Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Tolerability of Rizatriptan for Treatment of Acute Migraine in Children and Adolescents (MK-0462-082 AM7) (NCT NCT01001234)

Last Updated: 2024-05-07

Results Overview

Pain intensity was assessed using a 5-Face Pain Scale ranging from 1=no pain to 5=very bad pain. Pain freedom was defined as a reduction in severity from a rating of 3, 4 or 5 (moderate or severe pain) at the Stage 2 baseline (15 minutes post Stage 1 dose) to a rating of 1 (no pain) at 2 hours post Stage 2 dose. Missing data were imputed by carrying forward the preceding Stage 2 pain intensity values. Missing Stage 2 baseline values were imputed by carrying forward the Stage 1 baseline value, if available.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1382 participants

Primary outcome timeframe

2 hours post Stage 2 dose

Results posted on

2024-05-07

Participant Flow

Participants randomized to double-blind study medication (Stage 1 - placebo or rizatriptan in a 20:1 ratio) at the Screening visit were given study drug and administration instructions. If a participant had not treated a qualifying migraine attack within up to 2-4 months, he/she may have been discontinued from the study

Participant milestones

Participant milestones
Measure	Placebo/NA Stage 1 - Randomized to single placebo oral tablet to be taken within 30 minutes of onset of qualifying migraine / Stage 2 - If Stage 1 dose was taken and participant was Responder (mild or no pain 15 minutes after dose), no further study medication was to be administered.	Rizatriptan/NA Stage 1 - Randomized to single rizatriptan 5 or 10 mg oral tablet to be taken within 30 minutes of onset of qualifying migraine / Stage 2 - If Stage 1 dose was taken and participant was Responder (mild or no pain 15 minutes after dose), no further study medication was to be administered.	Placebo/Rizatriptan Stage 1 - Randomized to single placebo oral tablet to be taken within 30 minutes of onset of qualifying migraine / Stage 2 - If Stage 1 dose was taken and participant was Non-Responder (moderate or severe pain 15 minutes after dose), Stage 2 randomization was to occur and participants in this reporting group received single rizatriptan 5 or 10 mg oral tablet. Stage 2 dose was administered approximately 15 minutes post Stage 1 dose, to treat same qualifying migraine treated in Stage 1. Stage 2 randomization was in a ratio of 1:1 rizatriptan:placebo.	Placebo/Placebo Stage 1 - Randomized to single placebo oral tablet to be taken within 30 minutes of onset of qualifying migraine / Stage 2 - If Stage 1 dose was taken and participant was Non-Responder (moderate or severe pain 15 minutes after dose), Stage 2 randomization was to occur and participants in this reporting group received single placebo oral tablet. Stage 2 dose was administered approximately 15 minutes post Stage 1 dose, to treat same qualifying migraine treated in Stage 1. Stage 2 randomization was in a ratio of 1:1 rizatriptan:placebo.	Rizatriptan/Placebo Stage 1 - Randomized to single rizatriptan 5 or 10 mg oral tablet to be taken within 30 minutes of onset of qualifying migraine / Stage 2 - If Stage 1 dose was taken and participant was Non-Responder (moderate or severe pain 15 minutes after dose), allocated to receive single placebo oral tablet in Stage 2 to treat same qualifying migraine treated in Stage 1 (Stage 2 dose to be administered 15 minutes post Stage 1 dose).
Overall Study STARTED	492	31	409	410	40
Overall Study Particpants Treated	124	8	400	405	40
Overall Study Participants Not Treated	368	23	9	5	0
Overall Study COMPLETED	87	5	377	385	40
Overall Study NOT COMPLETED	405	26	32	25	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo/NA Stage 1 - Randomized to single placebo oral tablet to be taken within 30 minutes of onset of qualifying migraine / Stage 2 - If Stage 1 dose was taken and participant was Responder (mild or no pain 15 minutes after dose), no further study medication was to be administered.	Rizatriptan/NA Stage 1 - Randomized to single rizatriptan 5 or 10 mg oral tablet to be taken within 30 minutes of onset of qualifying migraine / Stage 2 - If Stage 1 dose was taken and participant was Responder (mild or no pain 15 minutes after dose), no further study medication was to be administered.	Placebo/Rizatriptan Stage 1 - Randomized to single placebo oral tablet to be taken within 30 minutes of onset of qualifying migraine / Stage 2 - If Stage 1 dose was taken and participant was Non-Responder (moderate or severe pain 15 minutes after dose), Stage 2 randomization was to occur and participants in this reporting group received single rizatriptan 5 or 10 mg oral tablet. Stage 2 dose was administered approximately 15 minutes post Stage 1 dose, to treat same qualifying migraine treated in Stage 1. Stage 2 randomization was in a ratio of 1:1 rizatriptan:placebo.	Placebo/Placebo Stage 1 - Randomized to single placebo oral tablet to be taken within 30 minutes of onset of qualifying migraine / Stage 2 - If Stage 1 dose was taken and participant was Non-Responder (moderate or severe pain 15 minutes after dose), Stage 2 randomization was to occur and participants in this reporting group received single placebo oral tablet. Stage 2 dose was administered approximately 15 minutes post Stage 1 dose, to treat same qualifying migraine treated in Stage 1. Stage 2 randomization was in a ratio of 1:1 rizatriptan:placebo.
Overall Study Withdrawal by Subject	2	0	3	0
Overall Study Protocol Violation	34	3	19	18
Overall Study Lost to Follow-up	0	0	1	2
Overall Study Physician Decision	1	0	0	0
Overall Study Not Treated: Adverse Event	1	0	0	0
Overall Study Not Treated: Withdrawal by Subject	23	2	2	0
Overall Study Not Treated: Protocol Violation	3	0	0	0
Overall Study Not Treated: Lost to Follow-up	53	4	7	5
Overall Study Not Treated: Pregnancy	3	0	0	0
Overall Study Not Treated: Physician Decision	37	4	0	0
Overall Study Not Treated: Lack of Qualifying Event	248	13	0	0

Baseline Characteristics

A Study to Evaluate the Efficacy and Tolerability of Rizatriptan for Treatment of Acute Migraine in Children and Adolescents (MK-0462-082 AM7)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo/NA n=124 Participants Stage 1 - Randomized to single placebo oral tablet to be taken within 30 minutes of onset of qualifying migraine / Stage 2 - If Stage 1 dose was taken and participant was Responder (mild or no pain 15 minutes after dose), no further study medication was to be administered.	Rizatriptan/NA n=8 Participants Stage 1 - Randomized to single rizatriptan 5 or 10 mg oral tablet to be taken within 30 minutes of onset of qualifying migraine / Stage 2 - If Stage 1 dose was taken and participant was Responder (mild or no pain 15 minutes after dose), no further study medication was to be administered.	Placebo/Rizatriptan n=400 Participants Stage 1 - Randomized to single placebo oral tablet to be taken within 30 minutes of onset of qualifying migraine / Stage 2 - If Stage 1 dose was taken and participant was Non-Responder (moderate or severe pain 15 minutes after dose), Stage 2 randomization was to occur and participants in this reporting group received single rizatriptan 5 or 10 mg oral tablet. Stage 2 dose was administered approximately 15 minutes post Stage 1 dose, to treat same qualifying migraine treated in Stage 1. Stage 2 randomization was in a ratio of 1:1 rizatriptan:placebo.	Placebo/Placebo n=405 Participants Stage 1 - Randomized to single placebo oral tablet to be taken within 30 minutes of onset of qualifying migraine / Stage 2 - If Stage 1 dose was taken and participant was Non-Responder (moderate or severe pain 15 minutes after dose), Stage 2 randomization was to occur and participants in this reporting group received single placebo oral tablet. Stage 2 dose was administered approximately 15 minutes post Stage 1 dose, to treat same qualifying migraine treated in Stage 1. Stage 2 randomization was in a ratio of 1:1 rizatriptan:placebo.	Rizatriptan/Placebo n=40 Participants Stage 1 - Randomized to single rizatriptan 5 or 10 mg oral tablet to be taken within 30 minutes of onset of qualifying migraine / Stage 2 - If Stage 1 dose was taken and participant was Non-Responder (moderate or severe pain 15 minutes after dose), allocated to receive single placebo oral tablet in Stage 2 to treat same qualifying migraine treated in Stage 1 (Stage 2 dose to be administered 15 minutes post Stage 1 dose).	Total n=977 Participants Total of all reporting groups
Age, Continuous	12.7 years STANDARD_DEVIATION 2.9 • n=5 Participants	13.4 years STANDARD_DEVIATION 2.1 • n=7 Participants	13.0 years STANDARD_DEVIATION 2.9 • n=5 Participants	13.1 years STANDARD_DEVIATION 2.9 • n=4 Participants	13.1 years STANDARD_DEVIATION 3.4 • n=21 Participants	13.0 years STANDARD_DEVIATION 2.9 • n=10 Participants
Sex: Female, Male Female	61 Participants n=5 Participants	4 Participants n=7 Participants	227 Participants n=5 Participants	238 Participants n=4 Participants	20 Participants n=21 Participants	550 Participants n=10 Participants
Sex: Female, Male Male	63 Participants n=5 Participants	4 Participants n=7 Participants	173 Participants n=5 Participants	167 Participants n=4 Participants	20 Participants n=21 Participants	427 Participants n=10 Participants

PRIMARY outcome

Timeframe: 2 hours post Stage 2 dose

Population: Includes participants who did not respond to placebo in Stage 1, were randomized to and took Stage 2 study drug and had both Stage 2 baseline migraine severity (moderate or severe) and at least one post Stage 2 dose efficacy measurement prior to or including the 2 hour post dose time point. Those randomized to rizatriptan in Stage 1 were excluded.

Outcome measures

Outcome measures
Measure	Rizatriptan n=284 Participants Participants randomized to rizatriptan in Stage 2	Placebo n=286 Participants Participants randomized to placebo in Stage 2
Pain Freedom at 2 Hours Post Dose in Participants Between 12 and 17 Years of Age 2-hour pain freedom	87 participants Interval 25.3 to 36.4	63 participants Interval 17.4 to 27.3
Pain Freedom at 2 Hours Post Dose in Participants Between 12 and 17 Years of Age No 2-hour pain freedom	197 participants	223 participants

SECONDARY outcome

Timeframe: 2 hours post Stage 2 dose

Pain intensity was assessed using a 5-Face Pain Scale ranging from 1=no pain to 5=very bad pain. Pain relief was defined as a reduction in severity from a rating of 3, 4 or 5 (moderate or severe pain) at the Stage 2 baseline (15 minutes post Stage 1 dose) to a rating of 2 or 1 (mild or no pain) at 2 hours post Stage 2 dose. Missing data were imputed by carrying forward the preceding Stage 2 pain intensity values. Missing Stage 2 baseline values were imputed by carrying forward the Stage 1 baseline value, if available.

Outcome measures

Outcome measures
Measure	Rizatriptan n=284 Participants Participants randomized to rizatriptan in Stage 2	Placebo n=286 Participants Participants randomized to placebo in Stage 2
Pain Relief at 2 Hours Post Dose in Participants Between 12 and 17 Years of Age 2-hour pain relief	167 participants Interval 52.8 to 64.6	147 participants Interval 45.4 to 57.3
Pain Relief at 2 Hours Post Dose in Participants Between 12 and 17 Years of Age No 2-hour pain relief	117 participants	139 participants

SECONDARY outcome

Timeframe: 2 hours post Stage 2 dose

Outcome measures

Outcome measures
Measure	Rizatriptan n=382 Participants Participants randomized to rizatriptan in Stage 2	Placebo n=388 Participants Participants randomized to placebo in Stage 2
Pain Freedom at 2 Hours Post Dose in Participants Between 6 and 17 Years of Age 2-hour pain freedom	126 participants Interval 28.3 to 37.9	94 participants Interval 20.0 to 28.8
Pain Freedom at 2 Hours Post Dose in Participants Between 6 and 17 Years of Age No 2-hour pain freedom	256 participants	294 participants

SECONDARY outcome

Timeframe: 2 hours post Stage 2 dose

Outcome measures

Outcome measures
Measure	Rizatriptan n=382 Participants Participants randomized to rizatriptan in Stage 2	Placebo n=388 Participants Participants randomized to placebo in Stage 2
Pain Relief at 2 Hours Post Dose in Participants Between 6 and 17 Years of Age 2-hour pain relief	220 participants Interval 52.5 to 62.6	204 participants Interval 47.5 to 57.6
Pain Relief at 2 Hours Post Dose in Participants Between 6 and 17 Years of Age No 2-hour pain relief	162 participants	184 participants

Adverse Events

Rizatriptan

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Rizatriptan n=462 participants at risk Participants who took any rizatriptan during the study (Stage 1 or 2)	Placebo n=515 participants at risk Participants who took only placebo during the study
Infections and infestations Enterobacter bacteremia	0.00% 0/462 • Up to 14 days post dose Includes all randomized participants who received at least one dose of study drug (i.e., participants who only took study drug in Stage 1 were also included). Participants were included in the treatment group corresponding to the study treatment they actually received, with active treatment taking precedence over placebo treatment.	0.19% 1/515 • Number of events 1 • Up to 14 days post dose Includes all randomized participants who received at least one dose of study drug (i.e., participants who only took study drug in Stage 1 were also included). Participants were included in the treatment group corresponding to the study treatment they actually received, with active treatment taking precedence over placebo treatment.
Nervous system disorders Migraine	0.00% 0/462 • Up to 14 days post dose Includes all randomized participants who received at least one dose of study drug (i.e., participants who only took study drug in Stage 1 were also included). Participants were included in the treatment group corresponding to the study treatment they actually received, with active treatment taking precedence over placebo treatment.	0.19% 1/515 • Number of events 1 • Up to 14 days post dose Includes all randomized participants who received at least one dose of study drug (i.e., participants who only took study drug in Stage 1 were also included). Participants were included in the treatment group corresponding to the study treatment they actually received, with active treatment taking precedence over placebo treatment.

Other adverse events

Adverse event data not reported

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