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

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

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.

Study Overview

• Status: Completed
• Conditions: Migraine Headache
• Intervention / Treatment: Drug: PLACEBO; Drug: NPS 1776 (400 mg); Drug: NPS 1776 (800 mg)

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 Type: Interventional
• Enrollment (Actual): 189
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

3

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Shire

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 31, 2003
• Primary Completion (ACTUAL): June 30, 2004
• Study Completion (ACTUAL): July 31, 2004

Study Registration Dates

• First Submitted: September 9, 2005
• First Submitted That Met QC Criteria: September 9, 2005
• First Posted (ESTIMATE): September 15, 2005

Study Record Updates

• Last Update Posted (ACTUAL): June 3, 2021
• Last Update Submitted That Met QC Criteria: May 30, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Migraine
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Headache
• Other Study ID Numbers: CL1776-005