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

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ClinicalTrials.gov Identifier: NCT02638103
Recruitment Status : Completed
First Posted : December 22, 2015
Results First Posted : August 28, 2019
Last Update Posted : February 28, 2020
Sponsor:
Information provided by (Responsible Party):
Teva Pharmaceutical Industries ( Teva Branded Pharmaceutical Products R&D, Inc. )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Migraine
Interventions Drug: Fremanezumab
Drug: Placebo
Enrollment 1890
Recruitment Details Participants with chronic or episodic migraine (CM or EM) who completed the pivotal efficacy studies of fremanezumab (TV48125-CNS-30049 [NCT02621931] and TV48125-CNS-30050 [NCT02629861]) and agreed to participate in this study; and new participants meeting eligibility criteria (not rolling over from pivotal studies), were enrolled in this study.
Pre-assignment Details A total of 1890 participants were enrolled, including 917 participants with CM rolled over from Study TV48125-CNS-30049, 661 participants with EM rolled over from Study TV48125-CNS-30050, and 312 newly enrolled participants (193 with CM and 119 with EM).
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
Hide 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 [1] 418 526 419 525
Full Analysis Set (FAS) [2] 416 520 419 523
Completed 313 408 335 383
Not Completed 106 118 85 142
Reason Not Completed
Adverse Event             13             12             19             12
Withdrawal by Subject             43             53             30             61
Protocol Violation             1             2             1             4
Pregnancy             2             3             0             1
Non-compliance to Study Procedures             2             1             1             1
Lost to Follow-up             26             33             20             37
Lack of Efficacy             14             10             12             22
Other than specified             5             4             2             4
[1]
Received at least 1 dose of study drug
[2]
Participants in safety analysis set who had at least 10 days of post-baseline efficacy assessment.
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
Hide 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 Number of Baseline Participants 419 526 420 525 1890
Hide Baseline Analysis Population Description
Intent-to-treat (ITT) analysis set included all participants who were randomized in this study for long-term safety evaluation, regardless if they receive study treatment or not.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 419 participants 526 participants 420 participants 525 participants 1890 participants
44.1  (12.09) 42.9  (11.97) 44.0  (11.67) 43.2  (11.73) 43.5  (11.87)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 419 participants 526 participants 420 participants 525 participants 1890 participants
Female
365
  87.1%
454
  86.3%
369
  87.9%
457
  87.0%
1645
  87.0%
Male
54
  12.9%
72
  13.7%
51
  12.1%
68
  13.0%
245
  13.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 419 participants 526 participants 420 participants 525 participants 1890 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
  92.0%
Unknown or Not Reported
3
   0.7%
0
   0.0%
0
   0.0%
3
   0.6%
6
   0.3%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 419 participants 526 participants 420 participants 525 participants 1890 participants
White
351
  83.8%
424
  80.6%
343
  81.7%
412
  78.5%
1530
  81.0%
Black
32
   7.6%
38
   7.2%
38
   9.0%
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
   0.0%
3
   0.6%
6
   0.3%
Native Hawaiian or other Pacific Islander
1
   0.2%
0
   0.0%
0
   0.0%
2
   0.4%
3
   0.2%
Other
5
   1.2%
0
   0.0%
3
   0.7%
4
   0.8%
12
   0.6%
Number of Migraine Days   [1] 
Mean (Standard Deviation)
Unit of measure:  Days
Number Analyzed 419 participants 526 participants 420 participants 525 participants 1890 participants
13.9  (5.99) 13.1  (5.49) 13.6  (5.86) 13.2  (5.26) 13.4  (5.63)
[1]
Measure 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 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 calendar day demonstrating a headache of any duration that was treated with migraine-specific medications.
Number of Headache Days of Any Severity   [1] 
Mean (Standard Deviation)
Unit of measure:  Days
Number Analyzed 419 participants 526 participants 420 participants 525 participants 1890 participants
13.6  (6.68) 12.7  (6.20) 13.2  (6.32) 12.9  (6.02) 13.1  (6.29)
[1]
Measure 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.
1.Primary Outcome
Title Number of Participants With Adverse Events (AEs)
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 418 526 419 525
Measure Type: Count of Participants
Unit of Measure: Participants
Any AEs
365
  87.3%
456
  86.7%
365
  87.1%
426
  81.1%
Severe AEs
47
  11.2%
51
   9.7%
45
  10.7%
50
   9.5%
Treatment-related AEs
263
  62.9%
288
  54.8%
242
  57.8%
270
  51.4%
Serious AEs
27
   6.5%
29
   5.5%
36
   8.6%
23
   4.4%
AEs leading to discontinuation from study
18
   4.3%
18
   3.4%
22
   5.3%
18
   3.4%
2.Primary Outcome
Title Number of Participants With Potentially Clinically Significant Abnormal Serum Chemistry Results
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 408 518 412 513
Measure Type: Count of Participants
Unit of Measure: Participants
27
   6.6%
26
   5.0%
11
   2.7%
23
   4.5%
3.Primary Outcome
Title Number of Participants With Potentially Clinically Significant Abnormal Hematology Results
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 408 518 412 513
Measure Type: Count of Participants
Unit of Measure: Participants
34
   8.3%
39
   7.5%
27
   6.6%
40
   7.8%
4.Primary Outcome
Title Number of Participants With Potentially Clinically Significant Abnormal Urinalysis Laboratory Tests Results
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 408 517 412 513
Measure Type: Count of Participants
Unit of Measure: Participants
128
  31.4%
170
  32.9%
120
  29.1%
146
  28.5%
5.Primary Outcome
Title Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Values
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 415 520 414 519
Measure Type: Count of Participants
Unit of Measure: Participants
20
   4.8%
33
   6.3%
24
   5.8%
40
   7.7%
6.Primary Outcome
Title Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 386 492 391 489
Measure Type: Count of Participants
Unit of Measure: Participants
Normal - Normal
239
  61.9%
295
  60.0%
230
  58.8%
296
  60.5%
Normal - Abnormal NCS
45
  11.7%
64
  13.0%
49
  12.5%
67
  13.7%
Normal - Abnormal CS
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.2%
Abnormal NCS - Normal
42
  10.9%
53
  10.8%
43
  11.0%
60
  12.3%
Abnormal NCS - Abnormal NCS
60
  15.5%
79
  16.1%
69
  17.6%
65
  13.3%
Abnormal NCS - Abnormal CS
0
   0.0%
1
   0.2%
0
   0.0%
0
   0.0%
Abnormal CS - Normal
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Abnormal CS - Abnormal NCS
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Abnormal CS - Abnormal CS
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
7.Primary Outcome
Title Number of Participants With Shift From Baseline to Endpoint in Coagulation Laboratory Test Results
Hide 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)
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 407 516 410 513
Measure Type: Count of Participants
Unit of Measure: Participants
PT Number Analyzed 407 participants 516 participants 410 participants 513 participants
Low-Low
0
   0.0%
0
   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
   0.0%
0
   0.0%
Normal-Low
1
   0.2%
3
   0.6%
3
   0.7%
2
   0.4%
Normal-Normal
370
  90.9%
465
  90.1%
374
  91.2%
451
  87.9%
Normal-High
10
   2.5%
10
   1.9%
14
   3.4%
14
   2.7%
High-Low
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
High-Normal
18
   4.4%
25
   4.8%
9
   2.2%
35
   6.8%
High-High
7
   1.7%
11
   2.1%
8
   2.0%
10
   1.9%
Prothrombin INR Number Analyzed 406 participants 516 participants 410 participants 513 participants
Low-Low
0
   0.0%
1
   0.2%
4
   1.0%
1
   0.2%
Low-Normal
11
   2.7%
11
   2.1%
11
   2.7%
9
   1.8%
Low-High
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Normal-Low
12
   3.0%
15
   2.9%
9
   2.2%
7
   1.4%
Normal-Normal
366
  90.1%
468
  90.7%
372
  90.7%
472
  92.0%
Normal-High
6
   1.5%
5
   1.0%
4
   1.0%
4
   0.8%
High-Low
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.2%
High-Normal
7
   1.7%
11
   2.1%
6
   1.5%
13
   2.5%
High-High
4
   1.0%
5
   1.0%
4
   1.0%
6
   1.2%
aPTT Number Analyzed 406 participants 516 participants 410 participants 513 participants
Low-Low
2
   0.5%
2
   0.4%
1
   0.2%
0
   0.0%
Low-Normal
4
   1.0%
1
   0.2%
7
   1.7%
7
   1.4%
Low-High
0
   0.0%
1
   0.2%
0
   0.0%
0
   0.0%
Normal-Low
3
   0.7%
11
   2.1%
7
   1.7%
10
   1.9%
Normal-Normal
341
  84.0%
423
  82.0%
334
  81.5%
414
  80.7%
Normal-High
14
   3.4%
18
   3.5%
19
   4.6%
22
   4.3%
High-Low
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.2%
High-Normal
26
   6.4%
43
   8.3%
26
   6.3%
37
   7.2%
High-High
16
   3.9%
17
   3.3%
16
   3.9%
22
   4.3%
8.Primary Outcome
Title Number of Participants With Injection Site Reactions
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 418 526 419 525
Measure Type: Count of Participants
Unit of Measure: Participants
Injection site induration
167
  40.0%
174
  33.1%
144
  34.4%
134
  25.5%
Injection site pain
149
  35.6%
156
  29.7%
135
  32.2%
140
  26.7%
Injection site erythema
130
  31.1%
144
  27.4%
99
  23.6%
124
  23.6%
Injection site haemorrhage
34
   8.1%
38
   7.2%
21
   5.0%
38
   7.2%
Injection site pruritus
31
   7.4%
43
   8.2%
17
   4.1%
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
   1.0%
3
   0.6%
Injection site rash
4
   1.0%
2
   0.4%
5
   1.2%
2
   0.4%
Injection site urticaria
4
   1.0%
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
   0.0%
1
   0.2%
0
   0.0%
1
   0.2%
Injection site haematoma
1
   0.2%
0
   0.0%
0
   0.0%
1
   0.2%
Injection site inflammation
0
   0.0%
1
   0.2%
1
   0.2%
0
   0.0%
Injection site discolouration
0
   0.0%
1
   0.2%
0
   0.0%
0
   0.0%
Injection site discomfort
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.2%
Injection site hypersensitivity
1
   0.2%
0
   0.0%
0
   0.0%
0
   0.0%
Injection site hypoaesthesia
1
   0.2%
1
   0.2%
0
   0.0%
0
   0.0%
Injection site irritation
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.2%
Injection site oedema
1
   0.2%
1
   0.2%
1
   0.2%
0
   0.0%
Injection site papule
1
   0.2%
0
   0.0%
0
   0.0%
0
   0.0%
Injection site paraesthesia
0
   0.0%
0
   0.0%
1
   0.2%
0
   0.0%
Injection site vesicles
0
   0.0%
1
   0.2%
1
   0.2%
0
   0.0%
Injection site pallor
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.2%
9.Primary Outcome
Title Number of Participants With Suicidal Ideation and Suicidal Behavior as Assessed by the Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 418 526 419 525
Measure Type: Count of Participants
Unit of Measure: Participants
Suicidal ideation
2
   0.5%
0
   0.0%
2
   0.5%
1
   0.2%
Suicidal attempt
0
   0.0%
0
   0.0%
1
   0.2%
0
   0.0%
10.Other Pre-specified Outcome
Title Change From Baseline in Monthly Average Number of Migraine Days During the 4-Week Period at Month 12
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 192 233 194 230 124 173 138 173
Mean (Standard Deviation)
Unit of Measure: 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)
11.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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 192 233 194 230 124 173 138 173
Mean (Standard Deviation)
Unit of Measure: 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)
12.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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 195 240 197 237 125 174 139 174
Measure Type: Number
Unit of Measure: percentage of participants
54 59 52 54 58 75 68 64
13.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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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).
Overall Number of Participants Analyzed 193 240 197 237 124 174 138 174
Measure Type: Number
Unit of Measure: percentage of participants
56 62 54 54 58 72 67 68
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
Hide 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 (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/418 (0.00%)      0/526 (0.00%)      1/419 (0.24%)      0/525 (0.00%)    
Hide 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 (6.46%)      29/526 (5.51%)      36/419 (8.59%)      23/525 (4.38%)    
Blood and lymphatic system disorders         
Anaemia † 1  0/418 (0.00%)  0 1/526 (0.19%)  1 0/419 (0.00%)  0 0/525 (0.00%)  0
Iron deficiency anaemia † 1  0/418 (0.00%)  0 1/526 (0.19%)  1 0/419 (0.00%)  0 0/525 (0.00%)  0
Cardiac disorders         
Atrial fibrillation † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 1/419 (0.24%)  2 0/525 (0.00%)  0
Pericarditis † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 0/419 (0.00%)  0 1/525 (0.19%)  1
Sinus tachycardia † 1  0/418 (0.00%)  0 1/526 (0.19%)  1 0/419 (0.00%)  0 0/525 (0.00%)  0
Congenital, familial and genetic disorders         
Arteriovenous malformation † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 0/419 (0.00%)  0 1/525 (0.19%)  1
Cerebrovascular arteriovenous malformation † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 0/419 (0.00%)  0 1/525 (0.19%)  1
Congenital cyst † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 0/419 (0.00%)  0 1/525 (0.19%)  1
Congenital cystic disease of liver † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 1/419 (0.24%)  1 0/525 (0.00%)  0
Hereditary haemochromatosis † 1  1/418 (0.24%)  1 0/526 (0.00%)  0 0/419 (0.00%)  0 0/525 (0.00%)  0
Ear and labyrinth disorders         
Sudden hearing loss † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 0/419 (0.00%)  0 1/525 (0.19%)  1
Endocrine disorders         
Hyperthyroidism † 1  0/418 (0.00%)  0 1/526 (0.19%)  1 0/419 (0.00%)  0 0/525 (0.00%)  0
Eye disorders         
Macular degeneration † 1  0/418 (0.00%)  0 1/526 (0.19%)  1 0/419 (0.00%)  0 0/525 (0.00%)  0
Retinal detachment † 1  1/418 (0.24%)  1 1/526 (0.19%)  1 0/419 (0.00%)  0 0/525 (0.00%)  0
Retinal tear † 1  0/418 (0.00%)  0 1/526 (0.19%)  1 1/419 (0.24%)  1 1/525 (0.19%)  1
Gastrointestinal disorders         
Abdominal pain † 1  2/418 (0.48%)  2 0/526 (0.00%)  0 0/419 (0.00%)  0 0/525 (0.00%)  0
Barrett's oesophagus † 1  0/418 (0.00%)  0 1/526 (0.19%)  1 0/419 (0.00%)  0 0/525 (0.00%)  0
Gastric ulcer † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 1/419 (0.24%)  1 0/525 (0.00%)  0
Haemorrhoidal haemorrhage † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 0/419 (0.00%)  0 1/525 (0.19%)  1
Ileal stenosis † 1  1/418 (0.24%)  1 0/526 (0.00%)  0 1/419 (0.24%)  1 0/525 (0.00%)  0
Small intestinal obstruction † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 1/419 (0.24%)  1 0/525 (0.00%)  0
General disorders         
Chest pain † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 0/419 (0.00%)  0 1/525 (0.19%)  1
Multi-organ failure † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 1/419 (0.24%)  1 0/525 (0.00%)  0
Hepatobiliary disorders         
Cholecystitis † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 1/419 (0.24%)  1 0/525 (0.00%)  0
Cholecystitis acute † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 0/419 (0.00%)  0 1/525 (0.19%)  1
Cholecystitis chronic † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 1/419 (0.24%)  1 0/525 (0.00%)  0
Cholelithiasis † 1  0/418 (0.00%)  0 1/526 (0.19%)  1 1/419 (0.24%)  1 0/525 (0.00%)  0
Hepatic cirrhosis † 1  1/418 (0.24%)  1 0/526 (0.00%)  0 0/419 (0.00%)  0 0/525 (0.00%)  0
Hepatitis alcoholic † 1  1/418 (0.24%)  1 0/526 (0.00%)  0 0/419 (0.00%)  0 0/525 (0.00%)  0
Immune system disorders         
Allergy to arthropod sting † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 0/419 (0.00%)  0 1/525 (0.19%)  1
Infections and infestations         
Abdominal abscess † 1  1/418 (0.24%)  1 0/526 (0.00%)  0 0/419 (0.00%)  0 0/525 (0.00%)  0
Appendicitis † 1  2/418 (0.48%)  2 0/526 (0.00%)  0 0/419 (0.00%)  0 0/525 (0.00%)  0
Bacterial sepsis † 1  1/418 (0.24%)  1 0/526 (0.00%)  0 0/419 (0.00%)  0 0/525 (0.00%)  0
Diverticulitis † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 1/419 (0.24%)  1 0/525 (0.00%)  0
Enteritis infectious † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 1/419 (0.24%)  1 0/525 (0.00%)  0
Meningitis aseptic † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 1/419 (0.24%)  1 0/525 (0.00%)  0
Peritonitis † 1  1/418 (0.24%)  1 0/526 (0.00%)  0 0/419 (0.00%)  0 0/525 (0.00%)  0
Petrositis † 1  0/418 (0.00%)  0 1/526 (0.19%)  1 0/419 (0.00%)  0 0/525 (0.00%)  0
Pneumonia † 1  1/418 (0.24%)  1 1/526 (0.19%)  1 0/419 (0.00%)  0 0/525 (0.00%)  0
Post procedural infection † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 1/419 (0.24%)  1 0/525 (0.00%)  0
Urinary tract infection † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 2/419 (0.48%)  2 0/525 (0.00%)  0
Injury, poisoning and procedural complications         
Abdominal wound dehiscence † 1  1/418 (0.24%)  1 0/526 (0.00%)  0 0/419 (0.00%)  0 0/525 (0.00%)  0
Fall † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 0/419 (0.00%)  0 1/525 (0.19%)  1
Intentional overdose † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 1/419 (0.24%)  1 0/525 (0.00%)  0
Pelvic fracture † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 0/419 (0.00%)  0 1/525 (0.19%)  1
Post procedural haemorrhage † 1  0/418 (0.00%)  0 1/526 (0.19%)  1 1/419 (0.24%)  1 0/525 (0.00%)  0
Procedural pain † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 1/419 (0.24%)  1 0/525 (0.00%)  0
Investigations         
Ammonia increased † 1  1/418 (0.24%)  1 0/526 (0.00%)  0 0/419 (0.00%)  0 0/525 (0.00%)  0
Metabolism and nutrition disorders         
Dehydration † 1  1/418 (0.24%)  1 0/526 (0.00%)  0 0/419 (0.00%)  0 0/525 (0.00%)  0
Hypoglycaemia † 1  1/418 (0.24%)  1 0/526 (0.00%)  0 0/419 (0.00%)  0 0/525 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Fibromyalgia † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 1/419 (0.24%)  1 0/525 (0.00%)  0
Lumbar spinal stenosis † 1  0/418 (0.00%)  0 1/526 (0.19%)  1 1/419 (0.24%)  1 0/525 (0.00%)  0
Musculoskeletal chest pain † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 0/419 (0.00%)  0 1/525 (0.19%)  1
Osteoarthritis † 1  1/418 (0.24%)  1 1/526 (0.19%)  1 0/419 (0.00%)  0 1/525 (0.19%)  1
Osteochondrosis † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 0/419 (0.00%)  0 1/525 (0.19%)  1
Periarthritis † 1  0/418 (0.00%)  0 1/526 (0.19%)  1 0/419 (0.00%)  0 0/525 (0.00%)  0
Spinal column stenosis † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 0/419 (0.00%)  0 1/525 (0.19%)  1
Spinal osteoarthritis † 1  1/418 (0.24%)  1 0/526 (0.00%)  0 0/419 (0.00%)  0 0/525 (0.00%)  0
Spinal pain † 1  0/418 (0.00%)  0 1/526 (0.19%)  1 0/419 (0.00%)  0 0/525 (0.00%)  0
Synovial cyst † 1  0/418 (0.00%)  0 1/526 (0.19%)  1 0/419 (0.00%)  0 0/525 (0.00%)  0
Vertebral osteophyte † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 0/419 (0.00%)  0 1/525 (0.19%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Basal cell carcinoma † 1  0/418 (0.00%)  0 2/526 (0.38%)  2 2/419 (0.48%)  3 0/525 (0.00%)  0
Benign breast neoplasm † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 1/419 (0.24%)  1 0/525 (0.00%)  0
Breast cancer stage III † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 1/419 (0.24%)  1 0/525 (0.00%)  0
Endometrial cancer † 1 [1]  0/365 (0.00%)  0 0/454 (0.00%)  0 1/369 (0.27%)  1 0/457 (0.00%)  0
High grade B-cell lymphoma Burkitt-like lymphoma † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 1/419 (0.24%)  1 0/525 (0.00%)  0
Intraductal proliferative breast lesion † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 1/419 (0.24%)  1 0/525 (0.00%)  0
Malignant melanoma † 1  1/418 (0.24%)  1 0/526 (0.00%)  0 1/419 (0.24%)  1 1/525 (0.19%)  1
Meningioma † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 1/419 (0.24%)  1 0/525 (0.00%)  0
Papillary thyroid cancer † 1  0/418 (0.00%)  0 1/526 (0.19%)  1 0/419 (0.00%)  0 1/525 (0.19%)  1
Phyllodes tumour † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 1/419 (0.24%)  1 0/525 (0.00%)  0
Pituitary tumour † 1  0/418 (0.00%)  0 1/526 (0.19%)  1 0/419 (0.00%)  0 0/525 (0.00%)  0
Prostate cancer † 1 [2]  0/54 (0.00%)  0 0/72 (0.00%)  0 1/51 (1.96%)  1 0/68 (0.00%)  0
Superficial spreading melanoma stage unspecified † 1  0/418 (0.00%)  0 1/526 (0.19%)  1 0/419 (0.00%)  0 0/525 (0.00%)  0
Thyroid cancer † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 0/419 (0.00%)  0 1/525 (0.19%)  1
Nervous system disorders         
Carpal tunnel syndrome † 1  0/418 (0.00%)  0 1/526 (0.19%)  1 0/419 (0.00%)  0 0/525 (0.00%)  0
Central nervous system lesion † 1  1/418 (0.24%)  1 0/526 (0.00%)  0 0/419 (0.00%)  0 0/525 (0.00%)  0
Cerebrovascular accident † 1  1/418 (0.24%)  1 0/526 (0.00%)  0 1/419 (0.24%)  1 1/525 (0.19%)  1
Cluster headache † 1  0/418 (0.00%)  0 1/526 (0.19%)  1 0/419 (0.00%)  0 0/525 (0.00%)  0
Hypoaesthesia † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 0/419 (0.00%)  0 1/525 (0.19%)  1
Intracranial aneurysm † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 1/419 (0.24%)  1 1/525 (0.19%)  1
Migraine † 1  0/418 (0.00%)  0 3/526 (0.57%)  4 0/419 (0.00%)  0 0/525 (0.00%)  0
Myasthenia gravis † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 1/419 (0.24%)  1 0/525 (0.00%)  0
Nerve compression † 1  0/418 (0.00%)  0 1/526 (0.19%)  3 0/419 (0.00%)  0 0/525 (0.00%)  0
Parkinson's disease † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 1/419 (0.24%)  1 0/525 (0.00%)  0
Parkinsonism † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 1/419 (0.24%)  1 0/525 (0.00%)  0
Perineurial cyst † 1  1/418 (0.24%)  1 0/526 (0.00%)  0 0/419 (0.00%)  0 0/525 (0.00%)  0
Primary progressive multiple sclerosis † 1  1/418 (0.24%)  1 0/526 (0.00%)  0 0/419 (0.00%)  0 0/525 (0.00%)  0
Sciatica † 1  0/418 (0.00%)  0 1/526 (0.19%)  1 0/419 (0.00%)  0 0/525 (0.00%)  0
Status migrainosus † 1  2/418 (0.48%)  4 1/526 (0.19%)  1 1/419 (0.24%)  1 0/525 (0.00%)  0
Transient global amnesia † 1  0/418 (0.00%)  0 1/526 (0.19%)  1 0/419 (0.00%)  0 0/525 (0.00%)  0
Pregnancy, puerperium and perinatal conditions         
Abortion spontaneous † 1 [1]  0/365 (0.00%)  0 1/454 (0.22%)  1 0/369 (0.00%)  0 0/457 (0.00%)  0
Foetal death † 1 [1]  0/365 (0.00%)  0 1/454 (0.22%)  1 0/369 (0.00%)  0 0/457 (0.00%)  0
Premature baby † 1 [1]  1/365 (0.27%)  1 0/454 (0.00%)  0 0/369 (0.00%)  0 0/457 (0.00%)  0
Premature separation of placenta † 1 [1]  0/365 (0.00%)  0 0/454 (0.00%)  0 1/369 (0.27%)  1 0/457 (0.00%)  0
Psychiatric disorders         
Adjustment disorder with mixed disturbance of emotion and conduct † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 1/419 (0.24%)  1 0/525 (0.00%)  0
Anxiety † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 0/419 (0.00%)  0 1/525 (0.19%)  1
Suicidal ideation † 1  1/418 (0.24%)  1 0/526 (0.00%)  0 1/419 (0.24%)  1 0/525 (0.00%)  0
Suicide attempt † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 1/419 (0.24%)  1 0/525 (0.00%)  0
Renal and urinary disorders         
Urinary retention † 1  0/418 (0.00%)  0 1/526 (0.19%)  1 0/419 (0.00%)  0 0/525 (0.00%)  0
Reproductive system and breast disorders         
Endometriosis † 1 [1]  1/365 (0.27%)  1 0/454 (0.00%)  0 0/369 (0.00%)  0 0/457 (0.00%)  0
Haemorrhagic ovarian cyst † 1 [1]  0/365 (0.00%)  0 1/454 (0.22%)  1 0/369 (0.00%)  0 0/457 (0.00%)  0
Ovarian cyst † 1 [1]  1/365 (0.27%)  1 0/454 (0.00%)  0 0/369 (0.00%)  0 0/457 (0.00%)  0
Ovarian cyst ruptured † 1 [1]  1/365 (0.27%)  1 0/454 (0.00%)  0 0/369 (0.00%)  0 1/457 (0.22%)  1
Ovarian mass † 1 [1]  1/365 (0.27%)  1 0/454 (0.00%)  0 0/369 (0.00%)  0 0/457 (0.00%)  0
Uterine haemorrhage † 1 [1]  1/365 (0.27%)  1 0/457 (0.00%)  0 0/369 (0.00%)  0 0/457 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Acute respiratory failure † 1  1/418 (0.24%)  1 0/526 (0.00%)  0 0/419 (0.00%)  0 0/525 (0.00%)  0
Asthma † 1  1/418 (0.24%)  1 0/526 (0.00%)  0 0/419 (0.00%)  0 0/525 (0.00%)  0
Bronchospasm † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 0/419 (0.00%)  0 1/525 (0.19%)  1
Laryngeal oedema † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 0/419 (0.00%)  0 1/525 (0.19%)  1
Lung consolidation † 1  0/418 (0.00%)  0 1/526 (0.19%)  1 0/419 (0.00%)  0 0/525 (0.00%)  0
Pneumothorax † 1  0/418 (0.00%)  0 1/526 (0.19%)  1 0/419 (0.00%)  0 0/525 (0.00%)  0
