drugset / Trial / NCT05603702
STTEPP: Safety, Tolerability and Dose Limiting Toxicity of Lacosamide in Patients With Painful Chronic Pancreatitis
Phase 1
Active not recruiting
21 enrolled
Indiana University
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) · collab
NaSingle-groupOpen-labelTreatment
Summary
The investigators propose to conduct a dose-escalation trial of an FDA-approved antiepileptic drug, lacosamide, added to opioid therapy in patients with chronic abdominal pain from chronic pancreatitis (CP). This pilot trial will test the feasibility of the study design and provide reassurance regarding the tolerability and safety of lacosamide used concomitantly with opioids in this patient population to reduce the condition known clinically as opioid-induced hyperalgesia (OIH).
Timeline
- Start
- 2023-03-17
- Primary completion
- 2027-03-31
- Completion
- 2027-03-31
Publications
- Results Agarwal D, Udoji MA, Trescot A. Genetic Testing for Opioid Pain Management: A Primer. Pain Ther. 2017 Jun;6(1):93-105. doi: 10.1007/s40122-017-0069-2. Epub 2017 Apr 13.
- Results Angst MS, Clark JD. Opioid-induced hyperalgesia: a qualitative systematic review. Anesthesiology. 2006 Mar;104(3):570-87. doi: 10.1097/00000542-200603000-00025.
- Results Bannister K. Opioid-induced hyperalgesia: where are we now? Curr Opin Support Palliat Care. 2015 Jun;9(2):116-21. doi: 10.1097/SPC.0000000000000137.
- Results Bannister K, Bee LA, Dickenson AH. Preclinical and early clinical investigations related to monoaminergic pain modulation. Neurotherapeutics. 2009 Oct;6(4):703-12. doi: 10.1016/j.nurt.2009.07.009.
- Results Ben-Menachem E, Biton V, Jatuzis D, Abou-Khalil B, Doty P, Rudd GD. Efficacy and safety of oral lacosamide as adjunctive therapy in adults with partial-onset seizures. Epilepsia. 2007 Jul;48(7):1308-17. doi: 10.1111/j.1528-1167.2007.01188.x.
- Results Cawello W. Clinical pharmacokinetic and pharmacodynamic profile of lacosamide. Clin Pharmacokinet. 2015 Sep;54(9):901-14. doi: 10.1007/s40262-015-0276-0.
- Results Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain - United States, 2016. MMWR Recomm Rep. 2016 Mar 18;65(1):1-49. doi: 10.15585/mmwr.rr6501e1.
- Results Colvin LA, Fallon MT. Opioid-induced hyperalgesia: a clinical challenge. Br J Anaesth. 2010 Feb;104(2):125-7. doi: 10.1093/bja/aep392. No abstract available.
- Results Cote GA, Yadav D, Slivka A, Hawes RH, Anderson MA, Burton FR, Brand RE, Banks PA, Lewis MD, Disario JA, Gardner TB, Gelrud A, Amann ST, Baillie J, Money ME, O'Connell M, Whitcomb DC, Sherman S; North American Pancreatitis Study Group. Alcohol and smoking as risk factors in an epidemiology study of patients with chronic pancreatitis. Clin Gastroenterol Hepatol. 2011 Mar;9(3):266-73; quiz e27. doi: 10.1016/j.cgh.2010.10.015. Epub 2010 Oct 26.
- Results Cote GA, Durkalski-Mauldin VL, Serrano J, Klintworth E, Williams AW, Cruz-Monserrate Z, Arain M, Buxbaum JL, Conwell DL, Fogel EL, Freeman ML, Gardner TB, van Geenen E, Groce JR, Jonnalagadda SS, Keswani RN, Menon S, Moffatt DC, Papachristou GI, Ross A, Tarnasky PR, Wang AY, Wilcox CM, Hamilton F, Yadav D; SHARP Consortium. SpHincterotomy for Acute Recurrent Pancreatitis Randomized Trial: Rationale, Methodology, and Potential Implications. Pancreas. 2019 Sep;48(8):1061-1067. doi: 10.1097/MPA.0000000000001370.
- Results Cotton PB, Durkalski V, Romagnuolo J, Pauls Q, Fogel E, Tarnasky P, Aliperti G, Freeman M, Kozarek R, Jamidar P, Wilcox M, Serrano J, Brawman-Mintzer O, Elta G, Mauldin P, Thornhill A, Hawes R, Wood-Williams A, Orrell K, Drossman D, Robuck P. Effect of endoscopic sphincterotomy for suspected sphincter of Oddi dysfunction on pain-related disability following cholecystectomy: the EPISOD randomized clinical trial. JAMA. 2014 May;311(20):2101-9. doi: 10.1001/jama.2014.5220.
- Results Dean L. Lacosamide Therapy and CYP2C19 Genotype. 2018 Apr 18. In: Pratt VM, Scott SA, Pirmohamed M, Esquivel B, Kattman BL, Malheiro AJ, editors. MINI Medical Genetics Summaries [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2012-. Available from http://www.ncbi.nlm.nih.gov/books/NBK493589/
- Results Deuis JR, Dekan Z, Wingerd JS, Smith JJ, Munasinghe NR, Bhola RF, Imlach WL, Herzig V, Armstrong DA, Rosengren KJ, Bosmans F, Waxman SG, Dib-Hajj SD, Escoubas P, Minett MS, Christie MJ, King GF, Alewood PF, Lewis RJ, Wood JN, Vetter I. Pharmacological characterisation of the highly NaV1.7 selective spider venom peptide Pn3a. Sci Rep. 2017 Jan 20;7:40883. doi: 10.1038/srep40883.
- Results Due MR, Piekarz AD, Wilson N, Feldman P, Ripsch MS, Chavez S, Yin H, Khanna R, White FA. Neuroexcitatory effects of morphine-3-glucuronide are dependent on Toll-like receptor 4 signaling. J Neuroinflammation. 2012 Aug 16;9:200. doi: 10.1186/1742-2094-9-200.
- Results Due MR, Yang XF, Allette YM, Randolph AL, Ripsch MS, Wilson SM, Dustrude ET, Khanna R, White FA. Carbamazepine potentiates the effectiveness of morphine in a rodent model of neuropathic pain. PLoS One. 2014 Sep 15;9(9):e107399. doi: 10.1371/journal.pone.0107399. eCollection 2014.
- Results Elmunzer BJ, Scheiman JM, Lehman GA, Chak A, Mosler P, Higgins PD, Hayward RA, Romagnuolo J, Elta GH, Sherman S, Waljee AK, Repaka A, Atkinson MR, Cote GA, Kwon RS, McHenry L, Piraka CR, Wamsteker EJ, Watkins JL, Korsnes SJ, Schmidt SE, Turner SM, Nicholson S, Fogel EL; U.S. Cooperative for Outcomes Research in Endoscopy (USCORE). A randomized trial of rectal indomethacin to prevent post-ERCP pancreatitis. N Engl J Med. 2012 Apr 12;366(15):1414-22. doi: 10.1056/NEJMoa1111103.
- Results Fogel EL, Lehman GA, Tarnasky P, Cote GA, Schmidt SE, Waljee AK, Higgins PDR, Watkins JL, Sherman S, Kwon RSY, Elta GH, Easler JJ, Pleskow DK, Scheiman JM, El Hajj II, Guda NM, Gromski MA, McHenry L Jr, Arol S, Korsnes S, Suarez AL, Spitzer R, Miller M, Hofbauer M, Elmunzer BJ; US Cooperative for Outcomes Research in Endoscopy (USCORE). Rectal indometacin dose escalation for prevention of pancreatitis after endoscopic retrograde cholangiopancreatography in high-risk patients: a double-blind, randomised controlled trial. Lancet Gastroenterol Hepatol. 2020 Feb;5(2):132-141. doi: 10.1016/S2468-1253(19)30337-1. Epub 2019 Nov 25.
- Results Gilron I, Bailey JM, Tu D, Holden RR, Weaver DF, Houlden RL. Morphine, gabapentin, or their combination for neuropathic pain. N Engl J Med. 2005 Mar 31;352(13):1324-34. doi: 10.1056/NEJMoa042580.
- Results Goodman CW, Brett AS. Gabapentin and Pregabalin for Pain - Is Increased Prescribing a Cause for Concern? N Engl J Med. 2017 Aug 3;377(5):411-414. doi: 10.1056/NEJMp1704633. No abstract available.
- Results Hall TC, Garcea G, Webb MA, Al-Leswas D, Metcalfe MS, Dennison AR. The socio-economic impact of chronic pancreatitis: a systematic review. J Eval Clin Pract. 2014 Jun;20(3):203-7. doi: 10.1111/jep.12117. Epub 2014 Mar 24.
- Results Haugan F, Rygh LJ, Tjolsen A. Ketamine blocks enhancement of spinal long-term potentiation in chronic opioid treated rats. Acta Anaesthesiol Scand. 2008 May;52(5):681-7. doi: 10.1111/j.1399-6576.2008.01637.x.
- Results Hearn L, Derry S, Moore RA. Lacosamide for neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev. 2012 Feb 15;2012(2):CD009318. doi: 10.1002/14651858.CD009318.pub2.
- Results Hewitt DJ. The use of NMDA-receptor antagonists in the treatment of chronic pain. Clin J Pain. 2000 Jun;16(2 Suppl):S73-9. doi: 10.1097/00002508-200006001-00013.
- Results Ibrahim SA, Albany Z, Albany C. Significant response to lacosamide in a patient with severe chemotherapy-induced peripheral neuropathy. J Community Support Oncol. 2015 May;13(5):202-4. doi: 10.12788/jcso.0136.
- Results Isensee J, Krahe L, Moeller K, Pereira V, Sexton JE, Sun X, Emery E, Wood JN, Hucho T. Synergistic regulation of serotonin and opioid signaling contributes to pain insensitivity in Nav1.7 knockout mice. Sci Signal. 2017 Jan 10;10(461):eaah4874. doi: 10.1126/scisignal.aah4874.
- Results Jo S, Bean BP. Lacosamide Inhibition of Nav1.7 Voltage-Gated Sodium Channels: Slow Binding to Fast-Inactivated States. Mol Pharmacol. 2017 Apr;91(4):277-286. doi: 10.1124/mol.116.106401. Epub 2017 Jan 24.
- Results Li X, Angst MS, Clark JD. A murine model of opioid-induced hyperalgesia. Brain Res Mol Brain Res. 2001 Jan 31;86(1-2):56-62. doi: 10.1016/s0169-328x(00)00260-6.
- Results Liang D, Shi X, Qiao Y, Angst MS, Yeomans DC, Clark JD. Chronic morphine administration enhances nociceptive sensitivity and local cytokine production after incision. Mol Pain. 2008 Feb 22;4:7. doi: 10.1186/1744-8069-4-7.
- Results Minville V, Fourcade O, Girolami JP, Tack I. Opioid-induced hyperalgesia in a mice model of orthopaedic pain: preventive effect of ketamine. Br J Anaesth. 2010 Feb;104(2):231-8. doi: 10.1093/bja/aep363. Epub 2009 Dec 22.
- Results Moore RA, Wiffen PJ, Derry S, McQuay HJ. Gabapentin for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev. 2011 Mar 16;(3):CD007938. doi: 10.1002/14651858.CD007938.pub2.
- Results Mullady DK, Yadav D, Amann ST, O'Connell MR, Barmada MM, Elta GH, Scheiman JM, Wamsteker EJ, Chey WD, Korneffel ML, Weinman BM, Slivka A, Sherman S, Hawes RH, Brand RE, Burton FR, Lewis MD, Gardner TB, Gelrud A, DiSario J, Baillie J, Banks PA, Whitcomb DC, Anderson MA; NAPS2 Consortium. Type of pain, pain-associated complications, quality of life, disability and resource utilisation in chronic pancreatitis: a prospective cohort study. Gut. 2011 Jan;60(1):77-84. doi: 10.1136/gut.2010.213835.
- Results Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982 Dec;5(6):649-55. No abstract available.
- Results Park KD, Yang XF, Dustrude ET, Wang Y, Ripsch MS, White FA, Khanna R, Kohn H. Chimeric agents derived from the functionalized amino acid, lacosamide, and the alpha-aminoamide, safinamide: evaluation of their inhibitory actions on voltage-gated sodium channels, and antiseizure and antinociception activities and comparison with lacosamide and safinamide. ACS Chem Neurosci. 2015 Feb 18;6(2):316-30. doi: 10.1021/cn5002182. Epub 2014 Dec 9.
- Results Rao RD, Michalak JC, Sloan JA, Loprinzi CL, Soori GS, Nikcevich DA, Warner DO, Novotny P, Kutteh LA, Wong GY; North Central Cancer Treatment Group. Efficacy of gabapentin in the management of chemotherapy-induced peripheral neuropathy: a phase 3 randomized, double-blind, placebo-controlled, crossover trial (N00C3). Cancer. 2007 Nov 1;110(9):2110-8. doi: 10.1002/cncr.23008.
- Results Rauck RL, Shaibani A, Biton V, Simpson J, Koch B. Lacosamide in painful diabetic peripheral neuropathy: a phase 2 double-blind placebo-controlled study. Clin J Pain. 2007 Feb;23(2):150-8. doi: 10.1097/01.ajp.0000210957.39621.b2.
- Results Sarner M, Cotton PB. Classification of pancreatitis. Gut. 1984 Jul;25(7):756-9. doi: 10.1136/gut.25.7.756.
- Results Serrano J, Andersen DK, Forsmark CE, Pandol SJ, Feng Z, Srivastava S, Rinaudo JAS; Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC). Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer: From Concept to Reality. Pancreas. 2018 Nov/Dec;47(10):1208-1212. doi: 10.1097/MPA.0000000000001167.
- Results Shaibani A, Biton V, Rauck R, Koch B, Simpson J. Long-term oral lacosamide in painful diabetic neuropathy: a two-year open-label extension trial. Eur J Pain. 2009 May;13(5):458-63. doi: 10.1016/j.ejpain.2008.05.016. Epub 2008 Jul 10.
- Results Shaibani A, Fares S, Selam JL, Arslanian A, Simpson J, Sen D, Bongardt S. Lacosamide in painful diabetic neuropathy: an 18-week double-blind placebo-controlled trial. J Pain. 2009 Aug;10(8):818-28. doi: 10.1016/j.jpain.2009.01.322. Epub 2009 May 5.
- Results Sheets PL, Heers C, Stoehr T, Cummins TR. Differential block of sensory neuronal voltage-gated sodium channels by lacosamide [(2R)-2-(acetylamino)-N-benzyl-3-methoxypropanamide], lidocaine, and carbamazepine. J Pharmacol Exp Ther. 2008 Jul;326(1):89-99. doi: 10.1124/jpet.107.133413. Epub 2008 Mar 31.
- Results Stohr T, Kupferberg HJ, Stables JP, Choi D, Harris RH, Kohn H, Walton N, White HS. Lacosamide, a novel anti-convulsant drug, shows efficacy with a wide safety margin in rodent models for epilepsy. Epilepsy Res. 2007 May;74(2-3):147-54. doi: 10.1016/j.eplepsyres.2007.03.004. Epub 2007 Apr 12.
- Results Sutton KG, Martin DJ, Pinnock RD, Lee K, Scott RH. Gabapentin inhibits high-threshold calcium channel currents in cultured rat dorsal root ganglion neurones. Br J Pharmacol. 2002 Jan;135(1):257-65. doi: 10.1038/sj.bjp.0704439.
- Results Tirkes T, Yadav D, Conwell DL, Territo PR, Zhao X, Venkatesh SK, Kolipaka A, Li L, Pisegna JR, Pandol SJ, Park WG, Topazian M, Serrano J, Fogel EL; Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer. Magnetic resonance imaging as a non-invasive method for the assessment of pancreatic fibrosis (MINIMAP): a comprehensive study design from the consortium for the study of chronic pancreatitis, diabetes, and pancreatic cancer. Abdom Radiol (NY). 2019 Aug;44(8):2809-2821. doi: 10.1007/s00261-019-02049-5.
- Results Vardanyan A, Wang R, Vanderah TW, Ossipov MH, Lai J, Porreca F, King T. TRPV1 receptor in expression of opioid-induced hyperalgesia. J Pain. 2009 Mar;10(3):243-52. doi: 10.1016/j.jpain.2008.07.004. Epub 2008 Sep 6.
- Results Venier J, Herrick R, Norris C, Liu S, Zhang L, Yuan Y Bayesian Optimal Interval (BOIN) Phase I Design (PID-862): Version 1.0.4. In. Houston, TX: The University of Texas MD Anderson Cancer Center.
