A doctor will, at some point in a patient’s life, ask them to take in a deep breath. It’s standard procedure to eavesdrop on the air moving in and out of a patient’s lungs in hopes of catching an early sign of chronic obstructive pulmonary disease, certain heart murmurs, or any abnormal sounds. One day, if an early stage therapy is successful, taking in a deep breath could be standard care for Parkinson’s patients.

The possibility could be in the reach of Civitas Therapeutics, which has received a second grant from The Michael J. Fox Foundation to support a Phase IIb clinical trial of CVT-301, an inhaled formulation of levodopa. CVT-301 is being developed as an adjunct Parkinson's therapy to provide rapid and reliable relief from intermittent debilitating motor fluctuations—the “off” episodes—that impact a large proportion of patients treated for Parkinson’s disease.

Civitas recently released positive top-line results from a Phase IIa clinical trial showing that CVT-301 dispensed in the “off” state produced a rapid and durable improvement in motor function in study participants. All doses of CVT-301 tested were generally safe and well tolerated, according to the company. These results provide the basis for dose selection for the Phase IIb trial.

Rick Batycky, PhD, Founder and Chief Scientific Officer of Civitas, believes the treatment has the potential to fill an unmet need in Parkinson’s. “Off episodes in Parkinson’s disease consistently rank as the number one unmet need that patients face. They are incredibly debilitating and can have a devastating impact on patient’s lives. There is currently no practical way to address these off [moments].”

For chronic symptomatic management, oral L-dopa is administered to maintain dopamine levels in the brain above the therapeutic threshold. Oral L-dopa’s efficacy wanes with the progression of Parkinson’s disease, due largely to a lost capability to accommodate L-dopa’s innately poor pharmacokinetics. It becomes compromised by delayed and unpredictable absorption and excessive variability in the circulating plasma drug concentrations inherent to the oral delivery route.

CVT-301’s spot as an adjunct Parkinson's therapy to standard oral L-dopa therapy is driven by an Arcus therapeutic technology. This incorporates L-dopa and is optimized to deliver a precise dose to the deep lung for rapid and predictable L-dopa absorption. To Batycky, the device is an incredibly important component.

“Civitas’ technology produces powders with unique properties. A key attribute of the technology is the ability to deliver a large and precise dose with a device that is simple for patients to use, even while in an ‘off’ state. This is an absolute requirement for a levodopa Parkinson’s therapy and is one reason that this technology is uniquely suited for this indication,” he said.

The CVT-301 powder is administered in a proprietary, simple, passive, breath-actuated, dry powder inhaler. The inhaler does not require coordination and works over a wide range of flow rates. “Because CVT-301 is an inhaled formulation, it is not subject to all the challenges that oral levodopa faces—esophagile motility, delayed gastric emptying, first pass effects, food effects, etc.,” Batycky said. “These challenges with oral l-dopa are what lead to these debilitating off [moments] that occur with the majority of Parkinson’s patients. As such, pulmonary levodopa gets quickly and precisely into the system and, hence, is immediately available to the central nervous system to address an off.”

A Phase I study in healthy volunteers showed that CVT-301 rapidly achieved target L-dopa plasma levels with a pharmacokinetic profile supportive of its therapeutic potential. The Phase IIa double-blind, placebo-controlled dose finding study (CVT-301-002) recapitulated the pharmacokinetic 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 in all doses tested. Civitas intends to present the comprehensive data from the Phase IIa study at a future scientific meeting.

As for the Phase IIb trial, Batycky said the objectives will take a step closer to reality. “This is more a ‘real world’ study, which will have both an in-office component, as did our Phase IIa, as well as an at-home component in which patients can manage their ‘off’ as part of their normal daily routine.”