Study of NXN 188 for the Treatment of Migraine With Aura

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

NXN-188 Dihydrochloride is being developed as an immediate release oral product for the treatment of acute migraine. This study is being conducted to evaluate NXN-188 in subjects with a migraine history of aura.

Study Overview

• Status: Completed
• Conditions: Migraine With Aura
• Intervention / Treatment: Drug: NXN-188; Drug: sumatriptan succinate; Drug: placebo

Detailed Description

This was a multicenter, double-blind, parallel group, active and placebo-controlled, three arm study of a single oral dose of NXN-188 for the treatment of acute migraine headache with aura.

After study eligibility was confirmed, subjects were randomized to NXN-188 600 mg, sumatriptan 100 mg, or placebo in a 1:1:1 ratio. Subjects left the clinic to self-administer the treatment at home at the onset of moderate to severe headache in a suitable dosing environment.

Treatment was not to exceed 42 days from Randomization. If the subject did not have a headache within 42 days of randomization (s)he did not take the study medication and returned it to the site. If the subject experienced a qualifying headache (s)he recorded the symptoms in a diary, dosed with the study drug, and called the IVRS to record assessments all adverse events and to report dosing. If the study drug provided insufficient relief 2 hours post dosing (s)he was permitted to use non-triptan rescue medication recommended by the investigator.

• Study Type: Interventional
• Enrollment (Actual): 239
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Newport Beach, California, United States, 92660
      • C. Philip O'Carrroll, MD, Inc.
    • Oceanside, California, United States, 92056
      • The Research Center of Southern California, LLC
    • San Francisco, California, United States, 94109
      • San Francisco Headache Clinic
    • Santa Monica, California, United States, 90404
      • California Medical Clinic for Headache
  • Florida
    • St. Petersburg, Florida, United States, 33702
      • Comprehensive NeuroScience, Inc.
  • Kansas
    • Overland Park, Kansas, United States, 66212
      • Vince and Associates Clinical Research
  • Michigan
    • Ann Arbor, Michigan, United States, 48104
      • Michigan Head-Pain and Neurological Institute
  • Missouri
    • Springfield, Missouri, United States, 65807
      • Headache Care Center/Clinvest
    • St. Louis, Missouri, United States, 63141
      • Mercy Health Research
  • Nebraska
    • Omaha, Nebraska, United States, 68134
      • Meridian Clinical Research, LLC
  • New York
    • Endwell, New York, United States, 13760
      • Regional Clinical Research, Inc.
    • Mount Vernon, New York, United States, 10550
      • Elkind Headache Center
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research, Inc
  • North Carolina
    • Greensboro, North Carolina, United States, 27405
      • Headache Wellness Center
  • South Carolina
    • Mt. PLeasant, South Carolina, United States, 29464
      • Coastal Carolina Research Center, Inc
  • Utah
    • West Jordan, Utah, United States, 84088
      • Advanced Clinical Research, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female migraineurs between 18 and 65 years old.

2. Subjects must have a headache history of migraine with aura as defined by:

   • Aura consisting of at least one of the following, but no muscle weakness or paralysis:

     • Fully reversible visual symptoms
     • Fully reversible sensory symptoms
     • Fully reversible dysphasia

   • Aura has at least two of the following characteristics:

     • Visual symptoms affecting only one side of the field of vision and/or sensory symptoms affecting only one side of the body
     • At least one aura symptom that develops gradually over more than 5 minutes and/or different aura symptoms occur in succession over more than 5 minutes
     • Each symptom lasts from 5-60 minutes
   • Headache begins during the aura or follows aura within 60 minutes
   • Headache not attributable to another disorder
3. Migraine pain following aura in at least 75% of occurrences

4. Headache frequency of at least 1 migraine attack (with or without aura) per month for the past 3 months but not more than 8 migraines in any 30 day period. Subjects must have at least 1 migraine headache with aura per month

   • Each migraine attack should last at least 4 hours (without treatment) and not longer than 72 hours.

5. At the time of the study migraine, prior to dosing with study medication, the headache severity, as judged and documented by the subject, is either moderate or severe (on a 4-point categorical scale)
6. Body mass index (BMI) range of 18 to 35

7. The subject is in general good health.

   • ALT cannot be above 1.5x upper limit of normal; creatinine and urea must be within normal limits

8. Speak, read, and understand English, French, or Spanish sufficiently to understand the nature of the study, to provide written informed consent, and complete all study assessments
9. The subject is willing and able to comply with all testing requirements defined in the protocol
10. All females will avoid pregnancy at least 10 days before randomization, and up until 3 months after dosing.
11. All subjects/partners must use a double-barrier method of birth control during the study and for 3 months after dosing.

Exclusion Criteria:

1. A diagnosis of headaches that is not consistent with migraine with aura.
2. Presence of any risk factors that would preclude the use of triptans:
3. Known allergy or hypersensitivity to triptans or history of any serious side effect with a triptan which would preclude further dosing with a triptan
4. Presence of any clinically significant condition that would preclude study participation, as evaluated by the investigator
5. Pregnancy or lactation
6. History of significant neurological, hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, rheumatologic, autoimmune, or metabolic disease

7. Use of the following if taken for migraine prevention:

   • Cardiovascular drugs (acceptable if reason for use is for treatment of cardiovascular disease and the subject has been on a stable dose for 3 months)
   • Valproate, topiramate, cyproheptadine, montelukast, or botulinum toxin.
8. Use of monoamine oxidase inhibitors within 30 days of randomization
9. Initiation of therapy with SSRIs or SNRIs for depression or other approved indication within 90 days of randomization (subjects on stable dose for >3 months for treatment of depression or other approved indication may be included)
10. 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
11. Participation in another drug or biologic study within 30 days of randomization into this study or during participation in this study
12. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NXN-188; NXN-188, 600 mg, PRN	Drug: NXN-188; NXN-188 hard gelatin capsules, 600 mg administered as three 200 mg capsules; Other Names: NXN-188 dihydrochloride
Active Comparator: sumatriptan succinate 100 mg; Sumatriptan, 100 mg, PRN	Drug: sumatriptan succinate; administered in a hard gelatin capsule with 2 capsules of placebo
Placebo Comparator: placebo; matching, PRN	Drug: placebo; administered as 3 placebo hard gelatin capsules; Other Names: placebo capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time (Hours) to First Use of Rescue Medication	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Headache Relief and Recurrence (Observed Cases)	Headache relief is defined as a ≥ 1-point reduction from baseline in Headache Severity Score. The Headache Severity Score is a four-point scale: 0=no pain; 1 = mild pain; 2 = moderate pain; and 3 = severe pain. Headache recurrence is defined as any subject that experiences headache relief within 4 hours, who did not use rescue medication, and who experienced a worsening of their headache to moderate or severe within 24 hours following study drug administration.	2, 4 and up to 24 hours
2 Hours Post Administration - Incidence of Complete Headache Relief, Photophobia, Phonophobia and Nausea	Complete headache relief is defined as reduction of headache severity from moderate or severe to absent. Presence of Photophobia and Phonophobia measured on a 2-point scale: 0 = absent; 1 = present Nausea was measured on a 4-point scale: 0 = no nausea; 1 = mild nausea; 2 = moderate nausea; 3 = severe nausea	2 hours
4 Hours Post Administration - Incidence of Complete Headache Relief, Photophobia, Phonophobia and Nausea	Complete headache relief is defined as reduction of headache severity from moderate or severe to absent. Presence of Photophobia and Phonophobia measured on a 2-point scale: 0 = absent; 1 = present Nausea was measured on a 4-point scale: 0 = no nausea; 1 = mild nausea; 2 = moderate nausea; 3 = severe nausea	4 hours
24 Hours Post Administration - Incidence of Complete Headache Relief, Photophobia, Phonophobia and Nausea	Complete headache relief is defined as reduction of headache severity from moderate or severe to absent. Presence of Photophobia and Phonophobia measured on a 2-point scale: 0 = absent; 1 = present Nausea was measured on a 4-point scale: 0 = no nausea; 1 = mild nausea; 2 = moderate nausea; 3 = severe nausea	24 hours

Collaborators and Investigators

• Sponsor: NeurAxon Inc.
• Investigators: Principal Investigator: Guy Boudreau, MD, Hopital Notre-Dame Du Chum, Montreal

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: June 12, 2009
• First Submitted That Met QC Criteria: June 12, 2009
• First Posted (Estimate): June 15, 2009

Study Record Updates

• Last Update Posted (Estimate): August 11, 2014
• Last Update Submitted That Met QC Criteria: July 20, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: Migraine; aura
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Migraine with Aura; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Serotonin Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Vasoconstrictor Agents; Sumatriptan
• Other Study ID Numbers: NXN-188-203