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

This study has been completed.
Information provided by (Responsible Party):
Shire Identifier:
First received: September 9, 2005
Last updated: November 11, 2015
Last verified: September 2005
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 Intervention Phase
Migraine Headache
Drug: NPS 1776 (800 mg)
Drug: NPS 1776 (400 mg)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2 Safety and Efficacy Study of NPS 1776 for the Acute Treatment of Migraine Headaches

Resource links provided by NLM:

Further study details as provided by Shire:

Primary Outcome Measures:
  • 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] [ Time Frame: 2 hours post-dose ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pain-free rate at 2 hours post-dose [ Time Frame: 2 hours post-dose ] [ Designated as safety issue: No ]
  • Response rate up to 48 (±24) hours post-dose [ Time Frame: 48 hours post-dose ] [ Designated as safety issue: No ]
  • Recurrence rate of migraine headache within 24 hours post dose [ Time Frame: 24 hours post-dose ] [ Designated as safety issue: No ]
  • Time to recurrence of migraine within 24 hours post-dose [ Time Frame: 24 hours post-dose ] [ Designated as safety issue: No ]
  • Area under the migraine pain curve in visual analogue scale (VAS) 0 4 hours post-dose [ Time Frame: 4 hours post-dose ] [ Designated as safety issue: No ]
  • VAS pain reduction: peak pain reduction in VAS score 0-4 hours post-dose [ Time Frame: 4 hours post-dose ] [ Designated as safety issue: No ]
  • Presence of nausea/vomiting, sensitivity to sound/light, skin sensitivity (cutaneous allodynia), intracranial sensitivity [ Time Frame: 24 hours post-dose ] [ Designated as safety issue: No ]
  • Brush allodynia [ Time Frame: 24 hours post-dose ] [ Designated as safety issue: No ]
  • Muscle tenderness [ Time Frame: 24 hours post-dose ] [ Designated as safety issue: No ]
  • Functional disability [ Time Frame: 24 hours post-dose ] [ Designated as safety issue: No ]
  • Use of rescue medication [ Time Frame: 4 hours post-dose ] [ Designated as safety issue: No ]
  • Time to meaningful pain relief [ Time Frame: 2 hours post-dose ] [ Designated as safety issue: No ]
  • Global Subject Impression (GSI) [ Time Frame: 24 hours post-dose ] [ Designated as safety issue: No ]

Enrollment: 189
Study Start Date: December 2003
Study Completion Date: July 2004
Primary Completion Date: June 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 1
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 Name: NPS1776
Experimental: 3
1776 (800 mg)
Drug: NPS 1776 (800 mg)
NPS 1776 (800 mg) powder
Other Name: NPS 1776

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.


Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
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
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Please refer to this study by its identifier: NCT00172094

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Sponsors and Collaborators
Principal Investigator: Stephen D. Silberstein, M.D. Jefferson Headache Center
  More Information

No publications provided

Responsible Party: Shire Identifier: NCT00172094     History of Changes
Other Study ID Numbers: CL1776-005
Study First Received: September 9, 2005
Last Updated: November 11, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Shire:

Additional relevant MeSH terms:
Migraine Disorders
Brain Diseases
Central Nervous System Diseases
Headache Disorders
Headache Disorders, Primary
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms processed this record on December 01, 2015