The D1/D5 Dopamine Partial Agonist PF-06412562 in Advanced-Stage Parkinson's Disease: A Feasibility Study.
J Parkinsons Dis
; 10(4): 1515-1527, 2020.
Article
em En
| MEDLINE
| ID: mdl-32986682
ABSTRACT
BACKGROUND:
Current drug treatments have little efficacy in advanced-to-end-stage Parkinson's disease (advPD), yet there are no reports of interventional trials in advPD. D1 dopamine agonists have the potential to provide benefit.OBJECTIVE:
To determine the feasibility and safety of the selective D1/D5 dopamine partial agonist PF 06412562 in advPD.METHODS:
A two-week, randomized, double blind, crossover phase Ib study in advPD patients compared standard-of-care (SoC) carbidopa/levodopa with PF 06412562. Each week, there was a Day 1 baseline evaluation with overnight levodopa washout, then treatment on Days 2 and 3 with either SoC or PF-06412562 (split dose 25â+â20âmg), followed by discharge on Day 4. Primary endpoints were safety and tolerability. Secondary endpoints were global clinical impression of change (GCI-C) rated by clinicians and caregivers.RESULTS:
Eight advPD patients and their caregivers consented to participate and six were randomized (average disease duration 22ây). None withdrew voluntarily. One participant with baseline Day 1 dehydration, pre-renal kidney injury, and autonomic dysfunction experienced symptomatic and serious hypotension after receiving PF-06412562 in Week 1 and was discontinued from the study. All other adverse events were rated mild (PF-06412562 nâ=â1, SoC nâ=â0), moderate (PF-06412562 nâ=â1, SoC nâ=â1), or severe but non-serious (PF-06412562 nâ=â3, SoC nâ=â2). No clinically meaningful laboratory changes were observed. Among the five participants who completed the study, GCI-C favored PF-06412562 in two per clinicians' and four participants per caregivers' rating.CONCLUSION:
PF-06412562 was tolerated in advPD patients. This study provides the feasibility for future safety and efficacy studies in this population with unmet needs.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
/
Carbidopa
/
Levodopa
/
Receptores de Dopamina D1
/
Agonistas de Dopamina
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos