Clinical trial NCT00148512: 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
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Parkinson Disease
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2005-09-08
Enrollment: 254
Sex: ALL
Minimum age (years): 42
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: UPDRS parts II (averaged "on" and "off")
timeFrame: 14 weeks
measure: "Off" time during waking hours
timeFrame: 14 weeks
Secondary outcomes:
measure: Percent on time without dyskinesia, or with non troublesome dyskinesia, or both, or with troublesome dyskinesia
timeFrame: 14 weeks
measure: Unified Parkinson's Disease Rating Scale (UPDRS) I to IV sub-scores
timeFrame: 14 weeks
measure: Clinical Global Impressions (CGI) Improvement and Severity
timeFrame: 14 weeks
measure: Auditory Verbal Learning test (AVLT)
timeFrame: 14 weeks
measure: Modified Schwab and England Disability scale
timeFrame: 14 weeks
measure: Snaith-Hamilton Pleasure Scale (SHAPS)
timeFrame: 14 weeks
measure: Percentage of patients with at least a 20%-improvement in percent "off" time during waking hours
timeFrame: 14 weeks
measure: Percentage of patients with at least a 20% or a 30%-improvement in UPDRS parts II+III total score
timeFrame: 14 weeks
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Krankenhaus d. Barmherzigen Brüder Graz-Eggenberg
city: Graz
country: Austria
facility: Univ.-Klinik für Neurologie
city: Innsbruck
country: Austria
facility: Univ.-Klinik für Neurologie
city: Linz
country: Austria
facility: Landesnervenklinik Wagner Jauregg Linz
city: Linz
country: Austria
facility: AKH der Stadt Linz
city: St. Pölten
country: Austria
facility: Landesklinikum St. Pölten
city: Aix en Provence
country: France
facility: Hôpital du Pays d'Aix
city: Bron cedex
country: France
facility: Hôpital Pierre Wertheimer
city: Clermont Ferrand
country: France
facility: Hôpital Gabriel Montpied
city: Lille cedex
country: France
facility: Hôpital Roger Salengro
city: Marseille
country: France
facility: Hôpital de la Timone
city: Paris
country: France
facility: Service de Neurologie
city: Pessac
country: France
facility: Hôpital du Haut-Levèque
city: Poitiers cedex
country: France
facility: Centre Hospitalier Universitaire JB Miletrie
city: Saint Herblain
country: France
facility: Hôpital Guillaume et René Laennec
city: Toulouse cedex 7
country: France
facility: Hôpital Purpan
city: Berlin
country: Germany
facility: Universitätsklinikum der Humboldt-Universität
city: Berlin
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Bochum
country: Germany
facility: St. Josef-Hospital
city: Gera
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Herborn
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Kassel
country: Germany
facility: Paracelsus-Elena-Klinik
city: Kiel
country: Germany
facility: Christian Albrechts Universität zu Kiel
city: Leipzig
country: Germany
facility: Universität Leipzig
city: Marburg
country: Germany
facility: Klinik für Neurologie
city: München
country: Germany
facility: Klinikum Großhadern der L.M.-Universität
city: Rostock
country: Germany
facility: Universitätsklinik Rostock
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
city: Wiesbaden
country: Germany
facility: Deutsche Klinik für Diagnostik GmbH
city: 's-Hertogenbosch
country: Netherlands
facility: Locatie Willem-Alexander
city: Breda
country: Netherlands
facility: Boehringer Ingelheim Investigational Site
city: Groningen
country: Netherlands
facility: Martini ziekenhuis
city: Sittard
country: Netherlands
facility: Maasland Ziekenhuis
city: Utrecht
country: Netherlands
facility: Boehringer Ingelheim Investigational Site
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebrón
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de BCN
city: Barcelona
country: Spain
facility: Hospital de la Sta. Creu i Sant Pau
city: Madrid
country: Spain
facility: Hospital Gregorio Marañón
city: Santiago de Compostela
country: Spain
facility: Hospital Clínico niversitario de Santiago de Compostela
city: Sevilla
country: Spain
facility: Hospital Clínico Universitario Vírgen de la Macarena
city: Birmingham
country: United Kingdom
facility: City Hospital
city: Blackburn
country: United Kingdom
facility: Neurology Department
city: Glasgow
country: United Kingdom
facility: Neurology Department
city: Liverpool
country: United Kingdom
facility: Walton Centre for Neurology
city: Newcastle upon Tyne
country: United Kingdom
facility: Regional Neurosciences Centre
city: Stoke-On-Trent
country: United Kingdom
facility: Neurology Research
city: Swansea
country: United Kingdom
facility: Neurology Department
Study officials:
affiliation: BI France S.A.S.
name: Boehringer Ingelheim Study Coordinator
role: STUDY_CHAIR
References:
citation: 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.