Migraine
Conditions
Brief summary
The purpose of this study is to investigate the efficacy and safety of telcagepant (MK-0974) compared to an approved medication for acute migraine. This study was conducted as a triple-dummy design; for each dose of study drug, participants each received 3 forms of study drug (2 capsules of active and/or placebo and 1 tablet of active and/or placebo) and were instructed to take one of each form of study drug at dosing time. The primary hypotheses of this study are that telcagepant is superior to placebo in Pain Freedom at 2 Hours Post-Dose, Pain Relief at 2 Hours Post-Dose, Absence of Photophobia at 2 Hours Post-Dose, Absence of Phonophobia at 2 Hours Post-Dose and Absence of Nausea at 2 Hours Post-Dose.
Interventions
DRUGTelcagepant potassium 150 mg
Telcagepant 150 mg liquid-filled soft gel capsules
DRUGTelcagepant potassium 300 mg
Telcagepant 300 mg liquid-filled soft gel capsules
DRUGZolmitriptan 5 mg
Zolmitriptan 5 mg tablets
DRUGPlacebo to telcagepant 150 mg
Placebo to match telcagepant 150 mg liquid-filled soft gel capsules
DRUGPlacebo to tecagepant 300 mg
Placebo to match tecagepant 300 mg liquid-filled soft gel capsules
DRUGPlacebo to zolmitriptan 5 mg
Placebo to match zolmitriptan 5 mg tablets
DRUGRescue medication
If moderate or severe migraine headache pain continues or recurs 2 hours after dose of study drug, participants are allowed to take an optional second dose of study drug or their own non-study rescue migraine medication, which may include analgesics (e.g., nonsteroidal anti-inflammatory drugs \[NSAIDs\] or opiates), anti-emetics, or zolmitriptan. Triptans other than zolmitriptan and ergot derivatives are prohibited for 24 hours following the last dose of study drug.
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
* Has at least 1 year history of migraine (with or without aura) * Females of child bearing potential must use acceptable contraception throughout trial.
Exclusion criteria
* Is pregnant/breast-feeding (or is a female expecting to conceive during study period) * Has history or evidence of stroke/transient ischemic attacks, heart disease, coronary artery vasospasm, other significant underlying cardiovascular diseases, uncontrolled hypertension (high blood pressure), uncontrolled diabetes, or human immunodeficiency virus (HIV) disease * Has major depression, other pain syndromes that might interfere with study assessments, psychiatric conditions, dementia, or significant neurological disorders (other than migraine) * Has a history of gastric, or small intestinal surgery, or has a disease that causes malabsorption * Has a history of cancer within the last 5 years.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Discontinue Study Drug Due to an AE | Up to 48 hours after first dose of study drug | An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. Participants who took both active and placebo study drug were counted in the active group. |
| Number of Participants With Absence of Phonophobia at 2 Hours Post-Dose | 2 hours post-dose | Participants were asked if they experienced any sensitivity to sound. The number of participants who experienced no phonophobia (sensitivity to sound) at 2 hours post-dose was determined. |
| Number of Participants With Absence of Nausea at 2 Hours Post-Dose | 2 hours post-dose | Participants were asked if they experienced any nausea. The number of participants who experienced no nausea at 2 hours post-dose was determined. |
| Number of Participants Who Experience At Least One Adverse Event (AE) | Up to 14 days after last dose of study drug | An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. Participants were monitored for occurrence AEs for up to 14 days after last dose study drug. Participants who took both active and placebo study drug were counted in the active group. |
| Number of Participants With Pain Freedom (PF) at 2 Hours Post-Dose | 2 hours post-dose | Participants were asked to rate their migraine headache severity with ratings of 0=No pain, 1=Mild pain, 2=Moderate pain, and 3=Severe pain. PF at 2 hours post-dose is defined as a decrease from a moderate or severe migraine headache (Grade 2 or 3) at baseline to no pain (Grade 0) at 2 hours post-dose. |
| Number of Participants With Pain Relief (PR) at 2 Hours Post-Dose | 2 hours post-dose | Participants were asked to rate their migraine headache severity with ratings of 0=No pain, 1=Mild pain, 2=Moderate pain, and 3=Severe pain. PR at 2 hours post-dose is defined as a shift from a moderate or severe migraine headache (Grade 2 or 3) at baseline to mild or no pain (Grade 1 or 0) at 2 hours post-dose. |
| Number of Participants With Absence of Photophobia at 2 Hours Post-Dose | 2 hours post-dose | Participants were asked if they experienced any sensitivity to light. The number of participants who experienced no photophobia (sensitivity to light) at 2 hours post-dose was determined. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Total Migraine Freedom (TMF) at 2 Hours Post-Dose | 2 hours post-dose | TMF at 2 hours post-dose is defined as PF at 2 hours post-dose without any of the following migraine-related symptoms: phonophobia, photophobia, nausea or vomiting at 2 hours post-dose. |
| Number of Participants With Total Migraine Freedom (TMF) at 2 to 24 Hours Post-Dose | 2 to 24 hours post-dose | TMF at 2 to 24 hours post-dose is defined as TMF at 2 hours post-dose with no administration of either the optional second dose of study drug or any rescue medication between 2 and 24 hours post-dose, no return of mild/moderate/severe headache within 24 hours and no presence of phonophobia, photophobia, nausea or vomiting within 24 hours post-dose. |
| Number of Participants With Sustained Pain Freedom (SPF) From 2 to 24 Hours Post-Dose | 2 to 24 hours post-dose | SPF is defined as PF at 2 hours post-dose with no return of mild/moderate/severe headache through 24 hours post-dose, and with no administration of either the optional second dose of study drug or any rescue medication between 2 and 24 hours post-dose. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Telcagepant 150 mg Participants receive telcagepant 150 mg capsules, one capsule administered orally at initial onset of moderate to severe migraine headache. If, after 2 hours post-dose, participants still have a moderate to severe migraine or migraine recurs, participants may receive an optional second dose of study drug (telcagepant 150 mg or placebo) or one dose of non-study rescue medication. | 333 |
| Telcagepant 300 mg Participants receive telcagepant 300 mg capsules, one capsule administered orally at initial onset of moderate to severe migraine headache. If, after 2 hours post-dose, participants still have a moderate to severe migraine or migraine recurs, participants may receive an optional second dose of study drug (telcagepant 300 mg or placebo) or one dose of non-study rescue medication. | 354 |
| Zolmitriptan 5 mg Participants receive zolmitriptan 5 mg tablets, one tablet administered orally at initial onset of moderate to severe migraine headache. If, after 2 hours post-dose, participants still have a moderate to severe migraine or migraine recurs, participants may receive an optional second dose of study drug (placebo) or one dose of non-study rescue medication. | 345 |
| Placebo Participants receive placebo matching capsules or tablets, one capsule or tablet administered orally at initial onset of moderate to severe migraine headache. If, after 2 hours post-dose, participants still have a moderate to severe migraine or migraine recurs, participants may receive an optional second dose of study drug (placebo) or one dose of non-study rescue medication. | 348 |
| Total | 1,380 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Protocol Violation | 1 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Telcagepant 150 mg | Telcagepant 300 mg | Zolmitriptan 5 mg | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 42.7 Years STANDARD_DEVIATION 11.2 | 42.6 Years STANDARD_DEVIATION 11.4 | 41.7 Years STANDARD_DEVIATION 11.7 | 42.3 Years STANDARD_DEVIATION 11.6 | 42.3 Years STANDARD_DEVIATION 11.4 |
| Sex: Female, Male Female | 277 Participants | 300 Participants | 298 Participants | 294 Participants | 1169 Participants |
| Sex: Female, Male Male | 56 Participants | 54 Participants | 47 Participants | 54 Participants | 211 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 | 66 / 334 | 74 / 352 | 107 / 345 | 54 / 349 |
| serious Total, serious adverse events | 0 / 334 | 0 / 352 | 0 / 345 | 1 / 349 |
Outcome results
Primary
Number of Participants Who Discontinue Study Drug Due to an AE
An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. Participants who took both active and placebo study drug were counted in the active group.
