Trial Outcomes & Findings for Hyper- and Hypokalemic Periodic Paralysis Study (NCT NCT00494507)

NCT ID: NCT00494507

Last Updated: 2017-06-14

Results Overview

The number of distinct attacks per week over the final 8 weeks (Weeks 2-9) of the double-blind treatment period as self-reported by HYP participants.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 71 participants
• Primary outcome timeframe: 8 weeks
• Results posted on: 2017-06-14

Participant Flow

The original trial design included an Acetazolamide (ACZ) drug arm which was subsequently removed. Five participants randomized to ACZ and one ineligible participant are not included in the trial results reported here.

Participant milestones

Measure	HYP Dichlorphenamide Hyperkalemic participants were randomized to Dichlorphenamide for a 9 week double-blind phase. All participants then received Dichlorphenamide for a 52 week open-label phase. Dichlorphenamide (double-blind): 50mg tablet; maximum dosage 400mg/day Dichlorphenamide (open-label): 50mg tablet; maximum dosage 400mg/day	HYP Placebo Hyperkalemic participants were randomized to Placebo for a 9 week double-blind phase. All participants then received Dichlorphenamide for a 52 week open-label phase. Placebo (double-blind): Inactive substance manufactured to look like Dichlorphenamide 50mg tablet Dichlorphenamide (open-label): 50mg tablet; maximum dosage 400mg/day	HOP Dichlorphenamide Hypokalemic participants were randomized to Dichlorphenamide for a 9 week double-blind phase. All participants then received Dichlorphenamide for a 52 week open-label phase. Dichlorphenamide (double-blind): 50mg tablet; maximum dosage 400mg/day Dichlorphenamide (open-label): 50mg tablet; maximum dosage 400mg/day	HOP Placebo Hypokalemic participants were randomized to Placebo for a 9 week double-blind phase. All participants then received Dichlorphenamide for a 52 week open-label phase. Placebo (double-blind): Inactive substance manufactured to look like Dichlorphenamide 50mg tablet Dichlorphenamide (open-label): 50mg tablet; maximum dosage 400mg/day
Double-Blind Phase STARTED	12	9	24	20
Double-Blind Phase Reached Endpoint of Acute Worsening	0	2	0	5
Double-Blind Phase COMPLETED	9	9	22	19
Double-Blind Phase NOT COMPLETED	3	0	2	1
Open-Label Phase STARTED	9	8	22	19
Open-Label Phase COMPLETED	9	7	17	14
Open-Label Phase NOT COMPLETED	0	1	5	5

Reasons for withdrawal

Measure	HYP Dichlorphenamide Hyperkalemic participants were randomized to Dichlorphenamide for a 9 week double-blind phase. All participants then received Dichlorphenamide for a 52 week open-label phase. Dichlorphenamide (double-blind): 50mg tablet; maximum dosage 400mg/day Dichlorphenamide (open-label): 50mg tablet; maximum dosage 400mg/day	HYP Placebo Hyperkalemic participants were randomized to Placebo for a 9 week double-blind phase. All participants then received Dichlorphenamide for a 52 week open-label phase. Placebo (double-blind): Inactive substance manufactured to look like Dichlorphenamide 50mg tablet Dichlorphenamide (open-label): 50mg tablet; maximum dosage 400mg/day	HOP Dichlorphenamide Hypokalemic participants were randomized to Dichlorphenamide for a 9 week double-blind phase. All participants then received Dichlorphenamide for a 52 week open-label phase. Dichlorphenamide (double-blind): 50mg tablet; maximum dosage 400mg/day Dichlorphenamide (open-label): 50mg tablet; maximum dosage 400mg/day	HOP Placebo Hypokalemic participants were randomized to Placebo for a 9 week double-blind phase. All participants then received Dichlorphenamide for a 52 week open-label phase. Placebo (double-blind): Inactive substance manufactured to look like Dichlorphenamide 50mg tablet Dichlorphenamide (open-label): 50mg tablet; maximum dosage 400mg/day
Double-Blind Phase Adverse Event	2	0	1	0
Double-Blind Phase Withdrawal by Subject	1	0	0	0
Double-Blind Phase Subject Non-compliance	0	0	1	0
Double-Blind Phase Negative DNA test	0	0	0	1
Open-Label Phase Adverse Event	0	1	5	3
Open-Label Phase Worsening Disease	0	0	0	2

Baseline Characteristics

Hyper- and Hypokalemic Periodic Paralysis Study

Baseline characteristics by cohort

Measure	HYP Dichlorphenamide n=12 Participants Hyperkalemic participants were randomized to Dichlorphenamide for a 9 week double-blind phase. All participants then received Dichlorphenamide for a 52 week open-label phase. Dichlorphenamide (double-blind): 50mg tablet; maximum dosage 400mg/day Dichlorphenamide (open-label): 50mg tablet; maximum dosage 400mg/day	HYP Placebo n=9 Participants Hyperkalemic participants were randomized to Placebo for a 9 week double-blind phase. All participants then received Dichlorphenamide for a 52 week open-label phase. Placebo (double-blind): Inactive substance manufactured to look like Dichlorphenamide 50mg tablet Dichlorphenamide (open-label): 50mg tablet; maximum dosage 400mg/day	HOP Dichlorphenamide n=24 Participants Hypokalemic participants were randomized to Dichlorphenamide for a 9 week double-blind phase. All participants then received Dichlorphenamide for a 52 week open-label phase. Dichlorphenamide (double-blind): 50mg tablet; maximum dosage 400mg/day Dichlorphenamide (open-label): 50mg tablet; maximum dosage 400mg/day	HOP Placebo n=20 Participants Hypokalemic participants were randomized to Placebo for a 9 week double-blind phase. All participants then received Dichlorphenamide for a 52 week open-label phase. Placebo (double-blind): Inactive substance manufactured to look like Dichlorphenamide 50mg tablet Dichlorphenamide (open-label): 50mg tablet; maximum dosage 400mg/day	Total n=65 Participants Total of all reporting groups
Age, Continuous	40.6 years STANDARD_DEVIATION 10.3 • n=5 Participants	45.2 years STANDARD_DEVIATION 17.7 • n=7 Participants	44.8 years STANDARD_DEVIATION 14.6 • n=5 Participants	44.0 years STANDARD_DEVIATION 15.6 • n=4 Participants	44.2 years STANDARD_DEVIATION 14.3 • n=21 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	6 Participants n=7 Participants	8 Participants n=5 Participants	4 Participants n=4 Participants	24 Participants n=21 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	3 Participants n=7 Participants	16 Participants n=5 Participants	16 Participants n=4 Participants	41 Participants n=21 Participants

PRIMARY outcome

Timeframe: 8 weeks

The number of distinct attacks per week over the final 8 weeks (Weeks 2-9) of the double-blind treatment period as self-reported by HYP participants.

Outcome measures

Measure	HYP Dichlorphenamide n=12 Participants Hyperkalemic participants randomized to Dichlorphenamide for a 9 week double-blind phase. Dichlorphenamide (double-blind): 50mg tablet; maximum dosage 400mg/day.	HYP Placebo n=9 Participants Hyperkalemic participants randomized to Placebo for a 9 week double-blind phase. Placebo (double-blind): Inactive substance manufactured to look like Dichlorphenamide 50mg tablet.
HYP Attack Rate	0.9 attacks per week Interval 0.4 to 1.5	4.8 attacks per week Interval 0.5 to 7.1

PRIMARY outcome

Timeframe: 8 weeks

The number of distinct attacks per week over the final 8 weeks (Weeks 2-9) of the double-blind treatment period as self-reported by HOP participants.

Outcome measures

Measure	HYP Dichlorphenamide n=24 Participants Hyperkalemic participants randomized to Dichlorphenamide for a 9 week double-blind phase. Dichlorphenamide (double-blind): 50mg tablet; maximum dosage 400mg/day.	HYP Placebo n=20 Participants Hyperkalemic participants randomized to Placebo for a 9 week double-blind phase. Placebo (double-blind): Inactive substance manufactured to look like Dichlorphenamide 50mg tablet.
HOP Attack Rate	0.3 attacks per week Interval 0.1 to 1.6	2.4 attacks per week Interval 0.5 to The upper quartile for the placebo group could not be calculated because more than 25% of placebo-treated subjects reached the endpoint of acute worsening.

SECONDARY outcome

Timeframe: 8 weeks

HYP participant severity-weighted attack rate is defined as the sum of average attack severity across all distinct attacks over the final 8 weeks (Weeks 2-9) of the double-blind treatment period divided by the number of weeks that the subject was followed. Attack severity (scored as 1-10 with increasing severity) is self-reported.

Outcome measures

Measure	HYP Dichlorphenamide n=12 Participants Hyperkalemic participants randomized to Dichlorphenamide for a 9 week double-blind phase. Dichlorphenamide (double-blind): 50mg tablet; maximum dosage 400mg/day.	HYP Placebo n=9 Participants Hyperkalemic participants randomized to Placebo for a 9 week double-blind phase. Placebo (double-blind): Inactive substance manufactured to look like Dichlorphenamide 50mg tablet.
HYP Severity-weighted Attack Rate	1.0 severity-weighted attacks per week Interval 0.4 to 2.9	5.8 severity-weighted attacks per week Interval 1.4 to 28.0

SECONDARY outcome

Timeframe: 8 weeks

HOP participant severity-weighted attack rate is defined as the sum of average attack severity across all distinct attacks over the final 8 weeks (Weeks 2-9) of the double-blind treatment period divided by the number of weeks that the subject was followed. Attack severity (scored as 1-10 with increasing severity) is self-reported.

Outcome measures

Measure	HYP Dichlorphenamide n=24 Participants Hyperkalemic participants randomized to Dichlorphenamide for a 9 week double-blind phase. Dichlorphenamide (double-blind): 50mg tablet; maximum dosage 400mg/day.	HYP Placebo n=20 Participants Hyperkalemic participants randomized to Placebo for a 9 week double-blind phase. Placebo (double-blind): Inactive substance manufactured to look like Dichlorphenamide 50mg tablet.
HOP Severity-weighted Attack Rate	0.6 severity-weighted attacks per week Interval 0.2 to 3.9	5.7 severity-weighted attacks per week Interval 1.2 to The upper quartile for the placebo group could not be calculated because more than 25% of placebo-treated subjects reached the endpoint of acute worsening and thus were assigned an arbitrarily large attack duration for purposes of analysis.

SECONDARY outcome

Timeframe: 8 weeks

HYP participant total attack duration per week, defined as the sum of attack durations across all distinct attacks over the final 8 weeks (Weeks 2-9) of the double-blind treatment period divided by the number of weeks that the subject was followed.

Outcome measures

Measure	HYP Dichlorphenamide n=12 Participants Hyperkalemic participants randomized to Dichlorphenamide for a 9 week double-blind phase. Dichlorphenamide (double-blind): 50mg tablet; maximum dosage 400mg/day.	HYP Placebo n=9 Participants Hyperkalemic participants randomized to Placebo for a 9 week double-blind phase. Placebo (double-blind): Inactive substance manufactured to look like Dichlorphenamide 50mg tablet.
HYP Attack Duration	10.5 hours per week Interval 2.5 to 21.3	39.4 hours per week Interval 6.2 to 139.4

SECONDARY outcome

Timeframe: 8 weeks

HOP participant total attack duration per week, defined as the sum of attack durations across all distinct attacks over the final 8 weeks (Weeks 2-9) of the double-blind treatment period divided by the number of weeks that the subject was followed.

Outcome measures

Measure	HYP Dichlorphenamide n=24 Participants Hyperkalemic participants randomized to Dichlorphenamide for a 9 week double-blind phase. Dichlorphenamide (double-blind): 50mg tablet; maximum dosage 400mg/day.	HYP Placebo n=20 Participants Hyperkalemic participants randomized to Placebo for a 9 week double-blind phase. Placebo (double-blind): Inactive substance manufactured to look like Dichlorphenamide 50mg tablet.
HOP Attack Duration	2.7 hours per week Interval 0.4 to 13.4	26.2 hours per week Interval 4.0 to The upper quartile for the placebo group could not be calculated because more than 25% of placebo-treated subjects reached the endpoint of acute worsening and thus were assigned an arbitrarily large attack duration for purposes of analysis.

SECONDARY outcome

Timeframe: 0-9 weeks

Increase in attack frequency or severity in HYP participants necessitating withdrawal from the initial nine-week double-blind treatment period and moving directly into the open-label phase.

Outcome measures

Measure	HYP Dichlorphenamide n=12 Participants Hyperkalemic participants randomized to Dichlorphenamide for a 9 week double-blind phase. Dichlorphenamide (double-blind): 50mg tablet; maximum dosage 400mg/day.	HYP Placebo n=9 Participants Hyperkalemic participants randomized to Placebo for a 9 week double-blind phase. Placebo (double-blind): Inactive substance manufactured to look like Dichlorphenamide 50mg tablet.
HYP Endpoint of Acute Worsening	0 participants	2 participants

SECONDARY outcome

Timeframe: 0-9 weeks

Increase in attack frequency or severity in HOP participants necessitating withdrawal from the initial nine-week double-blind treatment period and moving directly into the open-label phase.

Outcome measures

Measure	HYP Dichlorphenamide n=24 Participants Hyperkalemic participants randomized to Dichlorphenamide for a 9 week double-blind phase. Dichlorphenamide (double-blind): 50mg tablet; maximum dosage 400mg/day.	HYP Placebo n=20 Participants Hyperkalemic participants randomized to Placebo for a 9 week double-blind phase. Placebo (double-blind): Inactive substance manufactured to look like Dichlorphenamide 50mg tablet.
HOP Endpoint of Acute Worsening	0 participants	5 participants

SECONDARY outcome

Timeframe: Baseline and 9 weeks

Population: Participants with evaluable data at both timepoints

The strength of each of 26 individual muscles was graded using a modified 13-point Medical Research Council scale ranging from 0-5. Recorded grades were converted to numerical values as follows prior to averaging across muscles to form a composite score: 0 = 0; 1 = 1; 2- = 1.67; 2 = 2; 2+ = 2.33; 3- = 2.67; 3 = 3; 3+ = 3.33; 4- = 3.67; 4 = 4; 4+ = 4.33; 5- = 4.67; 5 = 5. A higher score represents a better outcome, i.e. 5 = normal strength.

The following muscles were tested: shoulder abductor (left/right), elbow extensor (left/right), elbow flexor (left/right), wrist extensor (left/right), wrist flexor (left/right), hip flexor (left/right), hip extensor (left/right), hip abductor (left/right), knee extensor (left/right), knee flexor (left/right), ankle dorsiflexor (left/right), ankle plantar flexor (left/right), neck extensor, neck flexor.

Outcome measures

Measure	HYP Dichlorphenamide n=11 Participants Hyperkalemic participants randomized to Dichlorphenamide for a 9 week double-blind phase. Dichlorphenamide (double-blind): 50mg tablet; maximum dosage 400mg/day.	HYP Placebo n=8 Participants Hyperkalemic participants randomized to Placebo for a 9 week double-blind phase. Placebo (double-blind): Inactive substance manufactured to look like Dichlorphenamide 50mg tablet.
HYP Change From Baseline to Week 9 in Average Manual Muscle Testing (MMT) Score	0.13 units on a scale Standard Deviation 0.26	0.00 units on a scale Standard Deviation 0.16

SECONDARY outcome

Timeframe: Baseline and 9 weeks

Population: Participants with evaluable data at both timepoints

The strength of each of 26 individual muscles was graded using a modified 13-point Medical Research Council scale ranging from 0-5. Recorded grades were converted to numerical values as follows prior to averaging across muscles to form a composite score: 0 = 0; 1 = 1; 2- = 1.67; 2 = 2; 2+ = 2.33; 3- = 2.67; 3 = 3; 3+ = 3.33; 4- = 3.67; 4 = 4; 4+ = 4.33; 5- = 4.67; 5 = 5. A higher score represents a better outcome, i.e. 5 = normal strength.

The following muscles were tested: shoulder abductor (left/right), elbow extensor (left/right), elbow flexor (left/right), wrist extensor (left/right), wrist flexor (left/right), hip flexor (left/right), hip extensor (left/right), hip abductor (left/right), knee extensor (left/right), knee flexor (left/right), ankle dorsiflexor (left/right), ankle plantar flexor (left/right), neck extensor, neck flexor.

Outcome measures

Measure	HYP Dichlorphenamide n=23 Participants Hyperkalemic participants randomized to Dichlorphenamide for a 9 week double-blind phase. Dichlorphenamide (double-blind): 50mg tablet; maximum dosage 400mg/day.	HYP Placebo n=17 Participants Hyperkalemic participants randomized to Placebo for a 9 week double-blind phase. Placebo (double-blind): Inactive substance manufactured to look like Dichlorphenamide 50mg tablet.
HOP Change From Baseline to Week 9 in Average Manual Muscle Testing (MMT) Score	0.05 units on a scale Standard Deviation 0.21	-0.08 units on a scale Standard Deviation 0.15

SECONDARY outcome

Timeframe: Baseline and 9 weeks

Population: Participants with evaluable data at both timepoints

The strength of each of 10 muscles was measured using quantitative myometry and expressed as the number of standard deviations from normal (Z-score) given the participant's age, gender, and height. The scores were averaged across muscles to form a composite MVICT score: average standardized MVICT score. A positive Z-score indicates a better outcome.

The following muscles were tested: elbow extensor (left/right), elbow flexor (left/right), knee extensor (left/right), knee flexor (left/right), and hand grip (left/right).

Outcome measures

Measure	HYP Dichlorphenamide n=10 Participants Hyperkalemic participants randomized to Dichlorphenamide for a 9 week double-blind phase. Dichlorphenamide (double-blind): 50mg tablet; maximum dosage 400mg/day.	HYP Placebo n=5 Participants Hyperkalemic participants randomized to Placebo for a 9 week double-blind phase. Placebo (double-blind): Inactive substance manufactured to look like Dichlorphenamide 50mg tablet.
HYP Change From Baseline to Week 9 in Average Maximum Voluntary Isometric Contraction Testing (MVICT) Scores	0.78 Z-score Standard Deviation 0.52	0.55 Z-score Standard Deviation 0.76

SECONDARY outcome

Timeframe: Baseline and 9 weeks

Population: Participants with evaluable data at both timepoints

The strength of each of 10 muscles was measured using quantitative myometry and expressed as the number of standard deviations from normal (Z-score) given the participant's age, gender, and height. The scores were averaged across muscles to form a composite MVICT score: average standardized MVICT score. A positive Z-score indicates a better outcome.

The following muscles were tested: elbow extensor (left/right), elbow flexor (left/right), knee extensor (left/right), knee flexor (left/right), and hand grip (left/right).

Outcome measures

Measure	HYP Dichlorphenamide n=21 Participants Hyperkalemic participants randomized to Dichlorphenamide for a 9 week double-blind phase. Dichlorphenamide (double-blind): 50mg tablet; maximum dosage 400mg/day.	HYP Placebo n=15 Participants Hyperkalemic participants randomized to Placebo for a 9 week double-blind phase. Placebo (double-blind): Inactive substance manufactured to look like Dichlorphenamide 50mg tablet.
HOP Change From Baseline to Week 9 in Average Maximum Voluntary Isometric Contraction Testing (MVICT) Scores	-0.08 Z-score Standard Deviation 0.92	-0.27 Z-score Standard Deviation 0.58

SECONDARY outcome

Timeframe: Baseline and 9 weeks

Population: Participants with evaluable data at both timepoints

The strength of each of 10 muscles was measured using quantitative myometry and expressed as the percent of predicted normal given the participant's age, gender, and height. The scores were averaged across muscles to form a composite MVICT score: average percent of predicted normal score. A higher number indicates a better outcome.

The following muscles were tested: elbow extensor (left/right), elbow flexor (left/right), knee extensor (left/right), knee flexor (left/right), and hand grip (left/right).

Outcome measures

Measure	HYP Dichlorphenamide n=10 Participants Hyperkalemic participants randomized to Dichlorphenamide for a 9 week double-blind phase. Dichlorphenamide (double-blind): 50mg tablet; maximum dosage 400mg/day.	HYP Placebo n=5 Participants Hyperkalemic participants randomized to Placebo for a 9 week double-blind phase. Placebo (double-blind): Inactive substance manufactured to look like Dichlorphenamide 50mg tablet.
HYP Change From Baseline to Week 9 in Average Maximum Voluntary Isometric Contraction Testing Percent of Predicted Normal	10.84 average percent of predicted normal Standard Deviation 8.27	10.17 average percent of predicted normal Standard Deviation 14.54

SECONDARY outcome

Timeframe: Baseline and 9 weeks

Population: Participants with evaluable data at both timepoints

The strength of each of 10 muscles was measured using quantitative myometry and expressed as the percent of predicted normal given the participant's age, gender, and height. The scores were averaged across muscles to form a composite MVICT score: average percent of predicted normal score. A higher number indicates a better outcome.

The following muscles were tested: elbow extensor (left/right), elbow flexor (left/right), knee extensor (left/right), knee flexor (left/right), and hand grip (left/right).

Outcome measures

Measure	HYP Dichlorphenamide n=21 Participants Hyperkalemic participants randomized to Dichlorphenamide for a 9 week double-blind phase. Dichlorphenamide (double-blind): 50mg tablet; maximum dosage 400mg/day.	HYP Placebo n=15 Participants Hyperkalemic participants randomized to Placebo for a 9 week double-blind phase. Placebo (double-blind): Inactive substance manufactured to look like Dichlorphenamide 50mg tablet.
HOP Change From Baseline to Week 9 in Average Maximum Voluntary Isometric Contraction Testing Percent of Predicted Normal	-0.81 average percent of predicted normal Standard Deviation 11.27	-2.94 average percent of predicted normal Standard Deviation 7.20

SECONDARY outcome

Timeframe: Baseline and 9 weeks

Population: Participants who had lean body mass data available at baseline and week 9.

Lean body mass was measured by dual-energy X-ray absorptiometry (DEXA).

Outcome measures

Measure	HYP Dichlorphenamide n=9 Participants Hyperkalemic participants randomized to Dichlorphenamide for a 9 week double-blind phase. Dichlorphenamide (double-blind): 50mg tablet; maximum dosage 400mg/day.	HYP Placebo n=6 Participants Hyperkalemic participants randomized to Placebo for a 9 week double-blind phase. Placebo (double-blind): Inactive substance manufactured to look like Dichlorphenamide 50mg tablet.
HYP Change From Baseline to Week 9 in Lean Body Mass	-1.31 kg Standard Deviation 1.94	-1.52 kg Standard Deviation 1.47

SECONDARY outcome

Timeframe: Baseline and 9 weeks

Population: Participants who had lean body mass data available at baseline and week 9.

Lean body mass was measured by dual-energy X-ray absorptiometry (DEXA).

Outcome measures

Measure	HYP Dichlorphenamide n=22 Participants Hyperkalemic participants randomized to Dichlorphenamide for a 9 week double-blind phase. Dichlorphenamide (double-blind): 50mg tablet; maximum dosage 400mg/day.	HYP Placebo n=15 Participants Hyperkalemic participants randomized to Placebo for a 9 week double-blind phase. Placebo (double-blind): Inactive substance manufactured to look like Dichlorphenamide 50mg tablet.
HOP Change From Baseline to Week 9 in Lean Body Mass	-0.78 kg Standard Deviation 1.65	0.44 kg Standard Deviation 2.39

SECONDARY outcome

Timeframe: Baseline and 9 weeks

Population: Participants with evaluable data at both timepoints

The Medical Outcomes Study Short Form (SF-36) questionnaire is a widely used profile measure of generic health-related quality of life. The 36 questions are allocated to eight scales: physical function (PF), physical role (RP), bodily pain (BP), general health perceptions (GH), vitality (VT), social function (SF), mental health (MH), and emotional role (RE). The physical component summary score is calculated from the four scales of PF, RP,BP, and GH. Scores are constructed as a T-score with a mean of 50 and standard deviation of 10 and no minimum or maximum score. Higher scores are associated with better quality of life.

