Civitas Therapeutics, Inc., a privately-held pharmaceutical company,  has initiated phase II a clinical trial in Parkinson’s disease patients evaluating CVT-301, an inhaled formulation of levodopa (L-dopa), for the rapid relief from motor fluctuations. CVT-301 provides immediate onset of a large and precise dose of L-dopa.

“Consistent with our commitment to rapidly develop important new therapies for patients, we demonstrated pharmacokinetic proof-of-concept for CVT-301 in less than 12 months from launching Civitas and are now initiating this phase II a study in Parkinson’s patients,” said Dr Martin Freed, chief medical officer and co-founder of Civitas. “Leveraging the ARCUS platform along with the 40 years of existing L-dopa clinical experience we hope to provide Parkinson’s patients with a new therapy enabling improved management of their motor fluctuations.”

The phase II a study is a randomized, placebo-controlled, single dose, cross-over design that will characterize the safety and tolerability of CVT-301 and evaluate pharmacodynamic effects and L-dopa pharmacokinetics in patients with Parkinson’s disease with motor fluctuations (“off episodes”). This phase II a study is designed to establish the dose for future clinical trials with CVT-301. Patients will receive oral Sinemet, inhaled placebo and CVT-301 which will be followed by serial evaluations of L- dopa pharmacokinetics, motor response and safety at each visit. Twenty-four (24) patients will be enrolled.

This phase II a study of CVT-301 is funded in part by a grant from The Michael J Fox Foundation for Parkinson’s Research.

Civitas’ lead programme, CVT-301, is an inhaled formulation of L-dopa for the immediate relief from debilitating motor fluctuations associated with Parkinson’s disease. For symptomatic relief, oral L-dopa is administered to maintain dopamine levels in the brain above the therapeutic threshold; yet the efficacy of oral L-dopa is significantly compromised by delayed absorption and excessive variability in the circulating plasma drug concentrations inherent to the oral delivery route. CVT-301 is an ARCUS therapeutic that incorporates L-dopa and is optimized to deliver a precise dose to the deep lung for rapid and predictable L-dopa absorption. The ARCUS platform is uniquely able to deliver the necessary L- dopa dose with the required precision. CVT-301 is being developed as an adjunct to standard oral L- dopa therapy to enable patients to manage motor fluctuations caused in part by the inter-dose variability of oral L-dopa. In preclinical models, CVT-301 has demonstrated rapid, durable symptomatic relief, even when compared to larger doses of oral L-dopa.

The phase I clinical study is complete, and pharmacokinetic proof-of-concept was demonstrated. Therapeutic plasma levels of L-dopa were achieved within five minutes of inhalation dosing with unprecedented precision. Dose proportional pharmacokinetics were seen across all doses tested. In addition, all doses tested of CVT-301 were safe and well tolerated.

Parkinson’s disease is a neurodegenerative disorder caused by the diminished production of dopamine, a key neurotransmitter, resulting in progressive impairment of motor function including tremors, rigidity and difficulty in moving. Even when treated with the current standard of care, the majority of Parkinson’s patients continue to experience motor fluctuations. These motor fluctuations reduce patients’ ability to lead productive, independent lives and are recognized by patients, care givers and healthcare professionals as one of the most troubling and debilitating issues associated with the disease.