Trial Outcomes & Findings for 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) (NCT NCT01004263)

Last Updated: 2024-04-22

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

674 participants

Primary outcome timeframe

Up to 24 hours post dose

Results posted on

2024-04-22

Participant Flow

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

Participant milestones

Participant milestones
Measure	Rizatriptan 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 Study STARTED	606
Overall Study COMPLETED	427
Overall Study NOT COMPLETED	179

Reasons for withdrawal

Reasons for withdrawal
Measure	Rizatriptan 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 Study Adverse Event	15
Overall Study Withdrawal by Subject	58
Overall Study Protocol Violation	10
Overall Study Lost to Follow-up	64
Overall Study Lack of Efficacy	13
Overall Study Pregnancy	2
Overall Study Physician Decision	15
Overall Study Lack of Qualifying Event	2

Baseline Characteristics

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)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Rizatriptan n=606 Participants 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).
Age, Continuous	14.7 years STANDARD_DEVIATION 1.7 • n=5 Participants
Sex: Female, Male Female	372 Participants n=5 Participants
Sex: Female, Male Male	234 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 24 hours post dose

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

Outcome measures

Outcome measures
Measure	Rizatriptan n=606 Participants 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).
Number of Participants With Adverse Events (AEs) Within 24 Hours Post Any Dose	322 participants

PRIMARY outcome

Timeframe: Up to 14 days post dose

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

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.

Outcome measures

Outcome measures
Measure	Rizatriptan n=606 Participants 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).
Number of Participants With AEs Within 14 Days Post Any Dose	400 participants

PRIMARY outcome

Timeframe: Up to 24 hours post dose

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

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.

Outcome measures

Outcome measures
Measure	Rizatriptan n=606 Participants 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).
Number of Participants Discontinued From Study Due to AEs Occurring Within 24 Hours Post Dose	4 participants

PRIMARY outcome

Timeframe: Up to 14 days post dose

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

Outcome measures

Outcome measures
Measure	Rizatriptan n=606 Participants 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).
Number of Participants Discontinued From Study Due to AEs Occurring Within 14 Days Post Dose	14 participants

SECONDARY outcome

Timeframe: 2 hours post dose

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

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.

Outcome measures

Outcome measures
Measure	Rizatriptan n=603 Participants 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).
Percentage of Participant's Migraine Attacks With Pain Freedom at 2 Hours Post Dose	46.3 percentage of participant's attacks Standard Deviation 31.9

Adverse Events

Rizatriptan

Serious events: 22 serious events

Other events: 284 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Rizatriptan n=606 participants at risk 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).
Cardiac disorders Sinus bradycardia	0.17% 1/606 • Number of events 1 • Up to 12 months after start of study drug administration AE tables include all enrolled participants who administered at least one dose of study medication
Gastrointestinal disorders Abdominal discomfort	0.33% 2/606 • Number of events 2 • Up to 12 months after start of study drug administration AE tables include all enrolled participants who administered at least one dose of study medication
General disorders Fatigue	0.17% 1/606 • Number of events 2 • Up to 12 months after start of study drug administration AE tables include all enrolled participants who administered at least one dose of study medication
Infections and infestations Appendicitis	0.33% 2/606 • Number of events 2 • Up to 12 months after start of study drug administration AE tables include all enrolled participants who administered at least one dose of study medication
Infections and infestations Gastroenteritis	0.17% 1/606 • Number of events 1 • Up to 12 months after start of study drug administration AE tables include all enrolled participants who administered at least one dose of study medication
Infections and infestations Viral infection	0.17% 1/606 • Number of events 1 • Up to 12 months after start of study drug administration AE tables include all enrolled participants who administered at least one dose of study medication
Injury, poisoning and procedural complications Fibula fracture	0.17% 1/606 • Number of events 1 • Up to 12 months after start of study drug administration AE tables include all enrolled participants who administered at least one dose of study medication
Injury, poisoning and procedural complications Road traffic accident	0.17% 1/606 • Number of events 1 • Up to 12 months after start of study drug administration AE tables include all enrolled participants who administered at least one dose of study medication
Injury, poisoning and procedural complications Tibia fracture	0.17% 1/606 • Number of events 1 • Up to 12 months after start of study drug administration AE tables include all enrolled participants who administered at least one dose of study medication
Injury, poisoning and procedural complications Upper limb fracture	0.17% 1/606 • Number of events 1 • Up to 12 months after start of study drug administration AE tables include all enrolled participants who administered at least one dose of study medication
Nervous system disorders Migraine	0.33% 2/606 • Number of events 2 • Up to 12 months after start of study drug administration AE tables include all enrolled participants who administered at least one dose of study medication
Nervous system disorders Syncope	0.17% 1/606 • Number of events 1 • Up to 12 months after start of study drug administration AE tables include all enrolled participants who administered at least one dose of study medication
Psychiatric disorders Conversion disorder	0.17% 1/606 • Number of events 1 • Up to 12 months after start of study drug administration AE tables include all enrolled participants who administered at least one dose of study medication
Psychiatric disorders Major depression	0.17% 1/606 • Number of events 1 • Up to 12 months after start of study drug administration AE tables include all enrolled participants who administered at least one dose of study medication
Psychiatric disorders Suicidal ideation	0.33% 2/606 • Number of events 2 • Up to 12 months after start of study drug administration AE tables include all enrolled participants who administered at least one dose of study medication
Psychiatric disorders Suicide attempt	0.50% 3/606 • Number of events 3 • Up to 12 months after start of study drug administration AE tables include all enrolled participants who administered at least one dose of study medication
Respiratory, thoracic and mediastinal disorders Dyspnea	0.17% 1/606 • Number of events 1 • Up to 12 months after start of study drug administration AE tables include all enrolled participants who administered at least one dose of study medication
Vascular disorders Peripheral ischemia	0.17% 1/606 • Number of events 1 • Up to 12 months after start of study drug administration AE tables include all enrolled participants who administered at least one dose of study medication

Other adverse events

Other adverse events
Measure	Rizatriptan n=606 participants at risk 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).
Gastrointestinal disorders Nausea	6.6% 40/606 • Number of events 77 • Up to 12 months after start of study drug administration AE tables include all enrolled participants who administered at least one dose of study medication
General disorders Fatigue	5.4% 33/606 • Number of events 111 • Up to 12 months after start of study drug administration AE tables include all enrolled participants who administered at least one dose of study medication
Infections and infestations Nasopharyngitis	7.8% 47/606 • Number of events 56 • Up to 12 months after start of study drug administration AE tables include all enrolled participants who administered at least one dose of study medication
Infections and infestations Upper respiratory tract infection	5.1% 31/606 • Number of events 33 • Up to 12 months after start of study drug administration AE tables include all enrolled participants who administered at least one dose of study medication
Injury, poisoning and procedural complications Accidental overdose	24.4% 148/606 • Number of events 216 • Up to 12 months after start of study drug administration AE tables include all enrolled participants who administered at least one dose of study medication
Nervous system disorders Dizziness	8.6% 52/606 • Number of events 94 • Up to 12 months after start of study drug administration AE tables include all enrolled participants who administered at least one dose of study medication
Nervous system disorders Somnolence	7.3% 44/606 • Number of events 123 • Up to 12 months after start of study drug administration AE tables include all enrolled participants who administered at least one dose of study medication

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER