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Trial record 54 of 231 for:    CALCITONIN SALMON

Efficacy and Safety of 2 Dose Regimens of TEV-48125 Versus Placebo for the Preventive Treatment of Episodic Migraine

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02629861
Recruitment Status : Completed
First Posted : December 14, 2015
Results First Posted : November 8, 2018
Last Update Posted : November 8, 2018
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 875
Recruitment Details  
Pre-assignment Details A total of 2995 patients with migraine provided written informed consent. Of the 2995 patients screened, 875 met entry criteria, including diagnostic criteria for episodic migraine (EM) and diary compliance during the run-in period, and were randomized into this study from 123 study centers by 123 investigators.
Arm/Group Title Placebo Fremanezumab 675 mg/Placebo/Placebo Fremanezumab 225/225/225 mg
Hide Arm/Group Description Participants randomized to receive placebo received three 1.5-mL placebo injections on Day 0, and a single 1.5-mL placebo injection on Days 28 and 56. Participants randomized to receive fremanezumab 675 mg/placebo/placebo received 675 mg of fremanezumab as 3 injections (225 mg/1.5 mL) on Day 0, and placebo as a single 1.5-mL injection on Days 28 and 56. Participants randomized to receive fremanezumab 225/225/225 mg received 1 active injection (225 mg/1.5 mL) on Days 0, 28 and 56.
Period Title: Overall Study
Started 294 291 290
Intent to Treat (ITT) 294 291 290
Safety Population 294 291 289
Full Analysis Set 290 288 287
Completed 265 264 262
Not Completed 29 27 28
Reason Not Completed
Adverse Event             7             5             4
Withdrawal by Subject             5             8             13
Protocol Violation             2             3             7
Lost to Follow-up             12             9             4
Not specified             1             1             0
Pregnancy             2             1             0
Arm/Group Title Placebo Fremanezumab 675 mg/Placebo/Placebo Fremanezumab 225/225/225 mg Total
Hide Arm/Group Description Participants randomized to receive placebo received three 1.5-mL placebo injections on Day 0, and a single 1.5-mL placebo injection on Days 28 and 56. Participants randomized to receive fremanezumab 675 mg/placebo/placebo received 675 mg of fremanezumab as 3 injections (225 mg/1.5 mL) on Day 0, and placebo as a single 1.5-mL injection on Days 28 and 56. Participants randomized to receive fremanezumab 225/225/225 mg received 1 active injection (225 mg/1.5 mL) on Days 0, 28 and 56. Total of all reporting groups
Overall Number of Baseline Participants 294 291 290 875
Hide Baseline Analysis Population Description
Intent to treat (ITT) population
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 294 participants 291 participants 290 participants 875 participants
41.3  (12.04) 41.1  (11.41) 42.9  (12.67) 41.8  (12.06)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 294 participants 291 participants 290 participants 875 participants
18-45 years
184
  62.6%
178
  61.2%
163
  56.2%
525
  60.0%
46-65 years
102
  34.7%
110
  37.8%
120
  41.4%
332
  37.9%
>65 years
8
   2.7%
3
   1.0%
7
   2.4%
18
   2.1%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 294 participants 291 participants 290 participants 875 participants
Female
247
  84.0%
251
  86.3%
244
  84.1%
742
  84.8%
Male
47
  16.0%
40
  13.7%
46
  15.9%
133
  15.2%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 294 participants 291 participants 290 participants 875 participants
White
225
  76.5%
232
  79.7%
243
  83.8%
700
  80.0%
Black
40
  13.6%
28
   9.6%
18
   6.2%
86
   9.8%
Asian
25
   8.5%
27
   9.3%
25
   8.6%
77
   8.8%
American Indian or Alaska Native
0
   0.0%
1
   0.3%
3
   1.0%
4
   0.5%
Native Hawaiian or Other Pacific Islander
0
   0.0%
1
   0.3%
0
   0.0%
1
   0.1%
Other
4
   1.4%
2
   0.7%
1
   0.3%
7
   0.8%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 294 participants 291 participants 290 participants 875 participants
Not Hispanic or Latino
267
  90.8%
251
  86.3%
252
  86.9%
770
  88.0%
Hispanic or Latino
27
   9.2%
39
  13.4%
37
  12.8%
103
  11.8%
Unknown
0
   0.0%
1
   0.3%
1
   0.3%
2
   0.2%
Preventive Medication Use During Baseline Period   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 294 participants 291 participants 290 participants 875 participants
Yes
62
  21.1%
58
  19.9%
62
  21.4%
182
  20.8%
No
232
  78.9%
233
  80.1%
228
  78.6%
693
  79.2%
[1]
Measure Description: Eligible patients entered a 28-day run-in/baseline period during which headache information was captured daily throughout study participation using the electronic headache diary device. During randomization, patients were stratified based on sex, country, and baseline preventive migraine medication use (yes, no) to ensure balance for the covariates.
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 294 participants 291 participants 290 participants 875 participants
75.3  (16.01) 74.2  (15.42) 72.1  (15.77) 73.9  (15.77)
Time Since Initial Migraine Diagnosis  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 294 participants 291 participants 290 participants 875 participants
19.9  (11.87) 20.0  (12.14) 20.7  (12.85) 20.2  (12.28)
Total Number of Headache Days of Any Duration And Any Severity During the 28 Day Baseline Period   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Days
Number Analyzed 293 participants 291 participants 288 participants 872 participants
11.2  (2.45) 11.1  (2.42) 11.0  (2.49) 11.1  (2.45)
[1]
Measure Description: Eligible patients entered a 28-day run-in/baseline period during which headache information was captured daily throughout study participation using the electronic headache diary device.
