Migraine
Conditions
Brief summary
To evaluate the long-term safety and tolerability of subcutaneous (SC) administration of TEV-48125 (at 225 mg once monthly \[except for a loading dose of 675 mg for CM patients\] or at 675 mg every 3 months) for the preventive treatment of Chronic Migraine and Episodic Migraine patients
Interventions
DRUGTEV-48125
TEV-48125 will be administered subcutaneously once every 4 weeks.
Sponsors
Otsuka Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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 Chronic migraine or 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 2 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
\- 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 |
|---|---|---|
| Percentage of Subjects With at Least One Treatment-Emergent Adverse Event (TEAE) | Baseline (Day 0) up to follow-up visit (Day 562) | * TEAEs are defined as the AEs that started after trial investigational medicinal product (IMP) treatment. Multiple occurrences of TEAEs are counted once per MedDRA preferred term. * Specific AE terms are provided in the Adverse Event section. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in the Monthly (28 Day) Average Number of Migraine Days | Baseline, Month 12 | 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 had experienced 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 mild, moderate, or severe. 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 (28 Day) Average Number of Headache Days of at Least Moderate Severity | Baseline, Month 12 | 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 had experienced 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 mild, moderate, or severe. Subjects also recorded the presence or absence of photophobia, phonophobia, nausea, or vomiting, and the status of use of any acute headache medications. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| TEV-48125 (225 mg/1 Month) Group TEV-48125 will be administered subcutaneously once every 4 weeks for a total of 13 doses (at 225 mg once monthly \[except for a loading dose of 675 mg in subjects with chronic migraine). | 25 |
| TEV-48125 (675 mg/3 Month) Group TEV-48125 will be administered subcutaneously once every 12 weeks for a total of 5 doses (at 675 mg once every 3 months). | 25 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 |
| Overall Study | Lack of Efficacy | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | TEV-48125 (225 mg/1 Month) Group | TEV-48125 (675 mg/3 Month) Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants | 25 Participants | 49 Participants |
| Age, Continuous | 46.8 years STANDARD_DEVIATION 7.9 | 45.8 years STANDARD_DEVIATION 7 | 46.3 years STANDARD_DEVIATION 7.4 |
| Race/Ethnicity, Customized Japanese | 25 Participants | 25 Participants | 50 Participants |
| Region of Enrollment Japan | 25 Participants | 25 Participants | 50 Participants |
| Sex: Female, Male Female | 23 Participants | 19 Participants | 42 Participants |
| Sex: Female, Male Male | 2 Participants | 6 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 25 |
| other Total, other adverse events | 20 / 25 | 16 / 25 |
| serious Total, serious adverse events | 0 / 25 | 2 / 25 |
Outcome results
Primary
Percentage of Subjects With at Least One Treatment-Emergent Adverse Event (TEAE)
* TEAEs are defined as the AEs that started after trial investigational medicinal product (IMP) treatment. Multiple occurrences of TEAEs are counted once per MedDRA preferred term. * Specific AE terms are provided in the Adverse Event section.
Time frame: Baseline (Day 0) up to follow-up visit (Day 562)
Population: Safety Set (SS): Newly enrolled subjects who received the IMP at least once
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TEV-48125 (225 mg/1 Month) Group | Percentage of Subjects With at Least One Treatment-Emergent Adverse Event (TEAE) | 92.0 percentage of participants |
| TEV-48125 (675 mg/3 Month) Group | Percentage of Subjects With at Least One Treatment-Emergent Adverse Event (TEAE) | 88.0 percentage of participants |
Secondary
Mean Change From Baseline in the Monthly (28 Day) Average Number of Headache Days of at Least Moderate Severity
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 had experienced 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 mild, moderate, or severe. 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, Month 12
Population: Full Analysis set (FAS): Newly enrolled subjects for whom electronic headache diary efficacy assessment data at baseline and after the first dose of IMP were available
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TEV-48125 (225 mg/1 Month) Group | Mean Change From Baseline in the Monthly (28 Day) Average Number of Headache Days of at Least Moderate Severity | -4.3 days/month | Standard Deviation 4.1 |
| TEV-48125 (675 mg/3 Month) Group | Mean Change From Baseline in the Monthly (28 Day) Average Number of Headache Days of at Least Moderate Severity | -2.1 days/month | Standard Deviation 4.1 |
Secondary
Mean Change From Baseline in the Monthly (28 Day) Average Number of Migraine Days
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 had experienced 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 mild, moderate, or severe. 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, Month 12
Population: Full Analysis set (FAS): Newly enrolled subjects for whom electronic headache diary efficacy assessment data at baseline and after the first dose of IMP were available
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TEV-48125 (225 mg/1 Month) Group | Mean Change From Baseline in the Monthly (28 Day) Average Number of Migraine Days | -5.9 days/month | Standard Deviation 4.3 |
| TEV-48125 (675 mg/3 Month) Group | Mean Change From Baseline in the Monthly (28 Day) Average Number of Migraine Days | -1.6 days/month | Standard Deviation 5.7 |