Multiple Attacks Study to Compare the Efficacy and Safety of MK-0974 With Placebo for Acute Migraine (MK-0974-031)

Study Overview
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Brief Summary
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The purpose of the study is to assess the safety and efficacy of telcagepant (MK-0974) in acute treatment of multiple migraine attacks with or without aura. Primary hypotheses of this study are that telcagepant is superior to placebo, as measured by the proportion of participants who have pain freedom, pain relief, pain freedom consistency, pain relief consistency, and absence of photophobia, phonophobia, and nausea at 2 hours post-dose.

Official Title
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A Multicenter, Double-Blind, Placebo-Controlled, Parallel Group Multiple Attacks Study to Compare the Efficacy and Safety of Oral MK-0974 With Placebo for the Acute Treatment of Migraine With or Without Aura

Conditions
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Migraines

Intervention / Treatment
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* Drug: Telcagepant 140 mg
* Drug: Talcagepant 280 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: History of migraines within the past year 1 to 8 moderate or severe migraine attacks per month in the past 2 months that lasted between 4 to 72 hours if untreated Use acceptable contraception throughout the study Able to complete the study questionnaire(s) and paper diary Limit consumption of grapefruit juice to no more than one 8 ounce glass a day Exclusion Criteria: Pregnant or breast-feeding or is expecting to become pregnant during the study Difficulty distinguishing his/her migraine attacks from tension or interval headaches A history of mostly mild migraine attacks or migraines that usually resolve spontaneously in less than 2 hours More than 15 headache-days per month or has taken medication for acute headache on more than 10 days a month in the past 3 months Greater than 50 years old at the age of migraine onset Previously taken telcagepant

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Telcagepant 140 mg<br>Telcagepant 140 mg, oral, tablet, across 4 migraine attacks. For migraine attack 1 only, if no headache relief is obtained after 2 hours post dose, or if the migraine recurs after 2 hours of the initial treatment, participants may receive an optional second dose of telcagepant 140 mg or placebo. | Drug: Telcagepant 140 mg<br>* Telcagepant 140 mg tablets<br>|
| Experimental: Telcagepant 280 mg<br>Telcagepant 280 mg, oral, tablet, across 4 migraine attacks. For migraine attack 1 only, if no headache relief is obtained after 2 hours post dose, or if the migraine recurs after 2 hours of the initial treatment, participants may receive an optional second dose of telcagepant 280 mg or placebo. | Drug: Talcagepant 280 mg<br>* Telcagepant 280 mg tablets<br>|
| Placebo Comparator: Control Group 1<br>Placebo, oral, tablet, across 3 migraine attacks (1st, 2nd, and 4th). Telcagepant 140 mg will be administered for the 3rd migraine attack. Participants will receive placebo for the optional second dose. For migraine attacks 2, 3, and 4, no study medication will be provided as an optional second dose. | Drug: Telcagepant 140 mg<br>* Telcagepant 140 mg tablets<br>Drug: Placebo<br>* Placebo tablets<br>|
| Placebo Comparator: Control Group 2<br>Placebo, oral, tablet, across 3 migraine attacks (1st, 2nd, and 3rd). Telcagepant 140 mg will be administered for the 4th migraine attack. Participants will receive placebo for the optional second dose. For migraine attacks 2, 3, and 4, no study medication will be provided as an optional second dose. | Drug: Telcagepant 140 mg<br>* Telcagepant 140 mg tablets<br>Drug: Placebo<br>* Placebo tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Reporting Pain Freedom at 2 Hours Post-dose (First Migraine Attack) | Pain Freedom (PF) at 2 hours post-dose (first migraine attack), with pain freedom defined as a reduction in headache severity from Grade 3/2 at baseline to Grade 0 at 2 hours post-dose. Headache severity was subjectively rated by the participant at predefined time points on a scale of Grade 0 to Grade 3: Grade 0 - No pain; Grade 1 - Mild pain; Grade 2 - Moderate Pain; and Grade 3 - Severe Pain. | 2 hours post-dose for the first migraine attack (up to 6 months) | 
| Percentage of Participants Reporting Pain Relief at 2 Hours Post-dose (First Migraine Attack) | Pain Relief (PR) at 2 hours post-dose (first migraine attack), with pain relief defined as a reduction in headache severity from Grade 3/2 at baseline to Grade 1/0 at 2 hours post-dose. Headache severity was subjectively rated by the participant at predefined time points on a scale of Grade 0 to Grade 3: Grade 0 - No pain; Grade 1 - Mild pain; Grade 2 - Moderate Pain; and Grade 3 - Severe Pain. | 2 hours post-dose for the first migraine attack (up to 6 months) | 
| Percentage of Participants Reporting Pain Freedom Consistency at 2 Hours Post-dose | Pain Freedom Consistency (PFC) at 2 hours post-dose, defined as having achieved PF at 2 hours post-dose on at least 3 treated migraine attacks. Note that for the control groups, a positive PF response arising from the administration of the 1 talcagepant treated migraine attack will count as one of the 3 positive PF responses needed to fulfill the criteria for PFC. | 2 hours post-dose (up to 6 months) | 
| Percentage of Participants Reporting Pain Relief Consistency at 2 Hours Post-dose | Pain Relief Consistency (PRC) at 2 hours post-dose, defined as having achieved PR at 2 hours post-dose on at least 3 treated migraine attacks. Note that for the control groups, a positive PR response arising from the administration of the 1 telcagepant treated migraine attack will count as one of the 3 positive PR responses needed to fulfill the criteria for PRC. | 2 hours post-dose (up to 6 months) | 
| Percentage of Participants Reporting Absence of Photophobia at 2 Hours Post-dose (First Migraine Attack) | The participant recorded whether photophobia (sensitivity to light) was present or absent at each of the predefined time points. | 2 hours post-dose for the first migraine attack (up to 6 months) | 
| Percentage of Participants Reporting Absence of Phonophobia at 2 Hours Post-dose (First Migraine Attack) | The participant recorded whether phonophobia (sensitivity to sound) was present or absent at each of the predefined time points. | 2 hours post-dose for the first migraine attack (up to 6 months) | 
| Percentage of Participants Reporting Absence of Nausea 2 Hours Post-dose (First Migraine Attack) | The participant recorded whether nausea was present or absent at each of the predefined time points. | 2 hours post-dose for the first migraine attack (up to 6 months) | 
| Number of Participants Experiencing an Adverse Event (AE) Within 48 Hours Post-dose (First Migraine Attack) | AEs were reported following treatment for the first migraine attack using a 48-hour post-dose window. AEs displayed are those reported by at least 4 participants in one or more treatment groups. | Up to 48 hours post-dose for the first migraine attack (up to 6 months) | 
| Number of Participants Discontinuing Study Medication Due to an AE | Participants discontinuing study medication due to an AE were reported for all migraine attacks. | Up to the 4th dose of study medication (up to 6 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Reporting Sustained Pain Freedom From 2 to 24 Hours Post-dose (First Migraine Attack) | Sustained Pain Freedom (SPF) from 2 to 24 hours after study medication administration. SPF from 2 to 24 hours post-dose is defined as PF at 2 hours, with no administration of either rescue medication or the optional second dose and with no occurrence thereafter of a mild/moderate/severe headache during the 2 to 24 hours after dosing with the study medication. | From 2 to 24 hours post-dose for the first migraine attack (up to 6 months) | 
| Percentage of Participants Reporting Sustained Pain Freedom From 2 to 48 Hours Post-dose (First Migraine Attack) | Sustained Pain Freedom (SPF) from 2 to 48 hours post-dose after study medication administration. SPF from 2 to 48 hours post-dose is defined as PF at 2 hours, with no administration of either rescue medication or the optional second dose and with no occurrence thereafter of a mild/moderate/severe headache during the 2 to 48 hours after dosing with the study medication. | From 2 to 48 hours post-dose for the first migraine attack (up to 6 months) | 
| Percentage of Participants Reporting Total Migraine Freedom at 2 Hours Post-dose (First Migraine Attack) | TMF 2 hours post-dose, which is defined as TMF at 2 hours post-dose, with no administration of either rescue medication or the optional second dose and with no occurrence thereafter of a mild/moderate/severe headache and no reported occurrence of photophobia, phonophobia, nausea, or vomiting during the 2 hours after dosing with the study medication. | 2 hours post-dose for the first migraine attack (up to 6 months) | 
| Percentage of Participants Reporting Total Migraine Freedom From 2 to 24 Hours Post-dose (First Migraine Attack) | TMF from 2 to 24 hours post-dose, which is defined as TMF at 2 hours post-dose, with no administration of either rescue medication or the optional second dose and with no occurrence thereafter of a mild/moderate/severe headache and no reported occurrence of photophobia, phonophobia, nausea, or vomiting during the 2 to 24 hours after dosing with the study medication. | From 2 to 24 hours post-dose for the first migraine attack (up to 6 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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multiple attacks of moderate to severe migraine headaches