Migraine
Conditions
Brief summary
The purpose of this study is to investigate the safety and tolerability of telcagepant (MK-0974) in the long-term treatment of acute migraine in adult participants. The primary hypothesis of this study is that telcagepant is well tolerated in the long-term treatment of acute migraine in adult participants.
Interventions
DRUGTelcagepant 300 mg soft gel capsules
One capsule taken orally at onset of migraine
DRUGTelcagepant 280 mg tablets
One tablet taken orally at onset of migraine
DRUGRizatriptan 10 mg tablets
One tablet taken orally at onset of migraine
DRUGPlacebo to telcagepant capsules
One capsule taken orally at onset of migraine
DRUGPlacebo to telcagepant tablets
One tablet taken orally at onset of migraine
DRUGPlacebo to rizatriptan tablets
One tablet taken orally at onset of migraine
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* At least 1 year history of migraine (with or without aura) * Females of child bearing potential must use acceptable contraception throughout trial * In general good health based on screening assessment
Exclusion criteria
* Pregnant/breast-feeding (or is a female expecting to conceive during study period) * 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 * Major depression, other pain syndromes that might interfere with study assessments, psychiatric conditions, dementia, or significant neurological disorders (other than migraine) * History of gastric, or small intestinal surgery, or has a disease that causes malabsorption * History of cancer within the last 5 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With At Least One Triptan-Related Adverse Experience (AE) | Within 14 days of any dose of study drug (Up to 18.5 months) | Triptan-related AEs are defined as: chest pain, chest tightness, asthenia, paraesthesia, dysaesthesia or hyperaesthesia. Participants were monitored for triptan-related AEs for 14 days after any dose of study drug. |
| Percentage of Participants With At Least One Clinical AE | Within 14 days of any dose of study drug (Up to 18.5 months) | 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 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 is temporally associated with the use of the study product, is also an AE. A clinical AE was an AE reported as a result of a clinical examination. Participants were monitored for clinical AEs for 14 days after any dose of study drug. |
| Percentage of Participants With At Least One Laboratory AE | Within 14 days of any dose of study drug (Up to 18.5 months) | 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 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 is temporally associated with the use of the study product, is also an AE. A laboratory AE was an AE reported as a result of a laboratory assessment or test. Participants were monitored for laboratory AEs for 14 days after any dose of study drug. |
| Percentage of Participants With At Least One Vital Sign Measurement Outside Predefined Limits of Change | Within 14 days of any dose of study drug (Up to 18.5 months) | Predefined limits of change were established for vital sign measurements: Systolic Blood Pressure (\>=180 mm Hg and 20 mm Hg increase OR \<=90 mm Hg and 20 mm Hg decrease), Diastolic Blood Pressure (\>=105 mm Hg and 15 mm Hg increase OR \<=50 mm Hg and 15 mm Hg decrease), Pulse (\>=120 beats per minute \[bpm\] and 15 bpm increase OR \<=50 bpm and 15 bpm decrease), Body Temperature (\>38º C \[oral equivalent\]) and Respiratory Rate (\>25 or increase of 10 OR \<5 or decrease of 10 \[per minute\]). Participants were monitored for vital sign measurements outside predefined limits of change for 14 days after any dose of study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participant Migraine Attacks With Pain Freedom (PF) at 2 Hours Post-Dose | 2 hours post-dose (Up to 18 months) | 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 mild, moderate or severe migraine headache (Grade 1, 2, or 3) at baseline to no pain (Grade 0) 2 hours post-dose. |
Participant flow
Pre-assignment details
The trial was considered to have achieved completion as defined by the treatment of 100 participants for 12 months.
