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

Parkinson Disease Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00148512
• Other study ID #: 1198.101
• Status: Completed
• Phase: Phase 2
• First received: September 7, 2005
• Last updated: October 28, 2013
• Start date: March 2003
• Est. completion date: February 2005

Study information

• Verified date: October 2013
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: AFSSAPSAustria: BMGFGermany: BfArMSpain: AEMPSUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyNetherlands: MEB
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 254
• Est. completion date: February 2005
• Est. primary completion date: February 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 42 Years to 80 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Parkinson Disease

Intervention

Drug:
• 1. Tesofensine (NS 2330)

Locations

Country	Name	City	State
Austria	Krankenhaus d. Barmherzigen Brüder Graz-Eggenberg	Graz
Austria	Univ.-Klinik für Neurologie	Graz
Austria	Univ.-Klinik für Neurologie	Innsbruck
Austria	AKH der Stadt Linz	Linz
Austria	Landesnervenklinik Wagner Jauregg Linz	Linz
Austria	Landesklinikum St. Pölten	St. Pölten
France	Hôpital du Pays d'Aix	Aix en Provence
France	Hôpital Pierre Wertheimer	Bron cedex
France	Hôpital Gabriel Montpied	Clermont Ferrand
France	Hôpital Roger Salengro	Lille cedex
France	Hôpital de la Timone	Marseille
France	Service de Neurologie	Paris
France	Hôpital du Haut-Levèque	Pessac
France	Centre Hospitalier Universitaire JB Miletrie	Poitiers cedex
France	Hôpital Guillaume et René Laennec	Saint Herblain
France	Hôpital Purpan	Toulouse cedex 7
Germany	Boehringer Ingelheim Investigational Site	Berlin
Germany	Boehringer Ingelheim Investigational Site	Berlin
Germany	Boehringer Ingelheim Investigational Site	Berlin
Germany	Boehringer Ingelheim Investigational Site	Berlin
Germany	Universitätsklinikum der Humboldt-Universität	Berlin
Germany	St. Josef-Hospital	Bochum
Germany	Boehringer Ingelheim Investigational Site	Gera
Germany	Boehringer Ingelheim Investigational Site	Herborn
Germany	Paracelsus-Elena-Klinik	Kassel
Germany	Christian Albrechts Universität zu Kiel	Kiel
Germany	Universität Leipzig	Leipzig
Germany	Klinik für Neurologie	Marburg
Germany	Klinikum Großhadern der L.M.-Universität	München
Germany	Universitätsklinik Rostock	Rostock
Germany	Universitätsklinikum Ulm	Ulm
Germany	Deutsche Klinik für Diagnostik GmbH	Wiesbaden
Netherlands	Locatie Willem-Alexander	's-Hertogenbosch
Netherlands	Boehringer Ingelheim Investigational Site	Breda
Netherlands	Martini ziekenhuis	Groningen
Netherlands	Maasland Ziekenhuis	Sittard
Netherlands	Boehringer Ingelheim Investigational Site	Utrecht
Spain	Hospital Clinic i Provincial de BCN	Barcelona
Spain	Hospital de la Sta. Creu i Sant Pau	Barcelona
Spain	Hospital Vall d'Hebrón	Barcelona
Spain	Hospital Gregorio Marañón	Madrid
Spain	Hospital Clínico niversitario de Santiago de Compostela	Santiago de Compostela
Spain	Hospital Clínico Universitario Vírgen de la Macarena	Sevilla
United Kingdom	City Hospital	Birmingham
United Kingdom	Neurology Department	Blackburn
United Kingdom	Neurology Department	Glasgow
United Kingdom	Walton Centre for Neurology	Liverpool
United Kingdom	Regional Neurosciences Centre	Newcastle upon Tyne
United Kingdom	Neurology Research	Stoke-On-Trent
United Kingdom	Neurology Department	Swansea

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

Austria,  France,  Germany,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	UPDRS parts II (averaged "on" and "off")		14 weeks	No
Primary	"Off" time during waking hours		14 weeks	No
Secondary	Percent on time without dyskinesia, or with non troublesome dyskinesia, or both, or with troublesome dyskinesia		14 weeks	No
Secondary	Unified Parkinson's Disease Rating Scale (UPDRS) I to IV sub-scores		14 weeks	No
Secondary	Clinical Global Impressions (CGI) Improvement and Severity		14 weeks	No
Secondary	Auditory Verbal Learning test (AVLT)		14 weeks	No
Secondary	Modified Schwab and England Disability scale		14 weeks	No
Secondary	Snaith-Hamilton Pleasure Scale (SHAPS)		14 weeks	No
Secondary	Percentage of patients with at least a 20%-improvement in percent "off" time during waking hours		14 weeks	No
Secondary	Percentage of patients with at least a 20% or a 30%-improvement in UPDRS parts II+III total score		14 weeks	No