Such periods are times when background L-dopa therapy does not control Parkinson’s symptoms. About 50 percent of patients using L-dopa have off periods, which are very disruptive to PD patients as well as their families and caregivers. The frequency and severity of these episodes increases during the course of the disease.
“We are greatly encouraged by the efficacy and safety results of this trial, which validate the positive Phase 2b results,” Burkhard Blank, MD, chief medical officer of Acorda, said in a press release. “We would like to express our gratitude to the study volunteers and clinical investigators who participated in this trial to advance our understanding of this potentially important therapy for people with Parkinson’s.”
The randomized, multicenter, placebo-controlled, double-blind SPAN-PD clinical trial (NCT02240030) evaluated the efficacy and safety of inhaled CVT-301 compared with placebo in 351 PD patients experiencing motor response fluctuations (off periods). The study included three treatment arms: CVT-301 84 mg and 60 mg doses (equivalent to 50 mg and 35 mg fine particle doses, respectively), and placebo.
The primary endpoint was the change in Unified Parkinson’s Disease Rating Scale (UPDRS) Part III motor score at 30 minutes following treatment with 84 mg of CVT-301 in patients experiencing an off episode at 12 weeks. UPDRS III is a scale that measures Parkinson’s motor impairment.
Acorda reported that the UPDRS III change was -9.83 compared to -5.91 for placebo, meaning that the treatment significantly improved patients’ motor function compared to placebo.
In terms of safety, the treatment was consistent with that observed in the Phase 2b trial, with no notable pulmonary safety signals, as measured by spirometry, a commonly used test to asses breathing function and diagnose respiratory disease, and diffusing capacity of the lung for carbon monoxide (DLCO), a test that determines the level of oxygen that passes from the tiny alveoli in the lungs into the bloodstream.
The most commonly reported adverse reactions occurring with CVT-301 at both 84 mg and 60 mg doses were cough (14.9% and 15%, respectively), upper respiratory tract infection (6.1% and 1.8%), and throat irritation (0.9% and 7.1%). Of the 227 patients who received the drug, three dropped out because of the cough.
Acorda is currently conducting two Phase 3 clinical trials evaluating the long-term (12 months) safety profile of CVT-301: NCT02352363, and NCT02242487. The last study is currently recruiting patients at multiple sites across the U.S. and in Ontario, Canada, the Czech Republic, Poland and Spain.
Results from these clinical trials are planned by March 31. Acorda then plans to file a New Drug Application to the U.S. Food and Drug Administration, as well as a Marketing Authorization Application in Europe.
“The re-emergence of Parkinson’s disease symptoms has a major negative impact on the lives of people with this disease, as well as on their families and care partners. Managing symptoms of off periods continues to be a significant unmet need for people taking oral carbidopa/levodopa regimens. Delivering levodopa by the pulmonary route offers an important treatment option for people with Parkinson’s disease,” said Peter LeWitt, MD, lead researcher and director of the PD and Movement Disorders Program at Detroit’s Henry Ford Hospital.
CVT-301 is a self-administered, inhaled levodopa (L-dopa) therapy for the episodic treatment of off periods in patients with Parkinson’s taking an oral carbidopa/levodopa regimen. It is being developed to provide delivery of a precise dose of L-dopa through the lungs to return people with Parkinson’s to an on state. The treatment has been shown to improve motor function in PD patients in a Phase 2 clinical trial.
Accord will also present these results at an upcoming medical meeting.