Trial Outcomes & Findings for Trial of Dronabinol Adjunctive Treatment of Agitation in Alzheimer's Disease (NCT NCT02792257)

Last Updated: 2025-05-09

Results Overview

The Pittsburgh Agitation Scale (PAS) is a tool used to assess the severity of agitation in patients, particularly with dementia. The minimum score is 0 and the maximum score is 16. A higher number means a worse outcome, meaning more agitation.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

84 participants

Primary outcome timeframe

Up to 3 weeks

Results posted on

2025-05-09

Participant Flow

There were 84 enrolled participants at 5 clinical research sites. Most of the recruitment was at three sites (Johns Hopkins, McLean, and Miami).

84 subjects signed consents to be screened for eligibility. 9 participants signed consents but did not meet the eligibility criteria to start the study (screen failures). 75 subjects were randomized to treatment groups in the study.

Participant milestones

Participant milestones
Measure	Dronabinol Study medication will be administered twice daily. Capsules of dronabinol will contain 2.5 mg per dose (5mg daily) during Week 1, then increase to 5 mg per dose (10mg daily) for Weeks 2 and 3. Dronabinol (Marinol®): 5mg - 10mg daily dose	Placebo Placebo medication will be administered twice daily. Placebo: Daily dose
Overall Study STARTED	37	38
Overall Study COMPLETED	32	31
Overall Study NOT COMPLETED	5	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Dronabinol Study medication will be administered twice daily. Capsules of dronabinol will contain 2.5 mg per dose (5mg daily) during Week 1, then increase to 5 mg per dose (10mg daily) for Weeks 2 and 3. Dronabinol (Marinol®): 5mg - 10mg daily dose	Placebo Placebo medication will be administered twice daily. Placebo: Daily dose
Overall Study Lost to Follow-up	3	4
Overall Study Allergy	0	1
Overall Study Protocol Violation	2	0
Overall Study Excessive Agitation	0	1
Overall Study Not Feeling Well	0	1

Baseline Characteristics

Trial of Dronabinol Adjunctive Treatment of Agitation in Alzheimer's Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dronabinol n=37 Participants Study medication will be administered twice daily. Capsules of dronabinol will contain 2.5 mg per dose (5mg daily) during Week 1, then increase to 5 mg per dose (10mg daily) for Weeks 2 and 3. Dronabinol (Marinol®): 5mg - 10mg daily dose	Placebo n=38 Participants Placebo medication will be administered twice daily. Placebo: Daily dose	Total n=75 Participants Total of all reporting groups
Ethnicity (NIH/OMB) Not Hispanic or Latino	33 Participants n=5 Participants	34 Participants n=7 Participants	67 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Age, Customized Mean Age	79.1 years STANDARD_DEVIATION 7.3 • n=5 Participants	77.9 years STANDARD_DEVIATION 7.7 • n=7 Participants	78.5 years STANDARD_DEVIATION 7.5 • n=5 Participants
Sex: Female, Male Female	22 Participants n=5 Participants	27 Participants n=7 Participants	49 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	11 Participants n=7 Participants	26 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) White	35 Participants n=5 Participants	32 Participants n=7 Participants	67 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Education	14.1 years STANDARD_DEVIATION 2.9 • n=5 Participants	13.6 years STANDARD_DEVIATION 3.6 • n=7 Participants	13.8 years STANDARD_DEVIATION 3.2 • n=5 Participants
Current Antidepressant Yes	7 Participants n=5 Participants	25 Participants n=7 Participants	32 Participants n=5 Participants
Current Antidepressant No	30 Participants n=5 Participants	13 Participants n=7 Participants	43 Participants n=5 Participants
Current Antipsychotic Yes	20 Participants n=5 Participants	18 Participants n=7 Participants	38 Participants n=5 Participants
Current Antipsychotic No	17 Participants n=5 Participants	20 Participants n=7 Participants	37 Participants n=5 Participants
NPI-C Agitation/Aggression	21.9 units on a scale STANDARD_DEVIATION 9.7 • n=5 Participants	19.0 units on a scale STANDARD_DEVIATION 11.2 • n=7 Participants	20.4 units on a scale STANDARD_DEVIATION 10.5 • n=5 Participants
NPI-C Sleep	3.3 units on a scale STANDARD_DEVIATION 5.1 • n=5 Participants	3.6 units on a scale STANDARD_DEVIATION 4.9 • n=7 Participants	3.5 units on a scale STANDARD_DEVIATION 5.0 • n=5 Participants
NPI-C Disinhibition	7.4 units on a scale STANDARD_DEVIATION 7.3 • n=5 Participants	5.8 units on a scale STANDARD_DEVIATION 7.0 • n=7 Participants	6.6 units on a scale STANDARD_DEVIATION 7.1 • n=5 Participants
NPI-C Irritability	10.3 units on a scale STANDARD_DEVIATION 7.6 • n=5 Participants	10.3 units on a scale STANDARD_DEVIATION 9.9 • n=7 Participants	10.3 units on a scale STANDARD_DEVIATION 8.8 • n=5 Participants
Activities of Daily Living (ADL) Checklist	25.4 units on a scale STANDARD_DEVIATION 20.3 • n=5 Participants	21.1 units on a scale STANDARD_DEVIATION 19.2 • n=7 Participants	23.2 units on a scale STANDARD_DEVIATION 19.8 • n=5 Participants
Mini Mental State Examination (MMSE)	9.1 units on a scale STANDARD_DEVIATION 7.8 • n=5 Participants	8.2 units on a scale STANDARD_DEVIATION 5.7 • n=7 Participants	8.6 units on a scale STANDARD_DEVIATION 6.8 • n=5 Participants
Severe Impairment Battery (SIB)	11.9 units on a scale STANDARD_DEVIATION 7.4 • n=5 Participants	12.6 units on a scale STANDARD_DEVIATION 6.3 • n=7 Participants	12.3 units on a scale STANDARD_DEVIATION 6.8 • n=5 Participants
Cohen Mansfield Agitation Inventory (CMAI)	30.5 units on a scale STANDARD_DEVIATION 7.9 • n=5 Participants	28.9 units on a scale STANDARD_DEVIATION 9.1 • n=7 Participants	29.7 units on a scale STANDARD_DEVIATION 8.5 • n=5 Participants
NPI-C Total	76.7 units on a scale STANDARD_DEVIATION 34.2 • n=5 Participants	76.4 units on a scale STANDARD_DEVIATION 48.6 • n=7 Participants	76.5 units on a scale STANDARD_DEVIATION 41.8 • n=5 Participants
NPI-C Caregiver Distress	89.8 units on a scale STANDARD_DEVIATION 57.4 • n=5 Participants	81.2 units on a scale STANDARD_DEVIATION 72.9 • n=7 Participants	85.4 units on a scale STANDARD_DEVIATION 65.4 • n=5 Participants
Pittsburgh Agitation Scale (PAS)	7.1 units on a scale STANDARD_DEVIATION 4.1 • n=5 Participants	5.6 units on a scale STANDARD_DEVIATION 4.2 • n=7 Participants	6.3 units on a scale STANDARD_DEVIATION 4.2 • n=5 Participants
Confusion Assessment Method (CAM) 0, Alert	32 Participants n=5 Participants	36 Participants n=7 Participants	68 Participants n=5 Participants
Confusion Assessment Method (CAM) 1, Vigilant	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Confusion Assessment Method (CAM) 1, Lethargic	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 3 weeks

Outcome measures

Outcome measures
Measure	Dronabinol n=37 Participants Study medication will be administered twice daily. Capsules of dronabinol will contain 2.5 mg per dose (5mg daily) during Week 1, then increase to 5 mg per dose (10mg daily) for Weeks 2 and 3. Dronabinol (Marinol®): 5mg - 10mg daily dose	Placebo n=38 Participants Placebo medication will be administered twice daily. Placebo: Daily dose
Symptoms of Agitation as Measured by the Pittsburgh Agitation Scale Week 0	7.14 score on a scale Standard Deviation 4.12	5.55 score on a scale Standard Deviation 4.18
Symptoms of Agitation as Measured by the Pittsburgh Agitation Scale Week 1	5.69 score on a scale Standard Deviation 4.36	4.97 score on a scale Standard Deviation 3.81
Symptoms of Agitation as Measured by the Pittsburgh Agitation Scale Week 2	5.73 score on a scale Standard Deviation 4.67	5.22 score on a scale Standard Deviation 4.24
Symptoms of Agitation as Measured by the Pittsburgh Agitation Scale Week 3	4 score on a scale Standard Deviation 3.52	5.13 score on a scale Standard Deviation 4.44

PRIMARY outcome

Timeframe: Up to 3 weeks

The Neuropsychiatric Inventory Clinician Version (NPI-C) is an assessment tool used to evaluate neuropsychiatric symptoms in patients, particularly those with dementia. The minimum score is 0 and the max is 426. Higher scores indicate worse outcomes, meaning more agitation.

Outcome measures

Outcome measures
Measure	Dronabinol n=37 Participants Study medication will be administered twice daily. Capsules of dronabinol will contain 2.5 mg per dose (5mg daily) during Week 1, then increase to 5 mg per dose (10mg daily) for Weeks 2 and 3. Dronabinol (Marinol®): 5mg - 10mg daily dose	Placebo n=38 Participants Placebo medication will be administered twice daily. Placebo: Daily dose
Symptoms of Agitation as Measured by the Neuropsychiatric Inventory, Clinician Version Week 0	76.68 score on a scale Standard Deviation 34.19	76.37 score on a scale Standard Deviation 48.62
Symptoms of Agitation as Measured by the Neuropsychiatric Inventory, Clinician Version Week 1	59 score on a scale Standard Deviation 37.95	56.54 score on a scale Standard Deviation 48.07
Symptoms of Agitation as Measured by the Neuropsychiatric Inventory, Clinician Version Week 2	55.56 score on a scale Standard Deviation 41.73	56.59 score on a scale Standard Deviation 47.38
Symptoms of Agitation as Measured by the Neuropsychiatric Inventory, Clinician Version Week 3	52.38 score on a scale Standard Deviation 38.21	51.06 score on a scale Standard Deviation 46.9

SECONDARY outcome

Timeframe: Up to 3 weeks

All Adverse Events (AE) s occurring after randomization and during the 3-week treatment period, regardless of adherence to study treatment, will be recorded at all contacts.

Outcome measures

Outcome measures
Measure	Dronabinol n=37 Participants Study medication will be administered twice daily. Capsules of dronabinol will contain 2.5 mg per dose (5mg daily) during Week 1, then increase to 5 mg per dose (10mg daily) for Weeks 2 and 3. Dronabinol (Marinol®): 5mg - 10mg daily dose	Placebo n=38 Participants Placebo medication will be administered twice daily. Placebo: Daily dose
Number of Participants With Adverse Events in Dronabinol Treatment as Compared to Placebo 0 AEs	16 Participants	18 Participants
Number of Participants With Adverse Events in Dronabinol Treatment as Compared to Placebo 1 AEs	10 Participants	11 Participants
Number of Participants With Adverse Events in Dronabinol Treatment as Compared to Placebo 2 AE	6 Participants	5 Participants
Number of Participants With Adverse Events in Dronabinol Treatment as Compared to Placebo 3 AE	3 Participants	1 Participants
Number of Participants With Adverse Events in Dronabinol Treatment as Compared to Placebo 4 AE	1 Participants	2 Participants
Number of Participants With Adverse Events in Dronabinol Treatment as Compared to Placebo 5 AE	0 Participants	1 Participants
Number of Participants With Adverse Events in Dronabinol Treatment as Compared to Placebo 8 AE	1 Participants	0 Participants

Adverse Events

Dronabinol

Serious events: 2 serious events

Other events: 21 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Dronabinol n=37 participants at risk Study medication will be administered twice daily. Capsules of dronabinol will contain 2.5 mg per dose (5mg daily) during Week 1, then increase to 5 mg per dose (10mg daily) for Weeks 2 and 3. Dronabinol (Marinol®): 5mg - 10mg daily dose	Placebo n=38 participants at risk Placebo medication will be administered twice daily. Placebo: Daily dose
Psychiatric disorders Delirium	2.7% 1/37 • Number of events 2 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.	0.00% 0/38 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.
Surgical and medical procedures Humeral Fracture	2.7% 1/37 • Number of events 1 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.	0.00% 0/38 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.