[2]
Measure Analysis Population Description: Three participants did not capture data in the e-diary.
Number of Migraine Days   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Days
Number Analyzed 293 participants 291 participants 288 participants 872 participants
9.1  (2.65) 9.3  (2.65) 8.9  (2.63) 9.1  (2.64)
[1]
Measure Description: Eligible patients entered a 28-day run-in/baseline period during which headache information was captured daily throughout study participation using the electronic headache diary device. Migraine headaches are as defined in The International Classification of Headache Disorders 3rd edition (ICHD-3).
[2]
Measure Analysis Population Description: Three participants did not capture data in the e-diary.
Number of Headache Days of At Least Moderate Severity   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Days
Number Analyzed 293 participants 291 participants 288 participants 872 participants
6.9  (3.12) 7.2  (3.14) 6.8  (2.90) 7.0  (3.06)
[1]
Measure Description: Eligible patients entered a 28-day run-in/baseline period during which headache information was captured daily throughout study participation using the electronic headache diary device. Headache severity was subjectively rated by the patient as mild, moderate or severe.
[2]
Measure Analysis Population Description: Three participants did not capture data in the e-diary.
Number of Days of Use of Any Acute Headache Medications   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Days
Number Analyzed 293 participants 291 participants 288 participants 872 participants
7.7  (3.60) 7.8  (3.74) 7.7  (3.37) 7.8  (3.57)
[1]
Measure Description: Eligible patients entered a 28-day run-in/baseline period during which headache information (including information about use of headache medications) was captured daily throughout study participation using the electronic headache diary device.
[2]
Measure Analysis Population Description: Three participants did not capture data in the e-diary.
Migraine Disability Assessment (MIDAS) Total Score   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 290 participants 287 participants 287 participants 864 participants
37.3  (27.59) 41.7  (32.96) 38.0  (33.19) 39.0  (31.36)
[1]
Measure Description: The MIDAS questionnaire is a 5-item instrument developed to assess headache-related disability based on lost days of activity in 3 domains (work, household work, and nonwork) over the previous 3 months. The total score, ie, the sum of the # lost days answered for the first 5 questions, is used for grading of disability, with scores of 0-5 = grade 1 (little or no disability), 6-10 =grade 2 (mild disability), 11-20 = grade 3 (moderate disability), and ≥21 interpreted as grade 4 (severe disability).
[2]
Measure Analysis Population Description: Eleven participants did not capture data in the e-diary.
1.Primary Outcome
Title Change From Baseline in the Monthly Average Number of Migraine Days During the 12-Week Period After the First Dose of Study Drug
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 of a headache endorsing criteria for migraine with or without aura - a calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache endorsing criteria for probable migraine, a migraine subtype where only 1 migraine criterion is 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 are derived and normalized to 28 days equivalent by the following formula: (# days of efficacy variable over relevant period / # days with assessments recorded in the e-diary over the relevant period) * 28. The change is calculated as postbaseline value – baseline value.
Time Frame Baseline (Days -28 to Day -1), Treatment (Days 1 – Week 12)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Fremanezumab 675 mg/Placebo/Placebo Fremanezumab 225/225/225 mg
Hide Arm/Group Description:
Participants randomized to receive placebo received three 1.5-mL placebo injections on Day 0, and a single 1.5-mL placebo injection on Days 28 and 56.
Participants randomized to receive fremanezumab 675 mg/placebo/placebo received 675 mg of fremanezumab as 3 injections (225 mg/1.5 mL) on Day 0, and placebo as a single 1.5-mL injection on Days 28 and 56.
Participants randomized to receive fremanezumab 225/225/225 mg received 1 active injection (225 mg/1.5 mL) on Days 0, 28 and 56.
Overall Number of Participants Analyzed 290 288 287
Median (Inter-Quartile Range)
Unit of Measure: days
-2.7
(-4.7 to -0.5)
-4.0
(-6.4 to -1.9)
-4.2
(-6.2 to -2.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Fremanezumab 675 mg/Placebo/Placebo
Comments Due to the deviation from the normal distribution assumption of the data, the primary analysis was conducted using the Wilcoxon rank-sum test as outlined in the SAP.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments 0.05 level of significance
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Fremanezumab 225/225/225 mg
Comments Due to the deviation from the normal distribution assumption of the data, the primary analysis was conducted using the Wilcoxon rank-sum test as outlined in the SAP.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments 0.05 level of significance
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
2.Primary Outcome
Title Participants With Adverse Events
Hide Description An adverse event was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an AE which prevents usual activities. Relationship of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, 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 the patient and required medical intervention to prevent the previously listed serious outcomes.
Time Frame Day 1 to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Placebo Fremanezumab 675 mg/Placebo/Placebo Fremanezumab 225/225/225 mg
Hide Arm/Group Description:
Participants randomized to receive placebo received three 1.5-mL placebo injections on Day 0, and a single 1.5-mL placebo injection on Days 28 and 56.
Participants randomized to receive fremanezumab 675 mg/placebo/placebo received 675 mg of fremanezumab as 3 injections (225 mg/1.5 mL) on Day 0, and placebo as a single 1.5-mL injection on Days 28 and 56.
