A Long-term, Phase 3 Study of TVP-1012 (1 mg) in Levodopa Treated Parkinson's Disease Participants

Study Overview
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Brief Summary
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The purpose of this study is to evaluate long-term safety of TVP-1012 (1 mg/day) with levodopa in Japanese participants with Parkinson's disease.

Detailed Description
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This is a multicenter, open-label, long-term, phase 3 study to evaluate the safety and efficacy of long-term administration of TVP-1012 at 1 mg with levodopa in Japanese participants with Parkinson's disease. The study period consisted of a 2-week run-in period and a subsequent 52-week treatment period. Participants fulfilling the inclusion criteria and did not meet any of the exclusion criteria at the start of the run-in period (Week -2) and also at the end of the run-in period (Week 0) were enrolled in the study, and received 1 mg of TVP-1012 once daily for 52 weeks, in an unblinded manner, from the day after Week 0.

Official Title
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A Multicenter, Open-label, Long-term, Phase 3 Study to Evaluate the Safety and Efficacy of TVP-1012 at 1 mg in Levodopa Treated Parkinson's Disease Patients

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Drug: TVP-1012 1mg


Participation Criteria
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Eligibility Criteria
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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 received a levodopa combination drug for >= 1 month at the start of the run-in period and has either of the following. Wearing off phenomenon Decreased response to levodopa combination drugs The participant has been receiving a levodopa combination drug a stable dose regimen since 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. 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 Modified Hoehn & Yahr stage 5 (or stage 5 at eather on-time or off-time for the participant with wearing off phenomenon) at the start of the run-in period. The participant has severe dyskinesia. The participant has unstable systemic disease. The participant has a Mini-Mental State Examinations (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 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 agonist 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 with 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.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TVP-1012 1mg<br>TVP-1012 1 mg once daily orally, either before or after breakfast, concomitantly with levodopa tablet for 52 weeks as treatment period after 2 weeks of run-in period. | Drug: TVP-1012 1mg<br>* TVP-1012 1mg Tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Experience at Least One Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) |  | Up to Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With TEAE Related to Clinical Laboratory Tests |  | Up to Week 52 | 
| Number of Participants With Markedly Abnormal Vital Signs Values |  | Up to Week 52 | 
| Number of Participants With TEAE Related to Electrocardiograms (ECG) |  | Up to Week 52 | 
| Number of Participants With TEAE Related to Body Weight (Weight Decreased) |  | Up to Week 52 | 
| Change From Baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II Total Score | Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) retained the four-scale structure with a reorganization of the various subscales; (Part I) non-motor experiences of daily living (13 items), (Part II) motor experiences of daily living (13 items), (Part III) motor examination (33 scores based on 18 items), and (Part IV) motor complications (6 items). Each items had 0-4 ratings, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. The scale range for Part II Total Score was 0-52, with higher scores reflecting greater severity. | Baseline and Week 52 (LOCF) | 
| Change From Baseline in MDS-UPDRS Part III Total Score | Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) retained the four-scale structure with a reorganization of the various subscales; (Part I) non-motor experiences of daily living (13 items), (Part II) motor experiences of daily living (13 items), (Part III) motor examination (33 scores based on 18 items), and (Part IV) motor complications (6 items). Each items had 0-4 ratings, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. The scale range for Part III Total Score was 0-132, with higher scores reflecting greater severity. | Baseline and Week 52 (LOCF) | 
| Change From Baseline to Week 52 (LOCF) in Mean Daily OFF-time | Off-time refers to times when levodopa is not working well, causing worsening symptoms. | Baseline and Week 52 (LOCF) |