Trial Outcomes & Findings for A Phase 2/3 Study of TVP-1012 at 0.5 mg or 1 mg in Levodopa Treated Parkinson's Disease Participants (NCT NCT02337738)

NCT ID: NCT02337738

Last Updated: 2022-03-02

Results Overview

Reported change from baseline during treatment period which was calculated as follows: Mean for a total of 21 days, consisting of three separate 7-day periods preceding the visits at Week 6, 14 and 26 of the treatment period - Mean for the 7 days preceding the visit at the end of the run-in period. Off-time refers to times when levodopa is not working well, causing worsening symptoms.

• Recruitment status: COMPLETED
• Study phase: PHASE2/PHASE3
• Target enrollment: 404 participants
• Primary outcome timeframe: From Baseline to Week 26
• Results posted on: 2022-03-02

Participant Flow

Participants took part in the study at 68 investigative sites in Japan, from 27-Jan-2015 to 15-Sep-2016.

Participants with diagnosis of Parkinson's disease with wearing-off phenomenon who were enrolled in run- in period (Week -2 to 0). After that, the participants who fulfilled the inclusion criteria and did not meet any of the exclusion criteria at Week -2 and Week 0 were randomized in 1:1:1 to TVP-1012 0.5 mg, TVP-1012 1 mg, or placebo at Week 0.

Participant milestones

Measure	Placebo For 2 weeks during the run-in period, followed by 26 weeks during the treatment period, one placebo tablet once daily orally, either before or after breakfast, concomitantly with levodopa tablet	TVP-1012 0.5 mg For 2 weeks during the run-in period, followed by 26 weeks during the treatment period, TVP-1012 0.5 mg once daily orally, either before or after breakfast, concomitantly with levodopa tablet	TVP-1012 1 mg For 2 weeks during the run-in period, followed by 26 weeks during the treatment period, TVP-1012 1 mg once daily orally, either before or after breakfast, concomitantly with levodopa tablet
Overall Study STARTED	141	134	129
Overall Study COMPLETED	119	104	103
Overall Study NOT COMPLETED	22	30	26

Reasons for withdrawal

Measure	Placebo For 2 weeks during the run-in period, followed by 26 weeks during the treatment period, one placebo tablet once daily orally, either before or after breakfast, concomitantly with levodopa tablet	TVP-1012 0.5 mg For 2 weeks during the run-in period, followed by 26 weeks during the treatment period, TVP-1012 0.5 mg once daily orally, either before or after breakfast, concomitantly with levodopa tablet	TVP-1012 1 mg For 2 weeks during the run-in period, followed by 26 weeks during the treatment period, TVP-1012 1 mg once daily orally, either before or after breakfast, concomitantly with levodopa tablet
Overall Study Major Protocol Deviation (Pre-Treatment)	0	1	0
Overall Study Pretreatment Event/Adverse Event	9	18	21
Overall Study Major Protocol Deviation (in-Treatment)	0	1	0
Overall Study Voluntary Withdrawal	10	5	2
Overall Study Lack of Efficacy	2	4	0
Overall Study Investigator's Judgment	1	1	3

Baseline Characteristics

The number analyzed is the number of participants with data available for analysis.

Baseline characteristics by cohort

Measure	Placebo n=141 Participants For 2 weeks during the run-in period, followed by 26 weeks during the treatment period, one placebo tablet once daily orally, either before or after breakfast, concomitantly with levodopa tablet	TVP-1012 0.5 mg n=134 Participants For 2 weeks during the run-in period, followed by 26 weeks during the treatment period, TVP-1012 0.5 mg once daily orally, either before or after breakfast, concomitantly with levodopa tablet	TVP-1012 1 mg n=129 Participants For 2 weeks during the run-in period, followed by 26 weeks during the treatment period, TVP-1012 1 mg once daily orally, either before or after breakfast, concomitantly with levodopa tablet	Total n=404 Participants Total of all reporting groups
Age, Continuous	66.3 years STANDARD_DEVIATION 7.62 • n=141 Participants	66.1 years STANDARD_DEVIATION 8.74 • n=134 Participants	65.8 years STANDARD_DEVIATION 8.48 • n=129 Participants	66.1 years STANDARD_DEVIATION 8.26 • n=404 Participants
Sex: Female, Male Female	88 Participants n=141 Participants	76 Participants n=134 Participants	83 Participants n=129 Participants	247 Participants n=404 Participants
Sex: Female, Male Male	53 Participants n=141 Participants	58 Participants n=134 Participants	46 Participants n=129 Participants	157 Participants n=404 Participants
Region of Enrollment Japan · Japan	141 Participants n=141 Participants	134 Participants n=134 Participants	129 Participants n=129 Participants	404 Participants n=404 Participants
Height	156.7 centimeter (cm) STANDARD_DEVIATION 9.61 • n=141 Participants	157.1 centimeter (cm) STANDARD_DEVIATION 10.49 • n=134 Participants	156.6 centimeter (cm) STANDARD_DEVIATION 8.78 • n=129 Participants	156.8 centimeter (cm) STANDARD_DEVIATION 9.64 • n=404 Participants
Weight	54.30 kilogram (kg) STANDARD_DEVIATION 12.723 • n=141 Participants	56.54 kilogram (kg) STANDARD_DEVIATION 12.545 • n=134 Participants	54.23 kilogram (kg) STANDARD_DEVIATION 11.762 • n=129 Participants	55.02 kilogram (kg) STANDARD_DEVIATION 12.377 • n=404 Participants
BMI	21.99 kg/m^2 STANDARD_DEVIATION 3.917 • n=141 Participants	22.87 kg/m^2 STANDARD_DEVIATION 4.049 • n=134 Participants	21.98 kg/m^2 STANDARD_DEVIATION 3.584 • n=129 Participants	22.28 kg/m^2 STANDARD_DEVIATION 3.871 • n=404 Participants
Smoking Classification Current Smoker	5 Participants n=141 Participants	12 Participants n=134 Participants	10 Participants n=129 Participants	27 Participants n=404 Participants
Smoking Classification Ex-Smoker	41 Participants n=141 Participants	43 Participants n=134 Participants	34 Participants n=129 Participants	118 Participants n=404 Participants
Smoking Classification Never Smoked	95 Participants n=141 Participants	79 Participants n=134 Participants	85 Participants n=129 Participants	259 Participants n=404 Participants
Timing of Study Drug Dose Before Breakfast	68 Participants n=141 Participants • The number analyzed is the number of participants with data available for analysis.	61 Participants n=133 Participants • The number analyzed is the number of participants with data available for analysis.	67 Participants n=129 Participants • The number analyzed is the number of participants with data available for analysis.	196 Participants n=403 Participants • The number analyzed is the number of participants with data available for analysis.
Timing of Study Drug Dose After Breakfast	73 Participants n=141 Participants • The number analyzed is the number of participants with data available for analysis.	72 Participants n=133 Participants • The number analyzed is the number of participants with data available for analysis.	62 Participants n=129 Participants • The number analyzed is the number of participants with data available for analysis.	207 Participants n=403 Participants • The number analyzed is the number of participants with data available for analysis.
Duration of Parkinson's Disease	8.90 years STANDARD_DEVIATION 4.465 • n=141 Participants	8.53 years STANDARD_DEVIATION 4.774 • n=134 Participants	9.49 years STANDARD_DEVIATION 4.992 • n=129 Participants	8.96 years STANDARD_DEVIATION 4.745 • n=404 Participants
Duration of Levodopa Use	6.49 years STANDARD_DEVIATION 4.402 • n=141 Participants	5.94 years STANDARD_DEVIATION 3.984 • n=134 Participants	7.17 years STANDARD_DEVIATION 4.800 • n=129 Participants	6.53 years STANDARD_DEVIATION 4.420 • n=404 Participants
Levodopa Total Daily Dose	399.3 mg per day STANDARD_DEVIATION 141.03 • n=141 Participants	407.8 mg per day STANDARD_DEVIATION 134.15 • n=134 Participants	420.7 mg per day STANDARD_DEVIATION 166.42 • n=129 Participants	409.0 mg per day STANDARD_DEVIATION 147.48 • n=404 Participants
Levodopa Frequency per Day	3.8 times per day STANDARD_DEVIATION 1.07 • n=141 Participants	3.9 times per day STANDARD_DEVIATION 1.32 • n=134 Participants	4.1 times per day STANDARD_DEVIATION 1.38 • n=129 Participants	3.9 times per day STANDARD_DEVIATION 1.26 • n=404 Participants
Concomitant Use of COMT Inhibitor Had COMT Inhibitor	54 Participants n=141 Participants	59 Participants n=134 Participants	54 Participants n=129 Participants	167 Participants n=404 Participants
Concomitant Use of COMT Inhibitor Had no COMT Inhibitor	87 Participants n=141 Participants	75 Participants n=134 Participants	75 Participants n=129 Participants	237 Participants n=404 Participants
Concomitant Use of Dopamine Agonist Had Dopamine Agonist	122 Participants n=141 Participants	106 Participants n=134 Participants	114 Participants n=129 Participants	342 Participants n=404 Participants
Concomitant Use of Dopamine Agonist Had no Dopamine Agonist	19 Participants n=141 Participants	28 Participants n=134 Participants	15 Participants n=129 Participants	62 Participants n=404 Participants
Concomitant Use of Amantadine Had Amantadine	23 Participants n=141 Participants	26 Participants n=134 Participants	33 Participants n=129 Participants	82 Participants n=404 Participants
Concomitant Use of Amantadine Had no Amantadine	118 Participants n=141 Participants	108 Participants n=134 Participants	96 Participants n=129 Participants	322 Participants n=404 Participants
Concomitant Use of Anticholinergics Had Anticholinergics	12 Participants n=141 Participants	13 Participants n=134 Participants	13 Participants n=129 Participants	38 Participants n=404 Participants
Concomitant Use of Anticholinergics Had no Anticholinergics	129 Participants n=141 Participants	121 Participants n=134 Participants	116 Participants n=129 Participants	366 Participants n=404 Participants
Concomitant Use of Droxidopa Had Droxidopa	8 Participants n=141 Participants	11 Participants n=134 Participants	11 Participants n=129 Participants	30 Participants n=404 Participants
Concomitant Use of Droxidopa Had no Droxidopa	133 Participants n=141 Participants	123 Participants n=134 Participants	118 Participants n=129 Participants	374 Participants n=404 Participants
Concomitant Use of Istradefylline Had Istradefylline	33 Participants 2.869 • n=141 Participants	24 Participants 2.749 • n=134 Participants	35 Participants 2.990 • n=129 Participants	92 Participants n=404 Participants
Concomitant Use of Istradefylline Had no Istradefylline	108 Participants n=141 Participants	110 Participants n=134 Participants	94 Participants n=129 Participants	312 Participants n=404 Participants
Concomitant Use of Zonisamide Had Zonisamide	45 Participants 0.608 • n=141 Participants	51 Participants 0.542 • n=134 Participants	52 Participants 0.566 • n=129 Participants	148 Participants n=404 Participants
Concomitant Use of Zonisamide Had no Zonisamide	96 Participants n=141 Participants	83 Participants n=134 Participants	77 Participants n=129 Participants	256 Participants n=404 Participants
Duration of Wearing Off Phenomenon	2.94 years STANDARD_DEVIATION 2.869 • n=141 Participants	2.89 years STANDARD_DEVIATION 2.749 • n=134 Participants	3.27 years STANDARD_DEVIATION 2.990 • n=129 Participants	3.03 years STANDARD_DEVIATION 2.867 • n=404 Participants
Modified Hoehn & Yahr Stage (ON State)	2.44 Units on a scale STANDARD_DEVIATION 0.608 • n=141 Participants	2.45 Units on a scale STANDARD_DEVIATION 0.542 • n=134 Participants	2.51 Units on a scale STANDARD_DEVIATION 0.566 • n=129 Participants	2.46 Units on a scale STANDARD_DEVIATION 0.573 • n=404 Participants
Modified Hoehn & Yahr Stage (OFF State)	3.22 Units on a scale STANDARD_DEVIATION 0.708 • n=141 Participants	3.25 Units on a scale STANDARD_DEVIATION 0.674 • n=134 Participants	3.30 Units on a scale STANDARD_DEVIATION 0.651 • n=129 Participants	3.26 Units on a scale STANDARD_DEVIATION 0.678 • n=404 Participants
Mean Daily OFF-time	6.05 hours per day STANDARD_DEVIATION 2.278 • n=141 Participants	6.33 hours per day STANDARD_DEVIATION 2.562 • n=134 Participants	6.12 hours per day STANDARD_DEVIATION 2.430 • n=129 Participants	6.17 hours per day STANDARD_DEVIATION 2.420 • n=404 Participants
Mean Percentage of Daily OFF-time	36.86 percentage of daily off time STANDARD_DEVIATION 13.373 • n=141 Participants	38.68 percentage of daily off time STANDARD_DEVIATION 14.278 • n=134 Participants	36.89 percentage of daily off time STANDARD_DEVIATION 13.490 • n=129 Participants	37.47 percentage of daily off time STANDARD_DEVIATION 13.708 • n=404 Participants
MDS-UPDRS Part II Total Score	13.0 Score on a scale STANDARD_DEVIATION 7.29 • n=141 Participants	13.7 Score on a scale STANDARD_DEVIATION 6.65 • n=134 Participants	14.1 Score on a scale STANDARD_DEVIATION 7.23 • n=129 Participants	13.6 Score on a scale STANDARD_DEVIATION 7.06 • n=404 Participants
MDS-UPDRS Part III Total Score	26.8 Score on a scale STANDARD_DEVIATION 13.99 • n=141 Participants	28.7 Score on a scale STANDARD_DEVIATION 13.28 • n=134 Participants	27.5 Score on a scale STANDARD_DEVIATION 13.09 • n=129 Participants	27.7 Score on a scale STANDARD_DEVIATION 13.46 • n=404 Participants
PDQ-39 Summary Index	19.97 Score on a scale STANDARD_DEVIATION 13.177 • n=141 Participants	20.94 Score on a scale STANDARD_DEVIATION 12.393 • n=134 Participants	22.39 Score on a scale STANDARD_DEVIATION 13.115 • n=129 Participants	21.07 Score on a scale STANDARD_DEVIATION 12.909 • n=404 Participants

PRIMARY outcome

Timeframe: From Baseline to Week 26

Population: Full Analysis Set included all randomized participants who received at least 1 dose of the study drug for the treatment period. Here number of participants analyzed are participants evaluable for this outcome measure.

Reported change from baseline during treatment period which was calculated as follows: Mean for a total of 21 days, consisting of three separate 7-day periods preceding the visits at Week 6, 14 and 26 of the treatment period - Mean for the 7 days preceding the visit at the end of the run-in period. Off-time refers to times when levodopa is not working well, causing worsening symptoms.

Outcome measures

Measure	Placebo n=138 Participants For 2 weeks during the run-in period, followed by 26 weeks during the treatment period, one placebo tablet once daily orally, either before or after breakfast, concomitantly with levodopa tablet	TVP-1012 0.5 mg n=126 Participants For 2 weeks during the run-in period, followed by 26 weeks during the treatment period, TVP-1012 0.5 mg once daily orally, either before or after breakfast, concomitantly with levodopa tablet	TVP-1012 1 mg n=122 Participants For 2 weeks during the run-in period, followed by 26 weeks during the treatment period, TVP-1012 1 mg once daily orally, either before or after breakfast, concomitantly with levodopa tablet
Change From Baseline in Mean Daily OFF-time During Treatment Period	-0.51 hours per day Standard Error 0.167	-1.11 hours per day Standard Error 0.174	-1.35 hours per day Standard Error 0.177

SECONDARY outcome

Timeframe: Baseline and Week 26 (LOCF)

Population: Full Analysis Set included all randomized participants who received at least 1 dose of the study drug for the treatment period. Here number of participants analyzed are participants evaluable for this outcome measure.

Outcome measures

Measure	Placebo n=138 Participants For 2 weeks during the run-in period, followed by 26 weeks during the treatment period, one placebo tablet once daily orally, either before or after breakfast, concomitantly with levodopa tablet	TVP-1012 0.5 mg n=126 Participants For 2 weeks during the run-in period, followed by 26 weeks during the treatment period, TVP-1012 0.5 mg once daily orally, either before or after breakfast, concomitantly with levodopa tablet	TVP-1012 1 mg n=122 Participants For 2 weeks during the run-in period, followed by 26 weeks during the treatment period, TVP-1012 1 mg once daily orally, either before or after breakfast, concomitantly with levodopa tablet
Change From Baseline to Week 26 (LOCF) in Mean Daily OFF-time	-0.50 hours per day Standard Error 0.207	-0.99 hours per day Standard Error 0.217	-1.40 hours per day Standard Error 0.220

SECONDARY outcome

Timeframe: Baseline and Week 26 (LOCF)

Population: Full Analysis Set included all randomized participants who received at least 1 dose of the study drug for the treatment period. Here number of participants analyzed are participants evaluable for this outcome measure.

MDS-UPDRS retains the four-scale structure with a reorganization of the various subscale; (Part I; 13 items) non-motor experiences of daily living, (Part II; 13) motor experiences of daily living, (Part III; 34) motor examination, and (Part IV; 6) motor complications. Each items had 0-4 ratings, where 0 (normal) to 4 (severe) and score for each was summed to calculate the total scores. The scale range for Part II Total Score was 0-52, with higher scores reflecting greater severity.

