Trial Outcomes & Findings for Clinical Trial of Ezogabine (Retigabine) in ALS Subjects (NCT NCT02450552)

NCT ID: NCT02450552

Last Updated: 2019-08-28

Results Overview

Short-interval intracortical inhibition (SICI) or paired-pulse SICI is defined as the ratio of the response after a conditioning pulse equal to 80% of resting motor threshold (RMT) is administered 3 ms prior to the signaling pulse divided by motor evoked potential (MEP) amplitude. Transcranial magnetic stimulation (TMS) is a neurophysiologic test for assessing upper motor neuron function. Change in SICI will be assessed by transcranial magnetic stimulation (TMS) after treatment with 900 mg/day or 600 mg/day of ezogabine vs. matched oral placebo.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 65 participants
• Primary outcome timeframe: Screening, Baseline, Week 6, Week 8
• Results posted on: 2019-08-28

Participant Flow

Participant milestones

Measure	Oral Ezogabine 900 mg/Day Ezogabine: Potiga is FDA-approved for adjunctive treatment of partial-onset seizures in patients aged 18 years and older who have responded inadequately to several alternative treatments.	Oral Ezogabine 600 mg/Day Ezogabine: Potiga is FDA-approved for adjunctive treatment of partial-onset seizures in patients aged 18 years and older who have responded inadequately to several alternative treatments.	Placebo Placebo: Matched placebo
Overall Study STARTED	19	23	23
Overall Study COMPLETED	14	23	18
Overall Study NOT COMPLETED	5	0	5

Reasons for withdrawal

Measure	Oral Ezogabine 900 mg/Day Ezogabine: Potiga is FDA-approved for adjunctive treatment of partial-onset seizures in patients aged 18 years and older who have responded inadequately to several alternative treatments.	Oral Ezogabine 600 mg/Day Ezogabine: Potiga is FDA-approved for adjunctive treatment of partial-onset seizures in patients aged 18 years and older who have responded inadequately to several alternative treatments.	Placebo Placebo: Matched placebo
Overall Study Withdrawal by Subject	4	0	4
Overall Study Physician Decision	1	0	1

Baseline Characteristics

Clinical Trial of Ezogabine (Retigabine) in ALS Subjects

Baseline characteristics by cohort

Measure	Oral Ezogabine 900 mg/Day n=19 Participants Ezogabine: Potiga is FDA-approved for adjunctive treatment of partial-onset seizures in patients aged 18 years and older who have responded inadequately to several alternative treatments.	Oral Ezogabine 600 mg/Day n=23 Participants Ezogabine: Potiga is FDA-approved for adjunctive treatment of partial-onset seizures in patients aged 18 years and older who have responded inadequately to several alternative treatments.	Placebo n=23 Participants Placebo: Matched placebo	Total n=65 Participants Total of all reporting groups
Age, Continuous	58.91 years STANDARD_DEVIATION 9.10 • n=5 Participants	57.4 years STANDARD_DEVIATION 8.01 • n=7 Participants	58.1 years STANDARD_DEVIATION 9.55 • n=5 Participants	58.34 years STANDARD_DEVIATION 8.78 • n=4 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	10 Participants n=7 Participants	4 Participants n=5 Participants	20 Participants n=4 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	13 Participants n=7 Participants	19 Participants n=5 Participants	45 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	19 Participants n=5 Participants	22 Participants n=7 Participants	22 Participants n=5 Participants	63 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 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	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) White	17 Participants n=5 Participants	23 Participants n=7 Participants	23 Participants n=5 Participants	63 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United States	19 Participants n=5 Participants	23 Participants n=7 Participants	23 Participants n=5 Participants	65 Participants n=4 Participants

PRIMARY outcome

Timeframe: Screening, Baseline, Week 6, Week 8

Population: As a result of electrophysiologic response, good quality data was defined based on the central reader's evaluation.

Short-interval intracortical inhibition (SICI) or paired-pulse SICI is defined as the ratio of the response after a conditioning pulse equal to 80% of resting motor threshold (RMT) is administered 3 ms prior to the signaling pulse divided by motor evoked potential (MEP) amplitude. Transcranial magnetic stimulation (TMS) is a neurophysiologic test for assessing upper motor neuron function. Change in SICI will be assessed by transcranial magnetic stimulation (TMS) after treatment with 900 mg/day or 600 mg/day of ezogabine vs. matched oral placebo.

Outcome measures

Measure	Oral Ezogabine 900 mg/Day n=19 Participants Ezogabine: Potiga is FDA-approved for adjunctive treatment of partial-onset seizures in patients aged 18 years and older who have responded inadequately to several alternative treatments.	Oral Ezogabine 600 mg/Day n=23 Participants Ezogabine: Potiga is FDA-approved for adjunctive treatment of partial-onset seizures in patients aged 18 years and older who have responded inadequately to several alternative treatments.	Placebo n=23 Participants Placebo: Matched placebo
Change in Short-interval Intracortical Inhibition (SICI) Measured by Transcranial Magnetic Stimulation (TMS) Screening	1.180 Unitless Standard Deviation 1.108	0.965 Unitless Standard Deviation 1.302	0.784 Unitless Standard Deviation 0.560
Change in Short-interval Intracortical Inhibition (SICI) Measured by Transcranial Magnetic Stimulation (TMS) Baseline	1.347 Unitless Standard Deviation 1.662	0.952 Unitless Standard Deviation 1.138	0.755 Unitless Standard Deviation 0.539
Change in Short-interval Intracortical Inhibition (SICI) Measured by Transcranial Magnetic Stimulation (TMS) Week 6	1.100 Unitless Standard Deviation 1.066	0.675 Unitless Standard Deviation 0.613	0.777 Unitless Standard Deviation 0.442
Change in Short-interval Intracortical Inhibition (SICI) Measured by Transcranial Magnetic Stimulation (TMS) Week 8	0.948 Unitless Standard Deviation 1.169	0.617 Unitless Standard Deviation 0.455	0.834 Unitless Standard Deviation 0.488

SECONDARY outcome

Timeframe: Screening, Baseline, Week 6, Week 8

Population: Data of low quality may have been removed from the number of participants analyzed based on the central reader's evaluation.

Resting Motor Evoked Potential (MEP) is the magnetic field strength, measured as a percentage of the maximum stimulator output, that produces at least a 0.05 mV response in at least 5 of 10 consecutive trials.Change in resting MEP threshold will be assessed by Transcranial Magnetic Stimulation (TMS).

Outcome measures

Measure	Oral Ezogabine 900 mg/Day n=19 Participants Ezogabine: Potiga is FDA-approved for adjunctive treatment of partial-onset seizures in patients aged 18 years and older who have responded inadequately to several alternative treatments.	Oral Ezogabine 600 mg/Day n=23 Participants Ezogabine: Potiga is FDA-approved for adjunctive treatment of partial-onset seizures in patients aged 18 years and older who have responded inadequately to several alternative treatments.	Placebo n=23 Participants Placebo: Matched placebo
Change in Resting Motor Evoked Potential (MEP) Threshold (Prespecified Secondary Outcome of Primary Importance) Screening	51.250 percentage of the maximum output Standard Deviation 14.379	52.000 percentage of the maximum output Standard Deviation 11.480	56.308 percentage of the maximum output Standard Deviation 13.804
Change in Resting Motor Evoked Potential (MEP) Threshold (Prespecified Secondary Outcome of Primary Importance) Baseline	48.385 percentage of the maximum output Standard Deviation 14.373	54.250 percentage of the maximum output Standard Deviation 11.018	57.231 percentage of the maximum output Standard Deviation 13.498
Change in Resting Motor Evoked Potential (MEP) Threshold (Prespecified Secondary Outcome of Primary Importance) Week 6	50.111 percentage of the maximum output Standard Deviation 14.066	57.583 percentage of the maximum output Standard Deviation 15.365	54.714 percentage of the maximum output Standard Deviation 12.313
Change in Resting Motor Evoked Potential (MEP) Threshold (Prespecified Secondary Outcome of Primary Importance) Week 8	46.00 percentage of the maximum output Standard Deviation 10.876	56.700 percentage of the maximum output Standard Deviation 13.039	55.357 percentage of the maximum output Standard Deviation 10.149

SECONDARY outcome

Timeframe: Screening, Baseline, Week 6, Week 8

Population: Data of low quality were removed from analysis as a result of the central reader's evaluation standards.

Motor Evoked Potential (MEP) amplitude is defined as the response when a stimulus equal to 120% of Resting Motor Threshold (RMT) is administered. MEP amplitude is calculated as the geometric mean of replicate estimates. Change in MEP will be assessed by Transcranial Magnetic Stimulation (TMS).

Outcome measures

Measure	Oral Ezogabine 900 mg/Day n=19 Participants Ezogabine: Potiga is FDA-approved for adjunctive treatment of partial-onset seizures in patients aged 18 years and older who have responded inadequately to several alternative treatments.	Oral Ezogabine 600 mg/Day n=23 Participants Ezogabine: Potiga is FDA-approved for adjunctive treatment of partial-onset seizures in patients aged 18 years and older who have responded inadequately to several alternative treatments.	Placebo n=23 Participants Placebo: Matched placebo
Change in MEP Amplitude Week 8	0.571 Millivolts Standard Deviation 0.345	1.129 Millivolts Standard Deviation 0.600	0.450 Millivolts Standard Deviation 0.299
Change in MEP Amplitude Screening	0.639 Millivolts Standard Deviation 0.635	1.210 Millivolts Standard Deviation 1.958	0.845 Millivolts Standard Deviation 0.626
Change in MEP Amplitude Baseline	0.395 Millivolts Standard Deviation 0.282	0.954 Millivolts Standard Deviation 1.402	1.098 Millivolts Standard Deviation 1.197
Change in MEP Amplitude Week 6	1.78 Millivolts Standard Deviation 1.568	0.914 Millivolts Standard Deviation 0.861	0.454 Millivolts Standard Deviation 0.339

SECONDARY outcome

Timeframe: Screening, Baseline, Week 6, Week 8

Population: Data of low quality were removed from analysis population as a result of the central reader's evaluation standards.

Cortical silent period (CSP) is the suppression of voluntary muscle contraction elicited by stimulation equal to 120% of resting motor threshold (RMT). CSP duration is measured from the time of the muscle activity suppression to return of muscle activity. Change in duration of cortical silent period is assessed by Transcranial Magnetic Stimulation (TMS).

Outcome measures

Measure	Oral Ezogabine 900 mg/Day n=19 Participants Ezogabine: Potiga is FDA-approved for adjunctive treatment of partial-onset seizures in patients aged 18 years and older who have responded inadequately to several alternative treatments.	Oral Ezogabine 600 mg/Day n=23 Participants Ezogabine: Potiga is FDA-approved for adjunctive treatment of partial-onset seizures in patients aged 18 years and older who have responded inadequately to several alternative treatments.	Placebo n=23 Participants Placebo: Matched placebo
Change in Duration of Cortical Silent Period Week 8	88.000 Milliseconds Standard Deviation 32.258	58.870 Milliseconds Standard Deviation 21761	87.479 Milliseconds Standard Deviation 39.839
Change in Duration of Cortical Silent Period Screening	99.542 Milliseconds Standard Deviation 39.153	69.273 Milliseconds Standard Deviation 29.921	88.831 Milliseconds Standard Deviation 39.519
Change in Duration of Cortical Silent Period Baseline	80.223 Milliseconds Standard Deviation 23.440	76.006 Milliseconds Standard Deviation 30.459	80.638 Milliseconds Standard Deviation 32.894
Change in Duration of Cortical Silent Period Week 6	96.844 Milliseconds Standard Deviation 43.426	74.917 Milliseconds Standard Deviation 36.338	83.479 Milliseconds Standard Deviation 32.920

SECONDARY outcome

Timeframe: Screening, Baseline, Week 6, Week 8

Population: Data of low quality were removed from analysis population as a result of the central reader's evaluation standards.

Paired-pulse Intracortical facilitation (ICF) is defined as the ratio of the response after a conditioning pulse equal to 80% of Resting Motor Threshold (RMT) is administered 15 milliseconds prior to the signaling pulse divided by Motor Evoked Potential (MEP) amplitude. ICF is calculated as the geometric mean of replicate estimates. Change in intracortical facilitation is assessed by Transcranial Magnetic Stimulation (TMS).

Outcome measures

Measure	Oral Ezogabine 900 mg/Day n=19 Participants Ezogabine: Potiga is FDA-approved for adjunctive treatment of partial-onset seizures in patients aged 18 years and older who have responded inadequately to several alternative treatments.	Oral Ezogabine 600 mg/Day n=23 Participants Ezogabine: Potiga is FDA-approved for adjunctive treatment of partial-onset seizures in patients aged 18 years and older who have responded inadequately to several alternative treatments.	Placebo n=23 Participants Placebo: Matched placebo
Change in Intracortical Facilitation Screening	1.829 Unitless Standard Deviation 0.862	1.849 Unitless Standard Deviation 1.669	1.653 Unitless Standard Deviation 0.907
Change in Intracortical Facilitation Baseline	2.420 Unitless Standard Deviation 2.356	2.073 Unitless Standard Deviation 2.075	1.531 Unitless Standard Deviation 0.906
Change in Intracortical Facilitation Week 6	1.894 Unitless Standard Deviation 1.177	1.535 Unitless Standard Deviation 1.472	1.571 Unitless Standard Deviation 1.298
Change in Intracortical Facilitation Week 8	1.779 Unitless Standard Deviation 1.627	1.466 Unitless Standard Deviation 0.836	1.514 Unitless Standard Deviation 0.817

SECONDARY outcome

Timeframe: Screening, Baseline, Week 6, Week 8

Population: Data of low quality were removed from analysis population as a result of the central reader's evaluation standards.

Change in depolarizing electrotonus at 90 to 100 milliseconds was assessed by threshold tracking axonal nerve conduction studies (TTNCS). TTNCS is a neurophysiologic test for assessing lower motor neuron function.

Outcome measures

Measure	Oral Ezogabine 900 mg/Day n=19 Participants Ezogabine: Potiga is FDA-approved for adjunctive treatment of partial-onset seizures in patients aged 18 years and older who have responded inadequately to several alternative treatments.	Oral Ezogabine 600 mg/Day n=23 Participants Ezogabine: Potiga is FDA-approved for adjunctive treatment of partial-onset seizures in patients aged 18 years and older who have responded inadequately to several alternative treatments.	Placebo n=23 Participants Placebo: Matched placebo
Change in Electrotonus Screening	52.275 percentage of threshold Standard Deviation 14.924	48.144 percentage of threshold Standard Deviation 8.636	44.532 percentage of threshold Standard Deviation 6.666
Change in Electrotonus Baseline	46.278 percentage of threshold Standard Deviation 7.663	48.901 percentage of threshold Standard Deviation 9.327	46.574 percentage of threshold Standard Deviation 6.689
Change in Electrotonus Week 6	50.187 percentage of threshold Standard Deviation 6.645	51.857 percentage of threshold Standard Deviation 7.303	44.898 percentage of threshold Standard Deviation 6.082
Change in Electrotonus Week 8	50.108 percentage of threshold Standard Deviation 2.533	48.552 percentage of threshold Standard Deviation 13.422	47.010 percentage of threshold Standard Deviation 6.212

SECONDARY outcome

Timeframe: Screening, Baseline, Week 6, Week 8

Population: Data of low quality were removed from analysis population as a result of the central reader's evaluation standards.

Assessed by threshold tracking axonal nerve conduction studies (TTNCS).

Outcome measures

Measure	Oral Ezogabine 900 mg/Day n=19 Participants Ezogabine: Potiga is FDA-approved for adjunctive treatment of partial-onset seizures in patients aged 18 years and older who have responded inadequately to several alternative treatments.	Oral Ezogabine 600 mg/Day n=23 Participants Ezogabine: Potiga is FDA-approved for adjunctive treatment of partial-onset seizures in patients aged 18 years and older who have responded inadequately to several alternative treatments.	Placebo n=23 Participants Placebo: Matched placebo
Change in Strength Duration Time Constant Week 8	0.341 Milliseconds Standard Deviation 0.079	0.461 Milliseconds Standard Deviation 0.134	0.497 Milliseconds Standard Deviation 0.173
Change in Strength Duration Time Constant Screening	0.521 Milliseconds Standard Deviation 0.084	0.451 Milliseconds Standard Deviation 0.096	0.505 Milliseconds Standard Deviation 0.086
Change in Strength Duration Time Constant Baseline	0.522 Milliseconds Standard Deviation 0.084	0.454 Milliseconds Standard Deviation 0.084	0.488 Milliseconds Standard Deviation 0.078
Change in Strength Duration Time Constant Week 6	0.416 Milliseconds Standard Deviation 0.141	0.480 Milliseconds Standard Deviation 0.165	0.546 Milliseconds Standard Deviation 0.120

SECONDARY outcome

Timeframe: Screening, Baseline, Week 6, Week 8

Population: Data of low quality were removed from analysis as a result of the central reader's evaluation standards.

Lower motor neuron excitability can be measured using change in recovery cycle of superexcitability. Change in recovery cycle of superexcitability after first pre-pulse is assessed by threshold tracking axonal nerve conduction studies (TTNCS). Threshold-tracking nerve conduction studies is a neurophysiologic test for assessing lower motor neuron function.

Outcome measures

Measure	Oral Ezogabine 900 mg/Day n=19 Participants Ezogabine: Potiga is FDA-approved for adjunctive treatment of partial-onset seizures in patients aged 18 years and older who have responded inadequately to several alternative treatments.	Oral Ezogabine 600 mg/Day n=23 Participants Ezogabine: Potiga is FDA-approved for adjunctive treatment of partial-onset seizures in patients aged 18 years and older who have responded inadequately to several alternative treatments.	Placebo n=23 Participants Placebo: Matched placebo
Change in Recovery Cycle Screening	-30.45 percentage of threshold Standard Deviation 8.694	-28.12 percentage of threshold Standard Deviation 8.401	-27.77 percentage of threshold Standard Deviation 7.955
Change in Recovery Cycle Baseline	-31.39 percentage of threshold Standard Deviation 6.896	-27.40 percentage of threshold Standard Deviation 6.993	-28.16 percentage of threshold Standard Deviation 7.589
Change in Recovery Cycle Week 6	-37.59 percentage of threshold Standard Deviation 5.066	-37.48 percentage of threshold Standard Deviation 7.451	-28.37 percentage of threshold Standard Deviation 7.835
Change in Recovery Cycle Week 8	-38.20 percentage of threshold Standard Deviation 4.965	-33.15 percentage of threshold Standard Deviation 13.874	-29.26 percentage of threshold Standard Deviation 5.880

SECONDARY outcome

Timeframe: Week 1 through Week 10

Population: Discrepancies in the number of subjects analyzed are a result of subjects with missed data collection during the specific time points.

Frequency of muscle cramping and maximum pain from muscle cramping was collected by subjects via self-report using a daily muscle cramping diary.

Outcome measures

Measure	Oral Ezogabine 900 mg/Day n=19 Participants Ezogabine: Potiga is FDA-approved for adjunctive treatment of partial-onset seizures in patients aged 18 years and older who have responded inadequately to several alternative treatments.	Oral Ezogabine 600 mg/Day n=23 Participants Ezogabine: Potiga is FDA-approved for adjunctive treatment of partial-onset seizures in patients aged 18 years and older who have responded inadequately to several alternative treatments.	Placebo n=23 Participants Placebo: Matched placebo
Muscle Cramping Frequency Week 1	12.176 Days Standard Deviation 15.233	8.738 Days Standard Deviation 14.477	9.536 Days Standard Deviation 15.909
Muscle Cramping Frequency Week 2	9.235 Days Standard Deviation 11.729	7.083 Days Standard Deviation 11.558	8.273 Days Standard Deviation 10.968
Muscle Cramping Frequency Week 3	10.906 Days Standard Deviation 13.532	7.750 Days Standard Deviation 12.268	10.170 Days Standard Deviation 13.915
Muscle Cramping Frequency Week 4	12.018 Days Standard Deviation 18.824	9.135 Days Standard Deviation 12.664	106.19 Days Standard Deviation 14.016
Muscle Cramping Frequency Week 5	12.533 Days Standard Deviation 15.824	10.265 Days Standard Deviation 13.404	8.955 Days Standard Deviation 13.268
Muscle Cramping Frequency Week 6	11.033 Days Standard Deviation 11.705	8.333 Days Standard Deviation 10.887	8.539 Days Standard Deviation 10.869
Muscle Cramping Frequency Week 7	9.400 Days Standard Deviation 10.716	9.714 Days Standard Deviation 12.755	9.609 Days Standard Deviation 12.551
Muscle Cramping Frequency Week 8	11.211 Days Standard Deviation 13.521	9.067 Days Standard Deviation 11.151	9.282 Days Standard Deviation 12.244
Muscle Cramping Frequency Week 9	12.786 Days Standard Deviation 14.154	9.933 Days Standard Deviation 11.750	11.190 Days Standard Deviation 16.162
Muscle Cramping Frequency Week 10	13.179 Days Standard Deviation 14.953	10.188 Days Standard Deviation 12.296	13.600 Days Standard Deviation 16.162

SECONDARY outcome

Timeframe: Screening, Baseline, Week 4, Week 6, Week 8, Week 12

Population: Discrepancies in the number of subjects analyzed are a result of subjects with missed data collection during the specific time points.

Hand held dynamometry (HHD) will be used as a quantitative measure of muscle strength of the abductor pollicis brevis (APB) muscle. HHD will be self-report by study participants using a daily muscle cramping diary.

Outcome measures

Measure	Oral Ezogabine 900 mg/Day n=19 Participants Ezogabine: Potiga is FDA-approved for adjunctive treatment of partial-onset seizures in patients aged 18 years and older who have responded inadequately to several alternative treatments.	Oral Ezogabine 600 mg/Day n=23 Participants Ezogabine: Potiga is FDA-approved for adjunctive treatment of partial-onset seizures in patients aged 18 years and older who have responded inadequately to several alternative treatments.	Placebo n=23 Participants Placebo: Matched placebo
Hand Held Dynamometry Force Measurement for Abductor Pollicis Brevis Screening	6.721 kilograms (kg) Standard Deviation 4.548	8.577 kilograms (kg) Standard Deviation 6.927	7.448 kilograms (kg) Standard Deviation 4.048
Hand Held Dynamometry Force Measurement for Abductor Pollicis Brevis Baseline	6.584 kilograms (kg) Standard Deviation 4.022	6.641 kilograms (kg) Standard Deviation 4.901	7.164 kilograms (kg) Standard Deviation 4.716
Hand Held Dynamometry Force Measurement for Abductor Pollicis Brevis Week 4	6.461 kilograms (kg) Standard Deviation 4.002	7.333 kilograms (kg) Standard Deviation 5.839	6.686 kilograms (kg) Standard Deviation 5.115
Hand Held Dynamometry Force Measurement for Abductor Pollicis Brevis Week 6	6.838 kilograms (kg) Standard Deviation 3.569	6.921 kilograms (kg) Standard Deviation 5.570	6.300 kilograms (kg) Standard Deviation 5.167
Hand Held Dynamometry Force Measurement for Abductor Pollicis Brevis Week 8	7.015 kilograms (kg) Standard Deviation 4.398	5.633 kilograms (kg) Standard Deviation 4.015	6.523 kilograms (kg) Standard Deviation 4.523
Hand Held Dynamometry Force Measurement for Abductor Pollicis Brevis Week 12	5.887 kilograms (kg) Standard Deviation 3.696	5.439 kilograms (kg) Standard Deviation 3.609	5.643 kilograms (kg) Standard Deviation 4.523

SECONDARY outcome

Timeframe: Week 1 through Week 10

Population: Discrepancies in the number of subjects analyzed are a result of subjects with missed data collection during the specific time points.

For the purpose of this study, a fasciculation is a brief, spontaneous contraction affecting a small number of muscle fibers, often causing a flicker of movement under the skin. Defining interference with daily activities may be different for each subject and defining daily activities will be different for each subject. Subjects will self report by diary, days with fasciculations.

Outcome measures

Measure	Oral Ezogabine 900 mg/Day n=19 Participants Ezogabine: Potiga is FDA-approved for adjunctive treatment of partial-onset seizures in patients aged 18 years and older who have responded inadequately to several alternative treatments.	Oral Ezogabine 600 mg/Day n=23 Participants Ezogabine: Potiga is FDA-approved for adjunctive treatment of partial-onset seizures in patients aged 18 years and older who have responded inadequately to several alternative treatments.	Placebo n=23 Participants Placebo: Matched placebo
Proportion of Days With Fasciculations Week 1	0.918 Proportion of Days Standard Deviation 0.134	0.659 Proportion of Days Standard Deviation 0.415	0.745 Proportion of Days Standard Deviation 0.368
Proportion of Days With Fasciculations Week 2	0.918 Proportion of Days Standard Deviation 0.229	0.637 Proportion of Days Standard Deviation 0.435	0.776 Proportion of Days Standard Deviation 0.325
Proportion of Days With Fasciculations Week 3	0.796 Proportion of Days Standard Deviation 0.366	0.648 Proportion of Days Standard Deviation 0.439	0.816 Proportion of Days Standard Deviation 0.334
Proportion of Days With Fasciculations Week 4	0.752 Proportion of Days Standard Deviation 0.352	0.637 Proportion of Days Standard Deviation 0.450	0.806 Proportion of Days Standard Deviation 0.348
Proportion of Days With Fasciculations Week 5	0.879 Proportion of Days Standard Deviation 0.285	0.659 Proportion of Days Standard Deviation 0.461	0.733 Proportion of Days Standard Deviation 0.374
Proportion of Days With Fasciculations Week 6	0.868 Proportion of Days Standard Deviation 0.288	0.714 Proportion of Days Standard Deviation 0.438	0.765 Proportion of Days Standard Deviation 0.418
Proportion of Days With Fasciculations Week 7	0.912 Proportion of Days Standard Deviation 0.277	0.767 Proportion of Days Standard Deviation 0.417	0.786 Proportion of Days Standard Deviation 0.379
Proportion of Days With Fasciculations Week 8	0.868 Proportion of Days Standard Deviation 0.294	0.688 Proportion of Days Standard Deviation 0.460	0.714 Proportion of Days Standard Deviation 0.432
Proportion of Days With Fasciculations Week 9	0.893 Proportion of Days Standard Deviation 0.293	0.657 Proportion of Days Standard Deviation 0.472	0.857 Proportion of Days Standard Deviation 0.296
Proportion of Days With Fasciculations Week 10	0.869 Proportion of Days Standard Deviation 0.319	0.700 Proportion of Days Standard Deviation 0.483	0.813 Proportion of Days Standard Deviation 0.380

SECONDARY outcome

Timeframe: 10 weeks

Participants will be judged tolerant of study drug if they reached their target dose and remain on study drug until planned discontinuation. Tolerability will be summarized as the proportion of participants in a treatment group who are tolerant of study drug.

Outcome measures

Measure	Oral Ezogabine 900 mg/Day n=19 Participants Ezogabine: Potiga is FDA-approved for adjunctive treatment of partial-onset seizures in patients aged 18 years and older who have responded inadequately to several alternative treatments.	Oral Ezogabine 600 mg/Day n=23 Participants Ezogabine: Potiga is FDA-approved for adjunctive treatment of partial-onset seizures in patients aged 18 years and older who have responded inadequately to several alternative treatments.	Placebo n=23 Participants Placebo: Matched placebo
Number of Participants Who Tolerate Study Drug	14 Participants	11 Participants	23 Participants

Adverse Events

Oral Ezogabine 900 mg/Day

Serious events: 1 serious events

Other events: 19 other events

Deaths: 0 deaths

Oral Ezogabine 600 mg/Day

Serious events: 2 serious events

Other events: 23 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Measure	Oral Ezogabine 900 mg/Day n=19 participants at risk Ezogabine: Potiga is FDA-approved for adjunctive treatment of partial-onset seizures in patients aged 18 years and older who have responded inadequately to several alternative treatments.	Oral Ezogabine 600 mg/Day n=23 participants at risk Ezogabine: Potiga is FDA-approved for adjunctive treatment of partial-onset seizures in patients aged 18 years and older who have responded inadequately to several alternative treatments.	Placebo n=23 participants at risk Placebo: Matched placebo
Infections and infestations Influenza	0.00% 0/19 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	4.3% 1/23 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Infections and infestations Pneumonia	0.00% 0/19 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	4.3% 1/23 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Nervous system disorders Cerebrovascular Accident	0.00% 0/19 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	4.3% 1/23 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Nervous system disorders Depressed Level of Consciousness	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.

Other adverse events

Measure	Oral Ezogabine 900 mg/Day n=19 participants at risk Ezogabine: Potiga is FDA-approved for adjunctive treatment of partial-onset seizures in patients aged 18 years and older who have responded inadequately to several alternative treatments.	Oral Ezogabine 600 mg/Day n=23 participants at risk Ezogabine: Potiga is FDA-approved for adjunctive treatment of partial-onset seizures in patients aged 18 years and older who have responded inadequately to several alternative treatments.	Placebo n=23 participants at risk Placebo: Matched placebo
Ear and labyrinth disorders Vertigo	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	4.3% 1/23 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Eye disorders Vision Blurred	10.5% 2/19 • Number of events 2 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	4.3% 1/23 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	8.7% 2/23 • Number of events 2 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Gastrointestinal disorders Abdominal Pain Lower	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Gastrointestinal disorders Constipation	21.1% 4/19 • Number of events 4 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	13.0% 3/23 • Number of events 3 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	8.7% 2/23 • Number of events 2 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Gastrointestinal disorders Diarrhoea	10.5% 2/19 • Number of events 2 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	8.7% 2/23 • Number of events 2 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	4.3% 1/23 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Gastrointestinal disorders Dry Mouth	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	4.3% 1/23 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Gastrointestinal disorders Hypoaesthesia Oral	10.5% 2/19 • Number of events 2 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	4.3% 1/23 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Gastrointestinal disorders Nausea	0.00% 0/19 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	13.0% 3/23 • Number of events 6 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	13.0% 3/23 • Number of events 3 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Gastrointestinal disorders Paraesthesia Oral	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	13.0% 3/23 • Number of events 5 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Gastrointestinal disorders Tongue Disorder	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
General disorders Asthenia	10.5% 2/19 • Number of events 2 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	13.0% 3/23 • Number of events 3 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
General disorders Fatigue	36.8% 7/19 • Number of events 7 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	47.8% 11/23 • Number of events 12 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	26.1% 6/23 • Number of events 6 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
General disorders Gait Disturbance	10.5% 2/19 • Number of events 2 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	4.3% 1/23 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
General disorders Oedema Peripheral	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
General disorders Pain	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
General disorders Pyrexia	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	4.3% 1/23 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Infections and infestations Bacterial Infection	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Infections and infestations Nasopharyngitis	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	8.7% 2/23 • Number of events 2 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Infections and infestations Upper Respiratory Tract Infection	10.5% 2/19 • Number of events 2 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	4.3% 1/23 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Injury, poisoning and procedural complications Contusion	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	4.3% 1/23 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Injury, poisoning and procedural complications Fall	21.1% 4/19 • Number of events 5 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	30.4% 7/23 • Number of events 7 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	17.4% 4/23 • Number of events 7 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Injury, poisoning and procedural complications Head Injury	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	4.3% 1/23 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Injury, poisoning and procedural complications Poisoning	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Injury, poisoning and procedural complications Post Lumbar Puncture Syndrome	0.00% 0/19 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	8.7% 2/23 • Number of events 2 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Injury, poisoning and procedural complications Skin Abrasion	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	4.3% 1/23 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Investigations Alanine Aminotransferase Increased	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Investigations Aspartate Aminotransferase Increased	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Investigations Bacterial Test	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Investigations Crystal Urine Present	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Investigations Electrocardiogram Qt Prolonged	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Investigations Weight Decreased	0.00% 0/19 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	8.7% 2/23 • Number of events 2 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Metabolism and nutrition disorders Decreased Appetite	0.00% 0/19 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	8.7% 2/23 • Number of events 2 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Musculoskeletal and connective tissue disorders Arthralgia	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	8.7% 2/23 • Number of events 2 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	4.3% 1/23 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Musculoskeletal and connective tissue disorders Back Pain	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	4.3% 1/23 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	4.3% 1/23 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Musculoskeletal and connective tissue disorders Muscle Spasms	10.5% 2/19 • Number of events 2 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	8.7% 2/23 • Number of events 2 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	21.7% 5/23 • Number of events 6 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Musculoskeletal and connective tissue disorders Muscular Weakness	10.5% 2/19 • Number of events 3 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	8.7% 2/23 • Number of events 2 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	13.0% 3/23 • Number of events 4 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Musculoskeletal and connective tissue disorders Musculoskeletal Chest Pain	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Musculoskeletal and connective tissue disorders Musculoskeletal Discomfort	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/19 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	8.7% 2/23 • Number of events 2 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	4.3% 1/23 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Nervous system disorders Aura	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Nervous system disorders Balance Disorder	10.5% 2/19 • Number of events 2 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	4.3% 1/23 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Nervous system disorders Cognitive Disorder	5.3% 1/19 • Number of events 2 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	4.3% 1/23 • Number of events 2 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	4.3% 1/23 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Nervous system disorders Dizziness	42.1% 8/19 • Number of events 9 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	21.7% 5/23 • Number of events 6 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	13.0% 3/23 • Number of events 3 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Nervous system disorders Dysarthria	10.5% 2/19 • Number of events 2 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	8.7% 2/23 • Number of events 2 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Nervous system disorders Dysstasia	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	4.3% 1/23 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Nervous system disorders Headache	10.5% 2/19 • Number of events 2 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	4.3% 1/23 • Number of events 3 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	21.7% 5/23 • Number of events 6 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Nervous system disorders Language Disorder	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	4.3% 1/23 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Nervous system disorders Memory Impairment	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Nervous system disorders Muscle Contractions Involuntary	15.8% 3/19 • Number of events 3 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	8.7% 2/23 • Number of events 2 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	4.3% 1/23 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Nervous system disorders Somnolence	36.8% 7/19 • Number of events 7 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	8.7% 2/23 • Number of events 2 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	4.3% 1/23 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Nervous system disorders Speech Disorder	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	4.3% 1/23 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Nervous system disorders Syncope	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	4.3% 1/23 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Psychiatric disorders Confusional State	15.8% 3/19 • Number of events 3 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	4.3% 1/23 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Psychiatric disorders Depression	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	4.3% 1/23 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Psychiatric disorders Disorientation	5.3% 1/19 • Number of events 3 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	4.3% 1/23 • Number of events 2 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Psychiatric disorders Euphoric Mood	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Psychiatric disorders Hallucination, Visual	21.1% 4/19 • Number of events 5 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Psychiatric disorders Mental Status Changes	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Psychiatric disorders Perseveration	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Renal and urinary disorders Chromaturia	10.5% 2/19 • Number of events 2 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	8.7% 2/23 • Number of events 2 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Renal and urinary disorders Urinary Hesitation	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	4.3% 1/23 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Renal and urinary disorders Urinary Retention	0.00% 0/19 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	17.4% 4/23 • Number of events 5 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	17.4% 4/23 • Number of events 5 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Respiratory, thoracic and mediastinal disorders Increased Viscosity Of Bronchial Secretion	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Respiratory, thoracic and mediastinal disorders Oropharyngeal Pain	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	4.3% 1/23 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Respiratory, thoracic and mediastinal disorders Sinus Congestion	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Respiratory, thoracic and mediastinal disorders Upper-Airway Cough Syndrome	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	4.3% 1/23 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Skin and subcutaneous tissue disorders Dermatitis Allergic	5.3% 1/19 • Number of events 1 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Skin and subcutaneous tissue disorders Erythema	5.3% 1/19 • Number of events 2 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	8.7% 2/23 • Number of events 5 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	4.3% 1/23 • Number of events 3 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Skin and subcutaneous tissue disorders Rash	0.00% 0/19 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	8.7% 2/23 • Number of events 2 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	0.00% 0/23 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.
Gastrointestinal disorders Hypersecretion	0.00% 0/19 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	8.7% 2/23 • Number of events 2 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.	8.7% 2/23 • Number of events 2 • Adverse Events were collected from the date the first subject signed consent, November 30, 2015, to the date the last subject completed the last study visit, February 27, 2018, a total of about 2 years, 3 months.

Additional Information

Protocol Investigator

Massachusetts General Hospital - Neurological Clinical Research Institute

Phone: 617-726-2000

Email: Brian.Wainger@MGH.HARVARD.EDU

Results disclosure agreements

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