Dec 25. |
| 40069789 | Derived | Ketron GL, Grun F, Grill JD, Feldman HH, Rissman RA, Brewer GJ. Pharmacokinetic and pharmacodynamic assessment of oral nicotinamide in the NEAT clinical trial for early Alzheimer's disease. Alzheimers Res Ther. 2025 Mar 11;17(1):59. doi: 10.1186/s13195-025-01693-y. |
| 39671543 | Derived | Grill JD, Tam S, Thai G, Vides B, Pierce AL, Green K, Gillen DL, Teng E, Kremen S, Beigi M, Rissman RA, Leger GC, Balasubramanian A, Revta C, Morrison R, Jennings R, Pa J, Zhang J, Jin S, Messer K, Feldman HH. Phase 2A Proof-of-Concept Double-Blind, Randomized, Placebo-Controlled Trial of Nicotinamide in Early Alzheimer Disease. Neurology. 2025 Jan 14;104(1):e210152. doi: 10.1212/WNL.0000000000210152. Epub 2024 Dec 13. |
| Participant unwilling or unable to participate |
|
| Lost to Follow-up |
|
1500mg twice daily: 2, 750mg tablets taken orally twice daily
Placebo Comparator: Oral Tablet
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Mini-Mental State Examination | The Mini-Mental State Examination is a brief mental status exam and widely used dementia screening instrument. It evaluates orientation to time and place, memory, attention, language, and visuospatial ability. Range: 0-30; a lower score indicates greater impairment. | Mean | Standard Deviation | units on a scale |
|
| Units | Counts |
|---|---|
| Participants |
|
|
|
| Primary | Vital Signs - Weight | Weight in kg was recorded at every study visit (screening, baseline, week 12, week 24, and week 48) | Numbers analyzed in some rows lower due to missing data (visit not completed, or participant refused measure). | Posted | Mean | Standard Deviation | kg | Screening through end of study (week 48) |
|
|
|
| Primary | Vital Signs - BMI | Body Mass Index (BMI) was recorded at every study visit (screening, baseline, week 12, week 24, and week 48) | Numbers analyzed in some rows lower due to missing data (visit not completed, or participant refused measure). | Posted | Mean | Standard Deviation | kg/m^2 | Screening through end of study (week 48) |
|
|
|
| Primary | Vital Signs - Systolic Blood Pressure | Systolic blood pressure was recorded at every study visit (screening, baseline, week 12, week 24, and week 48) | Numbers analyzed in some rows lower due to missing data (visit not completed, or participant refused measure). | Posted | Mean | Standard Deviation | mm Hg | Screening through end of study (week 48) |
|
|
|
| Primary | Vital Signs - Diastolic Blood Pressure | Diastolic blood pressure was recorded at every study visit (screening, baseline, week 12, week 24, and week 48) | Numbers analyzed in some rows lower due to missing data (visit not completed, or participant refused measure). | Posted | Mean | Standard Deviation | mm Hg | Screening through end of study (week 48) |
|
|
|
| Primary | Vital Signs - Pulse | Pulse rate was recorded at every study visit (screening, baseline, week 12, week 24, and week 48) | Numbers analyzed in some rows lower due to missing data (visit not completed, or participant refused measure). | Posted | Mean | Standard Deviation | bpm | Screening through end of study (week 48) |
|
|
|
| Primary | Count of Treatment Emergent Adverse Events | Count of treatment emergent adverse events (TEAEs) over the duration of the study period (baseline to 48 weeks). | Posted | Number | events | Baseline to 48 weeks |
|
|
|
| Primary | Count of Adverse Events by Severity | Count of treatment emergent adverse events (TEAEs) over the duration of the study period (baseline to 48 weeks). | Posted | Number | events | Baseline to 48 weeks |
|
|
|
| Primary | Columbia-Suicide Severity Rating Scale | The Columbia-Suicide Severity Rating Scale (C-SSRS) captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors during the corresponding assessment period. The scale includes suggested questions to elicit the type of information needed to determine if a suicide-related thought or behavior occurred. The number and proportion of subjects with treatment emergent Suicidal ideation or behavior during the study period of (baseline to week 48) will be reported overall and by study arm. Treatment emergent suicidal ideation or behavior is defined as a "yes" answer at any time during treatment to any one of the questions in the ten suicidal ideation and behavior categories (Categories 1- 10) on the C-SSRS. Self-injurious behavior without suicidal intent, while assessed on the C-SSRS, does not form part of this outcome. | Posted | Number | events | Baseline to 48 weeks |
|
|
|
| Primary | ECG Abnormalities | Count of participants experiencing at least one electrocardiogram (ECG) abnormality. | Posted | Count of Participants | Participants | Baseline to 48 weeks |
|
|
|
| Secondary | Change in ab40 | Change in key peptide in cerebrospinal fluid (CSF) from baseline to 48 weeks. Lower ab40 is associated with a greater probability of fibrillar amyloid burden in the brain. | Posted | Mean | Standard Deviation | pg/ml | Baseline to 48 weeks |
|
|
|
|