Participants randomized to receive fremanezumab 225/225/225 mg received 1 active injection (225 mg/1.5 mL) on Days 0, 28 and 56.
Overall Number of Participants Analyzed 293 291 290
Measure Type: Count of Participants
Unit of Measure: Participants
Any AEs
171
  58.4%
193
  66.3%
192
  66.2%
Severe AEs
11
   3.8%
16
   5.5%
10
   3.4%
Treatment-related AEs
109
  37.2%
137
  47.1%
138
  47.6%
Serious adverse events
7
   2.4%
3
   1.0%
3
   1.0%
Deaths
0
   0.0%
1
   0.3%
0
   0.0%
Discontinued from study due to AE
5
   1.7%
5
   1.7%
5
   1.7%
3.Secondary Outcome
Title Percentage of Participants With At Least 50% Reduction In Monthly Average Number of Migraine Days During the 12-Week Period After the First Dose of Study Drug
Hide Description Responder rates were defined as the percentage of total subjects who reached at least a 50% reduction in the monthly average of headache days (as subjectively reported by participants in the study diary) of at least moderate severity relative to the baseline period. For the overall analysis (Month 1-3), patients who discontinued early were considered nonresponders. Monthly averages are derived and normalized to 28 days equivalent by the following formula: (# days of efficacy variable over relevant period / # days with assessments recorded in the e-diary over the relevant period) * 28. The percentage reduction in monthly average is calculated as: ((baseline value - postbaseline value) / baseline value) * 100
Time Frame Baseline (Days -28 to Day -1), Treatment Month 1, Month 2, Month 3, Month 1-3 (Days 1 – Week 12)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Fremanezumab 675 mg/Placebo/Placebo Fremanezumab 225/225/225 mg
Hide Arm/Group Description:
Participants randomized to receive placebo received three 1.5-mL placebo injections on Day 0, and a single 1.5-mL placebo injection on Days 28 and 56.
Participants randomized to receive fremanezumab 675 mg/placebo/placebo received 675 mg of fremanezumab as 3 injections (225 mg/1.5 mL) on Day 0, and placebo as a single 1.5-mL injection on Days 28 and 56.
Participants randomized to receive fremanezumab 225/225/225 mg received 1 active injection (225 mg/1.5 mL) on Days 0, 28 and 56.
Overall Number of Participants Analyzed 290 288 287
Measure Type: Number
Unit of Measure: percentage of participants
Month 1 Number Analyzed 290 participants 288 participants 287 participants
25.2 44.1 47.0
Month 2 Number Analyzed 274 participants 274 participants 274 participants
34.8 46.9 48.4
Month 3 Number Analyzed 268 participants 269 participants 263 participants
37.2 49.0 51.2
Overall - Months 1-3 Number Analyzed 290 participants 288 participants 287 participants
27.9 44.4 47.7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Fremanezumab 675 mg/Placebo/Placebo
Comments Month 1 P-value based on Cochran-Mantel-Haenszel test stratified by baseline preventive medication use.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments 0.05 level of significance
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Fremanezumab 225/225/225 mg
Comments Month 1 P-value based on Cochran-Mantel-Haenszel test stratified by baseline preventive medication use.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments 0.05 level of significance
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Fremanezumab 675 mg/Placebo/Placebo
Comments Month 2 P-value based on Cochran-Mantel-Haenszel test stratified by baseline preventive medication use.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0032
Comments 0.05 level of significance
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Fremanezumab 225/225/225 mg
Comments Month 2 P-value based on Cochran-Mantel-Haenszel test stratified by baseline preventive medication use.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0010
Comments 0.05 level of significance
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Fremanezumab 675 mg/Placebo/Placebo
Comments Month 3 P-value based on Cochran-Mantel-Haenszel test stratified by baseline preventive medication use.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0048
Comments 0.05 level of significance
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Fremanezumab 225/225/225 mg
Comments Month 3 P-value based on Cochran-Mantel-Haenszel test stratified by baseline preventive medication use.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments 0.05 level of significance
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, Fremanezumab 675 mg/Placebo/Placebo
Comments Overall P-value based on Cochran-Mantel-Haenszel test stratified by baseline preventive medication use.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments 0.05 level of significance
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, Fremanezumab 225/225/225 mg
Comments Overall P-value based on Cochran-Mantel-Haenszel test stratified by baseline preventive medication use.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments 0.05 level of significance
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in the Monthly Average Number of Days of Use of Any Acute Headache Medicine During the 12 Week Period After the First Dose of Study Drug
Hide Description Patients recorded any migraine medications (name of drug, number of tablets/capsules, and the dose in milligrams per tablet/capsule) taken on each day in their electronic headache diary device. Acute migraine-specific medication included triptans or ergots. Monthly averages are derived and normalized to 28 days equivalent by the following formula: (# days of efficacy variable over relevant period / # days with assessments recorded in the e-diary over the relevant period) * 28. The change is calculated as postbaseline value – baseline value.
Time Frame Baseline (Days -28 to Day -1), Treatment (Days 1 – Week 12)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Fremanezumab 675 mg/Placebo/Placebo Fremanezumab 225/225/225 mg
Hide Arm/Group Description:
Participants randomized to receive placebo received three 1.5-mL placebo injections on Day 0, and a single 1.5-mL placebo injection on Days 28 and 56.
Participants randomized to receive fremanezumab 675 mg/placebo/placebo received 675 mg of fremanezumab as 3 injections (225 mg/1.5 mL) on Day 0, and placebo as a single 1.5-mL injection on Days 28 and 56.
