PMID- 34129236 OWN - NLM STAT- MEDLINE DCOM- 20210921 LR - 20220722 IS - 1097-4598 (Electronic) IS - 0148-639X (Print) IS - 0148-639X (Linking) VI - 64 IP - 3 DP - 2021 Sep TI - Long-term efficacy and safety of dichlorphenamide for treatment of primary periodic paralysis. PG - 342-346 LID - 10.1002/mus.27354 [doi] AB - INTRODUCTION/AIM: Long-term efficacy and safety of dichlorphenamide (DCP) were characterized in patients with primary periodic paralysis (PPP). METHODS: Patients with PPP in a double-blind, placebo-controlled study were randomly assigned to receive DCP 50 mg twice daily or placebo for 9 weeks, followed by a 52-week open-label DCP treatment phase (DCP/DCP and placebo/DCP populations). Efficacy (attack rate, severity-weighted attack rate) and safety were assessed in patients completing the study (61 weeks). In this post hoc analysis, efficacy and safety data were pooled from hyperkalemic and hypokalemic substudies. RESULTS: Sixty-three adults (age, 19-76 years) completed the double-blind phase; 47 (74.6%) of these patients completed 61 weeks. There were median decreases in weekly attack and severity-weighted attack rates from baseline to week 61 (DCP/DCP [n = 25], -1.00 [P < .0001]; placebo/DCP [n = 20], -0.63 [P = .01] and DCP/DCP, -2.25 [P < .0001]; placebo/DCP, -1.69 [P = .01]). Relatively smaller median decreases in weekly attack and severity-weighted attack rates occurred from weeks 9 to 61 among patients receiving DCP continuously (n = 26; -0.14 [P = .1] and -0.24 [P = .09]) than among those switching from placebo to DCP after 9 weeks (n = 16; -1.04 [P = .049] and -2.72 [P = .08]). Common adverse events (AEs) were paresthesia and cognition-related events, which typically first occurred within 1 month of blinded treatment initiation and in rare cases led to treatment discontinuation. Dose reductions were frequently associated with common AE resolution. DISCUSSION: One-year open-label DCP treatment after a 9-week randomized, controlled study confirmed long-term DCP remains safe and effective for chronic use. Tolerability issues (paresthesia, cognition-related AEs) were manageable in most patients. CI - (c) 2021 The Authors. Muscle & Nerve published by Wiley Periodicals LLC. FAU - Sansone, Valeria A AU - Sansone VA AD - Neuromuscular Omnicentre, Neurorehabilitation Unit, University of Milan, Niguarda Hospital, Milan, Italy. FAU - Johnson, Nicholas E AU - Johnson NE AUID- ORCID: 0000-0002-3917-4257 AD - Department of Neurology, Virginia Commonwealth University, Richmond, Virginia, USA. FAU - Hanna, Michael G AU - Hanna MG AD - MRC Centre for Neuromuscular Diseases, Department of Neuromuscular Diseases, UCL Institute of Neurology, London, UK. FAU - Ciafaloni, Emma AU - Ciafaloni E AD - Department of Neurology, University of Rochester Medical Center, Rochester, New York, USA. FAU - Statland, Jeffrey M AU - Statland JM AUID- ORCID: 0000-0003-0790-5315 AD - Department of Neurology, University of Kansas Medical Center, Kansas City, Kansas, USA. FAU - Shieh, Perry B AU - Shieh PB AUID- ORCID: 0000-0001-7145-7663 AD - Department of Neurology, Ronald Reagan UCLA Medical Center, Los Angeles, California, USA. FAU - Cohen, Fredric AU - Cohen F AD - Strongbridge Biopharma, Trevose, Pennsylvania, USA. FAU - Griggs, Robert C AU - Griggs RC AD - Department of Neurology, University of Rochester Medical Center, Rochester, New York, USA. LA - eng GR - R01 NS045686/NS/NINDS NIH HHS/United States PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. DEP - 20210709 PL - United States TA - Muscle Nerve JT - Muscle & nerve JID - 7803146 RN - 0 (Carbonic Anhydrase Inhibitors) RN - VVJ6673MHY (Dichlorphenamide) SB - IM MH - Adult MH - Aged MH - Carbonic Anhydrase Inhibitors/adverse effects/*therapeutic use MH - Dichlorphenamide/adverse effects/*therapeutic use MH - Double-Blind Method MH - Female MH - Humans MH - Male MH - Middle Aged MH - Paralyses, Familial Periodic/*drug therapy MH - Treatment Outcome MH - Young Adult PMC - PMC9290603 OTO - NOTNLM OT - efficacy OT - hypokalemic periodic OT - paralysis OT - safety OT - weakness COIS- Funding for medical writing and editorial assistance was provided by Strongbridge Biopharma, Trevose, PA. V.A.S. has served as a scientific consultant on advisory boards for AveXis, Biogen Idec, Dyne Therapeutics, PTC Therapeutics, Santhera, Sarepta Therapeutics, and for the Italian Spinal Muscular Atrophy Association. N.E.J. has received research support from the Centers for Disease Control and Prevention, Dyne Therapeutics, US Food and Drug Administration, Fulcrum Therapeutics, Muscular Dystrophy Association, Myotonic Dystrophy Foundation, National Institute of Neurological Disorders and Stroke, and Sarepta Therapeutics, and has served as a consultant for AMO Pharma, AskBio, Dyne Therapeutics, Sarepta Therapeutics, Triplet Therapeutics, and Strongbridge Biopharma. E.C. has received personal compensation for serving on advisory boards and/or as a consultant for AveXis, Biogen, Pfizer, PTC Therapeutics, Santhera, Sarepta Therapeutics, and Strongbridge Biopharma, and has received research support from the Centers for Disease Control and Prevention, Cure SMA, US Food and Drug Administration, the Muscular Dystrophy Association, National Institutes of Health, PCORI, Parent Project Muscular Dystrophy, PTC Therapeutics, Santhera, and Sarepta Therapeutics. J.M.S. has received research support from the FSHD Society, Muscular Dystrophy Association, and the National Institutes of Health, and has served as a consultant for Acceleron Pharma, Expansion Therapeutics, Fulcrum Therapeutics, Genea Biocells, and Strongbridge Biopharma. P.B.S. has received grant funding from Acceleron Pharma, Biogen, Fulcrum Therapeutics, the Muscular Dystrophy Association, the National Institutes of Health (NIH), Pfizer, PTC Therapeutics, Roche, Sanofi, and Sarepta Therapeutics, and has served as a consultant for Argenx, Alexion Pharmaceuticals, AveXis, Biogen, Catalyst Pharmaceuticals, Genentech, and Sarepta Therapeutics. F.C. is an employee of Strongbridge Biopharma. R.C.G. has received grant funding from the Muscular Dystrophy Association, the NIH, Parent Project Muscular Dystrophy, PTC Therapeutics, and Sarepta Therapeutics; served as a consultant for PTC Therapeutics, Sarepta Therapeutics, and Strongbridge Biopharma, and served on a data safety monitoring board for Solid Biosciences and Santhera Pharmaceuticals. M.G.H. declares no conflicts of interest. EDAT- 2021/06/16 06:00 MHDA- 2021/09/22 06:00 PMCR- 2022/07/18 CRDT- 2021/06/15 13:43 PHST- 2021/06/04 00:00 [revised] PHST- 2020/07/23 00:00 [received] PHST- 2021/06/13 00:00 [accepted] PHST- 2021/06/16 06:00 [pubmed] PHST- 2021/09/22 06:00 [medline] PHST- 2021/06/15 13:43 [entrez] PHST- 2022/07/18 00:00 [pmc-release] AID - MUS27354 [pii] AID - 10.1002/mus.27354 [doi] PST - ppublish SO - Muscle Nerve. 2021 Sep;64(3):342-346. doi: 10.1002/mus.27354. Epub 2021 Jul 9.