- Results Vera-Portocarrero LP, Zhang ET, King T, Ossipov MH, Vanderah TW, Lai J, Porreca F. Spinal NK-1 receptor expressing neurons mediate opioid-induced hyperalgesia and antinociceptive tolerance via activation of descending pathways. Pain. 2007 May;129(1-2):35-45. doi: 10.1016/j.pain.2006.09.033. Epub 2006 Nov 22.
- Results Wang Y, Wilson SM, Brittain JM, Ripsch MS, Salome C, Park KD, White FA, Khanna R, Kohn H. Merging Structural Motifs of Functionalized Amino Acids and alpha-Aminoamides Results in Novel Anticonvulsant Compounds with Significant Effects on Slow and Fast Inactivation of Voltage-gated Sodium Channels and in the Treatment of Neuropathic Pain. ACS Chem Neurosci. 2011 Jun 15;2(6):317-322. doi: 10.1021/cn200024z.
- Results Wehler M, Reulbach U, Nichterlein R, Lange K, Fischer B, Farnbacher M, Hahn EG, Schneider T. Health-related quality of life in chronic pancreatitis: a psychometric assessment. Scand J Gastroenterol. 2003 Oct;38(10):1083-9. doi: 10.1080/00365520310005956.
- Results Wiffen PJ, Derry S, Moore RA, McQuay HJ. Carbamazepine for acute and chronic pain in adults. Cochrane Database Syst Rev. 2011 Jan 19;(1):CD005451. doi: 10.1002/14651858.CD005451.pub2.
- Results Wonder C (2016) Multiple cause of death data on CDC WONDER. In. Atlanta, GA US Department of Health and Human Services.
- Results Xie JY, Herman DS, Stiller CO, Gardell LR, Ossipov MH, Lai J, Porreca F, Vanderah TW. Cholecystokinin in the rostral ventromedial medulla mediates opioid-induced hyperalgesia and antinociceptive tolerance. J Neurosci. 2005 Jan 12;25(2):409-16. doi: 10.1523/JNEUROSCI.4054-04.2005.
- Results Yadav D, Park WG, Fogel EL, Li L, Chari ST, Feng Z, Fisher WE, Forsmark CE, Jeon CY, Habtezion A, Hart PA, Hughes SJ, Othman MO, Rinaudo JAS, Pandol SJ, Tirkes T, Serrano J, Srivastava S, Van Den Eeden SK, Whitcomb DC, Topazian M, Conwell DL; Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC). PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies: Rationale and Study Design for PROCEED From the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer. Pancreas. 2018 Nov/Dec;47(10):1229-1238. doi: 10.1097/MPA.0000000000001170.
- Results Yang AL, Vadhavkar S, Singh G, Omary MB. Epidemiology of alcohol-related liver and pancreatic disease in the United States. Arch Intern Med. 2008 Mar 24;168(6):649-56. doi: 10.1001/archinte.168.6.649.
- Results Yuan Y, Hess KR, Hilsenbeck SG, Gilbert MR. Bayesian Optimal Interval Design: A Simple and Well-Performing Design for Phase I Oncology Trials. Clin Cancer Res. 2016 Sep 1;22(17):4291-301. doi: 10.1158/1078-0432.CCR-16-0592. Epub 2016 Jul 12.
- Results Yuan Y, Lin R, Li D, Nie L, Warren KE. Time-to-Event Bayesian Optimal Interval Design to Accelerate Phase I Trials. Clin Cancer Res. 2018 Oct 15;24(20):4921-4930. doi: 10.1158/1078-0432.CCR-18-0246. Epub 2018 May 16.
- Fogel EL, Easler JJ, Yuan Y, Yadav D, Conwell DL, Vege SS, Han SY, Park W, Patrick V, White FA. Safety, Tolerability, and Dose-Limiting Toxicity of Lacosamide in Patients With Painful Chronic Pancreatitis: Protocol for a Phase 1 Clinical Trial to Determine Safety and Identify Side Effects. JMIR Res Protoc. 2024 Mar 7;13:e50513. doi: 10.2196/50513.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Lacosamide | Other / unclassified | 100 mg | Oral |
| Subject | Lacosamide | Other / unclassified | 200 mg | Oral |
| Subject | Lacosamide | Other / unclassified | 300 mg | Oral |
| Subject | Lacosamide | Other / unclassified | 400 mg | Oral |