A Study to Evaluate the Safety and Tolerability of Rizatriptan for Long Term Treatment of Acute Migraine in Children and Adolescents (MK-0462-086 AM3)

• Sponsor: Organon and Co (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01004263
• Collaborator: (none)
• Enrollment: 674
• Arm: 1
• Actual Duration (Months): 16.5

Study Details

Study Description

Brief Summary

To provide long term safety data for rizatriptan in children and adolescents. The primary hypothesis of the study is that rizatriptan is well tolerated in the long term treatment of acute migraine in pediatric patients age 12-17 years.

Condition or Disease	Intervention/Treatment	Phase
Acute Migraine With or Without Aura in Adolescents	Drug: rizatriptan benzoate	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 674 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Worldwide, Open Label, Clinical Trial to Examine the Long Term Safety and Tolerability of Rizatriptan in Pediatric Migraineurs for the Treatment of Migraine With or Without Aura
• Actual Study Start Date: Dec 1, 2009
• Actual Primary Completion Date: Apr 18, 2011
• Actual Study Completion Date: Apr 18, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rizatriptan Rizatriptan benzoate	Drug: rizatriptan benzoate; Single dose of 5 mg or 10 mg orally disintegrating tablet at onset of migraine attack; Other Names: MK-0462 Maxalt

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events (AEs) Within 24 Hours Post Any Dose [Up to 24 hours post dose]

   An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration. Participants reported AEs in a diary and these were collected by the study site at visits at 1, 2, 3, 4, 6, 9, and 12 months after Screening visit. Participants with an AE occurring within 24 hours after any dose administered during the study are counted once in this summary.

2. Number of Participants With AEs Within 14 Days Post Any Dose [Up to 14 days post dose]

   An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration. Participants reported AEs in a diary and these were collected by the study site at visits at 1, 2, 3, 4, 6, 9, and 12 months after Screening visit. AEs were assessed in a phone contact 14 days after the last dose of study medication. Participants with an AE occurring within 14 days after any dose administered during the study are counted once in this summary.

3. Number of Participants Discontinued From Study Due to AEs Occurring Within 24 Hours Post Dose [Up to 24 hours post dose]

   An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration. Participants who discontinued due to an AE occurring within 24 hours post dose are counted in this summary.

4. Number of Participants Discontinued From Study Due to AEs Occurring Within 14 Days Post Dose [Up to 14 days post dose]

   An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration. Participants who discontinued due to an AE occurring within 14 days post dose are counted in this summary.

Secondary Outcome Measures

1. Percentage of Participant's Migraine Attacks With Pain Freedom at 2 Hours Post Dose [2 hours post dose]

   Pain intensity was assessed using a 5-Face Pain Scale ranging from 1=no pain to 5=very bad pain. Pain freedom (PF) was defined as a reduction in severity from a rating of 5, 4, 3 or 2 (mild, moderate or severe pain) before the dose to a rating of 1 (no pain) at 2 hours after dosing. Pain intensity ratings were reported in diaries returned at visits at 1, 2, 3, 4, 6, 9, and 12 months after Screening visit. PF at 2 hours was summarized as follows: the percentage of treated attacks with PF at 2 hours was calculated for each patient first, then the mean across all patients was calculated.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patient is between 12 and 17 years of age inclusive at screening Visit 1

• Patient weighs at least 20 kg (44 pounds)

• Patient has had a history of unilateral or bilateral migraine headache with or without aura >6 months with ≥1 to ≤8 mild, moderate or severe migraine attacks per month in the 2 months prior to screening Visit 1

• Patient has a history of migraine defined by International Headache Society (IHS) migraine definitions

• The parent or guardian and patient agree to the patient's participation in the study as indicated by parental/guardian signature on the consent form and patient assent

• For patients taking migraine prophylactic medication, treatment regimen is stable and has been taken for at least 3 months prior to Visit 1

Exclusion Criteria:

• Patient is pregnant or breast-feeding, or is a female expecting to conceive within the projected duration of study participation

• Patient has a history of mild migraine attacks or migraines that resolve in less than 2 hours

• Patient has basilar or hemiplegic migraine headaches

• Patient has >15 headache-days per month OR has taken medication for acute headache on more than 10 days per month in any of the 3 months prior to screening

• Patient has uncontrolled high blood pressure, uncontrolled diabetes, human immunodeficiency virus (HIV), any cancer, or any other significant disease

• Patient has a history cardiovascular problems or stroke

• Patient has either demonstrated hypersensitivity to or experienced a serious adverse event in response to rizatriptan

• Patient has demonstrated hypersensitivity to or experienced a serious adverse event in response to 3 or more classes of drugs (over-the-counter and prescription)

• Patient did not experience satisfactory relief from migraine pain to prior treatment with 2 or more adequate courses of 5-hydroxytryptamine 1 (5HT1) agonists

• Patient has a recent history (within the past year) or current evidence of drug or alcohol abuse or is a "recreational user" of illicit drugs

• Patient is currently taking monoamine oxidase inhibitors, methysergide, or propranolol, and is unable to tolerate withdrawal of these medications for the intervals required

• Patient is currently participating or has participated in a study with an investigational compound or device within 30 days of screening

• Patient is legally or mentally incapacitated

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Organon and Co

Investigators

• Study Director: Medical Monitor, Merck Sharp & Dohme LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Organon and Co
• ClinicalTrials.gov Identifier: NCT01004263
• Other Study ID Numbers: 0462-086; 2009_680
• First Posted: Oct 29, 2009
• Last Update Posted: Feb 8, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Organon and Co: acute migraine with or without aura in adolescents
• Additional relevant MeSH terms: Migraine Disorders; Rizatriptan

Study Results

Participant Flow

Pre-assignment Detail	A total of 674 patients met inclusion/exclusion criteria and were allocated study drug. Of these, 606 were treated with study drug.

Arm/Group Title	Rizatriptan
Arm/Group Description	Participants self-administered rizatriptan to treat up to 8 qualifying migraine headaches (mild, moderate, or severe pain intensity) per month, for up to 12 months. Rizatriptan dose, administered as a single oral tablet, was either 5 or 10 mg, based on participant weight (5 mg if <40 kg, 10 mg if ≥40 kg).
Period Title: Overall Study
STARTED	606
COMPLETED	427
NOT COMPLETED	179

Baseline Characteristics

Arm/Group Title	Rizatriptan
Arm/Group Description	Participants self-administered rizatriptan to treat up to 8 qualifying migraine headaches (mild, moderate, or severe pain intensity) per month, for up to 12 months. Rizatriptan dose, administered as a single oral tablet, was either 5 or 10 mg, based on participant weight (5 mg if <40 kg, 10 mg if ≥40 kg).
Overall Participants	606
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	14.7 (1.7)
Sex: Female, Male (Count of Participants)
Female	372 61.4%
Male	234 38.6%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events (AEs) Within 24 Hours Post Any Dose
Description	An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration. Participants reported AEs in a diary and these were collected by the study site at visits at 1, 2, 3, 4, 6, 9, and 12 months after Screening visit. Participants with an AE occurring within 24 hours after any dose administered during the study are counted once in this summary.
Time Frame	Up to 24 hours post dose

Outcome Measure Data

Analysis Population Description

All enrolled participants who administered at least one dose of study medication

Arm/Group Title	Rizatriptan
Arm/Group Description	Participants self-administered rizatriptan to treat up to 8 qualifying migraine headaches (mild, moderate, or severe pain intensity) per month, for up to 12 months. Rizatriptan dose, administered as a single oral tablet, was either 5 or 10 mg, based on participant weight (5 mg if <40 kg, 10 mg if ≥40 kg).
Measure Participants	606
Number [participants]	322 53.1%

2. Primary Outcome

Title	Number of Participants With AEs Within 14 Days Post Any Dose
Description	An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration. Participants reported AEs in a diary and these were collected by the study site at visits at 1, 2, 3, 4, 6, 9, and 12 months after Screening visit. AEs were assessed in a phone contact 14 days after the last dose of study medication. Participants with an AE occurring within 14 days after any dose administered during the study are counted once in this summary.
Time Frame	Up to 14 days post dose

Outcome Measure Data

Analysis Population Description

All enrolled participants who administered at least one dose of study medication

Arm/Group Title	Rizatriptan
Arm/Group Description	Participants self-administered rizatriptan to treat up to 8 qualifying migraine headaches (mild, moderate, or severe pain intensity) per month, for up to 12 months. Rizatriptan dose, administered as a single oral tablet, was either 5 or 10 mg, based on participant weight (5 mg if <40 kg, 10 mg if ≥40 kg).
Measure Participants	606
Number [participants]	400 66%

3. Secondary Outcome

Title	Percentage of Participant's Migraine Attacks With Pain Freedom at 2 Hours Post Dose
Description	Pain intensity was assessed using a 5-Face Pain Scale ranging from 1=no pain to 5=very bad pain. Pain freedom (PF) was defined as a reduction in severity from a rating of 5, 4, 3 or 2 (mild, moderate or severe pain) before the dose to a rating of 1 (no pain) at 2 hours after dosing. Pain intensity ratings were reported in diaries returned at visits at 1, 2, 3, 4, 6, 9, and 12 months after Screening visit. PF at 2 hours was summarized as follows: the percentage of treated attacks with PF at 2 hours was calculated for each patient first, then the mean across all patients was calculated.
Time Frame	2 hours post dose

Outcome Measure Data

Analysis Population Description

All participants who were enrolled and reported at least one treated migraine attack with at least one post treatment efficacy evaluation

Arm/Group Title	Rizatriptan
Arm/Group Description	Participants self-administered rizatriptan to treat up to 8 qualifying migraine headaches (mild, moderate, or severe pain intensity) per month, for up to 12 months. Rizatriptan dose, administered as a single oral tablet, was either 5 or 10 mg, based on participant weight (5 mg if <40 kg, 10 mg if ≥40 kg).
Measure Participants	603
Mean (Standard Deviation) [percentage of participant's attacks]	46.3 (31.9)

4. Primary Outcome

Title	Number of Participants Discontinued From Study Due to AEs Occurring Within 24 Hours Post Dose
Description	An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration. Participants who discontinued due to an AE occurring within 24 hours post dose are counted in this summary.
Time Frame	Up to 24 hours post dose

Outcome Measure Data

Analysis Population Description

All enrolled participants who administered at least one dose of study medication

Arm/Group Title	Rizatriptan
Arm/Group Description	Participants self-administered rizatriptan to treat up to 8 qualifying migraine headaches (mild, moderate, or severe pain intensity) per month, for up to 12 months. Rizatriptan dose, administered as a single oral tablet, was either 5 or 10 mg, based on participant weight (5 mg if <40 kg, 10 mg if ≥40 kg).
Measure Participants	606
Number [participants]	4 0.7%

5. Primary Outcome

Title	Number of Participants Discontinued From Study Due to AEs Occurring Within 14 Days Post Dose
Description	An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration. Participants who discontinued due to an AE occurring within 14 days post dose are counted in this summary.
Time Frame	Up to 14 days post dose

Outcome Measure Data

Analysis Population Description

All enrolled participants who administered at least one dose of study medication

Arm/Group Title	Rizatriptan
Arm/Group Description	Participants self-administered rizatriptan to treat up to 8 qualifying migraine headaches (mild, moderate, or severe pain intensity) per month, for up to 12 months. Rizatriptan dose, administered as a single oral tablet, was either 5 or 10 mg, based on participant weight (5 mg if <40 kg, 10 mg if ≥40 kg).
Measure Participants	606
Number [participants]	14 2.3%

Adverse Events

Time Frame	Up to 12 months after start of study drug administration
Adverse Event Reporting Description	AE tables include all enrolled participants who administered at least one dose of study medication
Arm/Group Title	Rizatriptan
Arm/Group Description	Participants self-administered rizatriptan to treat up to 8 qualifying migraine headaches (mild, moderate, or severe pain intensity) per month, for up to 12 months. Rizatriptan dose, administered as a single oral tablet, was either 5 or 10 mg, based on participant weight (5 mg if <40 kg, 10 mg if ≥40 kg).
All Cause Mortality
	Rizatriptan
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Rizatriptan
	Affected / at Risk (%)	# Events
Total	22/606 (3.6%)
Cardiac disorders
Sinus bradycardia	1/606 (0.2%)	1
Gastrointestinal disorders
Abdominal discomfort	2/606 (0.3%)	2
General disorders
Fatigue	1/606 (0.2%)	2
Infections and infestations
Appendicitis	2/606 (0.3%)	2
Gastroenteritis	1/606 (0.2%)	1
Viral infection	1/606 (0.2%)	1
Injury, poisoning and procedural complications
Fibula fracture	1/606 (0.2%)	1
Road traffic accident	1/606 (0.2%)	1
Tibia fracture	1/606 (0.2%)	1
Upper limb fracture	1/606 (0.2%)	1
Nervous system disorders
Migraine	2/606 (0.3%)	2
Syncope	1/606 (0.2%)	1
Psychiatric disorders
Conversion disorder	1/606 (0.2%)	1
Major depression	1/606 (0.2%)	1
Suicidal ideation	2/606 (0.3%)	2
Suicide attempt	3/606 (0.5%)	3
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/606 (0.2%)	1
Vascular disorders
Peripheral ischemia	1/606 (0.2%)	1
Other (Not Including Serious) Adverse Events
	Rizatriptan
	Affected / at Risk (%)	# Events
Total	284/606 (46.9%)
Gastrointestinal disorders
Nausea	40/606 (6.6%)	77
General disorders
Fatigue	33/606 (5.4%)	111
Infections and infestations
Nasopharyngitis	47/606 (7.8%)	56
Upper respiratory tract infection	31/606 (5.1%)	33
Injury, poisoning and procedural complications
Accidental overdose	148/606 (24.4%)	216
Nervous system disorders
Dizziness	52/606 (8.6%)	94
Somnolence	44/606 (7.3%)	123

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Investigator agrees to delay publication of study results until Food and Drug Administration (FDA) grants pediatric exclusivity on the study drug. Investigator may publish results for his/her study site after primary publication of results of entire multicenter trial. Sponsor must be able to review all proposed results communications regarding study 60 days prior to submission for publication/presentation. Information identified by the Sponsor as confidential must be deleted prior to submission.