2010: Year in Review

(Headache 2011;51:181-187) This section of Headache annually reviews the status of recently completed and ongoing clinical trials involving headache disorders. The review will focus on multicenter trials of new therapies as well as novel formulations of previously approved therapeutics. Table 1 summarizes major migraine therapeutic trials that have been completed recently, according to data obtained from the “ClinicalTrials.Gov” website as well as from corporate press releases. Table 2 summarizes the major therapeutic trials that are ongoing at the present time. Table 1.—. 2010 Completed Clinical Trials in Migraine Investigational Treatment Mechanism of Action Study Sponsor Phase # Subjects Start Date End Date NDA, New Drug Application; NINCDS, National Institute of Neurological Disorders and Stroke. Sumatriptan 5-HT1B receptor agonist An open-label study to evaluate the safety of NP101, a sumatriptan iontophoretic transdermal patch, in the treatment of acute migraine over 12 months NuPathe Inc. Phase 3 300 January 2009 March-10 (NDA in November 2010) Dihydroergocryptine inhaled 5-HT1B agonist plus other receptor interactions A randomized, double blind, placebo controlled, parallel group, Phase 3 study of MAP0004 in adult migraineurs for a single migraine followed by open label extensions to 26/52 weeks MAP Pharmaceuticals, Inc. Phase 3 950 March 2008 November 2010 (completed) Lasmiditan (COL-144) 5-HT1F agonist Dose-ranging study of oral COL-144 in acute migraine treatment CoLucid Phase 2b 391 July 2009 June 2010 (completed) NXN-188 5-HT1 agonist and nNOS antagonist A Phase 2 study of the safety and effectiveness of a single oral dose of NXN 188 for the treatment of moderate to severe migraine headache with aura NeurAxon Inc. Phase 2 300 June 2009 March 2010 (completed) NXN-188 5-HT1 agonist and nNOS antagonist Phase 2 study of the safety and effectiveness of a single oral dose of NXN-188 for the treatment of moderate to severe migraine headache without aura NeurAxon Inc. Phase 2 120 August 2009 March 2010 (completed) NXN-188 5-HT1 agonist and nNOS antagonist A Phase 2a study of the safety and effectiveness of NXN-188 for the acute treatment of migraine attacks with aura NeurAxon Inc. Phase 2a 40 May 2009 December 2010 (data pending) LY2590443 Unknown A safety, tolerability, and efficacy study of LY2590443 in the treatment of acute migraine headache Eli Lilly and Company Phase 2 200 December 2010 April 2010 (terminated) BGC20-1531 EP4 receptor antagonist A multinational, multicenter, randomized, double-blind, placebo-controlled, three-way crossover study in migraine patients, treated with 2 doses of BGC20-1531 and placebo BTG International Phase 2 100 June 2009 July 2010 (terminated) Prophylactic treatments GSK1838262 (XP13512) Gabapentin Prevention study in adult patients suffering from migraine headaches GSK/Xenoport Phase 2 450 August 2008 May 2010 (completed) ADX10059 mGluR5 A Phase 2b, randomized, double-blind, placebo-controlled, parallel group, dose-ranging, multicenter study to investigate the efficacy, safety and tolerability of the mGluR5 negative allosteric modulator ADX10059 for the prevention of migraine Addex Phase 2a 350 December 2010 December 2009 (terminated) Valproate acid (DP-VPA) Neuromodulator Double-blind, randomized, placebo-controlled, parallel-group, two-arm, multicenter phase ii trial to assess the safety, tolerability, and efficacy of DP-VPA (up to 900 mg) once daily for 10 weeks in adult subjects with migraine D-Pharm Ltd. Phase 2 40 July 2008 October 2009 (withdrawn before activation) Propranolol LA and topiramate Beta-adrenergic antagonist and channel antagonist NINDS CRC chronic migraine treatment trial NINCDS, Ortho-McNeil Janssen Scientific Affairs, LLC Phase 3 250 October 2008 September 2010 (suspended) Ramelteon Melatonin agonist A study of a melatonin receptor agonist to prevent migraine Swedish Medical Center|Takeda Global Research & Development Center, Inc. Phase 2 30 April 2008 April 2009 (closed) Ramelteon Hypnotic A double-blind placebo-controlled trial of rozerem in migraine headaches Takeda Pharmaceuticals North America Phase 4 24 October 2006 July 2009 (closed) Table 2.—. 2011 Ongoing Clinical Trials in Migraine and Chronic Daily Headache Investigational Treatment Mechanism of Action Study Sponsor Phase # Subjects Start Date End Date AMPA, α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate; CGRP, calcitonin gene-related peptide; NSAID, non-steroidal anti-inflammatory drug; PFO, patent foramen ovale. Acute treatments Metoclopramide Dopamine 2 receptor antagonist Metoclopramide for acute migraine: a dose finding study Montefiore Medical Center Phase 3 330 April 2008 May 10 (results pending) Metoclopramide and ketoprofen Dopamine 2 receptor antagonist and NSAID Randomized controlled trial on the effectiveness of metoclopramide alone or in combination with ketoprofen in acute migraine of child IRCCS Burlo Garofolo Phase 3 120 February 2009 June 10, 2010 (results pending) BGG492 AMPA antagonist A multicenter, randomized, double-blind, parallel group, active and placebo controlled, proof of concept study in patients with acute migraine to assess the efficacy, safety and tolerability of single oral doses of BGG492 Novartis Phase 2 75 April 2009 August 2010 (results pending) Prophylactic treatments Occipital nerve stimulation Neurostimulation Precision implantable stimulator for migraine study – occipital nerve stimulation for migraine Boston Scientific Corporation Phase 3 179 February 2006 March 2011 Bupivicaine/methylprednisolone Local anesthetic and steroid Greater occipital nerve block for migraine prophylaxis Mayo Clinic Phase 4 70 June 2009 May 2011 DR-105 Hormone A multicenter, randomized, double-blind study to evaluate the efficacy of DR-105 compared to placebo for the management of menstrually related migraine headaches Teva Women's Health Phase 2 120 November 2008 June 2011 Telcagepant CGRP antagonist Telcagepant for prevention of menstrually related migraine in female patients with episodic migraine Merck Phase 3 4500 June 2010 September 2011 LY2300559 Unknown A randomized, double-blind, placebo controlled proof of concept study of LY2300559 in patients with migraine Eli Lilly Phase 2 118 October 2010 April 2012 Cyclobenzaprine hydrochloride Efficacy and safety of cyclobenzaprine hydrochloride extended release for the treatment of chronic migraine University of Medicine and Dentistry New Jersey|Cephalon Phase 3 70 July 2010 July 2012 AMPLATZER® PFO Occluder Device PFO closure PRIMA PFO migraine trial AGA Medical Corporation Phase 2 144 May 2006 January 2013 Candesartan cilexitil Candesartan vs propranolol for migraine prevention University of Science and Technology|AstraZeneca|St. Olavs Hospital|Kragero Tablettproduksjon as, Norway Phase 2/3 72 April 2009 April 2013 Ethosuximide Comparison of a drug and placebo in the prevention of migraine headaches Department of Veterans Affairs, Thomas Jefferson University, University of Pittsburgh Phase 2 128 June 2010 October 2013 Occipital nerve stimulation Neurostimulation A prospective, randomized, double-blind, placebo-controlled trial of occipital nerve stimulation for drug refractory migraine Boston Scientific Corporation Phase 2 25 May 2006 December 2013 Duloxetine Jefferson Lilly Unknown Unknown Unknown Unknown NXN-462 NeurAxon Inc. Phase 2 Unknown January 2011 Unknown Chronic daily headache Oxytocin Hormone Effect of intranasal oxytocin on headache in chronic daily headache MedVadis Research Corporation/Trigemina, Inc.. Phase 2 80 November 2009 November 2010