Trial Outcomes & Findings for Nicotinamide as an Early Alzheimer's Disease Treatment (NCT NCT03061474)

NCT ID: NCT03061474

Last Updated: 2023-10-17

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 46 participants
• Primary outcome timeframe: Baseline to 48 weeks
• Results posted on: 2023-10-17

Participant Flow

46 participants received at least 1 dose of study drug.

Participant milestones

Measure	Nicotinamide 1500mg twice daily: 2, 750mg tablets taken orally twice daily Nicotinamide: Niacinamide (nicotinamide; 99%) is produced in a 750 mg sustained release tablet.	Placebo 1500mg twice daily: 2, 750mg tablets taken orally twice daily Placebo Comparator: Oral Tablet
Overall Study STARTED	24	22
Overall Study COMPLETED	22	18
Overall Study NOT COMPLETED	2	4

Reasons for withdrawal

Measure	Nicotinamide 1500mg twice daily: 2, 750mg tablets taken orally twice daily Nicotinamide: Niacinamide (nicotinamide; 99%) is produced in a 750 mg sustained release tablet.	Placebo 1500mg twice daily: 2, 750mg tablets taken orally twice daily Placebo Comparator: Oral Tablet
Overall Study Adverse Event	2	0
Overall Study Safety Risk	0	1
Overall Study Participant unwilling or unable to participate	0	2
Overall Study Lost to Follow-up	0	1

Baseline Characteristics

Nicotinamide as an Early Alzheimer's Disease Treatment

Baseline characteristics by cohort

Measure	Nicotinamide n=24 Participants 1500mg twice daily: 2, 750mg tablets taken orally twice daily Nicotinamide: Niacinamide (nicotinamide; 99%) is produced in a 750 mg sustained release tablet.	Placebo n=22 Participants 1500mg twice daily: 2, 750mg tablets taken orally twice daily Placebo Comparator: Oral Tablet	Total n=46 Participants Total of all reporting groups
Age, Continuous	74.56 years STANDARD_DEVIATION 8.97 • n=5 Participants	72.92 years STANDARD_DEVIATION 744 • n=7 Participants	73.78 years STANDARD_DEVIATION 8.23 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	10 Participants n=7 Participants	20 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	12 Participants n=7 Participants	26 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	23 Participants n=5 Participants	21 Participants n=7 Participants	44 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	21 Participants n=5 Participants	21 Participants n=7 Participants	42 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	24 participants n=5 Participants	22 participants n=7 Participants	46 participants n=5 Participants
Mini-Mental State Examination	25.62 units on a scale STANDARD_DEVIATION 2.87 • n=5 Participants	25.5 units on a scale STANDARD_DEVIATION 3.22 • n=7 Participants	25.57 units on a scale STANDARD_DEVIATION 3.01 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline to 48 weeks

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.

Outcome measures

Measure	Nicotinamide n=19 Participants 1500mg twice daily: 2, 750mg tablets taken orally twice daily Nicotinamide: Niacinamide (nicotinamide; 99%) is produced in a 750 mg sustained release tablet.	Placebo n=19 Participants 1500mg twice daily: 2, 750mg tablets taken orally twice daily Placebo Comparator: Oral Tablet
Change in P-tau 231	4.71 pg/ml Standard Deviation 14.46	2.28 pg/ml Standard Deviation 10.55

PRIMARY outcome

Timeframe: Screening through end of study (week 48)

Population: Numbers analyzed in some rows lower due to missing data (visit not completed, or participant refused measure).

Weight in kg was recorded at every study visit (screening, baseline, week 12, week 24, and week 48)

Outcome measures

Measure	Nicotinamide n=24 Participants 1500mg twice daily: 2, 750mg tablets taken orally twice daily Nicotinamide: Niacinamide (nicotinamide; 99%) is produced in a 750 mg sustained release tablet.	Placebo n=22 Participants 1500mg twice daily: 2, 750mg tablets taken orally twice daily Placebo Comparator: Oral Tablet
Vital Signs - Weight Screening Visit	76.39 kg Standard Deviation 12.99	68.11 kg Standard Deviation 14.3
Vital Signs - Weight Baseline Visit	76.29 kg Standard Deviation 12.57	70.05 kg Standard Deviation 11.86
Vital Signs - Weight Week 12 Visit	77.27 kg Standard Deviation 10.86	69.36 kg Standard Deviation 12.67
Vital Signs - Weight Week 24 Visit	76.88 kg Standard Deviation 11.49	72.22 kg Standard Deviation 11.35
Vital Signs - Weight Week 48 Visit	76.43 kg Standard Deviation 11.96	70.27 kg Standard Deviation 12.2

PRIMARY outcome

Timeframe: Screening through end of study (week 48)

Population: Numbers analyzed in some rows lower due to missing data (visit not completed, or participant refused measure).

