Contributions
Abstract: P629
Type: Poster Sessions
Abstract Category: Therapy - Symptomatic treatment
Introduction: FLX-787 is believed to dampen α-motor neuron and reflex hyperexcitability by chemical neurostimulation. In this process, TRPA1/TRPV1 coactivation in the oropharynx and esophagus leads to excitatory sensory input to stimulate brainstem nuclei and subsequently descending spinal tracts to inhibit hyperexcitability. The Flex-201 study was initiated in patients with Multiple Sclerosis (MS) to evaluate the safety and efficacy of FLX-787 in a disease state where the symptoms of cramps, spasms and spasticity are prevalent.
Objectives: To assess in an exploratory Phase 2 study: 1.)the frequency of cramps/spasms and associated-pain in MS patients; 2.)the efficacy of FLX-787 in treating cramps/spasms, pain and spasticity; 3.)the safety and tolerability of FLX-787.
Methods: Flex-201 was a multicenter, randomized, blinded, cross-over study which investigated the effects of FLX-787 in 57 MS patients with symptoms of spasticity, spasms and cramps versus inactive control. A daily questionnaire capturing cramp/spasm events, pain, stiffness and spasticity was administered using an interactive voice response system (IVRS). IVRS data, as well as in-clinic end-of-period assessments of spasticity, were analyzed.
Results: Analysis of the parallel portion of the study in the per-protocol population (n=45) showed that FLX-787 treatment caused a 27.3% reduction (p=0.0010) in the total number of cramps/spasms relative to baseline and a 42.5% reduction in total pain intensity (p=0.0486). Patients experienced a median increase of 1.4 cramp free days over the course of treatment (p=0.0457). Importantly, FLX-787 treatment caused a 1-point decrease relative to inactive control of the CGI-C spasticity score rated as a total improvement being entirely due to drug treatment (p=0.0427). CGI-C spasticity responders comprised 25% of the population and demonstrated a 2-point improvement on total modified Ashworth scale (p=0.025) and a 1-point improvement by NRS (0-10 scale) for spasticity (p=0.053). FLX-787 was generally well tolerated and resulted in infrequent GI-related adverse events (diarrhea and nausea).
Conclusion: This is the first report of FLX-787 being well-tolerated, safe and effective in treating common MS symptoms including cramps/spasms, pain and spasticity. These findings are similar to FLX-787 mediated reductions in cramp frequency associated with ALS and nocturnal leg cramps and suggest a broad applicability of FLX-787 across many neurological disorders.
Disclosure: Anneke van der Walt: nothing to disclose
Glenn F. Short III: Full-time employee and Stock holder of Flex Pharma
David A. Golod: Full-time employee and Stock holder of Flex Pharma
Brooke Hegarty: Full-time employee and Stock holder of Flex Pharma
Donna Cabral-Lilly: Full-time employee and Stock holder of Flex Pharma
William K. McVicar: Full-time employee and Stock holder of Flex Pharma
Thomas Wessel: Full-time employee and Stock holder of Flex Pharma
Abstract: P629
Type: Poster Sessions
Abstract Category: Therapy - Symptomatic treatment
Introduction: FLX-787 is believed to dampen α-motor neuron and reflex hyperexcitability by chemical neurostimulation. In this process, TRPA1/TRPV1 coactivation in the oropharynx and esophagus leads to excitatory sensory input to stimulate brainstem nuclei and subsequently descending spinal tracts to inhibit hyperexcitability. The Flex-201 study was initiated in patients with Multiple Sclerosis (MS) to evaluate the safety and efficacy of FLX-787 in a disease state where the symptoms of cramps, spasms and spasticity are prevalent.
Objectives: To assess in an exploratory Phase 2 study: 1.)the frequency of cramps/spasms and associated-pain in MS patients; 2.)the efficacy of FLX-787 in treating cramps/spasms, pain and spasticity; 3.)the safety and tolerability of FLX-787.
Methods: Flex-201 was a multicenter, randomized, blinded, cross-over study which investigated the effects of FLX-787 in 57 MS patients with symptoms of spasticity, spasms and cramps versus inactive control. A daily questionnaire capturing cramp/spasm events, pain, stiffness and spasticity was administered using an interactive voice response system (IVRS). IVRS data, as well as in-clinic end-of-period assessments of spasticity, were analyzed.
Results: Analysis of the parallel portion of the study in the per-protocol population (n=45) showed that FLX-787 treatment caused a 27.3% reduction (p=0.0010) in the total number of cramps/spasms relative to baseline and a 42.5% reduction in total pain intensity (p=0.0486). Patients experienced a median increase of 1.4 cramp free days over the course of treatment (p=0.0457). Importantly, FLX-787 treatment caused a 1-point decrease relative to inactive control of the CGI-C spasticity score rated as a total improvement being entirely due to drug treatment (p=0.0427). CGI-C spasticity responders comprised 25% of the population and demonstrated a 2-point improvement on total modified Ashworth scale (p=0.025) and a 1-point improvement by NRS (0-10 scale) for spasticity (p=0.053). FLX-787 was generally well tolerated and resulted in infrequent GI-related adverse events (diarrhea and nausea).
Conclusion: This is the first report of FLX-787 being well-tolerated, safe and effective in treating common MS symptoms including cramps/spasms, pain and spasticity. These findings are similar to FLX-787 mediated reductions in cramp frequency associated with ALS and nocturnal leg cramps and suggest a broad applicability of FLX-787 across many neurological disorders.
Disclosure: Anneke van der Walt: nothing to disclose
Glenn F. Short III: Full-time employee and Stock holder of Flex Pharma
David A. Golod: Full-time employee and Stock holder of Flex Pharma
Brooke Hegarty: Full-time employee and Stock holder of Flex Pharma
Donna Cabral-Lilly: Full-time employee and Stock holder of Flex Pharma
William K. McVicar: Full-time employee and Stock holder of Flex Pharma
Thomas Wessel: Full-time employee and Stock holder of Flex Pharma