Trial Outcomes & Findings for Effects of Huperzine A in Treatment of Moderate to Severe TBI (NCT NCT01676311)

NCT ID: NCT01676311

Last Updated: 2019-11-05

Results Overview

Measure of learning and memory function. Three indices of the CVLT-II were calculated. The full name, abbreviated name, and the minimum and maximum possible scores of each index are indicated below: 1. California Verbal Learning Test- 2nd Edition- Total Learning \[CVLT-II-TL\] (Minimum score=0; Maximum score= 80) 2. California Verbal Learning Test- 2nd Edition- Short delay free recall \[CVLT-II-SDFR\] (Minimum score=0; Maximum score=16) 3. California Verbal Learning Test- 2nd Edition- Long delay free recall \[CVLT-II-LDFR\] (Minimum score=0; Maximum score=16) High scores are indicative of greater memory and learning for each index (i.e. better outcome).

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 14 participants
• Primary outcome timeframe: Baseline, 6 weeks, 12 weeks, 24 weeks and at 52 weeks.
• Results posted on: 2019-11-05

Participant Flow

Participant milestones

Measure	Huperzine A Huperzine A will be administered to patients, titrating dose up from 100mcg/day to 600mcg per day over the course of 20 days - and remaining on the dose of 600mcg/day for the remainder of the drug phase (64 days) - for a total of 12 weeks on Huperzine A. Huperzine A: Huperzine A will be administered for 12 weeks as outlined in the Arm Description	Placebo Placebo will be administered to patients at the same frequency/intervals as the experimental arm (Huperzine-A). Placebo: Placebo Arm (blinded randomization) for Huperzine A Intervention
Overall Study STARTED	7	7
Overall Study COMPLETED	7	5
Overall Study NOT COMPLETED	0	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Effects of Huperzine A in Treatment of Moderate to Severe TBI

Baseline characteristics by cohort

Measure	Huperzine A n=7 Participants Huperzine A will be administered to patients, titrating dose up from 100mcg/day to 600mcg per day over the course of 20 days - and remaining on the dose of 600mcg/day for the remainder of the drug phase (64 days) - for a total of 12 weeks on Huperzine A. Huperzine A: Huperzine A will be administered for 12 weeks as outlined in the Arm Description	Placebo n=7 Participants Placebo will be administered to patients at the same frequency/intervals as the experimental arm (Huperzine-A). Placebo: Placebo Arm (blinded randomization) for Huperzine A Intervention	Total n=14 Participants Total of all reporting groups
Age, Continuous	37.00 years STANDARD_DEVIATION 16.21 • n=5 Participants	38.57 years STANDARD_DEVIATION 16.60 • n=7 Participants	37.79 years STANDARD_DEVIATION 15.78 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=5 Participants	7 Participants n=7 Participants	13 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
Region of Enrollment United States	7 participants n=5 Participants	7 participants n=7 Participants	14 participants n=5 Participants
Admission status Inpatient	1 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants
Admission status Outpatient	6 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants
Days post-injury	155.40 days STANDARD_DEVIATION 130.27 • n=5 Participants	226.86 days STANDARD_DEVIATION 120.30 • n=7 Participants	197.08 days STANDARD_DEVIATION 124.17 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 6 weeks, 12 weeks, 24 weeks and at 52 weeks.

Measure of learning and memory function. Three indices of the CVLT-II were calculated. The full name, abbreviated name, and the minimum and maximum possible scores of each index are indicated below:

1. California Verbal Learning Test- 2nd Edition- Total Learning [CVLT-II-TL] (Minimum score=0; Maximum score= 80)

2. California Verbal Learning Test- 2nd Edition- Short delay free recall [CVLT-II-SDFR] (Minimum score=0; Maximum score=16)

3. California Verbal Learning Test- 2nd Edition- Long delay free recall [CVLT-II-LDFR] (Minimum score=0; Maximum score=16)

High scores are indicative of greater memory and learning for each index (i.e. better outcome).

Outcome measures

Measure	Huperzine A n=7 Participants Huperzine A will be administered to patients, titrating dose up from 100mcg/day to 600mcg per day over the course of 20 days - and remaining on the dose of 600mcg/day for the remainder of the drug phase (64 days) - for a total of 12 weeks on Huperzine A. Huperzine A: Huperzine A will be administered for 12 weeks as outlined in the Arm Description	Placebo n=5 Participants Placebo will be administered to patients at the same frequency/intervals as the experimental arm (Huperzine-A). Placebo: Placebo Arm (blinded randomization) for Huperzine A Intervention
California Verbal Learning Test- 2nd Edition (CVLT-II): Learning and Memory CVLT-II-TL - Week 6	31.43 score on a scale Standard Deviation 11.37	45.00 score on a scale Standard Deviation 17.65
California Verbal Learning Test- 2nd Edition (CVLT-II): Learning and Memory CVLT-II-TL - Week 52	37.43 score on a scale Standard Deviation 11.30	49.40 score on a scale Standard Deviation 15.00
California Verbal Learning Test- 2nd Edition (CVLT-II): Learning and Memory CVLT-II-LDFR - Week 52	6.14 score on a scale Standard Deviation 4.67	10.00 score on a scale Standard Deviation 4.74
California Verbal Learning Test- 2nd Edition (CVLT-II): Learning and Memory CVLT-II-TL - Baseline	28.57 score on a scale Standard Deviation 12.35	34.40 score on a scale Standard Deviation 18.73
California Verbal Learning Test- 2nd Edition (CVLT-II): Learning and Memory CVLT-II-TL - Week 12	38.29 score on a scale Standard Deviation 14.20	49.60 score on a scale Standard Deviation 18.27
California Verbal Learning Test- 2nd Edition (CVLT-II): Learning and Memory CVLT-II-TL - Week 24	33.29 score on a scale Standard Deviation 14.29	44.60 score on a scale Standard Deviation 14.12
California Verbal Learning Test- 2nd Edition (CVLT-II): Learning and Memory CVLT-II-SDFR - Baseline	3.86 score on a scale Standard Deviation 4.38	5.80 score on a scale Standard Deviation 4.66
California Verbal Learning Test- 2nd Edition (CVLT-II): Learning and Memory CVLT-II-SDFR - Week 6	4.14 score on a scale Standard Deviation 3.53	7.83 score on a scale Standard Deviation 4.12
California Verbal Learning Test- 2nd Edition (CVLT-II): Learning and Memory CVLT-II-SDFR - Week 12	6.29 score on a scale Standard Deviation 4.99	10.40 score on a scale Standard Deviation 5.46
California Verbal Learning Test- 2nd Edition (CVLT-II): Learning and Memory CVLT-II-SDFR - Week 24	4.86 score on a scale Standard Deviation 4.45	10.00 score on a scale Standard Deviation 4.24
California Verbal Learning Test- 2nd Edition (CVLT-II): Learning and Memory CVLT-II-SDFR - Week 52	5.43 score on a scale Standard Deviation 3.36	9.80 score on a scale Standard Deviation 5.50
California Verbal Learning Test- 2nd Edition (CVLT-II): Learning and Memory CVLT-II-LDFR - Baseline	5.00 score on a scale Standard Deviation 4.80	7.00 score on a scale Standard Deviation 5.70
California Verbal Learning Test- 2nd Edition (CVLT-II): Learning and Memory CVLT-II-LDFR - Week 6	4.43 score on a scale Standard Deviation 4.39	8.33 score on a scale Standard Deviation 4.08
California Verbal Learning Test- 2nd Edition (CVLT-II): Learning and Memory CVLT-II-LDFR - Week 12	6.00 score on a scale Standard Deviation 4.76	10.00 score on a scale Standard Deviation 5.96
California Verbal Learning Test- 2nd Edition (CVLT-II): Learning and Memory CVLT-II-LDFR - Week 24	4.29 score on a scale Standard Deviation 4.46	8.40 score on a scale Standard Deviation 4.67

SECONDARY outcome

Timeframe: Baseline, 12 Weeks

Population: Of the 12 participants who completed the 12-week treatment period, P50 and P500 amplitude data could be analyzed for 4 participants. Data for the other 8 participants could not be analyzed as the data were compromised by movement artifact during recording.

Event Related Potentials (ERPs): P50 and P300 are neurophysiological measurements that index cortical electrical activity associated with a given stimulus. P50 and P300 were measured using auditory stimuli. P50 represents an index of activity in the cholinergic system and has been used to characterize presynaptic cholinergic deficit. P300 is a measure of general cognitive processing elicited during attention, memory, and executive tasks.

Outcome measures

Measure	Huperzine A n=3 Participants Huperzine A will be administered to patients, titrating dose up from 100mcg/day to 600mcg per day over the course of 20 days - and remaining on the dose of 600mcg/day for the remainder of the drug phase (64 days) - for a total of 12 weeks on Huperzine A. Huperzine A: Huperzine A will be administered for 12 weeks as outlined in the Arm Description	Placebo n=1 Participants Placebo will be administered to patients at the same frequency/intervals as the experimental arm (Huperzine-A). Placebo: Placebo Arm (blinded randomization) for Huperzine A Intervention
Amplitude of Event Related Potentials (ERPs) P50 and P300 P300 Amplitude - Baseline	13.57 mV Interval 9.28 to 17.86	9.96 mV
Amplitude of Event Related Potentials (ERPs) P50 and P300 P300 Amplitude - Week 12	12.69 mV Interval 4.1 to 21.28	9.69 mV
Amplitude of Event Related Potentials (ERPs) P50 and P300 P50 Amplitude - Baseline	7.89 mV Interval 4.59 to 11.19	NA mV The participant did not have P50 data that could be analyzed.
Amplitude of Event Related Potentials (ERPs) P50 and P300 P50 Amplitude - Week 12	5.89 mV Interval -0.36 to 12.14	NA mV The participant did not have P50 data that could be analyzed.

SECONDARY outcome

Timeframe: Baseline, 12 weeks

Population: Of the 12 participants who completed the 12-week treatment period, P50 and P500 latency data could be analyzed for 3 participants. Data for the other 9 participants could not be analyzed as the data were compromised by movement artifact during recording.

Event Related Potentials (ERPs): P50 and P300 are neurophysiological measurements that index cortical electrical activity associated with a given stimulus. P50 and P300 were measured using auditory stimuli. P50 represents an index of activity in the cholinergic system and has been used to characterize presynaptic cholinergic deficit and P300 is a measure of general cognitive processing elicited during attention, memory, and executive tasks.

Outcome measures

Measure	Huperzine A n=3 Participants Huperzine A will be administered to patients, titrating dose up from 100mcg/day to 600mcg per day over the course of 20 days - and remaining on the dose of 600mcg/day for the remainder of the drug phase (64 days) - for a total of 12 weeks on Huperzine A. Huperzine A: Huperzine A will be administered for 12 weeks as outlined in the Arm Description	Placebo Placebo will be administered to patients at the same frequency/intervals as the experimental arm (Huperzine-A). Placebo: Placebo Arm (blinded randomization) for Huperzine A Intervention
Latency of Event Related Potentials (ERPs) P50 and P300 P50 Latency - Baseline	50 ms Interval 48.0 to 52.0	—
Latency of Event Related Potentials (ERPs) P50 and P300 P300 Latency - Baseline	309 ms Interval 306.0 to 312.0	—
Latency of Event Related Potentials (ERPs) P50 and P300 P300 Latency - Week 12	311 ms Interval 291.0 to 331.0	—
Latency of Event Related Potentials (ERPs) P50 and P300 P50 Latency - Week 12	49 ms Interval 49.0 to 49.0	—

SECONDARY outcome

Timeframe: Baseline and weekly for 12 weeks.

To determine whether Huperzine A changes the prevalence of post-traumatic seizure after moderate and severe TBI as compared to placebo at 12 weeks post-enrollment (immediate seizures prevalence).

Outcome measures

Measure	Huperzine A n=7 Participants Huperzine A will be administered to patients, titrating dose up from 100mcg/day to 600mcg per day over the course of 20 days - and remaining on the dose of 600mcg/day for the remainder of the drug phase (64 days) - for a total of 12 weeks on Huperzine A. Huperzine A: Huperzine A will be administered for 12 weeks as outlined in the Arm Description	Placebo n=5 Participants Placebo will be administered to patients at the same frequency/intervals as the experimental arm (Huperzine-A). Placebo: Placebo Arm (blinded randomization) for Huperzine A Intervention
Number of Participants Who Experienced Post-traumatic Seizure During 12-week Treatment Window	2 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline and weekly for 12 weeks.

To evaluate the safety and tolerability of Huperzine A in this patient population as compared to placebo the frequency of self-reported side effects during the 12-week treatment window were grouped categorically by system (behavioral, cardiac-respiratory, dermatological,gastrointestinal, genitourinary/neurological, hematological, musculoskeletal, neurological).

Outcome measures

Measure	Huperzine A n=7 Participants Huperzine A will be administered to patients, titrating dose up from 100mcg/day to 600mcg per day over the course of 20 days - and remaining on the dose of 600mcg/day for the remainder of the drug phase (64 days) - for a total of 12 weeks on Huperzine A. Huperzine A: Huperzine A will be administered for 12 weeks as outlined in the Arm Description	Placebo n=6 Participants Placebo will be administered to patients at the same frequency/intervals as the experimental arm (Huperzine-A). Placebo: Placebo Arm (blinded randomization) for Huperzine A Intervention
Number of Participants With Self-reported Side Effects During 12-week Treatment Window Behavioral side effects	5 Participants	4 Participants
Number of Participants With Self-reported Side Effects During 12-week Treatment Window Cardiac-respiratory side effects	6 Participants	4 Participants
Number of Participants With Self-reported Side Effects During 12-week Treatment Window Dematological side effects	2 Participants	0 Participants
Number of Participants With Self-reported Side Effects During 12-week Treatment Window Gastrointestinal side effects	3 Participants	1 Participants
Number of Participants With Self-reported Side Effects During 12-week Treatment Window Genitourinary/neurological side effects	1 Participants	1 Participants
Number of Participants With Self-reported Side Effects During 12-week Treatment Window Hematological side effects	6 Participants	6 Participants
Number of Participants With Self-reported Side Effects During 12-week Treatment Window Musculoskeletal side effects	3 Participants	2 Participants
Number of Participants With Self-reported Side Effects During 12-week Treatment Window Neurological side effects	7 Participants	5 Participants

Adverse Events

Huperzine A

Serious events: 2 serious events

Other events: 7 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Measure	Huperzine A n=7 participants at risk Huperzine A will be administered to patients, titrating dose up from 100mcg/day to 600mcg per day over the course of 20 days - and remaining on the dose of 600mcg/day for the remainder of the drug phase (64 days) - for a total of 12 weeks on Huperzine A. Huperzine A: Huperzine A will be administered for 12 weeks as outlined in the Arm Description	Placebo n=6 participants at risk Placebo will be administered to patients at the same frequency/intervals as the experimental arm (Huperzine-A). Placebo: Placebo Arm (blinded randomization) for Huperzine A Intervention
Nervous system disorders Seizure	28.6% 2/7 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).	16.7% 1/6 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).

Other adverse events

Measure	Huperzine A n=7 participants at risk Huperzine A will be administered to patients, titrating dose up from 100mcg/day to 600mcg per day over the course of 20 days - and remaining on the dose of 600mcg/day for the remainder of the drug phase (64 days) - for a total of 12 weeks on Huperzine A. Huperzine A: Huperzine A will be administered for 12 weeks as outlined in the Arm Description	Placebo n=6 participants at risk Placebo will be administered to patients at the same frequency/intervals as the experimental arm (Huperzine-A). Placebo: Placebo Arm (blinded randomization) for Huperzine A Intervention
Psychiatric disorders Anxiety	57.1% 4/7 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).	66.7% 4/6 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).
Psychiatric disorders Irritability	42.9% 3/7 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).	50.0% 3/6 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).
Psychiatric disorders Depression	28.6% 2/7 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).	16.7% 1/6 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).
Respiratory, thoracic and mediastinal disorders Difficulty breathing	14.3% 1/7 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).	0.00% 0/6 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).
General disorders Increased blood pressure	85.7% 6/7 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).	66.7% 4/6 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).
General disorders Decrease in heart rate	85.7% 6/7 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).	66.7% 4/6 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).
Skin and subcutaneous tissue disorders Skin rash	28.6% 2/7 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).	0.00% 0/6 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).
Gastrointestinal disorders Nausea	42.9% 3/7 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).	16.7% 1/6 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).
Gastrointestinal disorders Loss of appetite	14.3% 1/7 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).	0.00% 0/6 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).
Gastrointestinal disorders Dry mouth	14.3% 1/7 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).	16.7% 1/6 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).
Gastrointestinal disorders Constipation	14.3% 1/7 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).	16.7% 1/6 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).
Gastrointestinal disorders Vomiting	14.3% 1/7 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).	0.00% 0/6 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).
Gastrointestinal disorders Increased saliva production	28.6% 2/7 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).	16.7% 1/6 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).
Renal and urinary disorders Incontinence	14.3% 1/7 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).	16.7% 1/6 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).
Blood and lymphatic system disorders Low white blood cell count	85.7% 6/7 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).	100.0% 6/6 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).
Musculoskeletal and connective tissue disorders Muscle cramps	14.3% 1/7 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).	33.3% 2/6 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).
Musculoskeletal and connective tissue disorders Muscle twitching	28.6% 2/7 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).	16.7% 1/6 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).
Nervous system disorders Dizziness	28.6% 2/7 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).	16.7% 1/6 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).
General disorders Difficulty sleeping	42.9% 3/7 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).	50.0% 3/6 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).
Nervous system disorders Confusion	71.4% 5/7 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).	50.0% 3/6 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).
Nervous system disorders Headache	42.9% 3/7 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).	33.3% 2/6 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).
General disorders Fatigue	57.1% 4/7 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).	83.3% 5/6 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).
Nervous system disorders Thinking abnormalities	28.6% 2/7 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).	33.3% 2/6 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).
Nervous system disorders Weakness	14.3% 1/7 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).	33.3% 2/6 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).
Nervous system disorders Slurred speech	0.00% 0/7 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).	33.3% 2/6 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).
Eye disorders Abnormal vision	28.6% 2/7 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).	33.3% 2/6 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).
Nervous system disorders Light sensitivity	14.3% 1/7 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).	16.7% 1/6 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).
Nervous system disorders Increased uncontrolled movement	28.6% 2/7 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).	0.00% 0/6 • Telephone: Weekly from baseline to 12 weeks (active treatment phase). In-person follow-up visits: Baseline, 6, 12, 13, 24, and 52 weeks. Subjects were instructed to call the Study Coordinator if a serious adverse event occurred between scheduled telephone or in-person follow-ups. Adverse events were collected and recorded using a standard adverse event form that included 35 possible adverse events. For 'Adverse Events', 'Serious Adverse Events', and 'Other (Not Including Serious) Adverse Events', results are reported for all participants who were 'at risk' i.e. received Huperzine A or placebo and completed at least one telephone or in-person follow-up visit (Huperzine A group: 7 participants; Placebo group: 6 participants).

Additional Information

Ross Zafonte, DO

Spaulding Rehabilitation Hospital

Phone: 617-952-5227

Email: rzafonte@mgh.harvard.edu

Results disclosure agreements

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