Pauline Anderson

June 09, 2017

VANCOUVER — A new inhaled formulation of levodopa effectively addresses "off" periods in patients with Parkinson's disease (PD), results of a phase 3 study have shown.

The study demonstrated significantly greater improvement in Unified Parkinson's Disease Rating Scale (UPDRS) motor scores for patients using this new agent (CVT-301) compared with those using a placebo.

"This is important in that it gives the Parkinson disease community an option to treat the off periods they experience, when their levodopa starts to wear off," Charles Oh, MD, vice president, clinical development, Acorda Therapeutics, told Medscape Medical News.

The formulation "quickly and reliably" addresses this wearing off and is intended as an adjunctive medication to be taken as needed in addition to an oral regimen, said Dr Oh.

He stressed that this new agent is "not a new drug molecular entity" but rather an inhaled formulation of levodopa.

He presented the research here at a Late Breaking Abstract session at the International Congress of Parkinson's Disease and Movement Disorders (MDS) 2017.

Normal Breathing

To inhale the product, patients use a small plastic device in which they insert a capsule containing the dry powder.

"You clip it together, put it to your mouth and breathe slowly like you normally would," explained Dr Oh. Unlike an asthma inhaler, "it does not require any quick inhalation or big gasp of air."

Patients with PD often have swallowing issues, but CVT-301 goes through the respiratory tract, not down the gastrointestinal tract, and so does not involve swallowing, added Dr Oh.

He stressed that the device is simple to use and that patients with PD were able to use it without difficulty during the study.

The 12-week, double-blind, multinational study included 339 patients with PD (mean age, 63.3 years) experiencing off periods for 2 or more hours a day (excluding morning off periods) and who were receiving a stable dopa decarboxylase inhibitor and levodopa regimen.

Among other inclusion criteria were an increase in the UPDRS motor score of more than 25% between on and off periods, ability to perform spirometry during on and  off, and no respiratory disease within the last 5 years.

Patients were randomly assigned to receive a higher dose (84 mg), lower dose (60 mg), or placebo to be taken as needed up to five times a day.

After 12 weeks, the change in UPDRS score at 30 minutes was significantly greater in patients using the higher dose (change, –9.83) than in those receiving placebo (change, –5.91) for a difference of –3.92 (P = .009).

A higher proportion of patients inhaling the active product compared with placebo achieved an on state within 60 minutes and continued to remain on at 60 minutes.

A greater proportion of patients in the treatment groups than in the placebo group indicated that they were "improved" or "much improved."

Rapid Effect

Dr Oh noted that the effect was rapid and significantly different for the treatment compared with placebo at all but one time points over 60 minutes, and that one time point barely missed significance.

"You can start seeing effects as early as 10 minutes, which you would never get with an oral medication."

The treatment was well tolerated. The most common adverse event was cough, which occurred in 15% of the treatment groups and 1.8% in the placebo group.

"The only side effect that came out as double digits was cough," commented Dr Oh. But he pointed out that most coughs were mild and very few patients dropped out of the study because of it (two in the higher-dose group and one in the lower-dose group).

"If you think about it, you're breathing in a dry powder, a particulate, and any time you breathe in something like that, it's going to irritate a little bit."

Other adverse events occurring more frequently in the treatment groups than in the placebo group included upper respiratory tract infection, nausea, and sputum discoloration.

The company plans to file a New Drug Application (NDA) by the end of this quarter, said Dr Oh.

Asked to comment, Janis Miyasaki, professor, neurology, and director, Movement Disorder Program, University of Alberta, Edmonton, Canada, called the device "novel" and "exciting" in that it's a handy new way to deliver PD medication.

It may act as a kind of rescue agent while, for example, a patient is at the theater or out socializing, she said.

"Patients definitely need treatments to address those off periods because, as people progress, they tend to get more and more off periods, and these off periods can become unpredictable, and they can become sudden."

An oral medication will take an hour to start working, "so an inhaled medicine that bypasses the need for the absorption and the first pass effect is a benefit," said Dr Miyasaki.

But she questioned whether all patients with PD would have the breathing power to use the device. In some patients, the thorax may become rigid, especially over time, making it difficult to take a deep breath.

"One of the nonmotor symptoms that patients can get that isn't often reported is shortness of breath."

Dr Oh reiterated that the device is not complicated and that only a normal full breath is needed to get the drug to the distal lung. 

"This is not like an asthma inhaler that requires pressurized gas and a quick inspiratory effort to drive the drug to the lungs. CVT is a dry power that is carried into the lung on a normal full breath without the need for any pressurized gas."

Also approached for comment, Mark Stacy, MD, professor of neurology, and vice dean for clinical research, Duke University School of Medicine, Durham, North Carolina, said he doesn't think many patients are aware of this new preparation of levodopa.

"There will need to be significant effort to educate patients and physicians about this therapy," he told Medscape Medical News.

The study was funded by Acorda Therapeutics Inc. Dr Oh is an employee and stockholder of Acorda Therapeutics Inc. Dr Miyasaki has disclosed no relevant financial relationships.

International Congress of Parkinson's Disease and Movement Disorders (MDS) 2017. Late Breaking Abstract 34. Presented June 7, 2017.

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