Migraine
Conditions
Brief summary
This study will provide additional efficacy data for rizatriptan when used for an acute migraine attack in patients already taking topiramate for migraine prophylaxis.
Interventions
rizatriptan 10 mg Orally Disintegrating Tablet (ODT) orally for a moderate or severe migraine attack
DRUGComparator: placebo
Placebo to rizatriptan 10 mg ODT orally for a moderate or severe migraine attack
Sponsors
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient has a history of migraine with or without aura for more than one year, with between 2 and 8 moderate to severe attacks per month * Patient is currently taking at least 50 mg topiramate daily for migraine prophylaxis * Patient can distinguish between migraine and other types of headache * Patient agrees to remain abstinent or use effective birth control during the study
Exclusion criteria
* Patient is pregnant or breast-feeding * Patient has a history of mostly mild migraines or migraines that resolve within 2 hours * Patient has more than 15 headache-days per month or has taken medication for acute headache on more than 10 days per month in the 3 months prior to screening. * Patient was \> 50 years old at age of migraine onset * Patient has history of heart disease * Patient has uncontrolled hypertension * Patient has had cancer within 5 years of screening (excepting certain skin and cervical cancers) * Patient has started taking Selective Serotonin Reuptake Inhibitors (SSRIs) or Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) or has changed doses within 3 months of screening * Patient is taking more than one other migraine prophylactic medication * Patient has repeatedly failed to respond to or tolerate rizatriptan
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pain Relief (PR) | 2 hours post dose | Pain severity was rated by the participants in a paper diary. Pain severity rating scale : 0 (no pain), 1 (mild pain), 2 (moderate pain), or 3 (severe pain). Pain relief (PR) is defined as a reduction in headache severity from Grade 3/2 at baseline to Grade 1/0 post dose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Sustained Pain Relief (SPR) | 2 - 24 hours post dose | 24-hour sustained pain relief (defined as pain relief at 2 hours post dose, with no administration of any rescue medication and with no occurrence of a moderate/severe headache during the respective period after dosing with the blinded study medication. |
| Pain Freedom (PF) | 2 hours post dose | Headache pain severity, relative to the administration of study medication, was rated by the participants in a paper diary. Pain severity rating scale: 0 (no pain), 1 (mild pain), 2 (moderate pain), or 3 (severe pain). Pain freedom (PF) is defined as a reduction in headache severity from Grade 3/2 at baseline to Grade 0 (no pain) post dose. |
| Normal Rating of Functional Disability (NRFD) | 2 hours post dose | Level of functional disability was assessed on a paper diary by the participants. Level of functional disability was rated as: normal, mildly impaired, severely impaired, or unable to do activities, requires bedrest. Functional disability ratings was dichotomized to Normal and Not Normal (mildly impaired, severely impaired, or unable to do activities, requires bedrest) for analysis. |
| Treatment Satisfaction (TS) | 24 hours post dose | Patient satisfaction was assessed on a paper diary by the participants. Level of satisfaction was rated as: completely satisfied, very satisfied, somewhat satisfied, neither satisfied nor dissatisfied, somewhat dissatisfied, very dissatisfied, or completely dissatisfied. The overall 24-hour assessment of study medication was dichotomized to Satisfaction (completely satisfied, very satisfied, somewhat satisfied) and Non-satisfaction (neither satisfied nor dissatisfied, somewhat dissatisfied, very dissatisfied, or completely dissatisfied) for analysis. |
Participant flow
Recruitment details
First Patient In: 26 March 2009; Last Patient Last Visit: 22 October 2009. 17 Outpatient centers worldwide (10 United States; 2 Canada; 2 Spain, 2 Italy; 1 France)
Pre-assignment details
Participants were assessed, using the protocol inclusion and exclusion criteria, at Visit 1, and if eligible, were randomized at the same visit.
Participants by arm
| Arm | Count |
|---|---|
| Rizatriptan / Rizatriptan / Placebo First migraine treated with Rizatriptan 10 mg Orally Disintegrating Tablet (ODT); second migraine treated with Rizatriptan 10 mg Orally Disintegrating Tablet (ODT); third migraine treated with Placebo | 36 |
| Rizatriptan / Placebo / Rizatriptan First migraine treated with Rizatriptan 10 mg Orally Disintegrating Tablet (ODT); second migraine treated with Placebo; third migraine treated with Rizatriptan 10 mg Orally Disintegrating Tablet (ODT) | 36 |
| Placebo / Rizatriptan / Rizatriptan First migraine treated with Placebo; second migraine treated with Rizatriptan 10 mg Orally Disintegrating Tablet (ODT); third migraine treated with Rizatriptan 10 mg Orally Disintegrating Tablet (ODT) | 36 |
| Total | 108 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lack of Qualifying Event | 4 | 2 | 2 |
| Overall Study | Lost to Follow-up | 0 | 0 | 2 |
| Overall Study | Physician Decision | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 1 | 1 |
Baseline characteristics
| Characteristic | Rizatriptan / Rizatriptan / Placebo | Rizatriptan / Placebo / Rizatriptan | Placebo / Rizatriptan / Rizatriptan | Total |
|---|---|---|---|---|
| Age, Continuous | 48.3 years STANDARD_DEVIATION 12 | 43.9 years STANDARD_DEVIATION 10.8 | 40.0 years STANDARD_DEVIATION 11.6 | 44.0 years STANDARD_DEVIATION 11.9 |
| Ethnicity Origin Black | 0 participants | 1 participants | 0 participants | 1 participants |
| Ethnicity Origin White | 36 participants | 35 participants | 36 participants | 107 participants |
| Racial Origin Hispanic or Latino | 11 participants | 9 participants | 10 participants | 30 participants |
| Racial Origin Not Hispanic or Latino | 25 participants | 27 participants | 26 participants | 78 participants |
| Sex: Female, Male Female | 32 Participants | 33 Participants | 34 Participants | 99 Participants |
| Sex: Female, Male Male | 4 Participants | 3 Participants | 2 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 16 / 101 | 3 / 94 |
| serious Total, serious adverse events | 0 / 101 | 0 / 94 |
Outcome results
Primary
Pain Relief (PR)
Pain severity was rated by the participants in a paper diary. Pain severity rating scale : 0 (no pain), 1 (mild pain), 2 (moderate pain), or 3 (severe pain). Pain relief (PR) is defined as a reduction in headache severity from Grade 3/2 at baseline to Grade 1/0 post dose.
Time frame: 2 hours post dose
Population: Full Analysis Set, which included all randomized participants who had at least one evaluable attack. To be considered an evaluable attack, the participant must have administered study treatment for this attack and have both a baseline severity measurement and at least one post-dose efficacy measurement at or prior to the 2-hour time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rizatriptan | Pain Relief (PR) | Resulting in PR at 2 hours post dose | 105 Attacks |
| Rizatriptan | Pain Relief (PR) | Not resulting in PR at 2 hours post dose | 88 Attacks |
| Placebo | Pain Relief (PR) | Resulting in PR at 2 hours post dose | 21 Attacks |
| Placebo | Pain Relief (PR) | Not resulting in PR at 2 hours post dose | 72 Attacks |
p-value: <0.001Generalized Linear Mixed Model
Secondary
Normal Rating of Functional Disability (NRFD)
Level of functional disability was assessed on a paper diary by the participants. Level of functional disability was rated as: normal, mildly impaired, severely impaired, or unable to do activities, requires bedrest. Functional disability ratings was dichotomized to Normal and Not Normal (mildly impaired, severely impaired, or unable to do activities, requires bedrest) for analysis.
Time frame: 2 hours post dose
Population: Full Analysis Set, which included all randomized participants who had at least one evaluable attack. To be considered an evaluable attack, the participant must have administered study treatment for this attack and have both a baseline severity measurement and at least one post-dose efficacy measurement at or prior to the 2-hour time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rizatriptan | Normal Rating of Functional Disability (NRFD) | Not resulting in NRFD at 2 hours post dose | 108 Attacks |
| Rizatriptan | Normal Rating of Functional Disability (NRFD) | Resulting in NRFD at 2 hours post dose | 85 Attacks |
| Placebo | Normal Rating of Functional Disability (NRFD) | Resulting in NRFD at 2 hours post dose | 16 Attacks |
| Placebo | Normal Rating of Functional Disability (NRFD) | Not resulting in NRFD at 2 hours post dose | 77 Attacks |
p-value: <0.001Generalized Linear Mixed Model
Secondary
Pain Freedom (PF)
Headache pain severity, relative to the administration of study medication, was rated by the participants in a paper diary. Pain severity rating scale: 0 (no pain), 1 (mild pain), 2 (moderate pain), or 3 (severe pain). Pain freedom (PF) is defined as a reduction in headache severity from Grade 3/2 at baseline to Grade 0 (no pain) post dose.
Time frame: 2 hours post dose
Population: Full Analysis Set, which included all randomized participants who had at least one evaluable attack. To be considered an evaluable attack, the participant must have administered study treatment for this attack and have both a baseline severity measurement and at least one post-dose efficacy measurement at or prior to the 2-hour time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rizatriptan | Pain Freedom (PF) | Resulting in PF 2 hours post dose | 74 Attacks |
| Rizatriptan | Pain Freedom (PF) | Not resulting in PF 2 hours post dose | 119 Attacks |
| Placebo | Pain Freedom (PF) | Resulting in PF 2 hours post dose | 9 Attacks |
| Placebo | Pain Freedom (PF) | Not resulting in PF 2 hours post dose | 84 Attacks |
p-value: <0.001Generalized Linear Mixed Model
Secondary
Sustained Pain Relief (SPR)
24-hour sustained pain relief (defined as pain relief at 2 hours post dose, with no administration of any rescue medication and with no occurrence of a moderate/severe headache during the respective period after dosing with the blinded study medication.
Time frame: 2 - 24 hours post dose
Population: Full Analysis Set, which included all randomized participants who had at least one evaluable attack. To be considered an evaluable attack, the attack must have met the FAS criteria for PR at 2 hours post-dose, and from 2-24 hours the participant either answered 24-hour headache recurrence question or didn't have PR at any time or took rescue.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rizatriptan | Sustained Pain Relief (SPR) | Resulting in SPR 2-24 hours post dose | 67 Attacks |
| Rizatriptan | Sustained Pain Relief (SPR) | Not resulting in SPR 2-24 hours post dose | 126 Attacks |
| Placebo | Sustained Pain Relief (SPR) | Not resulting in SPR 2-24 hours post dose | 81 Attacks |
| Placebo | Sustained Pain Relief (SPR) | Resulting in SPR 2-24 hours post dose | 12 Attacks |
p-value: <0.001Generalized Linear Mixed Model
Secondary
Treatment Satisfaction (TS)
Patient satisfaction was assessed on a paper diary by the participants. Level of satisfaction was rated as: completely satisfied, very satisfied, somewhat satisfied, neither satisfied nor dissatisfied, somewhat dissatisfied, very dissatisfied, or completely dissatisfied. The overall 24-hour assessment of study medication was dichotomized to Satisfaction (completely satisfied, very satisfied, somewhat satisfied) and Non-satisfaction (neither satisfied nor dissatisfied, somewhat dissatisfied, very dissatisfied, or completely dissatisfied) for analysis.
Time frame: 24 hours post dose
Population: Full Analysis Set, which included all randomized participants who had at least one evaluable attack. To be considered an evaluable attack, the participant must have administered study treatment for this attack and have both a baseline severity measurement and post-dose satisfaction measurement at the 24-hour time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rizatriptan | Treatment Satisfaction (TS) | Resulting in TS at 24 hours post dose | 117 Attacks |
| Rizatriptan | Treatment Satisfaction (TS) | Not resulting in TS at 24 hours post dose | 76 Attacks |
| Placebo | Treatment Satisfaction (TS) | Resulting in TS at 24 hours post dose | 31 Attacks |
| Placebo | Treatment Satisfaction (TS) | Not resulting in TS at 24 hours post dose | 62 Attacks |
p-value: <0.001Generalized Linear Mixed Model