Tags

Type your tag names separated by a space and hit enter

AFQ056 in Parkinson patients with levodopa-induced dyskinesia: 13-week, randomized, dose-finding study.
Mov Disord. 2013 Nov; 28(13):1838-46.MD

Abstract

AFQ056 is a novel, selective metabotropic glutamate receptor 5 antagonist. This was a 13-week, double-blind, placebo-controlled study. Patients with Parkinson's disease and moderate-to-severe levodopa (l-dopa)-induced dyskinesia who were receiving stable l-dopa/anti-parkinsonian treatment and were not currently receiving amantadine were randomized to receive either AFQ056 (at doses of 20, 50, 100, 150, or 200 mg daily) or placebo (1:1:1:1:2:3 ratio) for 12 weeks. The primary outcome was the modified Abnormal Involuntary Movements Scale. Secondary outcomes included the 26-item Parkinson's Disease Dyskinesia Scale, the Patient's/Clinician's Global Impression of Change, and the Unified Parkinson's Disease Rating Scale parts III (motor evaluation) and IV (severity of motor complications). Safety was assessed. In total, 98 of 133 (73.7%) AFQ056-treated patients and 47 of 64 (73.4%) patients in the placebo group completed the study. Baseline characteristics were comparable. Patients randomized to AFQ056 200 mg daily administered in 2 doses demonstrated significant improvements at Week 12 on the modified Abnormal Involuntary Movements Scale compared with placebo (difference, -2.8; 95% confidence interval [CI], -5.2, -0.4; P = 0.007). Based on final actual doses, there was a dose-response relationship on the modified Abnormal Involuntary Movements Scale, with 200 mg daily demonstrating the most robust effect (difference, -3.6; 95% CI, -7.0, -0.3; P = 0.012). Improvements in dyskinesia were supported by change on Unified Parkinson's Disease Rating Scale part IV item 32 (50 mg daily: difference, -0.7; 95% CI, -1.1, -0.2; P = 0.003; 200 mg daily: difference, -0.5; 95% CI, -0.8, -0.1; P = 0.005). No significant changes were observed on the 26-item Parkinson's Disease Dyskinesia Scale, the Unified Parkinson's Disease Rating Scale part IV item 33 or items 32 and 33, or the Patient's/Clinician's Global Impression of Change. Unified Parkinson's Disease Rating Scale part III scores were not significantly changed, indicating no worsening of motor symptoms. The most common adverse events (with incidence greater with AFQ056 than with placebo) were dizziness, hallucination, fatigue, nasopharyngitis, diarrhea, and insomnia. AFQ056 demonstrated anti-dyskinetic efficacy in this population without worsening underlying motor symptoms. These results will guide dose selection for future clinical trials.

Authors+Show Affiliations

Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Pisana, Rome, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23853029

