Last updated: 11/04/2018 09:52:48
Use Of GW274150 In The Prophylactic Treatment Of Migraine
GSK study ID
NOS103325
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
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.
Trial description: 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.
Primary purpose:
Prevention
Trial design:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:
Number of migraine headache days during the 4-week Baseline period and the 12-week treatment period- Part 1
Timeframe: Baseline (Week -4 to 0) to Week 12
Number of migraine headache day during the 4-week Baseline period and the 12-week treatment period- Part 2
Timeframe: Baseline (Week -4 to 0) to Week 12
Percentage change from Baseline in probability of a migraine headache day at Day 70- Part 1
Timeframe: Baseline (Week -4 to 0) and Day 70 (third 4-Week treatment period)
Percentage change from Baseline in probability of a migraine headache day at Day 70- Part 2
Timeframe: Baseline (Week -4 to 0) and Day 70 (third 4-Week treatment period)
Number of participants with adverse events (AEs) and their severity (mild, moderate and severe) and serious adverse events (SAEs) in Part 1
Timeframe: Up to Week 16
Number of participants with AEs and their severity (mild, moderate and severe) and SAEs in Part 2
Timeframe: Up to Week 16
Change from Baseline in clinical chemistry data- Alkaline Phosphatase (ALP), Alanine Transaminase (ALT), Aspartate Transaminase (AST), Creatine Kinase (CK), Gamma-Glutamyl Transpeptidase (GGT), Lactic dehydrogenase (LDH)-Part 1
Timeframe: Baseline (Week -4 to 0) up to Week 12
Change from Baseline in clinical chemistry data- ALP, ALT, AST, CK, GGT, LDH- Part 2
Timeframe: Baseline (Week -4 to 0) up to Week 12
Change from Baseline in clinical chemistry data- total bilirubin, creatinine- Part 1
Timeframe: Baseline (Week -4 to 0) up to Week 12
Change from Baseline in clinical chemistry data- total bilirubin, creatinine-Part 2
Timeframe: Baseline (Week -4 to 0) up to Week 12
Change from Baseline in clinical chemistry data- amylase, lipase-Part 1
Timeframe: Baseline (Week -4 to 0) up to Week 12
Change from Baseline in clinical chemistry data- amylase, lipase- Part 2
Timeframe: Baseline (Week -4 to 0) up to Week 12
Change from Baseline in clinical chemistry data- albumin, total protein-Part 1
Timeframe: Baseline (Week -4 to 0) up to Week 12
Change from Baseline in clinical chemistry data- albumin, total protein- Part 2
Timeframe: Baseline (Week -4 to 0) up to Week 12
Change from Baseline in clinical chemistry data- calcium, chloride, potassium, sodium, glucose, cholesterol, triglycerides, urea-Part 1
Timeframe: Baseline (Week -4 to 0) up to Week 12
Change from Baseline in clinical chemistry data- calcium, chloride, potassium, sodium, glucose, cholesterol, triglycerides, urea-Part 2
Timeframe: Baseline (Week -4 to 0) up to Week 12
Change from Baseline in hematology parameters- hemoglobin, mean cell hemoglobin concentration (MCHC)-Part 1
Timeframe: Baseline (Week -4 to 0) up to Week 12
Change from Baseline in hematology parameters- hemoglobin, MCHC-Part 2
Timeframe: Baseline (Week -4 to 0) up to Week 12
Change from Baseline in hematology parameters- hematocrit-Part 1
Timeframe: Baseline (Week -4 to 0) up to Week 12
Change from Baseline in hematology parameters- hematocrit-Part 2
Timeframe: Baseline (Week -4 to 0) up to Week 12
Change from Baseline in hematology parameters- mean corpuscle haemoglobin (MCH)-Part 1
Timeframe: Baseline (Week -4 to 0) up to Week 12
Change from Baseline in hematology parameters- MCH-Part 2
Timeframe: Baseline (Week -4 to 0) up to Week 12
Change from Baseline in hematology parameters- mean corpuscular volume (MCV)-Part 1
Timeframe: Baseline (Week -4 to 0) up to Week 12
Change from Baseline in hematology parameters- MCV-Part 2
Timeframe: Baseline (Week -4 to 0) up to Week 12
Change from Baseline in hematology parameters- platelet count, white blood cell count (WBC), basophils, eosinophils, lymphocytes, monocytes, total neutrophils-Part 1
Timeframe: Baseline (Week -4 to 0) up to Week 12
Change from Baseline in hematology parameters- platelet count, WBC, basophils, eosinophils, lymphocytes, monocytes, total neutrophils-Part 2
Timeframe: Baseline (Week -4 to 0) up to Week 12
Change from Baseline in hematology parameters- red blood cell count (RBC)-Part 1
Timeframe: Baseline (Week -4 to 0) up to Week 12
Change from Baseline in hematology parameters- RBC-Part 2
Timeframe: Baseline (Week -4 to 0) up to Week 12
Number of participants with abnormal urinalysis dipstick results- Part 1
Timeframe: Up to Week 12
Number of participants with abnormal urinalysis dipstick results- Part 2
Timeframe: Up to Week 12
Assessment of Urobilinogen- Part 1
Timeframe: Up to Week 12
Assessment of Urobilinogen- Part 2
Timeframe: Up to Week 12
Change from Baseline in vital signs- systolic blood pressure (SBP) and diastolic blood pressure (DBP)-Part 1
Timeframe: Baseline (Week -4 to 0) up to Week 12
Change from Baseline in vital signs- SBP and DBP-Part 2
Timeframe: Baseline (Week -4 to 0) up to Week 12
Change from Baseline in vital sign- Heart rate-Part 1
Timeframe: Baseline (Week -4 to 0) up to Week 12
Change from Baseline in vital sign- Heart rate- Part 2
Timeframe: Baseline (Week -4 to 0) up to Week 12
Number of participants with abnormal electrocardiogram (ECG) findings-Part 1
Timeframe: Up to Week 12
Number of participants with abnormal ECG findings-Part 2
Timeframe: Up to Week 12
Secondary outcomes:
Change from Baseline in the number of migraine headache days for each 4-week treatment period and for the entire treatment period-Part 1
Timeframe: Baseline (Week -4 to 0) up to Week 12
Change from Baseline in the number of migraine headache days for each 4-week treatment period and for the entire treatment period-Part 2
Timeframe: Baseline (Week -4 to 0) up to Week 12
Number of participants with percent reduction from Baseline in number of migraine headache days (responder rates) of at least 50 percent, 75 percent, 90 percent and 100 percent for each 4- week treatment period and for the entire treatment period-Part 1
Timeframe: Baseline (Week -4 to 0) up to Week 12
Number of participants with percent reduction from Baseline in number of migraine headache days (responder rates) of at least 50 percent, 75 percent, 90 percent,100 percent for each 4- week treatment period and for the entire treatment period-Part 2
Timeframe: Baseline (Week -4 to 0) up to Week 12
Change from Baseline in the number of migraine attacks for each 4-week treatment period and for the entire treatment period-Part 1
Timeframe: Baseline (Week -4 to 0) up to Week 12
Change from Baseline in the number of migraine attacks for each 4-week treatment period and for the entire treatment period-Part 2
Timeframe: Baseline (Week -4 to 0) up to Week 12
Number of participants with percent reduction from Baseline in number of migraine attacks of at least 50 percent, 75 percent, 90 percent, and 100 percent for each 4-week treatment period and for the entire treatment period-Part 1
Timeframe: Baseline (Week -4 to 0) up to Week 12
Number of participants with percent reduction from Baseline in number of migraine attacks of at least 50 percent, 75 percent, 90 percent, and 100 percent for each 4-week treatment period and for the entire treatment period-Part 2
Timeframe: Baseline (Week -4 to 0) up to Week 12
Change from Baseline in the mean peak migraine pain severity utilizing the 4-point pain scale for each 4-week treatment period and for the entire treatment period-Part 1
Timeframe: Baseline (Week -4 to 0) up to Week 12
Change from Baseline in the mean peak migraine pain severity utilizing the 4-point pain scale for each 4-week treatment period and for the entire treatment period-Part 2
Timeframe: Baseline (Week -4 to 0) up to Week 12
Change from Baseline in mean migraine headache duration for each 4-week treatment period and for the entire treatment period-Part 1
Timeframe: Baseline (Week -4 to 0) up to Week 12
Change from Baseline in mean migraine headache duration for each 4-week treatment period and for the entire treatment period-Part 2
Timeframe: Baseline (Week -4 to 0) up to Week 12
Change from Baseline in the number of migraine headache periods for each 4-week treatment period and for the entire treatment period-Part 2
Timeframe: Baseline (Week -4 to 0) up to Week 12
