Parkinson's Disease
Conditions
Brief summary
The purpose of this study is to evaluate the efficacy and safety of TVP-1012 (0.5 mg or 1 mg/day) as an add-on to levodopa in Japanese participants with Parkinson's disease with wearing-off phenomenon.
Detailed description
This is a multicenter, randomized, double-blind, placebo-controlled, parallel group, phase 2/3 study to evaluate the efficacy and safety of TVP-1012 as an add-on to levodopa in Japanese participants with Parkinson's disease with wearing-off phenomenon. The study period consisted of a 28-week trial period. The participants who fulfilled the inclusion criteria and did not meeting any of the exclusion criteria were enrolled, and randomized in a 1:1:1 ratio to the 0.5 mg of TVP-1012, the 1 mg of TVP-1012, or the placebo group. In each treatment group, participants received 0.5 mg of TVP-1012, 1 mg of TVP-1012, or placebo once daily in a double-blinded manner.
Interventions
DRUGTVP-1012 1mg
TVP-1012 1mg Tablets
DRUGTVP-1012 0.5mg
TVP-1012 0.5mg Tablets
DRUGPlacebo
Placebo Tablets
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
* In the opinion of the investigator or sub-investigator, the participant is capable of understanding and complying with protocol requirements. * The participant signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures. * The participant has a diagnosis of Parkinson's disease according to the diagnostic criteria of the UK Parkinson's Disease Society Brain Bank. * The participant has Modified Hoehn & Yahr stage 2 to 4 (in the Off state) at the start of the run-in period. * The participant has wearing off phenomenon and has been continuously receiving a levodopa combination drug for \>= 6 months prior to the start of the run-in period. * The participant has been receiving a levodopa combination drug with a stable dose regimen (dosing frequency, at least 3 times a day) since the start of the run-in period. * For participants receiving eantacapone concomitantly,the participant has been receiving entacapone with a stable dose regimen from the start of the run-in period. * For participants receiving a dopamine agonist, anticholinergic drug, amantadine, droxidopa, istradefylline, or zonisamide concomitantly, the participant has been receiving those drugs with a stable dose regimen since 14 days prior to the start of the run-in period. * The participant is an outpatient of either sex aged \>= 30 and \< 80 years at the time of consent. * A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent to 1 month after the last dose of the investigational drug. * The participant has completed patient diary for at least 4 of the 7 days preceding the study visit at the end of the run-in period. * The participant has mean daily off-time of \>= 2.5 hours at the end of the run-in period
Exclusion criteria
* The participant has received any investigational medication within 90 days prior to the start of the run-in period. * The participant has received TVP-1012 in the past. * The participant is a study site employee, an immediate family member, or in a dependent relationship with a study site employee who is involved in the conduct of this study (e.g., spouse, parent, child, sibling) or may consent under duress. * Participant has donated 400 mL or more of his or her blood volume within 90 days prior to the start of the run-in period. * The participant has unstable systemic disease. * The participant has severe dyskinesia. * The participant has Mini-Mental State Examination (MMSE) score of \<= 24 at the start of the run-in period. * The participant has known or a history of schizophrenia, major or severe depression, or any other clinically significant psychiatric disease * The participant has major depression or severe depression, or any other clinically significant psychiatric disease. * The participant has a history of hypersensitivity or allergies to TVP-1012 (including any associated excipients) or selegiline. * The participant has a history of clinically significant hypertension or other reactions associated with ingestion of tyramine-rich food (e.g., cheese, lever, herring, yeast, horsebean, banana, beer or wine). * The participant has a history or concurrent of drug abuse or alcohol dependence. * The participant has received neurosurgical intervention for Parkinson's disease (e.g., pallidotomy, thalamotomy, deep brain stimulation). * The participant has received transcranial magnetic stimulation within 6 months prior to the start of the run-in period. * The participant has received selegiline, pethidine, tramadol, reserpine or methyldopa within 90 days prior to the start of the run-in period. * The participant has received single agent of levodopa, any psychoneurotic agent or antiemetic medication of dopamine antagonist within 14 days prior to the start of the run-in period. However, the participant has been receiving quetiapine or domperidone with a stable dose regimen for \>= 14 days prior to the start of the run-in period may be included in the study. * The participant is required to take any of the prohibited concomitant medications or treatments. * If female, the participant is pregnant or lactating or intending to become pregnant during, or within 1 month after the last administration of study medication in this study; or intending to donate ova during such time period. * The participant has clinically significant neurologic, cardiovascular, pulmonary, hepatic (including mild cirrhosis), renal, metabolic, gastrointestinal, urological, endocrine, or hematological disease. * The participant has clinically significant or unstable brain or cardiovascular disease, such as: * clinically significant arrhythmia or cardiac valvulopathy, * heart failure of NYHA Class II or higher, * concurrent or a history of ischemic cardiac disease within 6 months prior to the start of the run-in period, * concurrent or a history of clinically significant cerebrovascular disease within 6 months prior to the stat of the run-in period, * severe hypertension (systolic blood pressure of 180 mmHg or higher, or diastolic blood pressure of 110 mmHg or higher), * clinically significant orthostatic hypotension (including those with diastolic pressure decrease of 30 mmHg or more following postural change from supine/sitting position to standing position), or * a history of syncope due to hypotension within 2 years prior to the stat of the run-in period. * The participant is required surgery or hospitalization for surgery during the study period. * Participant has a history of cancer within 5 years prior to the start of the run-in period, except cervix carcinoma in situ which has completely cured. * The participant has acquired immunodeficiency syndrome (AIDS) \[including human immunodeficiency virus (HIV) carrier\], or hepatitis \[including viral hepatitis carrier such as hepatitis B surface (HBs) antigen or hepatitis C antibody (HCV) positive\]. However, the participant who has a negative result for HCV antigen or HCV-RNA can be included in the study. * The participant has laboratory data meeting any of the following at the start of the run-in period: * Creatinine \>= 2 x upper limit of normal (ULN) * Total bilirubin \>= 2 x ULN * ALT or AST \>= 1.5 x ULN * ALP \>= 3 x ULN * The participant has received any of the prohibited concomitant medications or treatments during the run-in period. * The participant who, in the opinion of the investigator or sub-investigator, is unsuitable for any other reason.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Daily OFF-time During Treatment Period | From Baseline to Week 26 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II Total Score | Baseline and Week 26 (LOCF) | 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. |
| Change From Baseline in MDS-UPDRS Part III Total Score | Baseline and Week 26 (LOCF) | 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. |
| Change From Baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) Summary Index Score | Baseline and Week 26 (LOCF) | 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. |
| Change From Baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) Each Domain Score | Baseline and Week 26 (LOCF) | 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. |
| Change From Baseline to Week 26 (LOCF) in Mean Daily OFF-time | Baseline and Week 26 (LOCF) | — |
| Number of Participants With Markedly Abnormal Vital Signs Values | Up to Week 26 | — |
| Number of Participants With TEAE Related to Body Weight (Weight Decreased) | Up to Week 26 | — |
| Number of Participants With TEAE Related to Electrocardiograms (ECG) (Sinus Bradycardia) | Up to Week 26 | — |
| Number of Participants With TEAE Related to Clinical Laboratory Tests | Up to Week 26 | — |
| Number of Participants Who Experience at Least One Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Up to Week 26 | — |
Countries
Japan
Participant flow
Recruitment details
Participants took part in the study at 68 investigative sites in Japan, from 27-Jan-2015 to 15-Sep-2016.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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 | 141 |
| 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 | 134 |
| 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 | 129 |
| Total | 404 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Investigator's Judgment | 1 | 1 | 3 |
| Overall Study | Lack of Efficacy | 2 | 4 | 0 |
| Overall Study | Major Protocol Deviation (in-Treatment) | 0 | 1 | 0 |
| Overall Study | Major Protocol Deviation (Pre-Treatment) | 0 | 1 | 0 |
| Overall Study | Pretreatment Event/Adverse Event | 9 | 18 | 21 |
| Overall Study | Voluntary Withdrawal | 10 | 5 | 2 |
Baseline characteristics
| Characteristic | Total | Placebo | TVP-1012 0.5 mg | TVP-1012 1 mg |
|---|---|---|---|---|
| Age, Continuous | 66.1 years STANDARD_DEVIATION 8.26 | 66.3 years STANDARD_DEVIATION 7.62 | 66.1 years STANDARD_DEVIATION 8.74 | 65.8 years STANDARD_DEVIATION 8.48 |
| BMI | 22.28 kg/m^2 STANDARD_DEVIATION 3.871 | 21.99 kg/m^2 STANDARD_DEVIATION 3.917 | 22.87 kg/m^2 STANDARD_DEVIATION 4.049 | 21.98 kg/m^2 STANDARD_DEVIATION 3.584 |
| Concomitant Use of Amantadine Had Amantadine | 82 Participants | 23 Participants | 26 Participants | 33 Participants |
| Concomitant Use of Amantadine Had no Amantadine | 322 Participants | 118 Participants | 108 Participants | 96 Participants |
| Concomitant Use of Anticholinergics Had Anticholinergics | 38 Participants | 12 Participants | 13 Participants | 13 Participants |
| Concomitant Use of Anticholinergics Had no Anticholinergics | 366 Participants | 129 Participants | 121 Participants | 116 Participants |
| Concomitant Use of COMT Inhibitor Had COMT Inhibitor | 167 Participants | 54 Participants | 59 Participants | 54 Participants |
| Concomitant Use of COMT Inhibitor Had no COMT Inhibitor | 237 Participants | 87 Participants | 75 Participants | 75 Participants |
| Concomitant Use of Dopamine Agonist Had Dopamine Agonist | 342 Participants | 122 Participants | 106 Participants | 114 Participants |
| Concomitant Use of Dopamine Agonist Had no Dopamine Agonist | 62 Participants | 19 Participants | 28 Participants | 15 Participants |
| Concomitant Use of Droxidopa Had Droxidopa | 30 Participants | 8 Participants | 11 Participants | 11 Participants |
| Concomitant Use of Droxidopa Had no Droxidopa | 374 Participants | 133 Participants | 123 Participants | 118 Participants |
| Concomitant Use of Istradefylline Had Istradefylline | 92 Participants | 33 Participants 2.869 | 24 Participants 2.749 | 35 Participants 2.99 |
| Concomitant Use of Istradefylline Had no Istradefylline | 312 Participants | 108 Participants | 110 Participants | 94 Participants |
| Concomitant Use of Zonisamide Had no Zonisamide | 256 Participants | 96 Participants | 83 Participants | 77 Participants |
| Concomitant Use of Zonisamide Had Zonisamide | 148 Participants | 45 Participants 0.608 | 51 Participants 0.542 | 52 Participants 0.566 |
| Duration of Levodopa Use | 6.53 years STANDARD_DEVIATION 4.42 | 6.49 years STANDARD_DEVIATION 4.402 | 5.94 years STANDARD_DEVIATION 3.984 | 7.17 years STANDARD_DEVIATION 4.8 |
| Duration of Parkinson's Disease | 8.96 years STANDARD_DEVIATION 4.745 | 8.90 years STANDARD_DEVIATION 4.465 | 8.53 years STANDARD_DEVIATION 4.774 | 9.49 years STANDARD_DEVIATION 4.992 |
