Migraine
Conditions
Brief summary
The purpose of this study is to investigate the efficacy and safety of an MK 0974 for migraine headache and to identify an appropriate dose range for further study.
Interventions
DRUGComparator: Placebo
Placebo to match assigned treatment arm; one orally-administered dose
DRUGMK0974
MK0974 25 mg; one orally-administered dose
DRUGRizatriptan
Rizatriptan 10 mg; one orally-administered dose
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Patient has at least 1 year history of migraine (with or without aura) * Females of childbearing years must use acceptable contraception throughout trial * Patient is in general good health based on screening assessment
Exclusion criteria
* Patient is pregnant/breast-feeding (or is a female expecting to conceive during the study period) * Patient has heart disease, uncontrolled hypertension (high blood pressure), uncontrolled diabetes or other significant disease * Patient has major depression, other pain syndromes that might interfere with study assessments, psychiatric conditions, dementia, or significant neurological disorders (other then migraine) * Patient has a history of gastric or small intestinal surgery or has a disease that causes malabsorption * Patient has a history of cancer within the last 5 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pain Relief at 2 Hours | 2 hours post dose | Pain severity was rated by the participants in a paper diary. Pain severity rating scale: 0 (no pain), 1 (mild), 2 (moderate), 3 (severe). Pain Relief is defined as participants reporting relief from moderate to severe migraine headache (Grade 2 or 3) to mild or none (Grade 1 or 0) in the setting of a typical migraine attack. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pain Freedom at 2 Hours | 2 hours post dose | Pain severity was rated by the participants in a paper diary. Pain severity rating scale: 0 (no pain), 1 (mild), 2 (moderate), 3 (severe). Pain freedom is defined as no pain (Grade 0) at 2 hours post dose. |
| Sustained Pain Relief | 2-24 hours post dose | Pain severity was rated by the participants in a paper diary. Pain severity rating scale: 0 (no pain), 1 (mild), 2 (moderate), 3 (severe). Sustained pain relief is defined as pain relief at 2 hours and no headache recurrence, no need for the optional 2nd dose, or any rescue medication, between 2 and 24 hours post dose. |
| Sustained Pain Freedom | 2-24 hours post dose | Pain severity was rated by the participants in a paper diary. Pain severity rating scale: 0 (no pain), 1 (mild), 2 (moderate), 3 (severe). Sustained pain freedom is defined as pain freedom at 2 hours and no headache return to mild/moderate/severe, no need for the optional 2nd dose, or any rescue medication, between 2 and 24 hours post dose. |
Participant flow
Recruitment details
20 centers from the United States participated. First Patient treated on 01 December 2005; Last Patient Last Treatment was on 01 May 2006.
Pre-assignment details
Participants were assessed, using the protocol inclusion and exclusion criteria, at Visit 1, and if eligible were randomized at that same visit.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo to match assigned treatment arm; one orally-administered dose, plus an optional second dose of active drug, per assigned treatment arm, to treat a single moderate-to-severe migraine headache.
The reported number of participants are all patients randomized who received study drug and completed the study. | 115 |
| MK0974 25 mg MK0974 25 mg; one orally-administered dose, plus an optional second dose (placebo) to treat a single moderate-to-severe migraine headache.
The reported number of participants are all patients randomized who received study drug and completed the study. | 14 |
| MK0974 50 mg MK0974 50 mg; one orally-administered dose, plus an optional second dose (placebo) to treat a single moderate-to-severe migraine headache.
The reported number of participants are all patients randomized who received study drug and completed the study. | 15 |
| MK0974 100 mg MK0974 100 mg; one orally-administered dose, plus an optional second dose (placebo) to treat a single moderate-to-severe migraine headache.
The reported number of participants are all patients randomized who received study drug and completed the study. | 16 |
| MK0974 200 mg MK0974 200 mg; one orally-administered dose, plus an optional second dose (placebo) to treat a single moderate-to-severe migraine headache.
The reported number of participants are all patients randomized who received study drug and completed the study. | 12 |
| MK0974 300 mg MK0974 300 mg; one orally-administered dose, plus an optional second dose (placebo) to treat a single moderate-to-severe migraine headache.
The reported number of participants are all patients randomized who received study drug and completed the study. | 39 |
| MK0974 400 mg MK0974 400 mg; one orally-administered dose plus an optional second dose (placebo) to treat a single moderate-to-severe migraine headache.
The reported number of participants are all patients randomized who received study drug and completed the study. | 45 |
| MK0974 600 mg MK0974 600 mg; one orally-administered dose plus an optional second dose (placebo) to treat a single moderate-to-severe migraine headache.
The reported number of participants are all patients randomized who received study drug and completed the study. | 40 |
| Rizatriptan 10 mg Rizatriptan 10 mg; one orally-administered dose plus an optional second dose (placebo) to treat a single moderate-to-severe migraine headache.
The reported number of participants are all patients randomized who received study drug and completed the study. | 34 |
| Total | 330 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Abnormal baseline lab values | 7 | 0 | 2 | 0 | 0 | 2 | 2 | 0 | 4 |
| Overall Study | Lack of Qualifying Event | 8 | 2 | 1 | 1 | 1 | 3 | 3 | 2 | 5 |
| Overall Study | Lost to Follow-up | 3 | 0 | 0 | 0 | 2 | 2 | 1 | 2 | 0 |
| Overall Study | Overwhelmed | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 1 | 0 | 0 | 0 | 1 | 0 | 1 | 1 | 0 |
| Overall Study | Protocol Violator | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Reported as completing trial in error | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Site Terminated | 10 | 0 | 0 | 0 | 0 | 7 | 1 | 6 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | MK0974 25 mg | MK0974 50 mg | MK0974 100 mg | MK0974 200 mg | MK0974 300 mg | MK0974 400 mg | MK0974 600 mg | Rizatriptan 10 mg | Total | Placebo |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 43.0 years STANDARD_DEVIATION 10.1 | 41.5 years STANDARD_DEVIATION 10.9 | 40.9 years STANDARD_DEVIATION 7.5 | 34.3 years STANDARD_DEVIATION 11.7 | 40.5 years STANDARD_DEVIATION 10.4 | 40.1 years STANDARD_DEVIATION 11.9 | 44.5 years STANDARD_DEVIATION 12 | 40.2 years STANDARD_DEVIATION 10.8 | 41.5 years STANDARD_DEVIATION 10.9 | 42.2 years STANDARD_DEVIATION 10.6 |
| Baseline Severity Baseline Severity data missing | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Baseline Severity Moderate | 11 Participants | 9 Participants | 15 Participants | 6 Participants | 26 Participants | 34 Participants | 30 Participants | 27 Participants | 239 Participants | 81 Participants |
| Baseline Severity Severe | 3 Participants | 6 Participants | 1 Participants | 6 Participants | 12 Participants | 11 Participants | 10 Participants | 7 Participants | 90 Participants | 34 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Asian | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants | 2 participants | 0 participants |
| Race/Ethnicity, Customized Black | 4 participants | 3 participants | 3 participants | 5 participants | 7 participants | 10 participants | 2 participants | 5 participants | 57 participants | 18 participants |
| Race/Ethnicity, Customized European | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Hispanic American | 0 participants | 0 participants | 1 participants | 1 participants | 3 participants | 0 participants | 0 participants | 0 participants | 9 participants | 4 participants |
| Race/Ethnicity, Customized Multi-Racial | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized White | 10 participants | 11 participants | 11 participants | 6 participants | 29 participants | 34 participants | 38 participants | 28 participants | 259 participants | 92 participants |
| Sex: Female, Male Female | 11 Participants | 14 Participants | 14 Participants | 9 Participants | 34 Participants | 42 Participants | 36 Participants | 28 Participants | 292 Participants | 104 Participants |
| Sex: Female, Male Male | 3 Participants | 1 Participants | 2 Participants | 3 Participants | 5 Participants | 3 Participants | 4 Participants | 6 Participants | 38 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 10 / 47 | 4 / 17 | 9 / 19 | 4 / 27 | 7 / 18 | 9 / 51 | 12 / 52 | 14 / 49 | 10 / 50 |
| serious Total, serious adverse events | 1 / 47 | 0 / 17 | 0 / 19 | 0 / 27 | 0 / 18 | 0 / 51 | 0 / 52 | 0 / 49 | 0 / 50 |
Outcome results
Primary
Pain Relief at 2 Hours
Pain severity was rated by the participants in a paper diary. Pain severity rating scale: 0 (no pain), 1 (mild), 2 (moderate), 3 (severe). Pain Relief is defined as participants reporting relief from moderate to severe migraine headache (Grade 2 or 3) to mild or none (Grade 1 or 0) in the setting of a typical migraine attack.
Time frame: 2 hours post dose
Population: All Patients Treated (APT): included all randomized participants who took study medication and reported the post-dose assessment of the primary efficacy measure. Patients were counted in the treatment group to which they were randomized.~One patient in the MK974 300 mg group was excluded because baseline headache severity information was missing.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Pain Relief at 2 Hours | 52 Participants |
| MK0974 25 mg | Pain Relief at 2 Hours | 5 Participants |
| MK0974 50 mg | Pain Relief at 2 Hours | 9 Participants |
| MK0974 100 mg | Pain Relief at 2 Hours | 8 Participants |
| MK0974 200 mg | Pain Relief at 2 Hours | 5 Participants |
| MK0974 300 mg | Pain Relief at 2 Hours | 25 Participants |
| MK0974 400 mg | Pain Relief at 2 Hours | 22 Participants |
| MK0974 600 mg | Pain Relief at 2 Hours | 27 Participants |
| Rizatriptan 10 mg | Pain Relief at 2 Hours | 24 Participants |
Comparison: Only the MK0974 300mg, 400mg, and 600mg groups are included in the comparison with placebo based on the protocol-specified test statistics selection and the fact that all lower doses were discontinued after the interim analysis. Overall power =85%p-value: 0.015generalized linear model
Secondary
Pain Freedom at 2 Hours
Pain severity was rated by the participants in a paper diary. Pain severity rating scale: 0 (no pain), 1 (mild), 2 (moderate), 3 (severe). Pain freedom is defined as no pain (Grade 0) at 2 hours post dose.
Time frame: 2 hours post dose
Population: All Patients Treated (APT): included all randomized participants who took study medication and reported the post-dose assessment of the primary efficacy measure. Patients were counted in the treatment group to which they were randomized.~One patient in the MK974 300 mg group was excluded because baseline headache severity information was missing.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Pain Freedom at 2 Hours | 16 Participants |
| MK0974 25 mg | Pain Freedom at 2 Hours | 3 Participants |
| MK0974 50 mg | Pain Freedom at 2 Hours | 7 Participants |
| MK0974 100 mg | Pain Freedom at 2 Hours | 3 Participants |
| MK0974 200 mg | Pain Freedom at 2 Hours | 2 Participants |
| MK0974 300 mg | Pain Freedom at 2 Hours | 17 Participants |
| MK0974 400 mg | Pain Freedom at 2 Hours | 11 Participants |
| MK0974 600 mg | Pain Freedom at 2 Hours | 13 Participants |
| Rizatriptan 10 mg | Pain Freedom at 2 Hours | 11 Participants |
Comparison: Only the MK0974 300mg, 400mg, and 600mg groups are included in the comparison with placebo based on the protocol-specified test statistics selection and the fact that all lower doses were discontinued after the interim analysis.p-value: <0.001generalized linear model
Secondary
Sustained Pain Freedom
Pain severity was rated by the participants in a paper diary. Pain severity rating scale: 0 (no pain), 1 (mild), 2 (moderate), 3 (severe). Sustained pain freedom is defined as pain freedom at 2 hours and no headache return to mild/moderate/severe, no need for the optional 2nd dose, or any rescue medication, between 2 and 24 hours post dose.
Time frame: 2-24 hours post dose
Population: All Patients Treated (APT): included all randomized participants who took study medication and reported the post-dose assessment of the primary efficacy measure. Patients were counted in the treatment group to which they were randomized.~One patient in the MK974 300 mg group was excluded because baseline headache severity information was missing.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Sustained Pain Freedom | 12 Participants |
| MK0974 25 mg | Sustained Pain Freedom | 1 Participants |
| MK0974 50 mg | Sustained Pain Freedom | 7 Participants |
| MK0974 100 mg | Sustained Pain Freedom | 3 Participants |
| MK0974 200 mg | Sustained Pain Freedom | 1 Participants |
| MK0974 300 mg | Sustained Pain Freedom | 15 Participants |
| MK0974 400 mg | Sustained Pain Freedom | 10 Participants |
| MK0974 600 mg | Sustained Pain Freedom | 13 Participants |
| Rizatriptan 10 mg | Sustained Pain Freedom | 6 Participants |
Comparison: Only the MK0974 300mg, 400mg, and 600mg groups are included in the comparison with placebo based on the protocol-specified test statistics selection and the fact that all lower doses were discontinued after the interim analysis.p-value: <0.001generalized linear model
Secondary
Sustained Pain Relief
Pain severity was rated by the participants in a paper diary. Pain severity rating scale: 0 (no pain), 1 (mild), 2 (moderate), 3 (severe). Sustained pain relief is defined as pain relief at 2 hours and no headache recurrence, no need for the optional 2nd dose, or any rescue medication, between 2 and 24 hours post dose.
Time frame: 2-24 hours post dose
Population: All Patients Treated (APT): included all randomized participants who took study medication and reported the post-dose assessment of the primary efficacy measure. Patients were counted in the treatment group to which they were randomized.~One patient in the MK974 300 mg group was excluded because baseline headache severity information was missing
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Sustained Pain Relief | 27 Participants |
| MK0974 25 mg | Sustained Pain Relief | 1 Participants |
| MK0974 50 mg | Sustained Pain Relief | 9 Participants |
| MK0974 100 mg | Sustained Pain Relief | 3 Participants |
| MK0974 200 mg | Sustained Pain Relief | 3 Participants |
| MK0974 300 mg | Sustained Pain Relief | 20 Participants |
| MK0974 400 mg | Sustained Pain Relief | 17 Participants |
| MK0974 600 mg | Sustained Pain Relief | 21 Participants |
| Rizatriptan 10 mg | Sustained Pain Relief | 12 Participants |
Comparison: Only the MK0974 300mg, 400mg, and 600mg groups are included in the comparison with placebo based on the protocol-specified test statistics selection and the fact that all lower doses were discontinued after the interim analysis.p-value: <0.001generalized linear model