Time frame: Up to 48 hours after first dose of study drug
Population: The populaton consisted of all participants who received at least one dose of study drug. Participants were included in the treatment arm corresponding to the study treatment actually taken at the time of the AE.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Telcagepant 150 mg | Number of Participants Who Discontinue Study Drug Due to an AE | 0 Participants |
| Telcagepant 300 mg | Number of Participants Who Discontinue Study Drug Due to an AE | 0 Participants |
| Zolmitriptan 5 mg | Number of Participants Who Discontinue Study Drug Due to an AE | 0 Participants |
| Placebo | Number of Participants Who Discontinue Study Drug Due to an AE | 0 Participants |
Primary
Number of Participants Who Experience At Least One Adverse Event (AE)
An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. Participants were monitored for occurrence AEs for up to 14 days after last dose study drug. Participants who took both active and placebo study drug were counted in the active group.
Time frame: Up to 14 days after last dose of study drug
Population: The population consisted of all participants who received at least one dose of study drug. Participants were included in the treatment arm corresponding to the study treatment actually taken at the time of the AE.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Telcagepant 150 mg | Number of Participants Who Experience At Least One Adverse Event (AE) | 105 Participants |
| Telcagepant 300 mg | Number of Participants Who Experience At Least One Adverse Event (AE) | 131 Participants |
| Zolmitriptan 5 mg | Number of Participants Who Experience At Least One Adverse Event (AE) | 175 Participants |
| Placebo | Number of Participants Who Experience At Least One Adverse Event (AE) | 112 Participants |
Primary
Number of Participants With Absence of Nausea at 2 Hours Post-Dose
Participants were asked if they experienced any nausea. The number of participants who experienced no nausea at 2 hours post-dose was determined.
Time frame: 2 hours post-dose
Population: The population consisted of all participants who were randomized, took at least one dose of study drug, recorded a baseline nausea assessment, and had at least one nausea assessment within 2 hours post-dose.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Telcagepant 150 mg | Number of Participants With Absence of Nausea at 2 Hours Post-Dose | 212 Participants |
| Telcagepant 300 mg | Number of Participants With Absence of Nausea at 2 Hours Post-Dose | 218 Participants |
| Zolmitriptan 5 mg | Number of Participants With Absence of Nausea at 2 Hours Post-Dose | 232 Participants |
| Placebo | Number of Participants With Absence of Nausea at 2 Hours Post-Dose | 179 Participants |
p-value: <0.00195% CI: [1.25, 2.39]Regression, Logistic
p-value: 0.00695% CI: [1.13, 2.13]Regression, Logistic
Primary
Number of Participants With Absence of Phonophobia at 2 Hours Post-Dose
Participants were asked if they experienced any sensitivity to sound. The number of participants who experienced no phonophobia (sensitivity to sound) at 2 hours post-dose was determined.
Time frame: 2 hours post-dose
Population: The population consisted of all participants who were randomized, took at least one dose of study drug, recorded a baseline phonophobia assessment, and had at least one phonophobia assessment within 2 hours post-dose.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Telcagepant 150 mg | Number of Participants With Absence of Phonophobia at 2 Hours Post-Dose | 170 Participants |
| Telcagepant 300 mg | Number of Participants With Absence of Phonophobia at 2 Hours Post-Dose | 193 Participants |
| Zolmitriptan 5 mg | Number of Participants With Absence of Phonophobia at 2 Hours Post-Dose | 180 Participants |
| Placebo | Number of Participants With Absence of Phonophobia at 2 Hours Post-Dose | 120 Participants |
p-value: <0.00195% CI: [1.49, 2.82]Regression, Logistic
p-value: <0.00195% CI: [1.73, 3.25]Regression, Logistic
Primary
Number of Participants With Absence of Photophobia at 2 Hours Post-Dose
Participants were asked if they experienced any sensitivity to light. The number of participants who experienced no photophobia (sensitivity to light) at 2 hours post-dose was determined.
Time frame: 2 hours post-dose
Population: The population consisted of all participants who were randomized, took at least one dose of study drug, recorded a baseline photophobia assessment, and had at least one photophobia assessment within 2 hours post-dose.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Telcagepant 150 mg | Number of Participants With Absence of Photophobia at 2 Hours Post-Dose | 143 Participants |
| Telcagepant 300 mg | Number of Participants With Absence of Photophobia at 2 Hours Post-Dose | 169 Participants |
| Zolmitriptan 5 mg | Number of Participants With Absence of Photophobia at 2 Hours Post-Dose | 163 Participants |
| Placebo | Number of Participants With Absence of Photophobia at 2 Hours Post-Dose | 92 Participants |
p-value: <0.00195% CI: [1.54, 2.97]Regression, Logistic
p-value: <0.00195% CI: [1.89, 3.61]Regression, Logistic
Primary
Number of Participants With Pain Freedom (PF) at 2 Hours Post-Dose
Participants were asked to rate their migraine headache severity with ratings of 0=No pain, 1=Mild pain, 2=Moderate pain, and 3=Severe pain. PF at 2 hours post-dose is defined as a decrease from a moderate or severe migraine headache (Grade 2 or 3) at baseline to no pain (Grade 0) at 2 hours post-dose.
Time frame: 2 hours post-dose
Population: The population consisted of all participants who were randomized, took at least one dose of study drug, recorded a baseline pain score, and had at least one pain score measurement within 2 hours post-dose.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Telcagepant 150 mg | Number of Participants With Pain Freedom (PF) at 2 Hours Post-Dose | 56 Participants |
| Telcagepant 300 mg | Number of Participants With Pain Freedom (PF) at 2 Hours Post-Dose | 89 Participants |
| Zolmitriptan 5 mg | Number of Participants With Pain Freedom (PF) at 2 Hours Post-Dose | 101 Participants |
| Placebo | Number of Participants With Pain Freedom (PF) at 2 Hours Post-Dose | 29 Participants |
p-value: <0.00195% CI: [1.4, 3.66]Regression, Logistic
p-value: <0.00195% CI: [2.42, 6]Regression, Logistic
Primary
Number of Participants With Pain Relief (PR) at 2 Hours Post-Dose
Participants were asked to rate their migraine headache severity with ratings of 0=No pain, 1=Mild pain, 2=Moderate pain, and 3=Severe pain. PR at 2 hours post-dose is defined as a shift from a moderate or severe migraine headache (Grade 2 or 3) at baseline to mild or no pain (Grade 1 or 0) at 2 hours post-dose.
Time frame: 2 hours post-dose
Population: The population consisted of all participants who were randomized, took at least one dose of study drug, recorded a baseline pain score, and had at least one pain score measurement within 2 hours post-dose.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Telcagepant 150 mg | Number of Participants With Pain Relief (PR) at 2 Hours Post-Dose | 157 Participants |
| Telcagepant 300 mg | Number of Participants With Pain Relief (PR) at 2 Hours Post-Dose | 183 Participants |
| Zolmitriptan 5 mg | Number of Participants With Pain Relief (PR) at 2 Hours Post-Dose | 185 Participants |
| Placebo | Number of Participants With Pain Relief (PR) at 2 Hours Post-Dose | 88 Participants |
p-value: <0.00195% CI: [2.02, 3.95]Regression, Logistic
p-value: <0.00195% CI: [2.47, 4.79]Regression, Logistic
Secondary
Number of Participants With Sustained Pain Freedom (SPF) From 2 to 24 Hours Post-Dose
SPF is defined as PF at 2 hours post-dose with no return of mild/moderate/severe headache through 24 hours post-dose, and with no administration of either the optional second dose of study drug or any rescue medication between 2 and 24 hours post-dose.
Time frame: 2 to 24 hours post-dose
Population: The population consisted of all participants who were randomized, took at least one dose of study drug, recorded a baseline pain score, had at least one pain score measurement within 2 hours post-dose, and had at least one pain score measurement at between 2 and 24 hours post-dose.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Telcagepant 150 mg | Number of Participants With Sustained Pain Freedom (SPF) From 2 to 24 Hours Post-Dose | 34 Participants |
| Telcagepant 300 mg | Number of Participants With Sustained Pain Freedom (SPF) From 2 to 24 Hours Post-Dose | 66 Participants |
| Zolmitriptan 5 mg | Number of Participants With Sustained Pain Freedom (SPF) From 2 to 24 Hours Post-Dose | 59 Participants |
| Placebo | Number of Participants With Sustained Pain Freedom (SPF) From 2 to 24 Hours Post-Dose | 14 Participants |
p-value: 0.00295% CI: [1.47, 5.35]Regression, Logistic
p-value: <0.00195% CI: [3.15, 10.51]Regression, Logistic
Secondary
Number of Participants With Total Migraine Freedom (TMF) at 2 Hours Post-Dose
TMF at 2 hours post-dose is defined as PF at 2 hours post-dose without any of the following migraine-related symptoms: phonophobia, photophobia, nausea or vomiting at 2 hours post-dose.
Time frame: 2 hours post-dose
Population: The population consisted of all participants who were randomized, took at least one dose of study drug, recorded a baseline pain score, had at least one pain score measurement within 2 hours post-dose, and had at least one assessment for phonophobia, photophobia, nausea and vomiting within 2 hours post-dose.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Telcagepant 150 mg | Number of Participants With Total Migraine Freedom (TMF) at 2 Hours Post-Dose | 43 Participants |
| Telcagepant 300 mg | Number of Participants With Total Migraine Freedom (TMF) at 2 Hours Post-Dose | 76 Participants |
| Zolmitriptan 5 mg | Number of Participants With Total Migraine Freedom (TMF) at 2 Hours Post-Dose | 87 Participants |
| Placebo | Number of Participants With Total Migraine Freedom (TMF) at 2 Hours Post-Dose | 27 Participants |
p-value: 0.02695% CI: [1.07, 2.97]Regression, Logistic
p-value: <0.00195% CI: [2.08, 5.35]Regression, Logistic
Secondary
Number of Participants With Total Migraine Freedom (TMF) at 2 to 24 Hours Post-Dose
TMF at 2 to 24 hours post-dose is defined as TMF at 2 hours post-dose with no administration of either the optional second dose of study drug or any rescue medication between 2 and 24 hours post-dose, no return of mild/moderate/severe headache within 24 hours and no presence of phonophobia, photophobia, nausea or vomiting within 24 hours post-dose.
Time frame: 2 to 24 hours post-dose
Population: The population consisted of all participants who were randomized, took at least one dose of study drug, recorded a baseline pain score, had at least one pain score measurement within 2 to 24 hours post-dose, and had at least one assessment for phonophobia, photophobia, nausea and vomiting within 2 to 24 hours post-dose.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Telcagepant 150 mg | Number of Participants With Total Migraine Freedom (TMF) at 2 to 24 Hours Post-Dose | 26 Participants |
| Telcagepant 300 mg | Number of Participants With Total Migraine Freedom (TMF) at 2 to 24 Hours Post-Dose | 57 Participants |
| Zolmitriptan 5 mg | Number of Participants With Total Migraine Freedom (TMF) at 2 to 24 Hours Post-Dose | 51 Participants |
| Placebo | Number of Participants With Total Migraine Freedom (TMF) at 2 to 24 Hours Post-Dose | 13 Participants |
p-value: 0.02195% CI: [1.13, 4.47]Regression, Logistic
p-value: <0.00195% CI: [2.78, 9.76]Regression, Logistic