Migraine Headache
Conditions
Brief summary
A study to evaluate rizatriptan/MK0462 (5 and 10 mg) for the treatment of acute migraine attack and treatment of up to two headache recurrences compared to placebo. The long term extension study which pools patients from MK0462-022, -025, and -029 is described in NCT01286207.
Interventions
Single dose administration of 5 or 10 mg oral tablet of rizatriptan, taken immediately upon development of acute/severe migraine headache.
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 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 After the Initial Dose of Test Drug | 2 hours after initial dose of test drug | Patients reporting pain relief (defined as a reduction of headache severity from grades 2/3 at baseline to 0/1) at 2 hours after the initial dose of test drug. Pain severity was subjectively rated by patients on a scale from grade 0 to 3: Grade 0 - No headache, Grade 1 - Mild pain, Grade 2 - Moderate pain, Grade 3 - Severe pain. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pain Free at 2 Hours After the Initial Dose of Test Drug | 2 hours after initial dose of test drug | Patients reporting pain free (defined as a reduction of headache severity to grade 0 \[no pain\]) at 2 hours after the initial dose of test drug. Pain severity was subjectively rated by patients on a scale from grade 0 to 3: Grade 0 - No headache, Grade 1 - Mild pain, Grade 2 - Moderate pain, Grade 3 - Severe pain. |
| No Disability at 2 Hours After the Initial Dose of Test Drug | 2 hours after initial dose of test drug | Patients with no disability at 2 hours after the initial dose of test drug. Functional disability was subjectively rated on a scale from grade 0 to 3: Grade 0 - Normal, Grade 1 - Daily activities mildly impaired, Grade 2 - Daily activities severely impaired, Grade 3 - Unable to carry out daily activities, requires bedrest |
| Use of Escape Medication at 2 Hours After the Initial Dose of Test Drug | 2 hours after initial dose of test drug | — |
| Pain Relief 2 Hours After Treatment for Headache Recurrence | 2 hours after treatment for recurrence | Patients reporting pain relief 2 hours after treatment for headache recurrence (defined as the return of headache to grade 2 or 3 within 24 hours of the initial dose in patients who reported pain relief (grades 0 or 1) at 2 hours). |
Participant flow
Recruitment details
Patients were recruited at 28 sites in the United States and 18 in 9 other countries. First Patient Treated: Mar 1995 Last Patient Treated: Jan 1996.
Pre-assignment details
Outpatients randomized at the prestudy visit were given study drug and administration 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 | 458 |
| Rizatriptan 10 mg Rizatriptan 10 mg orally once for treatment of single migraine attack | 456 |
| Placebo Placebo matching Rizatiptan 5 mg and Rizatriptan 10 mg orally once for treatment | 304 |
| Total | 1,218 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Abnormal Baseline ECG | 2 | 2 | 4 |
| Overall Study | Abnormal Prestudy Labs | 2 | 3 | 4 |
| Overall Study | Adverse Event | 1 | 1 | 0 |
| Overall Study | Did not take study drug | 9 | 3 | 4 |
| Overall Study | Lack of Migraine Attack | 29 | 30 | 19 |
| Overall Study | Lost to Follow-up | 0 | 2 | 1 |
| Overall Study | Need for Concom. Med. | 0 | 1 | 1 |
| Overall Study | Patient Uncoorperative | 0 | 2 | 1 |
| Overall Study | Protocol Violation | 6 | 3 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 2 | 0 |
Baseline characteristics
| Characteristic | Placebo | Total | Rizatriptan 10 mg | Rizatriptan 5 mg |
|---|---|---|---|---|
| Age, Continuous | 40.6 years STANDARD_DEVIATION 10.5 | 40.6 years STANDARD_DEVIATION 9.9 | 40.7 years STANDARD_DEVIATION 9.6 | 40.5 years STANDARD_DEVIATION 9.6 |
| Baseline Headache Severity Grade 0, 1: No pain, Mild, or missing | 7 Participants | 24 Participants | 9 Participants | 8 Participants |
| Baseline Headache Severity Grade 2: Moderate | 202 Participants | 816 Participants | 316 Participants | 298 Participants |
| Baseline Headache Severity Grade 3: Severe | 95 Participants | 378 Participants | 131 Participants | 152 Participants |
| Race/Ethnicity, Customized Anglo-Asian | 0 participants | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Asian | 3 participants | 17 participants | 12 participants | 2 participants |
| Race/Ethnicity, Customized Black | 7 participants | 32 participants | 7 participants | 18 participants |
| Race/Ethnicity, Customized Caucasian | 286 participants | 1138 participants | 422 participants | 430 participants |
| Race/Ethnicity, Customized Hispanic | 1 participants | 2 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Mexican-American | 0 participants | 1 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Mixed | 1 participants | 8 participants | 4 participants | 3 participants |
| Race/Ethnicity, Customized Other | 5 participants | 18 participants | 9 participants | 4 participants |
| Race/Ethnicity, Customized Syrian | 1 participants | 1 participants | 0 participants | 0 participants |
| Sex: Female, Male Female | 259 Participants | 1055 Participants | 402 Participants | 394 Participants |
| Sex: Female, Male Male | 45 Participants | 163 Participants | 54 Participants | 64 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 | 155 / 456 | 254 / 455 | 83 / 307 |
| serious Total, serious adverse events | 3 / 456 | 0 / 455 | 0 / 307 |
Outcome results
Primary
Pain Relief at 2 Hours After the Initial Dose of Test Drug
Patients reporting pain relief (defined as a reduction of headache severity from grades 2/3 at baseline to 0/1) at 2 hours after the initial dose of test drug. Pain severity was subjectively rated by patients on a scale from grade 0 to 3: Grade 0 - No headache, Grade 1 - Mild pain, Grade 2 - Moderate pain, Grade 3 - Severe pain.
