Safety, tolerability, and efficacy of TEV-48125 for preventive treatment of high-frequency episodic migraine: A multicentre, randomised, double-blind, placebo-controlled, phase 2b study

The Lancet Neurology

Volumn 14, Issue 11, 2015, Pages 1081-1090

  Bigal, Marcelo E ^a   Dodick, David W ^b   Rapoport, Alan M ^c   Silberstein, Stephen D ^d   Ma, Yuju ^a   Yang, Ronghua ^a   Loupe, Pippa S ^a   Burstein, Rami ^e   Newman, Lawrence C ^f   Lipton, Richard B ^g  

^a TEVA PHARMACEUTICALS   (Israel)

^b MAYO CLINIC   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d THOMAS JEFFERSON UNIVERSITY   (United States)

^e HARVARD MEDICAL SCHOOL   (United States)

^f ST LUKE S ROOSEVELT HOSPITAL CENTER   (United States)

^g ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CALCITONIN GENE RELATED PEPTIDE RECEPTOR ANTAGONIST; PLACEBO; TEV 48125; UNCLASSIFIED DRUG; CALCITONIN GENE RELATED PEPTIDE; IMMUNOLOGIC FACTOR; MONOCLONAL ANTIBODY; TEV-48125;

ADULT; AGED; ANTIPHOSPHOLIPID SYNDROME; ARTHRALGIA; ARTICLE; BACKACHE; BRONCHITIS; CHEMOPROPHYLAXIS; CLINICAL ASSESSMENT; CONTROLLED STUDY; DEPRESSION; DISEASE DURATION; DIZZINESS; DOUBLE BLIND PROCEDURE; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; DYSPEPSIA; EPISODIC MIGRAINE; ERYTHEMA; FATIGUE; FEMALE; FIBULA FRACTURE; HEADACHE; HIGH FREQUENCY EPISODIC MIGRAINE; HUMAN; HYPERTENSION; INFLUENZA; INJECTION SITE CONTUSION; INJECTION SITE ERYTHEMA; INJECTION SITE HEMATOMA; INJECTION SITE PAIN; INJECTION SITE PRURITUS; INJECTION SITE REACTION; INTENTION TO TREAT ANALYSIS; LIMB INJURY; LIMB PAIN; MAJOR CLINICAL STUDY; MALE; MEDICATION COMPLIANCE; MIGRAINE; MULTICENTER STUDY; MULTIPLE CYCLE TREATMENT; NAUSEA; OROPHARYNX PAIN; OUTCOME ASSESSMENT; PARESTHESIA; PHASE 2 CLINICAL TRIAL; POPULATION; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; REGRESSION ANALYSIS; RHINOPHARYNGITIS; SINUSITIS; TACHYCARDIA; TRANSFORMED MIGRAINE; TREATMENT DURATION; TREMOR; UPPER RESPIRATORY TRACT INFECTION; URINARY TRACT INFECTION; WEB BROWSER; ADOLESCENT; CLINICAL TRIAL; DOSE RESPONSE; IMMUNOLOGY; MEDLINE; METABOLISM; MIDDLE AGED; MIGRAINE DISORDERS; STATISTICS AND NUMERICAL DATA; TREATMENT OUTCOME; YOUNG ADULT;

ADOLESCENT; ADULT; AGED; ANTIBODIES, MONOCLONAL; CALCITONIN GENE-RELATED PEPTIDE; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; FEMALE; HUMANS; IMMUNOLOGIC FACTORS; MALE; MEDLINE; MIDDLE AGED; MIGRAINE DISORDERS; TREATMENT OUTCOME; YOUNG ADULT;

EID: 84944059855     PISSN: 14744422     EISSN: 14744465     Source Type: Journal    
DOI: 10.1016/S1474-4422(15)00249-5     Document Type: Article

References (34)

1. The International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia 2013, 33:629-808. Headache Classification Committee of the International Headache Society (HIS).
2. Bigal ME, Lipton RB Clinical course in migraine: conceptualising migraine transformation. Neurology 2008, 71:848-855.
3. Silberstein SD, Holland S, Freitag F, et al. Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology 2012, 78:1337-1345.
4. Lipton RB, Bigal ME, Diamond M, et al. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology 2007, 68:343-349.
5. Blumenfeld AM, Bloudek LM, Becker WJ, et al. Patterns of use and reasons for discontinuation of prophylactic medications for episodic migraine and chronic migraine: results from the second international burden of migraine study (IBMS-II). Headache 2013, 53:644-655.
6. Lipton RB, Bigal ME, Kolodner K, Stewart WF, Liberman JN, Steiner TJ The family impact of migraine: population-based studies in the USA and UK. Cephalalgia 2003, 23:429-440.
7. Steiner TJ Lifting the burden: the global campaign against headache. Lancet Neurol 2004, 3:204-205. World Headache Alliance.
8. Scher AI, Lipton RB, Stewart W Risk factors for chronic daily headache. Curr Pain Headache Rep 2002, 6:486-491.
9. Goadsby PJ, Edvinsson L, Ekman R Release of vasoactive peptides in the extracerebral circulation of humans and the cat during activation of the trigeminovascular system. Ann Neurology 1988, 23:193-196.
10. Silberstein SD, Edvinsson L Is CGRP a marker for chronic migraine?. Neurology 2013, 81:1184-1185.
11. Eftekhari S, Edvinsson L Possible sites of action of the new calcitonin gene-related peptide receptor antagonists. Ther Adv Neurol Disord 2010, 3:369-378.
12. Eftekhari S, Salvatore CA, Johansson S, Chen TB, Zeng Z, Edvinsson L Localization of CGRP, CGRP receptor, PACAP and glutamate in trigeminal ganglion. Relation to the blood-brain barrier. Brain Res 2015, 1600:93-109.
13. Hostetler ED, Joshi AD, Sanabria-Bohorquez S, et al. In vivo quantification of calcitonin gene-related peptide receptor occupancy by telcagepant in rhesus monkeys and human brain using the positron emission tomography tracer [11C] MK-4232. J Pharmacol Exp Ther 2013, 347:478-486.
14. Olesen J, Diener HC, Husstedt IW, et al. Calcitonin gene-related peptide receptor antagonist BIBN 4096 BS for the acute treatment of migraine. N Engl J Med 2004, 350:1104-1110.
15. Ho TW, Ferrari MD, Dodick DW, et al. Efficacy and tolerability of MK-0974 (telcagepant), a new oral antagonist of calcitonin gene-related peptide receptor, compared with zolmitriptan for acute migraine: a randomised, placebo-controlled, parallel-treatment trial. Lancet 2008, 372:2115-2123.
16. Ho TW, Connor KM, Zhang Y, et al. Randomized controlled trial of the CGRP receptor antagonist telcagepant for migraine prevention. Neurology 2014, 83:958-966.
17. Bigal ME, Walter S, Rapoport AM Calcitonin gene-related peptide (CGRP) and migraine current understanding and state of development. Headache 2013, 53:1230-1244.
18. Dodick DW, Goadsby PJ, Silberstein SD, et al. Safety and efficacy of ALD403, an antibody to calcitonin gene-related peptide, for the prevention of frequent episodic migraine: a randomised, double-blind, placebo-controlled, exploratory phase 2 trial. Lancet Neurol 2014, 13:1100-1107.
19. Dodick DW, Goadsby PJ, Spierings EL, Scherer JC, Sweeney SP, Grayzel DS Safety and efficacy of LY2951742, a monoclonal antibody to calcitonin gene-related peptide, for the prevention of migraine: a phase 2, randomised, double-blind, placebo-controlled study. Lancet Neurol 2014, 13:885-892.
20. White V Amgen presents positive first Phase 2 data for AMG 334 in the prevention of episodic migraine (accessed May 18, 2015). http://www.europeanpharmaceuticalreview.com/31652/news/industry-news/amgen-presents-positive-first-phase-2-data-for-amg-334-in-the-prevention-of-episodic-migraine/.
21. Bigal ME, Escandon R, Bronson M, et al. Safety and tolerability of LBR-101, a humanized monoclonal antibody that blocks the binding of CGRP to its receptor: results of the phase 1 program. Cephalalgia 2013, 34:483-492.
22. Walter S, Alibhoy A, Escandon R, Bigal ME Evaluation of cardiovascular parameters in cynomolgus monkeys following IV administration of LBR-101, a monoclonal antibody against calcitonin gene-related peptide. mAbs 2014, 6:871-878.
23. Bigal ME, Edvinsson L, Rapoport AM, et al. Safety, tolerability, and efficacy of TEV-48125 for preventive treatment of chronic migraine: a multicentre, randomised, double-blind, placebo-controlled, phase 2b study. Lancet Neurol 2015, published online Sept 30. http://dx.doi.org/10.1016/S1474-4422(15)00245-8.
24. Zeller J, Poulsen KT, Sutton JE, et al. CGRP function-blocking antibodies inhibit neurogenic vasodilatation without affecting heart rate or arterial blood pressure in the rat. Br J Pharmacol 2008, 155:1093-1103.
25. Stewart WF, Lipton RB, Whyte J, et al. An international study to assess reliability of the Migraine Disability Assessment (MIDAS) score. Neurology 1999, 53:988-994.
26. Aurora SK, Winner P, Freeman MC, et al. OnabotulinumtoxinA for treatment of chronic migraine: pooled analyses of the 56-week PREEMPT clinical program. Headache 2011, 51:1358-1373.
27. Mathew NT, Saper JR, Silberstein SD, et al. Migraine prophylaxis with divalproex. Arch Neurol 1995, 52:281-286.
28. Brandes JL, Saper JR, Diamond M, et al. Topiramate for migraine prevention: a randomized controlled trial. JAMA 2004, 291:965-973.
29. Bigal ME, Walter S, Bronson M, Alibhoy A, Escandon R Cardiovascular and hemodynamic parameters in women following prolonged CGRP inhibition using LBR-101, a monoclonal antibody against CGRP. Cephalalgia 2014, 34:968-976.
30. Hewitt DJ, Aurora SK, Dodick DW, et al. Randomized controlled trial of the CGRP receptor antagonist MK-3207 in the acute treatment of migraine. Cephalalgia 2011, 31:712-722.
31. Guidance for industry: assay development for immunogenicity testing of therapeutic proteins US Department of Health and Human Services, Food and Drug AdministrationFood and Drug Administration, Center for Drug Evaluation and Research (CDER)Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER)Center for Biologics Evaluation and Research (CBER), (accessed April 20, 2015). http://www.fda.gov/downloads/Drugs/Guidances/UCM192750.pdf.
32. Ashina M, Bendtsen L, Jensen R, Schifter S, Olesen J Evidence for increased plasma levels of calcitonin gene-related peptide in migraine outside of attacks. Pain 2000, 86:133-138.
33. Goadsby PJ, Edvinsson L, Ekman R Vasoactive peptide release in the extracerebral circulation of humans during migraine headache. Ann Neurol 1990, 28:183-187.
34. Stanimirovic DB, Bani-Yaghoub M, Perkins M, Haqqani AS Blood-brain barrier models: in vitro to in vivo translation in preclinical development of CNS-targeting biotherapeutics. Expert Opin Drug Discov 2015, 10:141-155.