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

Migraine Headache Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00172094
• Other study ID #: CL1776-005
• Status: Completed
• Phase: Phase 2
• Start date: December 31, 2003
• Est. completion date: July 31, 2004

Study information

• Verified date: May 2021
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 189
• Est. completion date: July 31, 2004
• Est. primary completion date: June 30, 2004
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Headache
• Migraine Disorders
• Migraine Headache

Intervention

Drug:
• NPS 1776 (800 mg)
NPS 1776 (800 mg) powder
• PLACEBO
Placebo in non-carbonated fruit flavored drink (150 ml)
• NPS 1776 (400 mg)
NPS1776 in powdered form to be mixed with a non-carbonated fruit flavored drink

Locations

Country	Name	City	State
United States	Michigan Head-Pain & Neurological Institute	Ann Arbor	Michigan
United States	Mercy Health Research	Chesterfield	Missouri
United States	Diamond Headache Clinic	Chicago	Illinois
United States	Headache Wellness Center	Greensboro	North Carolina
United States	Houston Headache Clinic	Houston	Texas
United States	Medical Affiliated Research Center	Huntsville	Alabama
United States	Clinical Study Centers, LLC	Little Rock	Arkansas
United States	University of Medicine and Dentistry, New Jersey School of Osteopathic Medicine	Moorestown	New Jersey
United States	Neuroscience Center of Northern New Jersey	Morristown	New Jersey
United States	North County Neurological Associates	Oceanside	California
United States	University Clinical Research, Inc	Pembroke Pines	Florida
United States	Thomas Jefferson University Hospital/ Jefferson Headache Center	Philadelphia	Pennsylvania
United States	The Neurology Clinic	Portland	Oregon
United States	San Francisco Clinical Research Center	San Francisco	California
United States	Clinical Innovations	Santa Ana	California
United States	California Medical Clinic for Headache	Santa Monica	California
United States	Headache Care Center/ Clinvest	Springfield	Missouri
United States	The New England Center for Headache	Stamford	Connecticut
United States	Neurology & Neurosurgery Associates of Tacoma, Inc., PS	Tacoma	Washington
United States	Neurology Ctr. of Ohio	Toledo	Ohio
United States	MedTrial Boston	Wellesley Hills	Massachusetts
United States	Piedmont Medical Research Associates	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Shire

Country where clinical trial is conducted

United States, 

Outcome

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

External Links

•   American Headache Society - Site dedicated to the study and treatment of headaches of all types including but not limited to migraines.