Migraine Disorders
Conditions
Brief summary
A study to assess the safety, tolerability, and single dose pharmacokinetics of a marketed drug in pediatric subjects with migraines. After completion of a portion of the study (Panels A and B), a regulatory agency issued an amended request that the 12-17 year old age group studied should include a similar number of male and female subjects. Therefore, the study was amended to add an additional panel of subjects (Panel C) to ensure gender balance specifically in this age group.
Interventions
DRUGrizatriptan benzoate (5 mg)
A single dose of rizatriptan 5 mg administered on Day 1.
DRUGrizatriptan benzoate (10 mg)
A single dose of rizatriptan 10 mg administered on Day 1.
DRUGRizatriptan 5 mg Placebo
A single dose of rizatriptan 5 mg placebo administered on Day 1.
DRUGRizatriptan 10 mg Placebo
A single dose of rizatriptan 10 mg placebo administered on Day 1.
Sponsors
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
6 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Panel A and B: Male and female subjects (non-smokers) ages 6 to 17 with a history of migraines * Panel C: Male subjects (non-smokers) ages 12 to 17 with a history of migraines * Subject has a history of migraine headaches, and is not experiencing a migraine on the day of study drug administration
Exclusion criteria
* Subject has no history of migraine headaches * Taking medications that are monoamine oxidase inhibitors (MAOI) and selective serotonin reuptake inhibitors (SSRI) * Subject has a condition which, in the opinion of the investigator, may interfere with optimal participation in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of Single Doses of Rizatriptan in Pediatric Migraineurs | 24 Hours | All adverse experiences spontaneously reported by subject and/or observed by investigator and repeated clinical evaluation of physical examinations, vital signs, 12-lead ECG (electrocardiogram) and laboratory safety tests (hematology/blood chemistry/urinalysis) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Preliminary Pharmacokinetic Data Following Single Dose Administration of Rizatriptan- Area Under the Curve (AUC(0-∞)) | 24 Hours | Preliminary pharmacokinetics data; Area Under the Curve (AUC(0-∞)); i.e., area under the concentration-time plot |
| Preliminary Pharmacokinetic Data Following Single Dose Administration of Rizatriptan - Maximum Concentration (Cmax) | 24 Hours | Preliminary pharmacokinetics data; Maximum concentration (Cmax); i.e, highest concentration of drug achieved |
| Preliminary Pharmacokinetic Data Following Single Dose Administration of Rizatriptan - Time to Maximum Concentration (Tmax) | 24 Hours | Preliminary pharmacokinetics data; Time to maximum concentration (Tmax); i.e., amount of time required to reach maximum concentration |
| Preliminary Pharmacokinetic Data Following Single Dose Administration of Rizatriptan - Apparent Half-life (Apparent t½) | 24 Hours | Preliminary pharmacokinetics data; Apparent half-life (t½) |
Participant flow
Recruitment details
Panel C was added to the study by amendment after enrollment of Panels A and B were completed.
Participants by arm
| Arm | Count |
|---|---|
| Panel A Includes the participants from the 5 mg rizatriptan group (9) and the matching placebo group (3) | 12 |
| Panel B Includes the participants from the 10 mg rizatriptan group (10) and the matching placebo group (3) | 13 |
| Panel C Includes the participants who received 5 mg rizatriptan (n=1), 10 mg rizatriptan (n=4), and the matching placebo (n=1) | 6 |
| Total | 31 |
Baseline characteristics
| Characteristic | Panel A | Panel B | Panel C | Total |
|---|---|---|---|---|
| Age, Customized Ages 12 to 17 | 1 years | 11 years | 6 years | 18 years |
| Age, Customized Ages 6 to <12 | 11 years 1.44 | 2 years 2.14 | 0 years | 13 years |
| Sex: Female, Male Female | 5 Participants | 8 Participants | 0 Participants | 13 Participants |
| Sex: Female, Male Male | 7 Participants | 5 Participants | 6 Participants | 18 Participants |
| Weight 20-39 kg | 12 participants | 0 participants | 1 participants | 13 participants |
| Weight ≥ 40 kg | 0 participants | 13 participants | 5 participants | 18 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 10 | 7 / 14 | 3 / 7 |
| serious Total, serious adverse events | 0 / 10 | 0 / 14 | 0 / 7 |
Outcome results
Primary
Safety and Tolerability of Single Doses of Rizatriptan in Pediatric Migraineurs
All adverse experiences spontaneously reported by subject and/or observed by investigator and repeated clinical evaluation of physical examinations, vital signs, 12-lead ECG (electrocardiogram) and laboratory safety tests (hematology/blood chemistry/urinalysis)
Time frame: 24 Hours
Population: All Subjects as Treated- All subjects who received at least one dose of the investigational drug was used for assessments of safety and tolerability.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rizatriptan 5 mg | Safety and Tolerability of Single Doses of Rizatriptan in Pediatric Migraineurs | No Adverse Events Reported | 7 Participants |
| Rizatriptan 5 mg | Safety and Tolerability of Single Doses of Rizatriptan in Pediatric Migraineurs | Non-Serious Adverse Events | 3 Participants |
| Rizatriptan 5 mg | Safety and Tolerability of Single Doses of Rizatriptan in Pediatric Migraineurs | Serious Adverse Events | 0 Participants |
| Rizatriptan 10 mg | Safety and Tolerability of Single Doses of Rizatriptan in Pediatric Migraineurs | No Adverse Events Reported | 7 Participants |
| Rizatriptan 10 mg | Safety and Tolerability of Single Doses of Rizatriptan in Pediatric Migraineurs | Serious Adverse Events | 0 Participants |
| Rizatriptan 10 mg | Safety and Tolerability of Single Doses of Rizatriptan in Pediatric Migraineurs | Non-Serious Adverse Events | 7 Participants |
| Placebo | Safety and Tolerability of Single Doses of Rizatriptan in Pediatric Migraineurs | No Adverse Events Reported | 4 Participants |
| Placebo | Safety and Tolerability of Single Doses of Rizatriptan in Pediatric Migraineurs | Non-Serious Adverse Events | 3 Participants |
| Placebo | Safety and Tolerability of Single Doses of Rizatriptan in Pediatric Migraineurs | Serious Adverse Events | 0 Participants |
Secondary
Preliminary Pharmacokinetic Data Following Single Dose Administration of Rizatriptan - Apparent Half-life (Apparent t½)
Preliminary pharmacokinetics data; Apparent half-life (t½)
Time frame: 24 Hours
Population: Per Protocol-The set of data generated by the subset of subjects who comply with the protocol sufficiently to ensure that these data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers exposure to treatment, availability of measurements and absence of major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rizatriptan 5 mg | Preliminary Pharmacokinetic Data Following Single Dose Administration of Rizatriptan - Apparent Half-life (Apparent t½) | 1.3 Hours | Standard Deviation 0.1 |
| Rizatriptan 10 mg | Preliminary Pharmacokinetic Data Following Single Dose Administration of Rizatriptan - Apparent Half-life (Apparent t½) | 1.6 Hours | Standard Deviation 0.2 |
| Placebo | Preliminary Pharmacokinetic Data Following Single Dose Administration of Rizatriptan - Apparent Half-life (Apparent t½) | 1.6 Hours | Standard Deviation 0.4 |
Secondary
Preliminary Pharmacokinetic Data Following Single Dose Administration of Rizatriptan- Area Under the Curve (AUC(0-∞))
Preliminary pharmacokinetics data; Area Under the Curve (AUC(0-∞)); i.e., area under the concentration-time plot
Time frame: 24 Hours
Population: Per Protocol-The set of data generated by the subset of subjects who comply with the protocol sufficiently to ensure that these data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers exposure to treatment, availability of measurements and absence of major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rizatriptan 5 mg | Preliminary Pharmacokinetic Data Following Single Dose Administration of Rizatriptan- Area Under the Curve (AUC(0-∞)) | 59.4 ng hr/mL | Standard Deviation 11.5 |
| Rizatriptan 10 mg | Preliminary Pharmacokinetic Data Following Single Dose Administration of Rizatriptan- Area Under the Curve (AUC(0-∞)) | 84.0 ng hr/mL | Standard Deviation 19.8 |
| Placebo | Preliminary Pharmacokinetic Data Following Single Dose Administration of Rizatriptan- Area Under the Curve (AUC(0-∞)) | 67.93 ng hr/mL | Standard Deviation 25.17 |
Secondary
Preliminary Pharmacokinetic Data Following Single Dose Administration of Rizatriptan - Maximum Concentration (Cmax)
Preliminary pharmacokinetics data; Maximum concentration (Cmax); i.e, highest concentration of drug achieved
Time frame: 24 Hours
Population: Per Protocol-The set of data generated by the subset of subjects who comply with the protocol sufficiently to ensure that these data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers exposure to treatment, availability of measurements and absence of major protocol violations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rizatriptan 5 mg | Preliminary Pharmacokinetic Data Following Single Dose Administration of Rizatriptan - Maximum Concentration (Cmax) | 24.6 ng/mL | Standard Deviation 7.2 |
| Rizatriptan 10 mg | Preliminary Pharmacokinetic Data Following Single Dose Administration of Rizatriptan - Maximum Concentration (Cmax) | 25.0 ng/mL | Standard Deviation 8.1 |
| Placebo | Preliminary Pharmacokinetic Data Following Single Dose Administration of Rizatriptan - Maximum Concentration (Cmax) | 18.4 ng/mL | Standard Deviation 5.5 |
Secondary
Preliminary Pharmacokinetic Data Following Single Dose Administration of Rizatriptan - Time to Maximum Concentration (Tmax)
Preliminary pharmacokinetics data; Time to maximum concentration (Tmax); i.e., amount of time required to reach maximum concentration
Time frame: 24 Hours
Population: Per Protocol-The set of data generated by the subset of subjects who comply with the protocol sufficiently to ensure that these data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance covers exposure to treatment, availability of measurements and absence of major protocol violations.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rizatriptan 5 mg | Preliminary Pharmacokinetic Data Following Single Dose Administration of Rizatriptan - Time to Maximum Concentration (Tmax) | 1.0 Hours |
| Rizatriptan 10 mg | Preliminary Pharmacokinetic Data Following Single Dose Administration of Rizatriptan - Time to Maximum Concentration (Tmax) | 1.5 Hours |
| Placebo | Preliminary Pharmacokinetic Data Following Single Dose Administration of Rizatriptan - Time to Maximum Concentration (Tmax) | 1.3 Hours |