A Phase 3 Study of TVP-1012 (1 mg) in Early Parkinson's Disease Patients

This is a multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 study to evaluate the efficacy and safety of TVP-1012 in Japanese participants with early Parkinson's disease.

The study period consisted of a 28-week trial period. The participants who fulfill the inclusion criteria and not meeting any of the exclusion criteria were enrolled, and randomized in a 1:1 ratio to either the 1 mg of TVP-1012 or the placebo group. In each treatment group, participants received either 1 mg of TVP-1012 or placebo once daily in a double-blinded manner.

Inclusion criteria

Run-in period

• 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 with at least two of the following signs: resting tremor, akinesia/bradykinesia, and muscle rigidity.
• The participant has a Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II + Part III total score of >=14 at the start of the run-in period.
• The participant has Modified Hoehn & Yahr stage 1 to 3 at the start of the run-in period.
• The participant has the Parkinson's disease diagnosed within 5 years prior to the start of the run-in period.
• The participant is an outpatient of either sex aged >= 30 and < 80 years.
• 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.

Treatment period

• The participant has a MDS-UPDRS Part II + Part III total score of >= 14 at baseline.

Exclusion criteria

Run-in period

• 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 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 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 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 amantadine or anticholinergic medication for >= 180 days.
• The participant has received selegiline, a levodopa-containing product or dopamine agonist for >= 90 days.
• 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 a levodopa-containing product, dopamine agonist, amantadine or anticholinergic drug within 30 days prior to the start of the run-in period.
• The participant has received 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 has previously received a catechol-O-methyltransferase (COMT) inhibitor, droxidopa, zonisamide or istradefylline.
• 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 this study, or within 1 month after the last dose of the investigational drug; 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,
• cardiac arrest 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 start of the run-in period,
• sever 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 systolic pressure decrease of 30 mmHg or more following postural change from supine/sitting position to standing position),
• a history of syncope due to hypotension within 2 years prior to the start 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 who, in the opinion of the investigator or sub-investigator, is unsuitable for any other reason.

Treatment period

• The participant whose diagonosis of Parkinson's disease is ruled out by dopamine transporter scintigraphy performed during the run-in period if conducted.
• 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.