Migraine
Conditions
Brief summary
To evaluate the efficacy and safety of subcutaneous (SC) administration of TEV-48125 (monthly TEV-48125 225 mg and TEV-48125 675 mg once over a period of 3 months) compared with placebo for preventive treatment in Episodic Migraine patients
Interventions
DRUGTEV-48125
TEV-48125 will be subcutaneously administered once monthly for 3 months.
TEV-48125 or placebo will be subcutaneously administered once monthly for 3 months.
DRUGPlacebo
Placebo will be subcutaneously administered once monthly for 3 months.
Sponsors
Otsuka Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Patient has a history of migraine (according to The International Classification of Headache Disorders, third edition \[beta version\] criteria) or clinical judgment suggests a migraine diagnosis * Patient fulfills the criteria for Episodic migraine in baseline information collected during the 28 day screening period * Not using preventive migraine medications for migraine or other medical conditions or using no more than 1 preventive migraine medication for migraine or other medical conditions if the dose and regimen have been stable for at least 2 months prior to giving informed consent. * Patient demonstrates compliance with the electronic headache diary during the screening period by entry of headache data on a minimum of 24 of 28 days and the entered data is judged appropriate by the investigator.
Exclusion criteria
Patients who have previously failed (lack of efficacy) 2 or more of the clusters of the medications for treatment of migraine after use for at least 3 months at accepted migraine therapeutic doses \- Hematological, cardiac, renal, endocrine, pulmonary, gastrointestinal, genitourinary, neurologic, hepatic, or ocular disease considered clinically significant in the judgment of the investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in the Monthly (28 Days) Average Number of Migraine Days During the 12-week Period After the First Dose of Investigational Medicinal Product (IMP) | Baseline, 12 weeks | Headache-related efficacy endpoints were derived from headache variables collected using an eDiary. On each day, the subjects were asked to enter headache data in the electronic headache diary for the previous 24-hour period. Subjects who reported headache on the previous day answered questions about the headache (ie, occurrence of headache, duration of headache, maximum severity of headache, presence/absence of associated symptoms, and use of acute headache medications). Overall headache duration was recorded numerically, in hours, as well as number of hours with headache of at least moderate severity. If headache was reported, then headache severity was subjectively rated by the subject as follows: Mild headache, Moderate headache, Severe headache. Subjects also recorded the presence or absence of photophobia, phonophobia, nausea, or vomiting, and the status of use of any acute headache medications. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects Reaching at Least 50% Reduction in the Monthly Average Number of Migraine Days During the 12-week Period After the First Dose of IMP | 12 weeks | Headache-related efficacy endpoints were derived from headache variables collected using an eDiary. On each day, the subjects were asked to enter headache data in the electronic headache diary for the previous 24-hour period. Subjects who reported headache on the previous day answered questions about the headache (ie, occurrence of headache, duration of headache, maximum severity of headache, presence/absence of associated symptoms, and use of acute headache medications). Overall headache duration was recorded numerically, in hours, as well as number of hours with headache of at least moderate severity. If headache was reported, then headache severity was subjectively rated by the subject as follows: Mild headache, Moderate headache, Severe headache. Subjects also recorded the presence or absence of photophobia, phonophobia, nausea, or vomiting, and the status of use of any acute headache medications. |
| Mean Change From Baseline in the Monthly Average Number of Days With Use of Any Acute Headache Medications During the 12-week Period After the First Dose of IMP | Baseline, 12 weeks | Headache-related efficacy endpoints were derived from headache variables collected using an eDiary. On each day, subjects entered headache data in the electronic headache diary for the previous 24-hour period. Subjects who reported headache on the previous day answered questions about the headache (ie, occurrence of headache, duration of headache, maximum severity of headache, presence/absence of associated symptoms, and use of acute headache medications). |
| Mean Change From Baseline in the Monthly Average Number of Migraine Days During the 12-week Period After the First Dose of IMP in Patients Not Receiving Concomitant Preventive Migraine Medications | Baseline, 12 weeks | Headache-related efficacy endpoints were derived from headache variables collected using an eDiary. On each day, the subjects were asked to enter headache data in the electronic headache diary for the previous 24-hour period. Subjects who reported headache on the previous day answered questions about the headache (ie, occurrence of headache, duration of headache, maximum severity of headache, presence/absence of associated symptoms, and use of acute headache medications). Overall headache duration was recorded numerically, in hours, as well as number of hours with headache of at least moderate severity. If headache was reported, then headache severity was subjectively rated by the subject as follows: Mild headache, Moderate headache, Severe headache. Subjects also recorded the presence or absence of photophobia, phonophobia, nausea, or vomiting, and the status of use of any acute headache medications. |
| Mean Change From Baseline in Disability Score, as Measured by Migraine Disability Assessment (MIDAS) Questionnaire at 4 Weeks After the Final (Third) Dose of IMP | Baseline, 4 weeks | Using the MIDAS questionnaire, subjects assessed the degree of headache-related disability based on lost days of activity in 3 domains (work, household work, and nonwork) over the last 3 months. The MIDAS questionnaire was a 5-item instrument. The total of the scores of the first 5 questions was used for grading the level of disability, with scores of 0 to 5, 6 to 10, 11 to 20, and ≥ 21 interpreted as disability grades I (little or no disability), II (mild disability), III (moderate disability), and IV (severe disability), respectively. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| TEV-48125 (225/225/225 mg) Group TEV-48125 will be subcutaneously administered once monthly for 3 months (225/225/225 mg). | 121 |
| TEV-48125 (675 mg/Placebo/Placebo) Group TEV-48125 or placebo will be subcutaneously administered once monthly for 3 months (675 mg/placebo/placebo). | 119 |
| Placebo Group Placebo will be subcutaneously administered once monthly for 3 months (placebo/placebo/placebo). | 117 |
| Total | 357 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 5 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 3 |
Baseline characteristics
| Characteristic | TEV-48125 (225/225/225 mg) Group | TEV-48125 (675 mg/Placebo/Placebo) Group | Placebo Group | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 3 Participants | 5 Participants | 9 Participants |
| Age, Categorical Between 18 and 65 years | 120 Participants | 116 Participants | 112 Participants | 348 Participants |
| Age, Continuous | 44.4 years STANDARD_DEVIATION 9.5 | 41.9 years STANDARD_DEVIATION 10.1 | 44.2 years STANDARD_DEVIATION 10.7 | 43.5 years STANDARD_DEVIATION 10.1 |
| Race/Ethnicity, Customized Asian | 121 Participants | 119 Participants | 117 Participants | 357 Participants |
| Region of Enrollment Japan | 102 Participants | 101 Participants | 98 Participants | 301 Participants |
| Region of Enrollment South Korea | 19 Participants | 18 Participants | 19 Participants | 56 Participants |
| Sex: Female, Male Female | 101 Participants | 101 Participants | 100 Participants | 302 Participants |
| Sex: Female, Male Male | 20 Participants | 18 Participants | 17 Participants | 55 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 121 | 0 / 118 | 0 / 117 |
| other Total, other adverse events | 69 / 121 | 74 / 118 | 77 / 117 |
| serious Total, serious adverse events | 0 / 121 | 0 / 118 | 0 / 117 |
Outcome results
Primary
Mean Change From Baseline in the Monthly (28 Days) Average Number of Migraine Days During the 12-week Period After the First Dose of Investigational Medicinal Product (IMP)
Headache-related efficacy endpoints were derived from headache variables collected using an eDiary. On each day, the subjects were asked to enter headache data in the electronic headache diary for the previous 24-hour period. Subjects who reported headache on the previous day answered questions about the headache (ie, occurrence of headache, duration of headache, maximum severity of headache, presence/absence of associated symptoms, and use of acute headache medications). Overall headache duration was recorded numerically, in hours, as well as number of hours with headache of at least moderate severity. If headache was reported, then headache severity was subjectively rated by the subject as follows: Mild headache, Moderate headache, Severe headache. Subjects also recorded the presence or absence of photophobia, phonophobia, nausea, or vomiting, and the status of use of any acute headache medications.
Time frame: Baseline, 12 weeks
Population: Full Analysis set (FAS): Subjects who received the IMP at least once and had baseline and Week 12 data on monthly average number of migraine days.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TEV-48125 (225/225/225 mg) Group | Mean Change From Baseline in the Monthly (28 Days) Average Number of Migraine Days During the 12-week Period After the First Dose of Investigational Medicinal Product (IMP) | -4.00 days/month | Standard Error 0.37 |
| TEV-48125 (675 mg/Placebo/Placebo) Group | Mean Change From Baseline in the Monthly (28 Days) Average Number of Migraine Days During the 12-week Period After the First Dose of Investigational Medicinal Product (IMP) | -4.02 days/month | Standard Error 0.38 |
| Placebo Group | Mean Change From Baseline in the Monthly (28 Days) Average Number of Migraine Days During the 12-week Period After the First Dose of Investigational Medicinal Product (IMP) | -1.02 days/month | Standard Error 0.38 |
Secondary
Mean Change From Baseline in Disability Score, as Measured by Migraine Disability Assessment (MIDAS) Questionnaire at 4 Weeks After the Final (Third) Dose of IMP
Using the MIDAS questionnaire, subjects assessed the degree of headache-related disability based on lost days of activity in 3 domains (work, household work, and nonwork) over the last 3 months. The MIDAS questionnaire was a 5-item instrument. The total of the scores of the first 5 questions was used for grading the level of disability, with scores of 0 to 5, 6 to 10, 11 to 20, and ≥ 21 interpreted as disability grades I (little or no disability), II (mild disability), III (moderate disability), and IV (severe disability), respectively.
Time frame: Baseline, 4 weeks
Population: Full Analysis set (FAS): Subjects who received the IMP at least once and had baseline and Week 12 data on monthly average number of migraine days. Overall Number of Participants Analyzed = the number of subjects with both baseline and assessment at each visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TEV-48125 (225/225/225 mg) Group | Mean Change From Baseline in Disability Score, as Measured by Migraine Disability Assessment (MIDAS) Questionnaire at 4 Weeks After the Final (Third) Dose of IMP | -12.64 score on a scale | Standard Error 1.42 |
| TEV-48125 (675 mg/Placebo/Placebo) Group | Mean Change From Baseline in Disability Score, as Measured by Migraine Disability Assessment (MIDAS) Questionnaire at 4 Weeks After the Final (Third) Dose of IMP | -12.55 score on a scale | Standard Error 1.49 |
| Placebo Group | Mean Change From Baseline in Disability Score, as Measured by Migraine Disability Assessment (MIDAS) Questionnaire at 4 Weeks After the Final (Third) Dose of IMP | -7.41 score on a scale | Standard Error 1.46 |
Secondary
Mean Change From Baseline in the Monthly Average Number of Days With Use of Any Acute Headache Medications During the 12-week Period After the First Dose of IMP
Headache-related efficacy endpoints were derived from headache variables collected using an eDiary. On each day, subjects entered headache data in the electronic headache diary for the previous 24-hour period. Subjects who reported headache on the previous day answered questions about the headache (ie, occurrence of headache, duration of headache, maximum severity of headache, presence/absence of associated symptoms, and use of acute headache medications).
Time frame: Baseline, 12 weeks
Population: Full Analysis set (FAS): Subjects who received the IMP at least once and had baseline and Week 12 data on monthly average number of migraine days. Overall Number of Participants Analyzed = the number of subjects with both baseline and assessment at each visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TEV-48125 (225/225/225 mg) Group | Mean Change From Baseline in the Monthly Average Number of Days With Use of Any Acute Headache Medications During the 12-week Period After the First Dose of IMP | -3.30 days/month | Standard Error 0.34 |
| TEV-48125 (675 mg/Placebo/Placebo) Group | Mean Change From Baseline in the Monthly Average Number of Days With Use of Any Acute Headache Medications During the 12-week Period After the First Dose of IMP | -3.29 days/month | Standard Error 0.36 |
| Placebo Group | Mean Change From Baseline in the Monthly Average Number of Days With Use of Any Acute Headache Medications During the 12-week Period After the First Dose of IMP | -0.46 days/month | Standard Error 0.35 |
Secondary
Mean Change From Baseline in the Monthly Average Number of Migraine Days During the 12-week Period After the First Dose of IMP in Patients Not Receiving Concomitant Preventive Migraine Medications
Headache-related efficacy endpoints were derived from headache variables collected using an eDiary. On each day, the subjects were asked to enter headache data in the electronic headache diary for the previous 24-hour period. Subjects who reported headache on the previous day answered questions about the headache (ie, occurrence of headache, duration of headache, maximum severity of headache, presence/absence of associated symptoms, and use of acute headache medications). Overall headache duration was recorded numerically, in hours, as well as number of hours with headache of at least moderate severity. If headache was reported, then headache severity was subjectively rated by the subject as follows: Mild headache, Moderate headache, Severe headache. Subjects also recorded the presence or absence of photophobia, phonophobia, nausea, or vomiting, and the status of use of any acute headache medications.
Time frame: Baseline, 12 weeks
Population: Full Analysis set (FAS): Subjects who received the IMP at least once and had baseline and Week 12 data on monthly average number of migraine days. Overall Number of Participants Analyzed = the number of subjects with both baseline and assessment at each visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TEV-48125 (225/225/225 mg) Group | Mean Change From Baseline in the Monthly Average Number of Migraine Days During the 12-week Period After the First Dose of IMP in Patients Not Receiving Concomitant Preventive Migraine Medications | -4.42 days/month | Standard Error 0.36 |
| TEV-48125 (675 mg/Placebo/Placebo) Group | Mean Change From Baseline in the Monthly Average Number of Migraine Days During the 12-week Period After the First Dose of IMP in Patients Not Receiving Concomitant Preventive Migraine Medications | -4.21 days/month | Standard Error 0.37 |
| Placebo Group | Mean Change From Baseline in the Monthly Average Number of Migraine Days During the 12-week Period After the First Dose of IMP in Patients Not Receiving Concomitant Preventive Migraine Medications | -1.40 days/month | Standard Error 0.37 |
Secondary
Proportion of Subjects Reaching at Least 50% Reduction in the Monthly Average Number of Migraine Days During the 12-week Period After the First Dose of IMP
Headache-related efficacy endpoints were derived from headache variables collected using an eDiary. On each day, the subjects were asked to enter headache data in the electronic headache diary for the previous 24-hour period. Subjects who reported headache on the previous day answered questions about the headache (ie, occurrence of headache, duration of headache, maximum severity of headache, presence/absence of associated symptoms, and use of acute headache medications). Overall headache duration was recorded numerically, in hours, as well as number of hours with headache of at least moderate severity. If headache was reported, then headache severity was subjectively rated by the subject as follows: Mild headache, Moderate headache, Severe headache. Subjects also recorded the presence or absence of photophobia, phonophobia, nausea, or vomiting, and the status of use of any acute headache medications.
Time frame: 12 weeks
Population: Full Analysis set (FAS): Subjects who received the IMP at least once and had baseline and Week 12 data on monthly average number of migraine days. Overall Number of Participants Analyzed = the number of subjects meeting responder criteria.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TEV-48125 (225/225/225 mg) Group | Proportion of Subjects Reaching at Least 50% Reduction in the Monthly Average Number of Migraine Days During the 12-week Period After the First Dose of IMP | 41.3 percentage of participants |
| TEV-48125 (675 mg/Placebo/Placebo) Group | Proportion of Subjects Reaching at Least 50% Reduction in the Monthly Average Number of Migraine Days During the 12-week Period After the First Dose of IMP | 45.3 percentage of participants |
| Placebo Group | Proportion of Subjects Reaching at Least 50% Reduction in the Monthly Average Number of Migraine Days During the 12-week Period After the First Dose of IMP | 11.2 percentage of participants |