The primary objective of this exploratory study is to investigate the efficacy and safety of tesofensine in daily doses (from 0.125 mg to 1.0 mg) in comparison to placebo, over a 14-week treatment period in levodopa treated Parkinson patients with motor fluctuations.

This is a randomized, double-blind, placebo-controlled, five parallel groups efficacy and safety exploratory of tesofensine versus placebo in levodopa treated Parkinson patients with motor fluctuations.

Patients will be treated either with one of the 4 doses of tesofensine (0.125mg, 0.25mg, 0.50 mg or 1.0 mg) or with placebo, once daily, over 14 weeks.

The two co-primary efficacy endpoints are the change in off-time and the change in the Unified Parkinson Disease Rating Scale (UPDRS) II+III total score

Study Hypothesis:

The null hypothesis is that there is no difference between placebo and tesofensine.

The alternative hypothesis is that treatment with tesofensine is superior to treatment with placebo.

Comparison(s):

For the primary comparison between tesofensine and placebo, change in percentage off-time during waking hours will be based on reports from patient's diary (completed at day -3 and day-2 prior to the study visits) and change in the UPDRS II+III will be based on UPDRS II averaged for on and off periods and UPDRS III evaluated at on periods during the study visits.

Main inclusion criteria:

• Male or female patient with idiopathic Parkinson Disease (PD) diagnosed for at least 2 years.
• Patient aged 40 years or over at time of diagnosis of PD and not older than 80 years at screening visit.
• Modified Hoehn and Yahr stage of II to III at "on" time.
• Treatment with Levodopa at an optimised dose, 4 to 8 times per day, this dose being stable for at least 4 weeks prior to screening visit.
• Motor fluctuations, with 2.0 to 6.0 cumulative hours of "off" time every day during waking hours, documented from patient's diary completed for 2 consecutive days before baseline visit.

Main exclusion criteria:

• Neuropsychiatric exclusions: Non-idiopathic PD, dementia (Mini Mental State Exam <26), history of psychosis, history or current Axis I or Axis II mental disorder according to DSM-IV, etc
• Other medical exclusions, like ECG abnormalities, hypotension and/or symptomatic orthostatic hypotension, some abnormal laboratory parameters (e.g. severe renal impairment), etc
• Pharmacological exclusions, e.g. selegiline within 8 weeks prior to screening visit, regular use of anti-depressant drugs, any medication with central dopaminergic antagonist activity, etc