Trial Outcomes & Findings for A Long Term Safety Study of ND0612 Administered as a Continuous SC Infusion in Advanced Parkinson's Disease (NCT NCT02726386)

Last Updated: 2025-05-30

Results Overview

Long-term safety (systemic and local) assessment will be based on adverse events (AEs), with a focus on adverse events of special interest (AESI), i.e., infusion site reactions, cases of hypersensitivity, polyneuropathy.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

214 participants

Primary outcome timeframe

Baseline to Month 12

Results posted on

2025-05-30

Participant Flow

Participant milestones

Participant milestones
Measure	24-hour Dosing Regimen Continuous SC infusion over 24 hours: fixed day rate of up to 0.64 mL/h for 18 hours, followed by a night rate of 0.08 mL/h for 6 hours to deliver a total daily dose of up to 720/90 mg of levodopa/carbidopa. All patients who had been previously assigned to the 24-hour group in the prior study continued on this dosing regimen; patients who had previously been assigned to the 14-hour daytime regimen were switched to the 24-hour regimen. ND0612: ND0612, a solution of levodopa/carbidopa (LD/CD) delivered continuously subcutaneously (SC) via an infusion pump system	16-hour Dosing Regimen Continuous SC infusion for over 16 hours: fixed rate of 0.75 mL/h to deliver a total infusion dose of 720/90 mg of levodopa/carbidopa over 16 hours. The device is removed at night and patients in this group also receive a morning oral dose of levodopa/carbidopa upon awakening. ND0612: ND0612, a solution of levodopa/carbidopa (LD/CD) delivered continuously subcutaneously (SC) via an infusion pump system
Overall Study STARTED	90	124
Overall Study COMPLETED	52	68
Overall Study NOT COMPLETED	38	56

Reasons for withdrawal

Reasons for withdrawal
Measure	24-hour Dosing Regimen Continuous SC infusion over 24 hours: fixed day rate of up to 0.64 mL/h for 18 hours, followed by a night rate of 0.08 mL/h for 6 hours to deliver a total daily dose of up to 720/90 mg of levodopa/carbidopa. All patients who had been previously assigned to the 24-hour group in the prior study continued on this dosing regimen; patients who had previously been assigned to the 14-hour daytime regimen were switched to the 24-hour regimen. ND0612: ND0612, a solution of levodopa/carbidopa (LD/CD) delivered continuously subcutaneously (SC) via an infusion pump system	16-hour Dosing Regimen Continuous SC infusion for over 16 hours: fixed rate of 0.75 mL/h to deliver a total infusion dose of 720/90 mg of levodopa/carbidopa over 16 hours. The device is removed at night and patients in this group also receive a morning oral dose of levodopa/carbidopa upon awakening. ND0612: ND0612, a solution of levodopa/carbidopa (LD/CD) delivered continuously subcutaneously (SC) via an infusion pump system
Overall Study Adverse Event	17	20
Overall Study Withdrawal by Subject	14	28
Overall Study Other reasons	7	8

