a phase 2/3 study of tvp-1012 at 0.5 mg or 1 mg in levodopa treated parkinson's disease participants

Conditions: Parkinson's Disease

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.

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.

Eligibility criteria:
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.