| Secondary | Change in ab42 | Change in key peptide in cerebrospinal fluid (CSF) from baseline to 48 weeks. Lower ab42 is associated with a greater probability of fibrillar amyloid burden in the brain. | Posted | Mean | Standard Deviation | pg/ml | Baseline to 48 weeks |
|
|
|
|
| Secondary | Change in P-tau 181 | Change in key peptide in cerebrospinal fluid (CSF) from baseline to 48 weeks. Higher total value is associated with greater severity of Alzheimer's disease pathology. | Posted | Mean | Standard Deviation | pg/ml | Baseline to 48 weeks |
|
|
|
|
| Secondary | Change in Total Tau | Change in CSF total tau in individuals with mild Alzheimer's disease (AD) dementia or Mild Cognitive Impairment due to AD. | Posted | Mean | Standard Deviation | pg/ml | Baseline to 48 weeks |
|
|
|
|
| Secondary | Change in Ratio of Total Tau/ab40 | Change in ratio of key peptides in cerebrospinal fluid (CSF) from baseline to 48 weeks. A lower ab40/tau ratio is associated with a higher risk of dementia. | Posted | Mean | Standard Deviation | ratio | Baseline to 48 weeks |
|
|
|
|
| Secondary | Change in Ratio of Total Tau/ab42 | Change in ratio of key peptides in cerebrospinal fluid (CSF) from baseline to 48 weeks. A lower ab42/tau ratio is associated with a higher risk of dementia. | Posted | Mean | Standard Deviation | ratio | Baseline to 48 weeks |
|
|
|
|
| Secondary | ADASCog-13 | ADAS-Cog13 is a structured scale that evaluates memory (immediate and delayed word recall; immediate word recognition), receptive and expressive language, orientation, ideational praxis (preparing a letter for mailing), constructional praxis (copying figures), and attention (number cancellation). Ratings of spoken language, language comprehension, word finding difficulty, and ability to remember test instructions also are obtained. Range: 0-85; higher scores indicate greater impairment. | Posted | Mean | Standard Deviation | score on a scale | Baseline to 48 weeks |
|
|
|
|
| Secondary | Activities of Daily Living - Mild Cognitive Impairment | The ADCS-ADL-MCI is a measure of patient functional performance in Alzheimer's Disease and Mild Cognitive Impairment trials. The informant-based questionnaire assesses conduct of basic and instrumental Activities of Daily Living (ADLs). A total of 24 ADLs are evaluated. Scores range from 0 to 53, with higher scores representing more maintained function. | Posted | Mean | Standard Deviation | score on a scale | Baseline to 48 weeks |
|
|
|
|
| Secondary | CDR Sum of Boxes | CDR-SB is a composite rating of cognition and everyday function which incorporates both informant input and direct assessment of performance. It assesses through semi-structured interview three cognitive domains (memory, orientation, and judgement/problem solving) and three everyday functional domains (community affairs, home and hobbies, personal care). Level of impairment in each of the six domains is rated from none (score=0) to severe (score=3). The six domain scores are then summed to create the CDR-SB. Range 0-18; higher scores indicate greater impairment. | Posted | Mean | Standard Deviation | score on a scale | Baseline to 48 weeks |
|
|
|
|
| Primary | QTC Abnormalities | Count of participants experiencing at least one electrocardiogram (ECG) QT interval abnormality. Abnormal defined as above 460 for men and above 470 for women. | Posted | Count of Participants | Participants | Baseline to 48 weeks |
|
|
|
| Primary | Change in QTC | Average within-subject change in electrocardiogram QT interval. | Posted | Mean | Standard Deviation | ms | Baseline to 48 weeks |
|
|
|
| 0 |
| 24 |
| 2 |
| 24 |
| 23 |
| 24 |
| EG001 | Placebo | 1500mg twice daily: 2, 750mg tablets taken orally twice daily Placebo Comparator: Oral Tablet | 0 | 22 | 6 | 22 | 20 | 22 |
| Injury | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
|
| Transaminases increased | Investigations | MedDRA | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
|
| Colorectal cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.0 | Systematic Assessment |
|
| Seizure | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Orthostatic hypotension | Vascular disorders | MedDRA 20.0 | Systematic Assessment |
|
| Retinal detachment | Eye disorders | MedDRA 20.0 | Systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Colitis ulcerative | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Eructation | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Hiatus hernia | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Neusea | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Rectal haemorrhage | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 20.0 | Systematic Assessment |
|
| Corona virus infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
|
| Diverticulitis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
|
| Fungal infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
|
| Gastritis viral | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
|
