Unmet clinical needs in chronic migraine: Rationale for study and design of COMPEL, an open-label, multicenter study of the long-term efficacy, safety, and tolerability of onabotulinumtoxinA for headache prophylaxis in adults with chronic migraine

Andrew M Blumenfeld, Sheena K Aurora, Karen Laranjo, Spyros Papapetropoulos, Andrew M Blumenfeld, Sheena K Aurora, Karen Laranjo, Spyros Papapetropoulos

Abstract

Background: Chronic migraine is a neurological condition with a large individual and socioeconomic burden of disease. The recently completed Phase III REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical development program established the efficacy and safety of onabotulinumtoxinA as a prophylactic treatment for chronic migraine patients. However, clinical questions remain. A long-term evaluation study of onabotulinumtoxinA aims to address some of the remaining questions in the treatment of chronic migraine. The clinical rationale, study design, and treatment plan of this ongoing study are reviewed in this paper.

Methods/design: The Chronic migraine OnabotulinuMtoxinA Prolonged Efficacy open Label (COMPEL) study will enroll approximately 500 adult patients with chronic migraine at international sites. Patients will be evaluated over 108 weeks, following a 4-week baseline period. Qualified subjects will receive 155 U of onabotulinumtoxinA every 12 weeks for 9 open-label cycles. The primary endpoint will be mean change from baseline in frequency of headache days at 108 weeks. Other endpoints will include additional assessments of the efficacy and safety of onabotulinumtoxinA and the effect of onabotulinumtoxinA on quality-of-life measures, disability, and health economic outcomes. The impact of onabotulinumtoxinA on common comorbidities (eg, sleep, anxiety, and fatigue) will also be assessed.

Discussion: Recruitment and enrollment are ongoing. Post-approval, open-label studies are often designed to more closely resemble clinical practice and provide an opportunity to continue the evaluation of the efficacy and safety of approved treatments. By creating a large database and analyzing a variety of outcome measures over an extended time frame, the COMPEL study will seek to contribute substantially to the existing knowledge of the chronic migraine population and the long-term management of this debilitating disorder.

Clinical trial registration number: NCT01516892.

Figures

Fig. 1
Fig. 1
COMPEL study design. ACM-I = Assessment of Chronic Migraine Impacts; ACM-S = Assessment of Chronic Migraine Symptoms; FSS = Fatigue Severity Scale; GAD-7 = Generalized Anxiety Disorder Assessment; HIT-6 = Headache Impact Test-6; HRU = Healthcare Resource Utilization; IVRS = interactive voice response system; MIDAS = Migraine Disability Assessment Questionnaire; MSQ = Migraine-Specific Quality-of-Life Questionnaire v2.1; PHQ-9 = Patient Health Questionnaire-9; PSQI = Pittsburgh Sleep Quality Index; SF-36 = Short-Form 36 Health Survey; Wk = week
Fig. 2
Fig. 2
PREEMPT 56-week data showed continued improvement in headache days with onabotulinumtoxinA. Source: [31]. This is a pooled analysis of PREEMPT 1 and 2: the double-blind phase included 688 subjects in the onabotulinumtoxinA group and 696 in the placebo group. Headache days at baseline: 19.9 onabotulinumtoxinA group vs 19.8 placebo group, p = 0.498. PREEMPT = Phase 3 REsearch Evaluating Migraine Prophylaxis Therapy

References

    1. Natoli J, Manack A, Dean B, Butler Q, Turkel C, Stovner L, Lipton R. Global prevalence of chronic migraine: a systematic review. Cephalalgia. 2010;30:599–609.
    1. Olesen J. Headache Classification Committee of the International Headache Society (IHS): The International Classification of Headache Disorders, 3rd edition (beta version) Cephalalgia. 2013;33:629–808. doi: 10.1177/0333102413487610.
    1. Bigal ME, Serrano D, Reed M, Lipton RB. Chronic migraine in the population: burden, diagnosis, and satisfaction with treatment. Neurology. 2008;71:559–566. doi: 10.1212/01.wnl.0000323925.29520.e7.
    1. Munakata J, Hazard E, Serrano D, Klingman D, Rupnow MF, Tierce J, Reed M, Lipton RB. Economic burden of transformed migraine: Results from the American Migraine Prevalence and Prevention (AMPP) study. Headache. 2009;49:498–508. doi: 10.1111/j.1526-4610.2009.01369.x.
    1. Blumenfeld A, Varon S, Wilcox TK, Buse D, Kawata AK, Manack A, Goadsby PJ, Lipton RB. Disability, HRQoL and resource use among chronic and episodic migraineurs: Results from the International Burden of Migraine Study (IBMS) Cephalalgia. 2011;31:301–315. doi: 10.1177/0333102410381145.
    1. Stewart WF, Wood GC, Manack A, Varon SF, Buse DC, Lipton RB. Employment and Work Impact of Chronic Migraine and Episodic Migraine. J Occup Environ Med. 2010;52:8–14. doi: 10.1097/JOM.0b013e3181c1dc56.
    1. Buse DC, Manack A, Serrano D, Turkel C, Lipton RB. Sociodemographic and comorbidity profiles of chronic migraine and episodic migraine sufferers. J Neurol Neurosurg Psychiatry. 2010;81:428–432. doi: 10.1136/jnnp.2009.192492.
    1. Peres MF, Zukerman E, Young WB, Silberstein SD. Fatigue in chronic migraine patients. Cephalalgia. 2002;22:720–724. doi: 10.1046/j.1468-2982.2002.00426.x.
    1. Aoki KR. Evidence for antinociceptive activity of botulinum toxin type A in pain management. Headache. 2003;43(Suppl 1):S9–15. doi: 10.1046/j.1526-4610.43.7s.3.x.
    1. Aoki KR. Review of a proposed mechanism for the antinociceptive action of botulinum toxin type A. Neurotoxicology. 2005;26:785–793. doi: 10.1016/j.neuro.2005.01.017.
    1. Hargreaves R. New migraine and pain research. Headache. 2007;47:S26–S43. doi: 10.1111/j.1526-4610.2006.00675.x.
    1. Aoki KR, Francis J. Updates on the antinociceptive mechanism hypothesis of botulinum toxin A. Parkinsonism Relat Disord. 2011;17(Suppl 1):S28–S33. doi: 10.1016/j.parkreldis.2011.06.013.
    1. Dodick DW, Turkel CC, DeGryse R, Aurora SK, Silberstein SD, Lipton RB, Diener HC, Brin MF, on behalf of the PREEMPT Chronic Migraine Study Group OnabotulinumtoxinA for treatment of chronic migraine: Pooled results from the double-blind, randomized, placebo-controlled phases of the PREEMPT clinical program. Headache. 2010;50:921–936. doi: 10.1111/j.1526-4610.2010.01678.x.
    1. Silberstein S, Tfelt-Hansen P, Dodick DW, Limmroth V, Lipton RB, Pascual J, Wang SJ. Guidelines for controlled trials of prophylactic treatment of chronic migraine in adults. Cephalalgia. 2008;28:484–495. doi: 10.1111/j.1468-2982.2008.01555.x.
    1. Spitzer RL, Kroenke K, Williams JB, Lowe B. A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med. 2006;166:1092–1097. doi: 10.1001/archinte.166.10.1092.
    1. Stewart WF, Lipton RB, Whyte J, Dowson A, Kolodner K, Liberman JN, Sawyer J. An international study to assess reliability of the Migraine Disability Assessment (MIDAS) score. Neurology. 1999;53:988–994. doi: 10.1212/WNL.53.5.988.
    1. Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001;16:606–613. doi: 10.1046/j.1525-1497.2001.016009606.x.
    1. Buysse DJ, Reynolds CF, III, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989;28:193–213. doi: 10.1016/0165-1781(89)90047-4.
    1. Krupp LB, LaRocca NG, Muir-Nash J, Steinberg AD. The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol. 1989;46:1121–1123. doi: 10.1001/archneur.1989.00520460115022.
    1. Wang SJ, Fuh JL, Lu SR, Juang KD. Quality of life differs among headache diagnoses: analysis of SF-36 survey in 901 headache patients. Pain. 2001;89:285–292. doi: 10.1016/S0304-3959(00)00380-8.
    1. Jhingran P, Osterhaus JT, Miller DW, Lee JT, Kirchdoerfer L. Development and validation of the Migraine-Specific Quality of Life Questionnaire. Headache. 1998;38:295–302. doi: 10.1046/j.1526-4610.1998.3804295.x.
    1. Albanese A. Terminology for preparations of botulinum neurotoxins: what a difference a name makes. JAMA. 2011;305:89–90. doi: 10.1001/jama.2010.1937.
