Trial Outcomes & Findings for Enhancing Medication-based Analgesia in Humans- STUDY 2 (NCT NCT04036968)

NCT ID: NCT04036968

Last Updated: 2023-12-19

Results Overview

Peak amount of time participant submerged hand in cold pressor (5 degree circulating cold water) laboratory test of pain as a function of double- blinded study medications (range 0 -300).

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 31 participants
• Primary outcome timeframe: 8 hour study session
• Results posted on: 2023-12-19

Participant Flow

This is a within-subject study, and all participants (n=31) completed all study conditions. The same 31 participants moved from one treatment arm to the next.

Participant milestones

Measure	Full Participant Sample Each participant completed the following five study conditions (arms) in randomized order: Placebo + Placebo condition Hydromorphone (oral) 4mg + placebo condition Hydromorphone (oral) 4mg + Cannabidiol (oral) 50mg condition Hydromorphone (oral) 4mg + Cannabidiol (oral) 100mg condition Hydromorphone (oral) 4mg + Cannabidiol (oral) 200mg condition
Overall Study STARTED	31
Overall Study Placebo + Placebo	31
Overall Study Hydromorphoe 4mg + Placebo	31
Overall Study Hydromorphone 4mg + Cannabidiol 50mg	31
Overall Study Hydromorphone 4mg + Cannabidiol 100mg	31
Overall Study Hydromorphone 4mg + Cannabidiol 200mg	31
Overall Study COMPLETED	31
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Enhancing Medication-based Analgesia in Humans- STUDY 2

Baseline characteristics by cohort

Measure	All Participants n=31 Participants This is a within group study and same participants went through all treatment arms.
Age, Continuous	33.3 years STANDARD_DEVIATION 11.2 • n=93 Participants
Sex: Female, Male Female	17 Participants n=93 Participants
Sex: Female, Male Male	14 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	7 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	6 Participants n=93 Participants
Race (NIH/OMB) White	16 Participants n=93 Participants
Race (NIH/OMB) More than one race	2 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Region of Enrollment United States	31 Participants n=93 Participants

PRIMARY outcome

Timeframe: 8 hour study session

Peak amount of time participant submerged hand in cold pressor (5 degree circulating cold water) laboratory test of pain as a function of double- blinded study medications (range 0 -300).

Outcome measures

Measure	Placebo+Placebo n=31 Participants Within-subject double-blind, double-dummy administration of placebo + placebo. Order of dose randomized session days 2-5. Within-subject test of blinded study medications: Within-subject double-blind, double-dummy, study design wherein all participants received all doses in 8-hour outpatient sessions. Primary outcomes assessed during 8-hour outpatient sessions and included laboratory pain testing, subjective reports of drug effects, and cognitive performance, evaluated as a function of study medication condition.	Hydromorphone+Placebo n=31 Participants Within-subject double-blind, double-dummy administration of hydromorphone (oral) 4mg + placebo. Always administered during session 1. Within-subject test of blinded study medications: Within-subject double-blind, double-dummy, study design wherein all participants received all doses in 8-hour outpatient sessions. Primary outcomes assessed during 8-hour outpatient sessions and included laboratory pain testing, subjective reports of drug effects, and cognitive performance, evaluated as a function of study medication condition.	Hydromorphone (Oral) 4mg + Cannabidiol 50mg n=31 Participants Within-subject double-blind, double-dummy administration of hydromorphone (oral) 4mg + cannabidiol (oral) 50mg. Order of dose randomized session days 2-5. Within-subject test of blinded study medications: Within-subject double-blind, double-dummy, study design wherein all participants received all doses in 8-hour outpatient sessions. Primary outcomes assessed during 8-hour outpatient sessions and included laboratory pain testing, subjective reports of drug effects, and cognitive performance, evaluated as a function of study medication condition.	Hydromorphone (Oral) 4mg + Cannabidiol 100mg n=31 Participants Within-subject double-blind, double-dummy administration of hydromorphone (oral) 4mg + cannabidiol (oral) 100mg. Order of dose randomized session days 2-5. Within-subject test of blinded study medications: Within-subject double-blind, double-dummy, study design wherein all participants received all doses in 8-hour outpatient sessions. Primary outcomes assessed during 8-hour outpatient sessions and included laboratory pain testing, subjective reports of drug effects, and cognitive performance, evaluated as a function of study medication condition.	Hydromorphone (Oral) 4mg + Cannabidiol 200mg n=31 Participants Within-subject double-blind, double-dummy administration of hydromorphone (oral) 4mg + cannabidiol (oral) 200mg. Order of dose randomized session days 2-5. Within-subject test of blinded study medications: Within-subject double-blind, double-dummy, study design wherein all participants received all doses in 8-hour outpatient sessions. Primary outcomes assessed during 8-hour outpatient sessions and included laboratory pain testing, subjective reports of drug effects, and cognitive performance, evaluated as a function of study medication condition.
Peak Cold Pressor Tolerance	118.6 minutes Standard Error 8.8	130.8 minutes Standard Error 8.9	161.1 minutes Standard Error 10.1	163.2 minutes Standard Error 9.9	154.6 minutes Standard Error 9.6

PRIMARY outcome

Timeframe: 8 hour study session

Peak self-report rating of "Drug Effect" on a 0 ("none at all") to 100 ("extremely") visual analog scale as a function of double- blinded study medication, wherein higher values indicate stronger subjectively-experienced drug effects.

Outcome measures

Measure	Placebo+Placebo n=31 Participants Within-subject double-blind, double-dummy administration of placebo + placebo. Order of dose randomized session days 2-5. Within-subject test of blinded study medications: Within-subject double-blind, double-dummy, study design wherein all participants received all doses in 8-hour outpatient sessions. Primary outcomes assessed during 8-hour outpatient sessions and included laboratory pain testing, subjective reports of drug effects, and cognitive performance, evaluated as a function of study medication condition.	Hydromorphone+Placebo n=31 Participants Within-subject double-blind, double-dummy administration of hydromorphone (oral) 4mg + placebo. Always administered during session 1. Within-subject test of blinded study medications: Within-subject double-blind, double-dummy, study design wherein all participants received all doses in 8-hour outpatient sessions. Primary outcomes assessed during 8-hour outpatient sessions and included laboratory pain testing, subjective reports of drug effects, and cognitive performance, evaluated as a function of study medication condition.	Hydromorphone (Oral) 4mg + Cannabidiol 50mg n=31 Participants Within-subject double-blind, double-dummy administration of hydromorphone (oral) 4mg + cannabidiol (oral) 50mg. Order of dose randomized session days 2-5. Within-subject test of blinded study medications: Within-subject double-blind, double-dummy, study design wherein all participants received all doses in 8-hour outpatient sessions. Primary outcomes assessed during 8-hour outpatient sessions and included laboratory pain testing, subjective reports of drug effects, and cognitive performance, evaluated as a function of study medication condition.	Hydromorphone (Oral) 4mg + Cannabidiol 100mg n=31 Participants Within-subject double-blind, double-dummy administration of hydromorphone (oral) 4mg + cannabidiol (oral) 100mg. Order of dose randomized session days 2-5. Within-subject test of blinded study medications: Within-subject double-blind, double-dummy, study design wherein all participants received all doses in 8-hour outpatient sessions. Primary outcomes assessed during 8-hour outpatient sessions and included laboratory pain testing, subjective reports of drug effects, and cognitive performance, evaluated as a function of study medication condition.	Hydromorphone (Oral) 4mg + Cannabidiol 200mg n=31 Participants Within-subject double-blind, double-dummy administration of hydromorphone (oral) 4mg + cannabidiol (oral) 200mg. Order of dose randomized session days 2-5. Within-subject test of blinded study medications: Within-subject double-blind, double-dummy, study design wherein all participants received all doses in 8-hour outpatient sessions. Primary outcomes assessed during 8-hour outpatient sessions and included laboratory pain testing, subjective reports of drug effects, and cognitive performance, evaluated as a function of study medication condition.
Peak Self-report Rating of "Drug Effect" (0-100), as Measured by the Visual Analog Rating Scale	4.8 units on a scale Standard Error 0.7	12.6 units on a scale Standard Error 1.4	15.7 units on a scale Standard Error 1.7	18.0 units on a scale Standard Error 1.6	17.9 units on a scale Standard Error 1.6

PRIMARY outcome

Timeframe: 8 hour study session

Peak number accuracy on the Circular Lights fine motor task as a function of double-blinded study drug administration. Participants were provided 60 seconds to press buttons that are lit in randomized order and displayed automatically on a circular lights wall mounted unit. The primary outcome is the number of lit buttons that were accurately pressed within 60 seconds, which is a metric to assess fine motor impairment. Lower numbers are indicative of greater drug-related impairment. There is no upper limit on the circular lights task.

Outcome measures

Measure	Placebo+Placebo n=31 Participants Within-subject double-blind, double-dummy administration of placebo + placebo. Order of dose randomized session days 2-5. Within-subject test of blinded study medications: Within-subject double-blind, double-dummy, study design wherein all participants received all doses in 8-hour outpatient sessions. Primary outcomes assessed during 8-hour outpatient sessions and included laboratory pain testing, subjective reports of drug effects, and cognitive performance, evaluated as a function of study medication condition.	Hydromorphone+Placebo n=31 Participants Within-subject double-blind, double-dummy administration of hydromorphone (oral) 4mg + placebo. Always administered during session 1. Within-subject test of blinded study medications: Within-subject double-blind, double-dummy, study design wherein all participants received all doses in 8-hour outpatient sessions. Primary outcomes assessed during 8-hour outpatient sessions and included laboratory pain testing, subjective reports of drug effects, and cognitive performance, evaluated as a function of study medication condition.	Hydromorphone (Oral) 4mg + Cannabidiol 50mg n=31 Participants Within-subject double-blind, double-dummy administration of hydromorphone (oral) 4mg + cannabidiol (oral) 50mg. Order of dose randomized session days 2-5. Within-subject test of blinded study medications: Within-subject double-blind, double-dummy, study design wherein all participants received all doses in 8-hour outpatient sessions. Primary outcomes assessed during 8-hour outpatient sessions and included laboratory pain testing, subjective reports of drug effects, and cognitive performance, evaluated as a function of study medication condition.	Hydromorphone (Oral) 4mg + Cannabidiol 100mg n=31 Participants Within-subject double-blind, double-dummy administration of hydromorphone (oral) 4mg + cannabidiol (oral) 100mg. Order of dose randomized session days 2-5. Within-subject test of blinded study medications: Within-subject double-blind, double-dummy, study design wherein all participants received all doses in 8-hour outpatient sessions. Primary outcomes assessed during 8-hour outpatient sessions and included laboratory pain testing, subjective reports of drug effects, and cognitive performance, evaluated as a function of study medication condition.	Hydromorphone (Oral) 4mg + Cannabidiol 200mg n=31 Participants Within-subject double-blind, double-dummy administration of hydromorphone (oral) 4mg + cannabidiol (oral) 200mg. Order of dose randomized session days 2-5. Within-subject test of blinded study medications: Within-subject double-blind, double-dummy, study design wherein all participants received all doses in 8-hour outpatient sessions. Primary outcomes assessed during 8-hour outpatient sessions and included laboratory pain testing, subjective reports of drug effects, and cognitive performance, evaluated as a function of study medication condition.
Peak Number Accurate on Circular Lights	64.9 correct responses Standard Error 1.0	59.2 correct responses Standard Error 1.0	64.1 correct responses Standard Error 1.0	63.6 correct responses Standard Error 0.9	64.3 correct responses Standard Error 0.9

Adverse Events

Placebo+Placebo

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Hydromorphone+Placebo

Serious events: 0 serious events

Other events: 20 other events

Deaths: 0 deaths

Hydromorphone (Oral) 4mg + Cannabidiol 50mg

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

Hydromorphone (Oral) 4mg + Cannabidiol 100mg

Serious events: 0 serious events

Other events: 22 other events

Deaths: 0 deaths

Hydromorphone (Oral) 4mg + Cannabidiol 200mg

Serious events: 0 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Placebo+Placebo n=31 participants at risk Within-subject double-blind, double-dummy administration of placebo + placebo. Order of dose randomized session days 2-5. Within-subject test of blinded study medications: Within-subject double-blind, double-dummy, study design wherein all participants received all doses in 8-hour outpatient sessions. Primary outcomes assessed during 8-hour outpatient sessions and included laboratory pain testing, subjective reports of drug effects, and cognitive performance, evaluated as a function of study medication condition.	Hydromorphone+Placebo n=31 participants at risk Within-subject double-blind, double-dummy administration of hydromorphone (oral) 4mg + placebo. Always administered during session 1. Within-subject test of blinded study medications: Within-subject double-blind, double-dummy, study design wherein all participants received all doses in 8-hour outpatient sessions. Primary outcomes assessed during 8-hour outpatient sessions and included laboratory pain testing, subjective reports of drug effects, and cognitive performance, evaluated as a function of study medication condition.	Hydromorphone (Oral) 4mg + Cannabidiol 50mg n=31 participants at risk Within-subject double-blind, double-dummy administration of hydromorphone (oral) 4mg + cannabidiol (oral) 50mg. Order of dose randomized session days 2-5. Within-subject test of blinded study medications: Within-subject double-blind, double-dummy, study design wherein all participants received all doses in 8-hour outpatient sessions. Primary outcomes assessed during 8-hour outpatient sessions and included laboratory pain testing, subjective reports of drug effects, and cognitive performance, evaluated as a function of study medication condition.	Hydromorphone (Oral) 4mg + Cannabidiol 100mg n=31 participants at risk Within-subject double-blind, double-dummy administration of hydromorphone (oral) 4mg + cannabidiol (oral) 100mg. Order of dose randomized session days 2-5. Within-subject test of blinded study medications: Within-subject double-blind, double-dummy, study design wherein all participants received all doses in 8-hour outpatient sessions. Primary outcomes assessed during 8-hour outpatient sessions and included laboratory pain testing, subjective reports of drug effects, and cognitive performance, evaluated as a function of study medication condition.	Hydromorphone (Oral) 4mg + Cannabidiol 200mg n=31 participants at risk Within-subject double-blind, double-dummy administration of hydromorphone (oral) 4mg + cannabidiol (oral) 200mg. Order of dose randomized session days 2-5. Within-subject test of blinded study medications: Within-subject double-blind, double-dummy, study design wherein all participants received all doses in 8-hour outpatient sessions. Primary outcomes assessed during 8-hour outpatient sessions and included laboratory pain testing, subjective reports of drug effects, and cognitive performance, evaluated as a function of study medication condition.
Blood and lymphatic system disorders Chills	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	3.2% 1/31 • Number of events 1 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).
Blood and lymphatic system disorders Headache	9.7% 3/31 • Number of events 3 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	6.5% 2/31 • Number of events 2 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	3.2% 1/31 • Number of events 1 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	6.5% 2/31 • Number of events 2 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).
Cardiac disorders Tachycardia	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	3.2% 1/31 • Number of events 1 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).
Gastrointestinal disorders Abdominal Cramp	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	3.2% 1/31 • Number of events 1 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).
Gastrointestinal disorders Appetite Decrease	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	3.2% 1/31 • Number of events 1 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).
Gastrointestinal disorders Appetite Increase	3.2% 1/31 • Number of events 1 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	3.2% 1/31 • Number of events 1 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	6.5% 2/31 • Number of events 2 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).
Nervous system disorders Dry Mouth	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	6.5% 2/31 • Number of events 2 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	12.9% 4/31 • Number of events 4 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	19.4% 6/31 • Number of events 6 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).
Gastrointestinal disorders Nausea	6.5% 2/31 • Number of events 2 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	19.4% 6/31 • Number of events 6 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	6.5% 2/31 • Number of events 2 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	19.4% 6/31 • Number of events 6 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	22.6% 7/31 • Number of events 7 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).
Gastrointestinal disorders Vomiting	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	3.2% 1/31 • Number of events 1 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	3.2% 1/31 • Number of events 1 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	3.2% 1/31 • Number of events 1 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).
Nervous system disorders Clumsy	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	3.2% 1/31 • Number of events 1 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).
Nervous system disorders Confusion	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	3.2% 1/31 • Number of events 1 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).
Nervous system disorders Depression	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	3.2% 1/31 • Number of events 1 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).
Nervous system disorders Dizziness	3.2% 1/31 • Number of events 1 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	3.2% 1/31 • Number of events 1 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	16.1% 5/31 • Number of events 5 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	12.9% 4/31 • Number of events 4 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	3.2% 1/31 • Number of events 1 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).
Nervous system disorders Drowsiness	22.6% 7/31 • Number of events 7 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	41.9% 13/31 • Number of events 13 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	32.3% 10/31 • Number of events 10 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	48.4% 15/31 • Number of events 15 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	48.4% 15/31 • Number of events 15 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).
Nervous system disorders Euphoria	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	16.1% 5/31 • Number of events 5 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	3.2% 1/31 • Number of events 1 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	9.7% 3/31 • Number of events 3 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	3.2% 1/31 • Number of events 1 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).
Nervous system disorders Fatigue	3.2% 1/31 • Number of events 1 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).
Nervous system disorders Impaired	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	3.2% 1/31 • Number of events 1 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	6.5% 2/31 • Number of events 2 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).
Nervous system disorders Irritability	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	3.2% 1/31 • Number of events 1 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	3.2% 1/31 • Number of events 1 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).
Nervous system disorders Light Headed	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	9.7% 3/31 • Number of events 3 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	9.7% 3/31 • Number of events 3 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	12.9% 4/31 • Number of events 4 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	16.1% 5/31 • Number of events 5 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).
Nervous system disorders Nervousness	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	3.2% 1/31 • Number of events 1 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).
Nervous system disorders Tingling	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	3.2% 1/31 • Number of events 1 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).
Nervous system disorders Restlessness	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	3.2% 1/31 • Number of events 1 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).
Nervous system disorders Shaky	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	3.2% 1/31 • Number of events 1 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	3.2% 1/31 • Number of events 1 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	3.2% 1/31 • Number of events 1 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).
Nervous system disorders Tremor	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	3.2% 1/31 • Number of events 1 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).
Nervous system disorders Yawning	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	3.2% 1/31 • Number of events 1 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).
Nervous system disorders Photosensitivity	3.2% 1/31 • Number of events 1 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	3.2% 1/31 • Number of events 1 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).
Nervous system disorders Piloerection	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	3.2% 1/31 • Number of events 1 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).
Nervous system disorders Pruitus	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	3.2% 1/31 • Number of events 1 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	6.5% 2/31 • Number of events 2 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).
Nervous system disorders Dry Eyes	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	3.2% 1/31 • Number of events 1 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).
Renal and urinary disorders Frequent Urination	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	3.2% 1/31 • Number of events 1 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).	0.00% 0/31 • Up to 40 hours Adverse events were prompted systematically each hour throughout the session and documented according to good clinical practices. Spontaneously reported adverse events were also documented. All reports of symptoms were categorized as discrete events, such that one experience that included more than 1 symptom would be represented by more than 1 event. Events reported here were all rated as definitely or possibly related to study medication, collapsed across severity (mild, moderate, or severe).

Additional Information

Kelly Dunn, Professor

Johns Hopkins University School of Medicine

Phone: 410-550-2254

Email: kdunn9@jhmi.edu

Results disclosure agreements

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