| Hordeolum | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
|
| Infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
|
| Pyuria | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
|
| Tooth abscess | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
|
| Viral upper respiratory tract infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
|
| Fibula fracture | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
|
| Foot fracture | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
|
| Hand fracture | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
|
| Head Injury | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
|
| Laceration | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
|
| Limb injury | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
|
| Post lumbar puncture syndrome | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
|
| Antimitochondrial antibody positive | Investigations | MedDRA 20.0 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA 20.0 | Systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA 20.0 | Systematic Assessment |
|
| Blood testosterone decreased | Investigations | MedDRA 20.0 | Systematic Assessment |
|
| Glomerular Ffiltration rate decreased | Investigations | MedDRA 20.0 | Systematic Assessment |
|
| Laboratory test abnormal | Investigations | MedDRA | Systematic Assessment |
|
| Urine ketone body present | Investigations | MedDRA 20.0 | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA 20.0 | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
|
| Diabetes mellitus | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
|
| Hyperlipidaemia | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
|
| Vitamin D deficiency | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
|
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
|
| Coccydynia | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
|
| Foot deformity | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
|
| Osteoporosis | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
|
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.0 | Systematic Assessment |
|
| Squamous cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 20.0 | Systematic Assessment |
|
| Cognitive disorder | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
|
| Memory impairment | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
|
| Neuropathy peripheral | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
|
| Parkinson's disease | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
|
| Pleocytosis | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
|
| Postural tremor | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
|
| Presyncope | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
|
| Syncoper | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
|
| Tremor | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
|
| Agitation | Psychiatric disorders | MedDRA 20.0 | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA 20.0 | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA 20.0 | Systematic Assessment |
|
| Parasomnia | Psychiatric disorders | MedDRA 20.0 | Systematic Assessment |
|
| Haematuria | Renal and urinary disorders | MedDRA 20.0 | Systematic Assessment |
|
| Micturition urgency | Renal and urinary disorders | MedDRA 20.0 | Systematic Assessment |
|
| Renal cyst | Renal and urinary disorders | MedDRA 20.0 | Systematic Assessment |
|
| Urinary incontinence | Renal and urinary disorders | MedDRA 20.0 | Systematic Assessment |
|
| Urinary retention | Renal and urinary disorders | MedDRA 20.0 | Systematic Assessment |
|
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Actinic keratosis | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
|
| Miliaria | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
|
| Penile ulceration | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Psoriasis | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
|
| Cancer surgery | Surgical and medical procedures | MedDRA 20.0 | Systematic Assessment |
|
| Cataract operation | Surgical and medical procedures | MedDRA 20.0 | Systematic Assessment |
|
| Skin neoplasm excision | Surgical and medical procedures | MedDRA 20.0 | Systematic Assessment |
|
| Haemorrhage | Vascular disorders | MedDRA 20.0 | Systematic Assessment |
|
| Labile blood pressure | Vascular disorders | MedDRA 20.0 | Systematic Assessment |
|
Not provided
Not provided
Not provided
| D001523 | Mental Disorders |
| D003072 | Cognition Disorders |
| D006573 |
| Heterocyclic Compounds, 1-Ring |
| Baseline Visit |
|
|
| Week 12 Visit |
|
|
| Week 24 Visit |
|
|
| Week 48 Visit |
|
|
| Baseline Visit |
|
|
| Week 12 Visit |
|
|
| Week 24 Visit |
|
|
| Week 48 Visit |
|
|
| Baseline Visit |
|
|
| Week 12 Visit |
|
|
| Week 24 Visit |
|
|
| Week 48 Visit |
|
|
| Baseline Visit |
|
|
| Week 12 Visit |
|
|
| Week 24 Visit |
|
|
| Week 48 Visit |
|
|
| Baseline Visit |
|
|
| Week 12 Visit |
|
|
| Week 24 Visit |
|
|
| Week 48 Visit |
|
|
| Severe |
|
| Total |
|