A Phase 2/3 Study of TVP-1012 at 0.5 mg or 1 mg in Levodopa Treated Parkinson's Disease Participants

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Phase 2/3 Study to Evaluate the Efficacy and Safety of TVP-1012 at 0.5 mg or 1 mg in Levodopa Treated Parkinson's Disease Patients With Wearing Off

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.

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.