Outcome measures

Measure	Placebo n=141 Participants For 2 weeks during the run-in period, followed by 26 weeks during the treatment period, one placebo tablet once daily orally, either before or after breakfast, concomitantly with levodopa tablet	TVP-1012 0.5 mg n=132 Participants For 2 weeks during the run-in period, followed by 26 weeks during the treatment period, TVP-1012 0.5 mg once daily orally, either before or after breakfast, concomitantly with levodopa tablet	TVP-1012 1 mg n=126 Participants For 2 weeks during the run-in period, followed by 26 weeks during the treatment period, TVP-1012 1 mg once daily orally, either before or after breakfast, concomitantly with levodopa tablet
Change From Baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II Total Score	0.97 Units on a scale Standard Error 0.408	-0.30 Units on a scale Standard Error 0.421	-0.30 Units on a scale Standard Error 0.431

SECONDARY outcome

Timeframe: Baseline and Week 26 (LOCF)

Population: Full Analysis Set included all randomized participants who received at least 1 dose of the study drug for the treatment period. Here number of participants analyzed are participants evaluable for this outcome measure.

MDS-UPDRS retains the four-scale structure with a reorganization of the various subscale; (Part I; 13 items) non-motor experiences of daily living, (Part II; 13) motor experiences of daily living, (Part III; 34) motor examination, and (Part IV; 6) motor complications. Each items had 0-4 ratings, where 0 (normal) to 4 (severe) and score for each was summed to calculate the total scores. The scale range for Part III Total Score was 0-136, with higher scores reflecting greater severity.

Outcome measures

Measure	Placebo n=140 Participants For 2 weeks during the run-in period, followed by 26 weeks during the treatment period, one placebo tablet once daily orally, either before or after breakfast, concomitantly with levodopa tablet	TVP-1012 0.5 mg n=132 Participants For 2 weeks during the run-in period, followed by 26 weeks during the treatment period, TVP-1012 0.5 mg once daily orally, either before or after breakfast, concomitantly with levodopa tablet	TVP-1012 1 mg n=126 Participants For 2 weeks during the run-in period, followed by 26 weeks during the treatment period, TVP-1012 1 mg once daily orally, either before or after breakfast, concomitantly with levodopa tablet
Change From Baseline in MDS-UPDRS Part III Total Score	-3.50 Units on a scale Standard Error 0.605	-5.24 Units on a scale Standard Error 0.623	-5.65 Units on a scale Standard Error 0.637

SECONDARY outcome

Timeframe: Baseline and Week 26 (LOCF)

Population: Full Analysis Set included all randomized participants who received at least 1 dose of the study drug for the treatment period. Here number of participants analyzed are participants evaluable for this outcome measure.

PDQ-39 is a self-administered questionnaire. PDQ-39 comprises of 39 questions, relating to eight key areas (Mobility, Activities of Daily Living, Emotional Well-being, Stigma, Social Support, Cognitions, Communication, and Bodily Discomfort) of health and daily activities, including both Motor and Non-motor symptoms. It is scored on a scale of zero to 100, with lower scores indicating better health and high scores more severe symptoms.

Outcome measures

Measure	Placebo n=138 Participants For 2 weeks during the run-in period, followed by 26 weeks during the treatment period, one placebo tablet once daily orally, either before or after breakfast, concomitantly with levodopa tablet	TVP-1012 0.5 mg n=131 Participants For 2 weeks during the run-in period, followed by 26 weeks during the treatment period, TVP-1012 0.5 mg once daily orally, either before or after breakfast, concomitantly with levodopa tablet	TVP-1012 1 mg n=123 Participants For 2 weeks during the run-in period, followed by 26 weeks during the treatment period, TVP-1012 1 mg once daily orally, either before or after breakfast, concomitantly with levodopa tablet
Change From Baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) Summary Index Score	2.84 Units on a scale Standard Error 0.809	0.33 Units on a scale Standard Error 0.829	-1.00 Units on a scale Standard Error 0.857

SECONDARY outcome

Timeframe: Baseline and Week 26 (LOCF)

Population: Full Analysis Set included all randomized participants who received at least 1 dose of the study drug for the treatment period. Here number of participants analyzed are participants evaluable for this outcome measure.

PDQ-39 is a self-administered questionnaire. PDQ-39 comprises of 39 questions, relating to eight key areas (Mobility, Activities of Daily Living, Emotional Well-being, Stigma, Social Support, Cognitions, Communication, and Bodily Discomfort) of health and daily activities, including both Motor and Non-motor symptoms. It is scored on a scale of zero to 100, with lower scores indicating better health and high scores more severe symptoms.

Outcome measures

Measure	Placebo n=138 Participants For 2 weeks during the run-in period, followed by 26 weeks during the treatment period, one placebo tablet once daily orally, either before or after breakfast, concomitantly with levodopa tablet	TVP-1012 0.5 mg n=131 Participants For 2 weeks during the run-in period, followed by 26 weeks during the treatment period, TVP-1012 0.5 mg once daily orally, either before or after breakfast, concomitantly with levodopa tablet	TVP-1012 1 mg n=123 Participants For 2 weeks during the run-in period, followed by 26 weeks during the treatment period, TVP-1012 1 mg once daily orally, either before or after breakfast, concomitantly with levodopa tablet
Change From Baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) Each Domain Score Mobility	3.36 Units on a scale Standard Error 1.515	-0.64 Units on a scale Standard Error 1.552	-2.80 Units on a scale Standard Error 1.605
Change From Baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) Each Domain Score Activities of Daily Living	4.42 Units on a scale Standard Error 1.348	-1.28 Units on a scale Standard Error 1.382	-3.72 Units on a scale Standard Error 1.429
Change From Baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) Each Domain Score Emotional Well-being	3.75 Units on a scale Standard Error 1.295	-0.01 Units on a scale Standard Error 1.329	-0.36 Units on a scale Standard Error 1.372
Change From Baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) Each Domain Score Stigma	-1.14 Units on a scale Standard Error 1.161	-3.28 Units on a scale Standard Error 1.190	-2.90 Units on a scale Standard Error 1.229
Change From Baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) Each Domain Score Social Support	2.46 Units on a scale Standard Error 1.043	0.60 Units on a scale Standard Error 1.072	1.38 Units on a scale Standard Error 1.104
Change From Baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) Each Domain Score Cognitions	1.60 Units on a scale Standard Error 1.219	3.15 Units on a scale Standard Error 1.252	0.69 Units on a scale Standard Error 1.291
Change From Baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) Each Domain Score Communication	3.66 Units on a scale Standard Error 1.107	1.59 Units on a scale Standard Error 1.136	2.26 Units on a scale Standard Error 1.172
Change From Baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) Each Domain Score Bodily Discomfort	3.36 Units on a scale Standard Error 1.367	2.36 Units on a scale Standard Error 1.401	-0.92 Units on a scale Standard Error 1.449

SECONDARY outcome

Timeframe: Up to Week 26

Population: Safety Analysis set included all participants who received at least 1 dose of study drug.

Outcome measures

Measure	Placebo n=141 Participants For 2 weeks during the run-in period, followed by 26 weeks during the treatment period, one placebo tablet once daily orally, either before or after breakfast, concomitantly with levodopa tablet	TVP-1012 0.5 mg n=133 Participants For 2 weeks during the run-in period, followed by 26 weeks during the treatment period, TVP-1012 0.5 mg once daily orally, either before or after breakfast, concomitantly with levodopa tablet	TVP-1012 1 mg n=129 Participants For 2 weeks during the run-in period, followed by 26 weeks during the treatment period, TVP-1012 1 mg once daily orally, either before or after breakfast, concomitantly with levodopa tablet
Number of Participants Who Experience at Least One Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) TEAEs	71 Participants	93 Participants	95 Participants
Number of Participants Who Experience at Least One Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) SAEs	4 Participants	10 Participants	10 Participants

SECONDARY outcome

Timeframe: Up to Week 26

Population: Safety Analysis set included all participants who received at least 1 dose of study drug.

Outcome measures

Measure	Placebo n=141 Participants For 2 weeks during the run-in period, followed by 26 weeks during the treatment period, one placebo tablet once daily orally, either before or after breakfast, concomitantly with levodopa tablet	TVP-1012 0.5 mg n=133 Participants For 2 weeks during the run-in period, followed by 26 weeks during the treatment period, TVP-1012 0.5 mg once daily orally, either before or after breakfast, concomitantly with levodopa tablet	TVP-1012 1 mg n=129 Participants For 2 weeks during the run-in period, followed by 26 weeks during the treatment period, TVP-1012 1 mg once daily orally, either before or after breakfast, concomitantly with levodopa tablet
Number of Participants With Markedly Abnormal Vital Signs Values Temperature (<35.6 °C)	20 Participants	21 Participants	22 Participants
Number of Participants With Markedly Abnormal Vital Signs Values Temperature(>37.7 °C)	0 Participants	0 Participants	1 Participants
Number of Participants With Markedly Abnormal Vital Signs Values Systolic Blood Pressure (<90 mmHg)	19 Participants	11 Participants	27 Participants
Number of Participants With Markedly Abnormal Vital Signs Values Systolic Blood Pressure (>180 mmHg)	0 Participants	1 Participants	1 Participants
Number of Participants With Markedly Abnormal Vital Signs Values Diastolic Blood Pressure(<50 mmHg)	13 Participants	16 Participants	16 Participants
Number of Participants With Markedly Abnormal Vital Signs Values Diastolic Blood Pressure (>100 mmHg)	4 Participants	0 Participants	1 Participants
Number of Participants With Markedly Abnormal Vital Signs Values Pulse (<45 bpm)	2 Participants	1 Participants	1 Participants
Number of Participants With Markedly Abnormal Vital Signs Values Pulse ( >120 bpm)	1 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to Week 26

