Migraine Disorders
Conditions
Brief summary
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.
Interventions
Single oral dose of 2 x 300 mg capsules.
DRUGsumatriptan
single oral dose of 100 mg sumatriptan
DRUGsumatriptan placebo
single oral dose
DRUGtelcagepant potassium placebo
single oral dose of 2 MK-0974 placebo capsules
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time-weighted Mean Arterial Pressure (Sumatriptan With Telcagepant Versus Sumatriptan Alone) | Predose up to 150 minutes postdose of each treatment period (up to 10 weeks) | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time-weighted Mean Arterial Pressure (Telcagepant Versus Placebo) | Predose up to 150 minutes postdose of each treatment period (up to 10 weeks) | 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). |
| Number of Participants Who Experienced an Adverse Event During the Study | up to 14 days after last dose of study drug (up to 10 weeks) | 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. |
| Number of Participants Who Were Discontinued From Any Study Period Due to an Adverse Event | up to 10 weeks | 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. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Enrolled Participants All participants enrolled in the study | 24 |
| Total | 24 |
Baseline characteristics
| Characteristic | All Enrolled Participants |
|---|---|
| Age, Continuous | 35.0 years |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 24 | 7 / 24 | 5 / 24 | 7 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 24 |
Outcome results
Primary
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).
Time frame: Predose up to 150 minutes postdose of each treatment period (up to 10 weeks)
Population: Participants who were administered sumatriptan with telcagepant or sumatriptan alone in either Periods 1, 2, 3, or 4 regardless of sequence and had evaluable blood pressure data obtained.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 100 mg Sumatriptan/600 mg Telcagepant | Time-weighted Mean Arterial Pressure (Sumatriptan With Telcagepant Versus Sumatriptan Alone) | 89.0 mmHg |
| 100 mg Sumatriptan/Telcagepant Placebo | Time-weighted Mean Arterial Pressure (Sumatriptan With Telcagepant Versus Sumatriptan Alone) | 87.5 mmHg |
Comparison: 100 mg sumatriptan/600 mg telcagepant minus 100 mg sumatriptan/telcagepant placebo90% CI: [0, 3]Mixed Effect Model
Secondary
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.
Time frame: up to 14 days after last dose of study drug (up to 10 weeks)
Population: All Patients as Treated defined as all participants who received at least one dose of the investigational drug. Adverse events were reported by study drug taken at the time of the event and not by randomly assigned sequence.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 100 mg Sumatriptan/600 mg Telcagepant | Number of Participants Who Experienced an Adverse Event During the Study | 9 Participants |
| 100 mg Sumatriptan/Telcagepant Placebo | Number of Participants Who Experienced an Adverse Event During the Study | 12 Participants |
| Sumatriptan Placebo/600 mg Telcagepant | Number of Participants Who Experienced an Adverse Event During the Study | 8 Participants |
| Sumatriptan Placebo/Telcagepant Placebo | Number of Participants Who Experienced an Adverse Event During the Study | 10 Participants |
Secondary
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.
Time frame: up to 10 weeks
Population: All Patients as Treated defined as all participants who received at least one dose of the investigational drug. Adverse events were reported by study drug taken at the time of the event and not by randomly assigned sequence.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 100 mg Sumatriptan/600 mg Telcagepant | Number of Participants Who Were Discontinued From Any Study Period Due to an Adverse Event | 0 Participants |
| 100 mg Sumatriptan/Telcagepant Placebo | Number of Participants Who Were Discontinued From Any Study Period Due to an Adverse Event | 0 Participants |
| Sumatriptan Placebo/600 mg Telcagepant | Number of Participants Who Were Discontinued From Any Study Period Due to an Adverse Event | 0 Participants |
| Sumatriptan Placebo/Telcagepant Placebo | Number of Participants Who Were Discontinued From Any Study Period Due to an Adverse Event | 0 Participants |
Secondary
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).
Time frame: Predose up to 150 minutes postdose of each treatment period (up to 10 weeks)
Population: Participants who were administered telcagepant or placebo in either Periods 1, 2, 3, or 4 regardless of sequence.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| 100 mg Sumatriptan/600 mg Telcagepant | Time-weighted Mean Arterial Pressure (Telcagepant Versus Placebo) | 84.7 mmHg |
| 100 mg Sumatriptan/Telcagepant Placebo | Time-weighted Mean Arterial Pressure (Telcagepant Versus Placebo) | 83.5 mmHg |
Comparison: sumatriptan placebo/600 mg telcagepant minus sumatriptan placebo/telcagepant placebo90% CI: [-0.2, 2.7]Mixed Effect Model