Migraine Headache
Conditions
Brief summary
A study to compare rizatriptan (MK0462) 5 mg by mouth (p.o.) and sumatriptan 50 mg p.o. for the acute treatment of a migraine attack.
Interventions
single dose 5 mg rizatriptan p.o.
single dose 50 mg sumatriptan p.o.
DRUGComparator: Placebo
Placebo to rizatriptan or sumatriptan, single dose placebo tablet taken orally
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
* Participant had at least a 6-month history of migraine, with or without aura * Participant was male, or if female, must have been postmenopausal, surgically sterilized, or taking adequate contraceptive precautions * Participant was judged to be in good health, apart from migraine
Exclusion criteria
* Participant was Pregnant or a nursing mother * Participant had a history or current evidence of drug or alcohol abuse * Participant had a history or clinical evidence of cardiovascular disease * Participant had a clinically significant Electrocardiography (ECG) abnormality * Participant had a resting systolic blood pressure of greater than 145 mm Hg or diastolic of less than 95 mm Hg at screening * Participant had received treatment with an investigational device or compound within 30 days of the study * Participant typically suffered from less then 1 or more than 8 attacks of migraine per month * Participant had difficulty in distinguishing his/her migraine attacks from tension or interval headaches * Participant was currently taking monoamine oxidase inhibitors, methysergide or lithium
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pain Relief at 2 Hours After Treatment | 2 hours after treatment | Participants 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 Treatment | within 2 hours after treatment | Participants reporting time to relief (defined as the first time that a participant reported grade 0 or 1 in headache severity within 2 hours after treatment (for the comparison of rizatriptan 5 mg and sumatriptan 50 mg). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Presence or Absence of Associated Symptoms (Photophobia, Phonophobia, Nausea, and Vomiting) at 2 Hours After Treatment | 2 hours after treatment | Participants who recorded the presence or absence of the associated symptoms photophobia, phonophobia, nausea, and vomiting at 2 hours after treatment. |
| Pain Free at 2 Hours After Treatment | 2 hours after treatment | Participants pain free (defined as a reduction of headache severity to grade 0 \[no pain\]) at 2 hours after treatment. Each participant rated headache severity on a 4-grade scale (0 = no headache; 1 = mild pain; 2 = moderate pain; 3 = severe pain). |
| Duration of Relief (Time to Recurrence From the Time of First Recorded Pain Relief [Grade = 0 or 1]) | 24 hours | Duration of relief or the time to recurrence from the time of first recorded pain relief (grade = 0 or 1) was calculated for responders who had a headache recurrence |
| Participants Who Used Escape Medication 2 Hours After the Treatment Dose | 2 hours after treatment | Escape medication is defined as rescue medication for participants who experienced lack of efficacy from the study medication. |
| Lack of Functional Disability at 2 Hours After Treatment as Measured by the Level of Impairment in Daily Activities | 2 hours after treatment | Participants with no functional disability measured by the level of impairment to daily activities at 2 hours after treatment. Each participant rated functional disability on a 4-grade scale (0 =normal; 1 = daily activities mildly impaired; 2 = daily activities severely impaired; 3 =unable to carry out daily activities, required bed rest). |
Participant flow
Recruitment details
Participants were recruited at 31 sites: 6 in UK, 9 in Norway, 2 in Switzerland, and 14 in Sweden First Participant Treated: August 1995 Last Participant Treated: May 1996.
Pre-assignment details
Participants screened at a pretreatment visit were given allocated drug supply with instructions. If participants 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 participants 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 | 355 |
| Sumatriptan 5 mg Sumatriptan 5 mg orally once for treatment of single migraine attack | 357 |
| Placebo Placebo matching Rizatriptan 5 mg or Sumatriptan 5 mg orally once for treatment of single migraine attack | 80 |
| Total | 792 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Abnormal Baseline ECG | 2 | 2 | 0 |
| Overall Study | Abnormal Prestudy Labs | 2 | 0 | 0 |
| Overall Study | Lack of Migraine Attack | 20 | 22 | 1 |
| Overall Study | Lost to Follow-up | 12 | 17 | 2 |
| Overall Study | Need for Concom. Med. | 0 | 1 | 1 |
| Overall Study | No Longer Met Inc/Exc Criteria | 1 | 0 | 0 |
| Overall Study | Other | 3 | 0 | 0 |
| Overall Study | Pregnancy | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 23 | 27 | 3 |
Baseline characteristics
| Characteristic | Rizatriptan 5 mg | Sumatriptan 5 mg | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 39.9 years STANDARD_DEVIATION 10.3 | 41.8 years STANDARD_DEVIATION 10.1 | 44.3 years STANDARD_DEVIATION 10.5 | 41.2 years STANDARD_DEVIATION 10.3 |
| Baseline Headache Severity Grade 2: Moderate | 216 Participants | 221 Participants | 51 Participants | 488 Participants |
| Baseline Headache Severity Grade 3: Severe | 133 Participants | 128 Participants | 29 Participants | 290 Participants |
| Baseline Headache Severity Grades 0,1: no pain, Mild, or missing | 6 Participants | 8 Participants | 0 Participants | 14 Participants |
| Race/Ethnicity, Customized Asian | 3 participants | 1 participants | 0 participants | 4 participants |
| Race/Ethnicity, Customized Caucasian | 352 participants | 356 participants | 80 participants | 788 participants |
| Sex: Female, Male Female | 291 Participants | 291 Participants | 70 Participants | 652 Participants |
| Sex: Female, Male Male | 64 Participants | 66 Participants | 10 Participants | 140 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 | 92 / 355 | 108 / 357 | 16 / 80 |
| serious Total, serious adverse events | 0 / 355 | 0 / 357 | 0 / 80 |
Outcome results
Primary
Pain Relief at 2 Hours After Treatment
Participants 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 treatment
Population: An all-participants-treated approach was used in the primary analysis, including all participants who had at least one assessment of pain severity within 2 hours after 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 Treatment | 2-hour pain relief | 223 Participants |
| Rizatriptan 5 mg | Pain Relief at 2 Hours After Treatment | No 2-hour pain relief | 129 Participants |
| Sumatriptan 5 mg | Pain Relief at 2 Hours After Treatment | 2-hour pain relief | 238 Participants |
| Sumatriptan 5 mg | Pain Relief at 2 Hours After Treatment | No 2-hour pain relief | 118 Participants |
| Placebo | Pain Relief at 2 Hours After Treatment | 2-hour pain relief | 18 Participants |
| Placebo | Pain Relief at 2 Hours After Treatment | No 2-hour pain relief | 62 Participants |
Primary
Time to Relief Within 2 Hours After Treatment
Participants reporting time to relief (defined as the first time that a participant reported grade 0 or 1 in headache severity within 2 hours after treatment (for the comparison of rizatriptan 5 mg and sumatriptan 50 mg).
Time frame: within 2 hours after treatment
Population: An all-participants-treated approach was used in the primary analysis, including all participants 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 Treatment | First pain relief within 2 hrs | 231 Participants |
| Rizatriptan 5 mg | Time to Relief Within 2 Hours After Treatment | Pain relief did not occur within 2 hrs | 121 Participants |
| Sumatriptan 5 mg | Time to Relief Within 2 Hours After Treatment | First pain relief within 2 hrs | 247 Participants |
| Sumatriptan 5 mg | Time to Relief Within 2 Hours After Treatment | Pain relief did not occur within 2 hrs | 109 Participants |
| Placebo | Time to Relief Within 2 Hours After Treatment | First pain relief within 2 hrs | 24 Participants |
| Placebo | Time to Relief Within 2 Hours After Treatment | Pain relief did not occur within 2 hrs | 56 Participants |
Secondary
Duration of Relief (Time to Recurrence From the Time of First Recorded Pain Relief [Grade = 0 or 1])
Duration of relief or the time to recurrence from the time of first recorded pain relief (grade = 0 or 1) was calculated for responders who had a headache recurrence
Time frame: 24 hours
Population: The duration of relief, or the time to recurrence from the time of first recorded pain relief (grade = 0 or 1), was calculated for responders who had a headache recurrence.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rizatriptan 5 mg | Duration of Relief (Time to Recurrence From the Time of First Recorded Pain Relief [Grade = 0 or 1]) | 11.07 Hours | Standard Deviation 6.56 |
| Sumatriptan 5 mg | Duration of Relief (Time to Recurrence From the Time of First Recorded Pain Relief [Grade = 0 or 1]) | 11.58 Hours | Standard Deviation 5.86 |
| Placebo | Duration of Relief (Time to Recurrence From the Time of First Recorded Pain Relief [Grade = 0 or 1]) | 14.38 Hours | Standard Deviation 5 |
Secondary
Lack of Functional Disability at 2 Hours After Treatment as Measured by the Level of Impairment in Daily Activities
Participants with no functional disability measured by the level of impairment to daily activities at 2 hours after treatment. Each participant rated functional disability on a 4-grade scale (0 =normal; 1 = daily activities mildly impaired; 2 = daily activities severely impaired; 3 =unable to carry out daily activities, required bed rest).
Time frame: 2 hours after treatment
Population: An all-participants-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 | Lack of Functional Disability at 2 Hours After Treatment as Measured by the Level of Impairment in Daily Activities | Normal | 108 Participants |
| Rizatriptan 5 mg | Lack of Functional Disability at 2 Hours After Treatment as Measured by the Level of Impairment in Daily Activities | Mildly Impaired | 152 Participants |
| Rizatriptan 5 mg | Lack of Functional Disability at 2 Hours After Treatment as Measured by the Level of Impairment in Daily Activities | Severely Impaired | 38 Participants |
| Rizatriptan 5 mg | Lack of Functional Disability at 2 Hours After Treatment as Measured by the Level of Impairment in Daily Activities | Required Bed Rest | 52 Participants |
| Sumatriptan 5 mg | Lack of Functional Disability at 2 Hours After Treatment as Measured by the Level of Impairment in Daily Activities | Required Bed Rest | 49 Participants |
| Sumatriptan 5 mg | Lack of Functional Disability at 2 Hours After Treatment as Measured by the Level of Impairment in Daily Activities | Normal | 116 Participants |
| Sumatriptan 5 mg | Lack of Functional Disability at 2 Hours After Treatment as Measured by the Level of Impairment in Daily Activities | Severely Impaired | 42 Participants |
| Sumatriptan 5 mg | Lack of Functional Disability at 2 Hours After Treatment as Measured by the Level of Impairment in Daily Activities | Mildly Impaired | 148 Participants |
| Placebo | Lack of Functional Disability at 2 Hours After Treatment as Measured by the Level of Impairment in Daily Activities | Required Bed Rest | 30 Participants |
| Placebo | Lack of Functional Disability at 2 Hours After Treatment as Measured by the Level of Impairment in Daily Activities | Mildly Impaired | 28 Participants |
| Placebo | Lack of Functional Disability at 2 Hours After Treatment as Measured by the Level of Impairment in Daily Activities | Severely Impaired | 18 Participants |
| Placebo | Lack of Functional Disability at 2 Hours After Treatment as Measured by the Level of Impairment in Daily Activities | Normal | 4 Participants |
Secondary
Pain Free at 2 Hours After Treatment
Participants pain free (defined as a reduction of headache severity to grade 0 \[no pain\]) at 2 hours after treatment. Each participant rated headache severity on a 4-grade scale (0 = no headache; 1 = mild pain; 2 = moderate pain; 3 = severe pain).
Time frame: 2 hours after treatment
Population: An all-participants-treated approach was used in the secondary analysis, including all participants who had at least one assessment of pain severity within 2 hours after test medication. Missing data were replaced by carrying forward the preceding value.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rizatriptan 5 mg | Pain Free at 2 Hours After Treatment | 2-hour pain freedom | 95 Participants |
| Rizatriptan 5 mg | Pain Free at 2 Hours After Treatment | No 2-hour pain freedom | 257 Participants |
| Sumatriptan 5 mg | Pain Free at 2 Hours After Treatment | 2-hour pain freedom | 113 Participants |
| Sumatriptan 5 mg | Pain Free at 2 Hours After Treatment | No 2-hour pain freedom | 243 Participants |
| Placebo | Pain Free at 2 Hours After Treatment | 2-hour pain freedom | 2 Participants |
| Placebo | Pain Free at 2 Hours After Treatment | No 2-hour pain freedom | 78 Participants |
Secondary
Participants Who Used Escape Medication 2 Hours After the Treatment Dose
Escape medication is defined as rescue medication for participants who experienced lack of efficacy from the study medication.
Time frame: 2 hours after treatment
Population: An all-participants-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 | Participants Who Used Escape Medication 2 Hours After the Treatment Dose | Used Escape Medication | 73 Participants |
| Rizatriptan 5 mg | Participants Who Used Escape Medication 2 Hours After the Treatment Dose | Did not Use Escape Medication | 282 Participants |
| Sumatriptan 5 mg | Participants Who Used Escape Medication 2 Hours After the Treatment Dose | Used Escape Medication | 55 Participants |
| Sumatriptan 5 mg | Participants Who Used Escape Medication 2 Hours After the Treatment Dose | Did not Use Escape Medication | 302 Participants |
| Placebo | Participants Who Used Escape Medication 2 Hours After the Treatment Dose | Used Escape Medication | 33 Participants |
| Placebo | Participants Who Used Escape Medication 2 Hours After the Treatment Dose | Did not Use Escape Medication | 47 Participants |
Secondary
Presence or Absence of Associated Symptoms (Photophobia, Phonophobia, Nausea, and Vomiting) at 2 Hours After Treatment
Participants who recorded the presence or absence of the associated symptoms photophobia, phonophobia, nausea, and vomiting at 2 hours after treatment.
Time frame: 2 hours after treatment
Population: All-participants-treated approach was used. Missing data were replaced by carrying forward the preceding value. Participants Analyzed For Nausea: Rizatriptan 348; Sumatriptan 352; Placebo 78. Participants Analyzed for Vomiting: Rizatriptan 342; Sumatriptan 342; Placebo 73. Number of participants analyzed is correct for the other categories.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rizatriptan 5 mg | Presence or Absence of Associated Symptoms (Photophobia, Phonophobia, Nausea, and Vomiting) at 2 Hours After Treatment | 2-hour Photophobia | 161 Participants |
| Rizatriptan 5 mg | Presence or Absence of Associated Symptoms (Photophobia, Phonophobia, Nausea, and Vomiting) at 2 Hours After Treatment | No 2-hour Photophobia | 189 Participants |
| Rizatriptan 5 mg | Presence or Absence of Associated Symptoms (Photophobia, Phonophobia, Nausea, and Vomiting) at 2 Hours After Treatment | 2-hour Phonophobia | 126 Participants |
| Rizatriptan 5 mg | Presence or Absence of Associated Symptoms (Photophobia, Phonophobia, Nausea, and Vomiting) at 2 Hours After Treatment | No 2-hour Phonophobia | 224 Participants |
| Rizatriptan 5 mg | Presence or Absence of Associated Symptoms (Photophobia, Phonophobia, Nausea, and Vomiting) at 2 Hours After Treatment | 2-hour Nausea | 105 Participants |
| Rizatriptan 5 mg | Presence or Absence of Associated Symptoms (Photophobia, Phonophobia, Nausea, and Vomiting) at 2 Hours After Treatment | No 2-hour Nausea | 243 Participants |
| Rizatriptan 5 mg | Presence or Absence of Associated Symptoms (Photophobia, Phonophobia, Nausea, and Vomiting) at 2 Hours After Treatment | Not Analyzed for Nausea | 2 Participants |
| Rizatriptan 5 mg | Presence or Absence of Associated Symptoms (Photophobia, Phonophobia, Nausea, and Vomiting) at 2 Hours After Treatment | 2-hour Vomiting | 12 Participants |
| Rizatriptan 5 mg | Presence or Absence of Associated Symptoms (Photophobia, Phonophobia, Nausea, and Vomiting) at 2 Hours After Treatment | No 2-hour Vomiting | 330 Participants |
| Rizatriptan 5 mg | Presence or Absence of Associated Symptoms (Photophobia, Phonophobia, Nausea, and Vomiting) at 2 Hours After Treatment | Not Analyzed for Vomiting | 8 Participants |
| Sumatriptan 5 mg | Presence or Absence of Associated Symptoms (Photophobia, Phonophobia, Nausea, and Vomiting) at 2 Hours After Treatment | No 2-hour Vomiting | 330 Participants |
| Sumatriptan 5 mg | Presence or Absence of Associated Symptoms (Photophobia, Phonophobia, Nausea, and Vomiting) at 2 Hours After Treatment | 2-hour Photophobia | 153 Participants |
| Sumatriptan 5 mg | Presence or Absence of Associated Symptoms (Photophobia, Phonophobia, Nausea, and Vomiting) at 2 Hours After Treatment | No 2-hour Nausea | 221 Participants |
| Sumatriptan 5 mg | Presence or Absence of Associated Symptoms (Photophobia, Phonophobia, Nausea, and Vomiting) at 2 Hours After Treatment | 2-hour Nausea | 131 Participants |
| Sumatriptan 5 mg | Presence or Absence of Associated Symptoms (Photophobia, Phonophobia, Nausea, and Vomiting) at 2 Hours After Treatment | No 2-hour Photophobia | 201 Participants |
| Sumatriptan 5 mg | Presence or Absence of Associated Symptoms (Photophobia, Phonophobia, Nausea, and Vomiting) at 2 Hours After Treatment | Not Analyzed for Vomiting | 12 Participants |
| Sumatriptan 5 mg | Presence or Absence of Associated Symptoms (Photophobia, Phonophobia, Nausea, and Vomiting) at 2 Hours After Treatment | 2-hour Vomiting | 12 Participants |
| Sumatriptan 5 mg | Presence or Absence of Associated Symptoms (Photophobia, Phonophobia, Nausea, and Vomiting) at 2 Hours After Treatment | 2-hour Phonophobia | 125 Participants |
| Sumatriptan 5 mg | Presence or Absence of Associated Symptoms (Photophobia, Phonophobia, Nausea, and Vomiting) at 2 Hours After Treatment | Not Analyzed for Nausea | 2 Participants |
| Sumatriptan 5 mg | Presence or Absence of Associated Symptoms (Photophobia, Phonophobia, Nausea, and Vomiting) at 2 Hours After Treatment | No 2-hour Phonophobia | 229 Participants |
| Placebo | Presence or Absence of Associated Symptoms (Photophobia, Phonophobia, Nausea, and Vomiting) at 2 Hours After Treatment | 2-hour Vomiting | 6 Participants |
| Placebo | Presence or Absence of Associated Symptoms (Photophobia, Phonophobia, Nausea, and Vomiting) at 2 Hours After Treatment | No 2-hour Phonophobia | 33 Participants |
| Placebo | Presence or Absence of Associated Symptoms (Photophobia, Phonophobia, Nausea, and Vomiting) at 2 Hours After Treatment | 2-hour Nausea | 48 Participants |
| Placebo | Presence or Absence of Associated Symptoms (Photophobia, Phonophobia, Nausea, and Vomiting) at 2 Hours After Treatment | No 2-hour Nausea | 30 Participants |
| Placebo | Presence or Absence of Associated Symptoms (Photophobia, Phonophobia, Nausea, and Vomiting) at 2 Hours After Treatment | No 2-hour Vomiting | 67 Participants |
| Placebo | Presence or Absence of Associated Symptoms (Photophobia, Phonophobia, Nausea, and Vomiting) at 2 Hours After Treatment | Not Analyzed for Nausea | 2 Participants |
| Placebo | Presence or Absence of Associated Symptoms (Photophobia, Phonophobia, Nausea, and Vomiting) at 2 Hours After Treatment | 2-hour Photophobia | 66 Participants |
| Placebo | Presence or Absence of Associated Symptoms (Photophobia, Phonophobia, Nausea, and Vomiting) at 2 Hours After Treatment | Not Analyzed for Vomiting | 7 Participants |
| Placebo | Presence or Absence of Associated Symptoms (Photophobia, Phonophobia, Nausea, and Vomiting) at 2 Hours After Treatment | No 2-hour Photophobia | 14 Participants |
| Placebo | Presence or Absence of Associated Symptoms (Photophobia, Phonophobia, Nausea, and Vomiting) at 2 Hours After Treatment | 2-hour Phonophobia | 47 Participants |