Study to Evaluate the Safety, Tolerability, and Blood Pressure Effect of an Oral Dose of Sumatriptan Alone and in Combination With MK-0974 (Telcagepant) in Migraine Patients (0974-026)

Study Overview
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Brief Summary
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Study to understand the effects of migraine treatments on blood pressure in participants with migraine. The primary hypothesis is that the effect on semi-recumbent mean arterial pressure following the coadministration of telcagepant and sumatriptan is similar to that following administration of sumatriptan alone. That is, the true mean treatment difference (sumatriptan with telcagepant sumatriptan alone) in time-weighted mean arterial pressure for 2.5 hours following dosing is less than 5 mmHg.

Official Title
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A Double-Blind, Randomized, Placebo-Controlled, 3-Period, Single Dose Crossover Study to Evaluate the Safety, Tolerability, and Blood Pressure Effect of an Oral Dose of Sumatriptan Alone and in Combination With MK0974 in Migraine Patients

Conditions
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Migraine Disorders

Intervention / Treatment
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* Drug: telcagepant potassium
* Drug: sumatriptan
* Drug: sumatriptan placebo
* Drug: telcagepant potassium placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: History of migraine for longer than 6 months. Free from migraine 24 hours before each dosing. Judged to be in good health. Nonsmoker Exclusion Criteria: Under age of legal consent. Legally or mentally incapacitated or has significant emotional problems. Taking any medications from about 2 weeks before the first dose of study medication. Has had surgery or donated blood or participated in another investigation study within 4 weeks prior to screening Currently a regular user of any illicit drugs or has a history of drug/alcohol abuse within about 2 years Consumes more than 6 caffeinated beverages per day

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Sequence 1: A→C→D→B<br>Participants receive the following: Period 1: single oral dose of 100 mg sumatriptan/600 mg telcagepant (Treatment A); Period 2: single oral dose of sumatriptan placebo/600 mg telcagepant (Treatment C); Period 3: single oral dose of sumatriptan placebo/telcagepant placebo (Treatment D); Period 4: single oral dose of 100 mg sumatriptan/telcagepant placebo (Treatment B). Each dosing period is separated by a 5-day washout. | Drug: telcagepant potassium<br>* Single oral dose of 2 x 300 mg capsules.<br>Drug: sumatriptan<br>* single oral dose of 100 mg sumatriptan<br>Drug: sumatriptan placebo<br>* single oral dose<br>Drug: telcagepant potassium placebo<br>* single oral dose of 2 MK-0974 placebo capsules<br>|
| Experimental: Sequence 2: B→D→C→A<br>Participants receive the following: Period 1: single oral dose of 100 mg sumatriptan/telcagepant placebo (Treatment B); Period 2: single oral dose of sumatriptan placebo/telcagepant placebo (Treatment D): Period 3: single oral dose of sumatriptan placebo/600 mg telcagepant (Treatment C); Period 4:single oral dose of 100 mg sumatriptan/600 mg telcagepant (Treatment A). Each dosing period is separated by a 5-day washout. | Drug: telcagepant potassium<br>* Single oral dose of 2 x 300 mg capsules.<br>Drug: sumatriptan<br>* single oral dose of 100 mg sumatriptan<br>Drug: sumatriptan placebo<br>* single oral dose<br>Drug: telcagepant potassium placebo<br>* single oral dose of 2 MK-0974 placebo capsules<br>|
| Experimental: Sequence 3: C→B→A→D<br>Participants receive the following: Period 1 :single oral dose of sumatriptan placebo/600 mg telcagepant (Treatment C), Period 2: single oral dose of 100 mg sumatriptan/telcagepant placebo (Treatment B); Period 3: single oral dose of 100 mg sumatriptan/600 mg telcagepant (Treatment A): Period 4: single oral dose of sumatriptan placebo/telcagepant placebo (Treatment D). Each dosing period is separated by a 5-day washout. | Drug: telcagepant potassium<br>* Single oral dose of 2 x 300 mg capsules.<br>Drug: sumatriptan<br>* single oral dose of 100 mg sumatriptan<br>Drug: sumatriptan placebo<br>* single oral dose<br>Drug: telcagepant potassium placebo<br>* single oral dose of 2 MK-0974 placebo capsules<br>|
| Experimental: Sequence 4: D→A→B→C<br>Participants receive the following: Period 1: single oral dose of sumatriptan placebo/telcagepant placebo (Treatment D), Period 2: single oral dose of 100 mg sumatriptan/600 mg telcagepant (Treament A); Period 3: single oral dose of 100 mg sumatriptan/telcagepant placebo (Treatment B); Period 4: single oral dose of sumatriptan placebo/600 mg telcagepant (Treatment C). Each dosing period is separated by a 5-day washout. | Drug: telcagepant potassium<br>* Single oral dose of 2 x 300 mg capsules.<br>Drug: sumatriptan<br>* single oral dose of 100 mg sumatriptan<br>Drug: sumatriptan placebo<br>* single oral dose<br>Drug: telcagepant potassium placebo<br>* single oral dose of 2 MK-0974 placebo capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-weighted Mean Arterial Pressure (Sumatriptan With Telcagepant Versus Sumatriptan Alone) | In each treatment period (1 through 4), duplicate readings of semi-recumbent blood pressure (BP) were completed using an automated blood pressure machine at predose, 30, 60, 90, 120, 150, 180, and 360 minutes postdose. Mean arterial pressure (MAP) was calculated as follows: MAP = Diastolic Blood Pressure (DBP) + (0.33 * Pulse Pressure [PP]) where PP = Systolic Blood Pressure [SBP] minus DBP. Only mean arterial pressure measurements up to and including 150 minutes postdose (including the predose measurement) were used to calculate the time-weighted averages. Time-weighted averages for each participant were obtained by calculating the area under the measurement-time curve of mean arterial pressure divided by the time period over which measurements were made (i.e. 150 minutes). | Predose up to 150 minutes postdose of each treatment period (up to 10 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-weighted Mean Arterial Pressure (Telcagepant Versus Placebo) | In each treatment period (1 through 4), duplicate readings of semi-recumbent blood pressure (BP) were completed using an automated blood pressure machine at predose, 30, 60, 90, 120, 150, 180, and 360 minutes postdose. Mean arterial pressure (MAP) was calculated as follows: MAP = Diastolic Blood Pressure (DBP) + (0.33 * Pulse Pressure [PP]) where PP = Systolic Blood Pressure [SBP] minus DBP. Only mean arterial pressure measurements up to and including 150 minutes postdose (including the predose measurement) were used to calculate the time-weighted averages. Time-weighted averages for each participant were obtained by calculating the area under the measurement-time curve of mean arterial pressure divided by the time period over which measurements were made (i.e. 150 minutes). | Predose up to 150 minutes postdose of each treatment period (up to 10 weeks) | 
| Number of Participants Who Experienced an Adverse Event During the Study | Participants were assessed throughout the study for adverse events. An adverse event was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the product, was also an adverse event. | up to 14 days after last dose of study drug (up to 10 weeks) | 
| Number of Participants Who Were Discontinued From Any Study Period Due to an Adverse Event | Participants were assessed throughout the study for adverse events. An adverse event was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the product, was also an adverse event. The number of participants who were discontinued from the study due to adverse event was summarized. | up to 10 weeks |