Contributions
Abstract: EP1377
Type: ePoster
Abstract Category: Clinical aspects of MS - 7 MS symptoms
Background: FLX-787 is a TRPA1/TRPV1 ion channel activator that is efficacious in decreasing muscle cramp intensity in an electrically-induced cramp (EIC) model in healthy volunteers, and cramp frequency in otherwise healthy subjects with nocturnal leg cramps (NLC). Muscle cramps result from spontaneous activity arising from hyperexcitability of α-motor neurons in the spinal cord. FLX-787 is believed to dampen α-motor neuron hyperexcitability by chemical -rather than electrical- neurostimulation. In this process, TRPA1/TRPV1 activation in the oropharynx and esophagus leads to excitatory sensory input to stimulate brainstem nuclei and subsequently descending spinal tracts to inhibit motor neuron hyperexcitability. The Flex-201 study was initiated in patients to evaluate the safety and efficacy of FLX-787 in a disease state where cramps, spasms and spasticity are prevalent, such as Multiple Sclerosis (MS).
Objectives: To monitor the prevalence of cramps/spasms and pain severity in MS subjects during a 14-day placebo run-in period. Cramp/spasm frequency and subject-reported spasticity and pain were analyzed. The analysis was performed to confirm that the baseline signal was adequate, and initial power assumptions were appropriate.
Methods: Flex-201 is a multicenter, randomized, blinded, cross-over study to investigate the effects of FLX-787 in subjects with MS and symptoms of spasticity, spasms and cramps (n up to 60). Interactive voice response system (IVRS) data from the run-in period were analyzed to quantify cramps/spasm frequency, spasticity and pain. Pearson correlation analysis was performed to identify statistical associations between these datasets.
Results: This analysis of partial (n=25) run-in data demonstrated that 80% of subjects experienced ≥ 9 cramps/spasms, and 40% of subjects experienced ≥ 25 cramps/spasms over the 14-day run-in period. Pain was a common complaint reported by 84% of subjects. Muscle cramp/spasm frequency was highly correlated with self-reported pain (p=0.0002), and stiffness to a lesser degree (p< 0.05).
Conclusion: Correlations from this analysis suggest that subjects who experience higher cramp/spasm frequency suffer more pain. Given the potential of FLX-787 to reduce both muscle cramp frequency and pain, seen in healthy subjects with nocturnal leg cramps, if FLX-787 can reduce cramp/spasm frequency and alleviate pain, then the selected study population should allow these effects to be measured in subjects with MS.
Disclosure:
1. Glenn Short is an employee of Flex Pharma and Flex Pharma Stock Holder.
2. Brooke Hegarty is an employee of Flex Pharma and Flex Pharma Stock Holder.
3. Jennifer Szegda is an employee of Flex Pharma and Flex Pharma Stock Holder.
4. William McVicar is an employee of Flex Pharma and Flex Pharma Stock Holder.
5. Christoph Westphal is an employee of Flex Pharma and Flex Pharma Stock Holder.
6. Thomas Wessel is an employee of Flex Pharma and Flex Pharma Stock Holder.
Abstract: EP1377
Type: ePoster
Abstract Category: Clinical aspects of MS - 7 MS symptoms
Background: FLX-787 is a TRPA1/TRPV1 ion channel activator that is efficacious in decreasing muscle cramp intensity in an electrically-induced cramp (EIC) model in healthy volunteers, and cramp frequency in otherwise healthy subjects with nocturnal leg cramps (NLC). Muscle cramps result from spontaneous activity arising from hyperexcitability of α-motor neurons in the spinal cord. FLX-787 is believed to dampen α-motor neuron hyperexcitability by chemical -rather than electrical- neurostimulation. In this process, TRPA1/TRPV1 activation in the oropharynx and esophagus leads to excitatory sensory input to stimulate brainstem nuclei and subsequently descending spinal tracts to inhibit motor neuron hyperexcitability. The Flex-201 study was initiated in patients to evaluate the safety and efficacy of FLX-787 in a disease state where cramps, spasms and spasticity are prevalent, such as Multiple Sclerosis (MS).
Objectives: To monitor the prevalence of cramps/spasms and pain severity in MS subjects during a 14-day placebo run-in period. Cramp/spasm frequency and subject-reported spasticity and pain were analyzed. The analysis was performed to confirm that the baseline signal was adequate, and initial power assumptions were appropriate.
Methods: Flex-201 is a multicenter, randomized, blinded, cross-over study to investigate the effects of FLX-787 in subjects with MS and symptoms of spasticity, spasms and cramps (n up to 60). Interactive voice response system (IVRS) data from the run-in period were analyzed to quantify cramps/spasm frequency, spasticity and pain. Pearson correlation analysis was performed to identify statistical associations between these datasets.
Results: This analysis of partial (n=25) run-in data demonstrated that 80% of subjects experienced ≥ 9 cramps/spasms, and 40% of subjects experienced ≥ 25 cramps/spasms over the 14-day run-in period. Pain was a common complaint reported by 84% of subjects. Muscle cramp/spasm frequency was highly correlated with self-reported pain (p=0.0002), and stiffness to a lesser degree (p< 0.05).
Conclusion: Correlations from this analysis suggest that subjects who experience higher cramp/spasm frequency suffer more pain. Given the potential of FLX-787 to reduce both muscle cramp frequency and pain, seen in healthy subjects with nocturnal leg cramps, if FLX-787 can reduce cramp/spasm frequency and alleviate pain, then the selected study population should allow these effects to be measured in subjects with MS.
Disclosure:
1. Glenn Short is an employee of Flex Pharma and Flex Pharma Stock Holder.
2. Brooke Hegarty is an employee of Flex Pharma and Flex Pharma Stock Holder.
3. Jennifer Szegda is an employee of Flex Pharma and Flex Pharma Stock Holder.
4. William McVicar is an employee of Flex Pharma and Flex Pharma Stock Holder.
5. Christoph Westphal is an employee of Flex Pharma and Flex Pharma Stock Holder.
6. Thomas Wessel is an employee of Flex Pharma and Flex Pharma Stock Holder.