Migraine
Conditions
Brief summary
The purpose of the study is to demonstrate the effectiveness and appropriate dosage level of MK3207 in the treatment of acute migraine.
Interventions
DRUGMK3207- 2.5 mg
Arm 1: MK3207 2.5 mg taken after migraine onset.
DRUGMK3207- 5 mg
Arm 2: MK3207 5 mg taken after migraine onset.
DRUGMK3207- 10 mg
Arm 3: MK3207 10 mg taken after migraine onset.
DRUGMK3207- 20 mg
Arm 4: MK3207 20 mg taken after migraine onset.
DRUGMK3207- 50 mg
Arm 5: MK3207 50 mg taken after migraine onset.
DRUGMK3207- 100 mg
Arm 6: MK3207 100 mg taken after migraine onset.
DRUGComparator: placebo (unspecified)
Placebo taken after migraine onset.
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 65 Years
Healthy volunteers
No
Inclusion criteria
* Men and Women from 18 to 65 years of age * 1+ year history of migraine that typically last from 4 to 72 hours if untreated * Had from 2 to 8 moderate or severe migraine attacks per month in the last 2 months * Not pregnant or planning to become pregnant in next 6 months
Exclusion criteria
* Pregnant or breast-feeding, or planning to become pregnant in next 6 months * Cannot distinguish migraine attacks from tension type headaches * Migraines are mild or resolve without medication in less than 2 hours * More than 15 headache-days per month or have taken medication on more than 10 days per month in the last 3 months * Basilar type or hemiplegic migraine headaches * More than 50 years old when migraines began * History of cardiovascular disorder within last 6 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pain Freedom (PF) | 2 hours postdose | Reduction of a Grade 2 or 3 severity migraine at baseline to Grade 0 at 2 hours postdose. Rating of Headache Severity (Scale from Grade 0 to 3): * Grade 0: No pain * Grade 1: Mild pain * Grade 2: Moderate pain * Grade 3: Severe pain |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pain Relief (PR) | 2 hours postdose | Reduction of a Grade 2 or 3 severity migraine at baseline to mild or no pain (Grade 1 or 0) at 2 hours postdose. Rating of Headache Severity (Scale from Grade 0 to 3): * Grade 0: No pain * Grade 1: Mild pain * Grade 2: Moderate pain * Grade 3: Severe pain |
| Absence of Photophobia | 2 hours postdose | Absence of photophobia at 2 hours postdose as recorded by patient on paper diary. |
| Absence of Phonophobia | 2 hours postdose | Absence of phonophobia at 2 hours postdose as recorded by patient on paper diary. |
| Absence of Nausea | 2 hours postdose | Absence of nausea at 2 hours postdose as recorded by patient on paper diary. |
| Sustained Pain Freedom (SPF) | 2-24 hours postdose | Pain freedom (Grade 0) at 2 hours postdose, with no administration of any rescue medication and no occurrence thereafter of a mild/moderate/severe headache during the 2 to 24 hours after dosing with study medication. |
Participant flow
Recruitment details
Participants were recruited from 47 neurological and general research centers worldwide (19 in the United States and 28 internationally). The primary therapy period was between 2-Jul-08 to 16-Jan-09.
Pre-assignment details
Participants were assessed using the protocol inclusion and exclusion criteria at Visit 1 and, if eligible, were randomized at the same visit.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo; one orally administered dose to treat a single moderate-to-severe migraine headache.
The participants reported in the Baseline Characteristics are randomized participants that received study treatment. | 140 |
| MK3207 2.5 mg MK3207 2.5 mg; one orally administered dose to treat a single moderate-to-severe migraine headache.
The participants reported in the Baseline Characteristics are randomized participants that received study treatment. | 33 |
| MK3207 5 mg MK3207 5 mg; one orally administered dose to treat a single moderate-to-severe migraine headache.
The participants reported in the Baseline Characteristics are randomized participants that received study treatment. | 47 |
| MK3207 10 mg MK3207 10 mg; one orally administered dose to treat a single moderate-to-severe migraine headache.
The participants reported in the Baseline Characteristics are randomized participants that received study treatment. | 67 |
| MK3207 20 mg MK3207 20 mg; one orally administered dose to treat a single moderate-to-severe migraine headache.
The participants reported in the Baseline Characteristics are randomized participants that received study treatment. | 67 |
| MK3207 50 mg MK3207 50 mg; one orally administered dose to treat a single moderate-to-severe migraine headache.
The participants reported in the Baseline Characteristics are randomized participants that received study treatment. | 68 |
| MK3207 100 mg MK3207 100 mg; one orally administered dose to treat a single moderate-to-severe migraine headache.
The participants reported in the Baseline Characteristics are randomized participants that received study treatment. | 62 |
| MK3207 200 mg MK3207 200 mg; one orally administered dose to treat a single moderate-to-severe migraine headache.
The participants reported in the Baseline Characteristics are randomized participants that received study treatment. | 63 |
| Total | 547 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Lack of Qualifying Event | 16 | 2 | 6 | 8 | 11 | 13 | 11 | 6 |
| Overall Study | Lost to Follow-up | 3 | 2 | 1 | 1 | 2 | 2 | 3 | 1 |
| Overall Study | Physician Decision | 2 | 0 | 0 | 0 | 1 | 0 | 2 | 0 |
| Overall Study | Pregnancy | 0 | 1 | 0 | 0 | 1 | 0 | 2 | 0 |
| Overall Study | Protocol Specified Criteria | 3 | 0 | 1 | 2 | 1 | 0 | 2 | 1 |
| Overall Study | Protocol Violation | 2 | 0 | 1 | 3 | 2 | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 1 | 1 | 2 | 1 | 1 | 1 | 2 |
Baseline characteristics
| Characteristic | Total | MK3207 200 mg | MK3207 100 mg | MK3207 50 mg | MK3207 20 mg | MK3207 10 mg | MK3207 5 mg | MK3207 2.5 mg | Placebo |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 42.7 years STANDARD_DEVIATION 10.9 | 40.5 years STANDARD_DEVIATION 10.7 | 42.2 years STANDARD_DEVIATION 10.9 | 42.2 years STANDARD_DEVIATION 10.8 | 44.1 years STANDARD_DEVIATION 11.3 | 44.1 years STANDARD_DEVIATION 10 | 43.4 years STANDARD_DEVIATION 11.1 | 43.3 years STANDARD_DEVIATION 10.5 | 42.1 years STANDARD_DEVIATION 11.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 69 Participants | 10 Participants | 9 Participants | 13 Participants | 10 Participants | 4 Participants | 4 Participants | 4 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 478 Participants | 53 Participants | 53 Participants | 55 Participants | 57 Participants | 63 Participants | 43 Participants | 29 Participants | 125 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 3 participants | 0 participants | 0 participants | 0 participants | 1 participants | 1 participants | 0 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Asian | 6 participants | 1 participants | 1 participants | 1 participants | 1 participants | 0 participants | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Black | 17 participants | 3 participants | 2 participants | 2 participants | 1 participants | 3 participants | 1 participants | 0 participants | 5 participants |
| Race/Ethnicity, Customized Multi-Racial | 2 participants | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 2 participants | 0 participants | 0 participants | 1 participants | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized White | 517 participants | 59 participants | 59 participants | 64 participants | 63 participants | 62 participants | 46 participants | 32 participants | 132 participants |
| Sex: Female, Male Female | 476 Participants | 54 Participants | 52 Participants | 62 Participants | 54 Participants | 62 Participants | 40 Participants | 27 Participants | 125 Participants |
| Sex: Female, Male Male | 71 Participants | 9 Participants | 10 Participants | 6 Participants | 13 Participants | 5 Participants | 7 Participants | 6 Participants | 15 Participants |
| Study Region Ex-United States | 277 Participants | 43 Participants | 28 Participants | 23 Participants | 28 Participants | 37 Participants | 25 Participants | 19 Participants | 74 Participants |
| Study Region United States | 270 Participants | 20 Participants | 34 Participants | 45 Participants | 39 Participants | 30 Participants | 22 Participants | 14 Participants | 66 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 |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 20 / 142 | 10 / 32 | 18 / 47 | 9 / 66 | 14 / 67 | 16 / 68 | 17 / 62 | 11 / 63 |
| serious Total, serious adverse events | 1 / 142 | 0 / 32 | 0 / 47 | 1 / 66 | 0 / 67 | 0 / 68 | 0 / 62 | 0 / 63 |
Outcome results
Primary
Pain Freedom (PF)
Reduction of a Grade 2 or 3 severity migraine at baseline to Grade 0 at 2 hours postdose. Rating of Headache Severity (Scale from Grade 0 to 3): * Grade 0: No pain * Grade 1: Mild pain * Grade 2: Moderate pain * Grade 3: Severe pain
Time frame: 2 hours postdose
Population: Full Analysis Set (FAS), which included all randomized participants who administered study treatment, had both a baseline severity measurement and at least one postdose efficacy measurement prior to or including the 2-hour time point.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Pain Freedom (PF) | 13 Participants |
| MK3207 2.5 mg | Pain Freedom (PF) | 4 Participants |
| MK3207 5 mg | Pain Freedom (PF) | 5 Participants |
| MK3207 10 mg | Pain Freedom (PF) | 16 Participants |
| MK3207 20 mg | Pain Freedom (PF) | 12 Participants |
| MK3207 50 mg | Pain Freedom (PF) | 14 Participants |
| MK3207 100 mg | Pain Freedom (PF) | 14 Participants |
| MK3207 200 mg | Pain Freedom (PF) | 21 Participants |
p-value: <0.001Generalized linear regression model
Secondary
Absence of Nausea
Absence of nausea at 2 hours postdose as recorded by patient on paper diary.
Time frame: 2 hours postdose
Population: Full Analysis Set (FAS), which included all randomized participants who administered study treatment, had both a baseline severity measurement and at least one postdose efficacy measurement prior to or including the 2-hour time point.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Absence of Nausea | 79 Participants |
| MK3207 2.5 mg | Absence of Nausea | 19 Participants |
| MK3207 5 mg | Absence of Nausea | 25 Participants |
| MK3207 10 mg | Absence of Nausea | 44 Participants |
| MK3207 20 mg | Absence of Nausea | 42 Participants |
| MK3207 50 mg | Absence of Nausea | 44 Participants |
| MK3207 100 mg | Absence of Nausea | 41 Participants |
| MK3207 200 mg | Absence of Nausea | 45 Participants |
p-value: 0.007Generalized linear regression model
Secondary
Absence of Phonophobia
Absence of phonophobia at 2 hours postdose as recorded by patient on paper diary.
Time frame: 2 hours postdose
Population: Full Analysis Set (FAS), which included all randomized participants who administered study treatment, had both a baseline severity measurement and at least one postdose efficacy measurement prior to or including the 2-hour time point.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Absence of Phonophobia | 57 Participants |
| MK3207 2.5 mg | Absence of Phonophobia | 12 Participants |
| MK3207 5 mg | Absence of Phonophobia | 18 Participants |
| MK3207 10 mg | Absence of Phonophobia | 35 Participants |
| MK3207 20 mg | Absence of Phonophobia | 35 Participants |
| MK3207 50 mg | Absence of Phonophobia | 38 Participants |
| MK3207 100 mg | Absence of Phonophobia | 31 Participants |
| MK3207 200 mg | Absence of Phonophobia | 37 Participants |
p-value: <0.001Generalized linear regression model
Secondary
Absence of Photophobia
Absence of photophobia at 2 hours postdose as recorded by patient on paper diary.
Time frame: 2 hours postdose
Population: Full Analysis Set (FAS), which included all randomized participants who administered study treatment, had both a baseline severity measurement and at least one postdose efficacy measurement prior to or including the 2-hour time point.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Absence of Photophobia | 51 Participants |
| MK3207 2.5 mg | Absence of Photophobia | 10 Participants |
| MK3207 5 mg | Absence of Photophobia | 15 Participants |
| MK3207 10 mg | Absence of Photophobia | 32 Participants |
| MK3207 20 mg | Absence of Photophobia | 27 Participants |
| MK3207 50 mg | Absence of Photophobia | 32 Participants |
| MK3207 100 mg | Absence of Photophobia | 26 Participants |
| MK3207 200 mg | Absence of Photophobia | 33 Participants |
p-value: <0.001Generalized linear regression model
Secondary
Pain Relief (PR)
Reduction of a Grade 2 or 3 severity migraine at baseline to mild or no pain (Grade 1 or 0) at 2 hours postdose. Rating of Headache Severity (Scale from Grade 0 to 3): * Grade 0: No pain * Grade 1: Mild pain * Grade 2: Moderate pain * Grade 3: Severe pain
Time frame: 2 hours postdose
Population: Full Analysis Set (FAS), which included all randomized participants who administered study treatment, had both a baseline severity measurement and at least one postdose efficacy measurement prior to or including the 2-hour time point.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Pain Relief (PR) | 48 Participants |
| MK3207 2.5 mg | Pain Relief (PR) | 15 Participants |
| MK3207 5 mg | Pain Relief (PR) | 19 Participants |
| MK3207 10 mg | Pain Relief (PR) | 36 Participants |
| MK3207 20 mg | Pain Relief (PR) | 36 Participants |
| MK3207 50 mg | Pain Relief (PR) | 41 Participants |
| MK3207 100 mg | Pain Relief (PR) | 31 Participants |
| MK3207 200 mg | Pain Relief (PR) | 40 Participants |
p-value: <0.001Generalized linear regression model
Secondary
Sustained Pain Freedom (SPF)
Pain freedom (Grade 0) at 2 hours postdose, with no administration of any rescue medication and no occurrence thereafter of a mild/moderate/severe headache during the 2 to 24 hours after dosing with study medication.
Time frame: 2-24 hours postdose
Population: Full Analysis Set (FAS), which included all randomized participants who met the FAS criteria for PF at 2 hours postdose, and who, between 2-24 hours posedose, either 1) did not have PF at any time, 2) used rescue, or 3) answered the 24 hour recurrence question.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Sustained Pain Freedom (SPF) | 10 Participants |
| MK3207 2.5 mg | Sustained Pain Freedom (SPF) | 4 Participants |
| MK3207 5 mg | Sustained Pain Freedom (SPF) | 2 Participants |
| MK3207 10 mg | Sustained Pain Freedom (SPF) | 13 Participants |
| MK3207 20 mg | Sustained Pain Freedom (SPF) | 10 Participants |
| MK3207 50 mg | Sustained Pain Freedom (SPF) | 12 Participants |
| MK3207 100 mg | Sustained Pain Freedom (SPF) | 12 Participants |
| MK3207 200 mg | Sustained Pain Freedom (SPF) | 17 Participants |
p-value: <0.001Generalized linear regression model