| Duration of Wearing Off Phenomenon | 3.03 years STANDARD_DEVIATION 2.867 | 2.94 years STANDARD_DEVIATION 2.869 | 2.89 years STANDARD_DEVIATION 2.749 | 3.27 years STANDARD_DEVIATION 2.99 |
| Height | 156.8 centimeter (cm) STANDARD_DEVIATION 9.64 | 156.7 centimeter (cm) STANDARD_DEVIATION 9.61 | 157.1 centimeter (cm) STANDARD_DEVIATION 10.49 | 156.6 centimeter (cm) STANDARD_DEVIATION 8.78 |
| Levodopa Frequency per Day | 3.9 times per day STANDARD_DEVIATION 1.26 | 3.8 times per day STANDARD_DEVIATION 1.07 | 3.9 times per day STANDARD_DEVIATION 1.32 | 4.1 times per day STANDARD_DEVIATION 1.38 |
| Levodopa Total Daily Dose | 409.0 mg per day STANDARD_DEVIATION 147.48 | 399.3 mg per day STANDARD_DEVIATION 141.03 | 407.8 mg per day STANDARD_DEVIATION 134.15 | 420.7 mg per day STANDARD_DEVIATION 166.42 |
| MDS-UPDRS Part III Total Score | 27.7 Score on a scale STANDARD_DEVIATION 13.46 | 26.8 Score on a scale STANDARD_DEVIATION 13.99 | 28.7 Score on a scale STANDARD_DEVIATION 13.28 | 27.5 Score on a scale STANDARD_DEVIATION 13.09 |
| MDS-UPDRS Part II Total Score | 13.6 Score on a scale STANDARD_DEVIATION 7.06 | 13.0 Score on a scale STANDARD_DEVIATION 7.29 | 13.7 Score on a scale STANDARD_DEVIATION 6.65 | 14.1 Score on a scale STANDARD_DEVIATION 7.23 |
| Mean Daily OFF-time | 6.17 hours per day STANDARD_DEVIATION 2.42 | 6.05 hours per day STANDARD_DEVIATION 2.278 | 6.33 hours per day STANDARD_DEVIATION 2.562 | 6.12 hours per day STANDARD_DEVIATION 2.43 |
| Mean Percentage of Daily OFF-time | 37.47 percentage of daily off time STANDARD_DEVIATION 13.708 | 36.86 percentage of daily off time STANDARD_DEVIATION 13.373 | 38.68 percentage of daily off time STANDARD_DEVIATION 14.278 | 36.89 percentage of daily off time STANDARD_DEVIATION 13.49 |
| Modified Hoehn & Yahr Stage (OFF State) | 3.26 Units on a scale STANDARD_DEVIATION 0.678 | 3.22 Units on a scale STANDARD_DEVIATION 0.708 | 3.25 Units on a scale STANDARD_DEVIATION 0.674 | 3.30 Units on a scale STANDARD_DEVIATION 0.651 |
| Modified Hoehn & Yahr Stage (ON State) | 2.46 Units on a scale STANDARD_DEVIATION 0.573 | 2.44 Units on a scale STANDARD_DEVIATION 0.608 | 2.45 Units on a scale STANDARD_DEVIATION 0.542 | 2.51 Units on a scale STANDARD_DEVIATION 0.566 |
| PDQ-39 Summary Index | 21.07 Score on a scale STANDARD_DEVIATION 12.909 | 19.97 Score on a scale STANDARD_DEVIATION 13.177 | 20.94 Score on a scale STANDARD_DEVIATION 12.393 | 22.39 Score on a scale STANDARD_DEVIATION 13.115 |
| Region of Enrollment Japan Japan | 404 Participants | 141 Participants | 134 Participants | 129 Participants |
| Sex: Female, Male Female | 247 Participants | 88 Participants | 76 Participants | 83 Participants |
| Sex: Female, Male Male | 157 Participants | 53 Participants | 58 Participants | 46 Participants |
| Smoking Classification Current Smoker | 27 Participants | 5 Participants | 12 Participants | 10 Participants |
| Smoking Classification Ex-Smoker | 118 Participants | 41 Participants | 43 Participants | 34 Participants |
| Smoking Classification Never Smoked | 259 Participants | 95 Participants | 79 Participants | 85 Participants |
| Timing of Study Drug Dose After Breakfast | 207 Participants | 73 Participants | 72 Participants | 62 Participants |
| Timing of Study Drug Dose Before Breakfast | 196 Participants | 68 Participants | 61 Participants | 67 Participants |
| Weight | 55.02 kilogram (kg) STANDARD_DEVIATION 12.377 | 54.30 kilogram (kg) STANDARD_DEVIATION 12.723 | 56.54 kilogram (kg) STANDARD_DEVIATION 12.545 | 54.23 kilogram (kg) STANDARD_DEVIATION 11.762 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 31 / 141 | 44 / 133 | 48 / 129 |
| serious Total, serious adverse events | 4 / 141 | 10 / 133 | 10 / 129 |
Outcome results
Primary
Change From Baseline in Mean Daily OFF-time During Treatment Period
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Mean Daily OFF-time During Treatment Period | -0.51 hours per day | Standard Error 0.167 |
| TVP-1012 0.5 mg | Change From Baseline in Mean Daily OFF-time During Treatment Period | -1.11 hours per day | Standard Error 0.174 |
| TVP-1012 1 mg | Change From Baseline in Mean Daily OFF-time During Treatment Period | -1.35 hours per day | Standard Error 0.177 |
p-value: 0.000695% CI: [-1.32, -0.364]ANCOVA
p-value: 0.01495% CI: [-1.07, -0.122]ANCOVA
Secondary
Change From Baseline in MDS-UPDRS Part III Total Score
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in MDS-UPDRS Part III Total Score | -3.50 Units on a scale | Standard Error 0.605 |
| TVP-1012 0.5 mg | Change From Baseline in MDS-UPDRS Part III Total Score | -5.24 Units on a scale | Standard Error 0.623 |
| TVP-1012 1 mg | Change From Baseline in MDS-UPDRS Part III Total Score | -5.65 Units on a scale | Standard Error 0.637 |
Secondary
Change From Baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II Total Score
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 |
| TVP-1012 0.5 mg | Change From Baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II Total Score | -0.30 Units on a scale | Standard Error 0.421 |
| TVP-1012 1 mg | Change From Baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II Total Score | -0.30 Units on a scale | Standard Error 0.431 |
Secondary
Change From Baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) Each Domain Score
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.
Time frame: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| TVP-1012 0.5 mg | Change From Baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) Each Domain Score | Emotional Well-being | -0.01 Units on a scale | Standard Error 1.329 |
| TVP-1012 0.5 mg | Change From Baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) Each Domain Score | Communication | 1.59 Units on a scale | Standard Error 1.136 |
| TVP-1012 0.5 mg | Change From Baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) Each Domain Score | Stigma | -3.28 Units on a scale | Standard Error 1.19 |
| TVP-1012 0.5 mg | Change From Baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) Each Domain Score | Social Support | 0.60 Units on a scale | Standard Error 1.072 |
| TVP-1012 0.5 mg | Change From Baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) Each Domain Score | Cognitions | 3.15 Units on a scale | Standard Error 1.252 |
| TVP-1012 0.5 mg | Change From Baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) Each Domain Score | Mobility | -0.64 Units on a scale | Standard Error 1.552 |
| TVP-1012 0.5 mg | Change From Baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) Each Domain Score | Activities of Daily Living | -1.28 Units on a scale | Standard Error 1.382 |
| TVP-1012 0.5 mg | Change From Baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) Each Domain Score | Bodily Discomfort | 2.36 Units on a scale | Standard Error 1.401 |
| TVP-1012 1 mg | Change From Baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) Each Domain Score | Emotional Well-being | -0.36 Units on a scale | Standard Error 1.372 |
| TVP-1012 1 mg | Change From Baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) Each Domain Score | Activities of Daily Living | -3.72 Units on a scale | Standard Error 1.429 |
| TVP-1012 1 mg | Change From Baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) Each Domain Score | Mobility | -2.80 Units on a scale | Standard Error 1.605 |
| TVP-1012 1 mg | Change From Baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) Each Domain Score | Stigma | -2.90 Units on a scale | Standard Error 1.229 |
| TVP-1012 1 mg | Change From Baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) Each Domain Score | Communication | 2.26 Units on a scale | Standard Error 1.172 |
| TVP-1012 1 mg | Change From Baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) Each Domain Score | Cognitions | 0.69 Units on a scale | Standard Error 1.291 |
| TVP-1012 1 mg | Change From Baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) Each Domain Score | Social Support | 1.38 Units on a scale | Standard Error 1.104 |
| TVP-1012 1 mg | Change From Baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) Each Domain Score | Bodily Discomfort | -0.92 Units on a scale | Standard Error 1.449 |
Secondary
Change From Baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) Summary Index Score
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.
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) Summary Index Score | 2.84 Units on a scale | Standard Error 0.809 |
| TVP-1012 0.5 mg | Change From Baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) Summary Index Score | 0.33 Units on a scale | Standard Error 0.829 |
| TVP-1012 1 mg | Change From Baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) Summary Index Score | -1.00 Units on a scale | Standard Error 0.857 |
Secondary
Change From Baseline to Week 26 (LOCF) in Mean Daily OFF-time
Time frame: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 26 (LOCF) in Mean Daily OFF-time | -0.50 hours per day | Standard Error 0.207 |
| TVP-1012 0.5 mg | Change From Baseline to Week 26 (LOCF) in Mean Daily OFF-time | -0.99 hours per day | Standard Error 0.217 |
| TVP-1012 1 mg | Change From Baseline to Week 26 (LOCF) in Mean Daily OFF-time | -1.40 hours per day | Standard Error 0.22 |
Secondary
Number of Participants Who Experience at Least One Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: Up to Week 26
Population: Safety Analysis set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants Who Experience at Least One Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 71 Participants |
| Placebo | Number of Participants Who Experience at Least One Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 4 Participants |
| TVP-1012 0.5 mg | Number of Participants Who Experience at Least One Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 93 Participants |
| TVP-1012 0.5 mg | Number of Participants Who Experience at Least One Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 10 Participants |
| TVP-1012 1 mg | Number of Participants Who Experience at Least One Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 95 Participants |
| TVP-1012 1 mg | Number of Participants Who Experience at Least One Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 10 Participants |
Secondary
Number of Participants With Markedly Abnormal Vital Signs Values
Time frame: Up to Week 26
Population: Safety Analysis set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Markedly Abnormal Vital Signs Values | Temperature (<35.6 °C) | 20 Participants |
| Placebo | Number of Participants With Markedly Abnormal Vital Signs Values | Temperature(>37.7 °C) | 0 Participants |
| Placebo | Number of Participants With Markedly Abnormal Vital Signs Values | Systolic Blood Pressure (<90 mmHg) | 19 Participants |
| Placebo | Number of Participants With Markedly Abnormal Vital Signs Values | Systolic Blood Pressure (>180 mmHg) | 0 Participants |
| Placebo | Number of Participants With Markedly Abnormal Vital Signs Values | Diastolic Blood Pressure(<50 mmHg) | 13 Participants |
| Placebo | Number of Participants With Markedly Abnormal Vital Signs Values | Diastolic Blood Pressure (>100 mmHg) | 4 Participants |
| Placebo | Number of Participants With Markedly Abnormal Vital Signs Values | Pulse (<45 bpm) | 2 Participants |
| Placebo | Number of Participants With Markedly Abnormal Vital Signs Values | Pulse ( >120 bpm) | 1 Participants |
| TVP-1012 0.5 mg | Number of Participants With Markedly Abnormal Vital Signs Values | Systolic Blood Pressure (<90 mmHg) | 11 Participants |
| TVP-1012 0.5 mg | Number of Participants With Markedly Abnormal Vital Signs Values | Pulse (<45 bpm) | 1 Participants |
| TVP-1012 0.5 mg | Number of Participants With Markedly Abnormal Vital Signs Values | Systolic Blood Pressure (>180 mmHg) | 1 Participants |
| TVP-1012 0.5 mg | Number of Participants With Markedly Abnormal Vital Signs Values | Diastolic Blood Pressure(<50 mmHg) | 16 Participants |
| TVP-1012 0.5 mg | Number of Participants With Markedly Abnormal Vital Signs Values | Diastolic Blood Pressure (>100 mmHg) | 0 Participants |
| TVP-1012 0.5 mg | Number of Participants With Markedly Abnormal Vital Signs Values | Temperature (<35.6 °C) | 21 Participants |
| TVP-1012 0.5 mg | Number of Participants With Markedly Abnormal Vital Signs Values | Temperature(>37.7 °C) | 0 Participants |
| TVP-1012 0.5 mg | Number of Participants With Markedly Abnormal Vital Signs Values | Pulse ( >120 bpm) | 0 Participants |
| TVP-1012 1 mg | Number of Participants With Markedly Abnormal Vital Signs Values | Systolic Blood Pressure (<90 mmHg) | 27 Participants |
| TVP-1012 1 mg | Number of Participants With Markedly Abnormal Vital Signs Values | Temperature(>37.7 °C) | 1 Participants |
| TVP-1012 1 mg | Number of Participants With Markedly Abnormal Vital Signs Values | Temperature (<35.6 °C) | 22 Participants |
| TVP-1012 1 mg | Number of Participants With Markedly Abnormal Vital Signs Values | Systolic Blood Pressure (>180 mmHg) | 1 Participants |
| TVP-1012 1 mg | Number of Participants With Markedly Abnormal Vital Signs Values | Pulse (<45 bpm) | 1 Participants |
| TVP-1012 1 mg | Number of Participants With Markedly Abnormal Vital Signs Values | Diastolic Blood Pressure (>100 mmHg) | 1 Participants |
| TVP-1012 1 mg | Number of Participants With Markedly Abnormal Vital Signs Values | Diastolic Blood Pressure(<50 mmHg) | 16 Participants |
| TVP-1012 1 mg | Number of Participants With Markedly Abnormal Vital Signs Values | Pulse ( >120 bpm) | 0 Participants |
Secondary
Number of Participants With TEAE Related to Body Weight (Weight Decreased)
Time frame: Up to Week 26
Population: Safety Analysis set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With TEAE Related to Body Weight (Weight Decreased) | 1 Participants |
| TVP-1012 0.5 mg | Number of Participants With TEAE Related to Body Weight (Weight Decreased) | 1 Participants |
| TVP-1012 1 mg | Number of Participants With TEAE Related to Body Weight (Weight Decreased) | 2 Participants |
Secondary
Number of Participants With TEAE Related to Clinical Laboratory Tests
Time frame: Up to Week 26
Population: Safety Analysis set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With TEAE Related to Clinical Laboratory Tests | Blood creatine phosphokinase increased | 1 Participants |
| Placebo | Number of Participants With TEAE Related to Clinical Laboratory Tests | Blood urine present | 0 Participants |
| Placebo | Number of Participants With TEAE Related to Clinical Laboratory Tests | Gamma-glutamyltransferase increased | 0 Participants |
| Placebo | Number of Participants With TEAE Related to Clinical Laboratory Tests | Protein urine present | 1 Participants |
| Placebo | Number of Participants With TEAE Related to Clinical Laboratory Tests | Blood alkaline phosphatase increased | 0 Participants |
| Placebo | Number of Participants With TEAE Related to Clinical Laboratory Tests | Blood creatine increased | 0 Participants |
| Placebo | Number of Participants With TEAE Related to Clinical Laboratory Tests | Glucose urine present | 1 Participants |
| Placebo | Number of Participants With TEAE Related to Clinical Laboratory Tests | Platelet count decreased | 0 Participants |
| Placebo | Number of Participants With TEAE Related to Clinical Laboratory Tests | Urine ketone body present | 1 Participants |
