Effect of NP002, a centrally acting cholinergic agent, in reducing dyskinesia, freezing of gait, and falls in patients with Parkinson’s disease (S26.007)

Objective: To evaluate the safety and tolerability of NP002 (nicotine bi-tartrate) in Parkinson’s disease (PD), and the effect of NP002 (versus placebo) on levodopa-induced dyskinesia (LIDs), falls, and freezing of gait (FOG). Background: As PD advances, more than 30% of patients experience falls and FOG, which are relatively refractory to levodopa. LIDs also appear. NP002 may be able to reduce falls and LIDs by rapidly stimulating CNS cholinergic receptors without desensitizing cholinergic receptors for long-term use. Design/Methods: A 12- center, double-blind, randomized trial was undertaken in 65 patients with advanced PD. NP002 was administered 4 times/day for 10 weeks beginning at 1 mg every 6 hours, and increasing to 24 mg/day. Patients were assessed using the Unified Dyskinesia Rating Scale (UDysRS), the Lang-Fahn ADL Dyskinesia Scale, and the Unified Parkinson’s Disease Rating Scale (UPDRS). Results: NP002 was safe and well tolerated. Nausea was the main adverse effect. 14 of 35 (40%) of subjects taking NP002 and 3 of 30 (10%) of subjects on placebo experienced a reduction in falls (p=0.0098, Fisher’s test). Additionally, 12 of 35 patients (34%) on NP002 had a significant (p=0.04, Fisher’s test) reduction in FOG compared to 4 (13%) patients on placebo control. The ambulation part of the Unified Dyskinesia Rating Scale improved significantly (46.3% on NP002 vs 8.6% on placebo, p=0.011). Total dyskinesia symptoms measured on the UDysRS were reduced, but not significantly (p=0. 092). Conclusions: NP002, a novel direct cholinergic agonist, improved two relatively refractory symptoms of PD: falls and FOG, while probably reducing LIDs. Disclosure: Dr. Lieberman has nothing to disclose. Dr. Lockhart has nothing to disclose. Dr. Olson has nothing to disclose. Dr. Smith has nothing to disclose. Dr. Frames has nothing to disclose.