Other adverse events

Additional Information

Dr. Paul Rosenberg

Johns Hopkins University

Phone: 4105509883

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Dronabinol n=37 participants at risk Study medication will be administered twice daily. Capsules of dronabinol will contain 2.5 mg per dose (5mg daily) during Week 1, then increase to 5 mg per dose (10mg daily) for Weeks 2 and 3. Dronabinol (Marinol®): 5mg - 10mg daily dose	Placebo n=38 participants at risk Placebo medication will be administered twice daily. Placebo: Daily dose
Psychiatric disorders Delirium	2.7% 1/37 • Number of events 1 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.	5.3% 2/38 • Number of events 3 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.
General disorders Fall	8.1% 3/37 • Number of events 4 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.	13.2% 5/38 • Number of events 6 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.
Nervous system disorders Seizure	0.00% 0/37 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.	2.6% 1/38 • Number of events 1 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.
Blood and lymphatic system disorders Anemia	0.00% 0/37 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.	2.6% 1/38 • Number of events 1 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.
Blood and lymphatic system disorders Leukopenia	2.7% 1/37 • Number of events 1 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.	0.00% 0/38 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.
Ear and labyrinth disorders Vertigo	0.00% 0/37 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.	2.6% 1/38 • Number of events 1 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.
Gastrointestinal disorders Abdominal Pain	0.00% 0/37 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.	2.6% 1/38 • Number of events 1 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.
Gastrointestinal disorders Constipation	2.7% 1/37 • Number of events 1 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.	0.00% 0/38 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.
Gastrointestinal disorders Diarrhea	13.5% 5/37 • Number of events 7 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.	0.00% 0/38 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.
Renal and urinary disorders Urine Incontinence	0.00% 0/37 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.	2.6% 1/38 • Number of events 1 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.
General disorders Edema	2.7% 1/37 • Number of events 1 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.	0.00% 0/38 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.
General disorders Fatigue	0.00% 0/37 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.	2.6% 1/38 • Number of events 1 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.
General disorders Gait Disturbance	2.7% 1/37 • Number of events 1 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.	0.00% 0/38 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.
General disorders Neuroleptic Malignant Syndrome	0.00% 0/37 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.	2.6% 1/38 • Number of events 1 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.
Infections and infestations COVID-19	2.7% 1/37 • Number of events 1 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.	0.00% 0/38 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.
Eye disorders Conjunctivitis	0.00% 0/37 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.	2.6% 1/38 • Number of events 1 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.
Infections and infestations Prostatitis	0.00% 0/37 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.	2.6% 1/38 • Number of events 1 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.
Renal and urinary disorders UTI	2.7% 1/37 • Number of events 1 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.	2.6% 1/38 • Number of events 1 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.
Injury, poisoning and procedural complications Pressure Ulcer	2.7% 1/37 • Number of events 1 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.	0.00% 0/38 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.
Injury, poisoning and procedural complications Skin Tear	2.7% 1/37 • Number of events 1 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.	0.00% 0/38 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.
Musculoskeletal and connective tissue disorders Foot Pain	2.7% 1/37 • Number of events 1 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.	0.00% 0/38 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.
Musculoskeletal and connective tissue disorders Required Pain Management	0.00% 0/37 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.	2.6% 1/38 • Number of events 1 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.
Musculoskeletal and connective tissue disorders Weakness	2.7% 1/37 • Number of events 1 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.	0.00% 0/38 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.
Metabolism and nutrition disorders Appetite, Decreased	0.00% 0/37 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.	2.6% 1/38 • Number of events 1 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.
Metabolism and nutrition disorders Appetite, Increased	0.00% 0/37 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.	2.6% 1/38 • Number of events 1 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.
Metabolism and nutrition disorders Dehydration	2.7% 1/37 • Number of events 1 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.	0.00% 0/38 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.
Metabolism and nutrition disorders Hypokalemia	0.00% 0/37 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.	2.6% 1/38 • Number of events 2 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.
Metabolism and nutrition disorders Hyponatremia	2.7% 1/37 • Number of events 1 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.	0.00% 0/38 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.
Metabolism and nutrition disorders Weight Loss	2.7% 1/37 • Number of events 1 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.	0.00% 0/38 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.
Nervous system disorders Dysarthria	2.7% 1/37 • Number of events 1 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.	2.6% 1/38 • Number of events 1 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.
Nervous system disorders Somnolence	5.4% 2/37 • Number of events 2 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.	13.2% 5/38 • Number of events 7 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.
Psychiatric disorders Agitation	5.4% 2/37 • Number of events 4 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.	5.3% 2/38 • Number of events 2 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.
Psychiatric disorders Anxiety	0.00% 0/37 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.	2.6% 1/38 • Number of events 1 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.
Psychiatric disorders Confusion	8.1% 3/37 • Number of events 3 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.	5.3% 2/38 • Number of events 2 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.
Psychiatric disorders Insomnia	0.00% 0/37 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.	5.3% 2/38 • Number of events 2 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.
Psychiatric disorders Paranoia	0.00% 0/37 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.	2.6% 1/38 • Number of events 1 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.
Respiratory, thoracic and mediastinal disorders Nosebleed	2.7% 1/37 • Number of events 1 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.	0.00% 0/38 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.
Skin and subcutaneous tissue disorders Ingrown Toenail	0.00% 0/37 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.	2.6% 1/38 • Number of events 2 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.
Vascular disorders Hypotension	2.7% 1/37 • Number of events 1 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.	2.6% 1/38 • Number of events 1 • Up to 3 weeks Serious adverse events were defined per FDA guidelines and reported in a timely manner.