| Placebo | Number of Participants With TEAE Related to Clinical Laboratory Tests | White blood cell count decreased | 0 Participants |
| TVP-1012 0.5 mg | Number of Participants With TEAE Related to Clinical Laboratory Tests | Urine ketone body present | 0 Participants |
| TVP-1012 0.5 mg | Number of Participants With TEAE Related to Clinical Laboratory Tests | Blood creatine phosphokinase increased | 1 Participants |
| TVP-1012 0.5 mg | Number of Participants With TEAE Related to Clinical Laboratory Tests | Blood creatine increased | 1 Participants |
| TVP-1012 0.5 mg | Number of Participants With TEAE Related to Clinical Laboratory Tests | Blood alkaline phosphatase increased | 1 Participants |
| TVP-1012 0.5 mg | Number of Participants With TEAE Related to Clinical Laboratory Tests | Blood urine present | 2 Participants |
| TVP-1012 0.5 mg | Number of Participants With TEAE Related to Clinical Laboratory Tests | White blood cell count decreased | 1 Participants |
| TVP-1012 0.5 mg | Number of Participants With TEAE Related to Clinical Laboratory Tests | Platelet count decreased | 0 Participants |
| TVP-1012 0.5 mg | Number of Participants With TEAE Related to Clinical Laboratory Tests | Gamma-glutamyltransferase increased | 2 Participants |
| TVP-1012 0.5 mg | Number of Participants With TEAE Related to Clinical Laboratory Tests | Glucose urine present | 0 Participants |
| TVP-1012 0.5 mg | Number of Participants With TEAE Related to Clinical Laboratory Tests | Protein urine present | 0 Participants |
| TVP-1012 1 mg | Number of Participants With TEAE Related to Clinical Laboratory Tests | Platelet count decreased | 1 Participants |
| TVP-1012 1 mg | Number of Participants With TEAE Related to Clinical Laboratory Tests | Protein urine present | 1 Participants |
| TVP-1012 1 mg | Number of Participants With TEAE Related to Clinical Laboratory Tests | Blood alkaline phosphatase increased | 0 Participants |
| TVP-1012 1 mg | Number of Participants With TEAE Related to Clinical Laboratory Tests | Blood creatine increased | 0 Participants |
| TVP-1012 1 mg | Number of Participants With TEAE Related to Clinical Laboratory Tests | Urine ketone body present | 0 Participants |
| TVP-1012 1 mg | Number of Participants With TEAE Related to Clinical Laboratory Tests | Glucose urine present | 0 Participants |
| TVP-1012 1 mg | Number of Participants With TEAE Related to Clinical Laboratory Tests | Blood creatine phosphokinase increased | 1 Participants |
| TVP-1012 1 mg | Number of Participants With TEAE Related to Clinical Laboratory Tests | White blood cell count decreased | 0 Participants |
| TVP-1012 1 mg | Number of Participants With TEAE Related to Clinical Laboratory Tests | Blood urine present | 1 Participants |
| TVP-1012 1 mg | Number of Participants With TEAE Related to Clinical Laboratory Tests | Gamma-glutamyltransferase increased | 0 Participants |
Secondary
Number of Participants With TEAE Related to Electrocardiograms (ECG) (Sinus Bradycardia)
Time frame: Up to Week 26
Population: Safety Analysis set included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With TEAE Related to Electrocardiograms (ECG) (Sinus Bradycardia) | 0 Participants |
| TVP-1012 0.5 mg | Number of Participants With TEAE Related to Electrocardiograms (ECG) (Sinus Bradycardia) | 0 Participants |
| TVP-1012 1 mg | Number of Participants With TEAE Related to Electrocardiograms (ECG) (Sinus Bradycardia) | 1 Participants |