Outcome measures

Measure	HYP Dichlorphenamide n=12 Participants Hyperkalemic participants randomized to Dichlorphenamide for a 9 week double-blind phase. Dichlorphenamide (double-blind): 50mg tablet; maximum dosage 400mg/day.	HYP Placebo n=8 Participants Hyperkalemic participants randomized to Placebo for a 9 week double-blind phase. Placebo (double-blind): Inactive substance manufactured to look like Dichlorphenamide 50mg tablet.
HYP Change From Baseline to Week 9 in SF-36 Physical Component Summary Score	3.16 T-score Standard Deviation 7.84	-0.11 T-score Standard Deviation 7.82

SECONDARY outcome

Timeframe: Baseline and 9 weeks

Population: Participants with evaluable data at both timepoints

The Medical Outcomes Study Short Form (SF-36) questionnaire is a widely used profile measure of generic health-related quality of life. The 36 questions are allocated to eight scales: physical function (PF), physical role (RP), bodily pain (BP), general health perceptions (GH), vitality (VT), social function (SF), mental health (MH), and emotional role (RE). The physical component summary score is calculated from the four scales of PF, RP, BP, and GH. Scores are constructed as a T-score with a mean of 50 and standard deviation of 10 and no minimum or maximum score. Higher scores are associated with better quality of life.

Outcome measures

Measure	HYP Dichlorphenamide n=20 Participants Hyperkalemic participants randomized to Dichlorphenamide for a 9 week double-blind phase. Dichlorphenamide (double-blind): 50mg tablet; maximum dosage 400mg/day.	HYP Placebo n=17 Participants Hyperkalemic participants randomized to Placebo for a 9 week double-blind phase. Placebo (double-blind): Inactive substance manufactured to look like Dichlorphenamide 50mg tablet.
HOP Change From Baseline to Week 9 in SF-36 Physical Component Summary Score	4.83 T-score Standard Deviation 7.23	-3.75 T-score Standard Deviation 10.61

SECONDARY outcome

Timeframe: Baseline and 9 weeks

Population: Participants with evaluable data at both timepoints

The Medical Outcomes Study Short Form (SF-36) questionnaire is a widely used profile measure of generic health-related quality of life. The 36 questions are allocated to eight scales: physical function (PF), physical role (RP), bodily pain (BP), general health perceptions (GH), vitality (VT), social function (SF), mental health (MH), and emotional role (RE). The mental health component summary score is calculated from the four scales of VT, SF, MH, and RE. Scores are constructed as a T-score with a mean of 50 and standard deviation of 10 and no minimum or maximum score. Higher scores are associated with better quality of life.

Outcome measures

Measure	HYP Dichlorphenamide n=12 Participants Hyperkalemic participants randomized to Dichlorphenamide for a 9 week double-blind phase. Dichlorphenamide (double-blind): 50mg tablet; maximum dosage 400mg/day.	HYP Placebo n=8 Participants Hyperkalemic participants randomized to Placebo for a 9 week double-blind phase. Placebo (double-blind): Inactive substance manufactured to look like Dichlorphenamide 50mg tablet.
HYP Change From Baseline to Week 9 in SF-36 Mental Health Component Summary Score	-3.77 T-score Standard Deviation 14.09	2.65 T-score Standard Deviation 8.64

SECONDARY outcome

Timeframe: Baseline and 9 weeks

Population: Participants with evaluable data at both timepoints

The Medical Outcomes Study Short Form (SF-36) questionnaire is a widely used profile measure of generic health-related quality of life. The 36 questions are allocated to eight scales: physical function (PF), physical role (RP), bodily pain (BP), general health perceptions (GH), vitality (VT), social function (SF), mental health (MH), and emotional role (RE). The mental health component summary score is calculated from the four scales of VT, SF, MH, and RE. Scores are constructed as a T-score with a mean of 50 and standard deviation of 10 and no minimum or maximum score. Higher scores are associated with better quality of life.

Outcome measures

Measure	HYP Dichlorphenamide n=20 Participants Hyperkalemic participants randomized to Dichlorphenamide for a 9 week double-blind phase. Dichlorphenamide (double-blind): 50mg tablet; maximum dosage 400mg/day.	HYP Placebo n=17 Participants Hyperkalemic participants randomized to Placebo for a 9 week double-blind phase. Placebo (double-blind): Inactive substance manufactured to look like Dichlorphenamide 50mg tablet.
HOP Change From Baseline to Week 9 in SF-36 Mental Health Component Summary Score	-1.10 T-score Standard Deviation 9.93	-5.65 T-score Standard Deviation 12.58

Adverse Events

HYP Double-Blind Dichlorphenamide

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

HYP Double-Blind Placebo

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

HYP Open-Label Dichlorphenamide

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

HOP Double-Blind Dichlorphenamide

Serious events: 0 serious events

Other events: 20 other events

Deaths: 0 deaths

HOP Double-Blind Placebo

Serious events: 1 serious events

Other events: 11 other events

Deaths: 0 deaths

HOP Open-Label Dichlorphenamide

Serious events: 3 serious events

Other events: 32 other events

Deaths: 0 deaths

Serious adverse events

Measure	HYP Double-Blind Dichlorphenamide n=12 participants at risk Hyperkalemic participants were randomized to Dichlorphenamide for the 9 week double-blind phase.	HYP Double-Blind Placebo n=9 participants at risk Hyperkalemic participants were randomized to Placebo for the 9 week double-blind phase.	HYP Open-Label Dichlorphenamide n=17 participants at risk Hyperkalemic participants received Dichlorphenamide for the 52 week open-label phase.	HOP Double-Blind Dichlorphenamide n=24 participants at risk Hypokalemic participants were randomized to Dichlorphenamide for the 9 week double-blind phase.	HOP Double-Blind Placebo n=20 participants at risk Hypokalemic participants were randomized to Placebo for the 9 week double-blind phase.	HOP Open-Label Dichlorphenamide n=40 participants at risk Hypokalemic participants received Dichlorphenamide for the 52 week open-label phase.
Injury, poisoning and procedural complications Humerus fracture	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.0% 1/20 • Number of events 1 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Injury, poisoning and procedural complications Road traffic accident	8.3% 1/12 • Number of events 1 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid cancer	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	2.5% 1/40 • Number of events 1 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	2.5% 1/40 • Number of events 1 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Nervous system disorders Cauda equina syndrome	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	2.5% 1/40 • Number of events 1 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Skin and subcutaneous tissue disorders Rash	8.3% 1/12 • Number of events 1 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.

