Study of Telcagepant (MK-0974) in Participants With Moderate to Severe Acute Migraine With or Without Aura (MK-0974-011)

A Multicenter, Double-Blind, Placebo-Controlled, Parallel Group Study to Compare the Response to a Single Treatment With Oral MK0974 With Placebo and Comparator in Subjects With Moderate to Severe Acute Migraine With or Without Aura

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.

Study Overview

• Status: Completed
• Conditions: Migraine
• Intervention / Treatment: Drug: Telcagepant potassium 150 mg; Drug: Placebo to tecagepant 300 mg; Drug: Placebo to zolmitriptan 5 mg; Drug: Rescue medication; Drug: Telcagepant potassium 300 mg; Drug: Placebo to telcagepant 150 mg; Drug: Zolmitriptan 5 mg

• Study Type: Interventional
• Enrollment (Actual): 1380
• 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:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 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.	Drug: Telcagepant potassium 150 mg; Telcagepant 150 mg liquid-filled soft gel capsules; Drug: Placebo to tecagepant 300 mg; Placebo to match tecagepant 300 mg liquid-filled soft gel capsules; Drug: Placebo to zolmitriptan 5 mg; Placebo to match zolmitriptan 5 mg tablets; Drug: Rescue 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.
EXPERIMENTAL: 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.	Drug: Placebo to zolmitriptan 5 mg; Placebo to match zolmitriptan 5 mg tablets; Drug: Rescue 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.; Drug: Telcagepant potassium 300 mg; Telcagepant 300 mg liquid-filled soft gel capsules; Drug: Placebo to telcagepant 150 mg; Placebo to match telcagepant 150 mg liquid-filled soft gel capsules
ACTIVE_COMPARATOR: 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.	Drug: Placebo to tecagepant 300 mg; Placebo to match tecagepant 300 mg liquid-filled soft gel capsules; Drug: Rescue 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.; Drug: Placebo to telcagepant 150 mg; Placebo to match telcagepant 150 mg liquid-filled soft gel capsules; Drug: Zolmitriptan 5 mg; Zolmitriptan 5 mg tablets
PLACEBO_COMPARATOR: 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.	Drug: Placebo to tecagepant 300 mg; Placebo to match tecagepant 300 mg liquid-filled soft gel capsules; Drug: Placebo to zolmitriptan 5 mg; Placebo to match zolmitriptan 5 mg tablets; Drug: Rescue 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.; Drug: Placebo to telcagepant 150 mg; Placebo to match telcagepant 150 mg liquid-filled soft gel capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	2 hours post-dose
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.	2 hours post-dose
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.	2 hours post-dose
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.	2 hours post-dose
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.	2 hours post-dose
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.	Up to 14 days after last dose of study drug
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.	Up to 48 hours after first dose of study drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	2 to 24 hours post-dose
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.	2 hours post-dose
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.	2 to 24 hours post-dose

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Ho TW, Ferrari MD, Dodick DW, Galet V, Kost J, Fan X, Leibensperger H, Froman S, Assaid C, Lines C, Koppen H, Winner PK. Efficacy and tolerability of MK-0974 (telcagepant), a new oral antagonist of calcitonin gene-related peptide receptor, compared with zolmitriptan for acute migraine: a randomised, placebo-controlled, parallel-treatment trial. Lancet. 2008 Dec 20;372(9656):2115-23. doi: 10.1016/S0140-6736(08)61626-8. Epub 2008 Nov 25.
• Ho TW, Olesen J, Dodick DW, Kost J, Lines C, Ferrari MD. Antimigraine efficacy of telcagepant based on patient's historical triptan response. Headache. 2011 Jan;51(1):64-72. doi: 10.1111/j.1526-4610.2010.01790.x. Epub 2010 Nov 4.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 15, 2007
• Primary Completion (ACTUAL): October 2, 2007
• Study Completion (ACTUAL): October 2, 2007

Study Registration Dates

• First Submitted: February 28, 2007
• First Submitted That Met QC Criteria: March 2, 2007
• First Posted (ESTIMATE): March 5, 2007

Study Record Updates

• Last Update Posted (ACTUAL): October 17, 2018
• Last Update Submitted That Met QC Criteria: September 18, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Serotonin Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Protein Synthesis Inhibitors; Oxazolidinones; Zolmitriptan
• Other Study ID Numbers: 0974-011; MK-0974-011 (OTHER: Merck Protocol Number); 2006_525 (OTHER: 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