Trial Outcomes & Findings for A Phase 2 RCT Study of CX-8998 for Essential Tremor (NCT NCT03101241)

Last Updated: 2021-11-23

Results Overview

The Essential Tremor Rating Assessment Scale Performance Subscale (TETRAS-PS) was used to assess the efficacy of CX-8998 in reducing essential tremor as scored by the independent video raters. TETRAS-PS quantifies tremor in the head, face, voice, limbs, and trunk. The overall subscale score ranges from a minimum of 0 to a maximum of 64. A lower score is indicative of improvement and a better outcome.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

95 participants

Primary outcome timeframe

Baseline and Day 28 post-dose.

Results posted on

2021-11-23

Participant Flow

Participant milestones

Participant milestones
Measure	CX-8998 Participants were administered CX-8998 4 mg (2 capsules) BID in week 1, then 8 mg (4 capsules) BID in week 2, and then 10 mg (5 capsules) BID in weeks 3 and 4.	Placebo Participants were administered a Placebo comparator of 2 capsules BID in week 1, then 4 capsules BID in Week 2, and then 5 capsules BID in Weeks 3 and 4.
Overall Study STARTED	48	47
Overall Study COMPLETED	37	42
Overall Study NOT COMPLETED	11	5

Reasons for withdrawal

Reasons for withdrawal
Measure	CX-8998 Participants were administered CX-8998 4 mg (2 capsules) BID in week 1, then 8 mg (4 capsules) BID in week 2, and then 10 mg (5 capsules) BID in weeks 3 and 4.	Placebo Participants were administered a Placebo comparator of 2 capsules BID in week 1, then 4 capsules BID in Week 2, and then 5 capsules BID in Weeks 3 and 4.
Overall Study Intercurrent condition necessitating discontinuation	4	2
Overall Study Participant withdrew consent	3	1
Overall Study Investigator decision that withdrawal was in best interest of participant	2	0
Overall Study Lost to Follow-up	2	0
Overall Study Lack of Efficacy	0	1
Overall Study Lack of efficacy/subject withdrew consent	0	1

Baseline Characteristics

A Phase 2 RCT Study of CX-8998 for Essential Tremor

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	CX-8998 n=48 Participants Participants were administered CX-8998 4 mg (2 capsules) BID in week 1, then 8 mg (4 capsules) BID in week 2, and then 10 mg (5 capsules) BID in weeks 3 and 4.	Placebo n=47 Participants Participants were administered a Placebo comparator of 2 capsules BID in week 1, then 4 capsules BID in week 2, and then 5 capsules BID in weeks 3 and 4.	Total n=95 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	22 Participants n=5 Participants	22 Participants n=7 Participants	44 Participants n=5 Participants
Age, Categorical >=65 years	26 Participants n=5 Participants	25 Participants n=7 Participants	51 Participants n=5 Participants
Age, Continuous	64 years STANDARD_DEVIATION 9.6 • n=5 Participants	63 years STANDARD_DEVIATION 10.8 • n=7 Participants	63 years STANDARD_DEVIATION 10.2 • n=5 Participants
Sex: Female, Male Female	23 Participants n=5 Participants	22 Participants n=7 Participants	45 Participants n=5 Participants
Sex: Female, Male Male	25 Participants n=5 Participants	25 Participants n=7 Participants	50 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	48 Participants n=5 Participants	45 Participants n=7 Participants	93 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) White	45 Participants n=5 Participants	46 Participants n=7 Participants	91 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Day 28 post-dose.

Population: TETRAS-PS was assessed using the Full Analysis Set. The number analyzed by Day 28 decreased due to participants that did not complete the study to that time point.

Outcome measures

Outcome measures
Measure	CX-8998 n=39 Participants Participants were administered CX-8998 4 mg (2 capsules) BID in week 1, then 8 mg (4 capsules) BID in week 2, and then 10 mg (5 capsules) BID in weeks 3 and 4.	Placebo n=44 Participants Participants were administered a Placebo comparator of 2 capsules BID in week 1, then 4 capsules BID in week 2, and then 5 capsules BID in weeks 3 and 4.
Baseline and Day 28 on The Essential Tremor Rating Assessment Scale Performance Subscale (TETRAS-PS) Total Score Baseline	22.7 score on a scale Standard Deviation 6.44	22.8 score on a scale Standard Deviation 5.84
Baseline and Day 28 on The Essential Tremor Rating Assessment Scale Performance Subscale (TETRAS-PS) Total Score Day 28	21.1 score on a scale Standard Deviation 6.71	20.7 score on a scale Standard Deviation 7.96

PRIMARY outcome

Timeframe: Baseline up to Day 28 post-dose.

Population: TETRAS-PS was assessed using the Full Analysis Set. The number analyzed by Day 28 decreased due to participants that did not complete the study to that time point.

The Essential Tremor Rating Assessment Scale Performance Subscale (TETRAS-PS) was used to assess the efficacy of CX-8998 in reducing essential tremor as scored by the independent video raters. TETRAS-PS quantifies tremor in the head, face, voice, limbs, and trunk. The overall subscale score ranges from a minimum of 0 to a maximum of 64. A decrease or negative change in the score is indicative of improvement in outcome.

Outcome measures

Outcome measures
Measure	CX-8998 n=38 Participants Participants were administered CX-8998 4 mg (2 capsules) BID in week 1, then 8 mg (4 capsules) BID in week 2, and then 10 mg (5 capsules) BID in weeks 3 and 4.	Placebo n=43 Participants Participants were administered a Placebo comparator of 2 capsules BID in week 1, then 4 capsules BID in week 2, and then 5 capsules BID in weeks 3 and 4.
Change From Baseline to Day 28 on The Essential Tremor Rating Assessment Scale Performance Subscale (TETRAS-PS)	-1.6 score on a scale Standard Deviation 4.36	-2.0 score on a scale Standard Deviation 4.98

SECONDARY outcome

Timeframe: Baseline and Day 28 post-dose.

Population: TETRAS-ADL score was assessed using the Full Analysis Set. The number analyzed by Day 28 decreased due to participants that did not complete the study to that time point.

TETRAS-ADL subscale assesses items such as eating and drinking, dressing and personal hygiene, carrying items, and finer motor skills. Each item is rated on a scale for 0 to 4 on which 0 = normal activity and 4 = severe abnormality. The sum of the individual scores provides an overall score, which ranges from a minimum of 0 to a maximum of 48. A lower score is indicative of improvement or a better outcome.

Outcome measures

Outcome measures
Measure	CX-8998 n=39 Participants Participants were administered CX-8998 4 mg (2 capsules) BID in week 1, then 8 mg (4 capsules) BID in week 2, and then 10 mg (5 capsules) BID in weeks 3 and 4.	Placebo n=44 Participants Participants were administered a Placebo comparator of 2 capsules BID in week 1, then 4 capsules BID in week 2, and then 5 capsules BID in weeks 3 and 4.
Baseline and Day 28 on The Essential Tremor Rating Assessment Scale Activities of Daily Living (TETRAS-ADL) Subscale Score Baseline	25.7 score on a scale Standard Deviation 6.00	26.0 score on a scale Standard Deviation 7.13
Baseline and Day 28 on The Essential Tremor Rating Assessment Scale Activities of Daily Living (TETRAS-ADL) Subscale Score Day 28	21.5 score on a scale Standard Deviation 6.44	24.8 score on a scale Standard Deviation 9.19

SECONDARY outcome

Timeframe: Baseline up to Day 28 post-dose.

Population: TETRAS-ADL score was assessed using the Full Analysis Set. The number analyzed by Day 28 decreased due to participants that did not complete the study to that time point.

TETRAS-ADL subscale assesses items such as eating and drinking, dressing and personal hygiene, carrying items, and finer motor skills. Each item is rated on a scale for 0 to 4 on which 0 = normal activity and 4 = severe abnormality. The sum of the individual scores provides an overall score, which ranges from a minimum of 0 to a maximum of 48. A decrease or negative change in score is indicative of improvement or a better outcome.

Outcome measures

Outcome measures
Measure	CX-8998 n=37 Participants Participants were administered CX-8998 4 mg (2 capsules) BID in week 1, then 8 mg (4 capsules) BID in week 2, and then 10 mg (5 capsules) BID in weeks 3 and 4.	Placebo n=42 Participants Participants were administered a Placebo comparator of 2 capsules BID in week 1, then 4 capsules BID in week 2, and then 5 capsules BID in weeks 3 and 4.
Change From Baseline to Day 28 on The Essential Tremor Rating Assessment Scale Activities of Daily Living (TETRAS-ADL) Subscale Score	-4.2 score on a scale Standard Deviation 6.71	-1.3 score on a scale Standard Deviation 6.35

SECONDARY outcome

Timeframe: Baseline and Day 28 post-dose.

Population: Kinesia ONE score was assessed using the Full Analysis Set. The number analyzed by Day 28 decreased due to participants that did not complete the study to that time point.

Kinesia ONE was developed to provide a quantitative measurement of motor symptoms in individuals with Parkinson's disease. Scores are presented as the sum of the scores of the left and right hands. A total of 4 tasks were performed on the left side and then on the right side to assess resting, postural, kinetic, and lateral wing beating tremor. Values for each test range from 0 (no tremor) to 4 (severe tremor). The total overall score is the sum of all individual items and ranges from a minimum of 0 to a maximum of 32. A lower score is indicative of improvement or a better outcome.

Outcome measures

Outcome measures
Measure	CX-8998 n=39 Participants Participants were administered CX-8998 4 mg (2 capsules) BID in week 1, then 8 mg (4 capsules) BID in week 2, and then 10 mg (5 capsules) BID in weeks 3 and 4.	Placebo n=44 Participants Participants were administered a Placebo comparator of 2 capsules BID in week 1, then 4 capsules BID in week 2, and then 5 capsules BID in weeks 3 and 4.
Baseline and Day 28 in the Kinesia ONE Score Baseline	10.6 score on a scale Standard Deviation 4.33	12.0 score on a scale Standard Deviation 5.35
Baseline and Day 28 in the Kinesia ONE Score Day 28	9.3 score on a scale Standard Deviation 4.28	10.4 score on a scale Standard Deviation 4.84

SECONDARY outcome

Timeframe: Baseline up to Day 28 post-dose.

Population: Change from baseline to Day 28 in the Kinesia ONE Score was assessed using the Full Analysis Set. The number analyzed by Day 28 decreased due to participants that did not complete the study to that time point.

Kinesia ONE was developed to provide a quantitative measurement of motor symptoms in individuals with Parkinson's disease. Scores are presented as the sum of the scores of the left and right hands. A total of 4 tasks were performed on the left side and then on the right side to assess resting, postural, kinetic, and lateral wing beating tremor. Values for each test range from 0 (no tremor) to 4 (severe tremor). The total overall score is the sum of all individual items and ranges from a minimum of 0 to a maximum of 32. A decrease or negative change in score is indicative of improvement or a better outcome.

Outcome measures

Outcome measures
Measure	CX-8998 n=37 Participants Participants were administered CX-8998 4 mg (2 capsules) BID in week 1, then 8 mg (4 capsules) BID in week 2, and then 10 mg (5 capsules) BID in weeks 3 and 4.	Placebo n=41 Participants Participants were administered a Placebo comparator of 2 capsules BID in week 1, then 4 capsules BID in week 2, and then 5 capsules BID in weeks 3 and 4.
Change From Baseline to Day 28 in the Kinesia ONE Score	-1.4 score on a scale Standard Deviation 3.35	-1.8 score on a scale Standard Deviation 3.00

Adverse Events

CX-8998

Serious events: 1 serious events

Other events: 28 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 19 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	CX-8998 n=48 participants at risk Participants were administered CX-8998 4 mg (2 capsules) BID in week 1, then 8 mg (4 capsules) BID in week 2, and then 10 mg (5 capsules) BID in weeks 3 and 4.	Placebo n=47 participants at risk Participants were administered a Placebo comparator of 2 capsules BID in week 1, then 4 capsules BID in week 2, and then 5 capsules BID in weeks 3 and 4.
Psychiatric disorders Alcohol withdrawal syndrome	2.1% 1/48 • Adverse events (AEs) were collected from the time the informed consent form was signed through the follow-up telephone call on Day 56. AEs were followed until resolution or until the symptoms or values returned to normal or acceptable limits, whichever was earlier. Treatment-emergent adverse events (TEAEs) are adverse events (AEs) that occur after the initiation of the study drug through 30 days after the last dose or a pretreatment event that worsens in intensity during the same period.	0.00% 0/47 • Adverse events (AEs) were collected from the time the informed consent form was signed through the follow-up telephone call on Day 56. AEs were followed until resolution or until the symptoms or values returned to normal or acceptable limits, whichever was earlier. Treatment-emergent adverse events (TEAEs) are adverse events (AEs) that occur after the initiation of the study drug through 30 days after the last dose or a pretreatment event that worsens in intensity during the same period.
Psychiatric disorders Suicidal ideation	2.1% 1/48 • Adverse events (AEs) were collected from the time the informed consent form was signed through the follow-up telephone call on Day 56. AEs were followed until resolution or until the symptoms or values returned to normal or acceptable limits, whichever was earlier. Treatment-emergent adverse events (TEAEs) are adverse events (AEs) that occur after the initiation of the study drug through 30 days after the last dose or a pretreatment event that worsens in intensity during the same period.	0.00% 0/47 • Adverse events (AEs) were collected from the time the informed consent form was signed through the follow-up telephone call on Day 56. AEs were followed until resolution or until the symptoms or values returned to normal or acceptable limits, whichever was earlier. Treatment-emergent adverse events (TEAEs) are adverse events (AEs) that occur after the initiation of the study drug through 30 days after the last dose or a pretreatment event that worsens in intensity during the same period.
Psychiatric disorders Major depression	2.1% 1/48 • Adverse events (AEs) were collected from the time the informed consent form was signed through the follow-up telephone call on Day 56. AEs were followed until resolution or until the symptoms or values returned to normal or acceptable limits, whichever was earlier. Treatment-emergent adverse events (TEAEs) are adverse events (AEs) that occur after the initiation of the study drug through 30 days after the last dose or a pretreatment event that worsens in intensity during the same period.	0.00% 0/47 • Adverse events (AEs) were collected from the time the informed consent form was signed through the follow-up telephone call on Day 56. AEs were followed until resolution or until the symptoms or values returned to normal or acceptable limits, whichever was earlier. Treatment-emergent adverse events (TEAEs) are adverse events (AEs) that occur after the initiation of the study drug through 30 days after the last dose or a pretreatment event that worsens in intensity during the same period.

Other adverse events

Additional Information

Director, Disclosure & Transparency

Jazz Pharmaceuticals

Phone: 215-870-9177

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	CX-8998 n=48 participants at risk Participants were administered CX-8998 4 mg (2 capsules) BID in week 1, then 8 mg (4 capsules) BID in week 2, and then 10 mg (5 capsules) BID in weeks 3 and 4.	Placebo n=47 participants at risk Participants were administered a Placebo comparator of 2 capsules BID in week 1, then 4 capsules BID in week 2, and then 5 capsules BID in weeks 3 and 4.
Nervous system disorders Dizziness	20.8% 10/48 • Adverse events (AEs) were collected from the time the informed consent form was signed through the follow-up telephone call on Day 56. AEs were followed until resolution or until the symptoms or values returned to normal or acceptable limits, whichever was earlier. Treatment-emergent adverse events (TEAEs) are adverse events (AEs) that occur after the initiation of the study drug through 30 days after the last dose or a pretreatment event that worsens in intensity during the same period.	6.4% 3/47 • Adverse events (AEs) were collected from the time the informed consent form was signed through the follow-up telephone call on Day 56. AEs were followed until resolution or until the symptoms or values returned to normal or acceptable limits, whichever was earlier. Treatment-emergent adverse events (TEAEs) are adverse events (AEs) that occur after the initiation of the study drug through 30 days after the last dose or a pretreatment event that worsens in intensity during the same period.
Nervous system disorders Headache	8.3% 4/48 • Adverse events (AEs) were collected from the time the informed consent form was signed through the follow-up telephone call on Day 56. AEs were followed until resolution or until the symptoms or values returned to normal or acceptable limits, whichever was earlier. Treatment-emergent adverse events (TEAEs) are adverse events (AEs) that occur after the initiation of the study drug through 30 days after the last dose or a pretreatment event that worsens in intensity during the same period.	4.3% 2/47 • Adverse events (AEs) were collected from the time the informed consent form was signed through the follow-up telephone call on Day 56. AEs were followed until resolution or until the symptoms or values returned to normal or acceptable limits, whichever was earlier. Treatment-emergent adverse events (TEAEs) are adverse events (AEs) that occur after the initiation of the study drug through 30 days after the last dose or a pretreatment event that worsens in intensity during the same period.
Nervous system disorders Disturbance in attention	4.2% 2/48 • Adverse events (AEs) were collected from the time the informed consent form was signed through the follow-up telephone call on Day 56. AEs were followed until resolution or until the symptoms or values returned to normal or acceptable limits, whichever was earlier. Treatment-emergent adverse events (TEAEs) are adverse events (AEs) that occur after the initiation of the study drug through 30 days after the last dose or a pretreatment event that worsens in intensity during the same period.	2.1% 1/47 • Adverse events (AEs) were collected from the time the informed consent form was signed through the follow-up telephone call on Day 56. AEs were followed until resolution or until the symptoms or values returned to normal or acceptable limits, whichever was earlier. Treatment-emergent adverse events (TEAEs) are adverse events (AEs) that occur after the initiation of the study drug through 30 days after the last dose or a pretreatment event that worsens in intensity during the same period.
Nervous system disorders Dysgeusia	4.2% 2/48 • Adverse events (AEs) were collected from the time the informed consent form was signed through the follow-up telephone call on Day 56. AEs were followed until resolution or until the symptoms or values returned to normal or acceptable limits, whichever was earlier. Treatment-emergent adverse events (TEAEs) are adverse events (AEs) that occur after the initiation of the study drug through 30 days after the last dose or a pretreatment event that worsens in intensity during the same period.	0.00% 0/47 • Adverse events (AEs) were collected from the time the informed consent form was signed through the follow-up telephone call on Day 56. AEs were followed until resolution or until the symptoms or values returned to normal or acceptable limits, whichever was earlier. Treatment-emergent adverse events (TEAEs) are adverse events (AEs) that occur after the initiation of the study drug through 30 days after the last dose or a pretreatment event that worsens in intensity during the same period.
Nervous system disorders Paraesthesia	4.2% 2/48 • Adverse events (AEs) were collected from the time the informed consent form was signed through the follow-up telephone call on Day 56. AEs were followed until resolution or until the symptoms or values returned to normal or acceptable limits, whichever was earlier. Treatment-emergent adverse events (TEAEs) are adverse events (AEs) that occur after the initiation of the study drug through 30 days after the last dose or a pretreatment event that worsens in intensity during the same period.	2.1% 1/47 • Adverse events (AEs) were collected from the time the informed consent form was signed through the follow-up telephone call on Day 56. AEs were followed until resolution or until the symptoms or values returned to normal or acceptable limits, whichever was earlier. Treatment-emergent adverse events (TEAEs) are adverse events (AEs) that occur after the initiation of the study drug through 30 days after the last dose or a pretreatment event that worsens in intensity during the same period.