Other adverse events

Measure	HYP Double-Blind Dichlorphenamide n=12 participants at risk Hyperkalemic participants were randomized to Dichlorphenamide for the 9 week double-blind phase.	HYP Double-Blind Placebo n=9 participants at risk Hyperkalemic participants were randomized to Placebo for the 9 week double-blind phase.	HYP Open-Label Dichlorphenamide n=17 participants at risk Hyperkalemic participants received Dichlorphenamide for the 52 week open-label phase.	HOP Double-Blind Dichlorphenamide n=24 participants at risk Hypokalemic participants were randomized to Dichlorphenamide for the 9 week double-blind phase.	HOP Double-Blind Placebo n=20 participants at risk Hypokalemic participants were randomized to Placebo for the 9 week double-blind phase.	HOP Open-Label Dichlorphenamide n=40 participants at risk Hypokalemic participants received Dichlorphenamide for the 52 week open-label phase.
Musculoskeletal and connective tissue disorders MUSCLE TWITCHING	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	8.3% 2/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	2.5% 1/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Ear and labyrinth disorders EAR PAIN	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.9% 1/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Ear and labyrinth disorders TINNITUS	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.0% 1/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	2.5% 1/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Eye disorders EYE PAIN	8.3% 1/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Eye disorders LACRIMATION INCREASED	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.0% 1/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Eye disorders PHOTOPSIA	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.9% 1/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Eye disorders VISION BLURRED	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.9% 1/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	4.2% 1/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	2.5% 1/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Eye disorders VISUAL DISTURBANCE	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	4.2% 1/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.0% 1/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	2.5% 1/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Gastrointestinal disorders ABDOMINAL PAIN UPPER	8.3% 1/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.9% 1/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	2.5% 1/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Gastrointestinal disorders CONSTIPATION	8.3% 1/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.0% 1/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.0% 2/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Gastrointestinal disorders DIARRHOEA	8.3% 1/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.9% 1/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	4.2% 1/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.0% 1/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.0% 2/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Gastrointestinal disorders DRY MOUTH	8.3% 1/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Gastrointestinal disorders GASTROOESOPHAGEAL REFLUX DISEASE	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.9% 1/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	4.2% 1/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.0% 2/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Gastrointestinal disorders NAUSEA	16.7% 2/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Gastrointestinal disorders VOMITING	8.3% 1/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	2.5% 1/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
General disorders ASTHENIA	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	11.1% 1/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.9% 1/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.0% 1/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	2.5% 1/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
General disorders FATIGUE	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.9% 1/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	12.5% 3/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	10.0% 4/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
General disorders MALAISE	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	8.3% 2/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
General disorders OEDEMA	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.0% 1/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	2.5% 1/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
General disorders OEDEMA PERIPHERAL	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.0% 1/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.0% 2/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
General disorders PAIN	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.9% 1/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
General disorders PYREXIA	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.9% 1/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	4.2% 1/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Immune system disorders CORNEAL GRAFT REJECTION	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.9% 1/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Infections and infestations CELLULITIS	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.0% 1/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	2.5% 1/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Infections and infestations CYSTITIS ESCHERICHIA	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.0% 1/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	2.5% 1/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Infections and infestations INFECTION	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.9% 1/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	2.5% 1/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Infections and infestations INFLUENZA	8.3% 1/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	2.5% 1/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Infections and infestations NASOPHARYNGITIS	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.9% 1/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	10.0% 2/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	7.5% 3/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Infections and infestations PHARYNGITIS STREPTOCOCCAL	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.9% 1/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Infections and infestations TONSILLITIS	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.9% 1/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Injury, poisoning and procedural complications CONCUSSION	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.0% 1/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Injury, poisoning and procedural complications FALL	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.9% 1/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	4.2% 1/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	10.0% 2/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	12.5% 5/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Injury, poisoning and procedural complications HEAD INJURY	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.0% 1/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Injury, poisoning and procedural complications MUSCLE STRAIN	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.9% 1/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Injury, poisoning and procedural complications RIB FRACTURE	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.0% 1/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	2.5% 1/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Injury, poisoning and procedural complications SPINAL FRACTURE	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.0% 1/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	2.5% 1/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Investigations BLOOD CHOLESTEROL INCREASED	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.0% 1/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	2.5% 1/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Investigations BLOOD GLUCOSE INCREASED	8.3% 1/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.9% 1/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Investigations WEIGHT DECREASED	16.7% 2/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Metabolism and nutrition disorders ANOREXIA	8.3% 1/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Musculoskeletal and connective tissue disorders ARTHRALGIA	8.3% 1/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	4.2% 1/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.0% 1/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.0% 2/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Musculoskeletal and connective tissue disorders MUSCLE SPASMS	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	12.5% 3/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	7.5% 3/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Musculoskeletal and connective tissue disorders MUSCULAR WEAKNESS	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.0% 1/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	2.5% 1/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL DISCOMFORT	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.0% 1/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL STIFFNESS	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.0% 1/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Musculoskeletal and connective tissue disorders MYALGIA	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.9% 1/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	2.5% 1/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Musculoskeletal and connective tissue disorders PAIN IN EXTREMITY	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	7.5% 3/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Nervous system disorders COGNITIVE DISORDER	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	20.8% 5/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	10.0% 2/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	20.0% 8/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Nervous system disorders DIZZINESS	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	8.3% 2/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	2.5% 1/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Nervous system disorders DYSARTHRIA	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.9% 1/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Nervous system disorders DYSGEUSIA	8.3% 1/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.9% 1/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	16.7% 4/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	12.5% 5/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Nervous system disorders HEADACHE	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	11.1% 1/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.9% 1/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	12.5% 3/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.0% 1/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	7.5% 3/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Nervous system disorders HYPOAESTHESIA	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	12.5% 3/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	2.5% 1/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Nervous system disorders LETHARGY	8.3% 1/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.9% 1/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	8.3% 2/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.0% 2/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Nervous system disorders MEMORY IMPAIRMENT	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	11.1% 1/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	11.8% 2/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Nervous system disorders PARAESTHESIA	66.7% 8/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	33.3% 3/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	52.9% 9/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	37.5% 9/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.0% 1/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	30.0% 12/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Nervous system disorders POLYNEUROPATHY	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.9% 1/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Psychiatric disorders CONFUSIONAL STATE	16.7% 2/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.9% 1/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	8.3% 2/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.0% 2/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Psychiatric disorders DEPRESSED MOOD	8.3% 1/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.9% 1/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	2.5% 1/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Psychiatric disorders DEPRESSION	8.3% 1/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.9% 1/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Psychiatric disorders NERVOUSNESS	8.3% 1/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Psychiatric disorders NIGHTMARE	8.3% 1/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Renal and urinary disorders NEPHROLITHIASIS	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	7.5% 3/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Respiratory, thoracic and mediastinal disorders DYSPNOEA	8.3% 1/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	4.2% 1/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Respiratory, thoracic and mediastinal disorders PHARYNGOLARYNGEAL PAIN	8.3% 1/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	4.2% 1/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	2.5% 1/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Skin and subcutaneous tissue disorders ACNE	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.9% 1/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Skin and subcutaneous tissue disorders DRY SKIN	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	4.2% 1/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.0% 1/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	2.5% 1/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Skin and subcutaneous tissue disorders OILY SKIN	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.0% 1/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Skin and subcutaneous tissue disorders PHOTOSENSITIVITY REACTION	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.0% 1/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Skin and subcutaneous tissue disorders PRURITUS	8.3% 1/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.9% 1/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	4.2% 1/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	2.5% 1/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Skin and subcutaneous tissue disorders RASH	8.3% 1/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.9% 1/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	4.2% 1/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.0% 1/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.0% 2/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.
Surgical and medical procedures FOOT OPERATION	0.00% 0/12 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/9 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	5.9% 1/17 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/24 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/20 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.	0.00% 0/40 Adverse events were assessed via weekly phone calls with participants and at all study visits. One HOP participant inadvertently remained on placebo during the open-label phase and therefore is not reported in the Other Adverse Events for the HOP Open-Label Dichlorphenamide group.

Additional Information

Robert Griggs, MD

University of Rochester

Phone: 585-275-3707

Email: robert_griggs@urmc.rochester.edu

Results disclosure agreements

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