PMID- 25231896 OWN - NLM STAT- MEDLINE DCOM- 20150616 LR - 20220410 IS - 1935-5548 (Electronic) IS - 0149-5992 (Linking) VI - 37 IP - 12 DP - 2014 Dec TI - Efficacy and safety of mirogabalin (DS-5565) for the treatment of diabetic peripheral neuropathic pain: a randomized, double-blind, placebo- and active comparator-controlled, adaptive proof-of-concept phase 2 study. PG - 3253-61 LID - 10.2337/dc14-1044 [doi] AB - OBJECTIVE: We aimed to identify doses of mirogabalin (DS-5565) providing clinically meaningful efficacy with manageable side effects for treatment of diabetic peripheral neuropathic pain (DPNP). RESEARCH DESIGN AND METHODS: Adults (>/=18 years) with type 1 or 2 diabetes, HbA(1)c /=6 months were eligible for study participation. Subjects (n = 452) were randomized (2:1:1:1:1:1:1 ratio) to placebo, dose-ranging mirogabalin (5, 10, 15, 20, and 30 mg/day), or pregabalin (300 mg/day) for 5 weeks. The primary end point was weekly change in average daily pain score (ADPS; 0 to 10 numeric rating scale) from baseline to week 5 (minimally meaningful effect, >/=1.0-point decrease versus placebo). ANCOVA was conducted using last observation carried forward, and treatment effect least squares (LS) means were provided for each contrast. Safety assessments included adverse events (AEs), clinical laboratory tests, and electrocardiograms. RESULTS: LS mean differences in change in ADPS from baseline to week 5 versus placebo were -0.22, -0.53, -0.94, -0.88, and -1.01 for the mirogabalin 5-, 10-, 15-, 20-, and 30-mg/day treatment groups, respectively, and -0.05 in the pregabalin group (P < 0.05 versus placebo for mirogabalin 15, 20, and 30 mg/day). Most frequent AEs (n = 277) were primarily mild to moderate dizziness (9.4%), somnolence (6.1%), and headache (6.1%); otherwise, mirogabalin was well tolerated. CONCLUSIONS: Mirogabalin 15, 20, and 30 mg/day had statistically significant reductions in ADPS versus placebo, and mirogabalin 30 mg/day also met the criteria of minimally meaningful effect. Mirogabalin may be a promising new treatment option for patients with DPNP. CI - (c) 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. FAU - Vinik, Aaron AU - Vinik A AD - Eastern Virginia Medical School, Norfolk, VA vinikai@evms.edu. FAU - Rosenstock, Julio AU - Rosenstock J AD - Dallas Diabetes and Endocrine Center at Medical City, Dallas, TX. FAU - Sharma, Uma AU - Sharma U AD - MMS Holdings Inc., Canton, MI. FAU - Feins, Karen AU - Feins K AD - Daiichi Sankyo Pharma Development, Edison, NJ. FAU - Hsu, Ching AU - Hsu C AD - Daiichi Sankyo Pharma Development, Edison, NJ. FAU - Merante, Domenico AU - Merante D AD - Daiichi Sankyo Development, Gerrards Cross, Buckinghamshire, U.K. CN - DS5565-A-U201 US Phase II Study Investigators LA - eng PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20140917 PL - United States TA - Diabetes Care JT - Diabetes care JID - 7805975 RN - 0 (Analgesics) RN - 0 (Bridged Bicyclo Compounds) RN - 0 (Placebos) RN - 55JG375S6M (Pregabalin) RN - 56-12-2 (gamma-Aminobutyric Acid) RN - S7LK2KDM5U (mirogabalin) SB - IM MH - Adult MH - Aged MH - Analgesics/*administration & dosage/adverse effects MH - Bridged Bicyclo Compounds/*administration & dosage/adverse effects MH - Diabetes Mellitus, Type 1/complications/drug therapy MH - Diabetes Mellitus, Type 2/complications/drug therapy MH - Diabetic Neuropathies/*drug therapy MH - Dose-Response Relationship, Drug MH - Double-Blind Method MH - Female MH - Humans MH - Male MH - Middle Aged MH - Neuralgia/*drug therapy MH - Placebos MH - Pregabalin MH - Treatment Outcome MH - gamma-Aminobutyric Acid/analogs & derivatives/therapeutic use FIR - Akright, Laura IR - Akright L FIR - Andersen, James L IR - Andersen JL FIR - Aroda, Vanita IR - Aroda V FIR - Ratner, Robert IR - Ratner R FIR - Aronoff, Stephen IR - Aronoff S FIR - Arslanian, Armen IR - Arslanian A FIR - Bauch, Thomas IR - Bauch T FIR - Biton, Victor IR - Biton V FIR - Brownstone, Paul IR - Brownstone P FIR - Bruce, Tami IR - Bruce T FIR - Chaykin, Louis IR - Chaykin L FIR - Christensen, Jim IR - Christensen J FIR - Chuck, Leonard IR - Chuck L FIR - Cohen, Lisa IR - Cohen L FIR - Curtis, Craig T IR - Curtis CT FIR - Degarmo, Ronald IR - Degarmo R FIR - Denker, Paul IR - Denker P FIR - Ellenbogen, Aaron IR - Ellenbogen A FIR - Ervin, John IR - Ervin J FIR - Fried, David IR - Fried D FIR - Gerard, Gary IR - Gerard G FIR - Gibson, Michael IR - Gibson M FIR - Golden, Gordon IR - Golden G FIR - Haase, Gregory IR - Haase G FIR - Hernandez, Martha IR - Hernandez M FIR - Hudson, John IR - Hudson J FIR - Huffman, David IR - Huffman D FIR - Huling, Randall IR - Huling R FIR - Hull, Richard IR - Hull R FIR - Hurley, Sean IR - Hurley S FIR - Kesten, Jeffrey IR - Kesten J FIR - Kivitz, Alan IR - Kivitz A FIR - Klymiuk, Andrew IR - Klymiuk A FIR - Kudrow, David IR - Kudrow D FIR - Kumar, Vrijendra IR - Kumar V FIR - Liss, Jonathan IR - Liss J FIR - Mariano, Hipolito IR - Mariano H FIR - Martin, Paul IR - Martin P FIR - Mayfield, Ronald IR - Mayfield R FIR - McAllister, Peter IR - McAllister P FIR - McKenzie, Wilfred IR - McKenzie W FIR - Miller, Sam IR - Miller S FIR - Montano, C Brendan IR - Montano C FIR - Mosley, Jonathan IR - Mosley J FIR - Obiekwe, Michael IR - Obiekwe M FIR - Omidvar, Omid IR - Omidvar O FIR - Pellegrino, Richard IR - Pellegrino R FIR - Penc, Stanley IR - Penc S FIR - Perley, Michael IR - Perley M FIR - Posadas, Maria IR - Posadas M FIR - Goldberg, Cynthia IR - Goldberg C FIR - Raikhel, Marina IR - Raikhel M FIR - Recknor, Christopher IR - Recknor C FIR - Reed, Larry IR - Reed L FIR - Reichman, Alan IR - Reichman A FIR - Rendell, Marc IR - Rendell M FIR - Reyes, Hubert IR - Reyes H FIR - Richter, Ralph IR - Richter R FIR - Roberts, John IR - Roberts J FIR - Rosenblit, Paul IR - Rosenblit P FIR - Rosenstock, Julio IR - Rosenstock J FIR - Rovner, Sergio IR - Rovner S FIR - Samson, Mercedes B IR - Samson MB FIR - Sauter, Michael IR - Sauter M FIR - Shaibani, Aziz IR - Shaibani A FIR - Singer, Richard IR - Singer R FIR - Sligh, Teresa IR - Sligh T FIR - Smith, Timothy IR - Smith T FIR - Strout, Donna IR - Strout D FIR - Surprenant, Maria IR - Surprenant M FIR - Sussman, Allen IR - Sussman A FIR - Taber, Louise IR - Taber L FIR - Tark, Marvin IR - Tark M FIR - Trevino, Miguel IR - Trevino M FIR - Unger, Jeffrey R IR - Unger JR FIR - Vinik, Aaron IR - Vinik A FIR - Wilks, Kerri IR - Wilks K FIR - Wombolt, Duane IR - Wombolt D FIR - Young, Douglas IR - Young D FIR - Zemel, Leonard IR - Zemel L FIR - Zieve, Franklin IR - Zieve F FIR - Zimmerman, Tamela IR - Zimmerman T EDAT- 2014/09/19 06:00 MHDA- 2015/06/17 06:00 CRDT- 2014/09/19 06:00 PHST- 2014/09/19 06:00 [entrez] PHST- 2014/09/19 06:00 [pubmed] PHST- 2015/06/17 06:00 [medline] AID - dc14-1044 [pii] AID - 10.2337/dc14-1044 [doi] PST - ppublish SO - Diabetes Care. 2014 Dec;37(12):3253-61. doi: 10.2337/dc14-1044. Epub 2014 Sep 17.