Trial Outcomes & Findings for Rizatriptan for Episodic Dizziness in Vestibular Migraine (NCT NCT02447991)

NCT ID: NCT02447991

Last Updated: 2021-11-04

Results Overview

Episodes in which a reduction in symptom severity from moderate/severe (rating 2/3) at time of taking study medication to none/mild rating (0/1) was achieved. After taking study medication participants reported symptoms using a patient self-report of the severity of vestibular symptoms (vertigo and unsteadiness/dizziness) wherein 0=no symptoms, 1=mild symptoms (no interference with activities), 2=moderate symptoms (had to alter some activities), and 3=severe symptoms (had to stop most or all activities).

• Recruitment status: COMPLETED
• Study phase: PHASE2/PHASE3
• Target enrollment: 223 participants
• Primary outcome timeframe: 1 hour after taking study medication
• Results posted on: 2021-11-04

Participant Flow

Of the 222 enrolled, 134 completed the observation period and moved on to the treatment phase, having had 2 qualifying episodes in the observation phase. Participants who did not have 2 qualifying episodes in the 12 month observation phase were withdrawn from the study.

Participant milestones

Measure	Placebo During the Treatment Phase, three placebo capsules will be administered to each subject. One capsule will be taken during one acute episode, until three episodes are treated with the study drug. Placebo: During the study either placebo or Rizatriptan will be given to subjects to take during the treatment phase of the study.	Rizatriptan During the Treatment Phase, three Rizatriptan capsules will be administered to each subject. One capsule will be taken during one acute episode, until three episodes are treated with the study drug. Rizatriptan: During the study either placebo or Rizatriptan will be given to subjects to take during the treatment phase of this study.
Overall Study STARTED	45	89
Overall Study COMPLETED	35	59
Overall Study NOT COMPLETED	10	30

Reasons for withdrawal

Measure	Placebo During the Treatment Phase, three placebo capsules will be administered to each subject. One capsule will be taken during one acute episode, until three episodes are treated with the study drug. Placebo: During the study either placebo or Rizatriptan will be given to subjects to take during the treatment phase of the study.	Rizatriptan During the Treatment Phase, three Rizatriptan capsules will be administered to each subject. One capsule will be taken during one acute episode, until three episodes are treated with the study drug. Rizatriptan: During the study either placebo or Rizatriptan will be given to subjects to take during the treatment phase of this study.
Overall Study Withdrawn by subject - no data	0	2
Overall Study Withdrawn by Subject - with data	4	4
Overall Study Lost to Follow-up - no data	3	6
Overall Study Lost to follow-up - with data	0	3
Overall Study End of study - no treatment results	3	6
Overall Study End of study - partial treatment results	0	9

Baseline Characteristics

Rizatriptan for Episodic Dizziness in Vestibular Migraine

Baseline characteristics by cohort

Measure	Placebo n=45 Participants During the Treatment Phase, three placebo capsules were administered to each subject, one capsule to be taken during one acute episode, until three episodes are treated with the study drug.	Rizatriptan n=89 Participants During the Treatment Phase, three Rizatriptan capsules were administered to each subject, one capsule to be taken during one acute episode, until three episodes are treated with the study drug.	Total n=134 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	45 Participants n=5 Participants	89 Participants n=7 Participants	134 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	32 Participants n=5 Participants	69 Participants n=7 Participants	101 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	20 Participants n=7 Participants	33 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	9 Participants n=7 Participants	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	40 Participants n=5 Participants	80 Participants n=7 Participants	120 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	5 Participants n=5 Participants	9 Participants n=7 Participants	14 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	0 Participants n=5 Participants	7 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) White	39 Participants n=5 Participants	69 Participants n=7 Participants	108 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment United States	45 participants n=5 Participants	89 participants n=7 Participants	134 participants n=5 Participants

PRIMARY outcome

Timeframe: 1 hour after taking study medication

Population: Participants who experienced episodes with moderate/severe symptoms were included in the analyses

Episodes in which a reduction in symptom severity from moderate/severe (rating 2/3) at time of taking study medication to none/mild rating (0/1) was achieved. After taking study medication participants reported symptoms using a patient self-report of the severity of vestibular symptoms (vertigo and unsteadiness/dizziness) wherein 0=no symptoms, 1=mild symptoms (no interference with activities), 2=moderate symptoms (had to alter some activities), and 3=severe symptoms (had to stop most or all activities).

Outcome measures

Measure	Placebo n=88 Episodes of vertigo Participants were instructed to treat three separate episodes of moderate to server vestibular symptoms with study drug, (placebo capsule) orally.	Rizatriptan n=151 Episodes of vertigo Participants were instructed to treat three separate episodes of moderate to server vestibular symptoms with study drug, (rizatriptan 10 mg) orally.
Episodes With Vertigo Symptom Reduced From Moderate/Severe to None/Mild	50 Episodes	73 Episodes

PRIMARY outcome

Timeframe: 1 hour after taking study medication

Population: Participants who experienced episodes with moderate/severe symptoms were included in the analyses

Episodes of unsteadiness/dizziness in which a reduction in symptom severity from moderate/severe (rating 2/3) to none/mild rating (0/1) was achieved. After taking study medication participants reported symptoms using a patient self-report of the severity of vestibular symptoms (vertigo and unsteadiness/dizziness) wherein 0=no symptoms, 1=mild symptoms (no interference with activities), 2=moderate symptoms (had to alter some activities), and 3=severe symptoms (had to stop most or all activities).

Outcome measures

Measure	Placebo n=89 Episodes of Unsteadiness/Dizziness Participants were instructed to treat three separate episodes of moderate to server vestibular symptoms with study drug, (placebo capsule) orally.	Rizatriptan n=151 Episodes of Unsteadiness/Dizziness Participants were instructed to treat three separate episodes of moderate to server vestibular symptoms with study drug, (rizatriptan 10 mg) orally.
Episodes With Symptoms of Unsteadiness/Dizziness Reduced From Moderate/Severe to None/Mild	11 Episodes	29 Episodes

SECONDARY outcome

Timeframe: 1 hour after taking study medication

Population: Participants who experienced episodes with moderate/severe symptoms were included in the analyses.

The number of episodes in which complete relief of vertigo symptoms (rating 0) was achieved. After taking study medication participants reported symptoms using a patient self-report of the severity of vestibular symptoms (vertigo and unsteadiness/dizziness) wherein 0=no symptoms, 1=mild symptoms (no interference with activities), 2=moderate symptoms (had to alter some activities), and 3=severe symptoms (had to stop most or all activities).

Outcome measures

Measure	Placebo n=88 Episodes of vertigo Participants were instructed to treat three separate episodes of moderate to server vestibular symptoms with study drug, (placebo capsule) orally.	Rizatriptan n=151 Episodes of vertigo Participants were instructed to treat three separate episodes of moderate to server vestibular symptoms with study drug, (rizatriptan 10 mg) orally.
Episodes With Complete Relief of Vertigo as Vestibular Symptom	35 Episodes	56 Episodes

SECONDARY outcome

Timeframe: 1 hour after taking study medication

Population: Participants who experienced episodes with moderate/severe symptoms were included in the analyses.

The outcome was the number of episodes in which complete relief of symptoms of unsteadiness/dizziness (rating 0) was achieved. After taking study medication participants reported symptoms using a patient self-report of the severity of vestibular symptoms (vertigo and unsteadiness/dizziness) wherein 0=no symptoms, 1=mild symptoms (no interference with activities), 2=moderate symptoms (had to alter some activities), and 3=severe symptoms (had to stop most or all activities).

Outcome measures

Measure	Placebo n=89 Episodes of Unsteadiness/Dizziness Participants were instructed to treat three separate episodes of moderate to server vestibular symptoms with study drug, (placebo capsule) orally.	Rizatriptan n=151 Episodes of Unsteadiness/Dizziness Participants were instructed to treat three separate episodes of moderate to server vestibular symptoms with study drug, (rizatriptan 10 mg) orally.
Episodes With Complete Relief of Unsteadiness/Dizziness Vestibular Symptoms	2 Episodes	12 Episodes

SECONDARY outcome

Timeframe: 1 hour after taking study medication

Population: Participants who experienced episodes with moderate/severe symptoms were included in the analyses.

The outcome was the number of episodes in which a reduction of headache symptoms (rating 0) was achieved. After taking study medication participants reported symptoms using a patient self-report of the severity of vestibular symptoms wherein 0=no symptoms, 1=mild symptoms (no interference with activities), 2=moderate symptoms (had to alter some activities), and 3=severe symptoms (had to stop most or all activities).

Outcome measures

Measure	Placebo n=89 Episodes of headache Participants were instructed to treat three separate episodes of moderate to server vestibular symptoms with study drug, (placebo capsule) orally.	Rizatriptan n=149 Episodes of headache Participants were instructed to treat three separate episodes of moderate to server vestibular symptoms with study drug, (rizatriptan 10 mg) orally.
Episodes With Headache Reduced From Moderate/Severe to None/Mild	38 Episodes	44 Episodes

SECONDARY outcome

Timeframe: 1 hour after taking study medication

Population: Participants who experienced episodes with moderate/severe symptoms were included in the analyses.

The outcome was the number of episodes in which a reduction of symptoms (rating 0/1) was achieved. After taking study medication participants reported symptoms using a patient self-report of the severity of vestibular symptoms wherein 0=no symptoms, 1=mild symptoms (no interference with activities), 2=moderate symptoms (had to alter some activities), and 3=severe symptoms (had to stop most or all activities).

Outcome measures

Measure	Placebo n=89 Episodes of Photophobia/Phonophobia Participants were instructed to treat three separate episodes of moderate to server vestibular symptoms with study drug, (placebo capsule) orally.	Rizatriptan n=151 Episodes of Photophobia/Phonophobia Participants were instructed to treat three separate episodes of moderate to server vestibular symptoms with study drug, (rizatriptan 10 mg) orally.
Episodes With Photophobia/Phonophobia Reduced From Moderate/Severe to None/Mild	33 Episodes	59 Episodes

SECONDARY outcome

Timeframe: 1 hour after taking study medication

Population: Participants who experienced episodes with moderate/severe symptoms were included in the analyses.

The outcome was the number of episodes in which a reduction of sensitivity to motion symptoms (rating 0/1) was achieved. After taking study medication participants reported symptoms using a patient self-report of the severity of vestibular symptoms wherein 0=no symptoms, 1=mild symptoms (no interference with activities), 2=moderate symptoms (had to alter some activities), and 3=severe symptoms (had to stop most or all activities).

Outcome measures

Measure	Placebo n=89 Episodes of Sensitivity to Motion Participants were instructed to treat three separate episodes of moderate to server vestibular symptoms with study drug, (placebo capsule) orally.	Rizatriptan n=151 Episodes of Sensitivity to Motion Participants were instructed to treat three separate episodes of moderate to server vestibular symptoms with study drug, (rizatriptan 10 mg) orally.
Episodes With Sensitivity to Motion Reduced From Moderate/Severe to None/Mild	19 Episodes	39 Episodes

SECONDARY outcome

Timeframe: 1 hour after taking study medication

Population: Participants who experienced episodes with moderate/severe symptoms were included in the analyses.

The outcome was the number of episodes in which a reduction of symptoms (rating 0/1) was achieved. After taking study medication participants reported symptoms using a patient self-report of the severity of vestibular symptoms wherein 0=no symptoms, 1=mild symptoms (no interference with activities), 2=moderate symptoms (had to alter some activities), and 3=severe symptoms (had to stop most or all activities).

Outcome measures

Measure	Placebo n=89 Episodes of Nausea/Vomiting Participants were instructed to treat three separate episodes of moderate to server vestibular symptoms with study drug, (placebo capsule) orally.	Rizatriptan n=150 Episodes of Nausea/Vomiting Participants were instructed to treat three separate episodes of moderate to server vestibular symptoms with study drug, (rizatriptan 10 mg) orally.
Episodes With Nausea/Vomiting Reduced From Moderate/Severe to None/Mild	50 Episodes	67 Episodes

SECONDARY outcome

Timeframe: 48 hour after taking study medication

Population: Participants who experienced episodes with moderate/severe vestibular symptoms were included in the analyses.

Treatment Satisfaction Questionnaire for Medication (TSQM) assessed four domains of participants' satisfaction with treatment, with scale ranges from 0 (extremely dissatisfied) to 100 (not at all dissatisfied) for each of the categories (Effectiveness, Side Effects, Convenience, and Overall Satisfaction).

Outcome measures

Measure	Placebo n=39 Participants Participants were instructed to treat three separate episodes of moderate to server vestibular symptoms with study drug, (placebo capsule) orally.	Rizatriptan n=75 Participants Participants were instructed to treat three separate episodes of moderate to server vestibular symptoms with study drug, (rizatriptan 10 mg) orally.
Satisfaction With Treatment Effectiveness	37.2 score on a scale Standard Deviation 27.0	49.7 score on a scale Standard Deviation 28.6
Satisfaction With Treatment Side Effects	78.8 score on a scale Standard Deviation 26.0	81.6 score on a scale Standard Deviation 22.6
Satisfaction With Treatment Convenience	70.0 score on a scale Standard Deviation 17.4	71.0 score on a scale Standard Deviation 17.8
Satisfaction With Treatment Overall Satisfaction	45.9 score on a scale Standard Deviation 27.1	58.2 score on a scale Standard Deviation 26.7

SECONDARY outcome

Timeframe: 48 hour after taking study medication

Population: Episodes with moderate/severe symptoms were included in the analyses.

Short Form Survey - 12 (SF-12) assessed physical and mental well-being after taking study medication for each episode, generating composite scores in each domain from 12 questions. The range is 0-100 with higher scores indicated better physical and mental health functioning.

Outcome measures

Measure	Placebo n=89 episodes of vestibular symptoms Participants were instructed to treat three separate episodes of moderate to server vestibular symptoms with study drug, (placebo capsule) orally.	Rizatriptan n=151 episodes of vestibular symptoms Participants were instructed to treat three separate episodes of moderate to server vestibular symptoms with study drug, (rizatriptan 10 mg) orally.
Health-Related Quality of Life Physical well-being after study medication	37.5 score on a scale Standard Deviation 10.5	41.9 score on a scale Standard Deviation 8.9
Health-Related Quality of Life Mental well-being after study medication	44.2 score on a scale Standard Deviation 13.9	45.4 score on a scale Standard Deviation 11.4

SECONDARY outcome

Timeframe: 48 hour after taking study medication

Population: Participants who experienced episodes with moderate/severe vestibular symptoms were included in the analyses.

Number of adverse events experienced by participants. Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 categorizes all domains of physical and psychological side effects, grading them 1-mild, 2-moderate, 3-severe, 4-life threatening, 5-death.

Outcome measures

Measure	Placebo n=39 Participants Participants were instructed to treat three separate episodes of moderate to server vestibular symptoms with study drug, (placebo capsule) orally.	Rizatriptan n=75 Participants Participants were instructed to treat three separate episodes of moderate to server vestibular symptoms with study drug, (rizatriptan 10 mg) orally.
Side Effects Fatigue	7 Adverse Events	44 Adverse Events
Side Effects Sleepiness/Drowsiness	11 Adverse Events	51 Adverse Events
Side Effects Upset Stomach, nausea, vomiting	8 Adverse Events	19 Adverse Events
Side Effects Constipation or diarrhea	3 Adverse Events	3 Adverse Events
Side Effects Hearth rhythm problems	2 Adverse Events	5 Adverse Events
Side Effects Chest pain or decreased exercise tolerance	1 Adverse Events	0 Adverse Events
Side Effects Swelling or puffiness	0 Adverse Events	3 Adverse Events
Side Effects Fever or chills	0 Adverse Events	4 Adverse Events
Side Effects Worsening of dizziness or gait	3 Adverse Events	15 Adverse Events
Side Effects Worsening of headache	9 Adverse Events	13 Adverse Events
Side Effects Ataxia	1 Adverse Events	4 Adverse Events
Side Effects Speech problems	1 Adverse Events	3 Adverse Events
Side Effects Weakness of arms/legs/face or loss of sensation	5 Adverse Events	7 Adverse Events
Side Effects Agitation	1 Adverse Events	5 Adverse Events
Side Effects Anxiety	5 Adverse Events	12 Adverse Events
Side Effects Serious adverse effects	0 Adverse Events	0 Adverse Events
Side Effects Discontinuation due to adverse effects	0 Adverse Events	0 Adverse Events

SECONDARY outcome

Timeframe: 24 hours after taking study medication

Population: Participants who experienced episodes with moderate/severe symptoms were included in the analyses.

Episodes in which participants achieved reduction of symptoms (from rating 2-3 to 0-1). After taking study medication participants reported symptoms using a patient self-report of the severity of vestibular symptoms wherein 0=no symptoms, 1=mild symptoms (no interference with activities), 2=moderate symptoms (had to alter some activities), and 3=severe symptoms (had to stop most or all activities).

Outcome measures

Measure	Placebo n=61 Episodes of vertigo Participants were instructed to treat three separate episodes of moderate to server vestibular symptoms with study drug, (placebo capsule) orally.	Rizatriptan n=109 Episodes of vertigo Participants were instructed to treat three separate episodes of moderate to server vestibular symptoms with study drug, (rizatriptan 10 mg) orally.
Episodes With Sustained Reduction in Severity of Vertigo From Moderate/Severe to None/Mild Without Additional Medication	54 Episodes	97 Episodes

SECONDARY outcome

Timeframe: 24 hours after taking study medication

Population: Participants who experienced episodes with moderate/severe vestibular symptoms were included in the analyses.

Episodes in which participants achieved reduction of symptoms (from rating 2-3 to 0-1). After taking study medication participants reported symptoms using a patient self-report of the severity of vestibular symptoms wherein 0=no symptoms, 1=mild symptoms (no interference with activities), 2=moderate symptoms (had to alter some activities), and 3=severe symptoms (had to stop most or all activities).

Outcome measures

Measure	Placebo n=62 Episodes of Unsteadiness/Dizziness Participants were instructed to treat three separate episodes of moderate to server vestibular symptoms with study drug, (placebo capsule) orally.	Rizatriptan n=109 Episodes of Unsteadiness/Dizziness Participants were instructed to treat three separate episodes of moderate to server vestibular symptoms with study drug, (rizatriptan 10 mg) orally.
Episodes With Sustained Reduction in Severity of Dizziness/Unsteadiness From Moderate/Severe to None/Mild Without Additional Medication	41 Episodes	90 Episodes

SECONDARY outcome

Timeframe: 24 hours after taking study medication

Population: Participants who experienced episodes with moderate/severe vestibular symptoms were included in the analyses.

After taking study medication participants reported symptoms using a patient self-report of the severity of vestibular symptoms wherein 0=no symptoms, 1=mild symptoms (no interference with activities), 2=moderate symptoms (had to alter some activities), and 3=severe symptoms (had to stop most or all activities).

Outcome measures

Measure	Placebo n=62 Episodes of headache Participants were instructed to treat three separate episodes of moderate to server vestibular symptoms with study drug, (placebo capsule) orally.	Rizatriptan n=109 Episodes of headache Participants were instructed to treat three separate episodes of moderate to server vestibular symptoms with study drug, (rizatriptan 10 mg) orally.
Episodes With Headache Symptoms Reduced From Moderate/Severe (3/4) to None/Mild (0/1) Without Additional Medication	46 Episodes	94 Episodes

SECONDARY outcome

Timeframe: 24 hours after taking study medication

Population: Participants who experienced episodes with moderate/severe vestibular symptoms were included in the analyses.

After taking study medication participants reported symptoms using a patient self-report of the severity of vestibular symptoms wherein 0=no symptoms, 1=mild symptoms (no interference with activities), 2=moderate symptoms (had to alter some activities), and 3=severe symptoms (had to stop most or all activities).

Outcome measures

Measure	Placebo n=62 Episodes of photophobia/phonophobia Participants were instructed to treat three separate episodes of moderate to server vestibular symptoms with study drug, (placebo capsule) orally.	Rizatriptan n=109 Episodes of photophobia/phonophobia Participants were instructed to treat three separate episodes of moderate to server vestibular symptoms with study drug, (rizatriptan 10 mg) orally.
Episodes With Photophobia/Phonophobia Symptoms Reduced From Moderate/Severe (3/4) to None/Mild (0/1) Without Additional Medication	45 Episodes	95 Episodes

SECONDARY outcome

Timeframe: 24 hours after taking study medication

Population: Participants who experienced episodes with moderate/severe symptoms were included in the analyses.

After taking study medication participants reported symptoms using a patient self-report of the severity of vestibular symptoms wherein 0=no symptoms, 1=mild symptoms (no interference with activities), 2=moderate symptoms (had to alter some activities), and 3=severe symptoms (had to stop most or all activities).

Outcome measures

Measure	Placebo n=62 Episodes of sensitivity to motion Participants were instructed to treat three separate episodes of moderate to server vestibular symptoms with study drug, (placebo capsule) orally.	Rizatriptan n=109 Episodes of sensitivity to motion Participants were instructed to treat three separate episodes of moderate to server vestibular symptoms with study drug, (rizatriptan 10 mg) orally.
Episodes With Sensitivity to Motion Symptoms Reduced From Moderate/Severe (3/4) to None/Mild (0/1) Without Additional Medication	42 Episodes	95 Episodes

SECONDARY outcome

Timeframe: 24 hours after taking study medication

Population: Participants who experienced episodes with moderate/severe symptoms were included in the analyses.

After taking study medication participants reported symptoms using a patient self-report of the severity of vestibular symptoms wherein 0=no symptoms, 1=mild symptoms (no interference with activities), 2=moderate symptoms (had to alter some activities), and 3=severe symptoms (had to stop most or all activities).

Outcome measures

Measure	Placebo n=62 Episodes of nausea/vomiting Participants were instructed to treat three separate episodes of moderate to server vestibular symptoms with study drug, (placebo capsule) orally.	Rizatriptan n=108 Episodes of nausea/vomiting Participants were instructed to treat three separate episodes of moderate to server vestibular symptoms with study drug, (rizatriptan 10 mg) orally.
Episodes With Nausea/Vomiting Symptoms Reduced From Moderate/Severe (3/4) to None/Mild (0/1) Without Additional Medication	57 Episodes	101 Episodes

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 45 other events

Deaths: 0 deaths

Rizatriptan

Serious events: 0 serious events

Other events: 89 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Placebo n=45 participants at risk During the Treatment Phase, three placebo capsules will be administered to each subject. One capsule will be taken during one acute episode, until three episodes are treated with the study drug. Placebo: During the study either placebo or Rizatriptan will be given to subjects to take during the treatment phase of the study.	Rizatriptan n=89 participants at risk During the Treatment Phase, three Rizatriptan capsules will be administered to each subject. One capsule will be taken during one acute episode, until three episodes are treated with the study drug. Rizatriptan: During the study either placebo or Rizatriptan will be given to subjects to take during the treatment phase of this study.
General disorders Fatigue	15.6% 7/45 • Number of events 7 • Up to 5 years 48 hours after each episode, until 3 episodes occur, up to 5 years of study duration	49.4% 44/89 • Number of events 44 • Up to 5 years 48 hours after each episode, until 3 episodes occur, up to 5 years of study duration
General disorders Sleepiness/drowsiness	24.4% 11/45 • Number of events 11 • Up to 5 years 48 hours after each episode, until 3 episodes occur, up to 5 years of study duration	57.3% 51/89 • Number of events 51 • Up to 5 years 48 hours after each episode, until 3 episodes occur, up to 5 years of study duration
Gastrointestinal disorders Upset stomach, nausea, vomiting	17.8% 8/45 • Number of events 8 • Up to 5 years 48 hours after each episode, until 3 episodes occur, up to 5 years of study duration	21.3% 19/89 • Number of events 19 • Up to 5 years 48 hours after each episode, until 3 episodes occur, up to 5 years of study duration
Gastrointestinal disorders Constipation or diarrhea	6.7% 3/45 • Number of events 3 • Up to 5 years 48 hours after each episode, until 3 episodes occur, up to 5 years of study duration	3.4% 3/89 • Number of events 3 • Up to 5 years 48 hours after each episode, until 3 episodes occur, up to 5 years of study duration
Cardiac disorders Hearth rhythm problems	4.4% 2/45 • Number of events 2 • Up to 5 years 48 hours after each episode, until 3 episodes occur, up to 5 years of study duration	5.6% 5/89 • Number of events 5 • Up to 5 years 48 hours after each episode, until 3 episodes occur, up to 5 years of study duration
Cardiac disorders Chest pain or decreased exercise tolerance	2.2% 1/45 • Number of events 1 • Up to 5 years 48 hours after each episode, until 3 episodes occur, up to 5 years of study duration	0.00% 0/89 • Up to 5 years 48 hours after each episode, until 3 episodes occur, up to 5 years of study duration
General disorders Swelling or puffiness	0.00% 0/45 • Up to 5 years 48 hours after each episode, until 3 episodes occur, up to 5 years of study duration	3.4% 3/89 • Number of events 3 • Up to 5 years 48 hours after each episode, until 3 episodes occur, up to 5 years of study duration
General disorders Fever or chills	0.00% 0/45 • Up to 5 years 48 hours after each episode, until 3 episodes occur, up to 5 years of study duration	4.5% 4/89 • Number of events 4 • Up to 5 years 48 hours after each episode, until 3 episodes occur, up to 5 years of study duration
Nervous system disorders Worsening of dizziness or gait	6.7% 3/45 • Number of events 3 • Up to 5 years 48 hours after each episode, until 3 episodes occur, up to 5 years of study duration	16.9% 15/89 • Number of events 15 • Up to 5 years 48 hours after each episode, until 3 episodes occur, up to 5 years of study duration
Nervous system disorders Worsening of headache	20.0% 9/45 • Number of events 9 • Up to 5 years 48 hours after each episode, until 3 episodes occur, up to 5 years of study duration	14.6% 13/89 • Number of events 13 • Up to 5 years 48 hours after each episode, until 3 episodes occur, up to 5 years of study duration
Musculoskeletal and connective tissue disorders Ataxia	2.2% 1/45 • Number of events 1 • Up to 5 years 48 hours after each episode, until 3 episodes occur, up to 5 years of study duration	4.5% 4/89 • Number of events 4 • Up to 5 years 48 hours after each episode, until 3 episodes occur, up to 5 years of study duration
Nervous system disorders Speech problems	2.2% 1/45 • Number of events 1 • Up to 5 years 48 hours after each episode, until 3 episodes occur, up to 5 years of study duration	3.4% 3/89 • Number of events 3 • Up to 5 years 48 hours after each episode, until 3 episodes occur, up to 5 years of study duration
Musculoskeletal and connective tissue disorders Weakness of arm/legs/face or loss of sensation	11.1% 5/45 • Number of events 5 • Up to 5 years 48 hours after each episode, until 3 episodes occur, up to 5 years of study duration	7.9% 7/89 • Number of events 7 • Up to 5 years 48 hours after each episode, until 3 episodes occur, up to 5 years of study duration
Psychiatric disorders Agitations	2.2% 1/45 • Number of events 1 • Up to 5 years 48 hours after each episode, until 3 episodes occur, up to 5 years of study duration	5.6% 5/89 • Number of events 5 • Up to 5 years 48 hours after each episode, until 3 episodes occur, up to 5 years of study duration
Psychiatric disorders Anxiety	11.1% 5/45 • Number of events 5 • Up to 5 years 48 hours after each episode, until 3 episodes occur, up to 5 years of study duration	13.5% 12/89 • Number of events 12 • Up to 5 years 48 hours after each episode, until 3 episodes occur, up to 5 years of study duration

Additional Information

Jeffrey Staab, MD

Mayo Clnic

Phone: 507-293-9438

Email: staab.jeffrey@mayo.edu

Results disclosure agreements

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