In 1995, a committee of the International Headache Society developed and published the first edition of the Guidelines for Controlled Trials of Drugs in Cluster Headache. These have not been... Show moreIn 1995, a committee of the International Headache Society developed and published the first edition of the Guidelines for Controlled Trials of Drugs in Cluster Headache. These have not been revised. With the emergence of new medications, neuromodulation devices and trial designs, an updated version of the International Headache Society Guidelines for Controlled Clinical Trials in Cluster Headache is warranted. Given the scarcity of evidence-based data for cluster headache therapies, the update is largely consensus-based, but takes into account lessons learned from recent trials and demands by patients. It is intended to apply to both drug and neuromodulation treatments, with specific proposals for the latter when needed. The primary objective is to propose a template for designing high quality, state-of-the-art, controlled clinical trials of acute and preventive treatments in episodic and chronic cluster headache. The recommendations should not be regarded as dogma and alternative solutions to particular methodological problems should be explored in the future and scientifically validated. Show less
Diener, H.C.; Tassorelli, C.; Dodick, D.W.; Silberstein, S.D.; Lipton, R.B.; Ashina, M.; ... ; Int Headache Soc Clinical Trials C 2020
Clinical trials are a key component of the evidence base for the treatment of headache disorders. In 1991, the International Headache Society Clinical Trials Standing Committee developed and... Show moreClinical trials are a key component of the evidence base for the treatment of headache disorders. In 1991, the International Headache Society Clinical Trials Standing Committee developed and published the first edition of theGuidelines for Controlled Trials of Drugs in Migraine. Advances in drugs, devices, and biologicals, as well as novel trial designs, have prompted several updates over the nearly 30 years since, including most recently theGuidelines for controlled trials of preventive treatment of chronic migraine(2018), theGuidelines for controlled trials of acute treatment of migraine attacks in adults(2019), andGuidelines for controlled trials of preventive treatment of migraine in children and adolescents(2019). The present update incorporates findings from new research and is intended to optimize the design of controlled trials of preventive pharmacological treatment of episodic migraine in adults. A guideline for clinical trials with devices will be published separately. Show less
Diener, H.C.; Goadsby, P.J.; Ashina, M.; Al-Karagholi, M.A.; Sinclair, A.; Mitsikostas, D.; ... ; PREMIUM Study Group 2019
Introduction: Lasmiditan (COL-144; LY573144) is a novel, highly selective and potent agonist at 5-HTIF receptors that lacks vasoconstrictor activity. Preclinical and early clinical experiments... Show moreIntroduction: Lasmiditan (COL-144; LY573144) is a novel, highly selective and potent agonist at 5-HTIF receptors that lacks vasoconstrictor activity. Preclinical and early clinical experiments predict acute antimigraine efficacy of COL-144 that is mediated through a non-vascular, primarily neural, mechanism. Subjects and methods: In a randomised, multicentre, placebo-controlled, double-blind, group-sequential, adaptive treatment-assignment, proof-of-concept and dose-finding study, we treated 130 subjects in-hospital during a migraine attack. Subjects were allocated to an intravenous dose level of lasmiditan or placebo in small cohorts. The starting dose was 2.5 mg. Subsequent doses were adjusted, up or down, according to the safety and efficacy seen in the preceding cohort. The primary outcome measure was headache response defined as improvement from moderate or severe headache at baseline to mild or no headache at 2 h post-dose. The study was designed to explore the overall dose response relationship but was not powered to differentiate individual doses from placebo, nor to detect effect differences for other migraine symptoms. Results: Forty-two subjects received placebo and 88 received lasmiditan in doses of 2.5-45 mg. Subjects were observed in the clinic for 4 h after treatment and used a diary card to record symptoms and adverse events for up to 24 h. The study was terminated when the 20 mg dose met predefined efficacy stopping rules. Of subjects treated in the 10, 20, 30 and 45 mg lasmiditan dose groups, 54-75% showed a 2 h headache response, compared to 45% in the placebo group (P = 0.0126 for the linear association between response rates and dose levels). Patient global impression at 2 h and lack of need for rescue medication also showed statistically significant linear correlations with dose. Lasmiditan was generally well tolerated. Adverse events were reported by 65% of subjects on lasmiditan and by 43% on placebo and were generally mild. Dizziness, paresthesia and sensations of heaviness (usually limb) were more common on lasmiditan. Conclusions: At intravenous doses of 20 mg and higher, lasmiditan proved effective in the acute treatment of migraine. Further studies to assess the optimal oral dose and full efficacy and tolerability profile are under way. The non-vascular, neural mechanism of action of lasmiditan may offer an alternative means to treat migraine especially in patients who have contra-indications for agents with vasoconstrictor activity. The clinicaltrials.gov identifier for this study is NCT00384774. Show less
Ferrari, M.D.; Farkkila, M.; Reuter, U.; Pilgrim, A.; Davis, C.; Krauss, M.; ... ; European COL-144 Investigators 2010
INTRODUCTION Lasmiditan (COL-144; LY573144) is a novel, highly selective and potent agonist at 5-HT(1F) receptors that lacks vasoconstrictor activity. Preclinical and early clinical experiments... Show moreINTRODUCTION Lasmiditan (COL-144; LY573144) is a novel, highly selective and potent agonist at 5-HT(1F) receptors that lacks vasoconstrictor activity. Preclinical and early clinical experiments predict acute antimigraine efficacy of COL-144 that is mediated through a non-vascular, primarily neural, mechanism. SUBJECTS AND METHODS In a randomised, multicentre, placebo-controlled, double-blind, group-sequential, adaptive treatment-assignment, proof-of-concept and dose-finding study, we treated 130 subjects in-hospital during a migraine attack. Subjects were allocated to an intravenous dose level of lasmiditan or placebo in small cohorts. The starting dose was 2.5 mg. Subsequent doses were adjusted, up or down, according to the safety and efficacy seen in the preceding cohort. The primary outcome measure was headache response defined as improvement from moderate or severe headache at baseline to mild or no headache at 2 h post-dose. The study was designed to explore the overall dose response relationship but was not powered to differentiate individual doses from placebo, nor to detect effect differences for other migraine symptoms. RESULTS Forty-two subjects received placebo and 88 received lasmiditan in doses of 2.5-45 mg. Subjects were observed in the clinic for 4 h after treatment and used a diary card to record symptoms and adverse events for up to 24 h. The study was terminated when the 20 mg dose met predefined efficacy stopping rules. Of subjects treated in the 10, 20, 30 and 45 mg lasmiditan dose groups, 54-75% showed a 2 h headache response, compared to 45% in the placebo group (P = 0.0126 for the linear association between response rates and dose levels). Patient global impression at 2 h and lack of need for rescue medication also showed statistically significant linear correlations with dose. Lasmiditan was generally well tolerated. Adverse events were reported by 65% of subjects on lasmiditan and by 43% on placebo and were generally mild. Dizziness, paresthesia and sensations of heaviness (usually limb) were more common on lasmiditan. CONCLUSIONS At intravenous doses of 20 mg and higher, lasmiditan proved effective in the acute treatment of migraine. Further studies to assess the optimal oral dose and full efficacy and tolerability profile are under way. The non-vascular, neural mechanism of action of lasmiditan may offer an alternative means to treat migraine especially in patients who have contra-indications for agents with vasoconstrictor activity. The clinicaltrials.gov identifier for this study is NCT00384774. Show less
