Telcagepant (MK-0974) Treatment of Migraine in Participants With Stable Vascular Disease (MK-0974-034)

A Multicenter, Randomized, Double-Blind, Placebo- and Active Controlled, Crossover Study to Evaluate the Safety and Efficacy of MK-0974 in the Treatment of Acute Migraine in Patients With Stable Vascular Disease

The purpose of this study is to evaluate the safety and efficacy of telcagepant in the treatment of acute migraine in participants with stable vascular disease. Acetaminophen/paracetamol (APAP) will be used as an active comparator in this study. The primary hypothesis of this study is that telcagepant 300 mg is superior to placebo.

Study Overview

• Status: Completed
• Conditions: Vascular Diseases; Peripheral Vascular Diseases; Migraine Disorders; Heart Disease; Cerebrovascular Accident; TIA (Transient Ischemic Attack)
• Intervention / Treatment: Drug: Telcagepant; Drug: Acetaminophen/Paracetamol; Drug: Placebo to Telcagepant; Drug: Placebo to Acetaminophen/Paracetamol

• Study Type: Interventional
• Enrollment (Actual): 165
• 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:

• Stable coronary artery disease for 3 months or more
• 18 years of age or older with a history of migraine with or without aura
• Must use acceptable contraception throughout the study

Exclusion Criteria:

• Pregnant, breast-feeding, or planning to become pregnant during this study
• 50 years of age or older when migraines began
• Other pain syndromes that might interfere with study assessments, uncontrolled psychiatric conditions, dementia, or significant neurological disorders (other than migraine)
• History of gastric, or small intestinal surgery, or has a disease that causes malabsorption

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Telcagepant 300 mg→Acetaminophen/Paracetamol 1000 mg; Participants receive up to 12 doses of telcagepant (280 mg tablet/capsule 300 mg), orally, and placebo to acetaminophen/paracetamol (APAP) (2- 500 mg dry filled capsules), orally, for up to 12 migraine attacks in Period 1 (6 weeks). Participants receive APAP and placebo to telcagepant for up to 12 doses, for up to 12 migraine attacks in Period 2 (6 weeks). The participant may take a blinded optional second dose of study medication or their own rescue medication if 2 hours after initial treatment, the participant still has a moderate or severe migraine headache or if the headache has returned.	Drug: Telcagepant; Telcagepant (MK-0974) (300 mg soft gel capsules or 280 mg tablets); Drug: Acetaminophen/Paracetamol; Acetaminophen/Paracetamol (500 mg X 2 dosage units); Drug: Placebo to Telcagepant; Placebo 300 mg soft gel capsules or placebo 280 mg tablet.; Drug: Placebo to Acetaminophen/Paracetamol; Placebo to acetaminophen/paracetamol (500 mg X 2 dosage units)
Experimental: Placebo and APAP 1000 mg→Telcagepant 300 mg; Participants receive 1 dose of placebo to APAP and placebo to telcagepant for the first migraine attack and then up to 11 doses of APAP and placebo to telcagepant for up to 11 migraine attacks in Period 1 (6 weeks). Participants receive up to 12 doses of telcagepant and placebo to APAP for up to 12 migraine attacks in Period 2 (6 weeks). The participant may take a blinded optional second dose of study medication or their own rescue medication if 2 hours after initial treatment, the participant still has a moderate or severe migraine headache or if the headache has returned.	Drug: Telcagepant; Telcagepant (MK-0974) (300 mg soft gel capsules or 280 mg tablets); Drug: Acetaminophen/Paracetamol; Acetaminophen/Paracetamol (500 mg X 2 dosage units); Drug: Placebo to Telcagepant; Placebo 300 mg soft gel capsules or placebo 280 mg tablet.; Drug: Placebo to Acetaminophen/Paracetamol; Placebo to acetaminophen/paracetamol (500 mg X 2 dosage units)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Pain Freedom at 2 Hours Post-dose (Period 1, Migraine Attack 1)	Pain Freedom (PF) at 2 hours post-dose (Period 1, Attack 1) defined as a decrease from a moderate or severe migraine headache (Grade 2 or 3) at baseline to no pain (Grade 0). 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 (Up to 6 weeks)
Number of Participants Who Experienced an Adverse Event (AE) Within 14 Days Post-dose	An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.	Within 14 days of any dose of study medication (Up to 16 weeks)
Number of Participants Discontinuing Study Drug Due to an AE Within 48 Hours Post-dose	An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.	Up to 48 hours post-dose (Up to 14 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Pain Relief at 2 Hours Post-dose (Period 1, Migraine Attack 1)	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 (Up to 6 weeks)
Number of Participants With a Confirmed Vascular Event Within 48 Hours Post-dose	Confirmed Vascular Event included cardiac events, cerebrovascular events, and peripheral vascular events.	Up to 48 hours after the dose of any study medication (Up to 14 weeks)
Percentage of Participants With Absence of Phonophobia at 2 Hours Post-dose (Period 1, Migraine Attack 1)	The participant recorded whether phonophobia (sensitivity to sound) was present or absent at each of the predefined time points.	2 hours post-dose (Up to 6 weeks)
Percentage of Participants With Absence of Photophobia at 2 Hours Post-dose (Period 1, Migraine Attack 1)	The participant recorded whether photophobia (sensitivity to light) was present or absent at each of the predefined time points.	2 Hours post-dose (Up to 6 weeks)
Percentage of Participants With Absence of Nausea at 2 Hours Post-dose (Period 1, Migraine Attack 1)	The participant recorded whether nausea was present or absent at each of the predefined time points.	2 hours post-dose (Up to 6 weeks)
Percentage of Participants With Sustained Pain Freedom (SPF) at 2 to 24 Hours Post-dose	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.	Up to 24 hours post-dose (Up to 14 weeks)

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Ho TW, Ho AP, Chaitman BR, Johnson C, Mathew NT, Kost J, Fan X, Aurora SK, Brandes JL, Fei K, Beebe L, Lines C, Krucoff MW. Randomized, controlled study of telcagepant in patients with migraine and coronary artery disease. Headache. 2012 Feb;52(2):224-35. doi: 10.1111/j.1526-4610.2011.02052.x. Epub 2012 Jan 6.

Study record dates

Study Major Dates

• Study Start (Actual): March 17, 2008
• Primary Completion (Actual): September 2, 2009
• Study Completion (Actual): September 2, 2009

Study Registration Dates

• First Submitted: April 17, 2008
• First Submitted That Met QC Criteria: April 17, 2008
• First Posted (Estimate): April 21, 2008

Study Record Updates

• Last Update Posted (Actual): October 19, 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: Cardiovascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Atherosclerosis; Brain Ischemia; Headache Disorders, Primary; Headache Disorders; Heart Diseases; Stroke; Vascular Diseases; Peripheral Arterial Disease; Peripheral Vascular Diseases; Ischemic Attack, Transient; Migraine Disorders; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antipyretics; Acetaminophen
• Other Study ID Numbers: 0974-034; MK-0974-034 (Other Identifier: Merck Protocol Number); 2007_545 (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