Baseline Characteristics

A Long Term Safety Study of ND0612 Administered as a Continuous SC Infusion in Advanced Parkinson's Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	24-hour Dosing Regimen n=90 Participants Continuous SC infusion over 24 hours: fixed day rate of up to 0.64 mL/h for 18 hours, followed by a night rate of 0.08 mL/h for 6 hours to deliver a total daily dose of up to 720/90 mg of levodopa/carbidopa. All patients who had been previously assigned to the 24-hour group in the prior study continued on this dosing regimen; patients who had previously been assigned to the 14-hour daytime regimen were switched to the 24-hour regimen. ND0612: ND0612, a solution of levodopa/carbidopa (LD/CD) delivered continuously subcutaneously (SC) via an infusion pump system	16-hour Dosing Regimen n=124 Participants Continuous SC infusion for over 16 hours: fixed rate of 0.75 mL/h to deliver a total infusion dose of 720/90 mg of levodopa/carbidopa over 16 hours. The device is removed at night and patients in this group also receive a morning oral dose of levodopa/carbidopa upon awakening. ND0612: ND0612, a solution of levodopa/carbidopa (LD/CD) delivered continuously subcutaneously (SC) via an infusion pump system	Total n=214 Participants Total of all reporting groups
Age, Continuous	64.2 years STANDARD_DEVIATION 8.9 • n=5 Participants	63.9 years STANDARD_DEVIATION 8.9 • n=7 Participants	64.0 years STANDARD_DEVIATION 8.9 • n=5 Participants
Age, Customized Age (years) · <65 years	43 Participants n=5 Participants	63 Participants n=7 Participants	106 Participants n=5 Participants
Age, Customized Age (years) · ≥65 years	47 Participants n=5 Participants	61 Participants n=7 Participants	108 Participants n=5 Participants
Sex: Female, Male Female	32 Participants n=5 Participants	40 Participants n=7 Participants	72 Participants n=5 Participants
Sex: Female, Male Male	58 Participants n=5 Participants	84 Participants n=7 Participants	142 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Caucasian	86 Participants n=5 Participants	116 Participants n=7 Participants	202 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Other	4 Participants n=5 Participants	8 Participants n=7 Participants	12 Participants n=5 Participants
BMI	27.0 kg/m^2 STANDARD_DEVIATION 5.5 • n=5 Participants	27.2 kg/m^2 STANDARD_DEVIATION 5.9 • n=7 Participants	27.1 kg/m^2 STANDARD_DEVIATION 5.7 • n=5 Participants
BMI <20 kg/m2	11 Participants n=5 Participants	11 Participants n=7 Participants	22 Participants n=5 Participants
BMI ≥20 kg/m2	79 Participants n=5 Participants	113 Participants n=7 Participants	192 Participants n=5 Participants
Modified Hoehn & Yahr <2	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Modified Hoehn & Yahr 2	37 Participants n=5 Participants	52 Participants n=7 Participants	89 Participants n=5 Participants
Modified Hoehn & Yahr 2.5	17 Participants n=5 Participants	32 Participants n=7 Participants	49 Participants n=5 Participants
Modified Hoehn & Yahr 3	32 Participants n=5 Participants	35 Participants n=7 Participants	67 Participants n=5 Participants
MMSE total score	28.8 Points STANDARD_DEVIATION 1.2 • n=5 Participants	28.8 Points STANDARD_DEVIATION 1.2 • n=7 Participants	28.8 Points STANDARD_DEVIATION 1.2 • n=5 Participants
Time since PD diagnosis	10.6 years STANDARD_DEVIATION 5.3 • n=5 Participants	7.9 years STANDARD_DEVIATION 3.8 • n=7 Participants	9.0 years STANDARD_DEVIATION 4.7 • n=5 Participants
Time since onset of fluctuations	5.3 years STANDARD_DEVIATION 4.3 • n=5 Participants	5.2 years STANDARD_DEVIATION 4.2 • n=7 Participants	5.3 years STANDARD_DEVIATION 4.2 • n=5 Participants
Total daily levodopa dose	1090 mg STANDARD_DEVIATION 623 • n=5 Participants	1004 mg STANDARD_DEVIATION 540 • n=7 Participants	1040 mg STANDARD_DEVIATION 577 • n=5 Participants
Total daily levodopa frequency	5.9 Times per day STANDARD_DEVIATION 2.2 • n=5 Participants	5.1 Times per day STANDARD_DEVIATION 1.7 • n=7 Participants	5.5 Times per day STANDARD_DEVIATION 2.0 • n=5 Participants
Concomitant medications Dopamine agonists	52 Participants n=5 Participants	58 Participants n=7 Participants	110 Participants n=5 Participants
Concomitant medications MAO-B inhibitors	37 Participants n=5 Participants	44 Participants n=7 Participants	81 Participants n=5 Participants
Concomitant medications COMT inhibitors	28 Participants n=5 Participants	24 Participants n=7 Participants	52 Participants n=5 Participants
Concomitant medications Amantadine	25 Participants n=5 Participants	30 Participants n=7 Participants	55 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to Month 12

Population: Safety set

Outcome measures

Outcome measures
Measure	24-hour Dosing Regimen n=90 Participants Continuous SC infusion over 24 hours: fixed day rate of up to 0.64 mL/h for 18 hours, followed by a night rate of 0.08 mL/h for 6 hours to deliver a total daily dose of up to 720/90 mg of levodopa/carbidopa. All patients who had been previously assigned to the 24-hour group in the prior study continued on this dosing regimen; patients who had previously been assigned to the 14-hour daytime regimen were switched to the 24-hour regimen. ND0612: ND0612, a solution of levodopa/carbidopa (LD/CD) delivered continuously subcutaneously (SC) via an infusion pump system	16-hour Dosing Regimen n=124 Participants Continuous SC infusion for over 16 hours: fixed rate of 0.75 mL/h to deliver a total infusion dose of 720/90 mg of levodopa/carbidopa over 16 hours. The device is removed at night and patients in this group also receive a morning oral dose of levodopa/carbidopa upon awakening. ND0612: ND0612, a solution of levodopa/carbidopa (LD/CD) delivered continuously subcutaneously (SC) via an infusion pump system
Adverse Events (Long-term Safety) Drug-related TEAEs	65 Participants	78 Participants
Adverse Events (Long-term Safety) Death	0 Participants	1 Participants
Adverse Events (Long-term Safety) Any TEAE	78 Participants	105 Participants
Adverse Events (Long-term Safety) Infusion site TEAEs	55 Participants	66 Participants
Adverse Events (Long-term Safety) Serious TEAEs	17 Participants	14 Participants

PRIMARY outcome

Timeframe: Baseline to Month 12

Population: Intention-to-Treat (ITT) set

Tolerability will be assessed based on the percentage of subjects that complete the 12-month treatment period of the study and the percentage of subjects who discontinue from the 12-month treatment period due to an AE.

Outcome measures

Outcome measures
Measure	24-hour Dosing Regimen n=90 Participants Continuous SC infusion over 24 hours: fixed day rate of up to 0.64 mL/h for 18 hours, followed by a night rate of 0.08 mL/h for 6 hours to deliver a total daily dose of up to 720/90 mg of levodopa/carbidopa. All patients who had been previously assigned to the 24-hour group in the prior study continued on this dosing regimen; patients who had previously been assigned to the 14-hour daytime regimen were switched to the 24-hour regimen. ND0612: ND0612, a solution of levodopa/carbidopa (LD/CD) delivered continuously subcutaneously (SC) via an infusion pump system	16-hour Dosing Regimen n=124 Participants Continuous SC infusion for over 16 hours: fixed rate of 0.75 mL/h to deliver a total infusion dose of 720/90 mg of levodopa/carbidopa over 16 hours. The device is removed at night and patients in this group also receive a morning oral dose of levodopa/carbidopa upon awakening. ND0612: ND0612, a solution of levodopa/carbidopa (LD/CD) delivered continuously subcutaneously (SC) via an infusion pump system
Percentages of Subjects Who Complete the 12-month Treatment Period or Discontinue Due to AE (Tolerability) Completed the 12-month treatment period	52 Participants	68 Participants
Percentages of Subjects Who Complete the 12-month Treatment Period or Discontinue Due to AE (Tolerability) Discontinued due to AE	17 Participants	20 Participants

SECONDARY outcome

Timeframe: Month 12 to Month 102

Long-term safety (systemic and local) and tolerability will be based on AEs, with a focus on AESI, i.e., infusion site reactions, cases of hypersensitivity, polyneuropathy.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Month 12

Exploratory endpoint. "ON" time without troublesome dyskinesia is defined as the sum of "ON" time without dyskinesia and "ON" time with non-troublesome dyskinesia. Daily "ON" time without troublesome dyskinesia will be assessed based on home "ON/OFF" diaries and normalized to 16 hours of awake time.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Month 12

Exploratory endpoint. Daily "OFF" time will be assessed based on home "ON/OFF" diaries and normalized to 16 hours of awake time.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Month 12

Exploratory endpoint. Total daily dose of oral Levodopa (LD)/Dopa-Decarboxylase Inhibitor (DDI).

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Month 12

Exploratory endpoint. A responder is defined as a subject that experiences ≥50% reduction in "OFF" time from Baseline. Improvement of ≥50% in "OFF" time will be assessed based on home "ON/OFF" diaries and normalized to 16 hours of awake time.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Month 12

Exploratory endpoint. Daily "ON" time with troublesome dyskinesia will be assessed based on home "ON/OFF" diaries in a subset of subjects who had more than 1 hour of troublesome dyskinesia at baseline. It will be normalized to 16 hours of awake time.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Month 12

Exploratory endpoint. Quality of Life in Parkinson's Disease (PDQ)-39 is a 39-item, self-administered questionnaire with 8 discrete dimensions (mobility, activities of daily living, emotional well-being, stigma, social support, cognition, communication, and bodily discomfort.). The PDQ-39 Summary Index is the sum of the dimension scores divided by the number of dimensions. Higher scores indicate a worse quality of life.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Month 12

Exploratory endpoint. The perception of general quality of life (QoL) will be rated by the subjects using the EuroQoL 5-dimensions 5-severity levels (EQ-5D-5L) questionnaire. The EQ-5D-5L consists of 2 pages, the EQ-5D-5L descriptive system and the EQ Visual Analogue Scale (VAS). The descriptive system comprises 5 dimensions (mobility, self care, usual activities, pain/discomfort, anxiety/depression). Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The EQ VAS records the respondent's self-rated health on a 20 cm vertical VAS with endpoints labelled 'the best health you can imagine' and 'the worst health you can imagine'. Decrease in the 5-dimensions scores and increase in EQ VAS score will indicate improvement.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Month 12

Exploratory endpoint. The Unified Parkinson's disease rating scale (UPDRS) is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. The UPDRS Part II (activity of daily living) score was calculated as the sum of the individual UPDRS items 5-17. The Part II score is the sum of the answers to the 13 questions that comprise Part II, each of which are measured on a 5-point scale (i.e., 0 is normal and 4 indicates a severe abnormality). Higher scores correlate with greater impairments for daily activities.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Month 12

Exploratory endpoint. Clinical Global Impression (CGI) Severity (CGI-S) and Improvement (CGI-I) are rated by the investigator or designee. CGI-S employs a 7-point scale with 1 being "not at all ill" and 7 being "among the most severely ill subjects" for severity rating. The CGI-I employs a 7-point scale with 1 being "very much improved" and 7 being "very much worse" for improvement rating.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Month 12

Exploratory endpoint. Subjects Global Impression of Improvement (SGI-I) is rated by the subject. The SGI-I employs a 7-point scale with 1 being "very much improved" and 7 being "very much worse" for improvement rating.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Month 12

Exploratory endpoint. The quality of night sleep is rated by the subjects using the Parkinson's Disease Sleep Scale (PDSS)-2, which includes questions addressing 15 commonly reported symptoms associated with sleep disturbance in PD. Higher scores indicate a lower quality of sleep, i.e., a reduction in the score indicates an improvement in sleep quality.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Month 12

Exploratory endpoint. The Unified Parkinson's Disease Rating Scale (UPDRS) is an Investigator-used rating tool to follow the longitudinal course of Parkinson's disease. UPDRS part III (motor) score is calculated as the sum of the individual UPDRS items 18-31, each of which are measured on a 5-point scale (i.e., 0 is normal and 4 indicates a severe abnormality). Higher scores correlate with greater motor impairment.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Month 12

Exploratory endpoint. Good "ON" time (or "ON" time without troublesome dyskinesia) is defined as the sum of "ON" time without dyskinesia and "ON" time with non-troublesome dyskinesia. For this endpoint, Good "ON" time and "OFF" time will be assessed based on home "ON/OFF" diaries during the first 3 hours since the subject is awake after 06:00 (6 am).

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Month 12

Exploratory endpoint. Change in ND0612 total daily dose.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Month 102

Exploratory endpoint. Proportion of patients who reduced ND0612 total dose at any time during the study.

Outcome measures

Outcome data not reported

Adverse Events

24-hour Dosing Regimen

Serious events: 17 serious events

Other events: 69 other events

Deaths: 0 deaths

16-hour Dosing Regimen

Serious events: 14 serious events

Other events: 82 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Laurence Salin, MD, Senior Medical Director

NeuroDerm Ltd.

Phone: +33687548073

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The sponsor must review and approve any results of the study or abstracts for professional meetings prepared by the investigator(s). Published data must not compromise the objectives of the study. Data from individual study centers in multicenter studies must not be published separately.
Publication restrictions are in place

Restriction type: OTHER

Measure	24-hour Dosing Regimen n=90 participants at risk Continuous SC infusion over 24 hours: fixed day rate of up to 0.64 mL/h for 18 hours, followed by a night rate of 0.08 mL/h for 6 hours to deliver a total daily dose of up to 720/90 mg of levodopa/carbidopa. All patients who had been previously assigned to the 24-hour group in the prior study continued on this dosing regimen; patients who had previously been assigned to the 14-hour daytime regimen were switched to the 24-hour regimen. ND0612: ND0612, a solution of levodopa/carbidopa (LD/CD) delivered continuously subcutaneously (SC) via an infusion pump system	16-hour Dosing Regimen n=124 participants at risk Continuous SC infusion for over 16 hours: fixed rate of 0.75 mL/h to deliver a total infusion dose of 720/90 mg of levodopa/carbidopa over 16 hours. The device is removed at night and patients in this group also receive a morning oral dose of levodopa/carbidopa upon awakening. ND0612: ND0612, a solution of levodopa/carbidopa (LD/CD) delivered continuously subcutaneously (SC) via an infusion pump system
Gastrointestinal disorders Nausea	3.3% 3/90 • Baseline to Month 12 TEAEs are defined as all AEs that started or worsened on or after the start of first study drug administration or within 28 days after the last study drug administration in the present study and up to 12 months.	12.1% 15/124 • Baseline to Month 12 TEAEs are defined as all AEs that started or worsened on or after the start of first study drug administration or within 28 days after the last study drug administration in the present study and up to 12 months.
General disorders Fatigue	0.00% 0/90 • Baseline to Month 12 TEAEs are defined as all AEs that started or worsened on or after the start of first study drug administration or within 28 days after the last study drug administration in the present study and up to 12 months.	5.6% 7/124 • Baseline to Month 12 TEAEs are defined as all AEs that started or worsened on or after the start of first study drug administration or within 28 days after the last study drug administration in the present study and up to 12 months.
General disorders Infusion site edema	5.6% 5/90 • Baseline to Month 12 TEAEs are defined as all AEs that started or worsened on or after the start of first study drug administration or within 28 days after the last study drug administration in the present study and up to 12 months.	4.0% 5/124 • Baseline to Month 12 TEAEs are defined as all AEs that started or worsened on or after the start of first study drug administration or within 28 days after the last study drug administration in the present study and up to 12 months.
General disorders Infusion site erythema	10.0% 9/90 • Baseline to Month 12 TEAEs are defined as all AEs that started or worsened on or after the start of first study drug administration or within 28 days after the last study drug administration in the present study and up to 12 months.	5.6% 7/124 • Baseline to Month 12 TEAEs are defined as all AEs that started or worsened on or after the start of first study drug administration or within 28 days after the last study drug administration in the present study and up to 12 months.
General disorders Infusion site eschar	2.2% 2/90 • Baseline to Month 12 TEAEs are defined as all AEs that started or worsened on or after the start of first study drug administration or within 28 days after the last study drug administration in the present study and up to 12 months.	12.1% 15/124 • Baseline to Month 12 TEAEs are defined as all AEs that started or worsened on or after the start of first study drug administration or within 28 days after the last study drug administration in the present study and up to 12 months.
General disorders Infusion site hematoma	26.7% 24/90 • Baseline to Month 12 TEAEs are defined as all AEs that started or worsened on or after the start of first study drug administration or within 28 days after the last study drug administration in the present study and up to 12 months.	24.2% 30/124 • Baseline to Month 12 TEAEs are defined as all AEs that started or worsened on or after the start of first study drug administration or within 28 days after the last study drug administration in the present study and up to 12 months.
General disorders Infusion site infection	14.4% 13/90 • Baseline to Month 12 TEAEs are defined as all AEs that started or worsened on or after the start of first study drug administration or within 28 days after the last study drug administration in the present study and up to 12 months.	7.3% 9/124 • Baseline to Month 12 TEAEs are defined as all AEs that started or worsened on or after the start of first study drug administration or within 28 days after the last study drug administration in the present study and up to 12 months.
General disorders Infusion site nodule	34.4% 31/90 • Baseline to Month 12 TEAEs are defined as all AEs that started or worsened on or after the start of first study drug administration or within 28 days after the last study drug administration in the present study and up to 12 months.	28.2% 35/124 • Baseline to Month 12 TEAEs are defined as all AEs that started or worsened on or after the start of first study drug administration or within 28 days after the last study drug administration in the present study and up to 12 months.
General disorders Infusion site pain	14.4% 13/90 • Baseline to Month 12 TEAEs are defined as all AEs that started or worsened on or after the start of first study drug administration or within 28 days after the last study drug administration in the present study and up to 12 months.	12.1% 15/124 • Baseline to Month 12 TEAEs are defined as all AEs that started or worsened on or after the start of first study drug administration or within 28 days after the last study drug administration in the present study and up to 12 months.
Infections and infestations Urinary tract infection	7.8% 7/90 • Baseline to Month 12 TEAEs are defined as all AEs that started or worsened on or after the start of first study drug administration or within 28 days after the last study drug administration in the present study and up to 12 months.	9.7% 12/124 • Baseline to Month 12 TEAEs are defined as all AEs that started or worsened on or after the start of first study drug administration or within 28 days after the last study drug administration in the present study and up to 12 months.
Injury, poisoning and procedural complications Fall	13.3% 12/90 • Baseline to Month 12 TEAEs are defined as all AEs that started or worsened on or after the start of first study drug administration or within 28 days after the last study drug administration in the present study and up to 12 months.	6.5% 8/124 • Baseline to Month 12 TEAEs are defined as all AEs that started or worsened on or after the start of first study drug administration or within 28 days after the last study drug administration in the present study and up to 12 months.
Musculoskeletal and connective tissue disorders Back pain	5.6% 5/90 • Baseline to Month 12 TEAEs are defined as all AEs that started or worsened on or after the start of first study drug administration or within 28 days after the last study drug administration in the present study and up to 12 months.	1.6% 2/124 • Baseline to Month 12 TEAEs are defined as all AEs that started or worsened on or after the start of first study drug administration or within 28 days after the last study drug administration in the present study and up to 12 months.
Nervous system disorders Dyskinesia	8.9% 8/90 • Baseline to Month 12 TEAEs are defined as all AEs that started or worsened on or after the start of first study drug administration or within 28 days after the last study drug administration in the present study and up to 12 months.	5.6% 7/124 • Baseline to Month 12 TEAEs are defined as all AEs that started or worsened on or after the start of first study drug administration or within 28 days after the last study drug administration in the present study and up to 12 months.
Psychiatric disorders Anxiety	2.2% 2/90 • Baseline to Month 12 TEAEs are defined as all AEs that started or worsened on or after the start of first study drug administration or within 28 days after the last study drug administration in the present study and up to 12 months.	6.5% 8/124 • Baseline to Month 12 TEAEs are defined as all AEs that started or worsened on or after the start of first study drug administration or within 28 days after the last study drug administration in the present study and up to 12 months.
Psychiatric disorders Depression	1.1% 1/90 • Baseline to Month 12 TEAEs are defined as all AEs that started or worsened on or after the start of first study drug administration or within 28 days after the last study drug administration in the present study and up to 12 months.	6.5% 8/124 • Baseline to Month 12 TEAEs are defined as all AEs that started or worsened on or after the start of first study drug administration or within 28 days after the last study drug administration in the present study and up to 12 months.