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

• Sponsor: Shire (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00172094
• Collaborator: (none)
• Enrollment: 189
• Locations: 22
• Arms: 3
• Actual Duration (Months): 7
• Patients Per Site: 8.6
• Patients Per Site Per Month: 1.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Migraine Headache	Drug: NPS 1776 (800 mg); Drug: PLACEBO; Drug: NPS 1776 (400 mg)	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 189 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Safety and Efficacy Study of NPS 1776 for the Acute Treatment of Migraine Headaches
• Actual Study Start Date: Dec 31, 2003
• Actual Primary Completion Date: Jun 30, 2004
• Actual Study Completion Date: Jul 31, 2004

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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

1. Pain-free rate at 2 hours post-dose [2 hours post-dose]

2. Response rate up to 48 (±24) hours post-dose [48 hours post-dose]

3. Recurrence rate of migraine headache within 24 hours post dose [24 hours post-dose]

4. Time to recurrence of migraine within 24 hours post-dose [24 hours post-dose]

5. Area under the migraine pain curve in visual analogue scale (VAS) 0 4 hours post-dose [4 hours post-dose]

6. VAS pain reduction: peak pain reduction in VAS score 0-4 hours post-dose [4 hours post-dose]

7. Presence of nausea/vomiting, sensitivity to sound/light, skin sensitivity (cutaneous allodynia), intracranial sensitivity [24 hours post-dose]

8. Brush allodynia [24 hours post-dose]

9. Muscle tenderness [24 hours post-dose]

10. Functional disability [24 hours post-dose]

11. Use of rescue medication [4 hours post-dose]

12. Time to meaningful pain relief [2 hours post-dose]

13. Global Subject Impression (GSI) [24 hours post-dose]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medical Affiliated Research Center	Huntsville	Alabama	United States	35801
2	Clinical Study Centers, LLC	Little Rock	Arkansas	United States	72205
3	North County Neurological Associates	Oceanside	California	United States	92056
4	San Francisco Clinical Research Center	San Francisco	California	United States	94109
5	Clinical Innovations	Santa Ana	California	United States	92705
6	California Medical Clinic for Headache	Santa Monica	California	United States	90404
7	The New England Center for Headache	Stamford	Connecticut	United States	06902
8	University Clinical Research, Inc	Pembroke Pines	Florida	United States	33024
9	Diamond Headache Clinic	Chicago	Illinois	United States	60614
10	MedTrial Boston	Wellesley Hills	Massachusetts	United States	02481
11	Michigan Head-Pain & Neurological Institute	Ann Arbor	Michigan	United States	48104
12	Mercy Health Research	Chesterfield	Missouri	United States	63017
13	Headache Care Center/ Clinvest	Springfield	Missouri	United States	65804
14	University of Medicine and Dentistry, New Jersey School of Osteopathic Medicine	Moorestown	New Jersey	United States	08057
15	Neuroscience Center of Northern New Jersey	Morristown	New Jersey	United States	07960
16	Headache Wellness Center	Greensboro	North Carolina	United States	27401
17	Piedmont Medical Research Associates	Winston-Salem	North Carolina	United States	27103
18	Neurology Ctr. of Ohio	Toledo	Ohio	United States	43623
19	The Neurology Clinic	Portland	Oregon	United States	37210
20	Thomas Jefferson University Hospital/ Jefferson Headache Center	Philadelphia	Pennsylvania	United States	19107
21	Houston Headache Clinic	Houston	Texas	United States	77004
22	Neurology & Neurosurgery Associates of Tacoma, Inc., PS	Tacoma	Washington	United States	98405

Sponsors and Collaborators

• Shire

Investigators

• Study Director: Study Director, Takeda

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

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

Publications

None provided.

• Responsible Party: Shire
• ClinicalTrials.gov Identifier: NCT00172094
• Other Study ID Numbers: CL1776-005
• First Posted: Sep 15, 2005
• Last Update Posted: Jun 3, 2021
• Last Verified: May 1, 2021

• Keywords provided by Shire: Migraine
• Additional relevant MeSH terms: Migraine Disorders; Headache

Study Results

No Results Posted as of Jun 3, 2021