Migraine
Conditions
Brief summary
This study will test the safety and how effective telcagepant is when taken with ibuprofen or acetaminophen in participants with migraine with or without aura. The primary study hypothesis is that at least one drug combination is superior to telecagepant alone in the treatment of acute migraines.
Interventions
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
* Must be 18 years of age or older * History of migraine with or without aura for more than 1 year with 1-8 moderate or severe migraine attacks per month in the 2 months prior to starting in the study * Willing to stay awake for at least 2 hours after taking study drug * Able to read, understand and complete questionnaires and diaries
Exclusion criteria
* Breast-feeding, pregnant, or plan to become pregnant during the study * Not able to tell migraine attack from other headaches * Older than 50 years of age at migraine onset * Have more than 15 headache days per month or have taken medication for acute headache on more than 10 days per month in any of the 3 months before starting in the study * History of gastric or small intestinal surgery * History of heart attack, stroke, unstable angina, coronary artery bypass surgery or transient ischemic attack in the 3 months before starting in the study * Currently participating or have participated in a study with in investigational compound or device in the last 30 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Pain Freedom at Two Hours Post-dose | 2 hours post-dose | Pain severity was rated by the participants in a paper diary by grade; Grade 0 (no pain), Grade 1 (mild pain), Grade 2 (moderate pain), and Grade 3 (severe pain). Pain freedom was defined as a reduction in pain severity from moderate to severe migraine headache (Grade 2 or 3) to no pain (Grade 0). |
| Number of Participants Experiencing Adverse Events Within 48 Hours Post-dose (Count ≥4 in One or More Treatment Groups) | Up to 48 hours post-dose | An adverse event is any unfavorable and unintended change in the structure, function, or chemistry of the body whether or not considered related to the study treatment. |
| Number of Participants Experiencing Adverse Events Within 14 Days Post-dose (Count ≥4 in One or More Treatment Groups) | Up to 14 days post-dose | An adverse event is any unfavorable and unintended change in the structure, function, or chemistry of the body whether or not considered related to the study treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Pain Relief at 2 Hours Post-dose. | 2 hours post-dose | Pain severity was rated by the participants in a paper diary by grade; Grade 0 (no pain), Grade 1 (mild pain), Grade 2 (moderate pain), and Grade 3 (severe pain). Pain relief was defined as a reduction in pain severity from moderate to severe migraine headache (Grade 2 or 3) to mild or none (Grade 1 or 0). |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants take two placebo tablets and two placebo capsules, orally, at onset of migraine | 171 |
| Telcagepant 280 mg +Ibuprofen 400 mg Participants take one telcagepant 280 mg tablet, one ibuprofen 400 mg tablet, and two placebo capsules, orally, at onset of migraine | 171 |
| Telcagepant 280 mg +APAP 1000 mg Participants take one telcagepant 280 mg tablet, one placebo tablet, and two 500-mg APAP capsules, orally, at onset of migraine | 171 |
| Telcagepant 280 mg Participants take one telcagepant 280 mg tablet, one placebo tablet, and two placebo capsules, orally, at onset of migraine | 170 |
| Total | 683 |
Baseline characteristics
| Characteristic | Total | Placebo | Telcagepant 280 mg +Ibuprofen 400 mg | Telcagepant 280 mg +APAP 1000 mg | Telcagepant 280 mg |
|---|---|---|---|---|---|
| Age, Customized 20-29 years | 142 participants | 34 participants | 43 participants | 32 participants | 33 participants |
| Age, Customized <20 years | 10 participants | 4 participants | 0 participants | 3 participants | 3 participants |
| Age, Customized 30-39 years | 170 participants | 33 participants | 47 participants | 37 participants | 53 participants |
| Age, Customized 40-49 years | 209 participants | 58 participants | 51 participants | 49 participants | 51 participants |
| Age, Customized 50-59 years | 116 participants | 32 participants | 19 participants | 42 participants | 23 participants |
| Age, Customized 60-64 years | 18 participants | 4 participants | 6 participants | 6 participants | 2 participants |
| Age, Customized >=65 years | 18 participants | 6 participants | 5 participants | 2 participants | 5 participants |
| Sex: Female, Male Female | 583 Participants | 150 Participants | 139 Participants | 149 Participants | 145 Participants |
| Sex: Female, Male Male | 100 Participants | 21 Participants | 32 Participants | 22 Participants | 25 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 | 12 / 148 | 23 / 145 | 16 / 133 | 16 / 137 |
| serious Total, serious adverse events | 0 / 148 | 0 / 145 | 0 / 133 | 0 / 137 |
Outcome results
Primary
Number of Participants Experiencing Adverse Events Within 14 Days Post-dose (Count ≥4 in One or More Treatment Groups)
An adverse event is any unfavorable and unintended change in the structure, function, or chemistry of the body whether or not considered related to the study treatment.
Time frame: Up to 14 days post-dose
Population: All participants as treated (one participant assigned to the Telcagepant 280 mg arm only took the placebo tablet and is included in the Placebo arm for adverse event reporting).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants Experiencing Adverse Events Within 14 Days Post-dose (Count ≥4 in One or More Treatment Groups) | 31 participants |
| Telcagepant 280 mg +Ibuprofen 400 mg | Number of Participants Experiencing Adverse Events Within 14 Days Post-dose (Count ≥4 in One or More Treatment Groups) | 46 participants |
| Telcagepant 280 mg +APAP 1000 mg | Number of Participants Experiencing Adverse Events Within 14 Days Post-dose (Count ≥4 in One or More Treatment Groups) | 46 participants |
| Telcagepant 280 mg | Number of Participants Experiencing Adverse Events Within 14 Days Post-dose (Count ≥4 in One or More Treatment Groups) | 37 participants |
Primary
Number of Participants Experiencing Adverse Events Within 48 Hours Post-dose (Count ≥4 in One or More Treatment Groups)
An adverse event is any unfavorable and unintended change in the structure, function, or chemistry of the body whether or not considered related to the study treatment.
Time frame: Up to 48 hours post-dose
Population: All participants as treated (one participant assigned to the Telcagepant 280 mg arm only took the placebo tablet and is included in the Placebo arm for adverse event reporting).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants Experiencing Adverse Events Within 48 Hours Post-dose (Count ≥4 in One or More Treatment Groups) | 27 Participants |
| Telcagepant 280 mg +Ibuprofen 400 mg | Number of Participants Experiencing Adverse Events Within 48 Hours Post-dose (Count ≥4 in One or More Treatment Groups) | 44 Participants |
| Telcagepant 280 mg +APAP 1000 mg | Number of Participants Experiencing Adverse Events Within 48 Hours Post-dose (Count ≥4 in One or More Treatment Groups) | 42 Participants |
| Telcagepant 280 mg | Number of Participants Experiencing Adverse Events Within 48 Hours Post-dose (Count ≥4 in One or More Treatment Groups) | 34 Participants |
Primary
Percentage of Participants With Pain Freedom at Two Hours Post-dose
Pain severity was rated by the participants in a paper diary by grade; Grade 0 (no pain), Grade 1 (mild pain), Grade 2 (moderate pain), and Grade 3 (severe pain). Pain freedom was defined as a reduction in pain severity from moderate to severe migraine headache (Grade 2 or 3) to no pain (Grade 0).
Time frame: 2 hours post-dose
Population: The Full Analysis Set (FAS) comprised participants who were treated and had a baseline assessment and at least one post-dose assessment up to or including the 2-hour time point. Missing data were imputed by using a Last Observation Carried Forward (LOCF) approach; baseline values were not carried forward to impute the missing post-treatment data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Pain Freedom at Two Hours Post-dose | 10.9 Percentage of Participants |
| Telcagepant 280 mg +Ibuprofen 400 mg | Percentage of Participants With Pain Freedom at Two Hours Post-dose | 35.2 Percentage of Participants |
| Telcagepant 280 mg +APAP 1000 mg | Percentage of Participants With Pain Freedom at Two Hours Post-dose | 38.3 Percentage of Participants |
| Telcagepant 280 mg | Percentage of Participants With Pain Freedom at Two Hours Post-dose | 31.2 Percentage of Participants |
p-value: <0.00190% CI: [16.7, 32.2]Miettinen and Nurminen
p-value: <0.00190% CI: [19.6, 35.8]Miettinen and Nurminen
p-value: <0.00190% CI: [12.6, 28.2]Miettinen and Nurminen
p-value: 0.44990% CI: [-5, 13.3]Miettinen and Nurminen
p-value: 0.18290% CI: [-1.8, 17.1]Miettinen and Nurminen
Secondary
Percentage of Participants With Pain Relief at 2 Hours Post-dose.
Pain severity was rated by the participants in a paper diary by grade; Grade 0 (no pain), Grade 1 (mild pain), Grade 2 (moderate pain), and Grade 3 (severe pain). Pain relief was defined as a reduction in pain severity from moderate to severe migraine headache (Grade 2 or 3) to mild or none (Grade 1 or 0).
Time frame: 2 hours post-dose
Population: The FAS comprised participants who were treated and had a baseline assessment and at least one post-dose assessment up to or including the 2-hour time point. Missing data were imputed by using a Last Observation Carried Forward (LOCF) approach; baseline values were not carried forward to impute the missing post-treatment data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Pain Relief at 2 Hours Post-dose. | 30.6 Percentage of Participants |
| Telcagepant 280 mg +Ibuprofen 400 mg | Percentage of Participants With Pain Relief at 2 Hours Post-dose. | 71.0 Percentage of Participants |
| Telcagepant 280 mg +APAP 1000 mg | Percentage of Participants With Pain Relief at 2 Hours Post-dose. | 69.9 Percentage of Participants |
| Telcagepant 280 mg | Percentage of Participants With Pain Relief at 2 Hours Post-dose. | 65.2 Percentage of Participants |
p-value: <0.00190% CI: [31.9, 49]Miettinen and Nurminen
p-value: <0.00190% CI: [30.5, 48.5]Miettinen and Nurminen
p-value: 0.26590% CI: [-2.9, 14.9]Miettinen and Nurminen
p-value: 0.36290% CI: [-4.2, 14.5]Miettinen and Nurminen
p-value: <0.00190% CI: [25.3, 43.4]Miettinen and Nurminen