Migraine
Conditions
Brief summary
The purpose of this study is to investigate the efficacy and safety of MK0974 compared to a placebo for acute migraine.
Interventions
DRUGMK0974 50 mg
DRUGMK0974 150 mg
DRUGMK0974 300 mg
DRUGComparator: Placebo
MK0974 50 mg soft gel capsule Placebo; MK0974 150 mg soft gel capsule Placebo; MK0974 300 mg soft gel capsule Placebo.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Exclusion criteria
* Patient is pregnant/breast-feeding (or is a female expecting to conceive during the study period) * Patient has history or evidence of uncontrolled diabetes, or Human Immunodeficiency Virus (HIV) disease. Patient has uncontrolled cardiovascular disease * Patient has major depression, other pain syndromes that might interfere with study assessments, psychiatric conditions, dementia, or significant neurological disorders (other than 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 |
|---|---|---|
| Number of Patients Reporting Absence of Nausea at 2 Hours Post Dose | 2 hours post dose | Respective experience (yes/no) of migraine-associated symptoms (including nausea) was recorded by the patient in a diary. |
| Number of Patients Reporting Pain Relief at 2 Hours Post Dose | 2 hours post dose | Reduction of a Grade 2 or 3 severity migraine at baseline to mild or no pain (Grade 1 or 0) at 2 hours post dose. Headache severity was recorded by the patient in a diary. 0=no pain; 1=mild pain; 2=moderate pain; 3=severe pain. |
| Number of Patients Reporting Absence of Photophobia at 2 Hours Post Dose | 2 hours post dose | Respective experience (yes/no) of migraine-associated symptoms (including photophobia) was recorded by the patient in a diary. |
| Number of Patients Reporting Absence of Phonophobia at 2 Hours Post Dose | 2 hours post dose | Respective experience (yes/no) of migraine-associated symptoms (including phonophobia) was recorded by the patient in a diary. |
| Number of Patients Reporting Pain Freedom at 2 Hours Postdose | 2 hours post dose | Pain Freedom was defined as a reduction of a Grade 2 or 3 severity migraine at baseline to a no pain (Grade 0) at 2 hours post dose. Headache severity was recorded by the patient in a diary. 0=no pain; 1=mild pain; 2=moderate pain; 3=severe pain. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Who Have Total Migraine Freedom 2 to 24 Hours Postdose | 2 to 24 hours postdose | Pain Freedom and no migraine-associated symptoms at 2 hours postdose, with no administration of any rescue medication and no occurrence thereafter of a mild/moderate/severe headache or migraine-associated symptom during the 24 hours after dosing with study medication. |
| Number of Patients Who Have Total Migraine Freedom 2 Hours Postdose | 2 hours postdose | Pain Freedom and no migraine-associated symptoms at 2 hours postdose. |
| Number of Patients Who Have Sustained Pain-Freedom From 2 to 24 Hours Postdose | 2 to 24 hours postdose | Pain Freedom at 2 hours postdose, with no administration of any rescue medication and no occurrence thereafter of a mild/moderate/severe headache during the 24 hours after dosing with study medication. |
Participant flow
Recruitment details
There were 83 centers worldwide that participated: United States (36), Latin America (9), and Europe (38). First Patient Treated = 25 March 2007, and Last Patient Last Treatment = 29 November 2007.
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 |
|---|---|
| MK0974 50 mg MK0974 50 mg; one orally-administered dose, plus an optional second dose (MK0974 50 mg) to treat a single moderate-to-severe migraine attack
The reported number of participants are all patients randomized who received study drug and completed the study. | 177 |
| MK0974 150 mg MK0974 150 mg; one orally-administered dose, plus an optional second dose (MK0974 150 mg) to treat a single moderate-to-severe migraine attack
The reported number of participants are all patients randomized who received study drug and completed the study. | 381 |
| MK0974 300 mg MK0974 300 mg; one orally-administered dose, plus an optional second dose (MK0974 300 mg or placebo) to treat a single moderate-to-severe migraine attack
The reported number of participants are all patients randomized who received study drug and completed the study. | 371 |
| Placebo Placebo; one orally-administered dose, plus an optional second dose (placebo) to treat a single moderate-to-severe migraine attack
The reported number of participants are all patients randomized who received study drug and completed the study. | 365 |
| Total | 1,294 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 1 |
| Overall Study | Lack of Efficacy | 0 | 0 | 0 | 1 |
| Overall Study | Lack of Qualifying Event | 38 | 71 | 69 | 84 |
| Overall Study | Lost to Follow-up | 10 | 10 | 18 | 18 |
| Overall Study | Physician Decision | 1 | 3 | 2 | 1 |
| Overall Study | Pregnancy | 0 | 1 | 0 | 0 |
| Overall Study | Protocol Violation | 13 | 10 | 11 | 8 |
| Overall Study | Withdrawal by Subject | 5 | 6 | 9 | 11 |
Baseline characteristics
| Characteristic | MK0974 150 mg | MK0974 300 mg | Placebo | Total | MK0974 50 mg |
|---|---|---|---|---|---|
| Age, Continuous | 41.6 years STANDARD_DEVIATION 11 | 41.8 years STANDARD_DEVIATION 11.6 | 41.9 years STANDARD_DEVIATION 11.9 | 41.7 years STANDARD_DEVIATION 11.5 | 41.4 years STANDARD_DEVIATION 11.3 |
| Baseline Severity Baseline Severity missing | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Baseline Severity Moderate | 254 Participants | 237 Participants | 235 Participants | 834 Participants | 108 Participants |
| Baseline Severity Severe | 127 Participants | 133 Participants | 130 Participants | 459 Participants | 69 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 2 participants | 0 participants | 0 participants | 3 participants | 1 participants |
| Race/Ethnicity, Customized Asian | 6 participants | 1 participants | 8 participants | 16 participants | 1 participants |
| Race/Ethnicity, Customized Black | 16 participants | 23 participants | 20 participants | 69 participants | 10 participants |
| Race/Ethnicity, Customized Missing | 0 participants | 0 participants | 1 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Multi-Racial | 37 participants | 44 participants | 33 participants | 131 participants | 17 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 participants | 1 participants | 0 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized White | 320 participants | 302 participants | 303 participants | 1073 participants | 148 participants |
| Sex: Female, Male Female | 329 Participants | 320 Participants | 318 Participants | 1123 Participants | 156 Participants |
| Sex: Female, Male Male | 52 Participants | 51 Participants | 47 Participants | 171 Participants | 21 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 | 45 / 177 | 69 / 381 | 94 / 370 | 77 / 366 |
| serious Total, serious adverse events | 0 / 177 | 1 / 381 | 0 / 370 | 1 / 366 |
Outcome results
Primary
Number of Patients Reporting Absence of Nausea at 2 Hours Post Dose
Respective experience (yes/no) of migraine-associated symptoms (including nausea) was recorded by the patient in a diary.
Time frame: 2 hours post dose
Population: All randomized, treated patients who have at least one post-dose measurement at or prior to 2 hours.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK0974 50 mg | Number of Patients Reporting Absence of Nausea at 2 Hours Post Dose | 113 Participants |
| MK0974 150 mg | Number of Patients Reporting Absence of Nausea at 2 Hours Post Dose | 260 Participants |
| MK0974 300 mg | Number of Patients Reporting Absence of Nausea at 2 Hours Post Dose | 258 Participants |
| Placebo | Number of Patients Reporting Absence of Nausea at 2 Hours Post Dose | 196 Participants |
p-value: <0.001Regression, Logistic
p-value: <0.001Regression, Logistic
Primary
Number of Patients Reporting Absence of Phonophobia at 2 Hours Post Dose
Respective experience (yes/no) of migraine-associated symptoms (including phonophobia) was recorded by the patient in a diary.
Time frame: 2 hours post dose
Population: All randomized, treated patients who have at least one post-dose measurement at or prior to 2 hours.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK0974 50 mg | Number of Patients Reporting Absence of Phonophobia at 2 Hours Post Dose | 85 Participants |
| MK0974 150 mg | Number of Patients Reporting Absence of Phonophobia at 2 Hours Post Dose | 192 Participants |
| MK0974 300 mg | Number of Patients Reporting Absence of Phonophobia at 2 Hours Post Dose | 206 Participants |
| Placebo | Number of Patients Reporting Absence of Phonophobia at 2 Hours Post Dose | 152 Participants |
p-value: <0.001Regression, Logistic
p-value: <0.001Regression, Logistic
Primary
Number of Patients Reporting Absence of Photophobia at 2 Hours Post Dose
Respective experience (yes/no) of migraine-associated symptoms (including photophobia) was recorded by the patient in a diary.
Time frame: 2 hours post dose
Population: All randomized, treated patients who have at least one post-dose measurement at or prior to 2 hours.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK0974 50 mg | Number of Patients Reporting Absence of Photophobia at 2 Hours Post Dose | 72 Participants |
| MK0974 150 mg | Number of Patients Reporting Absence of Photophobia at 2 Hours Post Dose | 176 Participants |
| MK0974 300 mg | Number of Patients Reporting Absence of Photophobia at 2 Hours Post Dose | 179 Participants |
| Placebo | Number of Patients Reporting Absence of Photophobia at 2 Hours Post Dose | 119 Participants |
p-value: <0.001Regression, Logistic
p-value: <0.001Regression, Logistic
Primary
Number of Patients Reporting Pain Freedom at 2 Hours Postdose
Pain Freedom was defined as a reduction of a Grade 2 or 3 severity migraine at baseline to a no pain (Grade 0) at 2 hours post dose. Headache severity was recorded by the patient in a diary. 0=no pain; 1=mild pain; 2=moderate pain; 3=severe pain.
Time frame: 2 hours post dose
Population: All randomized, treated patients who have at least one post-dose measurement at or prior to 2 hours.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK0974 50 mg | Number of Patients Reporting Pain Freedom at 2 Hours Postdose | 29 Participants |
| MK0974 150 mg | Number of Patients Reporting Pain Freedom at 2 Hours Postdose | 88 Participants |
| MK0974 300 mg | Number of Patients Reporting Pain Freedom at 2 Hours Postdose | 88 Participants |
| Placebo | Number of Patients Reporting Pain Freedom at 2 Hours Postdose | 39 Participants |
p-value: <0.001Regression, Logistic
p-value: <0.001Regression, Logistic
Primary
Number of Patients Reporting Pain Relief at 2 Hours Post Dose
Reduction of a Grade 2 or 3 severity migraine at baseline to mild or no pain (Grade 1 or 0) at 2 hours post dose. Headache severity was recorded by the patient in a diary. 0=no pain; 1=mild pain; 2=moderate pain; 3=severe pain.
Time frame: 2 hours post dose
Population: All randomized, treated patients who have at least one post-dose measurement at or prior to 2 hours.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK0974 50 mg | Number of Patients Reporting Pain Relief at 2 Hours Post Dose | 78 Participants |
| MK0974 150 mg | Number of Patients Reporting Pain Relief at 2 Hours Post Dose | 205 Participants |
| MK0974 300 mg | Number of Patients Reporting Pain Relief at 2 Hours Post Dose | 205 Participants |
| Placebo | Number of Patients Reporting Pain Relief at 2 Hours Post Dose | 120 Participants |
p-value: <0.001Regression, Logistic
p-value: <0.001Regression, Logistic
Secondary
Number of Patients Who Have Sustained Pain-Freedom From 2 to 24 Hours Postdose
Pain Freedom at 2 hours postdose, with no administration of any rescue medication and no occurrence thereafter of a mild/moderate/severe headache during the 24 hours after dosing with study medication.
Time frame: 2 to 24 hours postdose
Population: All randomized, treated patients who have at least one post-dose measurement at or prior to 2 hours and who either 1) did not have pain freedom at any time between 2 and 24 hours postdose, 2) used rescue medication between 2 and 24 hours postdose or 3) answered the 24 hour recurrence question (a question that ascertains recurrence of migraine pain)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK0974 50 mg | Number of Patients Who Have Sustained Pain-Freedom From 2 to 24 Hours Postdose | 25 Participants |
| MK0974 150 mg | Number of Patients Who Have Sustained Pain-Freedom From 2 to 24 Hours Postdose | 62 Participants |
| MK0974 300 mg | Number of Patients Who Have Sustained Pain-Freedom From 2 to 24 Hours Postdose | 63 Participants |
| Placebo | Number of Patients Who Have Sustained Pain-Freedom From 2 to 24 Hours Postdose | 26 Participants |
p-value: <0.001Regression, Logistic
p-value: <0.001Regression, Logistic
Secondary
Number of Patients Who Have Total Migraine Freedom 2 Hours Postdose
Pain Freedom and no migraine-associated symptoms at 2 hours postdose.
Time frame: 2 hours postdose
Population: All randomized, treated patients who have at least one post-dose measurement at or prior to 2 hours.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK0974 50 mg | Number of Patients Who Have Total Migraine Freedom 2 Hours Postdose | 24 Participants |
| MK0974 150 mg | Number of Patients Who Have Total Migraine Freedom 2 Hours Postdose | 78 Participants |
| MK0974 300 mg | Number of Patients Who Have Total Migraine Freedom 2 Hours Postdose | 78 Participants |
| Placebo | Number of Patients Who Have Total Migraine Freedom 2 Hours Postdose | 36 Participants |
p-value: <0.001Regression, Logistic
p-value: <0.001Regression, Logistic
Secondary
Number of Patients Who Have Total Migraine Freedom 2 to 24 Hours Postdose
Pain Freedom and no migraine-associated symptoms at 2 hours postdose, with no administration of any rescue medication and no occurrence thereafter of a mild/moderate/severe headache or migraine-associated symptom during the 24 hours after dosing with study medication.
Time frame: 2 to 24 hours postdose
Population: All randomized, treated patients who have at least one post-dose measurement at or prior to 2 hours and who either 1) did not have pain freedom at any time between 2 and 24 hours postdose, 2) used rescue medication between 2 and 24 hours postdose or 3) answered the 24 hour recurrence question (a question that ascertains recurrence of migraine pain)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK0974 50 mg | Number of Patients Who Have Total Migraine Freedom 2 to 24 Hours Postdose | 20 Participants |
| MK0974 150 mg | Number of Patients Who Have Total Migraine Freedom 2 to 24 Hours Postdose | 55 Participants |
| MK0974 300 mg | Number of Patients Who Have Total Migraine Freedom 2 to 24 Hours Postdose | 54 Participants |
| Placebo | Number of Patients Who Have Total Migraine Freedom 2 to 24 Hours Postdose | 23 Participants |
p-value: <0.001Regression, Logistic
p-value: <0.001Regression, Logistic