Comparison of Ketorolac Nasal Spray to Sumatriptan Nasal Spray and Placebo for Acute Treatment of Migraine

Study Overview
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Brief Summary
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The investigators propose to test the efficacy of ketorolac nasal spray versus sumatriptan nasal spray versus placebo for acute abortive therapy of migraine head pain as well as for migraine associated symptoms including nausea and allodynia.

Detailed Description
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Participants are randomized to Ketorolac NS 31.5 mg, Sumatriptan NS 20 mg or placebo to treat three moderate to severe migraine attacks and switched treatments with each attack so that they received each treatment only once. For each treated attack (moderate to severe migraine attack), participants utilized two study treatments (A and B). Study treatment A administered as one spray in each nostril, and study treatment B administered as one spray in one nostril. Randomized to Ketorolac, A=Ketorolac, B=Placebo Randomized to Sumatriptan, A=Placebo, B=Sumatriptan Randomized to Placebo, A=Placebo, B=Placebo

Official Title
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Comparison of Ketorolac Nasal Spray to Sumatriptan Nasal Spray and Placebo for Acute Treatment of Migraine (The KSPN Migraine Study)

Conditions
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Migraines

Intervention / Treatment
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* Drug: Ketorolac
* Drug: Sumatriptan
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion/Exclusion Criteria At the Screening Visit, a subject must meet the following criteria to participate in this study: 1.18-65 years of age 2.Fulfills International Classification of Headache Disorders (ICHD)-II Criteria of migraine as noted below in Table 1 3.History of migraines for at least one year 4.Migraine onset prior to the age of 50 years of age 5.Headache frequency (of any headaches, migraine or non-migraine) < 9 days per month 6.At visit 2, participants must report two or more headache days during the 28-day run-in period on the headache diary. 7.At least 48 hours of freedom from headache between treated migraine attacks. 8.If currently using headache preventive medications, must be on a stable dose for at least 3 months prior to enrollment and throughout the study period and be on no more than one prophylactic agent. 9.Able to complete all study procedures, including the questionnaire (assessing demographics, headache characteristics, headache comorbidities and medical history at the initial visit and headache characteristics) and the required headache calendars, and all study visits; 10.Able to understand, read and sign an informed consent (English). Exclusion Criteria: Any condition (history or presence of) which contraindicates the use of triptans or NSAIDs including: Known hypersensitivity or intolerance to triptans or NSAIDs Contraindications to triptan use (uncontrolled hypertension, ischemic heart disease, prinz-metal angina, cardiac arrhythmias, multiple risk factors for atherosclerotic vascular disease, primary vasculopathies, and basilar and hemiplegic migraine) Cerebrovascular disease except for mild non-specific white matter disease Peripheral vascular disease or any other ischemic disease including myocardial infarction Uncontrolled hypertension (systolic BP 160 mmHg or diastolic BP 95 mmHg or (both) Migraine aura fulfilling ICHD-II criteria for hemiplegic or basilar-type migraine Any history of chronic renal or hepatic impairment Use of an ergotamine-containing medication or monamine oxidase inhibitor Known or suspected pregnancy, negative pregnancy test Lactation Bleeding dsycrasias including gastritis, peptic ulcer disease,gastrointestinal bleeding Physician diagnosis of any pain syndrome other than migraine Classification as treatment resistant by investigator Known drug or substance abuse Any opioid use in past 2 months Use of any medication, which could interfere with study assessments History of noncompliance with taking medication; Use of any experimental drug or device within 30 days prior to the Screening Visit (Visit 1); Any abnormal finding or condition deemed clinically significant by the investigator on history, screening, or physical exam that contraindicates the use of triptans or NSAIDs or that might interfere with the patient's safety, study participation, or which might confound the interpretation of the study results. Any history of chronic renal or hepatic disease already excluded above under number 1; plus see exclusion 9. History of chronic pulmonary disorder including nasal polyps (see 1) and asthma. History of upper respiratory infection or other respiratory tract condition that could interfere with the absorption of the nasal spray or with assessment of AEs including rhinitis medicamentosa (chronic daily use of topical decongestants). History of nasal surgery.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketorolac/Placebo<br>Ketorolac 31.5 mg single dose nasal spray and Placebo | Drug: Ketorolac<br>* Single dose of Ketorolac (Sprix) nasal spray 31.5 mg, one spray in each nostril for an acute migraine attack.<br>* Other names: Sprix;Drug: Placebo<br>* Placebo one spray in each nostril and placebo one nasal spray.<br>|
| Experimental: Sumatriptan/Placebo<br>Sumatriptan 20 mg single dose nasal spray and placebo | Drug: Sumatriptan<br>* Sumatriptan (Imitrex) 20 mg one single dose of nasal spray for an acute migraine attack.<br>* Other names: Imitrex;Drug: Placebo<br>* Placebo one spray in each nostril and placebo one nasal spray.<br>|
| Placebo Comparator: Ketorolac Placebo/Sumatriptan placebo<br>single dose Ketorolac placebo, single dose Sumatriptan placebo | Drug: Placebo<br>* Placebo one spray in each nostril and placebo one nasal spray.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2- Hour Pain Relief | The primary outcome was 2-hour headache relief; headache relief was defined as headache pain from moderate or severe pain to none or mild pain. Pain was assessed using a 4-point scale (none, mild, moderate, and severe) | 2 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Freedom | 1) Pain Freedom: Pain Freedom at 2 hours is defined as being free of pain. Pain was assessed using a 4-point scale (none, mild, moderate, and severe). | 2-hours | 
| Absence of Photophobia | 2) Defined as reduction of photophobia to none. Symptom was assessed using a 4-point scale (none, mild, moderate, and severe) | 2-hours | 
| Absence of Phonophobia | 3) Defined as reduction of phonophobia to none. Symptom was assessed using a 4-point scale (none, mild, moderate, and severe) | 2-hours | 
| Absence of Nausea | 4) Defined as reduction of nausea to none. Symptom was assessed using a 4-point scale (none, mild, moderate, and severe) | 2-hours | 
| Absence of Allodynia | 5) Absence of allodynia The presence of allodynia was assessed based on a series of 8 questions inquiring as to the presence of allodynia. Participants answering 2 or more questions positively were considered to have allodynia. | 2-hours | 
| Self-assessment of Disability: Percentage of Participants With Moderate or Severe Disability | Participants' self-assessment of disability was assessed using 4-point scales (none, mild, moderate, and severe). A binary outcome variable was created grouping none and mild vs moderate to severe. . | 2-hours | 
| Sustained Pain Relief (SPR) | 7) 24 and 48 hours sustained pain relief (SPR) Defined as the reduction of pain to none or mild from moderate or severe, on a 4-point scale (none, mild, moderate, and severe). | 24 and 48 hours | 
| Sustained Pain Freedom (SPF) | 8) 24 and 48 hours sustained pain freedom (SPF); Defined as the reduction of pain to none. Pain was assessed using a 4-point scale (none, mild, moderate, and severe). | 24 and 48 hours | 
| Time to Pain Relief | 9) The time, in minutes, will be measured from the time study drug is taken to the time when significant pain relief is first observed and maintained through 2 hours with no rescue medication use at or prior to this point. | following each treated migraine attack |