Trial Outcomes & Findings for Safety, Tolerability, PK and PD of Posiphen® in Subjects With Early Alzheimer's Disease (NCT NCT02925650)

Last Updated: 2023-05-09

Results Overview

Number of adverse events or study discontinuations, broken down by dose arm (i.e. Low vs. Medium vs. High vs. Placebo), and further broken down by relatedness to Posiphen (Definitely Related, Probably Related, Possibly Related, Unlikely Related, Unrelated)

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

18 participants

Primary outcome timeframe

Up to 25 days

Results posted on

2023-05-09

Participant Flow

Participant milestones

Participant milestones
Measure	Low Dose The study drug Posiphen dosage of 60mg is to be taken orally in divided doses, three times per day for a total 23-25 days. Posiphen: oral solid dosage form capsule	Medium Dose The study drug Posiphen dosage of 120mg is to be taken orally in divided doses, three times per day for a total 23-25 days. Posiphen: oral solid dosage form capsule	High Dose The study drug Posiphen dosage of 180mg is to be taken orally in divided doses, three times per day for a total 23-25 days. Posiphen: oral solid dosage form capsule	Placebo The Placebo comparator is to be taken orally in divided doses, three times per day for a total 23-25 days. Placebo: oral solid dosage form capsule
Overall Study STARTED	5	5	1	7
Overall Study COMPLETED	4	5	1	5
Overall Study NOT COMPLETED	1	0	0	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety, Tolerability, PK and PD of Posiphen® in Subjects With Early Alzheimer's Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Low Dose n=5 Participants The study drug Posiphen dosage of 60mg is to be taken orally in divided doses, three times per day for a total 23-25 days. Posiphen: oral solid dosage form capsule	Medium Dose n=5 Participants The study drug Posiphen dosage of 120mg is to be taken orally in divided doses, three times per day for a total 23-25 days. Posiphen: oral solid dosage form capsule	High Dose n=1 Participants The study drug Posiphen dosage of 180mg is to be taken orally in divided doses, three times per day for a total 23-25 days. Posiphen: oral solid dosage form capsule	Placebo n=7 Participants The Placebo comparator is to be taken orally in divided doses, three times per day for a total 23-25 days. Placebo: oral solid dosage form capsule	Total n=18 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	5 Participants n=21 Participants
Age, Categorical >=65 years	4 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	6 Participants n=4 Participants	13 Participants n=21 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants	8 Participants n=21 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	5 Participants n=7 Participants	1 Participants n=5 Participants	4 Participants n=4 Participants	10 Participants n=21 Participants
Race/Ethnicity, Customized White	5 Participants n=5 Participants	5 Participants n=7 Participants	1 Participants n=5 Participants	6 Participants n=4 Participants	17 Participants n=21 Participants
Race/Ethnicity, Customized Unknown, Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Race/Ethnicity, Customized Not-Hispanic or Latino	5 Participants n=5 Participants	5 Participants n=7 Participants	1 Participants n=5 Participants	6 Participants n=4 Participants	17 Participants n=21 Participants
Race/Ethnicity, Customized Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Region of Enrollment United States	5 participants n=5 Participants	5 participants n=7 Participants	1 participants n=5 Participants	7 participants n=4 Participants	18 participants n=21 Participants

PRIMARY outcome

Timeframe: Up to 25 days

Outcome measures

Outcome measures
Measure	Low Dose n=5 Participants The study drug Posiphen dosage of 60mg is to be taken orally in divided doses, three times per day for a total 23-25 days. Posiphen: oral solid dosage form capsule	Medium Dose n=5 Participants The study drug Posiphen dosage of 120mg is to be taken orally in divided doses, three times per day for a total 23-25 days. Posiphen: oral solid dosage form capsule	Placebo n=7 Participants The Placebo comparator is to be taken orally in divided doses, three times per day for a total 23-25 days. Placebo: oral solid dosage form capsule
Safety and Tolerability of Multiple Ascending Doses of Posiphen: Reports of Adverse Events or Study Discontinuations Probably Related	0 events	1 events	0 events
Safety and Tolerability of Multiple Ascending Doses of Posiphen: Reports of Adverse Events or Study Discontinuations Possibly Related	1 events	0 events	2 events
Safety and Tolerability of Multiple Ascending Doses of Posiphen: Reports of Adverse Events or Study Discontinuations Unlikely Related	2 events	3 events	2 events
Safety and Tolerability of Multiple Ascending Doses of Posiphen: Reports of Adverse Events or Study Discontinuations Definitely Related	0 events	0 events	0 events
Safety and Tolerability of Multiple Ascending Doses of Posiphen: Reports of Adverse Events or Study Discontinuations Unrelated	9 events	11 events	6 events
Safety and Tolerability of Multiple Ascending Doses of Posiphen: Reports of Adverse Events or Study Discontinuations Total	12 events	15 events	10 events

PRIMARY outcome

Timeframe: The confinement visit occurred following 21-23 days of treatment with either Posiphen or placebo, while also allowing a +/- 2-day visit window. Plasma was collected at 0, 2, 4, 8, 12, 16, 20, and 24hrs during the confinement visit.

Population: Participants in the Placebo Arm/Group were not given study drug. Therefore, measurements of study drug, Posiphen, and its metabolites were not performed on the Placebo Arm/Group.

Mean plasma concentrations of levels of posiphen tartrate, N1 desmethyl posiphen, and N8 desmethyl Posiphen metabolite were determined for each of the three dose cohorts (Low Dose, Medium Dose, High Dose) by a protein precipitation extraction method using a high performance liquid chromatographic mass spectrometric detection method, with a linear weighted regression to determine their concentrations.

Outcome measures

Outcome measures
Measure	Low Dose n=5 Participants The study drug Posiphen dosage of 60mg is to be taken orally in divided doses, three times per day for a total 23-25 days. Posiphen: oral solid dosage form capsule	Medium Dose n=5 Participants The study drug Posiphen dosage of 120mg is to be taken orally in divided doses, three times per day for a total 23-25 days. Posiphen: oral solid dosage form capsule	High Dose n=1 Participants The study drug Posiphen dosage of 180mg is to be taken orally in divided doses, three times per day for a total 23-25 days. Posiphen: oral solid dosage form capsule	Placebo The Placebo comparator is to be taken orally in divided doses, three times per day for a total 23-25 days. Placebo: oral solid dosage form capsule
The Levels of Posiphen and Its Metabolites Will be Determined in Plasma N8 metabolite	2.25 ng/mL Standard Deviation 1.36	5.04 ng/mL Standard Deviation 1.8	3.35 ng/mL Standard Deviation 0	—
The Levels of Posiphen and Its Metabolites Will be Determined in Plasma Posiphen	7.16 ng/mL Standard Deviation 4.25	9.51 ng/mL Standard Deviation 5.77	12.01 ng/mL Standard Deviation 0	—
The Levels of Posiphen and Its Metabolites Will be Determined in Plasma N1 metabolite	1.29 ng/mL Standard Deviation 0.77	3.02 ng/mL Standard Deviation 1.4	2.51 ng/mL Standard Deviation 0	—

PRIMARY outcome

Population: Participants in the Placebo Arm/Group were not given study drug. Therefore, measurements of study drug, Posiphen, and its metabolites were not performed on the Placebo Arm/Group.

Mean CSF concentrations of levels of posiphen tartrate, N1 desmethyl posiphen, and N8 desmethyl Posiphen metabolite were determined for each of the three dose cohorts (Low Dose, Medium Dose, High Dose) by a protein precipitation extraction method using a high performance liquid chromatographic mass spectrometric detection method, with a linear weighted regression to determine the concentrations.

Outcome measures

Outcome measures
Measure	Low Dose n=5 Participants The study drug Posiphen dosage of 60mg is to be taken orally in divided doses, three times per day for a total 23-25 days. Posiphen: oral solid dosage form capsule	Medium Dose n=5 Participants The study drug Posiphen dosage of 120mg is to be taken orally in divided doses, three times per day for a total 23-25 days. Posiphen: oral solid dosage form capsule	High Dose n=1 Participants The study drug Posiphen dosage of 180mg is to be taken orally in divided doses, three times per day for a total 23-25 days. Posiphen: oral solid dosage form capsule	Placebo The Placebo comparator is to be taken orally in divided doses, three times per day for a total 23-25 days. Placebo: oral solid dosage form capsule
The Levels of Posiphen and Its Metabolites Will be Determined in Cerebrospinal Fluid (CSF) Posiphen	0.46 ng/mL Standard Deviation 0.3	0.73 ng/mL Standard Deviation 0.52	0.71 ng/mL Standard Deviation 0	—
The Levels of Posiphen and Its Metabolites Will be Determined in Cerebrospinal Fluid (CSF) N1 metabolite	0.02 ng/mL Standard Deviation 0.04	0.28 ng/mL Standard Deviation 0.3	0 ng/mL Standard Deviation 0	—
The Levels of Posiphen and Its Metabolites Will be Determined in Cerebrospinal Fluid (CSF) N8 metabolite	0.35 ng/mL Standard Deviation 0.26	0.77 ng/mL Standard Deviation 0.43	0.15 ng/mL Standard Deviation 0	—

PRIMARY outcome

Timeframe: The confinement visit occurred following 21-23 days of treatment with either Posiphen or placebo, while also allowing a +/- 2-day visit window. CSF was collected between 6 and 16hrs during the confinement visit.

Population: 15 participants completed the Confinement visit and had sufficient samples to enable this analysis

The fractional synthesis rate (FSR) of Aβ40 was measured in the CSF using the SILK™ technique. FSR is a measure of the rate of Aβ synthesis in the brain. During 13C6-leucine infusion, 13C6-leucine is incorporated into newly synthesized proteins throughout the body, including the brain, in proportion to the available 13C6-leucine. This FSR is calculated as the rate of change of the ratio of 13C6-leucine-labeled Aβ proteins to unlabeled Aβ proteins in the lumbar CSF between 6 to 16 hours, normalized to the ratio of labeled to unlabeled leucine amino acid in plasma. It is reported as a fraction of 13C6-leucine-labeled to unlabeled Aβ proteins per hour. The ratio of Aβ in CSF containing 13C6-leucine to that containing unlabeled leucine is measured using mass spectrometry.

Outcome measures

Outcome measures
Measure	Low Dose n=4 Participants The study drug Posiphen dosage of 60mg is to be taken orally in divided doses, three times per day for a total 23-25 days. Posiphen: oral solid dosage form capsule	Medium Dose n=5 Participants The study drug Posiphen dosage of 120mg is to be taken orally in divided doses, three times per day for a total 23-25 days. Posiphen: oral solid dosage form capsule	High Dose n=1 Participants The study drug Posiphen dosage of 180mg is to be taken orally in divided doses, three times per day for a total 23-25 days. Posiphen: oral solid dosage form capsule	Placebo n=5 Participants The Placebo comparator is to be taken orally in divided doses, three times per day for a total 23-25 days. Placebo: oral solid dosage form capsule
Fractional Synthesis Rate of Aβ40 in CSF Using the SILK™ Technique With Multiple Doses of Posiphen	0.0405 fraction labeled:unlabeled Aβ40 per hr Interval 0.0298 to 0.0431	0.0400 fraction labeled:unlabeled Aβ40 per hr Interval 0.0373 to 0.0511	0.0206 fraction labeled:unlabeled Aβ40 per hr Interval 0.0206 to 0.0206	0.0375 fraction labeled:unlabeled Aβ40 per hr Interval 0.0319 to 0.0449

SECONDARY outcome

Timeframe: Up to 25 days

Population: Overall number of participants completing the protocol

Feasibility of CSF Catheter Study with SILK™ Technology was determined by comparing the total number of participants enrolled, randomized and treated with study drug in the trial to the total number of participants who completed the CSF Catheter Study across all participating sites.

Outcome measures

Outcome measures
Measure	Low Dose n=11 Participants The study drug Posiphen dosage of 60mg is to be taken orally in divided doses, three times per day for a total 23-25 days. Posiphen: oral solid dosage form capsule	Medium Dose n=7 Participants The study drug Posiphen dosage of 120mg is to be taken orally in divided doses, three times per day for a total 23-25 days. Posiphen: oral solid dosage form capsule	High Dose The study drug Posiphen dosage of 180mg is to be taken orally in divided doses, three times per day for a total 23-25 days. Posiphen: oral solid dosage form capsule	Placebo The Placebo comparator is to be taken orally in divided doses, three times per day for a total 23-25 days. Placebo: oral solid dosage form capsule
Feasibility of CSF Catheter Study With SILK™ Technology to Evaluate Rates of Enrollment	10 Participants	5 Participants	—	—

SECONDARY outcome

Timeframe: Up to 25 days

Population: The % of CSF samples with sufficient volume for testing will be determined across study participants during the SILK sampling procedure

The % of cerebrospinal fluid samples with sufficient volume for testing will be determined across study participants during the SILK sampling procedure

Outcome measures

Outcome measures
Measure	Low Dose n=15 Participants The study drug Posiphen dosage of 60mg is to be taken orally in divided doses, three times per day for a total 23-25 days. Posiphen: oral solid dosage form capsule	Medium Dose The study drug Posiphen dosage of 120mg is to be taken orally in divided doses, three times per day for a total 23-25 days. Posiphen: oral solid dosage form capsule	High Dose The study drug Posiphen dosage of 180mg is to be taken orally in divided doses, three times per day for a total 23-25 days. Posiphen: oral solid dosage form capsule	Placebo The Placebo comparator is to be taken orally in divided doses, three times per day for a total 23-25 days. Placebo: oral solid dosage form capsule
Feasibility of CSF Catheter Study With SILK™ Technology to Evaluate %CSF Samples With Enough Volume for Testing	81.75 percentage of CSF samples	—	—	—

SECONDARY outcome

Timeframe: Up to 25 days

Research satisfaction will be evaluated by qualitative response to 14 questions asked to participants about their experience with the study procedures. Responses will be grouped and reported by common themes

Outcome measures

Outcome measures
Measure	Low Dose n=15 Participants The study drug Posiphen dosage of 60mg is to be taken orally in divided doses, three times per day for a total 23-25 days. Posiphen: oral solid dosage form capsule	Medium Dose The study drug Posiphen dosage of 120mg is to be taken orally in divided doses, three times per day for a total 23-25 days. Posiphen: oral solid dosage form capsule	High Dose The study drug Posiphen dosage of 180mg is to be taken orally in divided doses, three times per day for a total 23-25 days. Posiphen: oral solid dosage form capsule	Placebo The Placebo comparator is to be taken orally in divided doses, three times per day for a total 23-25 days. Placebo: oral solid dosage form capsule
Feasibility of CSF Catheter Study With SILK™ Technology to Evaluate Research Satisfaction Rated "Excellent" for quality of tests and attention received during participation in the study.	94 percentage of participants	—	—	—
Feasibility of CSF Catheter Study With SILK™ Technology to Evaluate Research Satisfaction Reported "Yes, definitely" they would recommend this research program to a friend.	94 percentage of participants	—	—	—
Feasibility of CSF Catheter Study With SILK™ Technology to Evaluate Research Satisfaction Reported "No" adverse events were associated with the 36hr catheter procedure.	73 percentage of participants	—	—	—
Feasibility of CSF Catheter Study With SILK™ Technology to Evaluate Research Satisfaction Reported "Excellent" as the quality of the 36hr catheter procedure and attention they received.	80 percentage of participants	—	—	—
Feasibility of CSF Catheter Study With SILK™ Technology to Evaluate Research Satisfaction Reported the catheter procedure was "almost all of what I expected."	67 percentage of participants	—	—	—
Feasibility of CSF Catheter Study With SILK™ Technology to Evaluate Research Satisfaction Reported "Almost all of my expectations have been met" by the research program.	81 percentage of participants	—	—	—
Feasibility of CSF Catheter Study With SILK™ Technology to Evaluate Research Satisfaction Reported "Yes, definitely" they would choose to participate again.	87.5 percentage of participants	—	—	—
Feasibility of CSF Catheter Study With SILK™ Technology to Evaluate Research Satisfaction Reported "Volunteering" as what they liked best about the study.	31 percentage of participants	—	—	—
Feasibility of CSF Catheter Study With SILK™ Technology to Evaluate Research Satisfaction Reported "Time Commitment" as what they liked least about the study.	31 percentage of participants	—	—	—
Feasibility of CSF Catheter Study With SILK™ Technology to Evaluate Research Satisfaction Reported "Yes", the 36 hour catheter procedure was done.	100 percentage of participants	—	—	—
Feasibility of CSF Catheter Study With SILK™ Technology to Evaluate Research Satisfaction Reported they liked best was "participating in cutting edge research and interacting with the team".	100 percentage of participants	—	—	—
Feasibility of CSF Catheter Study With SILK™ Technology to Evaluate Research Satisfaction Reported "Other" as what they liked least about the 36hr catheter procedure.	47 percentage of participants	—	—	—
Feasibility of CSF Catheter Study With SILK™ Technology to Evaluate Research Satisfaction Reported "Other" as what they would change about the 36hr catheter procedure.	71 percentage of participants	—	—	—
Feasibility of CSF Catheter Study With SILK™ Technology to Evaluate Research Satisfaction Reported they would change the number of visits.	50 percentage of participants	—	—	—

SECONDARY outcome

Timeframe: CSF was sampled at Screening and at the start of the confinement visit, which occurred following 21-23 days of treatment with either Posiphen or placebo, while also allowing a +/- 2-day visit window.

Aβ38, Aβ40, Aβ42, sAPPα, sAPPβ, and T-Tau were sampled at Screening and at the start of the confinement visit. Results of these measures were reported as a least square means, calculated as the change between the measured values at the start of the confinement visit and Screening in ng/mL.

Outcome measures

Outcome measures
Measure	Low Dose n=10 Participants The study drug Posiphen dosage of 60mg is to be taken orally in divided doses, three times per day for a total 23-25 days. Posiphen: oral solid dosage form capsule	Medium Dose n=7 Participants The study drug Posiphen dosage of 120mg is to be taken orally in divided doses, three times per day for a total 23-25 days. Posiphen: oral solid dosage form capsule	High Dose The study drug Posiphen dosage of 180mg is to be taken orally in divided doses, three times per day for a total 23-25 days. Posiphen: oral solid dosage form capsule	Placebo The Placebo comparator is to be taken orally in divided doses, three times per day for a total 23-25 days. Placebo: oral solid dosage form capsule
Pharmacodynamic and PK-PD Effects on CSF Alzheimer's Disease Biomarkers Aβ38	0.391 ng/mL Standard Error 0.173	0.593 ng/mL Standard Error 0.199	—	—
Pharmacodynamic and PK-PD Effects on CSF Alzheimer's Disease Biomarkers Aβ40	1.73 ng/mL Standard Error 0.998	3.13 ng/mL Standard Error 1.151	—	—
Pharmacodynamic and PK-PD Effects on CSF Alzheimer's Disease Biomarkers Aβ42	0.107 ng/mL Standard Error 0.0653	0.211 ng/mL Standard Error 0.0753	—	—
Pharmacodynamic and PK-PD Effects on CSF Alzheimer's Disease Biomarkers Total Tau	186.4 ng/mL Standard Error 79.1	53.7 ng/mL Standard Error 124.9	—	—
Pharmacodynamic and PK-PD Effects on CSF Alzheimer's Disease Biomarkers sAPPα	6.49 ng/mL Standard Error 5.75	-3.5 ng/mL Standard Error 9.07	—	—
Pharmacodynamic and PK-PD Effects on CSF Alzheimer's Disease Biomarkers sAPPβ	19.1 ng/mL Standard Error 16.8	-28.6 ng/mL Standard Error 26.5	—	—

SECONDARY outcome

Timeframe: MMSE was administered at Baseline and at the Pre-Confinement Visit 1-3 days prior to the Confinement Visit. This confinement visit occurred following 21-23 days of treatment with either Posiphen or placebo, while also allowing a +/- 2-day visit window.

The short-term effects of Posiphen on mental status will be measured using the Mini-Mental State Examination (MMSE). The MMSE is a brief, global cognitive measure that includes orientation, memory, attention, concentration, naming, writing, repetition, comprehension, and construction. The total score ranges from 0 (worst) to 30 (best performance). Results of the MMSE for this trial were reported as a raw change score, calculated as the change between the total scores at two evaluation time points (Baseline, Pre-Confinement Visit) and where negative values are worse and positive values are better.

Outcome measures

Outcome measures
Measure	Low Dose n=5 Participants The study drug Posiphen dosage of 60mg is to be taken orally in divided doses, three times per day for a total 23-25 days. Posiphen: oral solid dosage form capsule	Medium Dose n=5 Participants The study drug Posiphen dosage of 120mg is to be taken orally in divided doses, three times per day for a total 23-25 days. Posiphen: oral solid dosage form capsule	High Dose n=1 Participants The study drug Posiphen dosage of 180mg is to be taken orally in divided doses, three times per day for a total 23-25 days. Posiphen: oral solid dosage form capsule	Placebo n=7 Participants The Placebo comparator is to be taken orally in divided doses, three times per day for a total 23-25 days. Placebo: oral solid dosage form capsule
Assessment of Mental Status Effects	-1.4 score on a scale Standard Deviation 0.89	1.2 score on a scale Standard Deviation 2.39	-1 score on a scale Standard Deviation 0	1.14 score on a scale Standard Deviation 2.12

SECONDARY outcome

Timeframe: NPI was administered at Baseline and at the Pre-Confinement Visit 1-3 days prior to the Confinement Visit. This confinement visit occurred following 21-23 days of treatment with either Posiphen or placebo, while also allowing a +/- 2-day visit window.

The Neuropsychiatric Inventory (NPI) was used to measure the frequency and severity of neuropsychiatric symptoms. On this scale frequency ratings range from 0 (no symptoms) to 4 (very frequently, once or more per day or continuously). Severity ratings range from 0 (no severity) to 3 (severe). The score for each of 12 symptoms measured in the scale is the product of severity and frequency within that symptom. The total score for the NPI is the sum of all 12 symptom item scores, for a highest possible total score of 144 in individuals with maximal symptoms, and a lowest possible total score of zero (0) in fully asymptomatic individuals. Lower scores are better and higher scores indicate more neuropsychiatric symptoms. Results are calculated as the change between the total scores at two evaluation time points (Baseline, Pre-Confinement Visit) with negative scores being better and positive scores being worse.

Outcome measures

Outcome measures
Measure	Low Dose n=5 Participants The study drug Posiphen dosage of 60mg is to be taken orally in divided doses, three times per day for a total 23-25 days. Posiphen: oral solid dosage form capsule	Medium Dose n=5 Participants The study drug Posiphen dosage of 120mg is to be taken orally in divided doses, three times per day for a total 23-25 days. Posiphen: oral solid dosage form capsule	High Dose n=1 Participants The study drug Posiphen dosage of 180mg is to be taken orally in divided doses, three times per day for a total 23-25 days. Posiphen: oral solid dosage form capsule	Placebo n=7 Participants The Placebo comparator is to be taken orally in divided doses, three times per day for a total 23-25 days. Placebo: oral solid dosage form capsule
Assessment of Neuropsychiatric Effects	-2.6 score on a scale Standard Deviation 2.88	3.4 score on a scale Standard Deviation 8.47	-9 score on a scale Standard Deviation 0	-3.86 score on a scale Standard Deviation 8.09

SECONDARY outcome

Timeframe: ADAS-Cog12 was administered at Baseline and at the Pre-Confinement Visit 1-3 days prior to the Confinement Visit. This confinement visit occurred following 21-23 days of treatment with either Posiphen or placebo, also allowing a +/- 2-day visit window.

The short-term effects of Posiphen on cognition were measured using the The Alzheimer's Disease Assessment Scale-Cognitive 12 (ADAS-Cog12). The ADAS-Cog is a structured scale that evaluates memory (word recall, word recognition), reasoning, language (naming, comprehension), orientation, ideational praxis and constructional praxis. The test is scored in terms of errors, with higher scores reflecting poorer performance and greater impairment. Total ADAS-Cog12 scores can range from 0 to 80, with lower scores being better and higher scores being worse. Results of the ADAS-Cog12 for this trial are reported as a raw change score, calculated as the change between the total scores at two evaluation time points (Baseline, Pre-Confinement Visit) with negative scores being better and positive scores being worse.

Outcome measures

Outcome measures
Measure	Low Dose n=11 Participants The study drug Posiphen dosage of 60mg is to be taken orally in divided doses, three times per day for a total 23-25 days. Posiphen: oral solid dosage form capsule	Medium Dose n=7 Participants The study drug Posiphen dosage of 120mg is to be taken orally in divided doses, three times per day for a total 23-25 days. Posiphen: oral solid dosage form capsule	High Dose The study drug Posiphen dosage of 180mg is to be taken orally in divided doses, three times per day for a total 23-25 days. Posiphen: oral solid dosage form capsule	Placebo The Placebo comparator is to be taken orally in divided doses, three times per day for a total 23-25 days. Placebo: oral solid dosage form capsule
Assessment of Cognitive Effects	-0.55 score on a scale Standard Deviation 6.04	-1.57 score on a scale Standard Deviation 5.19	—	—

Adverse Events

Low Dose

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Medium Dose

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

High Dose

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Howard Feldman MDCM, FRCP(C)

Alzheimer's Disease Cooperative Study

Phone: 858-246-1347

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Low Dose n=5 participants at risk The study drug Posiphen dosage of 60mg is to be taken orally in divided doses, three times per day for a total 23-25 days. Posiphen: oral solid dosage form capsule	Medium Dose n=5 participants at risk The study drug Posiphen dosage of 120mg is to be taken orally in divided doses, three times per day for a total 23-25 days. Posiphen: oral solid dosage form capsule	High Dose n=1 participants at risk The study drug Posiphen dosage of 180mg is to be taken orally in divided doses, three times per day for a total 23-25 days. Posiphen: oral solid dosage form capsule	Placebo n=7 participants at risk The Placebo comparator is to be taken orally in divided doses, three times per day for a total 23-25 days. Placebo: oral solid dosage form capsule
Psychiatric disorders agitation	0.00% 0/5 • From Randomization through Study Day 25.	20.0% 1/5 • From Randomization through Study Day 25.	0.00% 0/1 • From Randomization through Study Day 25.	0.00% 0/7 • From Randomization through Study Day 25.
Musculoskeletal and connective tissue disorders back pain	20.0% 1/5 • From Randomization through Study Day 25.	0.00% 0/5 • From Randomization through Study Day 25.	0.00% 0/1 • From Randomization through Study Day 25.	0.00% 0/7 • From Randomization through Study Day 25.
Injury, poisoning and procedural complications catheter site swelling	0.00% 0/5 • From Randomization through Study Day 25.	0.00% 0/5 • From Randomization through Study Day 25.	0.00% 0/1 • From Randomization through Study Day 25.	14.3% 1/7 • From Randomization through Study Day 25.
Respiratory, thoracic and mediastinal disorders cough	0.00% 0/5 • From Randomization through Study Day 25.	20.0% 1/5 • From Randomization through Study Day 25.	0.00% 0/1 • From Randomization through Study Day 25.	0.00% 0/7 • From Randomization through Study Day 25.
Gastrointestinal disorders diarrhoea	0.00% 0/5 • From Randomization through Study Day 25.	20.0% 1/5 • From Randomization through Study Day 25.	0.00% 0/1 • From Randomization through Study Day 25.	0.00% 0/7 • From Randomization through Study Day 25.
General disorders fatigue	20.0% 1/5 • From Randomization through Study Day 25.	0.00% 0/5 • From Randomization through Study Day 25.	0.00% 0/1 • From Randomization through Study Day 25.	0.00% 0/7 • From Randomization through Study Day 25.
Nervous system disorders headache	20.0% 1/5 • From Randomization through Study Day 25.	40.0% 2/5 • From Randomization through Study Day 25.	0.00% 0/1 • From Randomization through Study Day 25.	42.9% 3/7 • From Randomization through Study Day 25.
Injury, poisoning and procedural complications injection site pain	20.0% 1/5 • From Randomization through Study Day 25.	0.00% 0/5 • From Randomization through Study Day 25.	0.00% 0/1 • From Randomization through Study Day 25.	0.00% 0/7 • From Randomization through Study Day 25.
Injury, poisoning and procedural complications injection site swelling	20.0% 1/5 • From Randomization through Study Day 25.	0.00% 0/5 • From Randomization through Study Day 25.	0.00% 0/1 • From Randomization through Study Day 25.	0.00% 0/7 • From Randomization through Study Day 25.
General disorders lethargy	0.00% 0/5 • From Randomization through Study Day 25.	20.0% 1/5 • From Randomization through Study Day 25.	0.00% 0/1 • From Randomization through Study Day 25.	0.00% 0/7 • From Randomization through Study Day 25.
Gastrointestinal disorders medical device complication	0.00% 0/5 • From Randomization through Study Day 25.	40.0% 2/5 • From Randomization through Study Day 25.	0.00% 0/1 • From Randomization through Study Day 25.	0.00% 0/7 • From Randomization through Study Day 25.
Musculoskeletal and connective tissue disorders musculoskeletal pain	0.00% 0/5 • From Randomization through Study Day 25.	0.00% 0/5 • From Randomization through Study Day 25.	0.00% 0/1 • From Randomization through Study Day 25.	14.3% 1/7 • From Randomization through Study Day 25.
Musculoskeletal and connective tissue disorders musculoskeletal stiffness	20.0% 1/5 • From Randomization through Study Day 25.	0.00% 0/5 • From Randomization through Study Day 25.	0.00% 0/1 • From Randomization through Study Day 25.	0.00% 0/7 • From Randomization through Study Day 25.
Respiratory, thoracic and mediastinal disorders nasal congestion	0.00% 0/5 • From Randomization through Study Day 25.	20.0% 1/5 • From Randomization through Study Day 25.	0.00% 0/1 • From Randomization through Study Day 25.	0.00% 0/7 • From Randomization through Study Day 25.
Gastrointestinal disorders nausea	0.00% 0/5 • From Randomization through Study Day 25.	20.0% 1/5 • From Randomization through Study Day 25.	0.00% 0/1 • From Randomization through Study Day 25.	0.00% 0/7 • From Randomization through Study Day 25.
Musculoskeletal and connective tissue disorders neck pain	0.00% 0/5 • From Randomization through Study Day 25.	20.0% 1/5 • From Randomization through Study Day 25.	0.00% 0/1 • From Randomization through Study Day 25.	14.3% 1/7 • From Randomization through Study Day 25.
General disorders pain	0.00% 0/5 • From Randomization through Study Day 25.	0.00% 0/5 • From Randomization through Study Day 25.	0.00% 0/1 • From Randomization through Study Day 25.	14.3% 1/7 • From Randomization through Study Day 25.
Musculoskeletal and connective tissue disorders pain in extremity	40.0% 2/5 • From Randomization through Study Day 25.	0.00% 0/5 • From Randomization through Study Day 25.	0.00% 0/1 • From Randomization through Study Day 25.	0.00% 0/7 • From Randomization through Study Day 25.
Musculoskeletal and connective tissue disorders pain in jaw	0.00% 0/5 • From Randomization through Study Day 25.	0.00% 0/5 • From Randomization through Study Day 25.	0.00% 0/1 • From Randomization through Study Day 25.	14.3% 1/7 • From Randomization through Study Day 25.
Nervous system disorders paraesthesia	20.0% 1/5 • From Randomization through Study Day 25.	0.00% 0/5 • From Randomization through Study Day 25.	0.00% 0/1 • From Randomization through Study Day 25.	0.00% 0/7 • From Randomization through Study Day 25.
Injury, poisoning and procedural complications post lumbar puncture syndrome	40.0% 2/5 • From Randomization through Study Day 25.	20.0% 1/5 • From Randomization through Study Day 25.	0.00% 0/1 • From Randomization through Study Day 25.	14.3% 1/7 • From Randomization through Study Day 25.
Respiratory, thoracic and mediastinal disorders productive cough	0.00% 0/5 • From Randomization through Study Day 25.	20.0% 1/5 • From Randomization through Study Day 25.	0.00% 0/1 • From Randomization through Study Day 25.	0.00% 0/7 • From Randomization through Study Day 25.
Infections and infestations rhinitis	20.0% 1/5 • From Randomization through Study Day 25.	0.00% 0/5 • From Randomization through Study Day 25.	0.00% 0/1 • From Randomization through Study Day 25.	0.00% 0/7 • From Randomization through Study Day 25.
Injury, poisoning and procedural complications sunburn	0.00% 0/5 • From Randomization through Study Day 25.	20.0% 1/5 • From Randomization through Study Day 25.	0.00% 0/1 • From Randomization through Study Day 25.	0.00% 0/7 • From Randomization through Study Day 25.
Injury, poisoning and procedural complications traumatic lumbar puncture	0.00% 0/5 • From Randomization through Study Day 25.	20.0% 1/5 • From Randomization through Study Day 25.	0.00% 0/1 • From Randomization through Study Day 25.	0.00% 0/7 • From Randomization through Study Day 25.
Nervous system disorders tremor	0.00% 0/5 • From Randomization through Study Day 25.	0.00% 0/5 • From Randomization through Study Day 25.	0.00% 0/1 • From Randomization through Study Day 25.	28.6% 2/7 • From Randomization through Study Day 25.
Infections and infestations urinary tract infection	0.00% 0/5 • From Randomization through Study Day 25.	0.00% 0/5 • From Randomization through Study Day 25.	0.00% 0/1 • From Randomization through Study Day 25.	14.3% 1/7 • From Randomization through Study Day 25.