Population: Safety Analysis set included all participants who received at least 1 dose of study drug.

Outcome measures

Measure	Placebo n=141 Participants For 2 weeks during the run-in period, followed by 26 weeks during the treatment period, one placebo tablet once daily orally, either before or after breakfast, concomitantly with levodopa tablet	TVP-1012 0.5 mg n=133 Participants For 2 weeks during the run-in period, followed by 26 weeks during the treatment period, TVP-1012 0.5 mg once daily orally, either before or after breakfast, concomitantly with levodopa tablet	TVP-1012 1 mg n=129 Participants For 2 weeks during the run-in period, followed by 26 weeks during the treatment period, TVP-1012 1 mg once daily orally, either before or after breakfast, concomitantly with levodopa tablet
Number of Participants With TEAE Related to Body Weight (Weight Decreased)	1 Participants	1 Participants	2 Participants

SECONDARY outcome

Timeframe: Up to Week 26

Population: Safety Analysis set included all participants who received at least 1 dose of study drug.

Outcome measures

Measure	Placebo n=141 Participants For 2 weeks during the run-in period, followed by 26 weeks during the treatment period, one placebo tablet once daily orally, either before or after breakfast, concomitantly with levodopa tablet	TVP-1012 0.5 mg n=133 Participants For 2 weeks during the run-in period, followed by 26 weeks during the treatment period, TVP-1012 0.5 mg once daily orally, either before or after breakfast, concomitantly with levodopa tablet	TVP-1012 1 mg n=129 Participants For 2 weeks during the run-in period, followed by 26 weeks during the treatment period, TVP-1012 1 mg once daily orally, either before or after breakfast, concomitantly with levodopa tablet
Number of Participants With TEAE Related to Electrocardiograms (ECG) (Sinus Bradycardia)	0 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to Week 26

Population: Safety Analysis set included all participants who received at least 1 dose of study drug.

Outcome measures

Measure	Placebo n=141 Participants For 2 weeks during the run-in period, followed by 26 weeks during the treatment period, one placebo tablet once daily orally, either before or after breakfast, concomitantly with levodopa tablet	TVP-1012 0.5 mg n=133 Participants For 2 weeks during the run-in period, followed by 26 weeks during the treatment period, TVP-1012 0.5 mg once daily orally, either before or after breakfast, concomitantly with levodopa tablet	TVP-1012 1 mg n=129 Participants For 2 weeks during the run-in period, followed by 26 weeks during the treatment period, TVP-1012 1 mg once daily orally, either before or after breakfast, concomitantly with levodopa tablet
Number of Participants With TEAE Related to Clinical Laboratory Tests White blood cell count decreased	0 Participants	1 Participants	0 Participants
Number of Participants With TEAE Related to Clinical Laboratory Tests Blood creatine phosphokinase increased	1 Participants	1 Participants	1 Participants
Number of Participants With TEAE Related to Clinical Laboratory Tests Blood urine present	0 Participants	2 Participants	1 Participants
Number of Participants With TEAE Related to Clinical Laboratory Tests Gamma-glutamyltransferase increased	0 Participants	2 Participants	0 Participants
Number of Participants With TEAE Related to Clinical Laboratory Tests Protein urine present	1 Participants	0 Participants	1 Participants
Number of Participants With TEAE Related to Clinical Laboratory Tests Blood alkaline phosphatase increased	0 Participants	1 Participants	0 Participants
Number of Participants With TEAE Related to Clinical Laboratory Tests Blood creatine increased	0 Participants	1 Participants	0 Participants
Number of Participants With TEAE Related to Clinical Laboratory Tests Glucose urine present	1 Participants	0 Participants	0 Participants
Number of Participants With TEAE Related to Clinical Laboratory Tests Platelet count decreased	0 Participants	0 Participants	1 Participants
Number of Participants With TEAE Related to Clinical Laboratory Tests Urine ketone body present	1 Participants	0 Participants	0 Participants

Adverse Events

Placebo

Serious events: 4 serious events

Other events: 31 other events

Deaths: 0 deaths

TVP-1012 0.5 mg

Serious events: 10 serious events

Other events: 44 other events

Deaths: 0 deaths

TVP-1012 1 mg

Serious events: 10 serious events

Other events: 48 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=141 participants at risk For 2 weeks during the run-in period, followed by 26 weeks during the treatment period, one placebo tablet once daily orally, either before or after breakfast, concomitantly with levodopa tablet	TVP-1012 0.5 mg n=133 participants at risk For 2 weeks during the run-in period, followed by 26 weeks during the treatment period, TVP-1012 0.5 mg once daily orally, either before or after breakfast, concomitantly with levodopa tablet	TVP-1012 1 mg n=129 participants at risk For 2 weeks during the run-in period, followed by 26 weeks during the treatment period, TVP-1012 1 mg once daily orally, either before or after breakfast, concomitantly with levodopa tablet
Cardiac disorders Angina pectoris	0.00% 0/141 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/133 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.78% 1/129 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Cardiac disorders Cardiac failure congestive	0.71% 1/141 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/133 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/129 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Cardiac disorders Myocardial ischaemia	0.71% 1/141 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/133 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/129 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Cardiac disorders Stress cardiomyopathy	0.00% 0/141 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/133 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.78% 1/129 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Vomiting	0.00% 0/141 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/133 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.78% 1/129 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Disuse syndrome	0.00% 0/141 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.75% 1/133 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/129 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Appendicitis	0.00% 0/141 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.75% 1/133 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/129 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Cellulitis	0.00% 0/141 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/133 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.78% 1/129 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Herpes zoster	0.71% 1/141 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/133 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/129 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Infective spondylitis	0.00% 0/141 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/133 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.78% 1/129 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Pyelonephritis	0.00% 0/141 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.75% 1/133 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/129 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Anastomotic ulcer haemorrhage	0.00% 0/141 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.75% 1/133 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/129 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Contusion	0.00% 0/141 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/133 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.78% 1/129 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Femoral neck fracture	0.00% 0/141 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/133 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.78% 1/129 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Heat illness	0.00% 0/141 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/133 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.78% 1/129 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Dehydration	0.00% 0/141 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/133 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.78% 1/129 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/141 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.75% 1/133 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/129 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to lymph nodes	0.00% 0/141 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.75% 1/133 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/129 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal cancer metastatic	0.00% 0/141 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.75% 1/133 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/129 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid cancer	0.00% 0/141 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.75% 1/133 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/129 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Dyskinesia	0.00% 0/141 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/133 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.78% 1/129 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Haemorrhage intracranial	0.71% 1/141 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/133 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/129 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Hypoxic-ischaemic encephalopathy	0.00% 0/141 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/133 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.78% 1/129 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Parkinsonism	0.71% 1/141 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/133 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/129 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Radial nerve palsy	0.00% 0/141 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.75% 1/133 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/129 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Psychiatric disorders Hallucination	0.00% 0/141 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.75% 1/133 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/129 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.00% 0/141 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.75% 1/133 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/129 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Other adverse events

Measure	Placebo n=141 participants at risk For 2 weeks during the run-in period, followed by 26 weeks during the treatment period, one placebo tablet once daily orally, either before or after breakfast, concomitantly with levodopa tablet	TVP-1012 0.5 mg n=133 participants at risk For 2 weeks during the run-in period, followed by 26 weeks during the treatment period, TVP-1012 0.5 mg once daily orally, either before or after breakfast, concomitantly with levodopa tablet	TVP-1012 1 mg n=129 participants at risk For 2 weeks during the run-in period, followed by 26 weeks during the treatment period, TVP-1012 1 mg once daily orally, either before or after breakfast, concomitantly with levodopa tablet
Infections and infestations Nasopharyngitis	9.2% 13/141 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	18.0% 24/133 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	14.7% 19/129 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Fall	5.7% 8/141 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	9.8% 13/133 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	13.2% 17/129 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Contusion	1.4% 2/141 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.0% 8/133 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	5.4% 7/129 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Dyskinesia	7.1% 10/141 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	8.3% 11/133 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	15.5% 20/129 • Baseline up to Week 26 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: trialdisclosures@takeda.com

Results disclosure agreements

• Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
• Publication restrictions are in place

Restriction type: OTHER