Citation

Stocchi, Fabrizio, et al. "AFQ056 in Parkinson Patients With Levodopa-induced Dyskinesia: 13-week, Randomized, Dose-finding Study." Movement Disorders : Official Journal of the Movement Disorder Society, vol. 28, no. 13, 2013, pp. 1838-46.
Stocchi F, Rascol O, Destee A, et al. AFQ056 in Parkinson patients with levodopa-induced dyskinesia: 13-week, randomized, dose-finding study. Mov Disord. 2013;28(13):1838-46.
Stocchi, F., Rascol, O., Destee, A., Hattori, N., Hauser, R. A., Lang, A. E., Poewe, W., Stacy, M., Tolosa, E., Gao, H., Nagel, J., Merschhemke, M., Graf, A., Kenney, C., & Trenkwalder, C. (2013). AFQ056 in Parkinson patients with levodopa-induced dyskinesia: 13-week, randomized, dose-finding study. Movement Disorders : Official Journal of the Movement Disorder Society, 28(13), 1838-46. https://doi.org/10.1002/mds.25561
Stocchi F, et al. AFQ056 in Parkinson Patients With Levodopa-induced Dyskinesia: 13-week, Randomized, Dose-finding Study. Mov Disord. 2013;28(13):1838-46. PubMed PMID: 23853029.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - AFQ056 in Parkinson patients with levodopa-induced dyskinesia: 13-week, randomized, dose-finding study. AU - Stocchi,Fabrizio, AU - Rascol,Olivier, AU - Destee,Alain, AU - Hattori,Nobutaka, AU - Hauser,Robert A, AU - Lang,Anthony E, AU - Poewe,Werner, AU - Stacy,Mark, AU - Tolosa,Eduardo, AU - Gao,Haitao, AU - Nagel,Jennifer, AU - Merschhemke,Martin, AU - Graf,Ana, AU - Kenney,Christopher, AU - Trenkwalder,Claudia, Y1 - 2013/07/12/ PY - 2012/11/02/received PY - 2013/05/02/revised PY - 2013/05/09/accepted PY - 2013/7/16/entrez PY - 2013/7/16/pubmed PY - 2014/6/28/medline KW - AFQ056 KW - Parkinson's disease KW - dyskinesias KW - glutamate antagonists KW - levodopa (l-dopa) SP - 1838 EP - 46 JF - Movement disorders : official journal of the Movement Disorder Society JO - Mov Disord VL - 28 IS - 13 N2 - AFQ056 is a novel, selective metabotropic glutamate receptor 5 antagonist. This was a 13-week, double-blind, placebo-controlled study. Patients with Parkinson's disease and moderate-to-severe levodopa (l-dopa)-induced dyskinesia who were receiving stable l-dopa/anti-parkinsonian treatment and were not currently receiving amantadine were randomized to receive either AFQ056 (at doses of 20, 50, 100, 150, or 200 mg daily) or placebo (1:1:1:1:2:3 ratio) for 12 weeks. The primary outcome was the modified Abnormal Involuntary Movements Scale. Secondary outcomes included the 26-item Parkinson's Disease Dyskinesia Scale, the Patient's/Clinician's Global Impression of Change, and the Unified Parkinson's Disease Rating Scale parts III (motor evaluation) and IV (severity of motor complications). Safety was assessed. In total, 98 of 133 (73.7%) AFQ056-treated patients and 47 of 64 (73.4%) patients in the placebo group completed the study. Baseline characteristics were comparable. Patients randomized to AFQ056 200 mg daily administered in 2 doses demonstrated significant improvements at Week 12 on the modified Abnormal Involuntary Movements Scale compared with placebo (difference, -2.8; 95% confidence interval [CI], -5.2, -0.4; P = 0.007). Based on final actual doses, there was a dose-response relationship on the modified Abnormal Involuntary Movements Scale, with 200 mg daily demonstrating the most robust effect (difference, -3.6; 95% CI, -7.0, -0.3; P = 0.012). Improvements in dyskinesia were supported by change on Unified Parkinson's Disease Rating Scale part IV item 32 (50 mg daily: difference, -0.7; 95% CI, -1.1, -0.2; P = 0.003; 200 mg daily: difference, -0.5; 95% CI, -0.8, -0.1; P = 0.005). No significant changes were observed on the 26-item Parkinson's Disease Dyskinesia Scale, the Unified Parkinson's Disease Rating Scale part IV item 33 or items 32 and 33, or the Patient's/Clinician's Global Impression of Change. Unified Parkinson's Disease Rating Scale part III scores were not significantly changed, indicating no worsening of motor symptoms. The most common adverse events (with incidence greater with AFQ056 than with placebo) were dizziness, hallucination, fatigue, nasopharyngitis, diarrhea, and insomnia. AFQ056 demonstrated anti-dyskinetic efficacy in this population without worsening underlying motor symptoms. These results will guide dose selection for future clinical trials. SN - 1531-8257 UR - https://www.unboundmedicine.com/medline/citation/23853029/AFQ056_in_Parkinson_patients_with_levodopa_induced_dyskinesia:_13_week_randomized_dose_finding_study_ L2 - https://doi.org/10.1002/mds.25561 DB - PRIME DP - Unbound Medicine ER -