Acute Migraine
Conditions
Keywords
Treatment of acute migraine with or without aura in adults
Brief summary
A study to provide evidence supporting the benefit of Rizatriptan in patients who have an inadequate response to sumatriptan.
Interventions
DRUGrizatriptan
Single dose of 10 mg orally disintegrating tablet at onset of migraine attack
DRUGComparator: Placebo
Placebo to Rizatriptan
single dose of generic sumatriptan 100 mg at onset of 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 1 year or more with 2-8 moderate or severe migraine attacks per month * Patient generally does not respond to treatment with sumatriptan * Patient of reproductive potential agrees to remain abstinent or use one method of highly effective birth control (i.e. IUD, condoms, hormonal contraceptive, diaphragm, vasectomy) for the duration of the study * Patient is able to complete paper diary
Exclusion criteria
* Patient is pregnant or breast feeding or excepts to become pregnant during the study * Patient has history of mild migraine attacks or migraines that usually resolve spontaneously in less than 2 hours * Patient has basilar or hemiplegic migraines * Patient is unable to distinguish between migraine attacks from other types of headaches * Patient has more than 15 headache-days per month * Patient was greater than 50 years old at age of migraine onset * Patient has failed to respond to 3 or more triptans * Patient has a repeated history of failing to respond to or tolerate rizatriptan * Patient uses opioids as primary migraine therapy * Patient uses daily opioids * Patient has a history of Cerebrovascular Accident (CVA) or other significant cardiovascular disease * Patient has uncontrolled hypertension * Patient has a history of neoplastic disease * Patient is taking a serotonin reuptake inhibitor (SSRI or SNRI) where the dose has changed 3 months prior to screening * Patient has a history of drug or alcohol abuse
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 |
|---|---|---|
| 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. |
Participant flow
Recruitment details
Patients were recruited at 21 study centers in the United States. First Patient In: 10-Jun-2009; First Patient Treated: 26-Jun-2009 Last Patient Last Visit: 12-Jan-2010; Last Patient Treated: 25-Dec-2009
Pre-assignment details
Participants who met entry criteria but had evidence of suicidality or were severely depressed (based on questionnaire scores) were excluded. Within 2 months of entry, participants were to treat a moderate/ severe migraine attack with sumatriptan 100 mg and were randomized if they still had moderate or severe pain at 2 hours post-dose.
Participants by arm
| Arm | Count |
|---|---|
| Rizatriptan / Rizatriptan / Placebo The first migraine was treated with Rizatriptan 10 mg Orally Disintegrating Tablet (ODT); the second migraine with Rizatriptan 10 mg ODT; the third migraine with placebo. | 37 |
| Rizatriptan / Placebo / Rizatriptan The first migraine was treated with Rizatriptan 10 mg ODT; the second migraine with placebo; and the third migraine with Rizatriptan 10 mg ODT. | 36 |
| Placebo / Rizatriptan / Rizatriptan The first migraine was treated with Placebo; the second migraine with Rizatriptan 10mg ODT; and the third migraine with Rizatriptan 10 mg ODT | 36 |
| Total | 109 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Baseline Phase | Did not meet Randomization Criteria | 0 | 0 | 0 | 85 |
| Treatment Phase | Lack of Qualifying Event | 2 | 1 | 0 | 0 |
| Treatment Phase | Lost to Follow-up | 2 | 3 | 1 | 0 |
Baseline characteristics
| Characteristic | Rizatriptan / Rizatriptan / Placebo | Rizatriptan / Placebo / Rizatriptan | Placebo / Rizatriptan / Rizatriptan | Total |
|---|---|---|---|---|
| Age, Continuous | 42.2 years STANDARD_DEVIATION 13.4 | 43.6 years STANDARD_DEVIATION 8.9 | 43.5 years STANDARD_DEVIATION 10.2 | 43.1 years STANDARD_DEVIATION 10.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 1 Participants | 2 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 34 Participants | 35 Participants | 34 Participants | 103 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 4 Participants | 3 Participants | 11 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 1 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 31 Participants | 31 Participants | 30 Participants | 92 Participants |
| Sex: Female, Male Female | 32 Participants | 33 Participants | 30 Participants | 95 Participants |
| Sex: Female, Male Male | 5 Participants | 3 Participants | 6 Participants | 14 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 | 18 / 102 | 3 / 100 | 29 / 194 |
| serious Total, serious adverse events | 0 / 102 | 0 / 100 | 0 / 194 |
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: The FAS population 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 must have had both a baseline severity measurement and at least one post-dose efficacy measurement prior to or including the 2-hour time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rizatriptan | Pain Relief (PR) | Resulting in PR at 2 hours post dose | 102 attacks |
| Rizatriptan | Pain Relief (PR) | Not resulting in PR at 2 hours post dose | 100 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 | 78 attacks |
p-value: <0.001Generalized Linear Mixed Model (GLIMMIX)
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: The FAS population 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 must have had both a baseline severity measurement and at least one post-dose efficacy measurement prior to or including the 2-hour time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rizatriptan | Pain Freedom (PF) | Resulting in PF at 2 hours post dose | 46 attacks |
| Rizatriptan | Pain Freedom (PF) | Not resulting in PF at 2 hours post dose | 156 attacks |
| Placebo | Pain Freedom (PF) | Resulting in PF at 2 hours post dose | 12 attacks |
| Placebo | Pain Freedom (PF) | Not resulting in PF at 2 hours post dose | 87 attacks |
p-value: <0.001Generalized Linear Mixed Model (GLIMMIX)