Non-motor symptoms were evaluated using the NMSS which was divided into 30 questions in 9 different domains including such symptoms as dribbling saliva, constipation, depression, sleep disorders, apathy, hallucinations and dementia. Symptoms were quantified based on their severity (using a scale of 0 [none] to 3 [severe]) and frequency (using a scale of 0 [rarely] to 4 [very frequent]). Total score derived from adding up the product of the frequency score times severity score for each of the 30 questions. Total score ranged from 0 to 360, with a lower score indicating fewer symptoms.

The PDQ-39 is a self-administered questionnaire for participants with Parkinson's disease that has 39 questions grouped in 8 dimensions: mobility (items 1-10), activities of daily living (items 11-16), emotional well-being (items 17-22), stigma (items 23-26), social support (items 27-29), cognitions (items 30-33), communication (items 34-36), and bodily discomfort (items 37-39). Each item was scored on a 5-point Likert scale (0 to 4) to indicate the frequency of each event; 0 = never, 1 = occasionally, 2 = sometimes, 3 = often, and 4 = always or cannot do at all. Each dimension's total score ranged from 0-100, with lower scores indicating better health, and higher scores indicating more severe symptoms.

EQ-5D is a questionnaire designed to provide measures of health-related quality of life states, consisting of 5 domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Each dimension has a 3 point response scale designed to indicate the level of the problem: 1 = no problems, 2 = some problems, 3 = extreme problems. A higher score indicated an increase in the level of problem. The EQ-5D also contains a visual analog scale (EQ-VAS), which records the respondent's self-rated health status on a vertical graduated visual analog scale ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). Higher score indicated improvement.

MoCA is a 30-point questionnaire for cognitive dysfunction. It assesses different cognitive domains: attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. Scores on the MoCA range from 0-30 with 26-30 indicating normal global cognition; 18-25 mild cognitive impairment; 10-17 moderate cognitive impairment; and <10 severe cognitive impairment.

The BDI is a self-reporting 21-item scoring tool that measures characteristic attitudes and symptoms of depression, including physical symptoms. Each of the 21 items on BDI tool represent a depressive symptom. The symptoms are each scored on a 4-point Likert scale of 0 (symptom is absent) to 3 (symptom is severe). Scores for each symptom are added up to obtain the total scores for all 21 items, which are interpreted as follows 1-10 (normal); 11-16 (mild mood disturbance); 17-20 (borderline clinical depression); 21-30 (moderate depression); 31-40 (severe depression); and >40 (extreme depression). Participants with symptom score of 0 were not included in the summary.

The MADRS is a clinician-rated tool for measuring changes in depressive symptom severity. Ten core symptoms and cognitive features (feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and a lack of interest) were rated on a severity scale of 0 (no symptoms)) to 6 (symptoms of maximum severity). The total score was the sum of the scores on the 10 items, ranging from 0 to 60 with a higher score indicating increasing depressive symptoms.

Timed motor tests are simple, objective, quantitative measures for the assessment of Parkinson's disease. They include, in on-medication and off-medication state, timed recorded physical movements. Time Up and Go Test (TUG) is one of timed motor tests which is used to assess a person's mobility and requires both static and dynamic balance. This is a walking assessment. Participants start in the seated position, stand up, walk 7 meters, turn around, and sit back down. The entire process from leaving the chair to returning to the chair was timed. The total time was summarized under ON state with participants on dopamine therapy.

Glutathione lowest limit of quantification (LLOQ) = 0.01 micromoles (uM) and upper limit of quantification (ULOQ) = 27.83 uM in plasma.

Glutathione LLOQ = 0.002 uM and ULOQ = 0.35 uM in CSF.

Glutathione LLOQ = 0.01 uM, and ULOQ = 1.39 uM in urine.

The MDS-UPDRS is a tool for monitoring the impact of Parkinson's disease, the degree of disability caused, and complications from treatment. Part I (13 items) evaluates nonmotor experiences of daily living (nM-EDL); Part II (13 items) evaluates motor experiences of daily living (M-EDL; Part III (18 items) is a motor examination; Part IV (6 items) examines motor complications (for example, motor fluctuations and dyskinesias). Each item was rated on a 5-point scale, ranging from 0 (normal) to 4 (severe), with higher score indicating greater severity and more impairment. Total score for Part I (nM-EDL) and Part II (M-EDL) each ranges from 0-52; for Part III (motor examination) ranges from 0-72; and for Part IV (motor complications) ranges from 0-24; with higher scores in each range for all 4 parts reflecting greater severity.

Efficacy intent-to-treat (EITT) population included any participant who received at least 1 dose of PTC589 and had a minimum of the Month 3 assessment.

Non-motor symptoms were evaluated using the NMSS which was divided into 30 questions in 9 different domains including such symptoms as dribbling saliva, constipation, depression, sleep disorders, apathy, hallucinations and dementia. Symptoms were quantified based on their severity (using a scale of 0 [none] to 3 [severe]) and frequency (using a scale of 0 [rarely] to 4 [very frequent]). Total score derived from adding up the product of the frequency score times severity score for each of the 30 questions. Total score ranged from 0 to 360, with a lower score indicating fewer symptoms.

EITT population included any participant who received at least 1 dose of PTC589 and had a minimum of the Month 3 assessment.

The PDQ-39 is a self-administered questionnaire for participants with Parkinson's disease that has 39 questions grouped in 8 dimensions: mobility (items 1-10), activities of daily living (items 11-16), emotional well-being (items 17-22), stigma (items 23-26), social support (items 27-29), cognitions (items 30-33), communication (items 34-36), and bodily discomfort (items 37-39). Each item was scored on a 5-point Likert scale (0 to 4) to indicate the frequency of each event; 0 = never, 1 = occasionally, 2 = sometimes, 3 = often, and 4 = always or cannot do at all. Each dimension's total score ranged from 0-100, with lower scores indicating better health, and higher scores indicating more severe symptoms.

EITT population included any participant who received at least 1 dose of PTC589 and had a minimum of the Month 3 assessment.

EQ-5D is a questionnaire designed to provide measures of health-related quality of life states, consisting of 5 domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Each dimension has a 3 point response scale designed to indicate the level of the problem: 1 = no problems, 2 = some problems, 3 = extreme problems. A higher score indicated an increase in the level of problem. The EQ-5D also contains a visual analog scale (EQ-VAS), which records the respondent's self-rated health status on a vertical graduated visual analog scale ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). Higher score indicated improvement.

EITT population included any participant who received at least 1 dose of PTC589 and had a minimum of the Month 3 assessment.

MoCA is a 30-point questionnaire for cognitive dysfunction. It assesses different cognitive domains: attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. Scores on the MoCA range from 0-30 with 26-30 indicating normal global cognition; 18-25 mild cognitive impairment; 10-17 moderate cognitive impairment; and <10 severe cognitive impairment.

EITT population included any participant who received at least 1 dose of PTC589 and had a minimum of the Month 3 assessment. Here, 'Number analyzed' signifies participants with normal, mild, moderate, or severe cognition impairment. Data for a specific severity level was not collected if no evaluable participants were available.

The BDI is a self-reporting 21-item scoring tool that measures characteristic attitudes and symptoms of depression, including physical symptoms. Each of the 21 items on BDI tool represent a depressive symptom. The symptoms are each scored on a 4-point Likert scale of 0 (symptom is absent) to 3 (symptom is severe). Scores for each symptom are added up to obtain the total scores for all 21 items, which are interpreted as follows 1-10 (normal); 11-16 (mild mood disturbance); 17-20 (borderline clinical depression); 21-30 (moderate depression); 31-40 (severe depression); and >40 (extreme depression). Participants with symptom score of 0 were not included in the summary.

EITT population included any participant who received at least 1 dose of PTC589 and had a minimum of Month 3 assessment. 'Number analyzed' = participants with symptom score >1 for normal, mild, borderline, moderate, severe, or extreme depression. Data for a specific severity level was not collected if no evaluable participants were available.

The MADRS is a clinician-rated tool for measuring changes in depressive symptom severity. Ten core symptoms and cognitive features (feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty concentrating, and a lack of interest) were rated on a severity scale of 0 (no symptoms)) to 6 (symptoms of maximum severity). The total score was the sum of the scores on the 10 items, ranging from 0 to 60 with a higher score indicating increasing depressive symptoms.

EITT population included any participant who received at least 1 dose of PTC589 and had a minimum of the Month 3 assessment.

Timed motor tests are simple, objective, quantitative measures for the assessment of Parkinson's disease. They include, in on-medication and off-medication state, timed recorded physical movements. Time Up and Go Test (TUG) is one of timed motor tests which is used to assess a person's mobility and requires both static and dynamic balance. This is a walking assessment. Participants start in the seated position, stand up, walk 7 meters, turn around, and sit back down. The entire process from leaving the chair to returning to the chair was timed. The total time was summarized under ON state with participants on dopamine therapy.

EITT population included any participant who received at least 1 dose of PTC589 and had a minimum of the Month 3 assessment. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

EITT population included any participant who received at least 1 dose of PTC589 and had a minimum of the Month 3 assessment. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Glutathione lowest limit of quantification (LLOQ) = 0.01 micromoles (uM) and upper limit of quantification (ULOQ) = 27.83 uM in plasma.

EITT population included any participant who received at least 1 dose of EPI-589.

Glutathione LLOQ = 0.002 uM and ULOQ = 0.35 uM in CSF.

EITT population included any participant who received at least 1 dose of EPI-589. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Glutathione LLOQ = 0.01 uM, and ULOQ = 1.39 uM in urine.

EITT population included any participant who received at least 1 dose of EPI-589.