Trial Outcomes & Findings for A Study to Test the Safety and Tolerability of Single and Multiple Doses of Padsevonil in Adult and Elderly Study Participants (NCT NCT04013191)

NCT ID: NCT04013191

Last Updated: 2021-06-30

Results Overview

Cmax was measured in nanograms per milliliter (ng/mL).

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

28 participants

Primary outcome timeframe

Plasma samples were taken predose on Day 1 and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8, 12, 24, 48 and 72 hours postdose

Results posted on

2021-06-30

Participant Flow

The study started to enroll patients in July 2019 and concluded in October 2019.

The study included a 28 days Screening period, a 21 days Treatment period: Period 1A single dose (SD) on Days 1 to 7 and Period 1B multiple dose (MD) on Days 8 to 21 and a Safety Follow-up period on Day 22. Participant Flow refers to the Full Analysis Set.

Participant milestones

Participant milestones
Measure	Adults (18-64 Years) Participants received assigned single and multiple doses of padsevonil.	Elderly (>= 65 Years) Participants received assigned single and multiple doses of padsevonil.
Overall Study STARTED	10	18
Overall Study Completed Period 1A (Single Dose)	10	18
Overall Study Completed Period 1B (Multiple Dose)	9	18
Overall Study COMPLETED	9	18
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Adults (18-64 Years) Participants received assigned single and multiple doses of padsevonil.	Elderly (>= 65 Years) Participants received assigned single and multiple doses of padsevonil.
Overall Study Adverse Event	1	0

Baseline Characteristics

A Study to Test the Safety and Tolerability of Single and Multiple Doses of Padsevonil in Adult and Elderly Study Participants

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Adults (18-64 Years) n=10 Participants Participants received assigned single and multiple doses of padsevonil.	Elderly (>= 65 Years) n=18 Participants Participants received assigned single and multiple doses of padsevonil.	Total Title n=28 Participants
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	10 Participants n=5 Participants	0 Participants n=7 Participants	10 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	18 Participants n=7 Participants	18 Participants n=5 Participants
Age, Continuous	44.4 years STANDARD_DEVIATION 10.2 • n=5 Participants	69.7 years STANDARD_DEVIATION 4.5 • n=7 Participants	60.6 years STANDARD_DEVIATION 14.1 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	9 Participants n=7 Participants	15 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	9 Participants n=7 Participants	13 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized White	9 Participants n=5 Participants	18 Participants n=7 Participants	27 Participants n=5 Participants

PRIMARY outcome

Timeframe: Plasma samples were taken predose on Day 1 and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8, 12, 24, 48 and 72 hours postdose

Population: The Pharmacokinetic-Per Protocol Set (PK-PPS) was a subset of the FAS, consisting of study participants who had no important protocol deviation (IPD) affecting the PK parameters and for whom a sufficient number of samples were available to determine at least 1 PK parameter.

Cmax was measured in nanograms per milliliter (ng/mL).

Outcome measures

Outcome measures
Measure	Adults (18-64 Years) (PK-PPS) n=10 Participants Participants received assigned single and multiple doses of padsevonil, forming the Pharmacokinetic-Per Protocol Set (PK-PPS).	Elderly (>= 65 Years) (PK-PPS) n=18 Participants Participants received assigned single and multiple doses of padsevonil, forming the PK-PPS.
The Maximum Plasma Concentration (Cmax) of a Single Dose Padsevonil (PSL)	903.6 ng/mL Interval 712.0 to 1150.0	838.4 ng/mL Interval 702.0 to 1000.0

PRIMARY outcome

Timeframe: Plasma samples were taken predose on Day 1 and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8, 12, 24, 48 and 72 hours postdose

AUC0-t: area under the plasma concentration-time curve from time 0 to the last quantifiable concentration. It was measured in hours times nanograms per milliliter (h\*ng/mL).

Outcome measures

Outcome measures
Measure	Adults (18-64 Years) (PK-PPS) n=10 Participants Participants received assigned single and multiple doses of padsevonil, forming the Pharmacokinetic-Per Protocol Set (PK-PPS).	Elderly (>= 65 Years) (PK-PPS) n=18 Participants Participants received assigned single and multiple doses of padsevonil, forming the PK-PPS.
The Area Under the Curve From 0 to t (AUC0-t) of a Single Dose Padsevonil (PSL)	4915 h*ng/mL Interval 3630.0 to 6650.0	6011 h*ng/mL Interval 4800.0 to 7530.0

PRIMARY outcome

Timeframe: Plasma samples were taken predose on Day 1 and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8, 12, 24, 48 and 72 hours postdose

AUC was measured in hours times nanograms per milliliter (h\*ng/mL).

Outcome measures

Outcome measures
Measure	Adults (18-64 Years) (PK-PPS) n=10 Participants Participants received assigned single and multiple doses of padsevonil, forming the Pharmacokinetic-Per Protocol Set (PK-PPS).	Elderly (>= 65 Years) (PK-PPS) n=18 Participants Participants received assigned single and multiple doses of padsevonil, forming the PK-PPS.
The Area Under the Curve (AUC) of a Single Dose Padsevonil (PSL)	4950 h*ng/mL Interval 3650.0 to 6720.0	6061 h*ng/mL Interval 4830.0 to 7610.0

PRIMARY outcome

Timeframe: Plasma samples were taken predose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8 and 12 hours on Day 13

Population: The PK-PPS was a subset of the FAS, consisting of study participants who had no IPD affecting the PK parameters and for whom a sufficient number of samples were available to determine at least 1 PK parameter. 1 participant in the adult cohort discontinued due to a treatment emergent adverse event (TEAE) after 5 days of PSL administration in the MD Period.

Cmax, ss was measured in nanograms per milliliter (ng/mL).

Outcome measures

Outcome measures
Measure	Adults (18-64 Years) (PK-PPS) n=9 Participants Participants received assigned single and multiple doses of padsevonil, forming the Pharmacokinetic-Per Protocol Set (PK-PPS).	Elderly (>= 65 Years) (PK-PPS) n=18 Participants Participants received assigned single and multiple doses of padsevonil, forming the PK-PPS.
The Maximum Plasma Concentration at Steady-state (Cmax, ss) of Multiple Doses Padsevonil (PSL)	1157 ng/mL Interval 942.0 to 1420.0	1180 ng/mL Interval 1020.0 to 1360.0

PRIMARY outcome

Timeframe: Plasma samples were taken predose and 0.25, 0.5, 0.75, 1, 1.5, 3, 4, 6, 8 and 12 hours on Day 13

Population: The PK-PPS was a subset of the FAS, consisting of study participants who had no IPD affecting the PK parameters and for whom a sufficient number of samples were available to determine at least 1 PK parameter. 1 participant in the adult cohort discontinued due to a TEAE after 5 days of PSL administration in the MD Period.

AUCtau was measured in hours times nanograms per milliliter (h\*ng/mL).

Outcome measures

Outcome measures
Measure	Adults (18-64 Years) (PK-PPS) n=9 Participants Participants received assigned single and multiple doses of padsevonil, forming the Pharmacokinetic-Per Protocol Set (PK-PPS).	Elderly (>= 65 Years) (PK-PPS) n=18 Participants Participants received assigned single and multiple doses of padsevonil, forming the PK-PPS.
The Area Under the Curve (AUCtau) Over a Dosing Interval of Multiple Doses Padsevonil (PSL)	5346 h*ng/mL Interval 4130.0 to 6920.0	6307 h*ng/mL Interval 5260.0 to 7570.0

SECONDARY outcome

Timeframe: Urine samples were taken on Day 1, Day 2, Day 3, Day 4 and Day 13

Samples were taken to assess the amount of padsevonil that was excreted in urine. Ae,ss refers to cumulative amount of PSL excreted in the urine at steady state.

Outcome measures

Outcome measures
Measure	Adults (18-64 Years) (PK-PPS) n=10 Participants Participants received assigned single and multiple doses of padsevonil, forming the Pharmacokinetic-Per Protocol Set (PK-PPS).	Elderly (>= 65 Years) (PK-PPS) n=18 Participants Participants received assigned single and multiple doses of padsevonil, forming the PK-PPS.
The Amount of Padsevonil (PSL) Excreted in Urine Metabolite 2, Multiple dose: Day 13 (Ae,ss)	13.3 milligrams Geometric Coefficient of Variation 79.5	14.4 milligrams Geometric Coefficient of Variation 45.9
The Amount of Padsevonil (PSL) Excreted in Urine Single dose: Day 1 (Ae)	0.0862 milligrams Geometric Coefficient of Variation 153.9	0.0979 milligrams Geometric Coefficient of Variation 45.9
The Amount of Padsevonil (PSL) Excreted in Urine Multiple dose: Day 13 (Ae,ss)	0.0924 milligrams Geometric Coefficient of Variation 109.5	0.166 milligrams Geometric Coefficient of Variation 45.5
The Amount of Padsevonil (PSL) Excreted in Urine Metabolite 1, Single dose: Day 1 (Ae)	0.941 milligrams Geometric Coefficient of Variation 79.9	1.13 milligrams Geometric Coefficient of Variation 20.3
The Amount of Padsevonil (PSL) Excreted in Urine Metabolite 1, Multiple dose: Day 13 (Ae,ss)	1.16 milligrams Geometric Coefficient of Variation 96.9	1.86 milligrams Geometric Coefficient of Variation 35.9
The Amount of Padsevonil (PSL) Excreted in Urine Metabolite 2, Single dose: Day 1 (Ae)	18.7 milligrams Geometric Coefficient of Variation 68.3	14.6 milligrams Geometric Coefficient of Variation 54.2

SECONDARY outcome

Timeframe: Urine samples were taken on Day 1, Day 2, Day 3, Day 4 and Day 13

Samples were taken to assess the metabolic ratio of padsevonil that was excreted in urine. MRAe was defined as the metabolic ratio of PSL to its metabolites for cumulative amount of PSL metabolites excreted in the urine. ss refers to steady state.

Outcome measures

Outcome measures
Measure	Adults (18-64 Years) (PK-PPS) n=10 Participants Participants received assigned single and multiple doses of padsevonil, forming the Pharmacokinetic-Per Protocol Set (PK-PPS).	Elderly (>= 65 Years) (PK-PPS) n=18 Participants Participants received assigned single and multiple doses of padsevonil, forming the PK-PPS.
The Ratio of Padsevonil (PSL) to Its Metabolites Excreted in Urine Metabolite 1, Single dose: Day 1 (MRAe)	10.6 ratio Geometric Coefficient of Variation 52.8	11.2 ratio Geometric Coefficient of Variation 40.3
The Ratio of Padsevonil (PSL) to Its Metabolites Excreted in Urine Metabolite 1, Multiple dose: Day 13 (MRAe,ss)	12.2 ratio Geometric Coefficient of Variation 43.9	10.9 ratio Geometric Coefficient of Variation 38.2
The Ratio of Padsevonil (PSL) to Its Metabolites Excreted in Urine Metabolite 2, Single dose: Day 1 (MRAe)	217 ratio Geometric Coefficient of Variation 122.3	149 ratio Geometric Coefficient of Variation 81.8
The Ratio of Padsevonil (PSL) to Its Metabolites Excreted in Urine Metabolite 2, Multiple dose: Day 13 (MRAe,ss)	144 ratio Geometric Coefficient of Variation 81.1	86.8 ratio Geometric Coefficient of Variation 67.7

SECONDARY outcome

Timeframe: From Baseline until End-of-Treatment visit (up to Day 22)

Population: The Full Analysis Set (FAS) consisted of all study participants who signed the informed consent form (ICF) and received at least 1 dose of PSL.

An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study medication, whether or not considered related to the study medication. An AE could, therefore, be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study medication.

Outcome measures

Outcome measures
Measure	Adults (18-64 Years) (PK-PPS) n=10 Participants Participants received assigned single and multiple doses of padsevonil, forming the Pharmacokinetic-Per Protocol Set (PK-PPS).	Elderly (>= 65 Years) (PK-PPS) n=18 Participants Participants received assigned single and multiple doses of padsevonil, forming the PK-PPS.
Number of Participants With Treatment-emergent Adverse Events Single Dose Period (1A)	10 Participants	18 Participants
Number of Participants With Treatment-emergent Adverse Events Multiple Dose Period (1B)	10 Participants	17 Participants

SECONDARY outcome

Timeframe: From Baseline until End-of-Treatment visit (up to Day 22)

Population: The Full Analysis Set (FAS) consisted of all study participants who signed the informed consent form (ICF) and received at least 1 dose of PSL.

A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose: * Results in death * Is life-threatening * Requires in patient hospitalization or prolongation of existing hospitalization * Is a congenital anomaly or birth defect * Is an infection that requires treatment parenteral antibiotics * Other important medical events which based on medical or scientific judgement may jeopardize the patients, or may require medical or surgical intervention to prevent any of the above

Outcome measures

Outcome measures
Measure	Adults (18-64 Years) (PK-PPS) n=10 Participants Participants received assigned single and multiple doses of padsevonil, forming the Pharmacokinetic-Per Protocol Set (PK-PPS).	Elderly (>= 65 Years) (PK-PPS) n=18 Participants Participants received assigned single and multiple doses of padsevonil, forming the PK-PPS.
Number of Participants With Serious Adverse Events Single Dose Period (1A)	0 Participants	0 Participants
Number of Participants With Serious Adverse Events Multiple Dose Period (1B)	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From Baseline until End-of-Treatment visit (up to Day 22)

Population: The Full Analysis Set (FAS) consisted of all study participants who signed the informed consent form (ICF) and received at least 1 dose of PSL.

An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.

Outcome measures

Outcome measures
Measure	Adults (18-64 Years) (PK-PPS) n=10 Participants Participants received assigned single and multiple doses of padsevonil, forming the Pharmacokinetic-Per Protocol Set (PK-PPS).	Elderly (>= 65 Years) (PK-PPS) n=18 Participants Participants received assigned single and multiple doses of padsevonil, forming the PK-PPS.
Number of Participants With Treatment-emergent Adverse Events Leading to Discontinuation of the Study Single Dose Period (1A)	0 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events Leading to Discontinuation of the Study Multiple Dose Period (1B)	1 Participants	0 Participants

Adverse Events

Adults (18-64 Years) (FAS) SD Period (1A)

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Elderly (>= 65 Years) (FAS) SD Period (1A)

Serious events: 0 serious events

Other events: 18 other events

Deaths: 0 deaths

Adults (18-64 Years) (FAS) MD Period (1B)

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Elderly (>= 65 Years) (FAS) MD Period (1B)

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

UCB

Cares

Phone: +1844 599

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	Adults (18-64 Years) (FAS) SD Period (1A) n=10 participants at risk Participants received a single dose of padsevonil during Period (1A), forming the FAS.	Elderly (>= 65 Years) (FAS) SD Period (1A) n=18 participants at risk Participants received a single dose of padsevonil during Period (1A), forming the FAS.	Adults (18-64 Years) (FAS) MD Period (1B) n=10 participants at risk Participants received multiple doses of padsevonil during Period (1B), forming the FAS.	Elderly (>= 65 Years) (FAS) MD Period (1B) n=18 participants at risk Participants received multiple doses of padsevonil during Period (1B), forming the FAS.
Blood and lymphatic system disorders Neutrophilia	0.00% 0/10 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	5.6% 1/18 • Number of events 1 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	0.00% 0/10 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	0.00% 0/18 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)
Ear and labyrinth disorders Vertigo	10.0% 1/10 • Number of events 1 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	0.00% 0/18 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	0.00% 0/10 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	0.00% 0/18 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)
Eye disorders Diplopia	0.00% 0/10 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	5.6% 1/18 • Number of events 1 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	0.00% 0/10 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	0.00% 0/18 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)
Eye disorders Visual impairment	10.0% 1/10 • Number of events 1 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	0.00% 0/18 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	0.00% 0/10 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	0.00% 0/18 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)
Eye disorders Vision blurred	0.00% 0/10 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	0.00% 0/18 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	0.00% 0/10 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	11.1% 2/18 • Number of events 2 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)
Gastrointestinal disorders Constipation	10.0% 1/10 • Number of events 1 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	11.1% 2/18 • Number of events 2 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	10.0% 1/10 • Number of events 1 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	5.6% 1/18 • Number of events 1 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)
Gastrointestinal disorders Nausea	20.0% 2/10 • Number of events 2 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	5.6% 1/18 • Number of events 1 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	20.0% 2/10 • Number of events 2 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	5.6% 1/18 • Number of events 1 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)
Gastrointestinal disorders Vomiting	10.0% 1/10 • Number of events 1 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	0.00% 0/18 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	0.00% 0/10 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	0.00% 0/18 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)
Gastrointestinal disorders Diarrhoea	0.00% 0/10 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	0.00% 0/18 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	0.00% 0/10 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	5.6% 1/18 • Number of events 1 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)
Investigations Blood pressure systolic decreased	10.0% 1/10 • Number of events 1 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	0.00% 0/18 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	20.0% 2/10 • Number of events 2 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	0.00% 0/18 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)
Investigations White blood cell count increased	0.00% 0/10 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	5.6% 1/18 • Number of events 1 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	0.00% 0/10 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	0.00% 0/18 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/10 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	11.1% 2/18 • Number of events 2 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	0.00% 0/10 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	0.00% 0/18 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/10 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	5.6% 1/18 • Number of events 1 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	0.00% 0/10 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	5.6% 1/18 • Number of events 1 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/10 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	0.00% 0/18 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	0.00% 0/10 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	5.6% 1/18 • Number of events 1 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)
Nervous system disorders Somnolence	90.0% 9/10 • Number of events 9 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	94.4% 17/18 • Number of events 17 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	100.0% 10/10 • Number of events 10 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	88.9% 16/18 • Number of events 16 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)
Nervous system disorders Dizziness	20.0% 2/10 • Number of events 2 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	27.8% 5/18 • Number of events 5 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	40.0% 4/10 • Number of events 4 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	33.3% 6/18 • Number of events 6 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)
Nervous system disorders Headache	10.0% 1/10 • Number of events 1 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	5.6% 1/18 • Number of events 1 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	10.0% 1/10 • Number of events 1 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	22.2% 4/18 • Number of events 4 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)
Nervous system disorders Cognitive disorder	0.00% 0/10 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	5.6% 1/18 • Number of events 1 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	0.00% 0/10 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	0.00% 0/18 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)
Nervous system disorders Aphasia	0.00% 0/10 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	0.00% 0/18 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	0.00% 0/10 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	5.6% 1/18 • Number of events 1 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)
Nervous system disorders Memory impairment	0.00% 0/10 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	0.00% 0/18 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	0.00% 0/10 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	5.6% 1/18 • Number of events 1 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)
Psychiatric disorders Sleep disorder	0.00% 0/10 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	5.6% 1/18 • Number of events 1 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	0.00% 0/10 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	0.00% 0/18 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)
Psychiatric disorders Disinhibition	0.00% 0/10 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	0.00% 0/18 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	10.0% 1/10 • Number of events 1 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	0.00% 0/18 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)
Psychiatric disorders Enuresis	0.00% 0/10 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	0.00% 0/18 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	0.00% 0/10 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	5.6% 1/18 • Number of events 1 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)
Psychiatric disorders Initial insomnia	0.00% 0/10 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	0.00% 0/18 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	0.00% 0/10 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	5.6% 1/18 • Number of events 1 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)
Psychiatric disorders Insomnia	0.00% 0/10 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	0.00% 0/18 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	10.0% 1/10 • Number of events 1 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	0.00% 0/18 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)
Psychiatric disorders Irritability	0.00% 0/10 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	0.00% 0/18 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	0.00% 0/10 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	5.6% 1/18 • Number of events 1 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)
Psychiatric disorders Mania	0.00% 0/10 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	0.00% 0/18 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	10.0% 1/10 • Number of events 1 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	0.00% 0/18 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)
Skin and subcutaneous tissue disorders Skin erosion	0.00% 0/10 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	5.6% 1/18 • Number of events 1 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	0.00% 0/10 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)	0.00% 0/18 • Treatment emergent adverse events were collected from Baseline until End-of-Treatment visit (up to Day 22)