Clinical trial NCT00172094: Safety and Efficacy of NPS 1776 in the Acute Treatment of Migraine Headaches
Official title: A Phase 2 Safety and Efficacy Study of NPS 1776 for the Acute Treatment of Migraine Headaches
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Migraine Headache
Keywords: Migraine
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2005-09-15
Enrollment: 189
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Diagnosis of migraine for at least a year prior to screening.
2. 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.
3. 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).
4. Ability and willingness to abstain from taking medications not allowed by the protocol and to meet phone and check-in criteria.
5. Ability and willingness to undergo a comprehensive urine toxicology screen for both licit and illicit drugs.
6. 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:

1. Unstable or uncontrolled significant metabolic, hepatic, renal, hematological, pulmonary, gastrointestinal, urological, neurological (except migraine headaches), or psychiatric disorders.
2. Severe or acute cardiovascular or cerebrovascular disease, uncontrolled hypertension, or basilar or hemiplegic migraines.
3. History of hypersensitivity, allergies, or nonresponse to valproic acid.
4. 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.
5. Migraine attacks that in the investigator's opinion are associated with intractable nausea and/or vomiting.
6. 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.
7. 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.

Primary outcomes:
measure: 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]
timeFrame: 2 hours post-dose
Secondary outcomes:
measure: Pain-free rate at 2 hours post-dose
timeFrame: 2 hours post-dose
measure: Response rate up to 48 (±24) hours post-dose
timeFrame: 48 hours post-dose
measure: Recurrence rate of migraine headache within 24 hours post dose
timeFrame: 24 hours post-dose
measure: Time to recurrence of migraine within 24 hours post-dose
timeFrame: 24 hours post-dose
measure: Area under the migraine pain curve in visual analogue scale (VAS) 0 4 hours post-dose
timeFrame: 4 hours post-dose
measure: VAS pain reduction: peak pain reduction in VAS score 0-4 hours post-dose
timeFrame: 4 hours post-dose
measure: Presence of nausea/vomiting, sensitivity to sound/light, skin sensitivity (cutaneous allodynia), intracranial sensitivity
timeFrame: 24 hours post-dose
measure: Brush allodynia
timeFrame: 24 hours post-dose
measure: Muscle tenderness
timeFrame: 24 hours post-dose
measure: Functional disability
timeFrame: 24 hours post-dose
measure: Use of rescue medication
timeFrame: 4 hours post-dose
measure: Time to meaningful pain relief
timeFrame: 2 hours post-dose
measure: Global Subject Impression (GSI)
timeFrame: 24 hours post-dose
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Medical Affiliated Research Center
state: Alabama
city: Little Rock
country: United States
facility: Clinical Study Centers, LLC
state: Arkansas
city: Oceanside
country: United States
facility: North County Neurological Associates
state: California
city: San Francisco
country: United States
facility: San Francisco Clinical Research Center
state: California
city: Santa Ana
country: United States
facility: Clinical Innovations
state: California
city: Santa Monica
country: United States
facility: California Medical Clinic for Headache
state: California
city: Stamford
country: United States
facility: The New England Center for Headache
state: Connecticut
city: Pembroke Pines
country: United States
facility: University Clinical Research, Inc
state: Florida
city: Chicago
country: United States
facility: Diamond Headache Clinic
state: Illinois
city: Wellesley Hills
country: United States
facility: MedTrial Boston
state: Massachusetts
city: Ann Arbor
country: United States
facility: Michigan Head-Pain & Neurological Institute
state: Michigan
city: Chesterfield
country: United States
facility: Mercy Health Research
state: Missouri
city: Springfield
country: United States
facility: Headache Care Center/ Clinvest
state: Missouri
city: Moorestown
country: United States
facility: University of Medicine and Dentistry, New Jersey School of Osteopathic Medicine
state: New Jersey
city: Morristown
country: United States
facility: Neuroscience Center of Northern New Jersey
state: New Jersey
city: Greensboro
country: United States
facility: Headache Wellness Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Piedmont Medical Research Associates
state: North Carolina
city: Toledo
country: United States
facility: Neurology Ctr. of Ohio
state: Ohio
city: Portland
country: United States
facility: The Neurology Clinic
state: Oregon
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital/ Jefferson Headache Center
state: Pennsylvania
city: Houston
country: United States
facility: Houston Headache Clinic
state: Texas
city: Tacoma
country: United States
facility: Neurology & Neurosurgery Associates of Tacoma, Inc., PS
state: Washington
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: