Study of the Safety and Effectiveness of NXN-188 for the Acute Treatment of Migraine Attacks With Aura

NCT00877838 | Unknown Phase 2 DMC

• 1 other identifier: NXN-188-202
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The following study is being conducted to explore the safety and effectiveness of a new chemical entity called NXN-188 in subjects with a history of migraine with aura. In this study subjects will treat two attacks of migraine with aura during the aura phase - once with placebo and once with NXN-188.

Conditions

Migraine With Aura

Keywords

Headache; Migraine; Aura; Acute; Attack; Clinical; Trial; Intervention; Nitrogen Oxide; NOS; nNOS; Triptan; 5HT; Serotonin

Outcome Measures

Primary Outcomes (2)

• The severity of headache measured with a 4 point scale (The Headache Severity Score (HSS))

  2 hours after dosing

• Absence of headache

  2 hours after dosing

Secondary Outcomes (4)

• The occurence of any type(s) of adverse events(s)

  0-48 hours after dosing

• The severity of headache measured with a 4 point scale (The Headache Severity Score (HSS))

  0, 1, 2, 4, 8 and 24 hours after dosing

• Clinical Disability measured on a 4 point scale

  0, 1, 2, 4, 8 and 24 hours after dosing

• Overall evaluation of the study medication

  24 hours after dosing

Interventions

NXN-188 DRUG

NXN-188 600 mg (3 gelatin capsules each containing 200 mg) when experiencing migraine aura.

Placebo DRUG

Gelatin capsules resembling the ones containing the active substance

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female migraineurs with aura between 18 and 65 years old, inclusive
• Meets the following criteria for migraine headache with aura:
• Diagnosed with a history of migraine with aura
• Aura consisting of at least one of the following, but no muscle weakness or paralysis:
• Fully reversible visual symptoms (e.g. flickering lights, spots, lines, loss of vision)
• Fully reversible sensory symptoms (e.g. pins and needles, numbness)
• Fully reversible dysphasia (speech disturbance)
• Aura has at least two of the following characteristics:
• Visual symptoms affecting just one side of the field of vision and/or sensory symptoms affecting just one side of the body
• At least one aura symptom develops gradually over more than 5 minutes and/or different aura symptoms occur one after the other over more than 5 minutes
• Each symptom lasts from 5-60 minutes
• At least one migraine headache with aura every 8-weeks and resulting in moderate to severe pain (on a 4-point categorical scale) within 2 hours of the onset of aura.
• Migraine pain following aura in at least 75% of occurrences
• The subject has a body mass index (BMI) within the range of 18 to 32
• The subject is in general good health as determined by the medical history, physical exam, clinical laboratory tests, vital signs \[heart rate (HR) and blood pressure (BP; after a 3-minute sitting period)\] and ECG

You may not qualify if:

• Presence of any clinically significant condition that would preclude study participation, as evaluated by the investigator
• Are pregnant or lactating
• History of significant neurological, hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, rheumatologic, autoimmune, or metabolic disease
• Receiving any medication that, in the opinion of the Investigator or designee, may pose a risk of compromising tolerance or compliance
• Are known to or suspected to be currently abusing alcohol or drugs, or have a history (within the past 12 months) of active alcohol or drug abuse
• Participation in another drug or biologic study within 30 days preceding randomization into this study or during participation in this study
• Subjects who are unable or unwilling, in the opinion of the Investigator, to comply with all study procedures and cooperate fully with study center staff

Sponsors & Collaborators

• Danish Headache Center: lead
• NeurAxon Inc.: collaborator

Study Sites (1)

Danish Headache Center

Glostrup Municipality, 2600, Denmark

RECRUITING

Related Publications (19)

• Lassen LH, Christiansen I, Iversen HK, Jansen-Olesen I, Olesen J. The effect of nitric oxide synthase inhibition on histamine induced headache and arterial dilatation in migraineurs. Cephalalgia. 2003 Nov;23(9):877-86. doi: 10.1046/j.1468-2982.2003.00586.x.

  PMID: 14616929 BACKGROUND

• Afridi S, Kaube H, Goadsby PJ. Occipital activation in glyceryl trinitrate induced migraine with visual aura. J Neurol Neurosurg Psychiatry. 2005 Aug;76(8):1158-60. doi: 10.1136/jnnp.2004.050633.

  PMID: 16024898 BACKGROUND

• Alderton WK, Cooper CE, Knowles RG. Nitric oxide synthases: structure, function and inhibition. Biochem J. 2001 Aug 1;357(Pt 3):593-615. doi: 10.1042/0264-6021:3570593.

  PMID: 11463332 BACKGROUND

• Burstein R, Collins B, Jakubowski M. Defeating migraine pain with triptans: a race against the development of cutaneous allodynia. Ann Neurol. 2004 Jan;55(1):19-26. doi: 10.1002/ana.10786.

  PMID: 14705108 BACKGROUND

• Costa A, Smeraldi A, Tassorelli C, Greco R, Nappi G. Effects of acute and chronic restraint stress on nitroglycerin-induced hyperalgesia in rats. Neurosci Lett. 2005 Jul 22-29;383(1-2):7-11. doi: 10.1016/j.neulet.2005.03.026. Epub 2005 Apr 18.

  PMID: 15936504 BACKGROUND

• Handy RL, Moore PK. Effects of selective inhibitors of neuronal nitric oxide synthase on carrageenan-induced mechanical and thermal hyperalgesia. Neuropharmacology. 1998;37(1):37-43. doi: 10.1016/s0028-3908(97)00201-3.

  PMID: 9680257 BACKGROUND

• Heinzen EL, Pollack GM. Pharmacodynamics of morphine-induced neuronal nitric oxide production and antinociceptive tolerance development. Brain Res. 2004 Oct 15;1023(2):175-84. doi: 10.1016/j.brainres.2004.07.015.

  PMID: 15374743 BACKGROUND

• Inoue T, Mashimo T, Shibata M, Shibuta S, Yoshiya I. Rapid development of nitric oxide-induced hyperalgesia depends on an alternate to the cGMP-mediated pathway in the rat neuropathic pain model. Brain Res. 1998 May 11;792(2):263-70. doi: 10.1016/s0006-8993(98)00147-4.

  PMID: 9593928 BACKGROUND

• Levy D, Zochodne DW. NO pain: potential roles of nitric oxide in neuropathic pain. Pain Pract. 2004 Mar;4(1):11-8. doi: 10.1111/j.1533-2500.2004.04002.x.

  PMID: 17129298 BACKGROUND

• Martelletti P, D'Alo S, Stirparo G, Rinaldi C, Cifone MG, Giacovazzo M. Modulation of nitric oxide synthase by nitric oxide donor compounds in migraine. Int J Clin Lab Res. 1998;28(2):135-9. doi: 10.1007/s005990050033.

  PMID: 9689557 BACKGROUND

• Mungrue IN, Bredt DS, Stewart DJ, Husain M. From molecules to mammals: what's NOS got to do with it? Acta Physiol Scand. 2003 Oct;179(2):123-35. doi: 10.1046/j.1365-201X.2003.01182.x.

  PMID: 14510775 BACKGROUND

• Naik AK, Tandan SK, Kumar D, Dudhgaonkar SP. Nitric oxide and its modulators in chronic constriction injury-induced neuropathic pain in rats. Eur J Pharmacol. 2006 Jan 13;530(1-2):59-69. doi: 10.1016/j.ejphar.2005.11.029. Epub 2005 Dec 20.

  PMID: 16364289 BACKGROUND

• Osborne MG, Coderre TJ. Effects of intrathecal administration of nitric oxide synthase inhibitors on carrageenan-induced thermal hyperalgesia. Br J Pharmacol. 1999 Apr;126(8):1840-6. doi: 10.1038/sj.bjp.0702508.

  PMID: 10372828 BACKGROUND

• Shimomura T, Murakami F, Kotani K, Ikawa S, Kono S. Platelet nitric oxide metabolites in migraine. Cephalalgia. 1999 May;19(4):218-22. doi: 10.1046/j.1468-2982.1999.019004218.x.

  PMID: 10376166 BACKGROUND

• Taffi R, Vignini A, Lanciotti C, Luconi R, Nanetti L, Mazzanti L, Provinciali L, Silvestrini M, Bartolini M. Platelet membrane fluidity and peroxynitrite levels in migraine patients during headache-free periods. Cephalalgia. 2005 May;25(5):353-8. doi: 10.1111/j.1468-2982.2004.00863.x.

  PMID: 15839850 BACKGROUND

• Tfelt-Hansen P, De Vries P, Saxena PR. Triptans in migraine: a comparative review of pharmacology, pharmacokinetics and efficacy. Drugs. 2000 Dec;60(6):1259-87. doi: 10.2165/00003495-200060060-00003.

  PMID: 11152011 BACKGROUND

• Thomsen LL, Olesen J. Nitric oxide theory of migraine. Clin Neurosci. 1998;5(1):28-33.

  PMID: 9523055 BACKGROUND

• van der Kuy PH, Lohman JJ. The role of nitric oxide in vascular headache. Pharm World Sci. 2003 Aug;25(4):146-51. doi: 10.1023/a:1024800512790.

  PMID: 12964492 BACKGROUND

• Yoon YW, Sung B, Chung JM. Nitric oxide mediates behavioral signs of neuropathic pain in an experimental rat model. Neuroreport. 1998 Feb 16;9(3):367-72. doi: 10.1097/00001756-199802160-00002.

  PMID: 9512373 BACKGROUND

MeSH Terms

Conditions

Migraine with Aura; Headache; Migraine Disorders; Epilepsy

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Peer Tfelt-Hansen, MD, Dr Med Sci

  Department of Neurology, Glostrup Hospital, Denmark

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Peer Tfelt-Hansen, MD, Dr Med Sci

CONTACT

+4543 23 27 14; andhou05@glo.regionh.dk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: April 7, 2009
• First Posted: April 8, 2009
• Study Start: May 1, 2009
• Primary Completion: March 1, 2010
• Study Completion: December 1, 2010
• Last Updated: July 28, 2009

Record last verified: 2009-07

Locations

DK (1)