Inhaled dry powder apomorphine (VR040) for ‘off ’ periods in Parkinson's disease: an in‐clinic double‐blind dose ranging study

  title={Inhaled dry powder apomorphine (VR040) for ‘off ’ periods in Parkinson's disease: an in‐clinic double‐blind dose ranging study},
  author={Katherine Anne Grosset and Naveed Malek and Frazer Giles Morgan and Donald G. Grosset},
  journal={Acta Neurologica Scandinavica},
‘Off’ periods increase as Parkinson's disease (PD) progresses and the benefits of standard therapy wane. Subcutaneous apomorphine rescues ‘off’ periods, but patient self‐injection and adverse cutaneous effects are sometimes problematic. 
A randomized trial of inhaled levodopa (CVT‐301) for motor fluctuations in Parkinson's disease
CVT‐301 self‐administered by PD patients to relieve OFF episodes is evaluated, showing potential for rapid onset of action and sudden loss of dose effect and delayed benefit.
Apomorphine for Parkinson’s Disease: Efficacy and Safety of Current and New Formulations
The evidence regarding the efficacy and tolerability of apomorphine, both in its established formulations (subcutaneous intermittent injection and continuous infusion) and in the new preparations currently under investigation are summarized.
Pharmacotherapeutic Strategies to Treat or Prevent OFF Episodes in Adults with Parkinson's disease
Parkinson’s disease is a chronic, neurodegenerative disease which manifests with a mixture of motor, cognitive and behavioral symptoms. Levodopa is the most effective antiparkinsonian treatment to
An evaluation of subcutaneous apomorphine for the treatment of Parkinson’s disease
  • T. Müller
  • Medicine
    Expert opinion on pharmacotherapy
  • 2020
This narrative review summarizes the subcutaneous administration, efficacy, and side effects of the non-ergot derivative dopamine agonist apomorphine following a non-systematic literature research.
Apomorphine therapy in Parkinson's and future directions.
This review discusses interesting and novel delivery strategies of apomorphine or esters via oral, buccal, inhalation and a novel pump-patch route, and discusses recent research that has highlighted some important properties of apomorphicine in animal models.
Pharmacological Insights into the Use of Apomorphine in Parkinson’s Disease: Clinical Relevance
The ongoing progress in the development of analytical methods should be accompanied by new pharmacokinetic and pharmacodynamic studies of apomorphine metabolism and sites of action in humans, as its biochemistry has yet to be fully described.
Apomorphine - pharmacological properties and clinical trials in Parkinson's disease.
Apomorphine is often considered an archetypal dopamine agonist used in the treatment of Parkinson's disease, and when administered as an acute subcutaneous injection, it induces reliable and rapid relief from OFF periods underscoring its utility as a rescue medication.
Non-oral dopaminergic therapies for Parkinson’s disease: current treatments and the future
This review discusses and summarizes the most recent developments in this field with a focus on non-oral dopaminergic strategies in development or to be licensed for management of Parkinson’s disease.
Old Drugs, New Delivery Systems in Parkinson’s Disease
This review aims to provide up-to-date information about the newer delivery options for drugs used for Parkinson’s disease and provides a summary of infusion therapy with apomorphine, modifications to other dopamine agonists, various oral formulations of carbidopa/levodopa, inhaled levodOPA, intrajejunal infusion of levod opium, and sublingual apomorphicine.
Gastrointestinal problems (GI), the common non-motor symptom, are the most important cause of motor fluctuations that occur as a result of inadequate oral treatment with the progression of PD.


Phase IIa randomized double‐blind, placebo‐controlled study of inhaled apomorphine as acute challenge for rescuing ‘off’ periods in patients with established Parkinson's disease
In this first study of inhaled apomorphine (VR040) in patients with Parkinson's disease, the primary objective was to find the minimum efficacious dose of apomorphine that was useful in rescuing
Subcutaneous continuous apomorphine infusion in fluctuating patients with Parkinson's disease: long-term results
Clinical data of 30 PD patients having at least five years of treatment with subcutaneous continuous apomorphine infusion are reported, showing that Apomorphine is a potent water-soluble dopamine receptor agonist that has been shown to successfully control motor fluctuation when subcutaneously infused in complicated parkinsonian patients.
A double‐blind, placebo‐controlled study of intranasal apomorphine spray as a rescue agent for off‐states in Parkinson's disease
It is concluded that intranasal apomorphine is an effective rescue agent for parkinsonian off‐states although nasal irritation is a limiting factor.
Subcutaneous apomorphine in the treatment of Parkinson's disease.
Subcutaneous apomorphine is proposed as an effective treatment for patients with incapacitating "off" period disabilities refractory to oral medication and should be considered before experimental implantation procedures.
Orodispersible sublingual piribedil to abort OFF episodes: A single dose placebo‐controlled, randomized, double‐blind, cross‐over study
  • O. Rascol, J. Azulay, +12 authors Y. Agid
  • Psychology, Medicine
    Movement disorders : official journal of the Movement Disorder Society
  • 2010
A single dose of up to 60 mg of S90049 given sublingually was superior to placebo in improving UPDRS III and aborting a practical OFF in patients with advanced PD.
Comparison of orally dissolving carbidopa/levodopa (Parcopa) to conventional oral carbidopa/levodopa: A single‐dose, double‐blind, double‐dummy, placebo‐controlled, crossover trial
This small pilot study did not show significant group differences favoring OD C/L; however, larger studies may be justified, and individual patients may benefit.
Pharmacokinetic-Pharmacodynamic Relationships of Apomorphine in Patients with Parkinson’s Disease
The population pharmacokinetic-pharmacodynamic data reflect the clinical observations of steep dose-effect curves if apomorphine is used in patients with random ‘on-off’ fluctuations and could be helpful in predicting the clinical effects of apomorphicine in the several subgroups of patients with Parkinson’s disease.
Apomorphine in treatment of Parkinson's disease: comparison between subcutaneous and sublingual routes.
The efficacy of two routes of apomorphine, subcutaneous (SC) and sublingual (SL), successively administered in 7 Parkinsonian patients with motor fluctuations, was compared in reducing the daily
Melevodopa/carbidopa effervescent formulation in the treatment of motor fluctuations in advanced Parkinson's disease
This study failed to meet the primary endpoint of reducing total daily OFF time, but there was a trend in favour of the M/C preparation, which deserves further attention.
Pharmacokinetics of Etilevodopa Compared to Levodopa in Patient's With Parkinson's Disease: An Open-label, Randomized, Crossover Study
Clinical trials with etilevodopa/carbidopa tablets should be carried out in PD patients with response fluctuations such as “delayed on” and “dose failures”, with a safety profile comparable to that of levodopa / carbidopa.