Safety and Efficacy of NPS 1776 in the Acute Treatment of Migraine Headaches

Study Overview
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Brief Summary
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The purpose of this study was to evaluate the effectiveness and safety of a single oral dose of NPS 1776 in the acute treatment of migraine pain and associated symptoms.

Detailed Description
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Migraine, the most common cause of recurrent severe or disabling headache, is diagnosed on the basis of a clinical history of intermittent headache with autonomic, constitutional, and neurologic disturbances. Many antiepileptic drugs (AEDs) have demonstrated efficacy as acute and/or prophylaxis therapy for migraine, even though the mechanism of action of the various AEDs is poorly understood. NPS 1776, isovaleramide, is a neutral aliphatic amide. The mechanism by which NPS 1776 exerts its therapeutic actions in nonclinical animal models of disease is unclear. The same is true for many antiepileptics on the market today. NPS 1776 does not appear to bind directly to various CNS receptor centers, although it shows a broad range of anticonvulsant activity in multiple animal models of seizures. This broad profile of anticonvulsant activity is similar to that of valproic acid (VPA), and may also predict NPS 1776 efficacy in the treatment of migraine.

Official Title
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A Phase 2 Safety and Efficacy Study of NPS 1776 for the Acute Treatment of Migraine Headaches

Conditions
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Migraine Headache

Intervention / Treatment
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* Drug: NPS 1776 (800 mg)
* Drug: PLACEBO
* Drug: NPS 1776 (400 mg)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of migraine for at least a year prior to screening. Experiences 2-10 migraine headaches per month (with at least 24 hours between episodes) and no more than 15 headache days per month in the 3 months prior to screening. Ability and willingness to arrive at the investigator's center within 1 hour (±5 min) of migraine pain onset (defined as pain that is consistent with the subject's usual migraine and is of at least moderate severity). Ability and willingness to abstain from taking medications not allowed by the protocol and to meet phone and check-in criteria. Ability and willingness to undergo a comprehensive urine toxicology screen for both licit and illicit drugs. Ability and willingness to complete a migraine-history diary from screening to treatment with study drug and a migraine-treatment diary from discharge through the remainder of the 24-hour period following study-drug treatment. Exclusion Criteria: Unstable or uncontrolled significant metabolic, hepatic, renal, hematological, pulmonary, gastrointestinal, urological, neurological (except migraine headaches), or psychiatric disorders. Severe or acute cardiovascular or cerebrovascular disease, uncontrolled hypertension, or basilar or hemiplegic migraines. History of hypersensitivity, allergies, or nonresponse to valproic acid. Have taken VPA or other AED in the 30 days prior to screening, or are taking a migraine prophylaxis treatment other than a stable dose of propranolol or tricyclic antidepressant. Migraine attacks that in the investigator's opinion are associated with intractable nausea and/or vomiting. Any acute or chronic condition that in the investigator's opinion would limit the subject's ability to complete and/or participate in this clinical study or would place the subject at increased risk. Have newly started or changed the dose of either feverfew or magnesium (above 200 mg, the amount in common daily supplements) within 3 months prior to screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1<br>PLACEBO | Drug: PLACEBO<br>* Placebo in non-carbonated fruit flavored drink (150 ml)<br>|
| Experimental: 2<br>400 mg 1776 powder | Drug: NPS 1776 (400 mg)<br>* NPS1776 in powdered form to be mixed with a non-carbonated fruit flavored drink<br>* Other names: NPS1776;|
| Experimental: 3<br>1776 (800 mg) | Drug: NPS 1776 (800 mg)<br>* NPS 1776 (800 mg) powder<br>* Other names: NPS 1776;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The response rate at 2 hours post-dose such that the percentage of subjects whose migraine pain-intensity score is none [0] or mild [1] at 2 hours post-dose, after a baseline pain intensity of moderate [2] or severe [3] |  | 2 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain-free rate at 2 hours post-dose |  | 2 hours post-dose | 
| Response rate up to 48 (±24) hours post-dose |  | 48 hours post-dose | 
| Recurrence rate of migraine headache within 24 hours post dose |  | 24 hours post-dose | 
| Time to recurrence of migraine within 24 hours post-dose |  | 24 hours post-dose | 
| Area under the migraine pain curve in visual analogue scale (VAS) 0 4 hours post-dose |  | 4 hours post-dose | 
| VAS pain reduction: peak pain reduction in VAS score 0-4 hours post-dose |  | 4 hours post-dose | 
| Presence of nausea/vomiting, sensitivity to sound/light, skin sensitivity (cutaneous allodynia), intracranial sensitivity |  | 24 hours post-dose | 
| Brush allodynia |  | 24 hours post-dose | 
| Muscle tenderness |  | 24 hours post-dose | 
| Functional disability |  | 24 hours post-dose | 
| Use of rescue medication |  | 4 hours post-dose | 
| Time to meaningful pain relief |  | 2 hours post-dose | 
| Global Subject Impression (GSI) |  | 24 hours post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Migraine