Migraine Headache
Conditions
Brief summary
A study to evaluate rizatriptan for the treatment of multiple attacks of acute migraine compared to placebo.
Interventions
Rizatriptan 10 mg p.o. at onset of moderate to severe migraine headache
DRUGComparator: Placebo
Placebo to Rizatriptan, Oral Tablet
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 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 prior exposure to rizatriptan
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pain Relief at 2 Hours During the First Migraine Attack Period | 2 hours | Patients reporting pain relief defined as a reduction of headache severity from grades 2 or 3 (moderate or severe) at baseline to grades 0 or 1 (no headache or mild) at 2 hours after initial dosing for the first migraine attack |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pain Relief at 2 Hours During the Second Migraine Attack Period | 2 hours | Patients reporting pain relief defined as a reduction of headache severity from grades 2 or 3 (moderate or severe) to grades 0 or 1 (no headache or mild) at 2 hours after dosing for the second migraine attack |
| Pain Relief at 2 Hours During the Third Migraine Attack Period | 2 hours | Patients reporting pain relief defined as a reduction of headache severity from grades 2 or 3 (moderate or severe) to grades 0 or 1 (no headache or mild) at 2 hours after dosing for the third migraine attack |
| Pain Relief at 2 Hours During the Fourth Migraine Attack Period | 2 hours | Patients reporting pain relief defined as a reduction of headache severity from grades 2 or 3 (moderate or severe) to grades 0 or 1 (no headache or mild) at 2 hours after dosing for the fourth migraine attack |
Participant flow
Recruitment details
Patients were recruited at 23 sites in the United States. First Patient Treated: April, 1995 Last Patient Treated: January 1996
Pre-assignment details
Patients screened at a pretreatment visit were given allocated drug supply with instructions. If by 2 months after screening, a patient still had not treated a migraine attack with test medication, he/she was to be discontinued from the study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo/Rizatriptan/Rizatriptan/Rizatriptan Placebo/Rizatriptan 10 mg/Rizatriptan 10 mg/Rizatriptan 10 mg = sequence for single dose of study drug taken orally for each recurrence or new migraine (up to 4 headaches) | 83 |
| Rizatriptan/Placebo/Rizatriptan/Rizatriptan Rizatriptan 10 mg/Placebo/Rizatriptan 10 mg/Rizatriptan 10 mg = sequence for single dose of study drug taken orally for each recurrence or new migraine (up to 4 headaches) | 82 |
| Rizatriptan/Rizatriptan/Placebo/Rizatriptan Rizatriptan 10 mg/Rizatriptan 10 mg/Placebo/Rizatriptan 10 mg = sequence for single dose of study drug taken orally for each recurrence or new migraine (up to 4 headaches) | 84 |
| Rizatriptan/Rizatriptan/Rizatriptan/Placebo Rizatriptan 10 mg/Rizatriptan 10 mg/Rizatriptan 10 mg /Placebo = sequence for single dose of study drug taken orally for each recurrence or new migraine (up to 4 headaches) | 77 |
| Rizatriptan/Rizatriptan/Rizatriptan/Rizatriptan Rizatriptan 10 mg/Rizatriptan 10 mg/Rizatriptan 10 mg /Rizatriptan 10 mg = sequence for single dose of study drug taken orally for each recurrence or new migraine (up to 4 headaches) | 81 |
| Total | 407 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Abnormal Baseline ECG | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Abnormal Prestudy Labs | 0 | 0 | 0 | 0 | 2 |
| Overall Study | Adverse Event | 2 | 2 | 1 | 1 | 2 |
| Overall Study | Inc/Exc Criteria Not Met | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Lack of Efficacy | 0 | 4 | 3 | 0 | 1 |
| Overall Study | Lost to Follow-up | 9 | 3 | 0 | 6 | 2 |
| Overall Study | No Attack Pretreatment | 3 | 5 | 5 | 6 | 4 |
| Overall Study | No Longer Met Inc/Exc Criteria | 1 | 1 | 1 | 0 | 0 |
| Overall Study | Not Completed/Entered Extn | 5 | 1 | 6 | 4 | 3 |
| Overall Study | Patient Uncooperative | 0 | 1 | 0 | 1 | 2 |
| Overall Study | Pregnancy | 0 | 0 | 1 | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 0 | 1 | 1 | 0 |
| Overall Study | Study Terminated | 3 | 0 | 3 | 3 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 4 | 2 | 3 | 6 |
Baseline characteristics
| Characteristic | Placebo/Rizatriptan/Rizatriptan/Rizatriptan | Total | Rizatriptan/Rizatriptan/Rizatriptan/Rizatriptan | Rizatriptan/Rizatriptan/Rizatriptan/Placebo | Rizatriptan/Rizatriptan/Placebo/Rizatriptan | Rizatriptan/Placebo/Rizatriptan/Rizatriptan |
|---|---|---|---|---|---|---|
| Age, Continuous | 41.1 years STANDARD_DEVIATION 9.6 | 40.6 years STANDARD_DEVIATION 10.2 | 38.9 years STANDARD_DEVIATION 10.8 | 39.5 years STANDARD_DEVIATION 10.1 | 42.3 years STANDARD_DEVIATION 10.6 | 41.0 years STANDARD_DEVIATION 9.8 |
| Baseline Severity (First Attack) Grade 2: Moderate | 58 Participants | 303 Participants | 64 Participants | 46 Participants | 69 Participants | 66 Participants |
| Baseline Severity (First Attack) Grade 3: Severe | 24 Participants | 100 Participants | 17 Participants | 29 Participants | 15 Participants | 15 Participants |
| Baseline Severity (First Attack) Grades 0, 1: No pain, Mild, or Missing | 1 Participants | 4 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 1 participants | 2 participants | 0 participants | 0 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Black | 3 participants | 10 participants | 1 participants | 2 participants | 2 participants | 2 participants |