Participants by arm
| Arm | Count |
|---|---|
| Telcagepant 280 mg/300 mg Participants receive telcagepant 300 mg soft gel capsules or telcagepant 280 mg tablets, administered orally as a single dose at onset of migraine. If still experiencing a migraine 2 hours after the first dose of telcagepant, participants may take an optional second dose of study drug or non-study rescue medication. Participants may take up to 16 doses (for treatment of up to 8 migraines) of telcagepant per month for up to 18 months. | 641 |
| Rizatriptan 10 mg Participants receive rizatriptan tablets, administered orally as a single dose at onset of migraine. If still experiencing a migraine 2 hours after the first dose of rizatriptan, participants may take an optional second dose of study drug or non-study rescue medication. Participants may take up to 16 doses (for treatment of up to 8 migraines) of rizatriptan per month for up to 18 months. | 313 |
| Total | 954 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Months 13 to 18 Treatment Period | Adverse Event | 1 | 0 |
| Months 13 to 18 Treatment Period | Lack of Efficacy | 1 | 0 |
| Months 13 to 18 Treatment Period | Lost to Follow-up | 2 | 2 |
| Months 13 to 18 Treatment Period | Protocol Violation | 1 | 0 |
| Months 13 to 18 Treatment Period | Trial Terminated | 87 | 43 |
| Months 13 to 18 Treatment Period | Withdrawal by Subject | 7 | 2 |
| Months 1 to 12 Treatment Period | Adverse Event | 22 | 11 |
| Months 1 to 12 Treatment Period | Lack of Efficacy | 50 | 11 |
| Months 1 to 12 Treatment Period | Lack of Qualifying Event | 1 | 1 |
| Months 1 to 12 Treatment Period | Lost to Follow-up | 36 | 15 |
| Months 1 to 12 Treatment Period | Missing | 2 | 1 |
| Months 1 to 12 Treatment Period | Not Treated | 71 | 43 |
| Months 1 to 12 Treatment Period | Physician Decision | 8 | 4 |
| Months 1 to 12 Treatment Period | Pregnancy | 3 | 4 |
| Months 1 to 12 Treatment Period | Protocol Violation | 14 | 7 |
| Months 1 to 12 Treatment Period | Trial Terminated | 43 | 23 |
| Months 1 to 12 Treatment Period | Withdrawal by Subject | 95 | 34 |
Baseline characteristics
| Characteristic | Telcagepant 280 mg/300 mg | Rizatriptan 10 mg | Total |
|---|---|---|---|
| Age, Continuous | 42.5 Years STANDARD_DEVIATION 10.9 | 41.9 Years STANDARD_DEVIATION 11.1 | 42.3 Years STANDARD_DEVIATION 11 |
| Sex: Female, Male Female | 502 Participants | 237 Participants | 739 Participants |
| Sex: Female, Male Male | 139 Participants | 76 Participants | 215 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 187 / 641 | 127 / 313 |
| serious Total, serious adverse events | 12 / 641 | 6 / 313 |
Outcome results
Primary
Percentage of Participants With At Least One Clinical 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 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 is temporally associated with the use of the study product, is also an AE. A clinical AE was an AE reported as a result of a clinical examination. Participants were monitored for clinical AEs for 14 days after any dose of study drug.
Time frame: Within 14 days of any dose of study drug (Up to 18.5 months)
Population: The APAT population consisted of all participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Telcagepant 280 mg/300 mg | Percentage of Participants With At Least One Clinical AE | 58.7 Percentage of Participants |
| Rizatriptan 10 mg | Percentage of Participants With At Least One Clinical AE | 63.9 Percentage of Participants |
95% CI: [-11.7, 1.4]
Primary
Percentage of Participants With At Least One Laboratory 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 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 is temporally associated with the use of the study product, is also an AE. A laboratory AE was an AE reported as a result of a laboratory assessment or test. Participants were monitored for laboratory AEs for 14 days after any dose of study drug.
Time frame: Within 14 days of any dose of study drug (Up to 18.5 months)
Population: The APAT population consisted of all participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Telcagepant 280 mg/300 mg | Percentage of Participants With At Least One Laboratory AE | 1.9 Percentage of Participants |
| Rizatriptan 10 mg | Percentage of Participants With At Least One Laboratory AE | 1.6 Percentage of Participants |
95% CI: [-2, 2]
Primary
Percentage of Participants With At Least One Triptan-Related Adverse Experience (AE)
Triptan-related AEs are defined as: chest pain, chest tightness, asthenia, paraesthesia, dysaesthesia or hyperaesthesia. Participants were monitored for triptan-related AEs for 14 days after any dose of study drug.
Time frame: Within 14 days of any dose of study drug (Up to 18.5 months)
Population: The All-Patients-As-Treated (APAT) population consisted of all participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Telcagepant 280 mg/300 mg | Percentage of Participants With At Least One Triptan-Related Adverse Experience (AE) | 5.0 Percentage of Participants |
| Rizatriptan 10 mg | Percentage of Participants With At Least One Triptan-Related Adverse Experience (AE) | 11.2 Percentage of Participants |
p-value: <0.00195% CI: [-10.4, -2.6]Miettenen and Nurminen method
Primary
Percentage of Participants With At Least One Vital Sign Measurement Outside Predefined Limits of Change
Predefined limits of change were established for vital sign measurements: Systolic Blood Pressure (\>=180 mm Hg and 20 mm Hg increase OR \<=90 mm Hg and 20 mm Hg decrease), Diastolic Blood Pressure (\>=105 mm Hg and 15 mm Hg increase OR \<=50 mm Hg and 15 mm Hg decrease), Pulse (\>=120 beats per minute \[bpm\] and 15 bpm increase OR \<=50 bpm and 15 bpm decrease), Body Temperature (\>38º C \[oral equivalent\]) and Respiratory Rate (\>25 or increase of 10 OR \<5 or decrease of 10 \[per minute\]). Participants were monitored for vital sign measurements outside predefined limits of change for 14 days after any dose of study drug.
Time frame: Within 14 days of any dose of study drug (Up to 18.5 months)
Population: The APAT population consisted of all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Telcagepant 280 mg/300 mg | Percentage of Participants With At Least One Vital Sign Measurement Outside Predefined Limits of Change | Systolic Blood Pressure Increase | 0.2 Percentage of Participants |
| Telcagepant 280 mg/300 mg | Percentage of Participants With At Least One Vital Sign Measurement Outside Predefined Limits of Change | Systolic Blood Pressure Decrease | 1.4 Percentage of Participants |
| Telcagepant 280 mg/300 mg | Percentage of Participants With At Least One Vital Sign Measurement Outside Predefined Limits of Change | Diastolic Blood Pressure Increase | 0.3 Percentage of Participants |
| Telcagepant 280 mg/300 mg | Percentage of Participants With At Least One Vital Sign Measurement Outside Predefined Limits of Change | Diastolic Blood Pressure Decrease | 1.1 Percentage of Participants |
| Telcagepant 280 mg/300 mg | Percentage of Participants With At Least One Vital Sign Measurement Outside Predefined Limits of Change | Pulse Increase | 0.0 Percentage of Participants |
| Telcagepant 280 mg/300 mg | Percentage of Participants With At Least One Vital Sign Measurement Outside Predefined Limits of Change | Pulse Decrease | 0.6 Percentage of Participants |
| Telcagepant 280 mg/300 mg | Percentage of Participants With At Least One Vital Sign Measurement Outside Predefined Limits of Change | Body Temperature Increase | 0.3 Percentage of Participants |
| Telcagepant 280 mg/300 mg | Percentage of Participants With At Least One Vital Sign Measurement Outside Predefined Limits of Change | Respiratory Rate Increase or Decrease | 0.8 Percentage of Participants |
| Rizatriptan 10 mg | Percentage of Participants With At Least One Vital Sign Measurement Outside Predefined Limits of Change | Respiratory Rate Increase or Decrease | 0.6 Percentage of Participants |
| Rizatriptan 10 mg | Percentage of Participants With At Least One Vital Sign Measurement Outside Predefined Limits of Change | Systolic Blood Pressure Increase | 0.3 Percentage of Participants |
| Rizatriptan 10 mg | Percentage of Participants With At Least One Vital Sign Measurement Outside Predefined Limits of Change | Pulse Increase | 0.0 Percentage of Participants |
| Rizatriptan 10 mg | Percentage of Participants With At Least One Vital Sign Measurement Outside Predefined Limits of Change | Systolic Blood Pressure Decrease | 1.3 Percentage of Participants |
| Rizatriptan 10 mg | Percentage of Participants With At Least One Vital Sign Measurement Outside Predefined Limits of Change | Body Temperature Increase | 0.3 Percentage of Participants |
| Rizatriptan 10 mg | Percentage of Participants With At Least One Vital Sign Measurement Outside Predefined Limits of Change | Diastolic Blood Pressure Increase | 0.6 Percentage of Participants |
| Rizatriptan 10 mg | Percentage of Participants With At Least One Vital Sign Measurement Outside Predefined Limits of Change | Pulse Decrease | 1.6 Percentage of Participants |
| Rizatriptan 10 mg | Percentage of Participants With At Least One Vital Sign Measurement Outside Predefined Limits of Change | Diastolic Blood Pressure Decrease | 1.0 Percentage of Participants |
Secondary
Percentage of Participant Migraine Attacks 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 mild, moderate or severe migraine headache (Grade 1, 2, or 3) at baseline to no pain (Grade 0) 2 hours post-dose.
Time frame: 2 hours post-dose (Up to 18 months)
Population: The Full Analysis Set (FAS) population consisted of all participants who were randomized and reported at least one treated migraine attack with at least one post-treatment efficacy evaluation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Telcagepant 280 mg/300 mg | Percentage of Participant Migraine Attacks With Pain Freedom (PF) at 2 Hours Post-Dose | 38.9 Percentage of Migraine Attacks | Standard Deviation 29.5 |
| Rizatriptan 10 mg | Percentage of Participant Migraine Attacks With Pain Freedom (PF) at 2 Hours Post-Dose | 47.5 Percentage of Migraine Attacks | Standard Deviation 29.7 |
95% CI: [0.45, 0.75]