Clinical trial NCT00242866: Use Of GW274150 In The Prophylactic Treatment Of Migraine
Official title: A Multicentre, Two-part, Randomised, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy, Tolerability and Pharmacokinetics of the iNOS Inhibitor GW274150 Administered up to 120mg Daily for 12 Weeks in the Prophylactic Treatment of Migraine.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Migraine Disorders
Keywords: Productivity
Efficacy
without aura
iNOS
Safety
Nitric Oxide
Pharmacokinetics
GW274150
with aura
Migraine
Prophylaxis
Quality of Life
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2005-10-21
Enrollment: 430
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Nitric oxide (NO) is likely to be involved in the development of migraine headache. Nitric oxide synthase (NOS) is an important chemical involved in the production of NO. Reduction of NOS, and therefore NO, may be an effective technique for the prevention of migraine headache. GW274150 is a highly selective inhibitor of NOS and offers the potential of anti-inflammatory activity in migraine through a novel mechanism of action. The intent of this study is to investigate the safety and efficacy of GW274150 for the prophylactic treatment of migraine headache.


Eligibility criteria: Inclusion Criteria:

* Suffering from migraine with or without aura.
* Migraine for at least one year, and the age of onset was prior to 50 years.
* Consistent migraine headache over time and has had at least 3 migraine headache attacks but less than 15 days with headache (migraine or non-migraine) per month in each of the three months prior to the Screening Visit and maintains this requirement during the baseline period.
* Able to distinguish migraine headache attacks as discreet attacks from other headaches (i.e. tension-type headaches).
* No clinically significant abnormality identified on the medical or laboratory evaluation. A subject with a clinical abnormality or laboratory parameters outside the reference range may be included only if the doctor considers that the finding will not introduce additional risk factors and will not interfere with the study procedures.
* Written informed consent prior to entry into the study.
* Females who are: a) non-childbearing potential or, b) of child-bearing potential, has a negative pregnancy test at screen, and is taken adequate contraceptive measures.

Exclusion Criteria:

* As a result of the medical interview, physical examination or screening investigations, that the doctor considers the subject unfit for the study.
* Headache for 15 days per month or greater in any of the three months (90 days) preceding the Screening Visit.
* History of alcohol, substance or drug abuse within the last year.
* Taken a migraine prophylactic medication within 1 month of the Screening Visit.
* Uses an opiate as first line acute treatment for migraine attacks.
* History of ergotamine, triptan, opioid, or combination medication intake on greater than/equal 10 days per month on a regular basis for greater than/equal 3 months.
* History of simple analgesic intake on greater than/equal 15 days per month for greater than/equal 3 months.
* Failed two or more adequate treatments of migraine prophylaxis, where failure is defined as a lack of efficacy with a treatment duration of at least 8 weeks or withdrawal of treatment due to treatment intolerance.
* Uncontrolled hypertension at the Screening Visit, defined as systolic blood pressure \>140mmHg or diastolic blood pressure \>90mmHg.
* Taking cyclosporine and/or aminoglycosides.
* Evidence of renal impairment - calculated creatinine clearance \<60ml/min or clinically relevant finding on urinalysis.
* History of drug or other allergy which, in the opinion of the doctor, makes the subject unsuitable for participation in the study.
* Concurrently participating in another clinical study or investigational drug trial or has participated within the previous 3 months or is planning to participate in another drug or device study at any time during this study (screening through follow-up) or has had previous exposure to GW274150 in Part 1 of the study.
* Felt to be at risk of non-compliance (for taking study medication or for completing the electronic diary (e-diary)), in the doctor's opinion.
* Pregnant or nursing women.
* History of, or risk factors for, HIV, Hepatitis B and Hepatitis C.
* Past or present disease, which as judged by the doctor, may affect the outcome of this study. These diseases include, but are not limited to history of liver or renal disease in the 6 months prior to screening.
* Clinically significant abnormalities in safety laboratory analysis at the Screening Visit, particularly any abnormal liver or pancreatic function test at the Screening Visit.
* Not covered by social security.

Primary outcomes:
measure: Occurrence of a migraine headache day on each day during the 4-week baseline period and the 12-week treatment period.
timeFrame: 12 Weeks
Secondary outcomes:
measure: Change from baseline in the number of migraine headache days, migraine attacks, mean peak migraine pain severity and mean migraine headache duration for each 4 week treatment period and over the entire treatment period.
timeFrame: 12 Weeks
Other outcomes:
Locations:
city: Antwerpen
country: Belgium
facility: GSK Investigational Site
city: Leuven
country: Belgium
facility: GSK Investigational Site
city: Liège
country: Belgium
facility: GSK Investigational Site
city: Glostrup
country: Denmark
facility: GSK Investigational Site
city: Odense C
country: Denmark
facility: GSK Investigational Site
city: Oelstykke
country: Denmark
facility: GSK Investigational Site
city: Helsinki
country: Finland
facility: GSK Investigational Site
city: Jyvaskyla
country: Finland
facility: GSK Investigational Site
city: Mikkeli
country: Finland
facility: GSK Investigational Site
city: Tampere
country: Finland
facility: GSK Investigational Site
city: Turku
country: Finland
facility: GSK Investigational Site
city: Anzin
country: France
facility: GSK Investigational Site
city: Chilly Mazarin
country: France
facility: GSK Investigational Site
city: Evreux
country: France
facility: GSK Investigational Site
city: Lille Cedex
country: France
facility: GSK Investigational Site
city: Luynes
country: France
facility: GSK Investigational Site
city: Montbrison
country: France
facility: GSK Investigational Site
city: Toulouse
country: France
facility: GSK Investigational Site
city: Tours
country: France
facility: GSK Investigational Site
city: Vieux Condé
country: France
facility: GSK Investigational Site
city: Voiron
country: France
facility: GSK Investigational Site
city: Weinheim
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Huettenberg
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Wiesbaden
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Essen
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Muenster
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Kiel
country: Germany
facility: GSK Investigational Site
state: Schleswig-Holstein
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Modena
country: Italy
facility: GSK Investigational Site
state: Emilia-Romagna
city: Roma
country: Italy
facility: GSK Investigational Site
state: Lazio
city: Genova
country: Italy
facility: GSK Investigational Site
state: Liguria
city: Sestri Ponente (GE)
country: Italy
facility: GSK Investigational Site
state: Liguria
city: Catania
country: Italy
facility: GSK Investigational Site
state: Sicilia
city: Firenze
country: Italy
facility: GSK Investigational Site
state: Toscana
city: Feltre (BL)
country: Italy
facility: GSK Investigational Site
state: Veneto
city: Blaricum
country: Netherlands
facility: GSK Investigational Site
city: Eindhoven
country: Netherlands
facility: GSK Investigational Site
city: Etten-leur
country: Netherlands
facility: GSK Investigational Site
city: Geldermalsen
country: Netherlands
facility: GSK Investigational Site
city: Grubbenvorst
country: Netherlands
facility: GSK Investigational Site
city: Heerlen
country: Netherlands
facility: GSK Investigational Site
city: Hengelo
country: Netherlands
facility: GSK Investigational Site
city: Hoogwoud
country: Netherlands
facility: GSK Investigational Site
city: Nijmegen
country: Netherlands
facility: GSK Investigational Site
city: Spijkenisse
country: Netherlands
facility: GSK Investigational Site
city: Venray
country: Netherlands
facility: GSK Investigational Site
city: Zwolle
country: Netherlands
facility: GSK Investigational Site
city: Bergen
country: Norway
facility: GSK Investigational Site
city: Elverum
country: Norway
facility: GSK Investigational Site
city: Hamar
country: Norway
facility: GSK Investigational Site
city: Hønefoss
country: Norway
facility: GSK Investigational Site
city: Lier
country: Norway
facility: GSK Investigational Site
city: Oslo
country: Norway
facility: GSK Investigational Site
city: Sandvika
country: Norway
facility: GSK Investigational Site
city: Avila
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Oviedo
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: