Migraine
Conditions
Brief summary
A study to evaluate the long-term safety, tolerability, and efficacy of subcutaneous (SC) administration of TEV-48125 in adult participants with chronic migraine (CM) or episodic migraine (EM). Participants with CM or EM who complete the pivotal efficacy studies of TEV-48125 (TV48125-CNS-30049 \[NCT02621931\] and TV48125-CNS-30050 \[NCT02629861\]) and agree to participate in this study; and new participants meeting eligibility criteria (not rolling over from pivotal studies), will be enrolled in this study.
Interventions
DRUGFremanezumab
Fremanezumab will be administered as per the dose and schedule specified in the respective arms.
DRUGPlacebo
Placebo matching to fremanezumab will be administered as per schedule specified in the respective arms.
Sponsors
Teva Branded Pharmaceutical Products R&D, Inc.
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
Participants Rolling Over from the Pivotal Efficacy Studies: * Participant must have signed and dated the informed consent document. * Participant must have completed the pivotal efficacy study without major protocol violations. * Additional criteria apply, please contact the investigator for more information. Participants Not Rolling Over from the Pivotal Efficacy Studies: * Males or females aged 18 to 70 years, inclusive, with migraine onset at less than or equal to (≤) 50 years of age. * Participant signed and dated the informed consent document. * Participant has a history of migraine or clinical judgment suggests a migraine diagnosis. * Participant fulfills the criteria for EM or CM with prospectively collected baseline information during the 28-day run-in period. * Body mass index (BMI) of 17.5 to 37.5 kilograms/square meter (kg/m\^2) and a total body weight between 45 and 120 kg, inclusive. * All participants must be of non-childbearing potential. 1. Participants must simultaneously use 2 forms of highly effective contraception methods. 2. Participants will remain abstinent throughout the study. * Female participants of childbearing potential must have a negative serum beta-human chorionic gonadotropin (β-HCG) pregnancy test prior at screening (confirmed by urine dipstick β-HCG pregnancy test at baseline). * The participant must be willing and able to comply with study restrictions, to remain at the clinic for the required duration during the study period, and to return to the clinic for the follow-up evaluation. * Additional criteria apply, please contact the investigator for more information
Exclusion criteria
Participants Rolling Over from the Pivotal Efficacy Studies: * Pregnant or nursing females * Compliance with daily diary entry lower than 75 percent (%) at the last month of the double-blind treatment period of the pivotal efficacy study. * Additional criteria apply, please contact the investigator for more information. Participants Not Rolling Over from the Pivotal Efficacy Studies: * Clinically significant findings at the discretion of the investigator. * Evidence or medical history of clinically significant psychiatric issues, including any suicide attempt in the past, or suicidal ideation with a specific plan in the past 2 years. * History of clinically significant cardiovascular disease or vascular ischemia (such as myocardial, neurological \[for example; cerebral ischemia\], peripheral extremity ischemia, or other ischemic event) or thromboembolic events (arterial or venous thrombotic or embolic events) such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism -Known infection or history of human immunodeficiency virus, tuberculosis, or chronic hepatitis B or C infection. * Past or current history of cancer in the past 5 years, except for appropriately treated nonmelanoma skin carcinoma. * Pregnant or nursing females. * History of hypersensitivity reactions to injected proteins, including monoclonal antibodies. * Participation in a clinical study of a new chemical entity or a prescription medicine within 2 months before study drug administration or 5 half-lives, whichever is longer. * History of alcohol or drug abuse during the past 2 years, or alcohol or drug dependence during the past 5 years. * The participant cannot participate or successfully complete the study, in the opinion of their healthcare provider or the investigator, for any of the following reasons: 1. mentally or legally incapacitated or unable to give consent for any reason. 2. in custody due to an administrative or a legal decision, under guardianship, or institutionalized. 3. unable to be contacted in case of emergency. 4. has any other condition, which, in the opinion of the investigator, makes the participant inappropriate for inclusion in the study. * Participant is a study center or sponsor employee who is directly involved in the study or the relative of such an employee. * Additional criteria apply, please contact the investigator for more information.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Suicidal Ideation and Suicidal Behavior as Assessed by the Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) | Baseline (Day -28 to Day -1), Month 12 | eC-SSRS is a questionnaire to assess suicidal ideation and suicidal behavior. Suicidal behavior was defined as a yes answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation was defined as a yes answer to any one of 5 suicidal ideation questions: wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent, any self-injurious behavior with no suicidal intent. |
| Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Values | Baseline (Day 0) up to EOT visit (Day 336) | Potentially clinically significant abnormal vital signs findings included: pulse rate: \<=50 beats/minute (bpm) and decrease of \>=15 bpm, or \>=120 bpm and increase of \>=15 bpm; systolic blood pressure: \<=90 millimeters of mercury (mmHg) and decrease of \>=20 mmHg, or \>=180 mmHg and increase of \>=20 mmHg; diastolic blood pressure: \<=50 mmHg and decrease of \>=15 mmHg or \>=105 mmHg and increase of \>=15 mmHg; respiratory rate: \<10 breaths/minute; and body temperature \>=38.3 degrees centigrade and change of \>=1.1 degrees centigrade. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. |
| Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Baseline (Day 0), endpoint (Day 336) | ECG parameters included: heart rate, PR interval, QRS interval, QT interval corrected using the Fridericia formula (QTcF), QT interval corrected using the Bazett's formula (QTcB) and RR interval. Shifts represented as Baseline - endpoint value (last observed post-baseline value). Abnormal NCS indicated an abnormal but not clinically significant finding. Abnormal CS indicated an abnormal and clinically significant finding. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. |
| Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Baseline (Day 0), endpoint (Day 336) | Coagulation parameters included: prothrombin time (PT) (seconds), prothrombin international normalized ratio (INR), activated partial thromboplastin time (aPTT) (seconds). Shifts represented as Baseline - endpoint value (last observed post-baseline value). Shifts from baseline to endpoint were summarized using participant counts grouped into three categories: - Low (below normal range) - Normal (within the normal range of 9.4 to 12.5 seconds) - High (above normal range). A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. |
| Number of Participants With Injection Site Reactions | Baseline (Day -28 to Day -1), Month 12 | Number of participants who reported treatment-emergent injection site reactions are summarized. Preferred terms from MedDRA version 18.1 were offered without a threshold applied. Injection site reactions included injection site induration, pain, erythema, haemorrhage, pruritus, swelling, bruising, rash, urticaria, warmth, dermatitis, haematoma, inflammation, discolouration, discomfort, hypersensitivity, hypoaesthesia, irritation, oedema, papule, paraesthesia, vesicles and pallor. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. |
| Number of Participants With Adverse Events (AEs) | Baseline (Day 0) up to follow-up visit (Day 533) | An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severe AE was defined as inability to carry out usual activities. Treatment-related AEs were defined as AEs with possible, probable, definite, or missing relationship to study drug. Serious AEs were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. |
| Number of Participants With Potentially Clinically Significant Abnormal Serum Chemistry Results | Baseline (Day 0) up to end of treatment (EOT) visit (Day 336) | Potentially clinically significant abnormal serum chemistry findings included: Blood Urea Nitrogen (BUN): greater than or equal to (\>=) 10.71 millimoles/liter (mmol/L), creatinine: \>=177 micromoles/liter (µmol/L), bilirubin: \>=34.2 µmol/L, Alanine Aminotransferase (ALT) (units/liter \[U/L\]): \>=3\*upper limit of normal (ULN) Aspartate Aminotransferase (AST) (U/L): \>=3\*ULN, and Gamma Glutamyl Transferase (GGT) (U/L): \>=3\*ULN. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. |
| Number of Participants With Potentially Clinically Significant Abnormal Hematology Results | Baseline (Day 0) up to EOT visit (Day 336) | Potentially clinically significant abnormal hematology findings included: hemoglobin: less than (\<) 115 grams/liter (g/L) (in males) or less than or equal to (\<=) 95 g/L (in females), hematocrit: \<0.37 L/L (in male) or \<0.32 L/L (in female), leukocytes: \>=20\*10\^9/L or \<=3\*10\^9/L, eosinophils/leukocytes: \>=10%, and platelets: \>=700\*10\^9/L or \<=75\*10\^9/L. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. |
| Number of Participants With Potentially Clinically Significant Abnormal Urinalysis Laboratory Tests Results | Baseline (Day 0) up to EOT visit (Day 336) | Potentially clinically significant abnormal urinalysis findings included: blood: \>=2 unit increase from baseline, urine glucose (milligrams/decilitre \[mg/dL\]): \>=2 unit increase from baseline, ketones (mg/dL): \>=2 unit increase from baseline, urine protein (mg/dL): \>=2 unit increase from baseline. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Monthly Average Number of Headache Days of Any Severity During the 4-Week Period at Month 12 | Baseline (Day -28 to Day -1), Month 12 | Headaches were subjectively rated by participants as mild, moderate or severe. A headache day of any severity for both CM and EM participants was defined as a calendar day (00:00 to 23:59) where the participant (using the electronic headache diary device) reports: a day with headache pain that lasts at least 4 hours with a peak severity of any severity or; a day when the participant used acute migraine-specific medication (triptans or ergots) to treat a headache of any severity or duration. Monthly averages were derived and normalized to 28 days equivalent by the following formula: (number of days of efficacy variable over relevant period/number of days with assessments recorded in the e-diary over the relevant period) \* 28. The change was calculated as post-baseline value - baseline value. |
| Percentage of Participants With At Least 50% Reduction From Baseline in Monthly Average Number of Migraine Days During the 4-Week Period at Month 12 | Baseline (Day -28 to Day -1), Month 12 | A migraine day was defined as when at least 1 of the following situations occurred: A calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours (for CM participants) or at least 2 consecutive hours (for EM participants) of a headache meeting criteria for migraine with or without aura; a calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours (for CM participants) or at least 2 consecutive hours (for EM participants) of a headache meeting criteria for probable migraine, a migraine subtype where only 1 migraine criterion was missing; a calendar day (0:00 to 23:59) demonstrating a headache of any duration that was treated with migraine-specific medications (triptans and ergot compounds). Monthly averages were derived and normalized to 28 days equivalent by formula: (number of days of efficacy variable over relevant period/number of days with assessments recorded in e-diary over relevant period) \* 28. |
| Percentage of Participants With At Least 50% Reduction From Baseline in Monthly Average Number of Headache Days of at Least Moderate Severity During the 4-Week Period | Baseline (Day -28 to Day -1), Month 12 | Headaches were subjectively rated by participants as mild, moderate or severe. A headache day of at least moderate severity for both CM and EM participants was defined as a calendar day (00:00 to 23:59) where the participant (using the electronic headache diary device) reports: a day with headache pain that lasts at least 4 hours with a peak severity of at least moderate severity or; a day when the participant used acute migraine-specific medication (triptans or ergots) to treat a headache of any severity or duration. Monthly averages were derived and normalized to 28 days equivalent by the following formula: (number of days of efficacy variable over relevant period/number of days with assessments recorded in the e-diary over the relevant period) \* 28. |
| Change From Baseline in Monthly Average Number of Migraine Days During the 4-Week Period at Month 12 | Baseline (Day -28 to Day -1), Month 12 | A migraine day was defined as when at least 1 of the following situations occurred: A calendar day(0:00 to 23:59) demonstrating at least 4 consecutive hours (for CM participants) or at least 2 consecutive hours (for EM participants) of a headache meeting criteria for migraine with or without aura; a calendar day(0:00 to 23:59) demonstrating at least 4 consecutive hours (for CM participants) or at least 2 consecutive hours (for EM participants) of a headache meeting criteria for probable migraine, a migraine subtype where only 1 migraine criterion was missing; a calendar day(0:00 to 23:59) demonstrating a headache of any duration that was treated with migraine-specific medications (triptans and ergot compounds). Monthly averages were derived and normalized to 28 days equivalent by formula: (number of days of efficacy variable over relevant period/number of days with assessments recorded in e-diary over relevant period)\*28. Change was calculated as post-baseline value - baseline value. |
Countries
Canada, Czechia, Finland, Israel, Japan, Poland, Russia, Spain, United States
Participant flow
Recruitment details
Participants with chronic or episodic migraine (CM or EM) who completed the pivotal efficacy studies of fremanezumab (TV48125-CNS-30049 \[NCT02621931\] and TV48125-CNS-30050 \[NCT02629861\]) and agreed to participate in this study; and new participants meeting eligibility criteria (not rolling over from pivotal studies), were enrolled in this study.
Pre-assignment details
A total of 1890 participants were enrolled, including 917 participants with CM rolled over from Study TV48125-CNS-30049, 661 participants with EM rolled over from Study TV48125-CNS-30050, and 312 newly enrolled participants (193 with CM and 119 with EM).
Participants by arm
| Arm | Count |
|---|---|
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants Participants with CM who were randomized to the placebo treatment group or participants who did not rollover from the pivotal efficacy study, received fremanezumab 675 mg SC as loading dose (3 injections of fremanezumab 225 mg/1.5 mL on Day 0) followed by 11 monthly SC doses of fremanezumab at 225 mg (1 injection of fremanezumab 225 mg/1.5 mL and 2 injections of placebo 1.5 mL on Days 84, 168, and 252; and 1 injection of fremanezumab 225 mg/1.5 mL on Days 28, 56, 112, 140, 196, 224, 280, and 308). Participants with EM who were randomized to the placebo treatment group or participants who did not rollover from the pivotal efficacy study, received 12 monthly SC doses of fremanezumab at 225 mg (1 injection of fremanezumab 225 mg/1.5 mL and 2 injections of placebo 1.5 mL on Days 0, 84, 168, and 252; and 1 injection of fremanezumab 225 mg/1.5 mL on Days 28, 56, 112, 140, 196, 224, 280, and 308). | 419 |
| TEV-48125 225 mg Monthly: Active Rollover Participants Participants with CM who were randomized to the active treatment group (Fremanezumab 675/225 mg) in the pivotal efficacy study, received fremanezumab 675 mg SC as loading dose (3 injections of fremanezumab 225 mg/1.5 mL on Day 0) followed by 11 monthly SC doses of fremanezumab at 225 mg (1 injection of fremanezumab 225 mg/1.5 mL and 2 injections of placebo 1.5 mL on Days 84, 168, and 252; and 1 injection of fremanezumab 225 mg/1.5 mL on Days 28, 56, 112, 140, 196, 224, 280, and 308). Participants with EM who were randomized to the active treatment group (Fremanezumab 225 mg) in the pivotal efficacy study, received 12 monthly SC doses of fremanezumab at 225 mg (1 injection of fremanezumab 225 mg/1.5 mL and 2 injections of placebo 1.5 mL on Days 0, 84, 168, and 252; and 1 injection of fremanezumab 225 mg/1.5 mL on Days 28, 56, 112, 140, 196, 224, 280, and 308). | 526 |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants Participants with CM or EM who were randomized to the placebo treatment group or participants who did not rollover from the pivotal efficacy study, received fremanezumab 675 mg SC once every 3 months for 12 months for a total of 4 doses (3 injections of fremanezumab 225 mg/1.5 mL on Days 0, 84, 168, and 252; and 1 injection of placebo 1.5 mL on Days 28, 56, 112, 140, 196, 224, 280, and 308). | 420 |
| TEV-48125 675 mg Quarterly: Active Rollover Participants Participants with CM or EM who were randomized to the active treatment group (Fremanezumab 675 mg) in the pivotal efficacy study, received fremanezumab 675 mg SC once every 3 months for 12 months for a total of 4 doses (3 injections of fremanezumab 225 mg/1.5 mL on Days 0, 84, 168, and 252; and 1 injection of placebo 1.5 mL on Days 28, 56, 112, 140, 196, 224, 280, and 308). | 525 |
| Total | 1,890 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 13 | 12 | 19 | 12 |
| Overall Study | Lack of Efficacy | 14 | 10 | 12 | 22 |
| Overall Study | Lost to Follow-up | 26 | 33 | 20 | 37 |
| Overall Study | Non-compliance to Study Procedures | 2 | 1 | 1 | 1 |
| Overall Study | Other than specified | 5 | 4 | 2 | 4 |
| Overall Study | Pregnancy | 2 | 3 | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 2 | 1 | 4 |
| Overall Study | Withdrawal by Subject | 43 | 53 | 30 | 61 |
Baseline characteristics
| Characteristic | Total | TEV-48125 675 mg Quarterly: Active Rollover Participants | TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | TEV-48125 225 mg Monthly: Active Rollover Participants | TEV-48125 225 mg Monthly: New/Placebo Rollover Participants |
|---|---|---|---|---|---|
| Age, Continuous | 43.5 years STANDARD_DEVIATION 11.87 | 43.2 years STANDARD_DEVIATION 11.73 | 44.0 years STANDARD_DEVIATION 11.67 | 42.9 years STANDARD_DEVIATION 11.97 | 44.1 years STANDARD_DEVIATION 12.09 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 146 Participants | 38 Participants | 34 Participants | 45 Participants | 29 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1738 Participants | 484 Participants | 386 Participants | 481 Participants | 387 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 6 Participants | 3 Participants | 0 Participants | 0 Participants | 3 Participants |
| Number of Headache Days of Any Severity | 13.1 days STANDARD_DEVIATION 6.29 | 12.9 days STANDARD_DEVIATION 6.02 | 13.2 days STANDARD_DEVIATION 6.32 | 12.7 days STANDARD_DEVIATION 6.2 | 13.6 days STANDARD_DEVIATION 6.68 |
| Number of Migraine Days | 13.4 days STANDARD_DEVIATION 5.63 | 13.2 days STANDARD_DEVIATION 5.26 | 13.6 days STANDARD_DEVIATION 5.86 | 13.1 days STANDARD_DEVIATION 5.49 | 13.9 days STANDARD_DEVIATION 5.99 |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 6 Participants | 3 Participants | 0 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 191 Participants | 64 Participants | 36 Participants | 62 Participants | 29 Participants |
| Race/Ethnicity, Customized Black | 148 Participants | 40 Participants | 38 Participants | 38 Participants | 32 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 3 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 12 Participants | 4 Participants | 3 Participants | 0 Participants | 5 Participants |
| Race/Ethnicity, Customized White | 1530 Participants | 412 Participants | 343 Participants | 424 Participants | 351 Participants |
| Sex: Female, Male Female | 1645 Participants | 457 Participants | 369 Participants | 454 Participants | 365 Participants |
| Sex: Female, Male Male | 245 Participants | 68 Participants | 51 Participants | 72 Participants | 54 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 | 0 / 418 | 0 / 526 | 1 / 419 | 0 / 525 |
| other Total, other adverse events | 300 / 418 | 367 / 526 | 284 / 419 | 329 / 525 |
| serious Total, serious adverse events | 27 / 418 | 29 / 526 | 36 / 419 | 23 / 525 |
Outcome results
Primary
Number of Participants With Adverse Events (AEs)
An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severe AE was defined as inability to carry out usual activities. Treatment-related AEs were defined as AEs with possible, probable, definite, or missing relationship to study drug. Serious AEs were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Time frame: Baseline (Day 0) up to follow-up visit (Day 533)
Population: Safety population included all participants who received at least 1 dose of fremanezumab.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Adverse Events (AEs) | Serious AEs | 27 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Adverse Events (AEs) | Severe AEs | 47 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Adverse Events (AEs) | AEs leading to discontinuation from study | 18 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Adverse Events (AEs) | Treatment-related AEs | 263 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Adverse Events (AEs) | Any AEs | 365 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Adverse Events (AEs) | Treatment-related AEs | 288 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Adverse Events (AEs) | Serious AEs | 29 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Adverse Events (AEs) | AEs leading to discontinuation from study | 18 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Adverse Events (AEs) | Severe AEs | 51 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Adverse Events (AEs) | Any AEs | 456 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Adverse Events (AEs) | Treatment-related AEs | 242 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Adverse Events (AEs) | Any AEs | 365 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Adverse Events (AEs) | Severe AEs | 45 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Adverse Events (AEs) | Serious AEs | 36 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Adverse Events (AEs) | AEs leading to discontinuation from study | 22 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Adverse Events (AEs) | Serious AEs | 23 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Adverse Events (AEs) | Severe AEs | 50 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Adverse Events (AEs) | Any AEs | 426 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Adverse Events (AEs) | Treatment-related AEs | 270 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Adverse Events (AEs) | AEs leading to discontinuation from study | 18 Participants |
Primary
Number of Participants With Injection Site Reactions
Number of participants who reported treatment-emergent injection site reactions are summarized. Preferred terms from MedDRA version 18.1 were offered without a threshold applied. Injection site reactions included injection site induration, pain, erythema, haemorrhage, pruritus, swelling, bruising, rash, urticaria, warmth, dermatitis, haematoma, inflammation, discolouration, discomfort, hypersensitivity, hypoaesthesia, irritation, oedema, papule, paraesthesia, vesicles and pallor. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Time frame: Baseline (Day -28 to Day -1), Month 12
Population: Safety population included all participants who received at least 1 dose of fremanezumab.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Injection Site Reactions | Injection site vesicles | 0 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Injection Site Reactions | Injection site papule | 1 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Injection Site Reactions | Injection site bruising | 2 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Injection Site Reactions | Injection site discomfort | 0 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Injection Site Reactions | Injection site hypoaesthesia | 1 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Injection Site Reactions | Injection site paraesthesia | 0 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Injection Site Reactions | Injection site rash | 4 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Injection Site Reactions | Injection site hypersensitivity | 1 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Injection Site Reactions | Injection site pallor | 0 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Injection Site Reactions | Injection site oedema | 1 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Injection Site Reactions | Injection site urticaria | 4 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Injection Site Reactions | Injection site pruritus | 31 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Injection Site Reactions | Injection site erythema | 130 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Injection Site Reactions | Injection site discolouration | 0 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Injection Site Reactions | Injection site warmth | 3 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Injection Site Reactions | Injection site pain | 149 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Injection Site Reactions | Injection site inflammation | 0 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Injection Site Reactions | Injection site irritation | 0 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Injection Site Reactions | Injection site dermatitis | 0 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Injection Site Reactions | Injection site swelling | 7 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Injection Site Reactions | Injection site induration | 167 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Injection Site Reactions | Injection site haemorrhage | 34 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Injection Site Reactions | Injection site haematoma | 1 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Injection Site Reactions | Injection site oedema | 1 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Injection Site Reactions | Injection site paraesthesia | 0 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Injection Site Reactions | Injection site hypoaesthesia | 1 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Injection Site Reactions | Injection site inflammation | 1 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Injection Site Reactions | Injection site haemorrhage | 38 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Injection Site Reactions | Injection site discolouration | 1 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Injection Site Reactions | Injection site pallor | 0 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Injection Site Reactions | Injection site hypersensitivity | 0 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Injection Site Reactions | Injection site discomfort | 0 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Injection Site Reactions | Injection site pruritus | 43 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Injection Site Reactions | Injection site papule | 0 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Injection Site Reactions | Injection site swelling | 10 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Injection Site Reactions | Injection site pain | 156 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Injection Site Reactions | Injection site bruising | 2 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Injection Site Reactions | Injection site induration | 174 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Injection Site Reactions | Injection site haematoma | 0 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Injection Site Reactions | Injection site rash | 2 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Injection Site Reactions | Injection site urticaria | 2 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Injection Site Reactions | Injection site irritation | 0 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Injection Site Reactions | Injection site warmth | 2 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Injection Site Reactions | Injection site erythema | 144 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Injection Site Reactions | Injection site dermatitis | 1 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Injection Site Reactions | Injection site vesicles | 1 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Injection Site Reactions | Injection site hypoaesthesia | 0 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Injection Site Reactions | Injection site induration | 144 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Injection Site Reactions | Injection site pain | 135 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Injection Site Reactions | Injection site erythema | 99 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Injection Site Reactions | Injection site haemorrhage | 21 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Injection Site Reactions | Injection site pruritus | 17 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Injection Site Reactions | Injection site swelling | 6 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Injection Site Reactions | Injection site bruising | 4 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Injection Site Reactions | Injection site rash | 5 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Injection Site Reactions | Injection site urticaria | 3 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Injection Site Reactions | Injection site warmth | 1 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Injection Site Reactions | Injection site dermatitis | 0 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Injection Site Reactions | Injection site paraesthesia | 1 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Injection Site Reactions | Injection site haematoma | 0 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Injection Site Reactions | Injection site inflammation | 1 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Injection Site Reactions | Injection site discolouration | 0 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Injection Site Reactions | Injection site discomfort | 0 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Injection Site Reactions | Injection site hypersensitivity | 0 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Injection Site Reactions | Injection site irritation | 0 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Injection Site Reactions | Injection site oedema | 1 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Injection Site Reactions | Injection site papule | 0 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Injection Site Reactions | Injection site vesicles | 1 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Injection Site Reactions | Injection site pallor | 0 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Injection Site Reactions | Injection site dermatitis | 1 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Injection Site Reactions | Injection site hypoaesthesia | 0 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Injection Site Reactions | Injection site warmth | 1 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Injection Site Reactions | Injection site urticaria | 2 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Injection Site Reactions | Injection site vesicles | 0 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Injection Site Reactions | Injection site irritation | 1 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Injection Site Reactions | Injection site rash | 2 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Injection Site Reactions | Injection site bruising | 3 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Injection Site Reactions | Injection site pain | 140 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Injection Site Reactions | Injection site oedema | 0 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Injection Site Reactions | Injection site swelling | 8 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Injection Site Reactions | Injection site pruritus | 24 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Injection Site Reactions | Injection site induration | 134 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Injection Site Reactions | Injection site papule | 0 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Injection Site Reactions | Injection site haemorrhage | 38 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Injection Site Reactions | Injection site paraesthesia | 0 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Injection Site Reactions | Injection site erythema | 124 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Injection Site Reactions | Injection site discomfort | 1 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Injection Site Reactions | Injection site discolouration | 0 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Injection Site Reactions | Injection site pallor | 1 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Injection Site Reactions | Injection site hypersensitivity | 0 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Injection Site Reactions | Injection site inflammation | 0 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Injection Site Reactions | Injection site haematoma | 1 Participants |
Primary
Number of Participants With Potentially Clinically Significant Abnormal Hematology Results
Potentially clinically significant abnormal hematology findings included: hemoglobin: less than (\<) 115 grams/liter (g/L) (in males) or less than or equal to (\<=) 95 g/L (in females), hematocrit: \<0.37 L/L (in male) or \<0.32 L/L (in female), leukocytes: \>=20\*10\^9/L or \<=3\*10\^9/L, eosinophils/leukocytes: \>=10%, and platelets: \>=700\*10\^9/L or \<=75\*10\^9/L. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Time frame: Baseline (Day 0) up to EOT visit (Day 336)
Population: Safety population included all participants who received at least 1 dose of fremanezumab. Here, 'Overall number of participants analyzed'=participants with both baseline and post-baseline hematology parameter values.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Potentially Clinically Significant Abnormal Hematology Results | 34 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Potentially Clinically Significant Abnormal Hematology Results | 39 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Potentially Clinically Significant Abnormal Hematology Results | 27 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Potentially Clinically Significant Abnormal Hematology Results | 40 Participants |
Primary
Number of Participants With Potentially Clinically Significant Abnormal Serum Chemistry Results
Potentially clinically significant abnormal serum chemistry findings included: Blood Urea Nitrogen (BUN): greater than or equal to (\>=) 10.71 millimoles/liter (mmol/L), creatinine: \>=177 micromoles/liter (µmol/L), bilirubin: \>=34.2 µmol/L, Alanine Aminotransferase (ALT) (units/liter \[U/L\]): \>=3\*upper limit of normal (ULN) Aspartate Aminotransferase (AST) (U/L): \>=3\*ULN, and Gamma Glutamyl Transferase (GGT) (U/L): \>=3\*ULN. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Time frame: Baseline (Day 0) up to end of treatment (EOT) visit (Day 336)
Population: Safety population included all participants who received at least 1 dose of fremanezumab. Here, 'Overall number of participants analyzed'=participants with both baseline and post-baseline serum chemistry values.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Potentially Clinically Significant Abnormal Serum Chemistry Results | 27 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Potentially Clinically Significant Abnormal Serum Chemistry Results | 26 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Potentially Clinically Significant Abnormal Serum Chemistry Results | 11 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Potentially Clinically Significant Abnormal Serum Chemistry Results | 23 Participants |
Primary
Number of Participants With Potentially Clinically Significant Abnormal Urinalysis Laboratory Tests Results
Potentially clinically significant abnormal urinalysis findings included: blood: \>=2 unit increase from baseline, urine glucose (milligrams/decilitre \[mg/dL\]): \>=2 unit increase from baseline, ketones (mg/dL): \>=2 unit increase from baseline, urine protein (mg/dL): \>=2 unit increase from baseline. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Time frame: Baseline (Day 0) up to EOT visit (Day 336)
Population: Safety population included all participants who received at least 1 dose of fremanezumab. Here, 'Overall number of participants analyzed'=participants with both baseline and post-baseline urinalysis values.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Potentially Clinically Significant Abnormal Urinalysis Laboratory Tests Results | 128 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Potentially Clinically Significant Abnormal Urinalysis Laboratory Tests Results | 170 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Potentially Clinically Significant Abnormal Urinalysis Laboratory Tests Results | 120 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Potentially Clinically Significant Abnormal Urinalysis Laboratory Tests Results | 146 Participants |
Primary
Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Values
Potentially clinically significant abnormal vital signs findings included: pulse rate: \<=50 beats/minute (bpm) and decrease of \>=15 bpm, or \>=120 bpm and increase of \>=15 bpm; systolic blood pressure: \<=90 millimeters of mercury (mmHg) and decrease of \>=20 mmHg, or \>=180 mmHg and increase of \>=20 mmHg; diastolic blood pressure: \<=50 mmHg and decrease of \>=15 mmHg or \>=105 mmHg and increase of \>=15 mmHg; respiratory rate: \<10 breaths/minute; and body temperature \>=38.3 degrees centigrade and change of \>=1.1 degrees centigrade. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Time frame: Baseline (Day 0) up to EOT visit (Day 336)
Population: Safety population included all participants who received at least 1 dose of fremanezumab. Here, 'Overall number of participants analyzed'=participants with both baseline and post-baseline vital signs values.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Values | 20 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Values | 33 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Values | 24 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Values | 40 Participants |
Primary
Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results
Coagulation parameters included: prothrombin time (PT) (seconds), prothrombin international normalized ratio (INR), activated partial thromboplastin time (aPTT) (seconds). Shifts represented as Baseline - endpoint value (last observed post-baseline value). Shifts from baseline to endpoint were summarized using participant counts grouped into three categories: - Low (below normal range) - Normal (within the normal range of 9.4 to 12.5 seconds) - High (above normal range). A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Time frame: Baseline (Day 0), endpoint (Day 336)
Population: Safety population included all participants who received at least 1 dose of fremanezumab. Here, 'Overall number of participants analyzed' = participants with both baseline and endpoint coagulation laboratory test results. 'Number analyzed' = participants evaluable for specified categories.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | Normal-Normal | 366 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | High-Normal | 18 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | aPTT | Normal-Normal | 341 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | Normal-Low | 12 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | Low-High | 0 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | High-High | 7 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | Low-High | 0 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | Low-Normal | 11 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | Low-Low | 0 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | aPTT | High-Normal | 26 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | aPTT | Normal-Low | 3 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | aPTT | Low-High | 0 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | Normal-Low | 1 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | Low-Low | 0 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | aPTT | Low-Normal | 4 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | aPTT | Low-Low | 2 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | Normal-Normal | 370 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | Low-Normal | 1 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | High-High | 4 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | aPTT | High-Low | 0 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | Normal-High | 10 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | aPTT | High-High | 16 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | High-Normal | 7 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | High-Low | 0 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | High-Low | 0 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | aPTT | Normal-High | 14 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | Normal-High | 6 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | Normal-Low | 3 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | Low-Low | 0 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | Low-Normal | 2 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | Low-High | 0 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | Normal-Normal | 465 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | Normal-High | 10 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | High-Low | 0 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | High-Normal | 25 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | High-High | 11 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | Low-Low | 1 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | Low-Normal | 11 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | Low-High | 0 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | Normal-Low | 15 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | Normal-Normal | 468 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | Normal-High | 5 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | High-Low | 0 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | High-Normal | 11 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | High-High | 5 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | aPTT | Low-Low | 2 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | aPTT | Low-Normal | 1 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | aPTT | Low-High | 1 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | aPTT | Normal-Low | 11 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | aPTT | Normal-Normal | 423 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | aPTT | Normal-High | 18 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | aPTT | High-Low | 0 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | aPTT | High-Normal | 43 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | aPTT | High-High | 17 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | aPTT | Normal-Normal | 334 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | High-Low | 0 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | aPTT | Normal-High | 19 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | Normal-High | 4 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | High-Low | 0 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | Normal-High | 14 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | High-Normal | 6 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | Normal-Normal | 374 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | aPTT | High-Low | 0 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | High-High | 4 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | aPTT | Low-Low | 1 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | Normal-Low | 3 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | aPTT | Low-Normal | 7 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | aPTT | High-High | 16 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | aPTT | Low-High | 0 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | Low-High | 0 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | aPTT | High-Normal | 26 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | aPTT | Normal-Low | 7 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | Low-Low | 4 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | High-High | 8 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | Normal-Normal | 372 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | Low-Normal | 11 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | Low-High | 0 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | High-Normal | 9 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | Low-Normal | 2 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | Normal-Low | 9 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | Low-Low | 0 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | Low-High | 0 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | Normal-Normal | 472 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | Normal-Low | 7 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | Low-High | 0 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | aPTT | Low-High | 0 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | Normal-High | 4 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | Normal-High | 14 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | aPTT | Normal-High | 22 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | High-Low | 0 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | High-Low | 1 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | Low-Normal | 9 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | Normal-Normal | 451 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | aPTT | High-High | 22 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | High-Normal | 35 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | High-Normal | 13 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | aPTT | Normal-Low | 10 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | Low-Normal | 1 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | High-High | 10 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | High-High | 6 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | Normal-Low | 2 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | aPTT | High-Low | 1 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | aPTT | High-Normal | 37 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | aPTT | Low-Low | 0 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | aPTT | Normal-Normal | 414 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | PT | Low-Low | 0 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | Prothrombin INR | Low-Low | 1 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results | aPTT | Low-Normal | 7 Participants |
Primary
Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters
ECG parameters included: heart rate, PR interval, QRS interval, QT interval corrected using the Fridericia formula (QTcF), QT interval corrected using the Bazett's formula (QTcB) and RR interval. Shifts represented as Baseline - endpoint value (last observed post-baseline value). Abnormal NCS indicated an abnormal but not clinically significant finding. Abnormal CS indicated an abnormal and clinically significant finding. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Time frame: Baseline (Day 0), endpoint (Day 336)
Population: Safety population included all participants who received at least 1 dose of fremanezumab. Here, 'Overall number of participants analyzed' = participants with both baseline and endpoint electrocardiogram findings.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Abnormal CS - Normal | 0 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Abnormal NCS - Abnormal CS | 0 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Abnormal CS - Abnormal CS | 0 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Abnormal NCS - Normal | 42 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Normal - Abnormal CS | 0 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Normal - Abnormal NCS | 45 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Abnormal CS - Abnormal NCS | 0 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Abnormal NCS - Abnormal NCS | 60 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Normal - Normal | 239 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Abnormal NCS - Abnormal NCS | 79 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Abnormal CS - Normal | 0 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Abnormal NCS - Abnormal CS | 1 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Normal - Abnormal NCS | 64 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Normal - Normal | 295 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Normal - Abnormal CS | 0 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Abnormal CS - Abnormal CS | 0 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Abnormal CS - Abnormal NCS | 0 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Abnormal NCS - Normal | 53 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Abnormal NCS - Abnormal NCS | 69 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Normal - Normal | 230 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Normal - Abnormal NCS | 49 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Normal - Abnormal CS | 0 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Abnormal NCS - Normal | 43 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Abnormal NCS - Abnormal CS | 0 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Abnormal CS - Normal | 0 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Abnormal CS - Abnormal NCS | 0 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Abnormal CS - Abnormal CS | 0 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Abnormal CS - Normal | 0 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Abnormal NCS - Normal | 60 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Normal - Abnormal CS | 1 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Abnormal CS - Abnormal CS | 0 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Abnormal CS - Abnormal NCS | 0 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Normal - Abnormal NCS | 67 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Abnormal NCS - Abnormal CS | 0 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Abnormal NCS - Abnormal NCS | 65 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters | Normal - Normal | 296 Participants |
Primary
Number of Participants With Suicidal Ideation and Suicidal Behavior as Assessed by the Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS)
eC-SSRS is a questionnaire to assess suicidal ideation and suicidal behavior. Suicidal behavior was defined as a yes answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation was defined as a yes answer to any one of 5 suicidal ideation questions: wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent, any self-injurious behavior with no suicidal intent.
Time frame: Baseline (Day -28 to Day -1), Month 12
Population: Safety population included all participants who received at least 1 dose of fremanezumab.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Suicidal Ideation and Suicidal Behavior as Assessed by the Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) | Suicidal ideation | 2 Participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Number of Participants With Suicidal Ideation and Suicidal Behavior as Assessed by the Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) | Suicidal attempt | 0 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Suicidal Ideation and Suicidal Behavior as Assessed by the Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) | Suicidal attempt | 0 Participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Number of Participants With Suicidal Ideation and Suicidal Behavior as Assessed by the Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) | Suicidal ideation | 0 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Suicidal Ideation and Suicidal Behavior as Assessed by the Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) | Suicidal ideation | 2 Participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Number of Participants With Suicidal Ideation and Suicidal Behavior as Assessed by the Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) | Suicidal attempt | 1 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Suicidal Ideation and Suicidal Behavior as Assessed by the Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) | Suicidal ideation | 1 Participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Number of Participants With Suicidal Ideation and Suicidal Behavior as Assessed by the Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) | Suicidal attempt | 0 Participants |
Other Pre-specified
Change From Baseline in Monthly Average Number of Headache Days of Any Severity During the 4-Week Period at Month 12
Headaches were subjectively rated by participants as mild, moderate or severe. A headache day of any severity for both CM and EM participants was defined as a calendar day (00:00 to 23:59) where the participant (using the electronic headache diary device) reports: a day with headache pain that lasts at least 4 hours with a peak severity of any severity or; a day when the participant used acute migraine-specific medication (triptans or ergots) to treat a headache of any severity or duration. Monthly averages were derived and normalized to 28 days equivalent by the following formula: (number of days of efficacy variable over relevant period/number of days with assessments recorded in the e-diary over the relevant period) \* 28. The change was calculated as post-baseline value - baseline value.
Time frame: Baseline (Day -28 to Day -1), Month 12
Population: FAS: all participants who received at least 1 dose of fremanezumab, and had at least 10 days of efficacy assessments by electronic diary after first injection for this study. Data for this outcome was collected and reported separately for CM and EM participants. 'Overall number of participants analyzed' = participants evaluable for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Change From Baseline in Monthly Average Number of Headache Days of Any Severity During the 4-Week Period at Month 12 | -7.7 days/month | Standard Deviation 6.79 |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Change From Baseline in Monthly Average Number of Headache Days of Any Severity During the 4-Week Period at Month 12 | -7.9 days/month | Standard Deviation 6.01 |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Change From Baseline in Monthly Average Number of Headache Days of Any Severity During the 4-Week Period at Month 12 | -7.2 days/month | Standard Deviation 6.48 |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Change From Baseline in Monthly Average Number of Headache Days of Any Severity During the 4-Week Period at Month 12 | -7.1 days/month | Standard Deviation 6.88 |
| TEV-48125 225 mg Monthly: New/Placebo Rollover EM Participants | Change From Baseline in Monthly Average Number of Headache Days of Any Severity During the 4-Week Period at Month 12 | -4.4 days/month | Standard Deviation 4.25 |
| TEV-48125 225 mg Monthly: Active Rollover EM Participants | Change From Baseline in Monthly Average Number of Headache Days of Any Severity During the 4-Week Period at Month 12 | -5.0 days/month | Standard Deviation 3.9 |
| TEV-48125 675mg Quarterly:New/Placebo Rollover EM Participants | Change From Baseline in Monthly Average Number of Headache Days of Any Severity During the 4-Week Period at Month 12 | -5.0 days/month | Standard Deviation 3.63 |
| TEV-48125 675 mg Quarterly: Active Rollover EM Participants | Change From Baseline in Monthly Average Number of Headache Days of Any Severity During the 4-Week Period at Month 12 | -4.8 days/month | Standard Deviation 3.74 |
Other Pre-specified
Change From Baseline in Monthly Average Number of Migraine Days During the 4-Week Period at Month 12
A migraine day was defined as when at least 1 of the following situations occurred: A calendar day(0:00 to 23:59) demonstrating at least 4 consecutive hours (for CM participants) or at least 2 consecutive hours (for EM participants) of a headache meeting criteria for migraine with or without aura; a calendar day(0:00 to 23:59) demonstrating at least 4 consecutive hours (for CM participants) or at least 2 consecutive hours (for EM participants) of a headache meeting criteria for probable migraine, a migraine subtype where only 1 migraine criterion was missing; a calendar day(0:00 to 23:59) demonstrating a headache of any duration that was treated with migraine-specific medications (triptans and ergot compounds). Monthly averages were derived and normalized to 28 days equivalent by formula: (number of days of efficacy variable over relevant period/number of days with assessments recorded in e-diary over relevant period)\*28. Change was calculated as post-baseline value - baseline value.
Time frame: Baseline (Day -28 to Day -1), Month 12
Population: Full analysis set (FAS):all participants who received at least 1 dose of fremanezumab, had at least 10 days of efficacy assessments by e-diary after first injection for this study. Data for this outcome was collected and reported separately for CM and EM participants.'Overall number of participants analyzed'=participants evaluable for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Change From Baseline in Monthly Average Number of Migraine Days During the 4-Week Period at Month 12 | -7.8 days/month | Standard Deviation 6.98 |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Change From Baseline in Monthly Average Number of Migraine Days During the 4-Week Period at Month 12 | -8.2 days/month | Standard Deviation 6.14 |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Change From Baseline in Monthly Average Number of Migraine Days During the 4-Week Period at Month 12 | -7.6 days/month | Standard Deviation 6.87 |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Change From Baseline in Monthly Average Number of Migraine Days During the 4-Week Period at Month 12 | -7.0 days/month | Standard Deviation 6.54 |
| TEV-48125 225 mg Monthly: New/Placebo Rollover EM Participants | Change From Baseline in Monthly Average Number of Migraine Days During the 4-Week Period at Month 12 | -4.5 days/month | Standard Deviation 4.2 |
| TEV-48125 225 mg Monthly: Active Rollover EM Participants | Change From Baseline in Monthly Average Number of Migraine Days During the 4-Week Period at Month 12 | -5.5 days/month | Standard Deviation 4.01 |
| TEV-48125 675mg Quarterly:New/Placebo Rollover EM Participants | Change From Baseline in Monthly Average Number of Migraine Days During the 4-Week Period at Month 12 | -5.5 days/month | Standard Deviation 3.65 |
| TEV-48125 675 mg Quarterly: Active Rollover EM Participants | Change From Baseline in Monthly Average Number of Migraine Days During the 4-Week Period at Month 12 | -5.0 days/month | Standard Deviation 3.78 |
Other Pre-specified
Percentage of Participants With At Least 50% Reduction From Baseline in Monthly Average Number of Headache Days of at Least Moderate Severity During the 4-Week Period
Headaches were subjectively rated by participants as mild, moderate or severe. A headache day of at least moderate severity for both CM and EM participants was defined as a calendar day (00:00 to 23:59) where the participant (using the electronic headache diary device) reports: a day with headache pain that lasts at least 4 hours with a peak severity of at least moderate severity or; a day when the participant used acute migraine-specific medication (triptans or ergots) to treat a headache of any severity or duration. Monthly averages were derived and normalized to 28 days equivalent by the following formula: (number of days of efficacy variable over relevant period/number of days with assessments recorded in the e-diary over the relevant period) \* 28.
Time frame: Baseline (Day -28 to Day -1), Month 12
Population: FAS: all participants who received at least 1 dose of fremanezumab, and had at least 10 days of efficacy assessments by electronic diary after first injection for this study. Data for this outcome was collected and reported separately for CM and EM participants. 'Overall number of participants analyzed' = participants evaluable for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Percentage of Participants With At Least 50% Reduction From Baseline in Monthly Average Number of Headache Days of at Least Moderate Severity During the 4-Week Period | 56 percentage of participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Percentage of Participants With At Least 50% Reduction From Baseline in Monthly Average Number of Headache Days of at Least Moderate Severity During the 4-Week Period | 62 percentage of participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Percentage of Participants With At Least 50% Reduction From Baseline in Monthly Average Number of Headache Days of at Least Moderate Severity During the 4-Week Period | 54 percentage of participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Percentage of Participants With At Least 50% Reduction From Baseline in Monthly Average Number of Headache Days of at Least Moderate Severity During the 4-Week Period | 54 percentage of participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover EM Participants | Percentage of Participants With At Least 50% Reduction From Baseline in Monthly Average Number of Headache Days of at Least Moderate Severity During the 4-Week Period | 58 percentage of participants |
| TEV-48125 225 mg Monthly: Active Rollover EM Participants | Percentage of Participants With At Least 50% Reduction From Baseline in Monthly Average Number of Headache Days of at Least Moderate Severity During the 4-Week Period | 72 percentage of participants |
| TEV-48125 675mg Quarterly:New/Placebo Rollover EM Participants | Percentage of Participants With At Least 50% Reduction From Baseline in Monthly Average Number of Headache Days of at Least Moderate Severity During the 4-Week Period | 67 percentage of participants |
| TEV-48125 675 mg Quarterly: Active Rollover EM Participants | Percentage of Participants With At Least 50% Reduction From Baseline in Monthly Average Number of Headache Days of at Least Moderate Severity During the 4-Week Period | 68 percentage of participants |
Other Pre-specified
Percentage of Participants With At Least 50% Reduction From Baseline in Monthly Average Number of Migraine Days During the 4-Week Period at Month 12
A migraine day was defined as when at least 1 of the following situations occurred: A calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours (for CM participants) or at least 2 consecutive hours (for EM participants) of a headache meeting criteria for migraine with or without aura; a calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours (for CM participants) or at least 2 consecutive hours (for EM participants) of a headache meeting criteria for probable migraine, a migraine subtype where only 1 migraine criterion was missing; a calendar day (0:00 to 23:59) demonstrating a headache of any duration that was treated with migraine-specific medications (triptans and ergot compounds). Monthly averages were derived and normalized to 28 days equivalent by formula: (number of days of efficacy variable over relevant period/number of days with assessments recorded in e-diary over relevant period) \* 28.
Time frame: Baseline (Day -28 to Day -1), Month 12
Population: FAS: all participants who received at least 1 dose of fremanezumab, and had at least 10 days of efficacy assessments by electronic diary after first injection for this study. Data for this outcome was collected and reported separately for CM and EM participants. 'Overall number of participants analyzed' = participants evaluable for this outcome.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TEV-48125 225 mg Monthly: New/Placebo Rollover Participants | Percentage of Participants With At Least 50% Reduction From Baseline in Monthly Average Number of Migraine Days During the 4-Week Period at Month 12 | 54 percentage of participants |
| TEV-48125 225 mg Monthly: Active Rollover Participants | Percentage of Participants With At Least 50% Reduction From Baseline in Monthly Average Number of Migraine Days During the 4-Week Period at Month 12 | 59 percentage of participants |
| TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants | Percentage of Participants With At Least 50% Reduction From Baseline in Monthly Average Number of Migraine Days During the 4-Week Period at Month 12 | 52 percentage of participants |
| TEV-48125 675 mg Quarterly: Active Rollover Participants | Percentage of Participants With At Least 50% Reduction From Baseline in Monthly Average Number of Migraine Days During the 4-Week Period at Month 12 | 54 percentage of participants |
| TEV-48125 225 mg Monthly: New/Placebo Rollover EM Participants | Percentage of Participants With At Least 50% Reduction From Baseline in Monthly Average Number of Migraine Days During the 4-Week Period at Month 12 | 58 percentage of participants |
| TEV-48125 225 mg Monthly: Active Rollover EM Participants | Percentage of Participants With At Least 50% Reduction From Baseline in Monthly Average Number of Migraine Days During the 4-Week Period at Month 12 | 75 percentage of participants |
| TEV-48125 675mg Quarterly:New/Placebo Rollover EM Participants | Percentage of Participants With At Least 50% Reduction From Baseline in Monthly Average Number of Migraine Days During the 4-Week Period at Month 12 | 68 percentage of participants |
| TEV-48125 675 mg Quarterly: Active Rollover EM Participants | Percentage of Participants With At Least 50% Reduction From Baseline in Monthly Average Number of Migraine Days During the 4-Week Period at Month 12 | 64 percentage of participants |