Participants randomized to receive fremanezumab 225/225/225 mg received 1 active injection (225 mg/1.5 mL) on Days 0, 28 and 56.
Overall Number of Participants Analyzed 290 288 287
Median (Inter-Quartile Range)
Unit of Measure: days
-1.7
(-4.0 to 0.0)
-3.0
(-5.6 to -0.8)
-3.2
(-5.2 to -1.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Fremanezumab 675 mg/Placebo/Placebo
Comments Due to the deviation from the normal distribution assumption of the data, the Wilcoxon rank-sum test was conducted as the primary analysis for each active treatment group and placebo treatment group for this endpoint
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments 0.05 level of significance
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Fremanezumab 225/225/225 mg
Comments Due to the deviation from the normal distribution assumption of the data, the Wilcoxon rank-sum test was conducted as the primary analysis for each active treatment group and placebo treatment group for this endpoint
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments 0.05 level of significance
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in the Number of Migraine Days During the 4 Week Period After the First Dose of Study Drug
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 of a headache endorsing criteria for migraine with or without aura - a calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache endorsing criteria for probable migraine, a migraine subtype where only 1 migraine criterion is 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 are derived and normalized to 28 days equivalent by the following formula: (# days of efficacy variable over relevant period / # days with assessments recorded in the e-diary over the relevant period) * 28. The change is calculated as postbaseline value – baseline value.
Time Frame Baseline (Days -28 to Day -1), Treatment (Days 1 – Week 4)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; includes participants with observations
Arm/Group Title Placebo Fremanezumab 675 mg/Placebo/Placebo Fremanezumab 225/225/225 mg
Hide Arm/Group Description:
Participants randomized to receive placebo received three 1.5-mL placebo injections on Day 0, and a single 1.5-mL placebo injection on Days 28 and 56.
Participants randomized to receive fremanezumab 675 mg/placebo/placebo received 675 mg of fremanezumab as 3 injections (225 mg/1.5 mL) on Day 0, and placebo as a single 1.5-mL injection on Days 28 and 56.
Participants randomized to receive fremanezumab 225/225/225 mg received 1 active injection (225 mg/1.5 mL) on Days 0, 28 and 56.
Overall Number of Participants Analyzed 290 285 286
Median (Inter-Quartile Range)
Unit of Measure: days
-2.0
(-4.2 to 0.5)
-4.0
(-6.2 to -1.3)
-4.0
(-6.1 to -1.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Fremanezumab 675 mg/Placebo/Placebo
Comments Due to the deviation from the normal distribution assumption of the data, the Wilcoxon rank-sum test was conducted as the primary analysis for each active treatment group and placebo treatment group for this endpoint
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments 0.05 level of significance
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Fremanezumab 225/225/225 mg
Comments Due to the deviation from the normal distribution assumption of the data, the Wilcoxon rank-sum test was conducted as the primary analysis for each active treatment group and placebo treatment group for this endpoint
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments 0.05 level of significance
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline in the Monthly Average Number of Migraine Days During the 12 Week Period After the First Dose of Study Medication in Patients Not Receiving Concomitant Preventive Migraine Medications
Hide Description A subset of patients (specified in the protocol not to exceed 30%) were allowed to use 1 concomitant migraine preventive medication. This outcome only includes those participants who did not take concomitant preventive migraine medication during this study. A migraine day has been previously defined. Monthly averages are derived and normalized to 28 days equivalent by the following formula: (# days of efficacy variable over relevant period / # days with assessments recorded in the e-diary over the relevant period) * 28. The change is calculated as postbaseline value – baseline value.
Time Frame Baseline (Days -28 to Day -1), Treatment (Days 1 – Week 12)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set of participants who did not receive concomitant migraine prevention medication
Arm/Group Title Placebo Fremanezumab 675 mg/Placebo/Placebo Fremanezumab 225/225/225 mg
Hide Arm/Group Description:
Participants randomized to receive placebo received three 1.5-mL placebo injections on Day 0, and a single 1.5-mL placebo injection on Days 28 and 56.
Participants randomized to receive fremanezumab 675 mg/placebo/placebo received 675 mg of fremanezumab as 3 injections (225 mg/1.5 mL) on Day 0, and placebo as a single 1.5-mL injection on Days 28 and 56.
Participants randomized to receive fremanezumab 225/225/225 mg received 1 active injection (225 mg/1.5 mL) on Days 0, 28 and 56.
Overall Number of Participants Analyzed 230 230 225
Median (Inter-Quartile Range)
Unit of Measure: days
-2.9
(-4.9 to -0.6)
-4.0
(-6.3 to -2.0)
-4.2
(-6.2 to -2.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Fremanezumab 675 mg/Placebo/Placebo
Comments Due to the deviation from the normal distribution assumption of the data, the Wilcoxon rank-sum test was conducted as the primary analysis for each active treatment group and placebo treatment group for this endpoint.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments 0.05 level of significance
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Fremanezumab 225/225/225 mg
Comments Due to the deviation from the normal distribution assumption of the data, the Wilcoxon rank-sum test was conducted as the primary analysis for each active treatment group and placebo treatment group for this endpoint.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments 0.05 level of significance
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline in Migraine-Related Disability Score (MIDAS), As Measured by the Migraine Disability Assessment At 4 Weeks After the Last (3rd) Dose of Study Drug
Hide Description The MIDAS questionnaire is a 5-item instrument developed to assess headache-related disability based on lost days of activity in 3 domains (work, household work, and nonwork) over the previous 3 months. The total score, ie, the sum of the # lost days answered for the first 5 questions, is used for grading of disability, with scores of 0-5 lost days = grade 1 (little or no disability), 6-10 lost days =grade 2 (mild disability), 11-20 lost days = grade 3 (moderate disability), and ≥21 lost days interpreted as grade 4 (severe disability). Negative change from baseline scores indicate a reduction (improvement) in headache-related disability.
Time Frame Baseline (Day 0), Treatment Week 12 (4 weeks after the 3rd dose)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title Placebo Fremanezumab 675 mg/Placebo/Placebo Fremanezumab 225/225/225 mg
Hide Arm/Group Description:
Participants randomized to receive placebo received three 1.5-mL placebo injections on Day 0, and a single 1.5-mL placebo injection on Days 28 and 56.
Participants randomized to receive fremanezumab 675 mg/placebo/placebo received 675 mg of fremanezumab as 3 injections (225 mg/1.5 mL) on Day 0, and placebo as a single 1.5-mL injection on Days 28 and 56.
Participants randomized to receive fremanezumab 225/225/225 mg received 1 active injection (225 mg/1.5 mL) on Days 0, 28 and 56.
Overall Number of Participants Analyzed 290 288 287
Median (Inter-Quartile Range)
Unit of Measure: lost days
-12.5
(-29.5 to -2.0)
-18.0
(-39.0 to -6.0)
-19.0
(-36.0 to -7.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Fremanezumab 675 mg/Placebo/Placebo
Comments Due to the deviation from the normal distribution assumption of the data, the Wilcoxon rank-sum test was conducted as the primary analysis for each active treatment group and placebo treatment group for this endpoint.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0023
Comments 0.05 level of significance
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Fremanezumab 225/225/225 mg
Comments Due to the deviation from the normal distribution assumption of the data, the Wilcoxon rank-sum test was conducted as the primary analysis for each active treatment group and placebo treatment group for this endpoint.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0021
Comments 0.05 level of significance
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
8.Secondary Outcome
Title Electrocardiogram Finding Shifts From Baseline to Overall
Hide Description 12-lead ECGs were performed before other assessments (eg, blood draws and administration of questionnaires) and performed in triplicate. The worst post-baseline finding for the patient is summarized. Only patients with both baseline and post-baseline ECGs are included. The ECG was evaluated by the investigator at the time of recording (signed and dated), and the printout was kept in the source documentation file. When potentially clinically significant findings were detected by the investigator, a cardiologist at a central diagnostic center was consulted for a definitive interpretation. Any ECG finding that was judged by the investigator as a potentially clinically significant change (worsening) compared with a baseline value was considered an adverse event. - NCS = abnormal, not clinically significant - CS = abnormal, clinically significant Shift format is: baseline finding / worst post-baseline finding
Time Frame Baseline (Day 0), Treatment Week 12 (or early withdrawal)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population of participants with both baseline and post-treatment ECGs
Arm/Group Title Placebo Fremanezumab 675 mg/Placebo/Placebo Fremanezumab 225/225/225 mg
Hide Arm/Group Description:
Participants randomized to receive placebo received three 1.5-mL placebo injections on Day 0, and a single 1.5-mL placebo injection on Days 28 and 56.
Participants randomized to receive fremanezumab 675 mg/placebo/placebo received 675 mg of fremanezumab as 3 injections (225 mg/1.5 mL) on Day 0, and placebo as a single 1.5-mL injection on Days 28 and 56.
Participants randomized to receive fremanezumab 225/225/225 mg received 1 active injection (225 mg/1.5 mL) on Days 0, 28 and 56.
Overall Number of Participants Analyzed 278 276 281
Measure Type: Count of Participants
Unit of Measure: Participants
Normal / Normal
161
  57.9%
169
  61.2%
181
  64.4%
Normal / NCS
32
  11.5%
41
  14.9%
25
   8.9%
Normal / CS
0
   0.0%
0
   0.0%
0
   0.0%
NCS / Normal
27
   9.7%
23
   8.3%
29
  10.3%
NCS / NCS
58
  20.9%
43
  15.6%
46
  16.4%
NCS / CS
0
   0.0%
0
   0.0%
0
   0.0%
CS / Normal
0
   0.0%
0
   0.0%
0
   0.0%
CS / NCS
0
   0.0%
0
   0.0%
0
   0.0%
CS / CS
0
   0.0%
0
   0.0%
0
   0.0%
9.Secondary Outcome
Title Participants With Vital Signs Potentially Clinically Significant Abnormal Values
Hide Description Vital signs were performed before other assessments (eg, blood draws and administration of questionnaires). Vital signs with at least one participant showing potentially clinically significant abnormal findings included: - Pulse Rate Low: <=50 and decrease of >=15 beats per minute - Systolic Blood Pressure Low: <=90 mmHg and decrease of >=20 mmHg - Diastolic Blood Pressure High: >=105 mmHg and increase of >=15 mmHg - Diastolic Blood Pressure Low: <=50 mmHg and decrease of >=15 mmHg - Respiratory Rate Low: <10 breaths / minute
Time Frame Treatment Days 28, 56 and 84. Changes from previous reading may reflect the baseline reading performed on Day 0.
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population of participants with both baseline and post-treatment values for each vital sign.
Arm/Group Title Placebo Fremanezumab 675 mg/Placebo/Placebo Fremanezumab 225/225/225 mg
Hide Arm/Group Description:
Participants randomized to receive placebo received three 1.5-mL placebo injections on Day 0, and a single 1.5-mL placebo injection on Days 28 and 56.
Participants randomized to receive fremanezumab 675 mg/placebo/placebo received 675 mg of fremanezumab as 3 injections (225 mg/1.5 mL) on Day 0, and placebo as a single 1.5-mL injection on Days 28 and 56.
Participants randomized to receive fremanezumab 225/225/225 mg received 1 active injection (225 mg/1.5 mL) on Days 0, 28 and 56.
Overall Number of Participants Analyzed 285 285 285
Measure Type: Count of Participants
Unit of Measure: Participants
Participants with at least 1 abnormality
3
   1.1%
4
   1.4%
5
   1.8%
Pulse Rate Low
0
   0.0%
1
   0.4%
0
   0.0%
Systolic Blood Pressure Low
0
   0.0%
2
   0.7%
1
   0.4%
Diastolic Blood Pressure High
0
   0.0%
1
   0.4%
2
   0.7%
Diastolic Blood Pressure Low
2
   0.7%
1
   0.4%
0
   0.0%
Respiratory Rate Low
1
   0.4%
0
   0.0%
2
   0.7%
10.Secondary Outcome
Title Participants With Serum Chemistry and Hematology Potentially Clinically Significant Abnormal Results
Hide Description Serum chemistry and hematology laboratory tests with potentially clinically significant abnormal findings included: - Blood Urea Nitrogen (BUN) High: >=10.71 mmol/L - Bilirubin High: >=34.2 umol/L - Alanine Aminotransferase (ALT): >=3*upper limit of normal (ULN) - Aspartate Aminotransferase (AST): >=3*upper limit of normal (ULN) - Gamma Glutamyl Transferase (GGT): >=3*upper limit of normal (ULN) - Hemoglobin: Male: <115 g/L or Female: <=95 g/L - Hematocrit: Male: <0.37 L/L or Female: <0.32 L/L - Leukocytes: >=20*10^9/L or <=3*10^9/L - Eosinophils/Leukocytes: >=10% - Platelets: >=700*10^9/L or <=75*10^9/L
Time Frame Treatment Days 28, 56 and 84 (or early withdrawal)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population of participants with at least one postbaseline result for the tests.
Arm/Group Title Placebo Fremanezumab 675 mg/Placebo/Placebo Fremanezumab 225/225/225 mg
Hide Arm/Group Description:
Participants randomized to receive placebo received three 1.5-mL placebo injections on Day 0, and a single 1.5-mL placebo injection on Days 28 and 56.
Participants randomized to receive fremanezumab 675 mg/placebo/placebo received 675 mg of fremanezumab as 3 injections (225 mg/1.5 mL) on Day 0, and placebo as a single 1.5-mL injection on Days 28 and 56.
Participants randomized to receive fremanezumab 225/225/225 mg received 1 active injection (225 mg/1.5 mL) on Days 0, 28 and 56.
Overall Number of Participants Analyzed 285 285 285
Measure Type: Count of Participants
Unit of Measure: Participants
Blood Urea Nitrogen (BUN)
1
   0.4%
0
   0.0%
1
   0.4%
Bilirubin
1
   0.4%
0
   0.0%
1
   0.4%
Alanine Aminotransferase (ALT)
0
   0.0%
1
   0.4%
0
   0.0%
Aspartate Aminotransferase (AST)
0
   0.0%
0
   0.0%
1
   0.4%
Gamma Glutamyl Transferase (GGT)
4
   1.4%
4
   1.4%
8
   2.8%
Hemoglobin
1
   0.4%
4
   1.4%
2
   0.7%
Hematocrit
3
   1.1%
6
   2.1%
6
   2.1%
Leukocytes
4
   1.4%
1
   0.4%
6
   2.1%
Eosinophils/Leukocytes
7
   2.5%
3
   1.1%
5
   1.8%
Platelets
1
   0.4%
0
   0.0%
0
   0.0%
11.Secondary Outcome
Title Participants With Urinalysis Laboratory Tests Potentially Clinically Significant Abnormal Results
Hide Description Urinalysis with potentially clinically significant abnormal findings included: - Blood: >=2 unit increase from baseline - Urine Glucose (mg/dL): >=2 unit increase from baseline - Ketones (mg/dL): >=2 unit increase from baseline - Urine Protein (mg/dL): >=2 unit increase from baseline
Time Frame Treatment Days 28, 56 and 84. Changes from previous reading reflect the baseline reading performed on Day 0.
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population of participants with at least one postbaseline result for the tests
Arm/Group Title Placebo Fremanezumab 675 mg/Placebo/Placebo Fremanezumab 225/225/225 mg
Hide Arm/Group Description:
Participants randomized to receive placebo received three 1.5-mL placebo injections on Day 0, and a single 1.5-mL placebo injection on Days 28 and 56.
Participants randomized to receive fremanezumab 675 mg/placebo/placebo received 675 mg of fremanezumab as 3 injections (225 mg/1.5 mL) on Day 0, and placebo as a single 1.5-mL injection on Days 28 and 56.
Participants randomized to receive fremanezumab 225/225/225 mg received 1 active injection (225 mg/1.5 mL) on Days 0, 28 and 56.
Overall Number of Participants Analyzed 285 285 285
Measure Type: Count of Participants
Unit of Measure: Participants
Participants with at least 1 abnormality
55
  19.3%
54
  18.9%
49
  17.2%
Blood
29
  10.2%
30
  10.5%
23
   8.1%
Urine glucose
5
   1.8%
8
   2.8%
2
   0.7%
Ketones
5
   1.8%
7
   2.5%
9
   3.2%
Urine protein
25
   8.8%
19
   6.7%
23
   8.1%
12.Secondary Outcome
Title Prothrombin Time Shifts From Baseline to Endpoint
Hide Description Shifts in prothrombin time from baseline to endpoint were summarized using patient 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) Shift format is: baseline finding / endpoint finding
Time Frame Baseline (Day 0), Treatment Endpoint (Week 12)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population of participants with both baseline and posttreatment values
Arm/Group Title Placebo Fremanezumab 675 mg/Placebo/Placebo Fremanezumab 225/225/225 mg
Hide Arm/Group Description:
Participants randomized to receive placebo received three 1.5-mL placebo injections on Day 0, and a single 1.5-mL placebo injection on Days 28 and 56.
Participants randomized to receive fremanezumab 675 mg/placebo/placebo received 675 mg of fremanezumab as 3 injections (225 mg/1.5 mL) on Day 0, and placebo as a single 1.5-mL injection on Days 28 and 56.
Participants randomized to receive fremanezumab 225/225/225 mg received 1 active injection (225 mg/1.5 mL) on Days 0, 28 and 56.
Overall Number of Participants Analyzed 284 285 284
Measure Type: Count of Participants
Unit of Measure: Participants
Low / Low
0
   0.0%
0
   0.0%
0
   0.0%
Low / Normal
0
   0.0%
1
   0.4%
1
   0.4%
Low / High
0
   0.0%
0
   0.0%
0
   0.0%
Normal / Low
0
   0.0%
1
   0.4%
0
   0.0%
Normal / Normal
254
  89.4%
248
  87.0%
250
  88.0%
Normal / High
14
   4.9%
10
   3.5%
13
   4.6%
High / Low
0
   0.0%
0
   0.0%
0
   0.0%
High / Normal
8
   2.8%
15
   5.3%
12
   4.2%
High / High
8
   2.8%
10
   3.5%
8
   2.8%
13.Secondary Outcome
Title Injection Site Reaction Adverse Events
Hide Description Counts of participants who reported treatment-emergent injection site reactions as AEs are summarized. Preferred terms from MedDRA version 18.1 are offered without a threshold applied.
Time Frame Day 1 to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Placebo Fremanezumab 675 mg/Placebo/Placebo Fremanezumab 225/225/225 mg
Hide Arm/Group Description:
Participants randomized to receive placebo received three 1.5-mL placebo injections on Day 0, and a single 1.5-mL placebo injection on Days 28 and 56.
Participants randomized to receive fremanezumab 675 mg/placebo/placebo received 675 mg of fremanezumab as 3 injections (225 mg/1.5 mL) on Day 0, and placebo as a single 1.5-mL injection on Days 28 and 56.
Participants randomized to receive fremanezumab 225/225/225 mg received 1 active injection (225 mg/1.5 mL) on Days 0, 28 and 56.
Overall Number of Participants Analyzed 293 291 290
Measure Type: Count of Participants
Unit of Measure: Participants
Participants with >=1 injection site reaction
106
  36.2%
131
  45.0%
130
  44.8%
Injection site pain
76
  25.9%
86
  29.6%
87
  30.0%
Injection site induration
45
  15.4%
57
  19.6%
71
  24.5%
Injection site erythema
41
  14.0%
55
  18.9%
52
  17.9%
Injection site haemorrhage
6
   2.0%
9
   3.1%
3
   1.0%
Injection site pruritus
2
   0.7%
4
   1.4%
4
   1.4%
Injection site swelling
0
   0.0%
2
   0.7%
3
   1.0%
Injection site urticaria
2
   0.7%
2
   0.7%
1
   0.3%
Injection site rash
0
   0.0%
1
   0.3%
3
   1.0%
Fatigue
0
   0.0%
1
   0.3%
0
   0.0%
Injection site bruising
1
   0.3%
0
   0.0%
0
   0.0%
Injection site dermatitis
0
   0.0%
0
   0.0%
1
   0.3%
Injection site hypersensitivity
0
   0.0%
0
   0.0%
1
   0.3%
Injection site nodule
0
   0.0%
0
   0.0%
1
   0.3%
Injection site oedema
0
   0.0%
0
   0.0%
1
   0.3%
Injection site warmth
0
   0.0%
1
   0.3%
0
   0.0%
14.Secondary Outcome
Title Participants With Positive Electronic Columbia Suicide Severity Rating Scale Results After the First Dose of Study Drug
Hide Description The electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) was used to assess the patient’s suicidal ideation (severity and intensity) and behavior (Posner et al 2011). The eC-SSRS Baseline/Screening version was completed by the patient at visit 2, and the eC-SSRS Since Last Visit version was completed by the patient at all other time points. Any positive findings on the eC-SSRS Since Last Visit version required evaluation by a physician or doctoral-level psychologist. Findings after the first dose of study drug using the eC-SSRS Since Last Visit version are summarized.
Time Frame Day 1 to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Placebo Fremanezumab 675 mg/Placebo/Placebo Fremanezumab 225/225/225 mg
Hide Arm/Group Description:
Participants randomized to receive placebo received three 1.5-mL placebo injections on Day 0, and a single 1.5-mL placebo injection on Days 28 and 56.
Participants randomized to receive fremanezumab 675 mg/placebo/placebo received 675 mg of fremanezumab as 3 injections (225 mg/1.5 mL) on Day 0, and placebo as a single 1.5-mL injection on Days 28 and 56.
Participants randomized to receive fremanezumab 225/225/225 mg received 1 active injection (225 mg/1.5 mL) on Days 0, 28 and 56.
Overall Number of Participants Analyzed 294 291 289
Measure Type: Count of Participants
Unit of Measure: Participants
Suicidal Ideation
0
   0.0%
0
   0.0%
2
   0.7%
Suicidal Behaviour
0
   0.0%
0
   0.0%
0
   0.0%
Time Frame Day 1 to Week 12
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo Fremanezumab 225/225/225 mg Fremanezumab 675 mg/Placebo/Placebo
Hide Arm/Group Description Participants randomized to receive placebo received three 1.5-mL placebo injections Day 0, and a single 1.5-mL placebo injection on Days 28 and 56. Participants randomized to receive fremanezumab 225/225/225 mg received 1 active injection (225 mg/1.5 mL) on Days 0, 28 and 56. Participants randomized to receive fremanezumab 675 mg/placebo/placebo received 675 mg of fremanezumab as 3 active injections (225 mg/1.5 mL) on Day 0, and placebo as a single 1.5-mL injection on Days 28 and 56.
All-Cause Mortality
Placebo Fremanezumab 225/225/225 mg Fremanezumab 675 mg/Placebo/Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/294 (0.00%)      0/289 (0.00%)      1/291 (0.34%)    
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Fremanezumab 225/225/225 mg Fremanezumab 675 mg/Placebo/Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   7/294 (2.38%)      3/289 (1.04%)      3/291 (1.03%)    
Gastrointestinal disorders       
Intestinal haemorrhage  1  0/294 (0.00%)  0 0/289 (0.00%)  0 1/291 (0.34%)  1
General disorders       
Death  1  0/294 (0.00%)  0 0/289 (0.00%)  0 1/291 (0.34%)  1
Immune system disorders       
Drug hypersensitivity  1  1/294 (0.34%)  1 0/289 (0.00%)  0 0/291 (0.00%)  0
Infections and infestations       
Appendicitis  1  0/294 (0.00%)  0 1/289 (0.35%)  1 0/291 (0.00%)  0
Injury, poisoning and procedural complications       
Fall  1  1/294 (0.34%)  1 0/289 (0.00%)  0 0/291 (0.00%)  0
Road traffic accident  1  1/294 (0.34%)  1 0/289 (0.00%)  0 0/291 (0.00%)  0
Tendon injury  1  0/294 (0.00%)  0 0/289 (0.00%)  0 1/291 (0.34%)  1
Wrist fracture  1  1/294 (0.34%)  1 0/289 (0.00%)  0 0/291 (0.00%)  0
Metabolism and nutrition disorders       
Hypoglycaemia  1  1/294 (0.34%)  1 0/289 (0.00%)  0 0/291 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Lentigo maligna  1  1/294 (0.34%)  1 0/289 (0.00%)  0 0/291 (0.00%)  0
Nervous system disorders       
Dizziness  1  1/294 (0.34%)  1 0/289 (0.00%)  0 0/291 (0.00%)  0
Generalised tonic-clonic seizure  1  0/294 (0.00%)  0 1/289 (0.35%)  1 0/291 (0.00%)  0
Status migrainosus  1  1/294 (0.34%)  2 0/289 (0.00%)  0 0/291 (0.00%)  0
Pregnancy, puerperium and perinatal conditions       
Abortion spontaneous  1  1/294 (0.34%)  1 0/289 (0.00%)  0 0/291 (0.00%)  0
Reproductive system and breast disorders       
Menorrhagia  1  0/294 (0.00%)  0 1/289 (0.35%)  1 0/291 (0.00%)  0
1
Term from vocabulary, MedDRA (18.1)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Fremanezumab 225/225/225 mg Fremanezumab 675 mg/Placebo/Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   113/294 (38.44%)      132/289 (45.67%)      133/291 (45.70%)    
General disorders       
Injection site erythema  1  41/294 (13.95%)  88 52/289 (17.99%)  102 55/291 (18.90%)  110
Injection site induration  1  45/294 (15.31%)  93 71/289 (24.57%)  134 57/291 (19.59%)  126
Injection site pain  1  76/294 (25.85%)  191 87/289 (30.10%)  245 86/291 (29.55%)  234
Infections and infestations       
Upper respiratory tract infection  1  15/294 (5.10%)  15 16/289 (5.54%)  17 11/291 (3.78%)  11
1
Term from vocabulary, MedDRA (18.1)
Indicates events were collected by systematic assessment
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
Layout table for additonal information
Responsible Party: Teva Pharmaceutical Industries ( Teva Branded Pharmaceutical Products, R&D Inc. )
ClinicalTrials.gov Identifier: NCT02629861     History of Changes
Other Study ID Numbers: TV48125-CNS-30050
2015-004598-34 ( EudraCT Number )
First Submitted: December 10, 2015
First Posted: December 14, 2015
Results First Submitted: October 10, 2018
Results First Posted: November 8, 2018
Last Update Posted: November 8, 2018