| Race/Ethnicity, Customized Caucasian | 76 participants | 382 participants | 79 participants | 72 participants | 80 participants | 75 participants |
| Race/Ethnicity, Customized Oriental | 0 participants | 2 participants | 1 participants | 1 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Other | 3 participants | 10 participants | 0 participants | 2 participants | 2 participants | 3 participants |
| Race/Ethnicity, Customized Thai | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 1 participants |
| Sex: Female, Male Female | 68 Participants | 341 Participants | 67 Participants | 63 Participants | 72 Participants | 71 Participants |
| Sex: Female, Male Male | 15 Participants | 66 Participants | 14 Participants | 14 Participants | 12 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 199 / 323 | 31 / 84 |
| serious Total, serious adverse events | 0 / 337 | 0 / 84 |
Outcome results
Primary
Pain Relief at 2 Hours During the First Migraine Attack Period
Patients reporting pain relief defined as a reduction of headache severity from grades 2 or 3 (moderate or severe) at baseline to grades 0 or 1 (no headache or mild) at 2 hours after initial dosing for the first migraine attack
Time frame: 2 hours
Population: The primary efficacy analysis used an all-patients-treated approach which included all patients who had at least one record of an efficacy measure after the initial dose. Missing values were imputed by carrying forward the preceding values in the same phase.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rizatriptan 10 mg | Pain Relief at 2 Hours During the First Migraine Attack Period | Reporting pain relief | 246 participants |
| Rizatriptan 10 mg | Pain Relief at 2 Hours During the First Migraine Attack Period | Not reporting pain relief | 74 participants |
| Placebo | Pain Relief at 2 Hours During the First Migraine Attack Period | Reporting pain relief | 30 participants |
| Placebo | Pain Relief at 2 Hours During the First Migraine Attack Period | Not reporting pain relief | 52 participants |
Secondary
Pain Relief at 2 Hours During the Fourth Migraine Attack Period
Patients reporting pain relief defined as a reduction of headache severity from grades 2 or 3 (moderate or severe) to grades 0 or 1 (no headache or mild) at 2 hours after dosing for the fourth migraine attack
Time frame: 2 hours
Population: The secondary efficacy analysis used an all-patients-treated approach which included all patients who had at least one record of an efficacy measure after the initial dose. Missing values were imputed by carrying forward the preceding values in the same phase. Values were not carried forward from one attack period to the next.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rizatriptan 10 mg | Pain Relief at 2 Hours During the Fourth Migraine Attack Period | Reporting pain relief | 190 Participants |
| Rizatriptan 10 mg | Pain Relief at 2 Hours During the Fourth Migraine Attack Period | Not reporting pain relief | 65 Participants |
| Placebo | Pain Relief at 2 Hours During the Fourth Migraine Attack Period | Reporting pain relief | 31 Participants |
| Placebo | Pain Relief at 2 Hours During the Fourth Migraine Attack Period | Not reporting pain relief | 26 Participants |
Secondary
Pain Relief at 2 Hours During the Second Migraine Attack Period
Patients reporting pain relief defined as a reduction of headache severity from grades 2 or 3 (moderate or severe) to grades 0 or 1 (no headache or mild) at 2 hours after dosing for the second migraine attack
Time frame: 2 hours
Population: The secondary efficacy analysis used an all-patients-treated approach which included all patients who had at least one record of an efficacy measure after the initial dose. Missing values were imputed by carrying forward the preceding values in the same phase. Values were not carried forward from one attack period to the next.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rizatriptan 10 mg | Pain Relief at 2 Hours During the Second Migraine Attack Period | Reporting pain relief | 228 Participants |
| Rizatriptan 10 mg | Pain Relief at 2 Hours During the Second Migraine Attack Period | Not reporting pain relief | 63 Participants |
| Placebo | Pain Relief at 2 Hours During the Second Migraine Attack Period | Reporting pain relief | 27 Participants |
| Placebo | Pain Relief at 2 Hours During the Second Migraine Attack Period | Not reporting pain relief | 46 Participants |
Secondary
Pain Relief at 2 Hours During the Third Migraine Attack Period
Patients reporting pain relief defined as a reduction of headache severity from grades 2 or 3 (moderate or severe) to grades 0 or 1 (no headache or mild) at 2 hours after dosing for the third migraine attack
Time frame: 2 hours
Population: The secondary efficacy analysis used an all-patients-treated approach which included all patients who had at least one record of an efficacy measure after the initial dose. Missing values were imputed by carrying forward the preceding values in the same phase. Values were not carried forward from one attack period to the next.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rizatriptan 10 mg | Pain Relief at 2 Hours During the Third Migraine Attack Period | Reporting pain relief | 207 Participants |
| Rizatriptan 10 mg | Pain Relief at 2 Hours During the Third Migraine Attack Period | Not reporting pain relief | 52 Participants |
| Placebo | Pain Relief at 2 Hours During the Third Migraine Attack Period | Reporting pain relief | 21 Participants |
| Placebo | Pain Relief at 2 Hours During the Third Migraine Attack Period | Not reporting pain relief | 54 Participants |