A Antonini1, L Bauer2, E Dohin3, W H Oertel4, O Rascol5, H Reichmann6, M Schmid2, P Singh2, E Tolosa7, K Ray Chaudhuri8. 1. Parkinson and Movement Disorders Unit, IRCCS Hospital San Camillo, Venice, Italy. 2. UCB Pharma, Monheim am Rhein, Germany. 3. UCB Pharma, Paris, France. 4. Department of Neurology, Philipps University, Marburg, Germany. 5. Clinical Investigation Centre CIC1436, and Departments of Clinical Pharmacology and Neurosciences, INSERM and Toulouse University Hospital, Toulouse, France. 6. Department of Neurology, University of Dresden, Dresden, Germany. 7. Neurology Service, Hospital Clinic de Barcelona, Universitat de Barcelona, IDIBAPS, Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona Catalonia, Spain. 8. National Parkinson Foundation International Centre of Excellence, King's College Hospital, Kings College and Kings Health Partners, London, UK.
Abstract
BACKGROUND AND PURPOSE:Non-motor symptoms (NMS) of Parkinson's disease (PD) have a major impact on health-related quality of life. This is the first randomized controlled trial to use the NMS Scale (NMSS) as a primary outcome to assess treatment effects on NMS in PD. METHODS: In this double-blind trial (NCT01300819), patients with PD and a total NMSS score ≥40 were randomized (2:1) to rotigotine or placebo, titrated over 1-7 weeks to optimal dose (≤8 mg/24 h for patients not receiving levodopa, ≤16 mg/24 h for patients receiving levodopa), maintained for 12 weeks. The primary outcome was change in NMSS total score from baseline to end of maintenance. Secondary outcomes were the nine NMSS domains, Unified Parkinson's Disease Rating Scale (UPDRS) III (motor) and the 39-item Parkinson's Disease Questionnaire (PDQ-39). RESULTS: In total, 283/349 (81.1%) randomized patients completed the trial; 211 rotigotine and 122 placebo were included in the full analysis set. The NMSS total score decreased by 23 (rotigotine) and 19 (placebo) points; the treatment difference was not statistically significant (-3.58; 95% confidence interval -8.43, 1.26; P = 0.147). Numerically greater than placebo improvements were detected in the 'mood/apathy' and 'miscellaneous' NMSS domains (P < 0.05). Treatment differences in UPDRS III (-2.60; -4.27, -0.92; P = 0.002) and PDQ-39 (-2.79; -5.21, -0.37; P = 0.024) favoured rotigotine. Adverse events reported more frequently with rotigotine were nausea, application site reactions, somnolence and headache. CONCLUSIONS:Rotigotine improvement in the multi-domain NMSS total score was not superior to placebo. A different sensitivity of individual NMSS domains to dopaminergic therapy and a large placebo effect may have contributed to these findings.
RCT Entities:
BACKGROUND AND PURPOSE: Non-motor symptoms (NMS) of Parkinson's disease (PD) have a major impact on health-related quality of life. This is the first randomized controlled trial to use the NMS Scale (NMSS) as a primary outcome to assess treatment effects on NMS in PD. METHODS: In this double-blind trial (NCT01300819), patients with PD and a total NMSS score ≥40 were randomized (2:1) to rotigotine or placebo, titrated over 1-7 weeks to optimal dose (≤8 mg/24 h for patients not receiving levodopa, ≤16 mg/24 h for patients receiving levodopa), maintained for 12 weeks. The primary outcome was change in NMSS total score from baseline to end of maintenance. Secondary outcomes were the nine NMSS domains, Unified Parkinson's Disease Rating Scale (UPDRS) III (motor) and the 39-item Parkinson's Disease Questionnaire (PDQ-39). RESULTS: In total, 283/349 (81.1%) randomized patients completed the trial; 211 rotigotine and 122 placebo were included in the full analysis set. The NMSS total score decreased by 23 (rotigotine) and 19 (placebo) points; the treatment difference was not statistically significant (-3.58; 95% confidence interval -8.43, 1.26; P = 0.147). Numerically greater than placebo improvements were detected in the 'mood/apathy' and 'miscellaneous' NMSS domains (P < 0.05). Treatment differences in UPDRS III (-2.60; -4.27, -0.92; P = 0.002) and PDQ-39 (-2.79; -5.21, -0.37; P = 0.024) favoured rotigotine. Adverse events reported more frequently with rotigotine were nausea, application site reactions, somnolence and headache. CONCLUSIONS:Rotigotine improvement in the multi-domain NMSS total score was not superior to placebo. A different sensitivity of individual NMSS domains to dopaminergic therapy and a large placebo effect may have contributed to these findings.
Authors: D Santos García; T De Deus Fonticoba; J M Paz González; C Cores Bartolomé; L Valdés Aymerich; J G Muñoz Enríquez; E Suárez; S Jesús; M Aguilar; P Pastor; L L Planellas; M Cosgaya; J García Caldentey; N Caballol; I Legarda; J Hernández Vara; I Cabo; L López Manzanares; I González Aramburu; M A Ávila Rivera; M J Catalán; V Nogueira; V Puente; J M García Moreno; C Borrué; B Solano Vila; M Álvarez Sauco; L Vela; S Escalante; E Cubo; F Carrillo Padilla; J C Martínez Castrillo; P Sánchez Alonso; M G Alonso Losada; N López Ariztegui; I Gastón; J Kulisevsky; M Blázquez Estrada; M Seijo; J Rúiz Martínez; C Valero; M Kurtis; O de Fábregues; J González Ardura; C Ordás; L López Díaz; P Mir; P Martinez-Martin Journal: Parkinsons Dis Date: 2021-05-13
Authors: Robert A Hauser; Jaroslaw Slawek; Paolo Barone; Elisabeth Dohin; Erwin Surmann; Mahnaz Asgharnejad; Lars Bauer Journal: BMC Neurol Date: 2016-06-07 Impact factor: 2.474
Authors: David G Standaert; Ramon L Rodriguez; John T Slevin; Michael Lobatz; Susan Eaton; Krai Chatamra; Maurizio F Facheris; Coleen Hall; Kavita Sail; Yash J Jalundhwala; Janet Benesh Journal: Mov Disord Clin Pract Date: 2017-09-20