A Phase 3 Study of TVP-1012 (1 mg) in Early Parkinson's Disease Patients
Condition: Parkinson's Disease
MeSH terms: Parkinson Disease
Intervention: TVP-1012; Placebo
Intervention description: TVP-1012 1mg Tablets; Placebo tablets
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 244.0
Sex: All
Minimum age: 30 Years
Maximum age: 80 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to evaluate the efficacy and safety of TVP-1012 (1 mg/day)
      administered to Japanese patients with early Parkinson's disease.
    

Eligibility criteria:

        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.