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

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

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.

Study Overview

• Status: Completed
• Conditions: Migraines
• Intervention / Treatment: Drug: Telcagepant 140 mg; Drug: Talcagepant 280 mg; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 1935
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Telcagepant 140 mg; 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; Telcagepant 140 mg tablets
Experimental: Telcagepant 280 mg; 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; Telcagepant 280 mg tablets
Placebo Comparator: Control Group 1; 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; Telcagepant 140 mg tablets; Drug: Placebo; Placebo tablets
Placebo Comparator: Control Group 2; 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; Telcagepant 140 mg tablets; Drug: Placebo; Placebo tablets

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Ho AP, Dahlof CG, Silberstein SD, Saper JR, Ashina M, Kost JT, Froman S, Leibensperger H, Lines CR, Ho TW. Randomized, controlled trial of telcagepant over four migraine attacks. Cephalalgia. 2010 Dec;30(12):1443-57. doi: 10.1177/0333102410370878. Epub 2010 Jun 8.

Study record dates

Study Major Dates

• Study Start (Actual): August 14, 2008
• Primary Completion (Actual): March 25, 2009
• Study Completion (Actual): March 25, 2009

Study Registration Dates

• First Submitted: May 15, 2007
• First Submitted That Met QC Criteria: June 6, 2007
• First Posted (Estimate): June 7, 2007

Study Record Updates

• Last Update Posted (Actual): October 18, 2018
• Last Update Submitted That Met QC Criteria: September 18, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: multiple attacks of moderate to severe migraine headaches
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders
• Other Study ID Numbers: 0974-031; MK-0974-031 (Other Identifier: Merck Protocol Number); 2007_546 (Other Identifier: Telerx ID Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Study Data/Documents

1. CSR Synopsis