Double-Blind, Placebo-Controlled, Randomized Phase I/IIa Study (Safety and Efficacy) with Buspirone/Levodopa/Carbidopa (SpinalonTM) in Subjects with Complete AIS A or Motor-Complete AIS B Spinal Cord Injury

Title:Double-Blind, Placebo-Controlled, Randomized Phase I/IIa Study (Safety and Efficacy) with Buspirone/Levodopa/Carbidopa (SpinalonTM) in Subjects with Complete AIS A or Motor-Complete AIS B Spinal Cord Injury

Volume: 23 Issue: 12

Author(s): Mohan Radhakrishna*, Inge Steuer, Francois Prince, Mary Roberts, David Mongeon, Maryam Kia, Sasha Dyck, Gilbert Matte, Mario Vaillancourt and Pierre A. Guertin*

Affiliation:

• Research Institute of the McGill University Health Centre (MUHC), Department of Medicine, McGill University, Montreal, QC,Canada

• CHUQ-CHUL, Neurosciences Unit, RC-9800, 2705 Laurier Boulevard, Quebec City, QC, Canada, G1V 4G2,Canada

Keywords: Locomotion, drug treatment, paraplegia, tetraplegia, spinal locomotor neurons, Electromyographic (EMG).

Abstract: Background: No drug treatment capable of restoring locomotor capabilities in patients suffering a motor-complete spinal cord injury (SCI) has ever been developed. We assessed the safety and efficacy of an activator of spinal locomotor neurons in humans, which were shown in paraplegic animals to elicit temporary episodes of involuntary walking.

Methods: Single administration of buspirone/levodopa/carbidopa (SpinalonTM), levodopa/carbidopa (ratio 4: 1), and buspirone or placebo was performed using a dose-escalation design in 45 subjects placed in supine position who had had an SCI classified as complete (AIS A) or motor-complete/sensory incomplete (AIS B) for at least 3 months. Blood samples before and at regular intervals (15, 30, 60, 120, 240 min) after treatment were collected for hematological and pharmacokinetic (PK) analyses. Electromyographic (EMG) activity of eight muscles (four per leg) was monitored prior to and at several time points after drug administration.

Results: SpinalonTM (10-35 mg buspirone/100-350 mg levodopa/25-85 mg carbidopa) displayed no sign of safety concerns - only mild nausea was found in 3 cases. At higher doses, 50 mg/500 mg/125 mg SpinalonTM was considered to have reached maximum tolerated dose (MTD) since 3 out of 4 subjects experienced related adverse events including vomiting. PK analyses showed comparable data between groups suggesting no significant drugdrug interaction with SpinalonTM. Only the SpinalonTM–treated groups displayed significant EMG activity accompanied by locomotor-like characteristics - that is with rhythmic and bilaterally alternating bursts.

Conclusion: Therefore, this study provides evidence of safety and preliminary efficacy following a single administration of SpinalonTM in subjects with SCI.

Cite this article as:

Radhakrishna Mohan*, Steuer Inge, Prince Francois, Roberts Mary, Mongeon David, Kia Maryam, Dyck Sasha, Matte Gilbert, Vaillancourt Mario and Guertin A. Pierre*, Double-Blind, Placebo-Controlled, Randomized Phase I/IIa Study (Safety and Efficacy) with Buspirone/Levodopa/Carbidopa (SpinalonTM) in Subjects with Complete AIS A or Motor-Complete AIS B Spinal Cord Injury, Current Pharmaceutical Design 2017; 23 (12) . https://dx.doi.org/10.2174/1381612822666161227152200

DOI https://dx.doi.org/10.2174/1381612822666161227152200	Print ISSN 1381-6128
Publisher Name Bentham Science Publisher	Online ISSN 1873-4286