Migraine, Acute
Conditions
Brief summary
This Clinical Trial evaluates the Safety and Efficacy of Rizatriptan for the Acute Treatment of Migraine in Children and Adolescents.
Interventions
DRUGplacebo
For participants randomized to placebo in Stage 1: a single placebo ODT was to be taken within 30 minutes of onset of qualifying migraine.
DRUGrizatriptan
For participants randomized to rizatriptan in Stage 1: a single 5 or 10 mg rizatriptan orally disintegrating tablet (ODT) was to be taken within 30 minutes of onset of qualifying migraine (defined as a migraine of moderate or severe intensity). Rizatriptan dose administered was based on participant weight at Screening: those \<40 kg received 5 mg tablet, those ≥40 kg received 10 mg tablet.
Sponsors
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
6 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Patient weighs at least 20 kg (44 pounds) * Patient has had a history of migraine with or without aura \> 6 months with \>= 1 to \<= 8 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 * Patient is willing to stay awake for at least 2 hours after administration of the first dose of study medication * Patient has not experienced satisfactory relief from migraine pain with nonsteroidal anti-inflammatory drugs (NSAIDs) or N-acetyl-p-aminophenol (APAP) treatment * 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 or clinical evidence of cardiovascular problems or stroke * Patient has either demonstrated hypersensitivity to or experienced a serious adverse event in response to rizatriptan * 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, selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pain Freedom at 2 Hours Post Dose in Participants Between 12 and 17 Years of Age | 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 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pain Relief at 2 Hours Post Dose in Participants Between 12 and 17 Years of Age | 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. |
| Pain Freedom at 2 Hours Post Dose in Participants Between 6 and 17 Years of Age | 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 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. |
| Pain Relief at 2 Hours Post Dose in Participants Between 6 and 17 Years of Age | 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. |
Participant flow
Pre-assignment details
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
Participants by arm
| Arm | Count |
|---|---|
| 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. | 124 |
| 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. | 8 |
| 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. | 400 |
| 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. | 405 |
| 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). | 40 |
| Total | 977 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 2 | 0 |
| Overall Study | Not Treated: Adverse Event | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Not Treated: Lack of Qualifying Event | 248 | 13 | 0 | 0 | 0 |
| Overall Study | Not Treated: Lost to Follow-up | 53 | 4 | 7 | 5 | 0 |
| Overall Study | Not Treated: Physician Decision | 37 | 4 | 0 | 0 | 0 |
| Overall Study | Not Treated: Pregnancy | 3 | 0 | 0 | 0 | 0 |
| Overall Study | Not Treated: Protocol Violation | 3 | 0 | 0 | 0 | 0 |
| Overall Study | Not Treated: Withdrawal by Subject | 23 | 2 | 2 | 0 | 0 |
| Overall Study | Physician Decision | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 34 | 3 | 19 | 18 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 3 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo/NA | Rizatriptan/NA | Placebo/Rizatriptan | Placebo/Placebo | Rizatriptan/Placebo | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 12.7 years STANDARD_DEVIATION 2.9 | 13.4 years STANDARD_DEVIATION 2.1 | 13.0 years STANDARD_DEVIATION 2.9 | 13.1 years STANDARD_DEVIATION 2.9 | 13.1 years STANDARD_DEVIATION 3.4 | 13.0 years STANDARD_DEVIATION 2.9 |
| Sex: Female, Male Female | 61 Participants | 4 Participants | 227 Participants | 238 Participants | 20 Participants | 550 Participants |
| Sex: Female, Male Male | 63 Participants | 4 Participants | 173 Participants | 167 Participants | 20 Participants | 427 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 462 | 0 / 515 |
| serious Total, serious adverse events | 0 / 462 | 2 / 515 |
Outcome results
Primary
Pain Freedom at 2 Hours Post Dose in Participants Between 12 and 17 Years of Age
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rizatriptan | Pain Freedom at 2 Hours Post Dose in Participants Between 12 and 17 Years of Age | 2-hour pain freedom | 87 participants |
| Rizatriptan | Pain Freedom at 2 Hours Post Dose in Participants Between 12 and 17 Years of Age | No 2-hour pain freedom | 197 participants |
| Placebo | Pain Freedom at 2 Hours Post Dose in Participants Between 12 and 17 Years of Age | 2-hour pain freedom | 63 participants |
| Placebo | Pain Freedom at 2 Hours Post Dose in Participants Between 12 and 17 Years of Age | No 2-hour pain freedom | 223 participants |
Comparison: The comparison of rizatriptan versus placebo with respect to the primary outcome was conducted using a logistic regression model with factors for treatment, Stage 2 baseline pain severity (moderate or severe) and region (United States \[US\] or ex-US). Model-derived odds ratio and a two-sided p-value were provided. An odds ratio \>1 is in favor of the rizatriptan group.p-value: 0.02595% CI: [1.06, 2.26]Regression, Logistic
Secondary
Pain Freedom at 2 Hours Post Dose in Participants Between 6 and 17 Years of Age
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rizatriptan | Pain Freedom at 2 Hours Post Dose in Participants Between 6 and 17 Years of Age | 2-hour pain freedom | 126 participants |
| Rizatriptan | Pain Freedom at 2 Hours Post Dose in Participants Between 6 and 17 Years of Age | No 2-hour pain freedom | 256 participants |
| Placebo | Pain Freedom at 2 Hours Post Dose in Participants Between 6 and 17 Years of Age | 2-hour pain freedom | 94 participants |
| Placebo | Pain Freedom at 2 Hours Post Dose in Participants Between 6 and 17 Years of Age | No 2-hour pain freedom | 294 participants |
Comparison: The comparison of rizatriptan versus placebo with respect to pain freedom at 2 hours post Stage 2 dose for participants between 6 and 17 years of age was conducted using a logistic regression model with factors for treatment, Stage 2 baseline pain severity (moderate or severe), age (6 to 11 years old or 12 to 17 years old), and region (US or ex-US). Model-derived odds ratio and a two-sided p-value were provided. An odds ratio \>1 is in favor of the rizatriptan group.p-value: 0.0195% CI: [1.1, 2.1]Regression, Logistic
Secondary
Pain Relief at 2 Hours Post Dose in Participants Between 12 and 17 Years of Age
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rizatriptan | Pain Relief at 2 Hours Post Dose in Participants Between 12 and 17 Years of Age | 2-hour pain relief | 167 participants |
| Rizatriptan | Pain Relief at 2 Hours Post Dose in Participants Between 12 and 17 Years of Age | No 2-hour pain relief | 117 participants |
| Placebo | Pain Relief at 2 Hours Post Dose in Participants Between 12 and 17 Years of Age | 2-hour pain relief | 147 participants |
| Placebo | Pain Relief at 2 Hours Post Dose in Participants Between 12 and 17 Years of Age | No 2-hour pain relief | 139 participants |
Comparison: The comparison of rizatriptan versus placebo with respect to pain relief at 2 hours post Stage 2 dose for participants between 12 and 17 years of age was conducted using a logistic regression model with factors for treatment, Stage 2 baseline pain severity (moderate or severe) and region (US or ex-US). Model-derived odds ratio and a two-sided p-value were provided. An odds ratio \>1 is in favor of the rizatriptan group.p-value: 0.0895% CI: [0.96, 1.9]Regression, Logistic
Secondary
Pain Relief at 2 Hours Post Dose in Participants Between 6 and 17 Years of Age
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rizatriptan | Pain Relief at 2 Hours Post Dose in Participants Between 6 and 17 Years of Age | 2-hour pain relief | 220 participants |
| Rizatriptan | Pain Relief at 2 Hours Post Dose in Participants Between 6 and 17 Years of Age | No 2-hour pain relief | 162 participants |
| Placebo | Pain Relief at 2 Hours Post Dose in Participants Between 6 and 17 Years of Age | 2-hour pain relief | 204 participants |
| Placebo | Pain Relief at 2 Hours Post Dose in Participants Between 6 and 17 Years of Age | No 2-hour pain relief | 184 participants |
Comparison: The comparison of rizatriptan versus placebo with respect to pain relief at 2 hours post Stage 2 dose for participants between 6 and 17 years of age was conducted using a logistic regression model with factors for treatment, Stage 2 baseline pain severity (moderate or severe), age (6 to 11 years old or 12 to 17 years old), and region (US or ex-US). Model-derived odds ratio and a two-sided p-value were provided. An odds ratio \>1 is in favor of the rizatriptan group.p-value: 0.17895% CI: [0.91, 1.63]Regression, Logistic