Migraine Headache
Conditions
Brief summary
A study to compare rizatriptan 10 mg verse sumatriptan 100 mg in the treatment of migraine attacks and duration of relief provided. This study will also provide additional efficacy data on rizatriptan 5 mg and 10 mg for the treatment of migraine.
Interventions
single dose administration of 5mg rizatriptan (by Mouth) p.o.
single dose administration of sumatriptan 100 p.o.
DRUGComparator: Placebo
placebo to rizatriptan
Sponsors
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Patient had at least a 6-month history of migraine, with or without aura * Patient was male, or if female must have been postmenopausal, surgically sterilized, or taking adequate contraceptive precautions. * Patient was judged to be in good health, apart from migraine
Exclusion criteria
* Patient was pregnant or a nursing mother * Patient had abused drugs or alcohol within 12 months prior to entering the study * Patient had a history of cardiovascular disease * Patient had clinically significant Electrocardiography (ECG) abnormality * Patient had a resting systolic blood pressure of greater than 145 mm Hg or diastolic of less than 95 mm Hg at screening * Patient received treatment with an investigational device or compound within 30 days of the study start * Patient typically suffered from less then 1 or more than 8 attacks of migraine per month * Patient had difficulty in distinguishing his/her migraine attacks from tension or interval headaches * Patient had hypersensitivity to sumatriptan * Patient had participated in any previous study involving rizatriptan
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pain Relief at 2 Hours After Dose | 2 hours after dose | Patients reporting pain relief defined as a reduction of headache severity from grades 2 or 3 (moderate or severe pain) at baseline to grades 0 or 1 (no headache or mild pain) at 2 hours after treatment |
| Time to Relief Within 2 Hours After Dose | within 2 hours after dose | Patients reporting time to relief defined as the first time point at which a patient reported headache severity grade 1 or 0 (mild pain or no headache) within 2 hours after dose |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pain Free at 2 Hours After Dose | 2 hours after dose | Patients pain free (defined as a reduction of headache severity to grade 0 \[no pain\]) at 2 hours after treatment. Each patient rated headache severity on a 4-point scale (0 = no headache; 1 = mild pain; 2 = moderate pain; 3 = severe pain). |
| Functional Status at 2 Hours After Dose | 2 hours after dose | Patients with no functional disability measured by the level of impairment to daily activities at 2 hours after treatment. Each patient rated functional disability on a 4-grade scale (0 = no functional disability; 1 = daily activities mildly impaired; 2 = daily activities severely impaired; 3 = unable to carry out daily activities, requires bed rest). |
| Nausea at 2 Hours After Dose | 2 hours after dose | Patients who recorded the presence or absence of nausea 2 hours after dose |
Participant flow
Recruitment details
Patients were recruited at 47 sites in 21 countries in Canada, South America, Europe, Middle East, South Africa, and Australia First Patient Treated: September 1995 Last Patient Treated: May 1996
Pre-assignment details
Outpatients screened at a pretreatment visit were given allocated drug supply with instructions. If patients had not treated an attack within 2 months of being enrolled, they were required to return for a rescreen visit. If by 4 months after being enrolled patients still had not treated an attack, they were discontinued from the study.
Participants by arm
| Arm | Count |
|---|---|
| Rizatriptan 5 mg Rizatriptan 5 mg orally once for treatment of single migraine attack.
Baseline measure Participants reported are those participants that recieved study treatment. | 164 |
| Rizatriptan 10 mg Rizatriptan 10 mg orally once for treatment of single migraine attack
Baseline measure Participants reported are those participants that recieved study treatment. | 387 |
| Sumatriptan 100 mg Sumatriptan 100 mg orally once for treatment of single migraine attack
Baseline measure Participants reported are those participants that recieved study treatment. | 388 |
| Placebo Placebo matching Rizatriptan and Sumatriptan orally once for treatment of single migraine attack
Baseline measure Participants reported are those participants that recieved study treatment. | 160 |
| Total | 1,099 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 2 | 0 |
| Overall Study | Not Treated: Abnormal Baseline ECG | 1 | 0 | 0 | 0 |
| Overall Study | Not Treated: Abnormal Prestudy Labs | 0 | 0 | 0 | 1 |
| Overall Study | Not Treated: Adverse Event | 0 | 2 | 1 | 0 |
| Overall Study | Not Treated: Lack of Migraine Attack | 9 | 39 | 43 | 12 |
| Overall Study | Not Treated: Lost to Follow-Up | 0 | 5 | 5 | 2 |
| Overall Study | Not Treated: No Longer Met Inc Criteria | 0 | 3 | 1 | 0 |
| Overall Study | Not Treated: Other (Not Specified) | 0 | 0 | 2 | 0 |
| Overall Study | Not Treated: Patient uncooperative | 2 | 3 | 1 | 0 |
| Overall Study | Not Treated: Pregnancy | 0 | 0 | 1 | 0 |
| Overall Study | Not Treated: Protocol Violation | 2 | 0 | 2 | 0 |
| Overall Study | Not Treated: Withdraw by Subject | 2 | 16 | 11 | 3 |
| Overall Study | Protocol Violation | 1 | 1 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Rizatriptan 5 mg | Total | Placebo | Sumatriptan 100 mg | Rizatriptan 10 mg |
|---|---|---|---|---|---|
| Age, Continuous | 38.3 years STANDARD_DEVIATION 10.3 | 38.2 years STANDARD_DEVIATION 10.2 | 38.3 years STANDARD_DEVIATION 10.3 | 39.2 years STANDARD_DEVIATION 10.1 | 37.0 years STANDARD_DEVIATION 10 |
| Baseline Headache Severity Grade 2: Moderate | 72 participants | 512 participants | 75 participants | 191 participants | 174 participants |
| Baseline Headache Severity Grade 3: Severe | 92 participants | 585 participants | 84 participants | 196 participants | 213 participants |
| Baseline Headache Severity Grades 1, 0: Mild, no pain, or missing | 0 participants | 2 participants | 1 participants | 1 participants | 0 participants |
| Race/Ethnicity Asian | 0 participants | 3 participants | 0 participants | 2 participants | 1 participants |
| Race/Ethnicity Asian/Caucasian | 1 participants | 1 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity Black | 1 participants | 9 participants | 0 participants | 3 participants | 5 participants |
| Race/Ethnicity Caucasian | 117 participants | 800 participants | 120 participants | 281 participants | 282 participants |
| Race/Ethnicity Colored | 0 participants | 1 participants | 0 participants | 1 participants | 0 participants |
| Race/Ethnicity Hispanic | 33 participants | 222 participants | 32 participants | 77 participants | 80 participants |
| Race/Ethnicity Mestizo | 9 participants | 53 participants | 7 participants | 22 participants | 15 participants |
| Race/Ethnicity Mexican | 0 participants | 4 participants | 0 participants | 2 participants | 2 participants |
| Race/Ethnicity Mexican/Hispanic | 1 participants | 1 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity Mixed | 2 participants | 5 participants | 1 participants | 0 participants | 2 participants |
| Sex: Female, Male Female | 138 Participants | 898 Participants | 132 Participants | 309 Participants | 319 Participants |
| Sex: Female, Male Male | 26 Participants | 201 Participants | 28 Participants | 79 Participants | 68 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 62 / 164 | 159 / 387 | 188 / 388 | 51 / 160 |
| serious Total, serious adverse events | 1 / 164 | 0 / 387 | 0 / 388 | 0 / 160 |
Outcome results
Primary
Pain Relief at 2 Hours After Dose
Patients reporting pain relief defined as a reduction of headache severity from grades 2 or 3 (moderate or severe pain) at baseline to grades 0 or 1 (no headache or mild pain) at 2 hours after treatment
Time frame: 2 hours after dose
Population: An all-patients-treated approach was used in the primary analysis, including all patients who had at least one assessment of pain severity within 2 hours after test medication. Missing values in the treatment phase (i.e., after the baseline phase) were imputed by carrying forward the preceding values in the same phase.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rizatriptan 5 mg | Pain Relief at 2 Hours After Dose | 2-hour pain relief | 99 Participants |
| Rizatriptan 5 mg | Pain Relief at 2 Hours After Dose | No 2-hour pain relief | 65 Participants |
| Rizatriptan 10 mg | Pain Relief at 2 Hours After Dose | No 2-hour pain relief | 127 Participants |
| Rizatriptan 10 mg | Pain Relief at 2 Hours After Dose | 2-hour pain relief | 258 Participants |
| Sumatriptan 100 mg | Pain Relief at 2 Hours After Dose | 2-hour pain relief | 239 Participants |
| Sumatriptan 100 mg | Pain Relief at 2 Hours After Dose | No 2-hour pain relief | 148 Participants |
| Placebo | Pain Relief at 2 Hours After Dose | 2-hour pain relief | 64 Participants |
| Placebo | Pain Relief at 2 Hours After Dose | No 2-hour pain relief | 95 Participants |
Primary
Time to Relief Within 2 Hours After Dose
Patients reporting time to relief defined as the first time point at which a patient reported headache severity grade 1 or 0 (mild pain or no headache) within 2 hours after dose
Time frame: within 2 hours after dose
Population: An all-patients-treated approach was used in the primary analysis, including all patients who had at least one assessment of pain severity within 2 hours after test medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rizatriptan 5 mg | Time to Relief Within 2 Hours After Dose | First pain relief within 2 hrs | 102 Participants |
| Rizatriptan 5 mg | Time to Relief Within 2 Hours After Dose | Pain relief did not occur within 2 hrs | 62 Participants |
| Rizatriptan 10 mg | Time to Relief Within 2 Hours After Dose | Pain relief did not occur within 2 hrs | 120 Participants |
| Rizatriptan 10 mg | Time to Relief Within 2 Hours After Dose | First pain relief within 2 hrs | 265 Participants |
| Sumatriptan 100 mg | Time to Relief Within 2 Hours After Dose | First pain relief within 2 hrs | 247 Participants |
| Sumatriptan 100 mg | Time to Relief Within 2 Hours After Dose | Pain relief did not occur within 2 hrs | 140 Participants |
| Placebo | Time to Relief Within 2 Hours After Dose | First pain relief within 2 hrs | 72 Participants |
| Placebo | Time to Relief Within 2 Hours After Dose | Pain relief did not occur within 2 hrs | 87 Participants |
Secondary
Functional Status at 2 Hours After Dose
Patients with no functional disability measured by the level of impairment to daily activities at 2 hours after treatment. Each patient rated functional disability on a 4-grade scale (0 = no functional disability; 1 = daily activities mildly impaired; 2 = daily activities severely impaired; 3 = unable to carry out daily activities, requires bed rest).
Time frame: 2 hours after dose
Population: An all-patients-treated approach was used in the secondary analysis. Missing data were replaced by carrying forward the preceding value.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rizatriptan 5 mg | Functional Status at 2 Hours After Dose | No functional disability | 52 Participants |
| Rizatriptan 5 mg | Functional Status at 2 Hours After Dose | Mildly impaired | 62 Participants |
| Rizatriptan 5 mg | Functional Status at 2 Hours After Dose | Severely impaired | 27 Participants |
| Rizatriptan 5 mg | Functional Status at 2 Hours After Dose | Required bed rest | 23 Participants |
| Rizatriptan 10 mg | Functional Status at 2 Hours After Dose | Mildly impaired | 123 Participants |
| Rizatriptan 10 mg | Functional Status at 2 Hours After Dose | Severely impaired | 60 Participants |
| Rizatriptan 10 mg | Functional Status at 2 Hours After Dose | Required bed rest | 42 Participants |
| Rizatriptan 10 mg | Functional Status at 2 Hours After Dose | No functional disability | 160 Participants |
| Sumatriptan 100 mg | Functional Status at 2 Hours After Dose | Severely impaired | 67 Participants |
| Sumatriptan 100 mg | Functional Status at 2 Hours After Dose | Mildly impaired | 142 Participants |
| Sumatriptan 100 mg | Functional Status at 2 Hours After Dose | Required bed rest | 52 Participants |
| Sumatriptan 100 mg | Functional Status at 2 Hours After Dose | No functional disability | 126 Participants |
| Placebo | Functional Status at 2 Hours After Dose | Required bed rest | 36 Participants |
| Placebo | Functional Status at 2 Hours After Dose | Mildly impaired | 59 Participants |
| Placebo | Functional Status at 2 Hours After Dose | No functional disability | 31 Participants |
| Placebo | Functional Status at 2 Hours After Dose | Severely impaired | 33 Participants |
Secondary
Nausea at 2 Hours After Dose
Patients who recorded the presence or absence of nausea 2 hours after dose
Time frame: 2 hours after dose
Population: An all-patients-treated approach was used in the secondary analysis. Missing data were replaced by carrying forward the preceding value.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rizatriptan 5 mg | Nausea at 2 Hours After Dose | 2-hour Nausea | 37 participants |
| Rizatriptan 5 mg | Nausea at 2 Hours After Dose | No 2-hour Nausea | 127 participants |
| Rizatriptan 10 mg | Nausea at 2 Hours After Dose | No 2-hour Nausea | 290 participants |
| Rizatriptan 10 mg | Nausea at 2 Hours After Dose | 2-hour Nausea | 95 participants |
| Sumatriptan 100 mg | Nausea at 2 Hours After Dose | 2-hour Nausea | 128 participants |
| Sumatriptan 100 mg | Nausea at 2 Hours After Dose | No 2-hour Nausea | 259 participants |
| Placebo | Nausea at 2 Hours After Dose | 2-hour Nausea | 68 participants |
| Placebo | Nausea at 2 Hours After Dose | No 2-hour Nausea | 91 participants |
Secondary
Pain Free at 2 Hours After Dose
Patients pain free (defined as a reduction of headache severity to grade 0 \[no pain\]) at 2 hours after treatment. Each patient rated headache severity on a 4-point scale (0 = no headache; 1 = mild pain; 2 = moderate pain; 3 = severe pain).
Time frame: 2 hours after dose
Population: An all-patients-treated approach was used in the secondary analysis, including all patients who had at least one assessment of pain severity within 2 hours after test medication. Missing values in the treatment phase (i.e., after the baseline phase) were imputed by carrying forward the preceding values in the same phase.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rizatriptan 5 mg | Pain Free at 2 Hours After Dose | 2-hour Pain freedom | 41 Participants |
| Rizatriptan 5 mg | Pain Free at 2 Hours After Dose | No 2-hour pain freedom | 123 Participants |
| Rizatriptan 10 mg | Pain Free at 2 Hours After Dose | No 2-hour pain freedom | 230 Participants |
| Rizatriptan 10 mg | Pain Free at 2 Hours After Dose | 2-hour Pain freedom | 155 Participants |
| Sumatriptan 100 mg | Pain Free at 2 Hours After Dose | 2-hour Pain freedom | 127 Participants |
| Sumatriptan 100 mg | Pain Free at 2 Hours After Dose | No 2-hour pain freedom | 260 Participants |
| Placebo | Pain Free at 2 Hours After Dose | 2-hour Pain freedom | 15 Participants |
| Placebo | Pain Free at 2 Hours After Dose | No 2-hour pain freedom | 139 Participants |