Nervous system disorders Somnolence	2.1% 1/48 • Adverse events (AEs) were collected from the time the informed consent form was signed through the follow-up telephone call on Day 56. AEs were followed until resolution or until the symptoms or values returned to normal or acceptable limits, whichever was earlier. Treatment-emergent adverse events (TEAEs) are adverse events (AEs) that occur after the initiation of the study drug through 30 days after the last dose or a pretreatment event that worsens in intensity during the same period.	4.3% 2/47 • Adverse events (AEs) were collected from the time the informed consent form was signed through the follow-up telephone call on Day 56. AEs were followed until resolution or until the symptoms or values returned to normal or acceptable limits, whichever was earlier. Treatment-emergent adverse events (TEAEs) are adverse events (AEs) that occur after the initiation of the study drug through 30 days after the last dose or a pretreatment event that worsens in intensity during the same period.
Nervous system disorders Hypoaethesia	0.00% 0/48 • Adverse events (AEs) were collected from the time the informed consent form was signed through the follow-up telephone call on Day 56. AEs were followed until resolution or until the symptoms or values returned to normal or acceptable limits, whichever was earlier. Treatment-emergent adverse events (TEAEs) are adverse events (AEs) that occur after the initiation of the study drug through 30 days after the last dose or a pretreatment event that worsens in intensity during the same period.	4.3% 2/47 • Adverse events (AEs) were collected from the time the informed consent form was signed through the follow-up telephone call on Day 56. AEs were followed until resolution or until the symptoms or values returned to normal or acceptable limits, whichever was earlier. Treatment-emergent adverse events (TEAEs) are adverse events (AEs) that occur after the initiation of the study drug through 30 days after the last dose or a pretreatment event that worsens in intensity during the same period.
Psychiatric disorders Euphoric mood	6.2% 3/48 • Adverse events (AEs) were collected from the time the informed consent form was signed through the follow-up telephone call on Day 56. AEs were followed until resolution or until the symptoms or values returned to normal or acceptable limits, whichever was earlier. Treatment-emergent adverse events (TEAEs) are adverse events (AEs) that occur after the initiation of the study drug through 30 days after the last dose or a pretreatment event that worsens in intensity during the same period.	0.00% 0/47 • Adverse events (AEs) were collected from the time the informed consent form was signed through the follow-up telephone call on Day 56. AEs were followed until resolution or until the symptoms or values returned to normal or acceptable limits, whichever was earlier. Treatment-emergent adverse events (TEAEs) are adverse events (AEs) that occur after the initiation of the study drug through 30 days after the last dose or a pretreatment event that worsens in intensity during the same period.
Psychiatric disorders Insomnia	6.2% 3/48 • Adverse events (AEs) were collected from the time the informed consent form was signed through the follow-up telephone call on Day 56. AEs were followed until resolution or until the symptoms or values returned to normal or acceptable limits, whichever was earlier. Treatment-emergent adverse events (TEAEs) are adverse events (AEs) that occur after the initiation of the study drug through 30 days after the last dose or a pretreatment event that worsens in intensity during the same period.	0.00% 0/47 • Adverse events (AEs) were collected from the time the informed consent form was signed through the follow-up telephone call on Day 56. AEs were followed until resolution or until the symptoms or values returned to normal or acceptable limits, whichever was earlier. Treatment-emergent adverse events (TEAEs) are adverse events (AEs) that occur after the initiation of the study drug through 30 days after the last dose or a pretreatment event that worsens in intensity during the same period.
Psychiatric disorders Abnormal dreams	4.2% 2/48 • Adverse events (AEs) were collected from the time the informed consent form was signed through the follow-up telephone call on Day 56. AEs were followed until resolution or until the symptoms or values returned to normal or acceptable limits, whichever was earlier. Treatment-emergent adverse events (TEAEs) are adverse events (AEs) that occur after the initiation of the study drug through 30 days after the last dose or a pretreatment event that worsens in intensity during the same period.	2.1% 1/47 • Adverse events (AEs) were collected from the time the informed consent form was signed through the follow-up telephone call on Day 56. AEs were followed until resolution or until the symptoms or values returned to normal or acceptable limits, whichever was earlier. Treatment-emergent adverse events (TEAEs) are adverse events (AEs) that occur after the initiation of the study drug through 30 days after the last dose or a pretreatment event that worsens in intensity during the same period.
Psychiatric disorders Hallucination	4.2% 2/48 • Adverse events (AEs) were collected from the time the informed consent form was signed through the follow-up telephone call on Day 56. AEs were followed until resolution or until the symptoms or values returned to normal or acceptable limits, whichever was earlier. Treatment-emergent adverse events (TEAEs) are adverse events (AEs) that occur after the initiation of the study drug through 30 days after the last dose or a pretreatment event that worsens in intensity during the same period.	0.00% 0/47 • Adverse events (AEs) were collected from the time the informed consent form was signed through the follow-up telephone call on Day 56. AEs were followed until resolution or until the symptoms or values returned to normal or acceptable limits, whichever was earlier. Treatment-emergent adverse events (TEAEs) are adverse events (AEs) that occur after the initiation of the study drug through 30 days after the last dose or a pretreatment event that worsens in intensity during the same period.
Gastrointestinal disorders Dry mouth	4.2% 2/48 • Adverse events (AEs) were collected from the time the informed consent form was signed through the follow-up telephone call on Day 56. AEs were followed until resolution or until the symptoms or values returned to normal or acceptable limits, whichever was earlier. Treatment-emergent adverse events (TEAEs) are adverse events (AEs) that occur after the initiation of the study drug through 30 days after the last dose or a pretreatment event that worsens in intensity during the same period.	2.1% 1/47 • Adverse events (AEs) were collected from the time the informed consent form was signed through the follow-up telephone call on Day 56. AEs were followed until resolution or until the symptoms or values returned to normal or acceptable limits, whichever was earlier. Treatment-emergent adverse events (TEAEs) are adverse events (AEs) that occur after the initiation of the study drug through 30 days after the last dose or a pretreatment event that worsens in intensity during the same period.
Gastrointestinal disorders Nausea	2.1% 1/48 • Adverse events (AEs) were collected from the time the informed consent form was signed through the follow-up telephone call on Day 56. AEs were followed until resolution or until the symptoms or values returned to normal or acceptable limits, whichever was earlier. Treatment-emergent adverse events (TEAEs) are adverse events (AEs) that occur after the initiation of the study drug through 30 days after the last dose or a pretreatment event that worsens in intensity during the same period.	6.4% 3/47 • Adverse events (AEs) were collected from the time the informed consent form was signed through the follow-up telephone call on Day 56. AEs were followed until resolution or until the symptoms or values returned to normal or acceptable limits, whichever was earlier. Treatment-emergent adverse events (TEAEs) are adverse events (AEs) that occur after the initiation of the study drug through 30 days after the last dose or a pretreatment event that worsens in intensity during the same period.
Gastrointestinal disorders Vomiting	0.00% 0/48 • Adverse events (AEs) were collected from the time the informed consent form was signed through the follow-up telephone call on Day 56. AEs were followed until resolution or until the symptoms or values returned to normal or acceptable limits, whichever was earlier. Treatment-emergent adverse events (TEAEs) are adverse events (AEs) that occur after the initiation of the study drug through 30 days after the last dose or a pretreatment event that worsens in intensity during the same period.	4.3% 2/47 • Adverse events (AEs) were collected from the time the informed consent form was signed through the follow-up telephone call on Day 56. AEs were followed until resolution or until the symptoms or values returned to normal or acceptable limits, whichever was earlier. Treatment-emergent adverse events (TEAEs) are adverse events (AEs) that occur after the initiation of the study drug through 30 days after the last dose or a pretreatment event that worsens in intensity during the same period.
Infections and infestations Urinary tract infection	4.2% 2/48 • Adverse events (AEs) were collected from the time the informed consent form was signed through the follow-up telephone call on Day 56. AEs were followed until resolution or until the symptoms or values returned to normal or acceptable limits, whichever was earlier. Treatment-emergent adverse events (TEAEs) are adverse events (AEs) that occur after the initiation of the study drug through 30 days after the last dose or a pretreatment event that worsens in intensity during the same period.	2.1% 1/47 • Adverse events (AEs) were collected from the time the informed consent form was signed through the follow-up telephone call on Day 56. AEs were followed until resolution or until the symptoms or values returned to normal or acceptable limits, whichever was earlier. Treatment-emergent adverse events (TEAEs) are adverse events (AEs) that occur after the initiation of the study drug through 30 days after the last dose or a pretreatment event that worsens in intensity during the same period.
Ear and labyrinth disorders Tinnitus	4.2% 2/48 • Adverse events (AEs) were collected from the time the informed consent form was signed through the follow-up telephone call on Day 56. AEs were followed until resolution or until the symptoms or values returned to normal or acceptable limits, whichever was earlier. Treatment-emergent adverse events (TEAEs) are adverse events (AEs) that occur after the initiation of the study drug through 30 days after the last dose or a pretreatment event that worsens in intensity during the same period.	0.00% 0/47 • Adverse events (AEs) were collected from the time the informed consent form was signed through the follow-up telephone call on Day 56. AEs were followed until resolution or until the symptoms or values returned to normal or acceptable limits, whichever was earlier. Treatment-emergent adverse events (TEAEs) are adverse events (AEs) that occur after the initiation of the study drug through 30 days after the last dose or a pretreatment event that worsens in intensity during the same period.
Musculoskeletal and connective tissue disorders Pain in Extremity	4.2% 2/48 • Adverse events (AEs) were collected from the time the informed consent form was signed through the follow-up telephone call on Day 56. AEs were followed until resolution or until the symptoms or values returned to normal or acceptable limits, whichever was earlier. Treatment-emergent adverse events (TEAEs) are adverse events (AEs) that occur after the initiation of the study drug through 30 days after the last dose or a pretreatment event that worsens in intensity during the same period.	0.00% 0/47 • Adverse events (AEs) were collected from the time the informed consent form was signed through the follow-up telephone call on Day 56. AEs were followed until resolution or until the symptoms or values returned to normal or acceptable limits, whichever was earlier. Treatment-emergent adverse events (TEAEs) are adverse events (AEs) that occur after the initiation of the study drug through 30 days after the last dose or a pretreatment event that worsens in intensity during the same period.