    1. Saper JR, Lake AE, III, Cantrell DT, Winner PK, White JR. Chronic daily headache prophylaxis with tizanidine: a double-blind, placebo-controlled, multicenter outcome study. Headache. 2002;42:470–482. doi: 10.1046/j.1526-4610.2002.02122.x.
    1. Saper JR, Silberstein SD, Lake AE, III, Winters ME. Double-blind trial of fluoxetine: chronic daily headache and migraine. Headache. 1994;34:497–502. doi: 10.1111/j.1526-4610.1994.hed3409497.x.
    1. Yurekli VA, Akhan G, Kutluhan S, Uzar E, Koyuncuoglu HR, Gultekin F. The effect of sodium valproate on chronic daily headache and its subgroups. J Headache Pain. 2008;9:37–41. doi: 10.1007/s10194-008-0002-5.
    1. Spira PJ, Beran RG. Gabapentin in the prophylaxis of chronic daily headache: a randomized, placebo-controlled study. Neurology. 2003;61:1753–1759. doi: 10.1212/01.WNL.0000100121.58594.11.
    1. Silvestrini M, Bartolini M, Coccia M, Baruffaldi R, Taffi R, Provinciali L. Topiramate in the treatment of chronic migraine. Cephalalgia. 2003;23:820–824. doi: 10.1046/j.1468-2982.2003.00592.x.
    1. Silberstein SD, Lipton RB, Dodick DW, Freitag FG, Ramadan N, Mathew N, Brandes JL, Bigal M, Saper J, Ascher S, Jordan DM, Greenberg SJ, Hulihan J. Efficacy and safety of topiramate for the treatment of chronic migraine: a randomized, double-blind, placebo-controlled trial. Headache. 2007;47:170–180. doi: 10.1111/j.1526-4610.2006.00684.x.
    1. Diener HC, Dodick DW, Aurora SK, Turkel CC, DeGryse R, Lipton RB, Silberstein SD, Brin MF, on behalf of the PREEMPT 2 Chronic Migraine Study Group OnabotulinumtoxinA for treatment of chronic migraine: Results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 2 trial. Cephalalgia. 2010;30:804–814. doi: 10.1177/0333102410364677.
    1. Aurora SK, Dodick DW, Turkel CC, DeGryse R, Silberstein SD, Lipton RB, Diener HC, Brin MF, on behalf of PREEMPT 1 Chronic Migraine Study Group OnabotulinumtoxinA for treatment of chronic migraine: Results from the double-blind, randomized placebo-controlled phase of the PREEMPT 1 trial. Cephalalgia. 2010;30:793–803. doi: 10.1177/0333102410364676.
    1. Aurora SK, Winner P, Freeman MC, Spierings EL, Heiring JO, DeGryse R, VanDenburgh AM, Nolan ME, Turkel CC. OnabotulinumtoxinA for treatment of chronic migraine: Pooled analyses of the 56-week PREEMPT clinical program. Headache. 2011;51:1358–73. doi: 10.1111/j.1526-4610.2011.01990.x.
    1. Blumenfeld A, Silberstein SD, Dodick DW, Aurora SK, Turkel CC, Binder WJ. Method of injection of onabotulinumtoxinA for chronic migraine: a safe, well-tolerated, and effective treatment paradigm based on the PREEMPT clinical program. Headache. 2010;50:1406–1418. doi: 10.1111/j.1526-4610.2010.01766.x.
    1. Kosinski M, Bayliss MS, Bjorner JB, Ware JE, Jr, Garber WH, Batenhorst A, Cady R, Dahlöf CG, Dowson A, Tepper S. A six-item short-form survey for measuring headache impact: the HIT-6. Qual Life Res. 2003;12:963–974. doi: 10.1023/A:1026119331193.
    1. Stewart WF, Lipton RB, Kolodner K. Migraine disability assessment (MIDAS) score: relation to headache frequency, pain intensity, and headache symptoms. Headache. 2003;43:258–265. doi: 10.1046/j.1526-4610.2003.03050.x.
    1. Kroenke K, Spitzer RL. The PHQ-9: A new depression diagnostic and severity measure. Psych Ann. 2002;32:1–7.
    1. Bartolini M, Silvestrini M, Taffi R, Lanciotti C, Luconi R, Capecci M, Provinciali L. Efficacy of topiramate and valproate in chronic migraine. Clin Neuropharmacol. 2005;28:277–279. doi: 10.1097/01.wnf.0000192136.46145.44.
    1. Diener HC, Bussone G, Van Oene JC, Lahaye M, Schwalen S, Goadsby PJ. Topiramate reduces headache days in chronic migraine: a randomized, double-blind, placebo-controlled study. Cephalalgia. 2007;27:814–823. doi: 10.1111/j.1468-2982.2007.01326.x.
    1. Krymchantowski AV, Silva MT, Barbosa JS, Alves LA. Amitriptyline versus amitriptyline combined with fluoxetine in the preventative treatment of transformed migraine: a double-blind study. Headache. 2002;42:510–514. doi: 10.1046/j.1526-4610.2002.02125.x.
    1. Mathew NT, Jaffri SF. A double-blind comparison of onabotulinumtoxinA (BOTOX®) and topiramate (TOPAMAX®) for the prophylactic treatment of chronic migraine: a pilot study. Headache. 2009;49:1466–1478. doi: 10.1111/j.1526-4610.2009.01566.x.
    1. Cady RK, Schreiber CP, Porter JA, Blumenfeld AM, Farmer KU. A Multi-Center Double-Blind Pilot Comparison of OnabotulinumtoxinA and Topiramate for the Prophylactic Treatment of Chronic Migraine. Headache. 2011;51:21–32. doi: 10.1111/j.1526-4610.2010.01796.x.

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi