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AUSTIN, TEX. – Dichlorphenamide continues to reduce attacks from primary periodic paralysis (PPP) through 1 year with mild or moderate paresthesia and cognition-related adverse events, according to new research.
“These adverse events rarely resulted in discontinuation from the study and were sometimes managed by dichlorphenamide dose reductions,” concluded Nicholas E. Johnson, MD, of Virginia Commonwealth University, Richmond, and colleagues. “Reduction in dose was frequently associated with resolution of these events, suggesting a potential intervention to hasten resolution.” Dr. Johnson presented the findings in an abstract at the annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine.
Dichlorphenamide (Keveyis) was approved by the Food and Drug Administration in 2015 for treating primary hyperkalemic and hypokalemic periodic paralysis and similar variants. The original hyperkalemic/hypokalemic PPP trial was a phase 3 randomized, double-blind, placebo-controlled trial that lasted 9 weeks and assessed the efficacy of dichlorphenamide in reducing PPP attacks and its adverse events. In the dichlorphenamide group, 47% experienced paresthesia, compared with 14% in the placebo group, and 19% experienced cognitive disorder, compared with 7% in the placebo.
In a 52-week open-label extension, participants who had been receiving the placebo switched to receiving 50 mg of dichlorphenamide twice daily. The intervention group continued with the dose they had been receiving when the 9-week double-blind phase ended. (During the initial intervention, they took either 50 mg twice daily or the dose they had at baseline for those taking it before the study began.)
The researchers then tracked rates of attacks and their severity over the next year – through week 61 after baseline – to compare these endpoints both within the intervention groups and between them.
Among the 63 predominantly white (84.1%) male (61.9%) adults who began the trial, 36 received dichlorphenamide and 27 received placebo. Just over two-thirds (68.3%) had hypokalemic PPP. Among the 47 patients (74.6%) who completed the open-label extension phase, 26 had been in the original dichlorphenamide group and 21 had been in the placebo group.
The median weekly attack rate in the dichlorphenamide group dropped from 1.75 at baseline to 0.06 at week 61 (median decrease 1.00, 93.8%; P less than .0001). In the placebo group that switched over to dichlorphenamide at week 9, the median weekly attack rate dropped from 3.00 at baseline to 0.25 at week 61 (median decrease 0.63, 75%; P = .01).
The median attack rate weighted for severity in the dichlorphenamide group dropped from 2.25 at baseline to 0.06 at week 61 (median decrease 2.25, 97.1%; P less than .0001). In the placebo group, it dropped from 5.88 to 0.50 (median decrease 1.69, 80.8%; P = .01).
No significant difference in median weekly attack rates and severity-weighted attack rates was found between the intervention groups through week 61.
Across all patients during the extension, 39.7% patients experienced at least one paresthesia adverse event, none of which were determined to be severe and resulting in one discontinuation.
A quarter of the participants (25.4%) experienced at least one cognition-related adverse event, and four patients (6.3%) discontinued because of these side effects. Most (14.3%) were mild with 7.9% reporting moderate and 3.2% reporting severe effects.
Dr. Johnson has received research support from or consulted with a variety of pharmaceutical companies including Strongbridge Biopharma, the manufacturer of the drug. Other authors consulted for several pharmaceutical companies, and one author is an employee of Strongbridge Biopharma.
SOURCE: Johnson NE et al. AANEM 2019. Abstract 102. Long-term efficacy and adverse event characterization of dichlorphenamide for the treatment of primary periodic paralysis.
AUSTIN, TEX. – Dichlorphenamide continues to reduce attacks from primary periodic paralysis (PPP) through 1 year with mild or moderate paresthesia and cognition-related adverse events, according to new research.
“These adverse events rarely resulted in discontinuation from the study and were sometimes managed by dichlorphenamide dose reductions,” concluded Nicholas E. Johnson, MD, of Virginia Commonwealth University, Richmond, and colleagues. “Reduction in dose was frequently associated with resolution of these events, suggesting a potential intervention to hasten resolution.” Dr. Johnson presented the findings in an abstract at the annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine.
Dichlorphenamide (Keveyis) was approved by the Food and Drug Administration in 2015 for treating primary hyperkalemic and hypokalemic periodic paralysis and similar variants. The original hyperkalemic/hypokalemic PPP trial was a phase 3 randomized, double-blind, placebo-controlled trial that lasted 9 weeks and assessed the efficacy of dichlorphenamide in reducing PPP attacks and its adverse events. In the dichlorphenamide group, 47% experienced paresthesia, compared with 14% in the placebo group, and 19% experienced cognitive disorder, compared with 7% in the placebo.
In a 52-week open-label extension, participants who had been receiving the placebo switched to receiving 50 mg of dichlorphenamide twice daily. The intervention group continued with the dose they had been receiving when the 9-week double-blind phase ended. (During the initial intervention, they took either 50 mg twice daily or the dose they had at baseline for those taking it before the study began.)
The researchers then tracked rates of attacks and their severity over the next year – through week 61 after baseline – to compare these endpoints both within the intervention groups and between them.
Among the 63 predominantly white (84.1%) male (61.9%) adults who began the trial, 36 received dichlorphenamide and 27 received placebo. Just over two-thirds (68.3%) had hypokalemic PPP. Among the 47 patients (74.6%) who completed the open-label extension phase, 26 had been in the original dichlorphenamide group and 21 had been in the placebo group.
The median weekly attack rate in the dichlorphenamide group dropped from 1.75 at baseline to 0.06 at week 61 (median decrease 1.00, 93.8%; P less than .0001). In the placebo group that switched over to dichlorphenamide at week 9, the median weekly attack rate dropped from 3.00 at baseline to 0.25 at week 61 (median decrease 0.63, 75%; P = .01).
The median attack rate weighted for severity in the dichlorphenamide group dropped from 2.25 at baseline to 0.06 at week 61 (median decrease 2.25, 97.1%; P less than .0001). In the placebo group, it dropped from 5.88 to 0.50 (median decrease 1.69, 80.8%; P = .01).
No significant difference in median weekly attack rates and severity-weighted attack rates was found between the intervention groups through week 61.
Across all patients during the extension, 39.7% patients experienced at least one paresthesia adverse event, none of which were determined to be severe and resulting in one discontinuation.
A quarter of the participants (25.4%) experienced at least one cognition-related adverse event, and four patients (6.3%) discontinued because of these side effects. Most (14.3%) were mild with 7.9% reporting moderate and 3.2% reporting severe effects.
Dr. Johnson has received research support from or consulted with a variety of pharmaceutical companies including Strongbridge Biopharma, the manufacturer of the drug. Other authors consulted for several pharmaceutical companies, and one author is an employee of Strongbridge Biopharma.
SOURCE: Johnson NE et al. AANEM 2019. Abstract 102. Long-term efficacy and adverse event characterization of dichlorphenamide for the treatment of primary periodic paralysis.
AUSTIN, TEX. – Dichlorphenamide continues to reduce attacks from primary periodic paralysis (PPP) through 1 year with mild or moderate paresthesia and cognition-related adverse events, according to new research.
“These adverse events rarely resulted in discontinuation from the study and were sometimes managed by dichlorphenamide dose reductions,” concluded Nicholas E. Johnson, MD, of Virginia Commonwealth University, Richmond, and colleagues. “Reduction in dose was frequently associated with resolution of these events, suggesting a potential intervention to hasten resolution.” Dr. Johnson presented the findings in an abstract at the annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine.
Dichlorphenamide (Keveyis) was approved by the Food and Drug Administration in 2015 for treating primary hyperkalemic and hypokalemic periodic paralysis and similar variants. The original hyperkalemic/hypokalemic PPP trial was a phase 3 randomized, double-blind, placebo-controlled trial that lasted 9 weeks and assessed the efficacy of dichlorphenamide in reducing PPP attacks and its adverse events. In the dichlorphenamide group, 47% experienced paresthesia, compared with 14% in the placebo group, and 19% experienced cognitive disorder, compared with 7% in the placebo.
In a 52-week open-label extension, participants who had been receiving the placebo switched to receiving 50 mg of dichlorphenamide twice daily. The intervention group continued with the dose they had been receiving when the 9-week double-blind phase ended. (During the initial intervention, they took either 50 mg twice daily or the dose they had at baseline for those taking it before the study began.)
The researchers then tracked rates of attacks and their severity over the next year – through week 61 after baseline – to compare these endpoints both within the intervention groups and between them.
Among the 63 predominantly white (84.1%) male (61.9%) adults who began the trial, 36 received dichlorphenamide and 27 received placebo. Just over two-thirds (68.3%) had hypokalemic PPP. Among the 47 patients (74.6%) who completed the open-label extension phase, 26 had been in the original dichlorphenamide group and 21 had been in the placebo group.
The median weekly attack rate in the dichlorphenamide group dropped from 1.75 at baseline to 0.06 at week 61 (median decrease 1.00, 93.8%; P less than .0001). In the placebo group that switched over to dichlorphenamide at week 9, the median weekly attack rate dropped from 3.00 at baseline to 0.25 at week 61 (median decrease 0.63, 75%; P = .01).
The median attack rate weighted for severity in the dichlorphenamide group dropped from 2.25 at baseline to 0.06 at week 61 (median decrease 2.25, 97.1%; P less than .0001). In the placebo group, it dropped from 5.88 to 0.50 (median decrease 1.69, 80.8%; P = .01).
No significant difference in median weekly attack rates and severity-weighted attack rates was found between the intervention groups through week 61.
Across all patients during the extension, 39.7% patients experienced at least one paresthesia adverse event, none of which were determined to be severe and resulting in one discontinuation.
A quarter of the participants (25.4%) experienced at least one cognition-related adverse event, and four patients (6.3%) discontinued because of these side effects. Most (14.3%) were mild with 7.9% reporting moderate and 3.2% reporting severe effects.
Dr. Johnson has received research support from or consulted with a variety of pharmaceutical companies including Strongbridge Biopharma, the manufacturer of the drug. Other authors consulted for several pharmaceutical companies, and one author is an employee of Strongbridge Biopharma.
SOURCE: Johnson NE et al. AANEM 2019. Abstract 102. Long-term efficacy and adverse event characterization of dichlorphenamide for the treatment of primary periodic paralysis.
REPORTING FROM AANEM