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HALO: Efficacy and Safety of Subcutaneous Administration of Fremanezumab (TEV-48125) for the Preventive Treatment of Migraine

Sponsor
Teva Branded Pharmaceutical Products R&D, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT02638103
Collaborator
(none)
1,890
Enrollment
139
Locations
4
Arms
33.4
Actual Duration (Months)
13.6
Patients Per Site
0.4
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
1890 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Multicenter, Randomized, Double-Blind, Parallel-Group Study Evaluating the Long-Term Safety, Tolerability, and Efficacy of Subcutaneous Administration of Fremanezumab (TEV-48125) for the Preventive Treatment of Migraine
Actual Study Start Date :
Feb 26, 2016
Actual Primary Completion Date :
Jun 6, 2018
Actual Study Completion Date :
Dec 8, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: TEV-48125 225 mg Monthly: New/Placebo Rollover Participants

Participants with CM who were randomized to the placebo treatment group or participants who do not rollover from the pivotal efficacy study, will receive fremanezumab 675 milligrams (mg) SC as loading dose (3 injections of fremanezumab 225 mg/1.5 milliliters [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/1.5mL 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 do not rollover from the pivotal efficacy study, will receive 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).

Drug: Fremanezumab
Fremanezumab will be administered as per the dose and schedule specified in the respective arms.
Other Names:
  • TEV-48125

    • Drug: Placebo
    Placebo matching to fremanezumab will be administered as per schedule specified in the respective arms.
    Experimental: 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, will receive 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/1.5mL and 2 injections of placebo 1.5 mL on Days 84, 168, and 252; and 1 injection of fremanezumab 225 mg/1.5mL 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, will receive 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).

    Drug: Fremanezumab
    Fremanezumab will be administered as per the dose and schedule specified in the respective arms.
    Other Names:
  • TEV-48125

    • Drug: Placebo
    Placebo matching to fremanezumab will be administered as per schedule specified in the respective arms.
    Experimental: 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 do not rollover from the pivotal efficacy study, will receive 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).

    Drug: Fremanezumab
    Fremanezumab will be administered as per the dose and schedule specified in the respective arms.
    Other Names:
  • TEV-48125

    • Drug: Placebo
    Placebo matching to fremanezumab will be administered as per schedule specified in the respective arms.
    Experimental: 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, will receive 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).

    Drug: Fremanezumab
    Fremanezumab will be administered as per the dose and schedule specified in the respective arms.
    Other Names:
  • TEV-48125

    • Drug: Placebo
    Placebo matching to fremanezumab will be administered as per schedule specified in the respective arms.

    Outcome Measures

    Primary Outcome Measures

    1. 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.

    2. 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.

    3. 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.

    4. 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.

    5. 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.

    6. 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.

    7. 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.

    8. 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.

    9. 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.

    Other Outcome Measures

    1. 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.

    2. 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.

    3. 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.

    4. 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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 70 Years
    Sexes Eligible for Study:
    All
    Accepts 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Teva Investigational Site 13628 Birmingham Alabama United States 35211
    2 Teva Investigational Site 13577 Birmingham Alabama United States 35216
    3 Teva Investigational Site 13606 Phoenix Arizona United States 85018
    4 Teva Investigational Site 13579 Phoenix Arizona United States 85023
    5 Teva Investigational Site 13602 Little Rock Arkansas United States 72205
    6 Teva Investigational Site 13568 Encino California United States 91316
    7 Teva Investigational Site 13546 Fullerton California United States 92835
    8 Teva Investigational Site 13540 Long Beach California United States 90806
    9 Teva Investigational Site 13632 Redlands California United States 92374
    10 Teva Investigational Site 13571 Redondo Beach California United States 90277
    11 Teva Investigational Site 13573 San Diego California United States 92103
    12 Teva Investigational Site 13538 Santa Monica California United States 90404
    13 Teva Investigational Site 13594 Santa Rosa California United States 95405
    14 Teva Investigational Site 13595 Walnut Creek California United States 94598
    15 Teva Investigational Site 13629 Aurora Colorado United States 80014
    16 Teva Investigational Site 13557 Boulder Colorado United States 80301
    17 Teva Investigational Site 13593 Colorado Springs Colorado United States 80918
    18 Teva Investigational Site 13633 Denver Colorado United States 80210
    19 Teva Investigational Site 13612 Denver Colorado United States 80239
    20 Teva Investigational Site 13631 Englewood Colorado United States 80113
    21 Teva Investigational Site 13563 East Hartford Connecticut United States 06118
    22 Teva Investigational Site 13550 Stamford Connecticut United States 06905
    23 Teva Investigational Site 13635 Bradenton Florida United States 34201
    24 Teva Investigational Site 13597 Gainesville Florida United States 32607
    25 Teva Investigational Site 13607 Hialeah Florida United States 33012
    26 Teva Investigational Site 13559 Jacksonville Florida United States 32205
    27 Teva Investigational Site 13584 Ocala Florida United States 34471
    28 Teva Investigational Site 13587 Orlando Florida United States 32806
    29 Teva Investigational Site 13567 Palm Beach Gardens Florida United States 33410
    30 Teva Investigational Site 13553 Pembroke Pines Florida United States 33026
    31 Teva Investigational Site 13616 Pinellas Park Florida United States 33781
    32 Teva Investigational Site 13620 Atlanta Georgia United States 30312
    33 Teva Investigational Site 13537 Atlanta Georgia United States 30342
    34 Teva Investigational Site 13604 Boise Idaho United States 83642
    35 Teva Investigational Site 13585 Chicago Illinois United States 60607
    36 Teva Investigational Site 13621 Chicago Illinois United States 60654
    37 Teva Investigational Site 13627 Evanston Illinois United States 60201
    38 Teva Investigational Site 13596 Indianapolis Indiana United States 46254
    39 Teva Investigational Site 13617 Wichita Kansas United States 67207
    40 Teva Investigational Site 13598 Wichita Kansas United States 67211
    41 Teva Investigational Site 13566 Louisville Kentucky United States 40207
    42 Teva Investigational Site 13603 Metairie Louisiana United States 70006
    43 Teva Investigational Site 13582 Pikesville Maryland United States 21208
    44 Teva Investigational Site 13590 Boston Massachusetts United States 02131
    45 Teva Investigational Site 13589 New Bedford Massachusetts United States 02301
    46 Teva Investigational Site 13543 Watertown Massachusetts United States 02472
    47 Teva Investigational Site 13539 Ann Arbor Michigan United States 48104
    48 Teva Investigational Site 13542 Golden Valley Minnesota United States 55422
    49 Teva Investigational Site 13534 Kansas City Missouri United States 64114
    50 Teva Investigational Site 13619 Saint Louis Missouri United States 63141
    51 Teva Investigational Site 13536 Springfield Missouri United States 65807
    52 Teva Investigational Site 13618 Fremont Nebraska United States 68025
    53 Teva Investigational Site 13605 Las Vegas Nevada United States 89106
    54 Teva Investigational Site 13578 Lebanon New Hampshire United States 03756
    55 Teva Investigational Site 13575 Martinsville New Jersey United States 08836
    56 Teva Investigational Site 13622 Princeton New Jersey United States 08540
    57 Teva Investigational Site 13588 Albuquerque New Mexico United States 87102
    58 Teva Investigational Site 13576 Amherst New York United States 14226
    59 Teva Investigational Site 13565 Plainview New York United States 11803
    60 Teva Investigational Site 13544 Greensboro North Carolina United States 27405
    61 Teva Investigational Site 13574 Greensboro North Carolina United States 27408
    62 Teva Investigational Site 13545 Raleigh North Carolina United States 27612
    63 Teva Investigational Site 13609 Akron Ohio United States 44311
    64 Teva Investigational Site 13625 Akron Ohio United States 44311
    65 Teva Investigational Site 13634 Akron Ohio United States 44311
    66 Teva Investigational Site 13533 Cincinnati Ohio United States 45227
    67 Teva Investigational Site 13624 Cincinnati Ohio United States 45249
    68 Teva Investigational Site 13569 Cleveland Ohio United States 44195
    69 Teva Investigational Site 13626 Columbus Ohio United States 43212
    70 Teva Investigational Site 13561 Oklahoma City Oklahoma United States 73112
    71 Teva Investigational Site 13601 Eugene Oregon United States 97401
    72 Teva Investigational Site 13591 Jenkintown Pennsylvania United States 19046
    73 Teva Investigational Site 13554 Philadelphia Pennsylvania United States 19107
    74 Teva Investigational Site 13608 Uniontown Pennsylvania United States 15401
    75 Teva Investigational Site 13615 Greer South Carolina United States 29650
    76 Teva Investigational Site 13556 Mount Pleasant South Carolina United States 29464
    77 Teva Investigational Site 13560 Bristol Tennessee United States 37620
    78 Teva Investigational Site 13551 Memphis Tennessee United States 38119
    79 Teva Investigational Site 13532 Nashville Tennessee United States 37203
    80 Teva Investigational Site 13552 Nashville Tennessee United States 37203
    81 Teva Investigational Site 13541 Austin Texas United States 78731
    82 Teva Investigational Site 13623 Dallas Texas United States 75214
    83 Teva Investigational Site 13611 Plano Texas United States 75024
    84 Teva Investigational Site 13572 San Antonio Texas United States 78229
    85 Teva Investigational Site 13614 Murray Utah United States 84107
    86 Teva Investigational Site 13581 West Jordan Utah United States 84088
    87 Teva Investigational Site 13630 Virginia Beach Virginia United States 23454
    88 Teva Investigational Site 13564 Seattle Washington United States 98105
    89 Teva Investigational Site 13586 Seattle Washington United States 98105
    90 Teva Investigational Site 13600 Morgantown West Virginia United States 26506
    91 Teva Investigational Site 11124 Hamilton Ontario Canada L8N 1Y2
    92 Teva Investigational Site 11122 Newmarket Ontario Canada L3Y5G8
    93 Teva Investigational Site 11120 Calgary Canada T3M 1M4
    94 Teva Investigational Site 11121 Montreal Canada H2W 1V1
    95 Teva Investigational Site 11123 Sarnia Canada N7T 4X3
    96 Teva Investigational Site 54144 Brno Czechia 602 00
    97 Teva Investigational Site 54141 Kunratice Czechia 14800
    98 Teva Investigational Site 54145 Pardubice Czechia 53002
    99 Teva Investigational Site 54142 Prague 4 Czechia 140 59
    100 Teva Investigational Site 54146 Praha 3 Czechia 130 00
    101 Teva Investigational Site 54143 Praha Czechia 100 00
    102 Teva Investigational Site 40018 Helsinki Finland 00180
    103 Teva Investigational Site 40017 Helsinki Finland 00930
    104 Teva Investigational Site 40016 Turku Finland 20100
    105 Teva Investigational Site 80096 Holon Israel 58100
    106 Teva Investigational Site 80099 Jerusalem Israel 9112001
    107 Teva Investigational Site 80098 Nahariya Israel 221001
    108 Teva Investigational Site 80097 Netanya Israel 4244916
    109 Teva Investigational Site 80100 Ramat Gan Israel 5265601
    110 Teva Investigational Site 80095 Tel Aviv Israel 6423906
    111 Teva Investigational Site 84072 Chofu-shi Japan 182-0006
    112 Teva Investigational Site 84066 Kagoshima-shi Japan 892-0844
    113 Teva Investigational Site 84069 Kai Japan 400-0124
    114 Teva Investigational Site 84073 Kawasaki Japan 211-8588
    115 Teva Investigational Site 84067 Kyoto Japan 600-8811
    116 Teva Investigational Site 84062 Osaka-shi Japan 556-0015
    117 Teva Investigational Site 84070 Saitama Japan 338-8577
    118 Teva Investigational Site 84061 Sendai-shi Japan 982-0014
    119 Teva Investigational Site 84063 Shinjuku-ku Japan 160-8582
    120 Teva Investigational Site 84068 Shizuoka Japan 4200-853
    121 Teva Investigational Site 84065 Tochigi Japan 321-0293
    122 Teva Investigational Site 84064 Tokyo Japan 182-0006
    123 Teva Investigational Site 84071 Toyonaka Japan
    124 Teva Investigational Site 53364 Krakow Poland 31-523
    125 Teva Investigational Site 53363 Krakow Poland 33-332
    126 Teva Investigational Site 53366 Lublin Poland 20-022
    127 Teva Investigational Site 53365 Poznan Poland 60-529
    128 Teva Investigational Site 53367 Warsaw Poland 04-730
    129 Teva Investigational Site 50399 Kazan Russian Federation 420012
    130 Teva Investigational Site 50395 Kazan Russian Federation 420021
    131 Teva Investigational Site 50394 Moscow Russian Federation 121467
    132 Teva Investigational Site 50400 Moscow Russian Federation 129128
    133 Teva Investigational Site 50398 Nizhniy Novgorod Russian Federation 603126
    134 Teva Investigational Site 50396 Nizhniy Novgorod Russian Federation 603137
    135 Teva Investigational Site 50397 Ufa Russian Federation 450007
    136 Teva Investigational Site 31207 Madrid Spain 28046
    137 Teva Investigational Site 31208 Pamplona Spain 31008
    138 Teva Investigational Site 31205 Valladolid Spain 47003
    139 Teva Investigational Site 31206 Zaragoza Spain 50009

    Sponsors and Collaborators

    • Teva Branded Pharmaceutical Products R&D, Inc.

    Investigators

    • Study Director: Teva Medical Expert, MD, Teva Branded Pharmaceutical Products R&D, Inc.

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Teva Branded Pharmaceutical Products R&D, Inc.
    ClinicalTrials.gov Identifier:
    NCT02638103
    Other Study ID Numbers:
    • TV48125-CNS-30051
    • 2015-004550-18
    First Posted:
    Dec 22, 2015
    Last Update Posted:
    Nov 9, 2021
    Last Verified:
    Nov 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Migraine Disorders

    Study Results

    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 Detail 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).
    Arm/Group Title TEV-48125 225 mg Monthly: New/Placebo Rollover Participants TEV-48125 225 mg Monthly: Active Rollover Participants TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants TEV-48125 675 mg Quarterly: Active Rollover Participants
    Arm/Group Description Participants with CM who were randomized to the placebo treatment group or participants who did not rollover from the pivotal efficacy study, received fremanezumab (TEV-48125) 675 milligrams (mg) subcutaneously (SC) as loading dose (3 injections of fremanezumab 225 mg/1.5 milliliters [mL] on Day 0) followed by 11 monthly SC doses of fremanezumab at 225 mg (1 injection of fremanezumab 225 mg/1.5mL and 2 injections of placebo 1.5 mL on Days 84, 168, and 252; and 1 injection of fremanezumab 225 mg/1.5mL 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). 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/1.5mL 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). 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). 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).
    Period Title: Overall Study
    STARTED 419 526 420 525
    Safety Analysis Set 418 526 419 525
    Full Analysis Set (FAS) 416 520 419 523
    COMPLETED 313 408 335 383
    NOT COMPLETED 106 118 85 142

    Baseline Characteristics

    Arm/Group Title TEV-48125 225 mg Monthly: New/Placebo Rollover Participants TEV-48125 225 mg Monthly: Active Rollover Participants TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants TEV-48125 675 mg Quarterly: Active Rollover Participants Total
    Arm/Group Description 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). 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). 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). 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). Total of all reporting groups
    Overall Participants 419 526 420 525 1890
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    44.1
    (12.09)
    42.9
    (11.97)
    44.0
    (11.67)
    43.2
    (11.73)
    43.5
    (11.87)
    Sex: Female, Male (Count of Participants)
    Female
    365
    87.1%
    454
    86.3%
    369
    87.9%
    457
    87%
    1645
    87%
    Male
    54
    12.9%
    72
    13.7%
    51
    12.1%
    68
    13%
    245
    13%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    29
    6.9%
    45
    8.6%
    34
    8.1%
    38
    7.2%
    146
    7.7%
    Not Hispanic or Latino
    387
    92.4%
    481
    91.4%
    386
    91.9%
    484
    92.2%
    1738
    92%
    Unknown or Not Reported
    3
    0.7%
    0
    0%
    0
    0%
    3
    0.6%
    6
    0.3%
    Race/Ethnicity, Customized (Count of Participants)
    White
    351
    83.8%
    424
    80.6%
    343
    81.7%
    412
    78.5%
    1530
    81%
    Black
    32
    7.6%
    38
    7.2%
    38
    9%
    40
    7.6%
    148
    7.8%
    Asian
    29
    6.9%
    62
    11.8%
    36
    8.6%
    64
    12.2%
    191
    10.1%
    American Indian or Alaskan Native
    1
    0.2%
    2
    0.4%
    0
    0%
    3
    0.6%
    6
    0.3%
    Native Hawaiian or other Pacific Islander
    1
    0.2%
    0
    0%
    0
    0%
    2
    0.4%
    3
    0.2%
    Other
    5
    1.2%
    0
    0%
    3
    0.7%
    4
    0.8%
    12
    0.6%
    Number of Migraine Days (days) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [days]
    13.9
    (5.99)
    13.1
    (5.49)
    13.6
    (5.86)
    13.2
    (5.26)
    13.4
    (5.63)
    Number of Headache Days of Any Severity (days) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [days]
    13.6
    (6.68)
    12.7
    (6.20)
    13.2
    (6.32)
    12.9
    (6.02)
    13.1
    (6.29)

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants With Adverse Events (AEs)
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    Safety population included all participants who received at least 1 dose of fremanezumab.
    Arm/Group Title TEV-48125 225 mg Monthly: New/Placebo Rollover Participants TEV-48125 225 mg Monthly: Active Rollover Participants TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants TEV-48125 675 mg Quarterly: Active Rollover Participants
    Arm/Group Description 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). 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). 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). 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).
    Measure Participants 418 526 419 525
    Any AEs
    365
    87.1%
    456
    86.7%
    365
    86.9%
    426
    81.1%
    Severe AEs
    47
    11.2%
    51
    9.7%
    45
    10.7%
    50
    9.5%
    Treatment-related AEs
    263
    62.8%
    288
    54.8%
    242
    57.6%
    270
    51.4%
    Serious AEs
    27
    6.4%
    29
    5.5%
    36
    8.6%
    23
    4.4%
    AEs leading to discontinuation from study
    18
    4.3%
    18
    3.4%
    22
    5.2%
    18
    3.4%
    2. Other Pre-specified Outcome
    Title Change From Baseline in Monthly Average Number of Migraine Days During the 4-Week Period at Month 12
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title TEV-48125 225 mg Monthly: New/Placebo Rollover CM Participants TEV-48125 225 mg Monthly: Active Rollover CM Participants TEV-48125 675mg Quarterly:New/Placebo Rollover CM Participants TEV-48125 675 mg Quarterly: Active Rollover CM Participants TEV-48125 225 mg Monthly: New/Placebo Rollover EM Participants TEV-48125 225 mg Monthly: Active Rollover EM Participants TEV-48125 675mg Quarterly:New/Placebo Rollover EM Participants TEV-48125 675 mg Quarterly: Active Rollover EM Participants
    Arm/Group Description 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/1.5mL and 2 injections of placebo 1.5 mL on Days 84, 168, and 252; and 1 injection of fremanezumab 225 mg/1.5mL on Days 28, 56, 112, 140, 196, 224, 280, 308). 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/1.5mL and 2 injections of placebo 1.5 mL on Days 84, 168, and 252; and 1 injection of fremanezumab 225 mg/1.5mL on Days 28, 56, 112, 140, 196, 224, 280, 308). 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 once every 3 months for 12 months for a total of 4 doses (3 injections of fremanezumab 225 mg/1.5mL on Days 0, 84, 168, and 252; and 1 injection of placebo 1.5 mL on Days 28, 56, 112, 140, 196, 224, 280, 308). Participants with CM 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/1.5mL on Days 0, 84, 168, and 252; and 1 injection of placebo 1.5 mL on Days 28, 56, 112, 140, 196, 224, 280, 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/1.5mL and 2 injections of placebo 1.5 mL on Days 0, 84, 168, and 252; and 1 injection of fremanezumab 225 mg/1.5mL on Days 28, 56, 112, 140, 196, 224, 280, 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/1.5mL and 2 injections of placebo 1.5 mL on Days 0, 84, 168, and 252; and 1 injection of fremanezumab 225 mg/1.5mL on Days 28, 56, 112, 140, 196, 224, 280, 308). Participants with 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/1.5mL on Days 0, 84, 168, and 252; and 1 injection of placebo 1.5 mL on Days 28, 56, 112, 140, 196, 224, 280, 308). Participants with 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/1.5mL on Days 0, 84, 168, and 252; and 1 injection of placebo 1.5 mL on Days 28, 56, 112, 140, 196, 224, 280, 308).
    Measure Participants 192 233 194 230 124 173 138 173
    Mean (Standard Deviation) [days/month]
    -7.8
    (6.98)
    -8.2
    (6.14)
    -7.6
    (6.87)
    -7.0
    (6.54)
    -4.5
    (4.20)
    -5.5
    (4.01)
    -5.5
    (3.65)
    -5.0
    (3.78)
    3. Other Pre-specified Outcome
    Title Change From Baseline in Monthly Average Number of Headache Days of Any Severity During the 4-Week Period at Month 12
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title TEV-48125 225 mg Monthly: New/Placebo Rollover CM Participants TEV-48125 225 mg Monthly: Active Rollover CM Participants TEV-48125 675mg Quarterly:New/Placebo Rollover CM Participants TEV-48125 675 mg Quarterly: Active Rollover CM Participants TEV-48125 225 mg Monthly: New/Placebo Rollover EM Participants TEV-48125 225 mg Monthly: Active Rollover EM Participants TEV-48125 675mg Quarterly:New/Placebo Rollover EM Participants TEV-48125 675 mg Quarterly: Active Rollover EM Participants
    Arm/Group Description 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/1.5mL and 2 injections of placebo 1.5 mL on Days 84, 168, and 252; and 1 injection of fremanezumab 225 mg/1.5mL on Days 28, 56, 112, 140, 196, 224, 280, 308). 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/1.5mL and 2 injections of placebo 1.5 mL on Days 84, 168, and 252; and 1 injection of fremanezumab 225 mg/1.5mL on Days 28, 56, 112, 140, 196, 224, 280, 308). 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 once every 3 months for 12 months for a total of 4 doses (3 injections of fremanezumab 225 mg/1.5mL on Days 0, 84, 168, and 252; and 1 injection of placebo 1.5 mL on Days 28, 56, 112, 140, 196, 224, 280, 308). Participants with CM 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/1.5mL on Days 0, 84, 168, and 252; and 1 injection of placebo 1.5 mL on Days 28, 56, 112, 140, 196, 224, 280, 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/1.5mL and 2 injections of placebo 1.5 mL on Days 0, 84, 168, and 252; and 1 injection of fremanezumab 225 mg/1.5mL on Days 28, 56, 112, 140, 196, 224, 280, 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/1.5mL and 2 injections of placebo 1.5 mL on Days 0, 84, 168, and 252; and 1 injection of fremanezumab 225 mg/1.5mL on Days 28, 56, 112, 140, 196, 224, 280, 308). Participants with 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/1.5mL on Days 0, 84, 168, and 252; and 1 injection of placebo 1.5 mL on Days 28, 56, 112, 140, 196, 224, 280, 308). Participants with 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/1.5mL on Days 0, 84, 168, and 252; and 1 injection of placebo 1.5 mL on Days 28, 56, 112, 140, 196, 224, 280, 308).
    Measure Participants 192 233 194 230 124 173 138 173
    Mean (Standard Deviation) [days/month]
    -7.7
    (6.79)
    -7.9
    (6.01)
    -7.2
    (6.48)
    -7.1
    (6.88)
    -4.4
    (4.25)
    -5.0
    (3.90)
    -5.0
    (3.63)
    -4.8
    (3.74)
    4. Primary Outcome
    Title Number of Participants With Potentially Clinically Significant Abnormal Serum Chemistry Results
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    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/Group Title TEV-48125 225 mg Monthly: New/Placebo Rollover Participants TEV-48125 225 mg Monthly: Active Rollover Participants TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants TEV-48125 675 mg Quarterly: Active Rollover Participants
    Arm/Group Description 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). 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). 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). 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).
    Measure Participants 408 518 412 513
    Count of Participants [Participants]
    27
    6.4%
    26
    4.9%
    11
    2.6%
    23
    4.4%
    5. Primary Outcome
    Title Number of Participants With Potentially Clinically Significant Abnormal Hematology Results
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    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/Group Title TEV-48125 225 mg Monthly: New/Placebo Rollover Participants TEV-48125 225 mg Monthly: Active Rollover Participants TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants TEV-48125 675 mg Quarterly: Active Rollover Participants
    Arm/Group Description 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). 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). 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). 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).
    Measure Participants 408 518 412 513
    Count of Participants [Participants]
    34
    8.1%
    39
    7.4%
    27
    6.4%
    40
    7.6%
    6. Primary Outcome
    Title Number of Participants With Potentially Clinically Significant Abnormal Urinalysis Laboratory Tests Results
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    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/Group Title TEV-48125 225 mg Monthly: New/Placebo Rollover Participants TEV-48125 225 mg Monthly: Active Rollover Participants TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants TEV-48125 675 mg Quarterly: Active Rollover Participants
    Arm/Group Description 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). 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). 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). 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).
    Measure Participants 408 517 412 513
    Count of Participants [Participants]
    128
    30.5%
    170
    32.3%
    120
    28.6%
    146
    27.8%
    7. Primary Outcome
    Title Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Values
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    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/Group Title TEV-48125 225 mg Monthly: New/Placebo Rollover Participants TEV-48125 225 mg Monthly: Active Rollover Participants TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants TEV-48125 675 mg Quarterly: Active Rollover Participants
    Arm/Group Description 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). 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). 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). 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).
    Measure Participants 415 520 414 519
    Count of Participants [Participants]
    20
    4.8%
    33
    6.3%
    24
    5.7%
    40
    7.6%
    8. Primary Outcome
    Title Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    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/Group Title TEV-48125 225 mg Monthly: New/Placebo Rollover Participants TEV-48125 225 mg Monthly: Active Rollover Participants TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants TEV-48125 675 mg Quarterly: Active Rollover Participants
    Arm/Group Description 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). 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). 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). 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).
    Measure Participants 386 492 391 489
    Normal - Normal
    239
    57%
    295
    56.1%
    230
    54.8%
    296
    56.4%
    Normal - Abnormal NCS
    45
    10.7%
    64
    12.2%
    49
    11.7%
    67
    12.8%
    Normal - Abnormal CS
    0
    0%
    0
    0%
    0
    0%
    1
    0.2%
    Abnormal NCS - Normal
    42
    10%
    53
    10.1%
    43
    10.2%
    60
    11.4%
    Abnormal NCS - Abnormal NCS
    60
    14.3%
    79
    15%
    69
    16.4%
    65
    12.4%
    Abnormal NCS - Abnormal CS
    0
    0%
    1
    0.2%
    0
    0%
    0
    0%
    Abnormal CS - Normal
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Abnormal CS - Abnormal NCS
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Abnormal CS - Abnormal CS
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    9. Primary Outcome
    Title Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results
    Description 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)

    Outcome Measure Data

    Analysis Population Description
    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/Group Title TEV-48125 225 mg Monthly: New/Placebo Rollover Participants TEV-48125 225 mg Monthly: Active Rollover Participants TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants TEV-48125 675 mg Quarterly: Active Rollover Participants
    Arm/Group Description 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). 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). 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). 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).
    Measure Participants 407 516 410 513
    Low-Low
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Low-Normal
    1
    0.2%
    2
    0.4%
    2
    0.5%
    1
    0.2%
    Low-High
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Normal-Low
    1
    0.2%
    3
    0.6%
    3
    0.7%
    2
    0.4%
    Normal-Normal
    370
    88.3%
    465
    88.4%
    374
    89%
    451
    85.9%
    Normal-High
    10
    2.4%
    10
    1.9%
    14
    3.3%
    14
    2.7%
    High-Low
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    High-Normal
    18
    4.3%
    25
    4.8%
    9
    2.1%
    35
    6.7%
    High-High
    7
    1.7%
    11
    2.1%
    8
    1.9%
    10
    1.9%
    Low-Low
    0
    0%
    1
    0.2%
    4
    1%
    1
    0.2%
    Low-Normal
    11
    2.6%
    11
    2.1%
    11
    2.6%
    9
    1.7%
    Low-High
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Normal-Low
    12
    2.9%
    15
    2.9%
    9
    2.1%
    7
    1.3%
    Normal-Normal
    366
    87.4%
    468
    89%
    372
    88.6%
    472
    89.9%
    Normal-High
    6
    1.4%
    5
    1%
    4
    1%
    4
    0.8%
    High-Low
    0
    0%
    0
    0%
    0
    0%
    1
    0.2%
    High-Normal
    7
    1.7%
    11
    2.1%
    6
    1.4%
    13
    2.5%
    High-High
    4
    1%
    5
    1%
    4
    1%
    6
    1.1%
    Low-Low
    2
    0.5%
    2
    0.4%
    1
    0.2%
    0
    0%
    Low-Normal
    4
    1%
    1
    0.2%
    7
    1.7%
    7
    1.3%
    Low-High
    0
    0%
    1
    0.2%
    0
    0%
    0
    0%
    Normal-Low
    3
    0.7%
    11
    2.1%
    7
    1.7%
    10
    1.9%
    Normal-Normal
    341
    81.4%
    423
    80.4%
    334
    79.5%
    414
    78.9%
    Normal-High
    14
    3.3%
    18
    3.4%
    19
    4.5%
    22
    4.2%
    High-Low
    0
    0%
    0
    0%
    0
    0%
    1
    0.2%
    High-Normal
    26
    6.2%
    43
    8.2%
    26
    6.2%
    37
    7%
    High-High
    16
    3.8%
    17
    3.2%
    16
    3.8%
    22
    4.2%
    10. Other Pre-specified Outcome
    Title 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
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title TEV-48125 225 mg Monthly: New/Placebo Rollover CM Participants TEV-48125 225 mg Monthly: Active Rollover CM Participants TEV-48125 675mg Quarterly:New/Placebo Rollover CM Participants TEV-48125 675 mg Quarterly: Active Rollover CM Participants TEV-48125 225 mg Monthly: New/Placebo Rollover EM Participants TEV-48125 225 mg Monthly: Active Rollover EM Participants TEV-48125 675mg Quarterly:New/Placebo Rollover EM Participants TEV-48125 675 mg Quarterly: Active Rollover EM Participants
    Arm/Group Description 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/1.5mL and 2 injections of placebo 1.5 mL on Days 84, 168, and 252; and 1 injection of fremanezumab 225 mg/1.5mL on Days 28, 56, 112, 140, 196, 224, 280, 308). 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/1.5mL and 2 injections of placebo 1.5 mL on Days 84, 168, and 252; and 1 injection of fremanezumab 225 mg/1.5mL on Days 28, 56, 112, 140, 196, 224, 280, 308). 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 once every 3 months for 12 months for a total of 4 doses (3 injections of fremanezumab 225 mg/1.5mL on Days 0, 84, 168, and 252; and 1 injection of placebo 1.5 mL on Days 28, 56, 112, 140, 196, 224, 280, 308). Participants with CM 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/1.5mL on Days 0, 84, 168, and 252; and 1 injection of placebo 1.5 mL on Days 28, 56, 112, 140, 196, 224, 280, 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/1.5mL and 2 injections of placebo 1.5 mL on Days 0, 84, 168, and 252; and 1 injection of fremanezumab 225 mg/1.5mL on Days 28, 56, 112, 140, 196, 224, 280, 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/1.5mL and 2 injections of placebo 1.5 mL on Days 0, 84, 168, and 252; and 1 injection of fremanezumab 225 mg/1.5mL on Days 28, 56, 112, 140, 196, 224, 280, 308). Participants with 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/1.5mL on Days 0, 84, 168, and 252; and 1 injection of placebo 1.5 mL on Days 28, 56, 112, 140, 196, 224, 280, 308). Participants with 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/1.5mL on Days 0, 84, 168, and 252; and 1 injection of placebo 1.5 mL on Days 28, 56, 112, 140, 196, 224, 280, 308).
    Measure Participants 195 240 197 237 125 174 139 174
    Number [percentage of participants]
    54
    12.9%
    59
    11.2%
    52
    12.4%
    54
    10.3%
    58
    3.1%
    75
    NaN
    68
    NaN
    64
    NaN
    11. Other Pre-specified Outcome
    Title 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
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title TEV-48125 225 mg Monthly: New/Placebo Rollover CM Participants TEV-48125 225 mg Monthly: Active Rollover CM Participants TEV-48125 675mg Quarterly:New/Placebo Rollover CM Participants TEV-48125 675 mg Quarterly: Active Rollover CM Participants TEV-48125 225 mg Monthly: New/Placebo Rollover EM Participants TEV-48125 225 mg Monthly: Active Rollover EM Participants TEV-48125 675mg Quarterly:New/Placebo Rollover EM Participants TEV-48125 675 mg Quarterly: Active Rollover EM Participants
    Arm/Group Description 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/1.5mL and 2 injections of placebo 1.5 mL on Days 84, 168, and 252; and 1 injection of fremanezumab 225 mg/1.5mL on Days 28, 56, 112, 140, 196, 224, 280, 308). 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/1.5mL and 2 injections of placebo 1.5 mL on Days 84, 168, and 252; and 1 injection of fremanezumab 225 mg/1.5mL on Days 28, 56, 112, 140, 196, 224, 280, 308). 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 once every 3 months for 12 months for a total of 4 doses (3 injections of fremanezumab 225 mg/1.5mL on Days 0, 84, 168, and 252; and 1 injection of placebo 1.5 mL on Days 28, 56, 112, 140, 196, 224, 280, 308). Participants with CM 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/1.5mL on Days 0, 84, 168, and 252; and 1 injection of placebo 1.5 mL on Days 28, 56, 112, 140, 196, 224, 280, 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/1.5mL and 2 injections of placebo 1.5 mL on Days 0, 84, 168, and 252; and 1 injection of fremanezumab 225 mg/1.5mL on Days 28, 56, 112, 140, 196, 224, 280, 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/1.5mL and 2 injections of placebo 1.5 mL on Days 0, 84, 168, and 252; and 1 injection of fremanezumab 225 mg/1.5mL on Days 28, 56, 112, 140, 196, 224, 280, 308). Participants with 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/1.5mL on Days 0, 84, 168, and 252; and 1 injection of placebo 1.5 mL on Days 28, 56, 112, 140, 196, 224, 280, 308). Participants with 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/1.5mL on Days 0, 84, 168, and 252; and 1 injection of placebo 1.5 mL on Days 28, 56, 112, 140, 196, 224, 280, 308).
    Measure Participants 193 240 197 237 124 174 138 174
    Number [percentage of participants]
    56
    13.4%
    62
    11.8%
    54
    12.9%
    54
    10.3%
    58
    3.1%
    72
    NaN
    67
    NaN
    68
    NaN
    12. Primary Outcome
    Title Number of Participants With Injection Site Reactions
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Safety population included all participants who received at least 1 dose of fremanezumab.
    Arm/Group Title TEV-48125 225 mg Monthly: New/Placebo Rollover Participants TEV-48125 225 mg Monthly: Active Rollover Participants TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants TEV-48125 675 mg Quarterly: Active Rollover Participants
    Arm/Group Description 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). 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). 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). 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).
    Measure Participants 418 526 419 525
    Injection site induration
    167
    39.9%
    174
    33.1%
    144
    34.3%
    134
    25.5%
    Injection site pain
    149
    35.6%
    156
    29.7%
    135
    32.1%
    140
    26.7%
    Injection site erythema
    130
    31%
    144
    27.4%
    99
    23.6%
    124
    23.6%
    Injection site haemorrhage
    34
    8.1%
    38
    7.2%
    21
    5%
    38
    7.2%
    Injection site pruritus
    31
    7.4%
    43
    8.2%
    17
    4%
    24
    4.6%
    Injection site swelling
    7
    1.7%
    10
    1.9%
    6
    1.4%
    8
    1.5%
    Injection site bruising
    2
    0.5%
    2
    0.4%
    4
    1%
    3
    0.6%
    Injection site rash
    4
    1%
    2
    0.4%
    5
    1.2%
    2
    0.4%
    Injection site urticaria
    4
    1%
    2
    0.4%
    3
    0.7%
    2
    0.4%
    Injection site warmth
    3
    0.7%
    2
    0.4%
    1
    0.2%
    1
    0.2%
    Injection site dermatitis
    0
    0%
    1
    0.2%
    0
    0%
    1
    0.2%
    Injection site haematoma
    1
    0.2%
    0
    0%
    0
    0%
    1
    0.2%
    Injection site inflammation
    0
    0%
    1
    0.2%
    1
    0.2%
    0
    0%
    Injection site discolouration
    0
    0%
    1
    0.2%
    0
    0%
    0
    0%
    Injection site discomfort
    0
    0%
    0
    0%
    0
    0%
    1
    0.2%
    Injection site hypersensitivity
    1
    0.2%
    0
    0%
    0
    0%
    0
    0%
    Injection site hypoaesthesia
    1
    0.2%
    1
    0.2%
    0
    0%
    0
    0%
    Injection site irritation
    0
    0%
    0
    0%
    0
    0%
    1
    0.2%
    Injection site oedema
    1
    0.2%
    1
    0.2%
    1
    0.2%
    0
    0%
    Injection site papule
    1
    0.2%
    0
    0%
    0
    0%
    0
    0%
    Injection site paraesthesia
    0
    0%
    0
    0%
    1
    0.2%
    0
    0%
    Injection site vesicles
    0
    0%
    1
    0.2%
    1
    0.2%
    0
    0%
    Injection site pallor
    0
    0%
    0
    0%
    0
    0%
    1
    0.2%
    13. Primary Outcome
    Title Number of Participants With Suicidal Ideation and Suicidal Behavior as Assessed by the Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS)
    Description 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

    Outcome Measure Data

    Analysis Population Description
    Safety population included all participants who received at least 1 dose of fremanezumab.
    Arm/Group Title TEV-48125 225 mg Monthly: New/Placebo Rollover Participants TEV-48125 225 mg Monthly: Active Rollover Participants TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants TEV-48125 675 mg Quarterly: Active Rollover Participants
    Arm/Group Description 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). 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). 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). 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).
    Measure Participants 418 526 419 525
    Suicidal ideation
    2
    0.5%
    0
    0%
    2
    0.5%
    1
    0.2%
    Suicidal attempt
    0
    0%
    0
    0%
    1
    0.2%
    0
    0%

    Adverse Events

    Time Frame Baseline (Day 0) up to follow-up visit (Day 533)
    Adverse Event Reporting Description Safety population included all participants who received at least 1 dose of fremanezumab.
    Arm/Group Title TEV-48125 225 mg Monthly: New/Placebo Rollover Participants TEV-48125 225 mg Monthly: Active Rollover Participants TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants TEV-48125 675 mg Quarterly: Active Rollover Participants
    Arm/Group Description 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). 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). 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). 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).
    All Cause Mortality
    TEV-48125 225 mg Monthly: New/Placebo Rollover Participants TEV-48125 225 mg Monthly: Active Rollover Participants TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants TEV-48125 675 mg Quarterly: Active Rollover Participants
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/418 (0%) 0/526 (0%) 1/419 (0.2%) 0/525 (0%)
    Serious Adverse Events
    TEV-48125 225 mg Monthly: New/Placebo Rollover Participants TEV-48125 225 mg Monthly: Active Rollover Participants TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants TEV-48125 675 mg Quarterly: Active Rollover Participants
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 27/418 (6.5%) 29/526 (5.5%) 36/419 (8.6%) 23/525 (4.4%)
    Blood and lymphatic system disorders
    Anaemia 0/418 (0%) 0 1/526 (0.2%) 1 0/419 (0%) 0 0/525 (0%) 0
    Iron deficiency anaemia 0/418 (0%) 0 1/526 (0.2%) 1 0/419 (0%) 0 0/525 (0%) 0
    Cardiac disorders
    Atrial fibrillation 0/418 (0%) 0 0/526 (0%) 0 1/419 (0.2%) 2 0/525 (0%) 0
    Pericarditis 0/418 (0%) 0 0/526 (0%) 0 0/419 (0%) 0 1/525 (0.2%) 1
    Sinus tachycardia 0/418 (0%) 0 1/526 (0.2%) 1 0/419 (0%) 0 0/525 (0%) 0
    Congenital, familial and genetic disorders
    Arteriovenous malformation 0/418 (0%) 0 0/526 (0%) 0 0/419 (0%) 0 1/525 (0.2%) 1
    Cerebrovascular arteriovenous malformation 0/418 (0%) 0 0/526 (0%) 0 0/419 (0%) 0 1/525 (0.2%) 1
    Congenital cyst 0/418 (0%) 0 0/526 (0%) 0 0/419 (0%) 0 1/525 (0.2%) 1
    Congenital cystic disease of liver 0/418 (0%) 0 0/526 (0%) 0 1/419 (0.2%) 1 0/525 (0%) 0
    Hereditary haemochromatosis 1/418 (0.2%) 1 0/526 (0%) 0 0/419 (0%) 0 0/525 (0%) 0
    Ear and labyrinth disorders
    Sudden hearing loss 0/418 (0%) 0 0/526 (0%) 0 0/419 (0%) 0 1/525 (0.2%) 1
    Endocrine disorders
    Hyperthyroidism 0/418 (0%) 0 1/526 (0.2%) 1 0/419 (0%) 0 0/525 (0%) 0
    Eye disorders
    Macular degeneration 0/418 (0%) 0 1/526 (0.2%) 1 0/419 (0%) 0 0/525 (0%) 0
    Retinal detachment 1/418 (0.2%) 1 1/526 (0.2%) 1 0/419 (0%) 0 0/525 (0%) 0
    Retinal tear 0/418 (0%) 0 1/526 (0.2%) 1 1/419 (0.2%) 1 1/525 (0.2%) 1
    Gastrointestinal disorders
    Abdominal pain 2/418 (0.5%) 2 0/526 (0%) 0 0/419 (0%) 0 0/525 (0%) 0
    Barrett's oesophagus 0/418 (0%) 0 1/526 (0.2%) 1 0/419 (0%) 0 0/525 (0%) 0
    Gastric ulcer 0/418 (0%) 0 0/526 (0%) 0 1/419 (0.2%) 1 0/525 (0%) 0
    Haemorrhoidal haemorrhage 0/418 (0%) 0 0/526 (0%) 0 0/419 (0%) 0 1/525 (0.2%) 1
    Ileal stenosis 1/418 (0.2%) 1 0/526 (0%) 0 1/419 (0.2%) 1 0/525 (0%) 0
    Small intestinal obstruction 0/418 (0%) 0 0/526 (0%) 0 1/419 (0.2%) 1 0/525 (0%) 0
    General disorders
    Chest pain 0/418 (0%) 0 0/526 (0%) 0 0/419 (0%) 0 1/525 (0.2%) 1
    Multi-organ failure 0/418 (0%) 0 0/526 (0%) 0 1/419 (0.2%) 1 0/525 (0%) 0
    Hepatobiliary disorders
    Cholecystitis 0/418 (0%) 0 0/526 (0%) 0 1/419 (0.2%) 1 0/525 (0%) 0
    Cholecystitis acute 0/418 (0%) 0 0/526 (0%) 0 0/419 (0%) 0 1/525 (0.2%) 1
    Cholecystitis chronic 0/418 (0%) 0 0/526 (0%) 0 1/419 (0.2%) 1 0/525 (0%) 0
    Cholelithiasis 0/418 (0%) 0 1/526 (0.2%) 1 1/419 (0.2%) 1 0/525 (0%) 0
    Hepatic cirrhosis 1/418 (0.2%) 1 0/526 (0%) 0 0/419 (0%) 0 0/525 (0%) 0
    Hepatitis alcoholic 1/418 (0.2%) 1 0/526 (0%) 0 0/419 (0%) 0 0/525 (0%) 0
    Immune system disorders
    Allergy to arthropod sting 0/418 (0%) 0 0/526 (0%) 0 0/419 (0%) 0 1/525 (0.2%) 1
    Infections and infestations
    Abdominal abscess 1/418 (0.2%) 1 0/526 (0%) 0 0/419 (0%) 0 0/525 (0%) 0
    Appendicitis 2/418 (0.5%) 2 0/526 (0%) 0 0/419 (0%) 0 0/525 (0%) 0
    Bacterial sepsis 1/418 (0.2%) 1 0/526 (0%) 0 0/419 (0%) 0 0/525 (0%) 0
    Diverticulitis 0/418 (0%) 0 0/526 (0%) 0 1/419 (0.2%) 1 0/525 (0%) 0
    Enteritis infectious 0/418 (0%) 0 0/526 (0%) 0 1/419 (0.2%) 1 0/525 (0%) 0
    Meningitis aseptic 0/418 (0%) 0 0/526 (0%) 0 1/419 (0.2%) 1 0/525 (0%) 0
    Peritonitis 1/418 (0.2%) 1 0/526 (0%) 0 0/419 (0%) 0 0/525 (0%) 0
    Petrositis 0/418 (0%) 0 1/526 (0.2%) 1 0/419 (0%) 0 0/525 (0%) 0
    Pneumonia 1/418 (0.2%) 1 1/526 (0.2%) 1 0/419 (0%) 0 0/525 (0%) 0
    Post procedural infection 0/418 (0%) 0 0/526 (0%) 0 1/419 (0.2%) 1 0/525 (0%) 0
    Urinary tract infection 0/418 (0%) 0 0/526 (0%) 0 2/419 (0.5%) 2 0/525 (0%) 0
    Injury, poisoning and procedural complications
    Abdominal wound dehiscence 1/418 (0.2%) 1 0/526 (0%) 0 0/419 (0%) 0 0/525 (0%) 0
    Fall 0/418 (0%) 0 0/526 (0%) 0 0/419 (0%) 0 1/525 (0.2%) 1
    Intentional overdose 0/418 (0%) 0 0/526 (0%) 0 1/419 (0.2%) 1 0/525 (0%) 0
    Pelvic fracture 0/418 (0%) 0 0/526 (0%) 0 0/419 (0%) 0 1/525 (0.2%) 1
    Post procedural haemorrhage 0/418 (0%) 0 1/526 (0.2%) 1 1/419 (0.2%) 1 0/525 (0%) 0
    Procedural pain 0/418 (0%) 0 0/526 (0%) 0 1/419 (0.2%) 1 0/525 (0%) 0
    Investigations
    Ammonia increased 1/418 (0.2%) 1 0/526 (0%) 0 0/419 (0%) 0 0/525 (0%) 0
    Metabolism and nutrition disorders
    Dehydration 1/418 (0.2%) 1 0/526 (0%) 0 0/419 (0%) 0 0/525 (0%) 0
    Hypoglycaemia 1/418 (0.2%) 1 0/526 (0%) 0 0/419 (0%) 0 0/525 (0%) 0
    Musculoskeletal and connective tissue disorders
    Fibromyalgia 0/418 (0%) 0 0/526 (0%) 0 1/419 (0.2%) 1 0/525 (0%) 0
    Lumbar spinal stenosis 0/418 (0%) 0 1/526 (0.2%) 1 1/419 (0.2%) 1 0/525 (0%) 0
    Musculoskeletal chest pain 0/418 (0%) 0 0/526 (0%) 0 0/419 (0%) 0 1/525 (0.2%) 1
    Osteoarthritis 1/418 (0.2%) 1 1/526 (0.2%) 1 0/419 (0%) 0 1/525 (0.2%) 1
    Osteochondrosis 0/418 (0%) 0 0/526 (0%) 0 0/419 (0%) 0 1/525 (0.2%) 1
    Periarthritis 0/418 (0%) 0 1/526 (0.2%) 1 0/419 (0%) 0 0/525 (0%) 0
    Spinal column stenosis 0/418 (0%) 0 0/526 (0%) 0 0/419 (0%) 0 1/525 (0.2%) 1
    Spinal osteoarthritis 1/418 (0.2%) 1 0/526 (0%) 0 0/419 (0%) 0 0/525 (0%) 0
    Spinal pain 0/418 (0%) 0 1/526 (0.2%) 1 0/419 (0%) 0 0/525 (0%) 0
    Synovial cyst 0/418 (0%) 0 1/526 (0.2%) 1 0/419 (0%) 0 0/525 (0%) 0
    Vertebral osteophyte 0/418 (0%) 0 0/526 (0%) 0 0/419 (0%) 0 1/525 (0.2%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma 0/418 (0%) 0 2/526 (0.4%) 2 2/419 (0.5%) 3 0/525 (0%) 0
    Benign breast neoplasm 0/418 (0%) 0 0/526 (0%) 0 1/419 (0.2%) 1 0/525 (0%) 0
    Breast cancer stage III 0/418 (0%) 0 0/526 (0%) 0 1/419 (0.2%) 1 0/525 (0%) 0
    Endometrial cancer 0/365 (0%) 0 0/454 (0%) 0 1/369 (0.3%) 1 0/457 (0%) 0
    High grade B-cell lymphoma Burkitt-like lymphoma 0/418 (0%) 0 0/526 (0%) 0 1/419 (0.2%) 1 0/525 (0%) 0
    Intraductal proliferative breast lesion 0/418 (0%) 0 0/526 (0%) 0 1/419 (0.2%) 1 0/525 (0%) 0
    Malignant melanoma 1/418 (0.2%) 1 0/526 (0%) 0 1/419 (0.2%) 1 1/525 (0.2%) 1
    Meningioma 0/418 (0%) 0 0/526 (0%) 0 1/419 (0.2%) 1 0/525 (0%) 0
    Papillary thyroid cancer 0/418 (0%) 0 1/526 (0.2%) 1 0/419 (0%) 0 1/525 (0.2%) 1
    Phyllodes tumour 0/418 (0%) 0 0/526 (0%) 0 1/419 (0.2%) 1 0/525 (0%) 0
    Pituitary tumour 0/418 (0%) 0 1/526 (0.2%) 1 0/419 (0%) 0 0/525 (0%) 0
    Prostate cancer 0/54 (0%) 0 0/72 (0%) 0 1/51 (2%) 1 0/68 (0%) 0
    Superficial spreading melanoma stage unspecified 0/418 (0%) 0 1/526 (0.2%) 1 0/419 (0%) 0 0/525 (0%) 0
    Thyroid cancer 0/418 (0%) 0 0/526 (0%) 0 0/419 (0%) 0 1/525 (0.2%) 1
    Nervous system disorders
    Carpal tunnel syndrome 0/418 (0%) 0 1/526 (0.2%) 1 0/419 (0%) 0 0/525 (0%) 0
    Central nervous system lesion 1/418 (0.2%) 1 0/526 (0%) 0 0/419 (0%) 0 0/525 (0%) 0
    Cerebrovascular accident 1/418 (0.2%) 1 0/526 (0%) 0 1/419 (0.2%) 1 1/525 (0.2%) 1
    Cluster headache 0/418 (0%) 0 1/526 (0.2%) 1 0/419 (0%) 0 0/525 (0%) 0
    Hypoaesthesia 0/418 (0%) 0 0/526 (0%) 0 0/419 (0%) 0 1/525 (0.2%) 1
    Intracranial aneurysm 0/418 (0%) 0 0/526 (0%) 0 1/419 (0.2%) 1 1/525 (0.2%) 1
    Migraine 0/418 (0%) 0 3/526 (0.6%) 4 0/419 (0%) 0 0/525 (0%) 0
    Myasthenia gravis 0/418 (0%) 0 0/526 (0%) 0 1/419 (0.2%) 1 0/525 (0%) 0
    Nerve compression 0/418 (0%) 0 1/526 (0.2%) 3 0/419 (0%) 0 0/525 (0%) 0
    Parkinson's disease 0/418 (0%) 0 0/526 (0%) 0 1/419 (0.2%) 1 0/525 (0%) 0
    Parkinsonism 0/418 (0%) 0 0/526 (0%) 0 1/419 (0.2%) 1 0/525 (0%) 0
    Perineurial cyst 1/418 (0.2%) 1 0/526 (0%) 0 0/419 (0%) 0 0/525 (0%) 0
    Primary progressive multiple sclerosis 1/418 (0.2%) 1 0/526 (0%) 0 0/419 (0%) 0 0/525 (0%) 0
    Sciatica 0/418 (0%) 0 1/526 (0.2%) 1 0/419 (0%) 0 0/525 (0%) 0
    Status migrainosus 2/418 (0.5%) 4 1/526 (0.2%) 1 1/419 (0.2%) 1 0/525 (0%) 0
    Transient global amnesia 0/418 (0%) 0 1/526 (0.2%) 1 0/419 (0%) 0 0/525 (0%) 0
    Pregnancy, puerperium and perinatal conditions
    Abortion spontaneous 0/365 (0%) 0 1/454 (0.2%) 1 0/369 (0%) 0 0/457 (0%) 0
    Foetal death 0/365 (0%) 0 1/454 (0.2%) 1 0/369 (0%) 0 0/457 (0%) 0
    Premature baby 1/365 (0.3%) 1 0/454 (0%) 0 0/369 (0%) 0 0/457 (0%) 0
    Premature separation of placenta 0/365 (0%) 0 0/454 (0%) 0 1/369 (0.3%) 1 0/457 (0%) 0
    Psychiatric disorders
    Adjustment disorder with mixed disturbance of emotion and conduct 0/418 (0%) 0 0/526 (0%) 0 1/419 (0.2%) 1 0/525 (0%) 0
    Anxiety 0/418 (0%) 0 0/526 (0%) 0 0/419 (0%) 0 1/525 (0.2%) 1
    Suicidal ideation 1/418 (0.2%) 1 0/526 (0%) 0 1/419 (0.2%) 1 0/525 (0%) 0
    Suicide attempt 0/418 (0%) 0 0/526 (0%) 0 1/419 (0.2%) 1 0/525 (0%) 0
    Renal and urinary disorders
    Urinary retention 0/418 (0%) 0 1/526 (0.2%) 1 0/419 (0%) 0 0/525 (0%) 0
    Reproductive system and breast disorders
    Endometriosis 1/365 (0.3%) 1 0/454 (0%) 0 0/369 (0%) 0 0/457 (0%) 0
    Haemorrhagic ovarian cyst 0/365 (0%) 0 1/454 (0.2%) 1 0/369 (0%) 0 0/457 (0%) 0
    Ovarian cyst 1/365 (0.3%) 1 0/454 (0%) 0 0/369 (0%) 0 0/457 (0%) 0
    Ovarian cyst ruptured 1/365 (0.3%) 1 0/454 (0%) 0 0/369 (0%) 0 1/457 (0.2%) 1
    Ovarian mass 1/365 (0.3%) 1 0/454 (0%) 0 0/369 (0%) 0 0/457 (0%) 0
    Uterine haemorrhage 1/365 (0.3%) 1 0/457 (0%) 0 0/369 (0%) 0 0/457 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure 1/418 (0.2%) 1 0/526 (0%) 0 0/419 (0%) 0 0/525 (0%) 0
    Asthma 1/418 (0.2%) 1 0/526 (0%) 0 0/419 (0%) 0 0/525 (0%) 0
    Bronchospasm 0/418 (0%) 0 0/526 (0%) 0 0/419 (0%) 0 1/525 (0.2%) 1
    Laryngeal oedema 0/418 (0%) 0 0/526 (0%) 0 0/419 (0%) 0 1/525 (0.2%) 1
    Lung consolidation 0/418 (0%) 0 1/526 (0.2%) 1 0/419 (0%) 0 0/525 (0%) 0
    Pneumothorax 0/418 (0%) 0 1/526 (0.2%) 1 0/419 (0%) 0 0/525 (0%) 0
    Pulmonary embolism 1/418 (0.2%) 1 0/526 (0%) 0 0/419 (0%) 0 0/525 (0%) 0
    Pulmonary mass 0/418 (0%) 0 0/526 (0%) 0 1/419 (0.2%) 1 0/525 (0%) 0
    Surgical and medical procedures
    Salpingo-oophorectomy 0/418 (0%) 0 0/526 (0%) 0 0/419 (0%) 0 1/525 (0.2%) 1
    Vascular disorders
    Deep vein thrombosis 1/418 (0.2%) 1 0/526 (0%) 0 1/419 (0.2%) 1 0/525 (0%) 0
    Hypertension 0/418 (0%) 0 0/526 (0%) 0 1/419 (0.2%) 1 0/525 (0%) 0
    Hypovolaemic shock 0/418 (0%) 0 0/526 (0%) 0 1/419 (0.2%) 1 0/525 (0%) 0
    Venous thrombosis limb 0/418 (0%) 0 1/526 (0.2%) 1 0/419 (0%) 0 0/525 (0%) 0
    Other (Not Including Serious) Adverse Events
    TEV-48125 225 mg Monthly: New/Placebo Rollover Participants TEV-48125 225 mg Monthly: Active Rollover Participants TEV-48125 675 mg Quarterly: New/Placebo Rollover Participants TEV-48125 675 mg Quarterly: Active Rollover Participants
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 300/418 (71.8%) 367/526 (69.8%) 284/419 (67.8%) 329/525 (62.7%)
    General disorders
    Injection site erythema 130/418 (31.1%) 430 144/526 (27.4%) 446 99/419 (23.6%) 284 124/525 (23.6%) 386
    Injection site haemorrhage 34/418 (8.1%) 43 38/526 (7.2%) 66 21/419 (5%) 38 38/525 (7.2%) 62
    Injection site induration 167/418 (40%) 717 174/526 (33.1%) 753 144/419 (34.4%) 543 134/525 (25.5%) 666
    Injection site pain 149/418 (35.6%) 980 156/526 (29.7%) 982 135/419 (32.2%) 981 140/525 (26.7%) 811
    Injection site pruritus 31/418 (7.4%) 101 43/526 (8.2%) 107 17/419 (4.1%) 64 24/525 (4.6%) 64
    Infections and infestations
    Bronchitis 24/418 (5.7%) 25 15/526 (2.9%) 16 20/419 (4.8%) 22 24/525 (4.6%) 26
    Influenza 14/418 (3.3%) 18 27/526 (5.1%) 29 8/419 (1.9%) 9 25/525 (4.8%) 28
    Nasopharyngitis 43/418 (10.3%) 61 69/526 (13.1%) 107 37/419 (8.8%) 58 68/525 (13%) 108
    Sinusitis 30/418 (7.2%) 40 27/526 (5.1%) 28 28/419 (6.7%) 35 31/525 (5.9%) 38
    Upper respiratory tract infection 55/418 (13.2%) 65 62/526 (11.8%) 76 73/419 (17.4%) 97 63/525 (12%) 78
    Urinary tract infection 25/418 (6%) 38 27/526 (5.1%) 43 26/419 (6.2%) 29 33/525 (6.3%) 37

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.

    Results Point of Contact

    Name/Title Director, Clinical Research
    Organization Teva Branded Pharmaceutical Products, R&D Inc.
    Phone 1-888-483-8279
    Email USMedInfo@tevapharm.com
    Responsible Party:
    Teva Branded Pharmaceutical Products R&D, Inc.
    ClinicalTrials.gov Identifier:
    NCT02638103
    Other Study ID Numbers:
    • TV48125-CNS-30051
    • 2015-004550-18
    First Posted:
    Dec 22, 2015
    Last Update Posted:
    Nov 9, 2021
    Last Verified:
    Nov 1, 2021