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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Five Parallel Groups Efficacy and Safety Exploratory Study of NS 2330 (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 (Study for Proof of Concept in ADVAnced Parkinson Disease of NS 2330 / ADVANS)

Conditions
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Parkinson Disease

Intervention / Treatment
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* Drug: 1. Tesofensine (NS 2330)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 42 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: 1. Tesofensine (NS 2330)|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| UPDRS parts II (averaged on and off) |  | 14 weeks | 
| Off time during waking hours |  | 14 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent on time without dyskinesia, or with non troublesome dyskinesia, or both, or with troublesome dyskinesia |  | 14 weeks | 
| Unified Parkinson's Disease Rating Scale (UPDRS) I to IV sub-scores |  | 14 weeks | 
| Clinical Global Impressions (CGI) Improvement and Severity |  | 14 weeks | 
| Auditory Verbal Learning test (AVLT) |  | 14 weeks | 
| Modified Schwab and England Disability scale |  | 14 weeks | 
| Snaith-Hamilton Pleasure Scale (SHAPS) |  | 14 weeks | 
| Percentage of patients with at least a 20%-improvement in percent off time during waking hours |  | 14 weeks | 
| Percentage of patients with at least a 20% or a 30%-improvement in UPDRS parts II+III total score |  | 14 weeks |