Time frame: 2 hours after initial dose of test drug
Population: The primary analysis employed an all-patients-treated approach that included all patients who had at least one record of pain severity within 2 hours after the initial dose. Missing data were replaced by carrying forward the preceding value.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rizatriptan 5 mg | Pain Relief at 2 Hours After the Initial Dose of Test Drug | Reporting pain relief | 285 Participants |
| Rizatriptan 5 mg | Pain Relief at 2 Hours After the Initial Dose of Test Drug | Not reporting pain relief | 172 Participants |
| Rizatriptan 10 mg | Pain Relief at 2 Hours After the Initial Dose of Test Drug | Reporting pain relief | 322 Participants |
| Rizatriptan 10 mg | Pain Relief at 2 Hours After the Initial Dose of Test Drug | Not reporting pain relief | 133 Participants |
| Placebo | Pain Relief at 2 Hours After the Initial Dose of Test Drug | Reporting pain relief | 106 Participants |
| Placebo | Pain Relief at 2 Hours After the Initial Dose of Test Drug | Not reporting pain relief | 196 Participants |
Secondary
No Disability at 2 Hours After the Initial Dose of Test Drug
Patients with no disability at 2 hours after the initial dose of test drug. Functional disability was subjectively rated on a scale from grade 0 to 3: Grade 0 - Normal, Grade 1 - Daily activities mildly impaired, Grade 2 - Daily activities severely impaired, Grade 3 - Unable to carry out daily activities, requires bedrest
Time frame: 2 hours after initial dose of test drug
Population: An all-patients-treated approach was employed that included all patients who had at least one record of functional disability within 2 hours after the initial dose. Missing data were replaced by carrying forward the preceding value.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rizatriptan 5 mg | No Disability at 2 Hours After the Initial Dose of Test Drug | Normal | 175 Participants |
| Rizatriptan 5 mg | No Disability at 2 Hours After the Initial Dose of Test Drug | Mildly Impaired | 160 Participants |
| Rizatriptan 5 mg | No Disability at 2 Hours After the Initial Dose of Test Drug | Severely Impaired | 56 Participants |
| Rizatriptan 5 mg | No Disability at 2 Hours After the Initial Dose of Test Drug | Requires Bedrest | 66 Participants |
| Rizatriptan 10 mg | No Disability at 2 Hours After the Initial Dose of Test Drug | Requires Bedrest | 52 Participants |
| Rizatriptan 10 mg | No Disability at 2 Hours After the Initial Dose of Test Drug | Normal | 209 Participants |
| Rizatriptan 10 mg | No Disability at 2 Hours After the Initial Dose of Test Drug | Severely Impaired | 45 Participants |
| Rizatriptan 10 mg | No Disability at 2 Hours After the Initial Dose of Test Drug | Mildly Impaired | 148 Participants |
| Placebo | No Disability at 2 Hours After the Initial Dose of Test Drug | Requires Bedrest | 75 Participants |
| Placebo | No Disability at 2 Hours After the Initial Dose of Test Drug | Mildly Impaired | 118 Participants |
| Placebo | No Disability at 2 Hours After the Initial Dose of Test Drug | Severely Impaired | 53 Participants |
| Placebo | No Disability at 2 Hours After the Initial Dose of Test Drug | Normal | 54 Participants |
Secondary
Pain Free at 2 Hours After the Initial Dose of Test Drug
Patients reporting pain free (defined as a reduction of headache severity to grade 0 \[no pain\]) at 2 hours after the initial dose of test drug. Pain severity was subjectively rated by patients on a scale from grade 0 to 3: Grade 0 - No headache, Grade 1 - Mild pain, Grade 2 - Moderate pain, Grade 3 - Severe pain.
Time frame: 2 hours after initial dose of test drug
Population: An all-patients-treated approach was employed that included all patients who had at least one record of pain severity within 2 hours after the initial dose. Missing data were replaced by carrying forward the preceding value.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rizatriptan 5 mg | Pain Free at 2 Hours After the Initial Dose of Test Drug | Reporting no pain | 150 Participants |
| Rizatriptan 5 mg | Pain Free at 2 Hours After the Initial Dose of Test Drug | Reporting pain | 307 Participants |
| Rizatriptan 10 mg | Pain Free at 2 Hours After the Initial Dose of Test Drug | Reporting no pain | 193 Participants |
| Rizatriptan 10 mg | Pain Free at 2 Hours After the Initial Dose of Test Drug | Reporting pain | 262 Participants |
| Placebo | Pain Free at 2 Hours After the Initial Dose of Test Drug | Reporting no pain | 30 Participants |
| Placebo | Pain Free at 2 Hours After the Initial Dose of Test Drug | Reporting pain | 272 Participants |
Secondary
Pain Relief 2 Hours After Treatment for Headache Recurrence
Patients reporting pain relief 2 hours after treatment for headache recurrence (defined as the return of headache to grade 2 or 3 within 24 hours of the initial dose in patients who reported pain relief (grades 0 or 1) at 2 hours).
Time frame: 2 hours after treatment for recurrence
Population: Patients with initial headache recurrence who took rizatriptan 5 mg or 10 mg were prerandomized (ratio=1:1) to either rizatriptan 5 mg or 10 mg, respectively, or to placebo (ratio=1:1); and who took placebo, to either 5 mg or 10 mg of rizatriptan (ratio=1:1). Only those who took rizatriptan for their initial headache were considered for analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rizatriptan 5 mg | Pain Relief 2 Hours After Treatment for Headache Recurrence | Pain relief | 39 Participants |
| Rizatriptan 5 mg | Pain Relief 2 Hours After Treatment for Headache Recurrence | No pain relief | 16 Participants |
| Rizatriptan 10 mg | Pain Relief 2 Hours After Treatment for Headache Recurrence | Pain relief | 32 Participants |
| Rizatriptan 10 mg | Pain Relief 2 Hours After Treatment for Headache Recurrence | No pain relief | 27 Participants |
| Placebo | Pain Relief 2 Hours After Treatment for Headache Recurrence | Pain relief | 53 Participants |
| Placebo | Pain Relief 2 Hours After Treatment for Headache Recurrence | No pain relief | 12 Participants |
| Rizatriptan 10 mg / Placebo | Pain Relief 2 Hours After Treatment for Headache Recurrence | Pain relief | 33 Participants |
| Rizatriptan 10 mg / Placebo | Pain Relief 2 Hours After Treatment for Headache Recurrence | No pain relief | 42 Participants |
| Placebo / Rizatriptan 5 mg | Pain Relief 2 Hours After Treatment for Headache Recurrence | Pain relief | 12 Participants |
| Placebo / Rizatriptan 5 mg | Pain Relief 2 Hours After Treatment for Headache Recurrence | No pain relief | 5 Participants |
| Placebo / Rizatriptan 10 mg | Pain Relief 2 Hours After Treatment for Headache Recurrence | Pain relief | 18 Participants |
| Placebo / Rizatriptan 10 mg | Pain Relief 2 Hours After Treatment for Headache Recurrence | No pain relief | 4 Participants |
Secondary
Use of Escape Medication at 2 Hours After the Initial Dose of Test Drug
Time frame: 2 hours after initial dose of test drug
Population: An all-patients-treated approach was employed that included all patients who had at least one record of pain severity within 2 hours after the initial dose. Missing data were replaced by carrying forward the preceding value.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rizatriptan 5 mg | Use of Escape Medication at 2 Hours After the Initial Dose of Test Drug | Used escape medication | 101 Participants |
| Rizatriptan 5 mg | Use of Escape Medication at 2 Hours After the Initial Dose of Test Drug | Did not use escape medication | 357 Participants |
| Rizatriptan 10 mg | Use of Escape Medication at 2 Hours After the Initial Dose of Test Drug | Used escape medication | 76 Participants |
| Rizatriptan 10 mg | Use of Escape Medication at 2 Hours After the Initial Dose of Test Drug | Did not use escape medication | 380 Participants |
| Placebo | Use of Escape Medication at 2 Hours After the Initial Dose of Test Drug | Used escape medication | 128 Participants |
| Placebo | Use of Escape Medication at 2 Hours After the Initial Dose of Test Drug | Did not use escape medication | 176 Participants |