Body Mass Index (BMI) was recorded at every study visit (screening, baseline, week 12, week 24, and week 48)

Outcome measures

Measure	Nicotinamide n=24 Participants 1500mg twice daily: 2, 750mg tablets taken orally twice daily Nicotinamide: Niacinamide (nicotinamide; 99%) is produced in a 750 mg sustained release tablet.	Placebo n=22 Participants 1500mg twice daily: 2, 750mg tablets taken orally twice daily Placebo Comparator: Oral Tablet
Vital Signs - BMI Week 24 Visit	26.52 kg/m^2 Standard Deviation 4.56	25.08 kg/m^2 Standard Deviation 3.68
Vital Signs - BMI Week 48 Visit	26.24 kg/m^2 Standard Deviation 4.75	24.68 kg/m^2 Standard Deviation 3.68
Vital Signs - BMI Screening Visit	26.35 kg/m^2 Standard Deviation 4.75	24.09 kg/m^2 Standard Deviation 4.17
Vital Signs - BMI Baseline Visit	26.33 kg/m^2 Standard Deviation 4.69	24.85 kg/m^2 Standard Deviation 3.43
Vital Signs - BMI Week 12 Visit	26.42 kg/m^2 Standard Deviation 4.51	24.72 kg/m^2 Standard Deviation 3.79

PRIMARY outcome

Timeframe: Screening through end of study (week 48)

Population: Numbers analyzed in some rows lower due to missing data (visit not completed, or participant refused measure).

Systolic blood pressure was recorded at every study visit (screening, baseline, week 12, week 24, and week 48)

Outcome measures

Measure	Nicotinamide n=24 Participants 1500mg twice daily: 2, 750mg tablets taken orally twice daily Nicotinamide: Niacinamide (nicotinamide; 99%) is produced in a 750 mg sustained release tablet.	Placebo n=22 Participants 1500mg twice daily: 2, 750mg tablets taken orally twice daily Placebo Comparator: Oral Tablet
Vital Signs - Systolic Blood Pressure Screening Visit	134.67 mm Hg Standard Deviation 19.17	126.09 mm Hg Standard Deviation 14.32
Vital Signs - Systolic Blood Pressure Baseline Visit	137.42 mm Hg Standard Deviation 15.99	125.41 mm Hg Standard Deviation 17.66
Vital Signs - Systolic Blood Pressure Week 12 Visit	133.36 mm Hg Standard Deviation 14.91	128.05 mm Hg Standard Deviation 18.61
Vital Signs - Systolic Blood Pressure Week 24 Visit	130.4 mm Hg Standard Deviation 14.04	130.16 mm Hg Standard Deviation 13.12
Vital Signs - Systolic Blood Pressure Week 48 Visit	129.43 mm Hg Standard Deviation 17.76	129.37 mm Hg Standard Deviation 17.16

PRIMARY outcome

Timeframe: Screening through end of study (week 48)

Population: Numbers analyzed in some rows lower due to missing data (visit not completed, or participant refused measure).

Diastolic blood pressure was recorded at every study visit (screening, baseline, week 12, week 24, and week 48)

