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

October 28, 2013 updated by: Boehringer Ingelheim

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)

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.

Study Overview

Status

Completed

Conditions

Parkinson Disease

Intervention / Treatment

Drug: 1. Tesofensine (NS 2330)

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

254

Phase

Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Austria
- - Graz, Austria, 8036
    - Univ.-Klinik für Neurologie
  - Graz, Austria, 8020
    - Krankenhaus d. Barmherzigen Brüder Graz-Eggenberg
  - Innsbruck, Austria, 6020
    - Univ.-Klinik für Neurologie
  - Linz, Austria, 4021
    - AKH der Stadt Linz
  - Linz, Austria, 4020
    - Landesnervenklinik Wagner Jauregg Linz
  - St. Pölten, Austria, 3100
    - Landesklinikum St. Pölten
France
- - Aix en Provence, France, 13616
    - Hôpital du Pays d'Aix
  - Bron cedex, France, 69677
    - Hopital Pierre Wertheimer
  - Clermont Ferrand, France, 63003
    - Hopital Gabriel Montpied
  - Lille cedex, France, 59037
    - Hopital Roger Salengro
  - Marseille, France, 13385
    - hopital de la Timone
  - Paris, France, 75013
    - Service de Neurologie
  - Pessac, France, 33604
    - Hopital Du Haut-Leveque
  - Poitiers cedex, France, 86021
    - Centre Hospitalier Universitaire JB Miletrie
  - Saint Herblain, France, 44800
    - Hopital Guillaume Et Rene Laennec
  - Toulouse cedex 7, France, 31073
    - Hopital Purpan
Germany
- - Berlin, Germany, 10117
    - Universitätsklinikum der Humboldt-Universität
  - Berlin, Germany, 10178
    - Boehringer Ingelheim Investigational Site
  - Berlin, Germany, 12163
    - Boehringer Ingelheim Investigational Site
  - Berlin, Germany, 12167
    - Boehringer Ingelheim Investigational Site
  - Berlin, Germany, 13507
    - Boehringer Ingelheim Investigational Site
  - Bochum, Germany, 44791
    - St. Josef-Hospital
  - Gera, Germany, 07551
    - Boehringer Ingelheim Investigational Site
  - Herborn, Germany, 35745
    - Boehringer Ingelheim Investigational Site
  - Kassel, Germany, 34128
    - Paracelsus-Elena-Klinik
  - Kiel, Germany, 24105
    - Christian Albrechts Universität zu Kiel
  - Leipzig, Germany, 04103
    - Universität Leipzig
  - Marburg, Germany, 35033
    - Klinik fur Neurologie
  - München, Germany, 81377
    - Klinikum Großhadern der L.M.-Universität
  - Rostock, Germany, 18147
    - Universitätsklinik Rostock
  - Ulm, Germany, 89075
    - Universitätsklinikum Ulm
  - Wiesbaden, Germany, 65191
    - Deutsche Klinik für Diagnostik GmbH
Netherlands
- - 's-Hertogenbosch, Netherlands, 5223 GV
    - Locatie Willem-Alexander
  - Breda, Netherlands, 4818 CK
    - Boehringer Ingelheim Investigational Site
  - Groningen, Netherlands, 9728 RM
    - Martini ziekenhuis
  - Sittard, Netherlands, 6163 BK
    - Maasland Ziekenhuis
  - Utrecht, Netherlands, 3584 CX
    - Boehringer Ingelheim Investigational Site
Spain
- - Barcelona, Spain, 08035
    - Hospital Vall d'Hebron
  - Barcelona, Spain, 08036
    - Hospital Clinic i Provincial de BCN
  - Barcelona, Spain, 08041
    - Hospital de la Sta. Creu i Sant Pau
  - Madrid, Spain, 28007
    - Hospital Gregorio Marañón
  - Santiago de Compostela, Spain, 15706
    - Hospital Clínico niversitario de Santiago de Compostela
  - Sevilla, Spain, 41071
    - Hospital Clínico Universitario Vírgen de la Macarena
United Kingdom
- - Birmingham, United Kingdom, B18 7QH
    - City Hospital
  - Blackburn, United Kingdom, BB2 3L0
    - Neurology department
  - Glasgow, United Kingdom, G51 4TF
    - Neurology department
  - Liverpool, United Kingdom, L9 7LJ
    - Walton Centre for Neurology
  - Newcastle upon Tyne, United Kingdom, NE4 6BE
    - Regional Neurosciences Centre
  - Stoke-On-Trent, United Kingdom, ST4 7LN
    - Neurology Research
  - Swansea, United Kingdom, 6AS 6NL
    - Neurology department

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

42 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Boehringer Ingelheim

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Rascol O, Poewe W, Lees A, Aristin M, Salin L, Juhel N, Waldhauser L, Schindler T; ADVANS Study Group. Tesofensine (NS 2330), a monoamine reuptake inhibitor, in patients with advanced Parkinson disease and motor fluctuations: the ADVANS Study. Arch Neurol. 2008 May;65(5):577-83. doi: 10.1001/archneur.65.5.577.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2003

Primary Completion (Actual)

February 1, 2005

Study Completion