Study to Evaluate the Efficacy and Safety of Oral Sumatriptan for the Acute Treatment of Migraine in Children and Adolescents

• ClinicalTrials.gov Identifier: NCT00963937
• Recruitment Status: Completed
• First Posted: August 24, 2009
• Results First Posted: August 26, 2011
• Last Update Posted: August 6, 2018
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Study Description

Brief Summary:

The purpose of this study is to evaluate the efficacy and safety of a range of doses of oral sumatriptan for the acute treatment of migraine in children ages 10 to 17.

Condition or disease	Intervention/treatment	Phase
Migraine Disorders	Drug: Sumatriptan 25 mg; Drug: Sumatriptan 50 mg; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 178 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Multicenter, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Oral Sumatriptan for the Acute Treatment of Migraine in Children and Adolescents
• Study Start Date: September 28, 2009
• Actual Primary Completion Date: December 1, 2010
• Actual Study Completion Date: December 3, 2010

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Sumatriptan 25 mg	Drug: Sumatriptan 25 mg; One Sumatriptan 25mg tablet and one Matching Placebo tablet should be administered as soon as possible (within 30 minutes) after the development of a migraine associated with 3 or more pain on a 5-grade scale.
Active Comparator: Sumatriptan 50 mg	Drug: Sumatriptan 50 mg; Two Sumatriptan 25mg tablets should be administered as soon as possible (within 30 minutes) after the development of a migraine associated with 3 or more pain on a 5-grade scale.
Placebo Comparator: Placebo	Drug: Placebo; Two Matching Placebo tablets should be administered as soon as possible (within 30 minutes) after the development of a migraine associated with 3 or more pain on a 5-grade scale.

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants Who Reported Pain Relief at 120 Minutes Post-Treatment [ Time Frame: 120 minutes post-treatment (Randomization through Final Visit [Week 6]) ]
   Pain relief was defined as at least a 2-grade reduction in pain intensity on a 5-grade scale in participants who had not used headache rescue medication before assessment. A pain intensity score of 5 was assigned for all subsequent assessments if a participant took rescue medication (a single oral dose for the treatment of migraine pain or associated symptoms). The 5-grade scale is a participant's self-rating scale to assess the pain intensity of a migraine with the following scores: 1 = none, 2 = mild, 3 = mild to moderate, 4 = moderate to severe, and 5 = severe.

Secondary Outcome Measures :

1. Percentage of Participants Who Reported Pain Relief at 30, 60, 120, and 240 Minutes Post-Treatment [ Time Frame: 30, 60, 120, and 240 minutes post-treatment (Randomization through Final Visit [Week 6]) ]
   Pain relief was defined as at least a 2-grade reduction in pain intensity on a 5-grade scale in participants who had not used headache rescue medication before assessment. A pain intensity score of 5 was assigned for all subsequent assessments if a participant took rescue medication (a single oral dose for the treatment of migraine pain or associated symptoms). The 5-grade scale is a participant's self-rating scale to assess the pain intensity of a migraine with the following scores: 1 = none, 2 = mild, 3 = mild to moderate, 4 = moderate to severe, and 5 = severe.
2. Percentage of Participants Who Were Pain Free at 30, 60, 120, and 240 Minutes Post-Treatment [ Time Frame: 30, 60, 120, and 240 minutes post-treatment (Randomization through Final Visit [Week 6]) ]
   Pain free was defined as a post-treatment pain intensity score of 1 on a 5-grade scale in participants who had not used headache rescue medication before assessment. A pain intensity score of 5 was assigned for all subsequent assessments if a participant took a rescue medication. The 5-grade scale is a participant's self-rating scale to assess the pain intensity of a migraine with the following scores: 1 = none, 2 =mild, 3=mild to moderate, 4=moderate to severe, and 5=severe.
3. Percentage of Participants Who Were Photophobia Free at 30, 60, 120, and 240 Minutes Post-Treatment [ Time Frame: 30, 60, 120, and 240 minutes post-treatment (Randomization through Final Visit [Week 6]) ]
   Photophobia (sensitivity to light) is one of the associated symptoms of a migraine. A participant was assessed as photophobia free when the symptom was recorded as "absent" at each time point in his or her patient diary. Photophobia was recorded as "present" for all subsequent assessments if a participant took rescue medication.
4. Percentage of Participants Who Were Phonophobia Free at 30, 60, 120, and 240 Minutes Post-Treatment [ Time Frame: 30, 60, 120, and 240 minutes post-treatment (Randomization through Final Visit [Week 6]) ]
   Phonophobia (sensitivity to sound) is one of the associated symptoms of a migraine. A participant was assessed as phonophobia free when the symptom was recorded as "absent" at each time point in his or her patient diary. Phonophobia was recorded as "present" for all subsequent assessments if a participant took rescue medication.
5. Percentage of Participants Who Were Nausea Free at 30, 60, 120, and 240 Minutes Post-Treatment [ Time Frame: 30, 60, 120, and 240 minutes post-treatment (Randomization through Final Visit [Week 6]) ]
   Nausea is one of the associated symptoms of a migraine. A participant was assessed as nausea free when the symptom was recorded as "absent" at each time point in his or her patient diary. Nausea was recorded as "present" for all subsequent assessments if a participant took rescue medication.
6. Percentage of Participants Who Were Free of Vomiting at 30, 60, 120, and 240 Minutes Post-Treatment [ Time Frame: 30, 60, 120, and 240 minutes post-treatment (Randomization through Final Visit [Week 6]) ]
   Vomiting is one of the associated symptoms of a migraine. A participant was assessed as being free of vomiting when the symptom was recorded as "absent" at each time point in his or her patient diary. Vomiting was recorded as "present" for all subsequent assessments if a participant took a rescue medication.
7. Percentage of Participants Who Used Rescue Medication Between the Time of Dosing and 240 Minutes Post-Treatment [ Time Frame: within 240 minutes post-treatment (Randomization through Final Visit [Week 6]) ]
   Rescue medication included one of the following: a single oral dose of a nonsteroidal anti-inflammatory drug (NSAID) or acetaminophen, not to exceed the maximum recommended single dose; and anti-emetics (a drug to prevent vomiting).

Eligibility Criteria

• Ages Eligible for Study: 10 Years to 17 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Subject is >10 years of age and <17 years of age at the informed consent and the Randomization Visit.
• Subject has migraine with or without aura (ICHD-II criteria, 1.1 or 1.2.1). A minimum of a six month history of migraine prior to entry into the study is required.
• Subject has a history of at least two, but no more than eight, attacks per month for the two months prior to entry into the study.
• All migraine attacks associated with 3 or more pain on a 5-grade scale should last a minimum of three hours for the two months prior to entry into the study.
• Subject has shown nonresponse to at least one NSAIDs or acetaminophen for the two months prior to entry into the study.
• Subject is able to distinguish migraine from other headaches (e.g., tension-type headache).
• Subject is able to read, comprehend, and complete subject diaries.
• Males or female subjects. Female subjects are eligible for participation in the study if they are one of the following
• Females of non-childbearing potential (i.e., physiologically incapable of becoming pregnant or have undergone female sterilization)
• Females of childbearing potential, and who have a negative pregnancy test at the Screening Visit, and agree to use one of the following GlaxoSmithKline (GSK)-specified highly effective methods for avoiding pregnancy:
• Abstinence
• Oral Contraceptive, either combined or progestogen alone
• Male partner sterilization (vasectomy with documentation of azoospermia) prior to the female subject's entry into the study, and this male is the sole partner for that subject)
• Double barrier method: condom or occlusive cap (diaphragm or cervical/vault caps) plus spermicidal agent (foam/gel/film/cream/suppository)
• Subject's parent or legal guardian is willing and able to provide informed consent prior to subject entry into the study.
• Subject is willing and able to provide informed assent prior to entry into the study.
• Subjects considered for enrolment must have a QTc (either QTc B (Bazett's correction) or QTc F (Fridericia's correction)) <450msec at the Screening Visit, with the exception of subjects with bundle branch block (for whom either QTc B or QTc F must be <480msec).

Note: For the purposes of these criteria, QTc B is defined as (QT interval msec) / (square root of RR interval seconds); and QTc F is defined as (QT interval msec) / (cube root of RR interval seconds).)

• Liver function test at the Screening Visit: AST and ALT <2xULN; alkaline phosphatase and total bilirubin <1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)

Exclusion Criteria:

• Subject is < 30 kg.
• Subject has 15 or more headache days per month in total (migraine, probable migraine, or tension-type). Subject has retinal (ICHD-II 1.4), basilar (ICHD-II 1.2.6), hemiplegic (ICHD-II 1.2.4 or 1.2.5), or Ophthalmoplegic migraine (ICHD-II 13.17). Subject has secondary headaches.
• Subject has a history of cerebrovascular disease or ischemic cerebrovascular disease.
• Subject has a history of myocardial infarction.
• Subject has uncontrolled hypertension.
• Subject has symptoms or signs of ischemic cardiac syndromes.
• Subject has variant angina.
• Subject has evidence of a peripheral vascular syndrome.
• Subject has evidence or history of epilepsy or structural brain lesions which lower the convulsive threshold, or has been treated with an antiepileptic drug for seizure control.
• Subject has a history of impaired hepatic or renal function that, in the investigator (or subinvestigator)'s opinion, contraindicates participation in this study. Subject has unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, esophageal or gastric varices or persistent jaundice). Subject has cirrhosis. Subject has known biliary abnormalities (with the exception of Gilberts's syndrome or asymptomatic gallstones).
• Subject has hypersensitivity, allergy, intolerance, or contraindication to the use of any triptan (including all sumatriptan preparations) or sulfonamide compounds.
• Subject has used an ergot medication in the previous three months for migraine prophylaxis or is taking a medication that is not stabilized (i.e., change of dose within the past 2 months) for either chronic or intermittent migraine prophylaxis.
• Subject has taken, or plans to take, a monoamine oxidase inhibitor (MAOI) anytime within the two weeks prior to entry into the study.
• Subject has evidence of psychotropic, alcohol, or substance abuse within the last year.
• Subject has participated in any investigational drug trial within the previous 3 months or plans to participate in another study at any time during this study.
• Subject has any concurrent medical or psychiatric condition which, in the investigator (or subinvestigator)'s judgment, contraindicates participation in this clinical trial.

Contacts and Locations

Locations

Japan

GSK Investigational Site

Aichi, Japan, 450-0002

GSK Investigational Site

Aichi, Japan, 467-8602

GSK Investigational Site

Hokkaido, Japan, 060-0004

GSK Investigational Site

Hokkaido, Japan, 060-8570

GSK Investigational Site

Hyogo, Japan, 658-0064

GSK Investigational Site

Hyogo, Japan, 663-8204

GSK Investigational Site

Kagoshima, Japan, 892-0844

GSK Investigational Site

Kanagawa, Japan, 215-0021

GSK Investigational Site

Kanagawa, Japan, 221-0835

GSK Investigational Site

Kanagawa, Japan, 252-0375

GSK Investigational Site

Kyoto, Japan, 600-8811

GSK Investigational Site

Osaka, Japan, 560-0012

GSK Investigational Site

Saitama, Japan, 336-8522

GSK Investigational Site

Tokyo, Japan, 101-0021

GSK Investigational Site

Tokyo, Japan, 105-7103

GSK Investigational Site

Tokyo, Japan, 132-0024

Sponsors and Collaborators

GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

More Information

Additional Information:

Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research. 

Study Data/Documents: Individual Participant Data Set 

Identifier: 111035
For additional information about this study please refer to the GSK Clinical Study Register

Statistical Analysis Plan 

Identifier: 111035
For additional information about this study please refer to the GSK Clinical Study Register

Annotated Case Report Form 

Identifier: 111035
For additional information about this study please refer to the GSK Clinical Study Register

Dataset Specification 

Identifier: 111035
For additional information about this study please refer to the GSK Clinical Study Register

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00963937
• Other Study ID Numbers: 111035
• First Posted: August 24, 2009
• Results First Posted: August 26, 2011
• Last Update Posted: August 6, 2018
• Last Verified: June 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Keywords provided by GlaxoSmithKline:

adolescent; sumatriptan; children; migraine

Additional relevant MeSH terms:

Migraine Disorders; Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Sumatriptan; Vasoconstrictor Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Serotonin Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs