Grants & Funding > The Michael J. Fox Foundation for Parkinson`s Research Grants 2013

 

The Michael J. Fox Foundation for Parkinson's Research is using its 2013 distribution to fund the following:

Inhaled Levodopa as a Treatment for Intermittent Motor Fluctuations in Parkinson’s Disease Patients

Continuous Subcutaneous Administration of Levodopa/carbidopa (ND0612) for the Treatment of Parkinson's Disease

PROJECT TITLE:  Inhaled Levodopa as a Treatment for Intermittent Motor Fluctuations in Parkinson’s Disease Patients

Investigators/Authors: Martin I. Freed, MD and Richard Batycky, PhD

Promising Outcomes of Original Grant:  Intrapulmonary delivery of L-dopa results in rapid, consistent and predictable augmentation of plasma L-dopa levels in both healthy volunteers and subjects with Parkinson’s disease.  The unique pharmacokinetic profile translates into rapid and durable improvement in motor function without worsening dyskinesia in Parkinson’s patients.  Results from prior clinical studies enabled dose selection for this, Phase 2b study of CVT-301, Civitas’ proprietary inhaled L-dopa which is being developed as a treatment to provide rapid relief of intermittent OFF episodes.

Objectives for Supplemental Investigation:    The objective of this study is to demonstrate that inhaled L-dopa safely provides rapid symptomatic relief of OFF episodes during chronic, at-home use.  The clinical benefit of adjunct CVT-301 use will be quantified both in the clinic, by evaluation of time course of change in UPDRS motor score following drug administration, and “at-home” by evaluation of the time to ON following drug administration upon the emergence of OFF symptoms.  This work is part of the continued clinical development of CVT-301 and will investigate, for the first time, its use at home as an adjunct to a patient’s standard combination L-dopa and decarboxylase inhibitor (for example, carbidopa) oral regimen.

Importance of This Research for the Development of a New PD Therapy:  This study is part of an integrated project plan to develop a new treatment to Parkinson’s patients to address an unmet medical need.  Successful results should enable the study of CVT-301 in pivotal Phase 3 studies.

September 2014 Project Update:

The Phase 2b study investigating the “as needed” use of CVT-301 adjunct to a scheduled daily regimen was designed to investigate the safety and efficacy of CVT-301 when self-administered “as needed” by patients for the treatment of OFF episodes. Patients were permitted to use CVT-301 up to 3 times a day to treat their emerging OFF episodes over a 1-month period of observation. Two doses of CVT-301 were studied; these doses delivered approximately 35 mg and 50 mg levodopa to the lung, respectively.
    
86 PD patients who experienced frequent OFF periods were administered CVT-301 or placebo. Clinically and statistically significant improvements in motor response, as measured by the Unified Parkinson’s Disease Rating Scale (UPDRS) Part 3 motor score, were observed with onset of benefit apparent at about 10 minutes post-dose. In addition CVT-301 resulted in significant improvements in subjective motor response. These ‘in-office’ measurements translated to clinically important and statistically significant improvements in OFF time, recorded by patients without an increase in time ON with dyskinesia, relative to placebo.

CVT-301 was generally safe and well tolerated in both doses.  There were no adverse changes in any respiratory (spirometry) endpoints.
Results:

Civitas is now planning a larger Phase 3 clinical trial, which is expected to begin in Q1 2015.

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PROJECT TITLE:  Continuous Subcutaneous Administration of Levodopa/carbidopa (ND0612) for the Treatment of Parkinson's Disease

Investigators/Authors: Sheila Oren, MD

Objective: Improving consistency of plasma levodopa (LD) has been a longstanding pharmacological challenge. ND0612 is a proprietary formulation of LD and carbidopa (CD) continuously administered subcutaneously (SC). It proposes a practical and efficacious symptomatic treatment strategy, providing more continuous dopaminergic stimulation that would consequently reduce or prevent motor complications in Parkinson’s disease (PD) patients.  ND0612 was safe, tolerable and exhibited dose-dependent constant LD plasma levels when administered for 24 hours in Phase I-II trials in healthy volunteers and PD patients. The present study will evaluate the clinical effects and the pharmacokinetics of a 14-day repeated ND0612 administration in advanced PD patients.

Project Description:  ND-0612 will be administered SC, continuously for 24h/day, via a delivery pump system during two weeks, using different day and night rates, to evaluate the safety, tolerability and pharmacokinetics of ND0612 in advanced PD patients.  The ease of use and logistics associated with the patients’ use of the SC pump in a conventional home setting will be evaluated. The patients will be evaluated for their symptoms improvement by recording their motor symptoms and activity of daily living, quality of life, quality of sleep and “on”-“off” periods during visit days.Oral LD dose supplementation or adjustment will be made, if needed. Blood samples will be collected at predetermined time points for the determination of plasma LD and CD concentrations. Dermal examinations will ensure the follow up on safety.

Relevance to Diagnosis/Treatment of Parkinson’s disease:  Continuous dopaminergic stimulation has shown to greatly improve disability and quality of life in advanced PD patients.  We anticipate that continuous administration of SC LD and CD (ND0612) will provide a highly effective, practical new therapy for the treatment of advanced PD, and potentially for slowing disease progression in early stage PD patients.

Anticipated Outcome: We anticipate that ND0612 will be safe, tolerable and maintain therapeutic LD plasma concentrations in PD patients.  Using exploratory clinical endpoints, it is anticipated that ND0612 will exhibit improved PD symptoms.   Furthermore, it is anticipated that the ease of use and logistics accompanying the use of the SC delivery pump, as well as the requested oral LD adjustment will be determined.

September 2014 Project Update:

As of August 5, 2014 the enrollment of 30 subjects for the 14-day “at home feasibility” study has been completed. No safety concerns have been reported during the execution of the study. The Neuroderm team is now in the process of analyzing the data, which should be presented officially at the PD Therapeutics conference October 29, 2014, in New York City.

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