Number of participants with percent reduction from Baseline in number of migraine headache periods of at least 50 percent, 75 percent, 90 percent, and 100 percent for each 4-week treatment period and for the entire treatment period-Part 2
Timeframe: Baseline (Week -4 to 0) up to Week 12
Change from Baseline in percent of migraine attacks with nausea for each 4-week treatment period and for the entire treatment period-Part 2
Timeframe: Baseline (Week -4 to 0) up to Week 12
Change from Baseline in percent of migraine attacks with vomiting for each 4-week treatment period and for the entire treatment period-Part 2
Timeframe: Baseline (Week -4 to 0) up to 12
Change from Baseline in percent of migraine attacks with photophobia for each 4-week treatment period and for the entire treatment period-Part 2
Timeframe: Baseline (Week -4 to 0) up to Week 12
Change from Baseline in percent of migraine attacks with phonophobia for each 4-week treatment period and for the entire treatment period-Part 2
Timeframe: Baseline (Week -4 to 0) up to Week 12
Change from Baseline in percent of migraine attacks with aura for each 4-week treatment period and for the entire treatment period-Part 2
Timeframe: Baseline (Week -4 to 0) up to Week 12
Change from Baseline in number of days of acute breakthrough medication administration for each 4-week treatment period and for the entire treatment period-Part 2
Timeframe: Baseline (Week -4 to 0) up to Week 12
Change from Baseline (Randomisation Visit) in Migraine Specific Quality of Life Questionnaire Version 2.1 (MSQ v2.1) at Week 4, 8, 12 and Follow-Up visits-Part 2
Timeframe: Baseline (Week 0) up to follow-up (Week 16)
Change from Baseline in productivity as measured by lost time equivalents (LTE) for each 4-week treatment period and for the entire treatment period-Part 2
Timeframe: Baseline (Week -4 to 0) up to Week 12
Number of participants with treatment satisfaction measured using three global items: satisfaction with overall medication effectiveness, satisfaction with side effects, and overall satisfaction at randomization, Week 4, 8 and 12 visits-Part 2
Timeframe: Baseline (Week 0) up to Week 12
Assessment of pharmacokinetic (PK) parameters of GW274150: Minimum concentration at steady state (Cmin-ss), Maximum concentration at steady state (Cmax-ss)- Part 2
Timeframe: Week 4, 8 and 12
Assessment of PK parameters of GW274150: Area under the concentration time curve over the dosing interval at steady state (AUCtss)- Part 2
Timeframe: Week 4, 8 and 12
Change from Baseline in Nitro-tyrosine and tyrosine at Week 4, 8 and 12-Part 2
Timeframe: Baseline (Week 0) and Week 4, 8, 12
Change from Baseline in Nitro-tyrosine: tyrosine ratio at Week 4,8 and 12-Part 2
Timeframe: Baseline (Week 0) and Week 4, 8, 12
Interventions:
Drug: GW274150
Other: Placebo
Enrollment:
425
Observational study model:
Not applicable
Primary completion date:
2007-11-09
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Migraine Disorders
Product
GW274150
Collaborators
Not applicable
Study date(s)
October 2005 to September 2007
Type
Interventional
Phase
2
Participation criteria
Sex
Female
Age
18 - 55 years
Accepts healthy volunteers
No
- Suffering from migraine with or without aura.
- Migraine for at least one year, and the age of onset was prior to 50 years.
- 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.
Inclusion and exclusion 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.
Trial location(s)
Location
GSK Investigational Site
Kiel, Schleswig-Holstein, Germany, 24149
Status
Study Complete
Location
GSK Investigational Site
Weinheim, Baden-Wuerttemberg, Germany, 69469
Status
Study Complete
Location
GSK Investigational Site
Sestri Ponente (GE), Liguria, Italy, 16153
Status
Study Complete
Location
GSK Investigational Site
Muenster, Nordrhein-Westfalen, Germany, 48149
Status
Study Complete
Location
GSK Investigational Site
Essen, Nordrhein-Westfalen, Germany, 45122
Status
Terminated/Withdrawn
Study documents
No study documents available.
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Completed
Actual primary completion date
2007-11-09
Actual study completion date
2007-11-09
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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