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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Migraine Disorders, Heart Disease, Cerebrovascular Accident, TIA (Transient Ischemic Attack), Vascular Diseases, Peripheral Vascular Diseases

Intervention / Treatment
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* Drug: Telcagepant
* Drug: Acetaminophen/Paracetamol
* Drug: Placebo to Telcagepant
* Drug: Placebo to Acetaminophen/Paracetamol


Participation Criteria
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Eligibility Criteria
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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

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: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Telcagepant 300 mg→Acetaminophen/Paracetamol 1000 mg<br>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<br>* Telcagepant (MK-0974) (300 mg soft gel capsules or 280 mg tablets)<br>Drug: Acetaminophen/Paracetamol<br>* Acetaminophen/Paracetamol (500 mg X 2 dosage units)<br>Drug: Placebo to Telcagepant<br>* Placebo 300 mg soft gel capsules or placebo 280 mg tablet.<br>Drug: Placebo to Acetaminophen/Paracetamol<br>* Placebo to acetaminophen/paracetamol (500 mg X 2 dosage units)<br>|
| Experimental: Placebo and APAP 1000 mg→Telcagepant 300 mg<br>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<br>* Telcagepant (MK-0974) (300 mg soft gel capsules or 280 mg tablets)<br>Drug: Acetaminophen/Paracetamol<br>* Acetaminophen/Paracetamol (500 mg X 2 dosage units)<br>Drug: Placebo to Telcagepant<br>* Placebo 300 mg soft gel capsules or placebo 280 mg tablet.<br>Drug: Placebo to Acetaminophen/Paracetamol<br>* Placebo to acetaminophen/paracetamol (500 mg X 2 dosage units)<br>|

What is the study measuring?
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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) |