Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
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; 65(5): 577-583.
Doi: 10.1001/archneur.65.5.577
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Study Group Mitglieder der Med Uni Graz:
- Schwingenschuh Petra
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- OBJECTIVE: To assess the safety and efficacy of tesofensine, a triple monoamine reuptake inhibitor, in patients with advanced Parkinson disease (PD). DESIGN: A pilot phase 2, randomized, double-blind, placebo-controlled, parallel-group trial. The study occurred in hospital-based outpatient clinics and in clinical trial units. Patients with advanced PD and levodopa-related motor fluctuations were enrolled. Tesofensine (0.125, 0.25, 0.5, or 1 mg) or placebo tablets were administered once daily for 14 weeks. MAIN OUTCOME MEASURES: Coprimary end points were the changes from baseline in Unified Parkinson Disease Rating Scale (UPDRS) subscale II (activities of daily living) plus subscale III (motor function) total score and in percentage of waking hours spent in "off" time noted in self-scoring diaries. Secondary end points were safety, pharmacokinetics, responder analysis (> or =20% reduction in UPDRS score and in off time), and changes in percentage of waking hours spent in "on" time with and without troublesome dyskinesia. RESULTS: The adjusted mean differences (relative to placebo) were -4.7 points in UPDRS subscale II plus subscale III total score (P =.005) with tesofensine, 0.5 mg, and -7.1% in off time (-68 minutes, P =.02) with tesofensine, 0.25 mg. Other dosages did not induce statistically significant effects. The plasma concentration increased with the dosage, but no clear dose-response relationship was observed. Gastrointestinal tract and neuropsychiatric adverse events were more frequent with tesofensine than with placebo, especially at the higher dosages. CONCLUSIONS: Patients with PD in advanced stages showed modest improvements in UPDRS subscale II plus subscale III total score and in off time when treated with tesofensine, but a dose-response relationship could not be established for efficacy, while adverse drug reactions tended to be more frequent at higher dosages. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00148512.
- Find related publications in this database (using NLM MeSH Indexing)
- Activities of Daily Living -
- Adult -
- Aged -
- Aged, 80 and over -
- Bicyclo Compounds, Heterocyclic - administration and dosageBicyclo Compounds, Heterocyclic - adverse effectsBicyclo Compounds, Heterocyclic - blood
- Biogenic Monoamines - agonists
- Disease Progression -
- Dose-Response Relationship, Drug -
- Double-Blind Method -
- Female -
- Gastrointestinal Diseases - chemically induced
- Humans -
- Male -
- Mental Disorders - chemically induced
- Middle Aged -
- Neurotransmitter Uptake Inhibitors - administration and dosageNeurotransmitter Uptake Inhibitors - adverse effectsNeurotransmitter Uptake Inhibitors - blood
- Parkinson Disease - drug therapy
- Pilot Projects -
- Placebos -
- Treatment Outcome -