Pulmonary embolism † 1  1/418 (0.24%)  1 0/526 (0.00%)  0 0/419 (0.00%)  0 0/525 (0.00%)  0
Pulmonary mass † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 1/419 (0.24%)  1 0/525 (0.00%)  0
Surgical and medical procedures         
Salpingo-oophorectomy † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 0/419 (0.00%)  0 1/525 (0.19%)  1
Vascular disorders         
Deep vein thrombosis † 1  1/418 (0.24%)  1 0/526 (0.00%)  0 1/419 (0.24%)  1 0/525 (0.00%)  0
Hypertension † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 1/419 (0.24%)  1 0/525 (0.00%)  0
Hypovolaemic shock † 1  0/418 (0.00%)  0 0/526 (0.00%)  0 1/419 (0.24%)  1 0/525 (0.00%)  0
Venous thrombosis limb † 1  0/418 (0.00%)  0 1/526 (0.19%)  1 0/419 (0.00%)  0 0/525 (0.00%)  0
1
Term from vocabulary, MedDRA 18.1
†
Indicates events were collected by systematic assessment
[1]
This is a gender-specific AE. Only female participants were at risk.
[2]
This is a gender-specific AE. Only male participants were at risk.
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
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 (71.77%)      367/526 (69.77%)      284/419 (67.78%)      329/525 (62.67%)    
General disorders         
Injection site erythema † 1  130/418 (31.10%)  430 144/526 (27.38%)  446 99/419 (23.63%)  284 124/525 (23.62%)  386
Injection site haemorrhage † 1  34/418 (8.13%)  43 38/526 (7.22%)  66 21/419 (5.01%)  38 38/525 (7.24%)  62
Injection site induration † 1  167/418 (39.95%)  717 174/526 (33.08%)  753 144/419 (34.37%)  543 134/525 (25.52%)  666
Injection site pain † 1  149/418 (35.65%)  980 156/526 (29.66%)  982 135/419 (32.22%)  981 140/525 (26.67%)  811
Injection site pruritus † 1  31/418 (7.42%)  101 43/526 (8.17%)  107 17/419 (4.06%)  64 24/525 (4.57%)  64
Infections and infestations         
Bronchitis † 1  24/418 (5.74%)  25 15/526 (2.85%)  16 20/419 (4.77%)  22 24/525 (4.57%)  26
Influenza † 1  14/418 (3.35%)  18 27/526 (5.13%)  29 8/419 (1.91%)  9 25/525 (4.76%)  28
Nasopharyngitis † 1  43/418 (10.29%)  61 69/526 (13.12%)  107 37/419 (8.83%)  58 68/525 (12.95%)  108
Sinusitis † 1  30/418 (7.18%)  40 27/526 (5.13%)  28 28/419 (6.68%)  35 31/525 (5.90%)  38
Upper respiratory tract infection † 1  55/418 (13.16%)  65 62/526 (11.79%)  76 73/419 (17.42%)  97 63/525 (12.00%)  78
Urinary tract infection † 1  25/418 (5.98%)  38 27/526 (5.13%)  43 26/419 (6.21%)  29 33/525 (6.29%)  37
1
Term from vocabulary, MedDRA 18.1
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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
Layout table for Results Point of Contact information
Name/Title: Director, Clinical Research
Organization: Teva Branded Pharmaceutical Products, R&D Inc.
Phone: 1-888-483-8279
EMail: USMedInfo@tevapharm.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Teva Pharmaceutical Industries ( Teva Branded Pharmaceutical Products R&D, Inc. )
ClinicalTrials.gov Identifier: NCT02638103    
Other Study ID Numbers: TV48125-CNS-30051
2015-004550-18 ( EudraCT Number )
First Submitted: December 18, 2015
First Posted: December 22, 2015
Results First Submitted: June 5, 2019
Results First Posted: August 28, 2019
Last Update Posted: February 28, 2020