Outcome measures

Measure	Nicotinamide n=24 Participants 1500mg twice daily: 2, 750mg tablets taken orally twice daily Nicotinamide: Niacinamide (nicotinamide; 99%) is produced in a 750 mg sustained release tablet.	Placebo n=22 Participants 1500mg twice daily: 2, 750mg tablets taken orally twice daily Placebo Comparator: Oral Tablet
Vital Signs - Diastolic Blood Pressure Week 12 Visit	72.45 mm Hg Standard Deviation 7.61	71.4 mm Hg Standard Deviation 10.23
Vital Signs - Diastolic Blood Pressure Week 24 Visit	75.2 mm Hg Standard Deviation 7.35	71.4 mm Hg Standard Deviation 10.23
Vital Signs - Diastolic Blood Pressure Screening Visit	75.42 mm Hg Standard Deviation 9.31	71.32 mm Hg Standard Deviation 8.97
Vital Signs - Diastolic Blood Pressure Baseline Visit	74.21 mm Hg Standard Deviation 11.87	70.45 mm Hg Standard Deviation 8.78
Vital Signs - Diastolic Blood Pressure Week 48 Visit	71.9 mm Hg Standard Deviation 10.4	69.74 mm Hg Standard Deviation 8.53

PRIMARY outcome

Timeframe: Screening through end of study (week 48)

Population: Numbers analyzed in some rows lower due to missing data (visit not completed, or participant refused measure).

Pulse rate was recorded at every study visit (screening, baseline, week 12, week 24, and week 48)

Outcome measures

Measure	Nicotinamide n=24 Participants 1500mg twice daily: 2, 750mg tablets taken orally twice daily Nicotinamide: Niacinamide (nicotinamide; 99%) is produced in a 750 mg sustained release tablet.	Placebo n=22 Participants 1500mg twice daily: 2, 750mg tablets taken orally twice daily Placebo Comparator: Oral Tablet
Vital Signs - Pulse Screening Visit	56.42 bpm Standard Deviation 6.98	62.5 bpm Standard Deviation 10.92
Vital Signs - Pulse Baseline Visit	59.33 bpm Standard Deviation 12.85	64.91 bpm Standard Deviation 8.78
Vital Signs - Pulse Week 12 Visit	58.86 bpm Standard Deviation 6.14	63.45 bpm Standard Deviation 11.65
Vital Signs - Pulse Week 24 Visit	58.6 bpm Standard Deviation 7.42	62.26 bpm Standard Deviation 8.75
Vital Signs - Pulse Week 48 Visit	59.57 bpm Standard Deviation 8.33	64.84 bpm Standard Deviation 12.65

PRIMARY outcome

Timeframe: Baseline to 48 weeks

Count of treatment emergent adverse events (TEAEs) over the duration of the study period (baseline to 48 weeks).

Outcome measures

Measure	Nicotinamide n=24 Participants 1500mg twice daily: 2, 750mg tablets taken orally twice daily Nicotinamide: Niacinamide (nicotinamide; 99%) is produced in a 750 mg sustained release tablet.	Placebo n=22 Participants 1500mg twice daily: 2, 750mg tablets taken orally twice daily Placebo Comparator: Oral Tablet
Count of Treatment Emergent Adverse Events	79 events	71 events

PRIMARY outcome

Timeframe: Baseline to 48 weeks

Count of treatment emergent adverse events (TEAEs) over the duration of the study period (baseline to 48 weeks).

Outcome measures

Measure	Nicotinamide n=24 Participants 1500mg twice daily: 2, 750mg tablets taken orally twice daily Nicotinamide: Niacinamide (nicotinamide; 99%) is produced in a 750 mg sustained release tablet.	Placebo n=22 Participants 1500mg twice daily: 2, 750mg tablets taken orally twice daily Placebo Comparator: Oral Tablet
Count of Adverse Events by Severity Mild	49 events	38 events
Count of Adverse Events by Severity Moderate	27 events	31 events
Count of Adverse Events by Severity Severe	3 events	2 events
Count of Adverse Events by Severity Total	79 events	71 events

PRIMARY outcome

Timeframe: Baseline to 48 weeks

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.

Outcome measures

Measure	Nicotinamide n=24 Participants 1500mg twice daily: 2, 750mg tablets taken orally twice daily Nicotinamide: Niacinamide (nicotinamide; 99%) is produced in a 750 mg sustained release tablet.	Placebo n=22 Participants 1500mg twice daily: 2, 750mg tablets taken orally twice daily Placebo Comparator: Oral Tablet
Columbia-Suicide Severity Rating Scale Baseline Number of abnormal C-SSRS events	0 events	3 events
Columbia-Suicide Severity Rating Scale Post-baseline number of abnormal C-SSRS events	1 events	3 events

PRIMARY outcome

Timeframe: Baseline to 48 weeks

Count of participants experiencing at least one electrocardiogram (ECG) abnormality.

Outcome measures

Measure	Nicotinamide n=24 Participants 1500mg twice daily: 2, 750mg tablets taken orally twice daily Nicotinamide: Niacinamide (nicotinamide; 99%) is produced in a 750 mg sustained release tablet.	Placebo n=22 Participants 1500mg twice daily: 2, 750mg tablets taken orally twice daily Placebo Comparator: Oral Tablet
ECG Abnormalities	24 Participants	20 Participants

PRIMARY outcome

Timeframe: Baseline to 48 weeks

Count of participants experiencing at least one electrocardiogram (ECG) QT interval abnormality. Abnormal defined as above 460 for men and above 470 for women.

Outcome measures

Measure	Nicotinamide n=24 Participants 1500mg twice daily: 2, 750mg tablets taken orally twice daily Nicotinamide: Niacinamide (nicotinamide; 99%) is produced in a 750 mg sustained release tablet.	Placebo n=22 Participants 1500mg twice daily: 2, 750mg tablets taken orally twice daily Placebo Comparator: Oral Tablet
QTC Abnormalities	2 Participants	1 Participants

PRIMARY outcome

Timeframe: Baseline to 48 weeks

Average within-subject change in electrocardiogram QT interval.

Outcome measures

Measure	Nicotinamide n=22 Participants 1500mg twice daily: 2, 750mg tablets taken orally twice daily Nicotinamide: Niacinamide (nicotinamide; 99%) is produced in a 750 mg sustained release tablet.	Placebo n=21 Participants 1500mg twice daily: 2, 750mg tablets taken orally twice daily Placebo Comparator: Oral Tablet
Change in QTC	6.41 ms Standard Deviation 16.02	2.1 ms Standard Deviation 11.85

SECONDARY outcome

Timeframe: Baseline to 48 weeks

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.

Outcome measures

Measure	Nicotinamide n=19 Participants 1500mg twice daily: 2, 750mg tablets taken orally twice daily Nicotinamide: Niacinamide (nicotinamide; 99%) is produced in a 750 mg sustained release tablet.	Placebo n=19 Participants 1500mg twice daily: 2, 750mg tablets taken orally twice daily Placebo Comparator: Oral Tablet
Change in ab40	2307 pg/ml Standard Deviation 2516.4	1961.1 pg/ml Standard Deviation 4252.97

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Nicotinamide n=19 Participants 1500mg twice daily: 2, 750mg tablets taken orally twice daily Nicotinamide: Niacinamide (nicotinamide; 99%) is produced in a 750 mg sustained release tablet.	Placebo n=19 Participants 1500mg twice daily: 2, 750mg tablets taken orally twice daily Placebo Comparator: Oral Tablet
Change in ab42	127.74 pg/ml Standard Deviation 161.54	113.79 pg/ml Standard Deviation 321.92

SECONDARY outcome

Timeframe: Baseline to 48 weeks

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.

Outcome measures

Measure	Nicotinamide n=19 Participants 1500mg twice daily: 2, 750mg tablets taken orally twice daily Nicotinamide: Niacinamide (nicotinamide; 99%) is produced in a 750 mg sustained release tablet.	Placebo n=19 Participants 1500mg twice daily: 2, 750mg tablets taken orally twice daily Placebo Comparator: Oral Tablet
Change in P-tau 181	-0.41 pg/ml Standard Deviation 29.83	-10.43 pg/ml Standard Deviation 41.79

SECONDARY outcome

Timeframe: Baseline to 48 weeks

Change in CSF total tau in individuals with mild Alzheimer's disease (AD) dementia or Mild Cognitive Impairment due to AD.

Outcome measures

Measure	Nicotinamide n=19 Participants 1500mg twice daily: 2, 750mg tablets taken orally twice daily Nicotinamide: Niacinamide (nicotinamide; 99%) is produced in a 750 mg sustained release tablet.	Placebo n=19 Participants 1500mg twice daily: 2, 750mg tablets taken orally twice daily Placebo Comparator: Oral Tablet
Change in Total Tau	-8.42 pg/ml Standard Deviation 228.59	-60.47 pg/ml Standard Deviation 237.54

SECONDARY outcome

Timeframe: Baseline to 48 weeks

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.

Outcome measures

Measure	Nicotinamide n=19 Participants 1500mg twice daily: 2, 750mg tablets taken orally twice daily Nicotinamide: Niacinamide (nicotinamide; 99%) is produced in a 750 mg sustained release tablet.	Placebo n=19 Participants 1500mg twice daily: 2, 750mg tablets taken orally twice daily Placebo Comparator: Oral Tablet
Change in Ratio of Total Tau/ab40	-0.02 ratio Standard Deviation 0.02	-0.02 ratio Standard Deviation 0.02

SECONDARY outcome

Timeframe: Baseline to 48 weeks

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.

Outcome measures

Measure	Nicotinamide n=19 Participants 1500mg twice daily: 2, 750mg tablets taken orally twice daily Nicotinamide: Niacinamide (nicotinamide; 99%) is produced in a 750 mg sustained release tablet.	Placebo n=19 Participants 1500mg twice daily: 2, 750mg tablets taken orally twice daily Placebo Comparator: Oral Tablet
Change in Ratio of Total Tau/ab42	-0.46 ratio Standard Deviation 0.56	-0.5 ratio Standard Deviation 0.55

SECONDARY outcome

Timeframe: Baseline to 48 weeks

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.

Outcome measures

Measure	Nicotinamide n=20 Participants 1500mg twice daily: 2, 750mg tablets taken orally twice daily Nicotinamide: Niacinamide (nicotinamide; 99%) is produced in a 750 mg sustained release tablet.	Placebo n=20 Participants 1500mg twice daily: 2, 750mg tablets taken orally twice daily Placebo Comparator: Oral Tablet
ADASCog-13	3.2 score on a scale Standard Deviation 5.72	5.16 score on a scale Standard Deviation 7.46

SECONDARY outcome

Timeframe: Baseline to 48 weeks

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.

Outcome measures

Measure	Nicotinamide n=20 Participants 1500mg twice daily: 2, 750mg tablets taken orally twice daily Nicotinamide: Niacinamide (nicotinamide; 99%) is produced in a 750 mg sustained release tablet.	Placebo n=20 Participants 1500mg twice daily: 2, 750mg tablets taken orally twice daily Placebo Comparator: Oral Tablet
Activities of Daily Living - Mild Cognitive Impairment	-4.05 score on a scale Standard Deviation 4.88	-1.39 score on a scale Standard Deviation 6.06

SECONDARY outcome

Timeframe: Baseline to 48 weeks

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.

Outcome measures

Measure	Nicotinamide n=21 Participants 1500mg twice daily: 2, 750mg tablets taken orally twice daily Nicotinamide: Niacinamide (nicotinamide; 99%) is produced in a 750 mg sustained release tablet.	Placebo n=20 Participants 1500mg twice daily: 2, 750mg tablets taken orally twice daily Placebo Comparator: Oral Tablet
CDR Sum of Boxes	0.76 score on a scale Standard Deviation 2.03	2.18 score on a scale Standard Deviation 2.82

Adverse Events

Nicotinamide

Serious events: 2 serious events

Other events: 23 other events

Deaths: 0 deaths

Placebo

Serious events: 6 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Measure	Nicotinamide n=24 participants at risk 1500mg twice daily: 2, 750mg tablets taken orally twice daily Nicotinamide: Niacinamide (nicotinamide; 99%) is produced in a 750 mg sustained release tablet.	Placebo n=22 participants at risk 1500mg twice daily: 2, 750mg tablets taken orally twice daily Placebo Comparator: Oral Tablet
Blood and lymphatic system disorders Leukocytosis	0.00% 0/24 • 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.	4.5% 1/22 • Number of events 1 • 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.
Injury, poisoning and procedural complications Injury	0.00% 0/24 • 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.	4.5% 1/22 • Number of events 1 • 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.
Investigations Transaminases increased	4.2% 1/24 • Number of events 1 • 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.	0.00% 0/22 • 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.
Metabolism and nutrition disorders Dehydration	0.00% 0/24 • 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.	4.5% 1/22 • Number of events 1 • 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colorectal cancer	4.2% 1/24 • Number of events 1 • 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.	0.00% 0/22 • 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.
Nervous system disorders Seizure	0.00% 0/24 • 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.	4.5% 1/22 • Number of events 1 • 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.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/24 • 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.	4.5% 1/22 • Number of events 1 • 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.
Vascular disorders Orthostatic hypotension	0.00% 0/24 • 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.	4.5% 1/22 • Number of events 1 • 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.

Other adverse events

Measure	Nicotinamide n=24 participants at risk 1500mg twice daily: 2, 750mg tablets taken orally twice daily Nicotinamide: Niacinamide (nicotinamide; 99%) is produced in a 750 mg sustained release tablet.	Placebo n=22 participants at risk 1500mg twice daily: 2, 750mg tablets taken orally twice daily Placebo Comparator: Oral Tablet
Blood and lymphatic system disorders Thrombocytopenia	4.2% 1/24 • Number of events 1 • 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.	0.00% 0/22 • 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.
Eye disorders Retinal detachment	0.00% 0/24 • 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.	4.5% 1/22 • Number of events 1 • 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.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/24 • 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.	4.5% 1/22 • Number of events 1 • 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.
Gastrointestinal disorders Colitis ulcerative	4.2% 1/24 • Number of events 1 • 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.	0.00% 0/22 • 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.
Gastrointestinal disorders Constipation	8.3% 2/24 • Number of events 2 • 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.	0.00% 0/22 • 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.
Gastrointestinal disorders Diarrhoea	25.0% 6/24 • Number of events 8 • 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.	9.1% 2/22 • Number of events 2 • 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.
Gastrointestinal disorders Dyspepsia	4.2% 1/24 • Number of events 1 • 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.	4.5% 1/22 • Number of events 1 • 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.
Gastrointestinal disorders Eructation	4.2% 1/24 • Number of events 1 • 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.	0.00% 0/22 • 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.
Gastrointestinal disorders Hiatus hernia	4.2% 1/24 • Number of events 1 • 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.	0.00% 0/22 • 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.
Gastrointestinal disorders Neusea	0.00% 0/24 • 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.	9.1% 2/22 • Number of events 2 • 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.
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/24 • 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.	4.5% 1/22 • Number of events 1 • 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.
Gastrointestinal disorders Vomiting	8.3% 2/24 • Number of events 2 • 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.	4.5% 1/22 • Number of events 1 • 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.
General disorders Fatigue	0.00% 0/24 • 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.	13.6% 3/22 • Number of events 3 • 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.
Infections and infestations Corona virus infection	0.00% 0/24 • 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.	9.1% 2/22 • Number of events 2 • 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.
Infections and infestations Diverticulitis	0.00% 0/24 • 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.	4.5% 1/22 • Number of events 1 • 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.
Infections and infestations Fungal infection	4.2% 1/24 • Number of events 1 • 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.	0.00% 0/22 • 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.
Infections and infestations Gastritis viral	0.00% 0/24 • 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.	4.5% 1/22 • Number of events 1 • 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.
Infections and infestations Hordeolum	0.00% 0/24 • 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.	4.5% 1/22 • Number of events 1 • 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.
Infections and infestations Infection	4.2% 1/24 • Number of events 1 • 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.	0.00% 0/22 • 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.
Infections and infestations Pneumonia	4.2% 1/24 • Number of events 1 • 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.	4.5% 1/22 • Number of events 1 • 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.
Infections and infestations Pyuria	0.00% 0/24 • 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.	4.5% 1/22 • Number of events 1 • 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.
Infections and infestations Tooth abscess	4.2% 1/24 • Number of events 1 • 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.	4.5% 1/22 • Number of events 1 • 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.
Infections and infestations Upper respiratory tract infection	4.2% 1/24 • Number of events 1 • 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.	9.1% 2/22 • Number of events 2 • 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.
Infections and infestations Urinary tract infection	16.7% 4/24 • Number of events 5 • 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.	18.2% 4/22 • Number of events 5 • 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.
Infections and infestations Viral upper respiratory tract infection	4.2% 1/24 • Number of events 1 • 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.	0.00% 0/22 • 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.
Injury, poisoning and procedural complications Fall	16.7% 4/24 • Number of events 5 • 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.	22.7% 5/22 • Number of events 5 • 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.
Injury, poisoning and procedural complications Fibula fracture	0.00% 0/24 • 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.	4.5% 1/22 • Number of events 1 • 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.
Injury, poisoning and procedural complications Foot fracture	4.2% 1/24 • Number of events 1 • 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.	0.00% 0/22 • 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.
Injury, poisoning and procedural complications Hand fracture	0.00% 0/24 • 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.	4.5% 1/22 • Number of events 1 • 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.
Injury, poisoning and procedural complications Head Injury	4.2% 1/24 • Number of events 1 • 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.	0.00% 0/22 • 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.
Injury, poisoning and procedural complications Laceration	4.2% 1/24 • Number of events 2 • 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.	0.00% 0/22 • 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.
Injury, poisoning and procedural complications Limb injury	4.2% 1/24 • Number of events 1 • 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.	0.00% 0/22 • 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.
Injury, poisoning and procedural complications Post lumbar puncture syndrome	4.2% 1/24 • Number of events 1 • 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.	4.5% 1/22 • Number of events 1 • 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.
Investigations Antimitochondrial antibody positive	0.00% 0/24 • 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.	4.5% 1/22 • Number of events 2 • 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.
Investigations Aspartate aminotransferase increased	0.00% 0/24 • 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.	4.5% 1/22 • Number of events 1 • 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.
Investigations Blood alkaline phosphatase increased	0.00% 0/24 • 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.	4.5% 1/22 • Number of events 1 • 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.
Investigations Blood testosterone decreased	4.2% 1/24 • Number of events 1 • 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.	0.00% 0/22 • 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.
Investigations Glomerular Ffiltration rate decreased	4.2% 1/24 • Number of events 1 • 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.	0.00% 0/22 • 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.
Investigations Laboratory test abnormal	8.3% 2/24 • Number of events 2 • 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.	0.00% 0/22 • 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.
Investigations Urine ketone body present	0.00% 0/24 • 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.	4.5% 1/22 • Number of events 1 • 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.
Investigations Weight decreased	4.2% 1/24 • Number of events 1 • 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.	0.00% 0/22 • 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.
Metabolism and nutrition disorders Dehydration	4.2% 1/24 • Number of events 1 • 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.	4.5% 1/22 • Number of events 1 • 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.
Metabolism and nutrition disorders Diabetes mellitus	4.2% 1/24 • Number of events 1 • 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.	0.00% 0/22 • 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.
Metabolism and nutrition disorders Hyperlipidaemia	4.2% 1/24 • Number of events 1 • 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.	0.00% 0/22 • 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.
Metabolism and nutrition disorders Hypokalaemia	4.2% 1/24 • Number of events 1 • 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.	0.00% 0/22 • 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.
Metabolism and nutrition disorders Vitamin D deficiency	4.2% 1/24 • Number of events 1 • 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.	0.00% 0/22 • 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.
Musculoskeletal and connective tissue disorders Arthralgia	4.2% 1/24 • Number of events 1 • 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.	0.00% 0/22 • 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.
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/24 • 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.	4.5% 1/22 • Number of events 1 • 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.
Musculoskeletal and connective tissue disorders Back pain	8.3% 2/24 • Number of events 2 • 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.	0.00% 0/22 • 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.
Musculoskeletal and connective tissue disorders Coccydynia	4.2% 1/24 • Number of events 1 • 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.	0.00% 0/22 • 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.
Musculoskeletal and connective tissue disorders Foot deformity	4.2% 1/24 • Number of events 1 • 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.	0.00% 0/22 • 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.
Musculoskeletal and connective tissue disorders Myalgia	4.2% 1/24 • Number of events 1 • 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.	0.00% 0/22 • 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.
Musculoskeletal and connective tissue disorders Osteoporosis	4.2% 1/24 • Number of events 1 • 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.	0.00% 0/22 • 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.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/24 • 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.	4.5% 1/22 • Number of events 1 • 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	4.2% 1/24 • Number of events 1 • 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.	0.00% 0/22 • 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.00% 0/24 • 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.	9.1% 2/22 • Number of events 2 • 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.
Nervous system disorders Cognitive disorder	4.2% 1/24 • Number of events 1 • 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.	4.5% 1/22 • Number of events 1 • 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.
Nervous system disorders Dizziness	4.2% 1/24 • Number of events 1 • 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.	4.5% 1/22 • Number of events 2 • 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.
Nervous system disorders Dysgeusia	4.2% 1/24 • Number of events 1 • 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.	0.00% 0/22 • 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.
Nervous system disorders Headache	4.2% 1/24 • Number of events 1 • 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.	0.00% 0/22 • 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.
Nervous system disorders Memory impairment	0.00% 0/24 • 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.	4.5% 1/22 • Number of events 1 • 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.
Nervous system disorders Neuropathy peripheral	4.2% 1/24 • Number of events 1 • 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.	0.00% 0/22 • 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.
Nervous system disorders Parkinson's disease	4.2% 1/24 • Number of events 1 • 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.	0.00% 0/22 • 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.
Nervous system disorders Pleocytosis	4.2% 1/24 • Number of events 1 • 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.	0.00% 0/22 • 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.
Nervous system disorders Postural tremor	0.00% 0/24 • 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.	4.5% 1/22 • Number of events 1 • 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.
Nervous system disorders Presyncope	0.00% 0/24 • 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.	4.5% 1/22 • Number of events 1 • 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.
Nervous system disorders Syncoper	4.2% 1/24 • Number of events 1 • 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.	0.00% 0/22 • 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.
Nervous system disorders Tremor	4.2% 1/24 • Number of events 1 • 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.	0.00% 0/22 • 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.
Psychiatric disorders Agitation	4.2% 1/24 • Number of events 1 • 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.	4.5% 1/22 • Number of events 1 • 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.
Psychiatric disorders Anxiety	8.3% 2/24 • Number of events 2 • 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.	4.5% 1/22 • Number of events 1 • 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.
Psychiatric disorders Depression	0.00% 0/24 • 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.	4.5% 1/22 • Number of events 1 • 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.
Psychiatric disorders Parasomnia	0.00% 0/24 • 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.	4.5% 1/22 • Number of events 1 • 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.
Renal and urinary disorders Haematuria	0.00% 0/24 • 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.	9.1% 2/22 • Number of events 2 • 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.
Renal and urinary disorders Micturition urgency	0.00% 0/24 • 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.	4.5% 1/22 • Number of events 1 • 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.
Renal and urinary disorders Renal cyst	4.2% 1/24 • Number of events 1 • 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.	0.00% 0/22 • 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.
Renal and urinary disorders Urinary incontinence	0.00% 0/24 • 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.	4.5% 1/22 • Number of events 1 • 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.
Renal and urinary disorders Urinary retention	0.00% 0/24 • 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.	4.5% 1/22 • Number of events 1 • 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.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.00% 0/24 • 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.	4.5% 1/22 • Number of events 1 • 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.
Skin and subcutaneous tissue disorders Actinic keratosis	4.2% 1/24 • Number of events 1 • 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.	0.00% 0/22 • 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.
Skin and subcutaneous tissue disorders Miliaria	4.2% 1/24 • Number of events 1 • 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.	0.00% 0/22 • 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.
Respiratory, thoracic and mediastinal disorders Penile ulceration	4.2% 1/24 • Number of events 1 • 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.	0.00% 0/22 • 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.
Skin and subcutaneous tissue disorders Psoriasis	4.2% 1/24 • Number of events 1 • 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.	0.00% 0/22 • 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.
Skin and subcutaneous tissue disorders Rash	4.2% 1/24 • Number of events 1 • 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.	0.00% 0/22 • 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.
Skin and subcutaneous tissue disorders Urticaria	4.2% 1/24 • Number of events 1 • 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.	0.00% 0/22 • 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.
Surgical and medical procedures Cancer surgery	4.2% 1/24 • Number of events 1 • 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.	0.00% 0/22 • 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.
Surgical and medical procedures Cataract operation	0.00% 0/24 • 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.	4.5% 1/22 • Number of events 1 • 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.
Surgical and medical procedures Skin neoplasm excision	0.00% 0/24 • 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.	4.5% 1/22 • Number of events 1 • 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.
Vascular disorders Haemorrhage	0.00% 0/24 • 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.	4.5% 1/22 • Number of events 1 • 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.
Vascular disorders Labile blood pressure	0.00% 0/24 • 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.	4.5% 1/22 • Number of events 1 • 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.

Additional Information

Dr. Joshua Grill

University of California, Irvine

Phone: (949) 824-5905

Email: jgrill@uci.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place