A Randomized, Double-blind, Placebo-controlled, Five Parallel Groups Efficacy and Safety Study of NS 2330 (Tesofensine) (0.125 mg, 0.25 mg, 0.5 mg and 1.0 mg) Administered Orally Once Daily Over 14 Weeks in Levodopa Treated Parkinson Patients With Motor Fluctuations
A Randomized, Double-blind, Placebo-controlled, Five Parallel Groups Efficacy and Safety Study of NS 2330 (Tesofensine) (0.125 mg, 0.25 mg, 0.5 mg and 1.0 mg) Administered Orally Once Daily Over 14 Weeks in Levodopa Treated Parkinson Patients With Motor Fluctuations
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