Civitas Therapeutics, Inc., a biopharmaceutical company developing transformative therapeutics using the ARCUS respiratory delivery platform, has begun a phase II b clinical study of CVT-301, an inhaled formulation of levodopa (Ldopa). This phase II study will evaluate the efficacy and safety of CVT-301 in treating emergent OFF episodes during one month of continued use.

CVT-301 is being developed as an adjunct, as needed (PRN) therapy that will provide rapid and reliable relief from intermittent debilitating motor fluctuations (OFF episodes) that affect many Parkinson’s disease patients.

The phase IIb study follows a successful phase IIa study for CVT-301, which demonstrated that the administration of CVT-301 to patients in the OFF state produced a rapid and durable improvement in motor function. The pharmacokinetic data recapitulated the phase I study results showing CVT-301 provided immediate L-dopa absorption and consistent increases in plasma concentrations in marked contrast to the delayed and variable L-dopa levels seen with Sinemet (oral L-dopa/carbidopa). All doses of CVT-301 were safe and well tolerated with no increase in the frequency or severity of dyskinesias relative to oral.

“We are excited to move to this next stage of development in which patients will  self-administer CVT-301 upon the emergence of their OFF symptoms as they go about their normal daily activities, exactly aligned with the intended treatment paradigm,” said Martin Freed, MD, chief medical officer of Civitas. “The ease of use of the simple ARCUS inhaler allows patients to use CVT-301 wherever and whenever their oral Parkinson’s medications begin to fail them in between their regularly scheduled doses.”

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

CVT-301-003 is a randomized, double blind, placebo controlled, parallel group trial that is being conducted in the United States and Europe. Patients will use CVT-301 to treat emerging OFF episodes over a 28 day study period. The study is intended to test the efficacy, safety and tolerability of CVT-301 in the treatment of intermittent OFF episodes. Objective motor responses will be evaluated during regularly schedule clinic visits using the Unified Parkinson’s Disease Rating Scale (UPDRS) Part 3. In addition, efficacy will also be evaluated during out-patient use with diary based outcomes measures. Eighty (80) patients will be enrolled in the study.  The company will report preliminary data from this study in the first half of 2014.

Civitas’ lead programme, CVT-301, is an inhaled formulation of L-dopa being developed for the rapid and reliable relief from debilitating motor fluctuations (OFF episodes) associated with Parkinson’s disease. For chronic symptomatic management, oral L-dopa is administered to maintain dopamine levels in the brain above the therapeutic threshold; yet the reliability of oral L-dopa is significantly compromised by delayed and unpredictable absorption and excessive variability in the circulating plasma drug concentrations inherent to the oral delivery route. Oral L-dopa remains widely recognized as the most efficacious treatment of Parkinson’s disease symptoms in spite of this intrinsic unreliability and the resulting OFF episodes.  CVT-301 is being developed as an adjunct PRN therapy to standard oral L-dopa therapy to address the OFF episodes as they emerge and enable patients to reliably manage their symptoms.

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. A phase I study in healthy volunteers showed that CVT-301 rapidly achieved target L-dopa plasma levels with a pharmacokinetic (PK) profile supportive of its therapeutic potential. The phase II a double blind placebo controlled dose finding study (CVT-301-002) recapitulated the PK profile in patients, produced rapid and durable improvement in motor function when administered to patients in the OFF state, and was generally safe and well tolerated at all doses tested.

The ARCUS platform is a proprietary dry powder and device combination with a unique ability to deliver a large, precise dose independent of inspiratory flow rate from a simple, breath actuated device. The platform is protected by a large intellectual property estate including over 130 issued patents. The technology has successfully delivered more than one million doses to patients and the manufacturing technology has been scaled to accommodate a significant commercial launch.

As the world's largest private funder of Parkinson's research, The Michael J. Fox Foundation is dedicated to accelerating a cure for Parkinson's disease and improved therapies for those living with the condition today.