FOCUS: An Efficacy and Safety Study of Fremanezumab in Adults With Migraine
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate the efficacy, safety, and tolerability of monthly and quarterly subcutaneous (sc) injections of fremanezumab compared with sc injections of placebo in participants with chronic migraine (CM) or episodic migraine (EM) who have responded inadequately to 2 to 4 classes of prior preventive treatments.
Approximately equal numbers of participants from each subgroup (CM and EM) are randomized in blinded-fashion 1:1:1 into one of 3 treatments for the subgroup - 2 active treatments and 1 placebo treatment- consisting of monthly injections for 3 months (up to Week 12). Then all participants continue into an open-label extension of 3 months (up to Week 24) during which everyone is administered sc injections of fremanezumab.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Placebo Double-blind (DB) period: Participants with CM or EM will receive 3 injections of placebo 1.5 milliliters (mL) SC on Day 0 and single injection of placebo 1.5 mL SC on Days 28 and 56. Open-label (OL) period: Participants with CM or EM will receive fremanezumab (TEV-48125) 225 milligrams (mg) SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. |
Drug: Fremanezumab
Fremanezumab will be administered per dose and schedule specified in the arm.
Other Names:
Drug: Placebo
Placebo matching to fremanezumab will be administered per schedule specified in the arm.
|
| Experimental: Fremanezumab Quarterly DB period: Participants with CM or EM will receive fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of placebo 1.5 mL for 2 months (on Days 28 and 56). OL period: Participants with CM or EM will receive fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. |
Drug: Fremanezumab
Fremanezumab will be administered per dose and schedule specified in the arm.
Other Names:
Drug: Placebo
Placebo matching to fremanezumab will be administered per schedule specified in the arm.
|
| Experimental: Fremanezumab Monthly DB period: Participants with CM will receive fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). Participants with EM will receive fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL and 2 injections of placebo 1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). OL period: Participants with CM or EM will receive fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. |
Drug: Fremanezumab
Fremanezumab will be administered per dose and schedule specified in the arm.
Other Names:
Drug: Placebo
Placebo matching to fremanezumab will be administered per schedule specified in the arm.
|
Outcome Measures
Primary Outcome Measures
- DB Period: Change From Baseline in Monthly Average Number of Migraine Days During the 12-Week Period After the First Dose of Fremanezumab [Baseline (Day -28 to Day -1), up to Week 12]
A migraine day was defined as when at least 1 of the following situations occurred: A calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours 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 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.
Secondary Outcome Measures
- DB Period: Percentage of Participants Reaching at Least 50 Percent (%) Reduction From Baseline in Monthly Average Number of Migraine Days During the 12-Week Period After the First Dose of Fremanezumab [Baseline (Day -28 to Day-1), up to Week 12]
A migraine day was defined as when at least 1 of the following situations occurred: A calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours 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 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.
- DB Period: Change From Baseline in Monthly Average Number of Headache Days of at Least Moderate Severity During the 12-Week Period After the First Dose of Fremanezumab [Baseline (Day -28 to Day -1), up to Week 12]
A headache day of at least moderate severity was defined as a calendar day (00:00 to 23:59) demonstrating at least 4 consecutive hours of headache of at least moderate severity or; a calendar day (0:00 to 23:59) demonstrating a headache of any duration that was treated with migraine-specific acute medications (triptans and ergot compounds). 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. LS mean calculated using ANCOVA model with treatment, gender, region, special group of treatment failure (yes/no), migraine classification (EM/CM), and treatment*migraine classification as fixed effects and baseline number of headache days of at least moderate severity and years since onset of migraine as covariates.
- DB Period: Change From Baseline in Monthly Average Number of Migraine Days During the 4-Week Period After the First Dose of Fremanezumab [Baseline (Day -28 to Day -1), up to Week 4]
A migraine day was defined as when at least 1 of following occurred: A calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache meeting criteria for migraine with or without aura; a calendar day demonstrating at least 4 consecutive hours of a headache meeting criteria for probable migraine, a migraine subtype where only 1 migraine criterion was missing; a calendar day demonstrating a headache of any duration that was treated with migraine-specific medications. 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. LS mean calculated using ANCOVA model with treatment, gender, region, special group of treatment failure (yes/no), migraine classification (EM/CM), and treatment*migraine classification as fixed effects, and baseline number of migraine days and years since onset of migraines as covariates.
- DB Period: Percentage of Participants Reaching at Least 50% Reduction From Baseline in Monthly Average Number of Migraine Days During the 4-Week Period After the First Dose of Fremanezumab [Baseline (Day -28 to Day-1), up to Week 4]
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 meeting criteria for migraine with or without aura; a calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours 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.
- DB Period: Change From Baseline in Monthly Average Number of Days of Use of Any Acute Headache Medications During the 12-Week Period After the First Dose of Fremanezumab [Baseline (Day -28 to Day -1), up to Week 12]
Baseline data and the mean change from baseline in the monthly average number of days of use of any acute headache medications during the 12-week period after administration of the first dose of study drug (based on Week 0 to 12 data) is reported. Least Squares (LS) mean calculated using analysis of covariance (ANCOVA) model with treatment, gender, region, special group of treatment failure (yes/no), migraine classification (EM/CM), and treatment*migraine classification as fixed effects, and baseline number of migraine days and years since onset of migraines as covariates.
- DB Period: Change From Baseline in Monthly Average Number of Headache Days of at Least Moderate Severity During the 4-Week Period After the First Dose of Fremanezumab [Baseline (Day -28 to Day -1), up to Week 4]
A headache day of at least moderate severity was defined as a calendar day (00:00 to 23:59) demonstrating at least 4 consecutive hours of headache of at least moderate severity or; a calendar day (0:00 to 23:59) demonstrating a headache of any duration that was treated with migraine-specific acute medications (triptans and ergot compounds). 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. LS mean calculated using ANCOVA model with treatment, gender, region, special group of treatment failure (yes/no), migraine classification (EM/CM), and treatment*migraine classification as fixed effects, and baseline number of headache days of at least moderate severity and years since onset of migraines as covariates.
- DB Period: Number of Participants With Adverse Events (AEs) and Who Did Not Complete the Study Due to AEs [Baseline (Day 0) up to Week 12]
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.
- OL Period: Number of Participants With AEs and Who Did Not Complete the Study Due to AEs [Week 12 up to Week 24]
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.
- DB Period: Number of Participants With Potentially Clinically Significant Abnormal Serum Chemistry Results [Baseline up to Week 12]
Criteria for potentially clinically significant abnormal serum chemistry values included: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), and lactate dehydrogenase (LDH) (units/liter [U/L]): greater than or equal to (≥) 3*upper limit of normal (ULN); Blood Urea Nitrogen (BUN): ≥10.71 millimoles/liter (mmol/L); creatinine: ≥177 micromoles/liter (µmol/L); bilirubin (total): ≥34.2 µmol/L; and uric acid: ≥625 µmol/L (men), and ≥506 µmol/L (women). A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
- OL Period: Number of Participants With Potentially Clinically Significant Abnormal Serum Chemistry Results [Week 12 up to Week 24]
Criteria for potentially clinically significant abnormal serum chemistry values included: ALT, AST, ALP, GGT, and LDH (U/L): ≥3*ULN; BUN: ≥10.71 mmol/L; creatinine: ≥177 µmol/L; bilirubin (total): ≥34.2 µmol/L; and uric acid: ≥625 µmol/L (men), and ≥506 µmol/L (women). A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
- DB Period: Number of Participants With Potentially Clinically Significant Abnormal Hematology Results [Baseline up to Week 12]
Criteria for potentially clinically significant abnormal hematology values included: hemoglobin: less than (<) 115 grams/liter (g/L) (in men) or less than or equal to (≤) 95 g/L (in women), hematocrit: <0.37 L/L (in men) or <0.32 L/L (in women), leukocytes: ≥20*10^9/L or ≤3*10^9/L, eosinophils: >=10%, platelets: ≥700*10^9/L or ≤75*10^9/L, and absolute neutrophil count (ANC): ≤1*10^9/L. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
- OL Period: Number of Participants With Potentially Clinically Significant Abnormal Hematology Results [Week 12 up to Week 24]
Criteria for potentially clinically significant abnormal hematology values included: hemoglobin: <115 g/L (in men) or ≤95 g/L (in women), hematocrit: <0.37 L/L (in men) or <0.32 L/L (in women), leukocytes: ≥20*10^9/L or ≤3*10^9/L, eosinophils: >=10%, platelets: ≥700*10^9/L or ≤75*10^9/L, and ANC: ≤1*10^9/L. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
- DB Period: Number of Participants With Potentially Clinically Significant Abnormal Coagulation Laboratory Test Results [Baseline up to Week 12]
Criteria for potentially clinically significant abnormal coagulation values included: prothrombin international normalized ratio (INR): greater than (>) 1.5. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
- OL Period: Number of Participants With Potentially Clinically Significant Abnormal Coagulation Laboratory Test Results [Week 12 up to Week 24]
Criteria for potentially clinically significant abnormal coagulation values included: prothrombin INR: >1.5. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
- DB Period: Number of Participants With Potentially Clinically Significant Abnormal Urinalysis Laboratory Tests Results [Baseline up to Week 12]
Criteria for potentially clinically significant abnormal urinalysis values included: urine glucose (milligrams/deciliter [mg/dL]): ≥2 unit increase from baseline, ketones (mg/dL): ≥2 unit increase from baseline, urine total protein (mg/dL): ≥2 unit increase from baseline, and haemoglobin ≥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.
- OL Period: Number of Participants With Potentially Clinically Significant Abnormal Urinalysis Laboratory Tests Results [Week 12 up to Week 24]
Criteria for potentially clinically significant abnormal urinalysis values included: urine glucose (mg/dL): ≥2 unit increase from baseline, ketones (mg/dL): ≥2 unit increase from baseline, urine total protein (mg/dL): ≥2 unit increase from baseline, and haemoglobin ≥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.
- DB Period: Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Values [Baseline up to Week 12]
Criteria for potentially clinically significant abnormal vital signs values 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 celsius and change of ≥1.1 degrees celsius. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
- OL Period: Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Values [Week 12 up to Week 24]
Criteria for potentially clinically significant abnormal vital signs values included: pulse rate: ≤50 bpm and decrease of ≥15 bpm, or ≥120 bpm and increase of ≥15 bpm; systolic blood pressure: ≤90 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 celsius and change of ≥1.1 degrees celsius. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
- DB Period: Number of Participants With Shift From Baseline to Week 12 in Electrocardiogram (ECG) Parameters [Baseline, Week 12]
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 - Week 12 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.
- OL Period: Number of Participants With Shift From Baseline to Week 24 in ECG Parameters [Baseline, Week 24]
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 - Week 24 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.
- DB Period: Number of Participants Who Received Concomitant Medications for Adverse Events [Baseline up to Week 12]
Concomitant medications included: agents acting on the renin-angiotensin system, all other therapeutic products (for example: homeopathic preparation), allergens, analgesics, anesthetics, anti-parkinson drugs, antianemic preparations, antibacterials for systemic use, antibiotics and chemotherapeutics for dermatological use, antidiarrheals, intestinal antiinflammatory/antiinfective agents, antiemetic, antiepileptics, antifungals for dermatologiocal use, antigout preparations, antihemorrhagics, antihistamines for systemic use, antihypertensives, antiinflammatory and antirheumatic products, antimycotics for systemic use, antipruritics, antipsoriatics, antivirals for systemic use, beta blocking agents, blood substitutes and perfusion solutions, cardiac therapy, corticosteroids, cough and cold preparations, diagnostic radiopharmaceuticals, diuretics, thyroid therapy, urologicals, vaccines, psycoleptics, psycoanaleptics, ophthalmologicals, muscle relaxants, drugs used in diabetes etc.
- OL Period: Number of Participants Who Received Concomitant Medications for Adverse Events [Week 12 up to Week 24]
Concomitant medications included: agents acting on the renin-angiotensin system, all other therapeutic products (for example: homeopathic preparation), allergens, analgesics, anesthetics, anti-parkinson drugs, antianemic preparations, antibacterials for systemic use, antibiotics and chemotherapeutics for dermatological use, antidiarrheals, intestinal antiinflammatory/antiinfective agents, antiemetic, antiepileptics, antifungals for dermatologiocal use, antigout preparations, antihemorrhagics, antihistamines for systemic use, antihypertensives, antiinflammatory and antirheumatic products, antimycotics for systemic use, antipruritics, antipsoriatics, antivirals for systemic use, beta blocking agents, blood substitutes and perfusion solutions, cardiac therapy, corticosteroids, cough and cold preparations, diagnostic radiopharmaceuticals, diuretics, thyroid therapy, urologicals, vaccines, psycoleptics, psycoanaleptics, ophthalmologicals, muscle relaxants, drugs used in diabetes etc.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
The participant has a diagnosis of migraine with onset at ≤50 years of age.
-
Body weight ≥45 kilograms.
-
The participant has a history of migraine for ≥12 months prior to screening.
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Women of childbearing potential (WOCBP) whose male partners are potentially fertile (that is; no vasectomy) must use highly effective birth control methods for the duration of the study and the follow-up period and for 6.0 months after discontinuation of investigational medicinal product (IMP)
-
Men must be sterile, or if they are potentially fertile/reproductively competent (not surgically [that is; vasectomy] or congenitally sterile) and their female partners are of childbearing potential, must use, together with their female partners, acceptable birth control methods for the duration of the study and for 6.0 months after discontinuation of the investigational medicinal product (IMP).
-
Additional criteria apply, please contact the investigator for more information.
Exclusion Criteria:
-
At the time of screening visit, participant is receiving any preventive migraine medications, regardless of the medical indication for more than 5 days and expects to continue with these medications.
-
Participant has received onabotulinumtoxinA for migraine or for any medical or cosmetic reasons requiring injections in the head, face, or neck during the 3 months before screening visit.
-
The participant has used an intervention/device (for example; scheduled nerve blocks and transcranial magnetic stimulation) for migraine during the 2 months prior to screening.
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The participant uses triptans/ergots as preventive therapies for migraine.
-
Participant uses non-steroidal anti-inflammatory drugs (NSAIDs) as preventive therapy for migraine on nearly daily basis for other indications. Note: Low dose aspirin (for example; 81 mg) used for cardiovascular disease prevention is allowed.
-
Additional criteria apply, please contact the investigator for more information.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Teva Investigational Site 14742 | Huntsville | Alabama | United States | 35801 |
| 2 | Teva Investigational Site 14729 | Long Beach | California | United States | 90806 |
| 3 | Teva Investigational Site 14739 | San Diego | California | United States | 92103 |
| 4 | Teva Investigational Site 14843 | Santa Monica | California | United States | 90404 |
| 5 | Teva Investigational Site 14749 | Colorado Springs | Colorado | United States | 80918 |
| 6 | Teva Investigational Site 14758 | Maitland | Florida | United States | 32751 |
| 7 | Teva Investigational Site 14738 | Orlando | Florida | United States | 32819 |
| 8 | Teva Investigational Site 14760 | Decatur | Georgia | United States | 30030 |
| 9 | Teva Investigational Site 14737 | Meridian | Idaho | United States | 83642 |
| 10 | Teva Investigational Site 14730 | Chicago | Illinois | United States | 60607 |
| 11 | Teva Investigational Site 14740 | Evanston | Illinois | United States | 60201 |
| 12 | Teva Investigational Site 14735 | Louisville | Kentucky | United States | 40223 |
| 13 | Teva Investigational Site 14747 | Pikesville | Maryland | United States | 21208 |
| 14 | Teva Investigational Site 14750 | Fall River | Massachusetts | United States | 02720 |
| 15 | Teva Investigational Site 14734 | Watertown | Massachusetts | United States | 02472 |
| 16 | Teva Investigational Site 14731 | Ann Arbor | Michigan | United States | 48104 |
| 17 | Teva Investigational Site 14748 | Plymouth | Minnesota | United States | 55441 |
| 18 | Teva Investigational Site 14746 | Omaha | Nebraska | United States | 68114 |
| 19 | Teva Investigational Site 14754 | Berlin | New Jersey | United States | 08009 |
| 20 | Teva Investigational Site 14752 | Albuquerque | New Mexico | United States | 87102 |
| 21 | Teva Investigational Site 14753 | Amherst | New York | United States | 14226 |
| 22 | Teva Investigational Site 14736 | Greensboro | North Carolina | United States | 27405 |
| 23 | Teva Investigational Site 14741 | Greensboro | North Carolina | United States | 27408 |
| 24 | Teva Investigational Site 14732 | Raleigh | North Carolina | United States | 27607 |
| 25 | Teva Investigational Site 14761 | Lincoln | Rhode Island | United States | 02865 |
| 26 | Teva Investigational Site 14756 | Warwick | Rhode Island | United States | 02886 |
| 27 | Teva Investigational Site 14745 | Memphis | Tennessee | United States | 38119 |
| 28 | Teva Investigational Site 14743 | Nashville | Tennessee | United States | 37203 |
| 29 | Teva Investigational Site 14733 | Austin | Texas | United States | 78731 |
| 30 | Teva Investigational Site 14751 | West Jordan | Utah | United States | 84088 |
| 31 | Teva Investigational Site 37092 | Brugge | Belgium | 8000 | |
| 32 | Teva Investigational Site 37089 | Brussels | Belgium | 1090 | |
| 33 | Teva Investigational Site 37091 | Hasselt | Belgium | 3500 | |
| 34 | Teva Investigational Site 37090 | Liege | Belgium | 4000 | |
| 35 | Teva Investigational Site 54162 | Brno | Czechia | 602 00 | |
| 36 | Teva Investigational Site 54165 | Ostrava-Moravska | Czechia | 702 00 | |
| 37 | Teva Investigational Site 54159 | Ostrava | Czechia | 70200 | |
| 38 | Teva Investigational Site 54158 | Pardubice | Czechia | 53002 | |
| 39 | Teva Investigational Site 54164 | Prague 4 | Czechia | 140 59 | |
| 40 | Teva Investigational Site 54163 | Prague | Czechia | 100 00 | |
| 41 | Teva Investigational Site 54160 | Praha 10 | Czechia | 160 00 | |
| 42 | Teva Investigational Site 54161 | Praha 3 | Czechia | 130 00 | |
| 43 | Teva Investigational Site 54166 | Praha 8 | Czechia | 186 00 | |
| 44 | Teva Investigational Site 54157 | Rychnov nad Kneznou | Czechia | 51601 | |
| 45 | Teva Investigational Site 39051 | Aalborg | Denmark | 9000 | |
| 46 | Teva Investigational Site 39049 | Arhus | Denmark | 8000 | |
| 47 | Teva Investigational Site 39052 | Ballerup | Denmark | 2750 | |
| 48 | Teva Investigational Site 39048 | Glostrup | Denmark | 2600 | |
| 49 | Teva Investigational Site 39050 | Vejle | Denmark | 7100 | |
| 50 | Teva Investigational Site 40034 | Helsinki | Finland | 00180 | |
| 51 | Teva Investigational Site 40035 | Helsinki | Finland | 00930 | |
| 52 | Teva Investigational Site 40036 | Oulu | Finland | 90100 | |
| 53 | Teva Investigational Site 40033 | Tampere | Finland | FI-33100 | |
| 54 | Teva Investigational Site 40032 | Turku | Finland | 20100 | |
| 55 | Teva Investigational Site 40037 | Turku | Finland | 20520 | |
| 56 | Teva Investigational Site 35237 | Bron Cedex | France | 69677 | |
| 57 | Teva Investigational Site 35238 | Lille | France | 59037 | |
| 58 | Teva Investigational Site 35235 | Marseille | France | 13005 | |
| 59 | Teva Investigational Site 35240 | Nice | France | 06000 | |
| 60 | Teva Investigational Site 35239 | Strasbourg | France | 67098 | |
| 61 | Teva Investigational Site 35236 | Voiron | France | 38500 | |
| 62 | Teva Investigational Site 32697 | Berlin | Germany | 10177 | |
| 63 | Teva Investigational Site 32690 | Berlin | Germany | D-10435 | |
| 64 | Teva Investigational Site 32694 | Bochum | Germany | 44787 | |
| 65 | Teva Investigational Site 32699 | Essen | Germany | 45147 | |
| 66 | Teva Investigational Site 32692 | Goppingen | Germany | 73033 | |
| 67 | Teva Investigational Site 32691 | Halle | Germany | 06120 | |
| 68 | Teva Investigational Site 32698 | Hamburg | Germany | 20251 | |
| 69 | Teva Investigational Site 32700 | Kiel | Germany | 24149 | |
| 70 | Teva Investigational Site 32695 | Konigstein im Taunus | Germany | 61462 | |
| 71 | Teva Investigational Site 32689 | Muenchen | Germany | 81377 | |
| 72 | Teva Investigational Site 32701 | Rostock | Germany | 18147 | |
| 73 | Teva Investigational Site 32693 | Ulm | Germany | 89073 | |
| 74 | Teva Investigational Site 30199 | Firenze | Italy | 50134 | |
| 75 | Teva Investigational Site 30204 | Roma | Italy | 00128 | |
| 76 | Teva Investigational Site 38126 | Amsterdam | Netherlands | 1078VV | |
| 77 | Teva Investigational Site 38127 | Blaricum | Netherlands | 1261 AN | |
| 78 | Teva Investigational Site 38124 | Leiden | Netherlands | 2333 ZA | |
| 79 | Teva Investigational Site 38125 | Tilburg | Netherlands | 5042 AD | |
| 80 | Teva Investigational Site 53420 | Krakow | Poland | 31-209 | |
| 81 | Teva Investigational Site 53425 | Krakow | Poland | 33-332 | |
| 82 | Teva Investigational Site 53422 | Lodz | Poland | 90-338 | |
| 83 | Teva Investigational Site 53424 | Lodz | Poland | 90-368 | |
| 84 | Teva Investigational Site 53418 | Lublin | Poland | 20-022 | |
| 85 | Teva Investigational Site 53416 | Poznan | Poland | 60-529 | |
| 86 | Teva Investigational Site 53419 | Szczecin | Poland | 70-111 | |
| 87 | Teva Investigational Site 53417 | Warszawa | Poland | 00-909 | |
| 88 | Teva Investigational Site 53423 | Warszawa | Poland | 04-730 | |
| 89 | Teva Investigational Site 31231 | Barcelona | Spain | 08035 | |
| 90 | Teva Investigational Site 31235 | Madrid | Spain | 28223 | |
| 91 | Teva Investigational Site 31236 | Madrid | Spain | 28942 | |
| 92 | Teva Investigational Site 31226 | Pamplona | Spain | 31008 | |
| 93 | Teva Investigational Site 31229 | Santander | Spain | 39008 | |
| 94 | Teva Investigational Site 31230 | Santiago de Compostela | Spain | 15706 | |
| 95 | Teva Investigational Site 31234 | Sevilla | Spain | 41013 | |
| 96 | Teva Investigational Site 31233 | Valencia | Spain | 46010 | |
| 97 | Teva Investigational Site 31227 | Valencia | Spain | 46026 | |
| 98 | Teva Investigational Site 31225 | Valladolid | Spain | 47003 | |
| 99 | Teva Investigational Site 31228 | Zaragoza | Spain | 50009 | |
| 100 | Teva Investigational Site 42050 | Helsingborg | Sweden | 252 20 | |
| 101 | Teva Investigational Site 42049 | Huddinge | Sweden | 141 86 | |
| 102 | Teva Investigational Site 42051 | Lund | Sweden | 260 83 | |
| 103 | Teva Investigational Site 42052 | Stockholm | Sweden | 112 81 | |
| 104 | Teva Investigational Site 42054 | Stockholm | Sweden | 114 33 | |
| 105 | Teva Investigational Site 45018 | Bad Zurzach | Switzerland | 5330 | |
| 106 | Teva Investigational Site 45016 | Bern | Switzerland | 3010 | |
| 107 | Teva Investigational Site 45017 | Lugano | Switzerland | 6900 | |
| 108 | Teva Investigational Site 34231 | Glasgow | United Kingdom | G51 4TF | |
| 109 | Teva Investigational Site 34232 | Hull | United Kingdom | HU3 2JZ | |
| 110 | Teva Investigational Site 34233 | London | United Kingdom | SE5 9NT | |
| 111 | Teva Investigational Site 34230 | Oxford | United Kingdom | OX3 9DU | |
| 112 | Teva Investigational Site 34235 | Salford | United Kingdom | M6 8HD | |
| 113 | Teva Investigational Site 34236 | Stoke-on-Trent | United Kingdom | ST4 6QG |
Sponsors and Collaborators
- Teva Branded Pharmaceutical Products R&D, Inc.
Investigators
- Study Director: Teva Medical Expert, MD, Teva Branded Pharmaceutical Products R&D, Inc.
Study Documents (Full-Text)
More Information
Publications
None provided.- TV48125-CNS-30068
- 2017-002441-30
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | A total of 838 participants were randomized in a 1:1:1 ratio to placebo, fremanezumab quarterly, or fremanezumab monthly treatment groups. |
| Arm/Group Title | Placebo | Fremanezumab Quarterly | Fremanezumab Monthly |
|---|---|---|---|
| Arm/Group Description | Double-blind (DB) period: Participants with chronic migraine (CM) or episodic migraine (EM) received 3 injections of placebo 1.5 milliliters (mL) subcutaneously (SC) on Day 0 and single injection of placebo 1.5 mL SC on Days 28 and 56. Open-label (OL) period: Participants with CM or EM received fremanezumab (TEV-48125) 225 milligrams (mg) SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. | DB period: Participants with CM or EM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of placebo 1.5 mL for 2 months (on Days 28 and 56). OL period: Participants with CM or EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. | DB period: Participants with CM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). Participants with EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL and 2 injections of placebo 1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56).OL period: Participants with CM or EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. |
| Period Title: Double-Blind Period (12 Weeks) | |||
| STARTED | 279 | 276 | 283 |
| DB Safety Analysis Set | 277 | 276 | 285 |
| DB Modified ITT (mITT) Analysis Set | 278 | 276 | 283 |
| COMPLETED | 264 | 271 | 272 |
| NOT COMPLETED | 15 | 5 | 11 |
| Period Title: Double-Blind Period (12 Weeks) | |||
| STARTED | 264 | 271 | 272 |
| OL mITT Analysis Set | 263 | 271 | 272 |
| COMPLETED | 253 | 259 | 260 |
| NOT COMPLETED | 11 | 12 | 12 |
Baseline Characteristics
| Arm/Group Title | Placebo | Fremanezumab Quarterly | Fremanezumab Monthly | Total |
|---|---|---|---|---|
| Arm/Group Description | DB period: Participants with CM or EM received 3 injections of placebo 1.5 mL SC on Day 0 and single injection of placebo 1.5 mL SC on Days 28 and 56. OL period: Participants with CM or EM received fremanezumab (TEV-48125) 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. | DB period: Participants with CM or EM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of placebo 1.5 mL for 2 months (on Days 28 and 56). OL period: Participants with CM or EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. | DB period: Participants with CM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). Participants with EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL and 2 injections of placebo 1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). OL period: Participants with CM or EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. | Total of all reporting groups |
| Overall Participants | 279 | 276 | 283 | 838 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
46.8
(11.10)
|
45.8
(10.97)
|
45.9
(11.05)
|
46.2
(11.04)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
233
83.5%
|
229
83%
|
238
84.1%
|
700
83.5%
|
| Male |
46
16.5%
|
47
17%
|
45
15.9%
|
138
16.5%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||
| Hispanic or Latino |
11
3.9%
|
6
2.2%
|
7
2.5%
|
24
2.9%
|
| Not Hispanic or Latino |
255
91.4%
|
260
94.2%
|
264
93.3%
|
779
93%
|
| Unknown or Not Reported |
13
4.7%
|
10
3.6%
|
12
4.2%
|
35
4.2%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
1
0.4%
|
1
0.1%
|
| Asian |
1
0.4%
|
0
0%
|
3
1.1%
|
4
0.5%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
2
0.7%
|
2
0.7%
|
4
1.4%
|
8
1%
|
| White |
262
93.9%
|
262
94.9%
|
262
92.6%
|
786
93.8%
|
| Other |
1
0.4%
|
2
0.7%
|
1
0.4%
|
4
0.5%
|
| Unknown or Not Reported |
13
4.7%
|
10
3.6%
|
12
4.2%
|
35
4.2%
|
| Number of Migraine Days During the 28 Day Baseline Period (days) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [days] |
14.3
(6.12)
|
14.1
(5.61)
|
14.1
(5.58)
|
14.2
(5.77)
|
| Number of Headache Days of at Least Moderate Severity During the 28 Day Baseline Period (days) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [days] |
12.8
(5.92)
|
12.4
(5.84)
|
12.7
(5.82)
|
12.6
(5.85)
|
Outcome Measures
| Title | DB Period: Change From Baseline in Monthly Average Number of Migraine Days During the 12-Week Period After the First Dose of Fremanezumab |
|---|---|
| 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 meeting criteria for migraine with or without aura; a calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours 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), up to Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| DB mITT analysis set included participants who received at least 1 dose of study drug and had at least 10 days of postbaseline efficacy assessment on the primary endpoint. |
| Arm/Group Title | Placebo | Fremanezumab Quarterly | Fremanezumab Monthly |
|---|---|---|---|
| Arm/Group Description | DB period: Participants with CM or EM received 3 injections of placebo 1.5 mL SC on Day 0 and single injection of placebo 1.5 mL SC on Days 28 and 56. | DB period: Participants with CM or EM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of placebo 1.5 mL for 2 months (on Days 28 and 56). | DB period: Participants with CM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). Participants with EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL and 2 injections of placebo 1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). |
| Measure Participants | 278 | 276 | 283 |
| Least Squares Mean (Standard Error) [days/month] |
-0.6
(0.34)
|
-3.7
(0.34)
|
-4.1
(0.34)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Fremanezumab Quarterly |
|---|---|---|
| Comments | Analysis was performed using analysis of covariance (ANCOVA) method with treatment, sex, region, special group of treatment failure (yes or no), migraine classification (that is; CM or EM), and treatment-by-migraine classification interaction as fixed effects, and baseline number of migraine days and years since onset of migraines as covariates. The stratification factors (as randomized) were used in the model. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least square (LS) mean difference |
| Estimated Value | -3.1 | |
| Confidence Interval |
(2-Sided) 95% -3.84 to -2.42 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.36 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Fremanezumab Monthly |
|---|---|---|
| Comments | Analysis was performed using ANCOVA method with treatment, sex, region, special group of treatment failure (yes or no), migraine classification (that is; CM or EM), and treatment-by-migraine classification interaction as fixed effects, and baseline number of migraine days and years since onset of migraines as covariates. The stratification factors (as randomized) were used in the model. | |
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS mean difference |
| Estimated Value | -3.5 | |
| Confidence Interval |
(2-Sided) 95% -4.19 to -2.78 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.36 |
|
| Estimation Comments | ||
| Title | DB Period: Percentage of Participants Reaching at Least 50 Percent (%) Reduction From Baseline in Monthly Average Number of Migraine Days During the 12-Week Period After the First Dose of Fremanezumab |
|---|---|
| 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 meeting criteria for migraine with or without aura; a calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours 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), up to Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| DB mITT analysis set included participants who received at least 1 dose of study drug and had at least 10 days of postbaseline efficacy assessment on the primary endpoint. |
| Arm/Group Title | Placebo | Fremanezumab Quarterly | Fremanezumab Monthly |
|---|---|---|---|
| Arm/Group Description | DB period: Participants with CM or EM received 3 injections of placebo 1.5 mL SC on Day 0 and single injection of placebo 1.5 mL SC on Days 28 and 56. | DB period: Participants with CM or EM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of placebo 1.5 mL for 2 months (on Days 28 and 56). | DB period: Participants with CM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). Participants with EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL and 2 injections of placebo 1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). |
| Measure Participants | 278 | 276 | 283 |
| Number [percentage of participants] |
9
3.2%
|
34
12.3%
|
34
12%
|
| Title | DB Period: Change From Baseline in Monthly Average Number of Headache Days of at Least Moderate Severity During the 12-Week Period After the First Dose of Fremanezumab |
|---|---|
| Description | A headache day of at least moderate severity was defined as a calendar day (00:00 to 23:59) demonstrating at least 4 consecutive hours of headache of at least moderate severity or; a calendar day (0:00 to 23:59) demonstrating a headache of any duration that was treated with migraine-specific acute medications (triptans and ergot compounds). 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. LS mean calculated using ANCOVA model with treatment, gender, region, special group of treatment failure (yes/no), migraine classification (EM/CM), and treatment*migraine classification as fixed effects and baseline number of headache days of at least moderate severity and years since onset of migraine as covariates. |
| Time Frame | Baseline (Day -28 to Day -1), up to Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| DB mITT analysis set included participants who received at least 1 dose of study drug and had at least 10 days of postbaseline efficacy assessment on the primary endpoint. |
| Arm/Group Title | Placebo | Fremanezumab Quarterly | Fremanezumab Monthly |
|---|---|---|---|
| Arm/Group Description | DB period: Participants with CM or EM received 3 injections of placebo 1.5 mL SC on Day 0 and single injection of placebo 1.5 mL SC on Days 28 and 56. | DB period: Participants with CM or EM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of placebo 1.5 mL for 2 months (on Days 28 and 56). | DB period: Participants with CM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). Participants with EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL and 2 injections of placebo 1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). |
| Measure Participants | 278 | 276 | 283 |
| Least Squares Mean (Standard Error) [days/month] |
-0.6
(0.33)
|
-3.9
(0.34)
|
-4.2
(0.34)
|
| Title | DB Period: Change From Baseline in Monthly Average Number of Migraine Days During the 4-Week Period After the First Dose of Fremanezumab |
|---|---|
| Description | A migraine day was defined as when at least 1 of following occurred: A calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache meeting criteria for migraine with or without aura; a calendar day demonstrating at least 4 consecutive hours of a headache meeting criteria for probable migraine, a migraine subtype where only 1 migraine criterion was missing; a calendar day demonstrating a headache of any duration that was treated with migraine-specific medications. 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. LS mean calculated using ANCOVA model with treatment, gender, region, special group of treatment failure (yes/no), migraine classification (EM/CM), and treatment*migraine classification as fixed effects, and baseline number of migraine days and years since onset of migraines as covariates. |
| Time Frame | Baseline (Day -28 to Day -1), up to Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| DB mITT analysis set included participants who received at least 1 dose of study drug and had at least 10 days of postbaseline efficacy assessment on the primary endpoint. |
| Arm/Group Title | Placebo | Fremanezumab Quarterly | Fremanezumab Monthly |
|---|---|---|---|
| Arm/Group Description | DB period: Participants with CM or EM received 3 injections of placebo 1.5 mL SC on Day 0 and single injection of placebo 1.5 mL SC on Days 28 and 56. | DB period: Participants with CM or EM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of placebo 1.5 mL for 2 months (on Days 28 and 56). | DB period: Participants with CM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). Participants with EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL and 2 injections of placebo 1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). |
| Measure Participants | 278 | 276 | 283 |
| Least Squares Mean (Standard Error) [days/month] |
-0.6
(0.35)
|
-4.1
(0.35)
|
-4.1
(0.35)
|
| Title | DB Period: Percentage of Participants Reaching at Least 50% Reduction From Baseline in Monthly Average Number of Migraine Days During the 4-Week Period After the First Dose of Fremanezumab |
|---|---|
| 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 meeting criteria for migraine with or without aura; a calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours 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), up to Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| DB mITT analysis set included participants who received at least 1 dose of study drug and had at least 10 days of postbaseline efficacy assessment on the primary endpoint. |
| Arm/Group Title | Placebo | Fremanezumab Quarterly | Fremanezumab Monthly |
|---|---|---|---|
| Arm/Group Description | DB period: Participants with CM or EM received 3 injections of placebo 1.5 mL SC on Day 0 and single injection of placebo 1.5 mL SC on Days 28 and 56. | DB period: Participants with CM or EM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of placebo 1.5 mL for 2 months (on Days 28 and 56). | DB period: Participants with CM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). Participants with EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL and 2 injections of placebo 1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). |
| Measure Participants | 278 | 276 | 283 |
| Number [percentage of participants] |
10
3.6%
|
38
13.8%
|
36
12.7%
|
| Title | DB Period: Change From Baseline in Monthly Average Number of Days of Use of Any Acute Headache Medications During the 12-Week Period After the First Dose of Fremanezumab |
|---|---|
| Description | Baseline data and the mean change from baseline in the monthly average number of days of use of any acute headache medications during the 12-week period after administration of the first dose of study drug (based on Week 0 to 12 data) is reported. Least Squares (LS) mean calculated using analysis of covariance (ANCOVA) model with treatment, gender, region, special group of treatment failure (yes/no), migraine classification (EM/CM), and treatment*migraine classification as fixed effects, and baseline number of migraine days and years since onset of migraines as covariates. |
| Time Frame | Baseline (Day -28 to Day -1), up to Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| DB mITT analysis set included participants who received at least 1 dose of study drug and had at least 10 days of postbaseline efficacy assessment on the primary endpoint. |
| Arm/Group Title | Placebo | Fremanezumab Quarterly | Fremanezumab Monthly |
|---|---|---|---|
| Arm/Group Description | DB period: Participants with CM or EM received 3 injections of placebo 1.5 mL SC on Day 0 and single injection of placebo 1.5 mL SC on Days 28 and 56. | DB period: Participants with CM or EM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of placebo 1.5 mL for 2 months (on Days 28 and 56). | DB period: Participants with CM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). Participants with EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL and 2 injections of placebo 1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). |
| Measure Participants | 278 | 276 | 283 |
| Least Squares Mean (Standard Error) [days/month] |
-0.6
(0.32)
|
-3.7
(0.32)
|
-3.9
(0.32)
|
| Title | DB Period: Change From Baseline in Monthly Average Number of Headache Days of at Least Moderate Severity During the 4-Week Period After the First Dose of Fremanezumab |
|---|---|
| Description | A headache day of at least moderate severity was defined as a calendar day (00:00 to 23:59) demonstrating at least 4 consecutive hours of headache of at least moderate severity or; a calendar day (0:00 to 23:59) demonstrating a headache of any duration that was treated with migraine-specific acute medications (triptans and ergot compounds). 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. LS mean calculated using ANCOVA model with treatment, gender, region, special group of treatment failure (yes/no), migraine classification (EM/CM), and treatment*migraine classification as fixed effects, and baseline number of headache days of at least moderate severity and years since onset of migraines as covariates. |
| Time Frame | Baseline (Day -28 to Day -1), up to Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| DB mITT analysis set included participants who received at least 1 dose of study drug and had at least 10 days of postbaseline efficacy assessment on the primary endpoint. |
| Arm/Group Title | Placebo | Fremanezumab Quarterly | Fremanezumab Monthly |
|---|---|---|---|
| Arm/Group Description | DB period: Participants with CM or EM received 3 injections of placebo 1.5 mL SC on Day 0 and single injection of placebo 1.5 mL SC on Days 28 and 56. | DB period: Participants with CM or EM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of placebo 1.5 mL for 2 months (on Days 28 and 56). | DB period: Participants with CM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). Participants with EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL and 2 injections of placebo 1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). |
| Measure Participants | 278 | 276 | 283 |
| Least Squares Mean (Standard Error) [days/month] |
-0.5
(0.34)
|
-4.2
(0.35)
|
-4.5
(0.34)
|
| Title | DB Period: Number of Participants With Adverse Events (AEs) and Who Did Not Complete the Study Due to AEs |
|---|---|
| Description | An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severe AE was defined as inability to carry out usual activities. Treatment-related AEs were defined as AEs with possible, probable, definite, or missing relationship to study drug. Serious AEs were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. |
| Time Frame | Baseline (Day 0) up to Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. |
| Arm/Group Title | Placebo | Fremanezumab Quarterly | Fremanezumab Monthly |
|---|---|---|---|
| Arm/Group Description | DB period: Participants with CM or EM received 3 injections of placebo 1.5 mL SC on Day 0 and single injection of placebo 1.5 mL SC on Days 28 and 56. | DB period: Participants with CM or EM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of placebo 1.5 mL for 2 months (on Days 28 and 56). | DB period: Participants with CM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). Participants with EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL and 2 injections of placebo 1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). |
| Measure Participants | 277 | 276 | 285 |
| Any AEs |
134
48%
|
151
54.7%
|
129
45.6%
|
| AEs leading to withdrawal from study |
3
1.1%
|
1
0.4%
|
4
1.4%
|
| Title | OL Period: Number of Participants With AEs and Who Did Not Complete the Study Due to AEs |
|---|---|
| Description | An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Severe AE was defined as inability to carry out usual activities. Treatment-related AEs were defined as AEs with possible, probable, definite, or missing relationship to study drug. Serious AEs were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. |
| Time Frame | Week 12 up to Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| OL safety analysis set included all participants who received at least 1 dose of study drug during the OL treatment period. |
| Arm/Group Title | Placebo | Fremanezumab Quarterly | Fremanezumab Monthly |
|---|---|---|---|
| Arm/Group Description | OL period: Participants with CM or EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. | OL period: Participants with CM or EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. | OL period: Participants with CM or EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. |
| Measure Participants | 262 | 271 | 274 |
| Any AEs |
137
49.1%
|
149
54%
|
155
54.8%
|
| AEs leading to withdrawal from study |
4
1.4%
|
1
0.4%
|
2
0.7%
|
| Title | DB Period: Number of Participants With Potentially Clinically Significant Abnormal Serum Chemistry Results |
|---|---|
| Description | Criteria for potentially clinically significant abnormal serum chemistry values included: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), and lactate dehydrogenase (LDH) (units/liter [U/L]): greater than or equal to (≥) 3*upper limit of normal (ULN); Blood Urea Nitrogen (BUN): ≥10.71 millimoles/liter (mmol/L); creatinine: ≥177 micromoles/liter (µmol/L); bilirubin (total): ≥34.2 µmol/L; and uric acid: ≥625 µmol/L (men), and ≥506 µmol/L (women). A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. |
| Time Frame | Baseline up to Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. |
| Arm/Group Title | Placebo | Fremanezumab Quarterly | Fremanezumab Monthly |
|---|---|---|---|
| Arm/Group Description | DB period: Participants with CM or EM received 3 injections of placebo 1.5 mL SC on Day 0 and single injection of placebo 1.5 mL SC on Days 28 and 56. | DB period: Participants with CM or EM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of placebo 1.5 mL for 2 months (on Days 28 and 56). | DB period: Participants with CM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). Participants with EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL and 2 injections of placebo 1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). |
| Measure Participants | 272 | 268 | 280 |
| Count of Participants [Participants] |
1
0.4%
|
3
1.1%
|
4
1.4%
|
| Title | OL Period: Number of Participants With Potentially Clinically Significant Abnormal Serum Chemistry Results |
|---|---|
| Description | Criteria for potentially clinically significant abnormal serum chemistry values included: ALT, AST, ALP, GGT, and LDH (U/L): ≥3*ULN; BUN: ≥10.71 mmol/L; creatinine: ≥177 µmol/L; bilirubin (total): ≥34.2 µmol/L; and uric acid: ≥625 µmol/L (men), and ≥506 µmol/L (women). A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. |
| Time Frame | Week 12 up to Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| OL safety analysis set included all participants who received at least 1 dose of study drug during the OL treatment period. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. |
| Arm/Group Title | Placebo | Fremanezumab Quarterly | Fremanezumab Monthly |
|---|---|---|---|
| Arm/Group Description | OL period: Participants with CM or EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. | OL period: Participants with CM or EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. | OL period: Participants with CM or EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. |
| Measure Participants | 259 | 270 | 273 |
| Count of Participants [Participants] |
2
0.7%
|
3
1.1%
|
2
0.7%
|
| Title | DB Period: Number of Participants With Potentially Clinically Significant Abnormal Hematology Results |
|---|---|
| Description | Criteria for potentially clinically significant abnormal hematology values included: hemoglobin: less than (<) 115 grams/liter (g/L) (in men) or less than or equal to (≤) 95 g/L (in women), hematocrit: <0.37 L/L (in men) or <0.32 L/L (in women), leukocytes: ≥20*10^9/L or ≤3*10^9/L, eosinophils: >=10%, platelets: ≥700*10^9/L or ≤75*10^9/L, and absolute neutrophil count (ANC): ≤1*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 up to Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. |
| Arm/Group Title | Placebo | Fremanezumab Quarterly | Fremanezumab Monthly |
|---|---|---|---|
| Arm/Group Description | DB period: Participants with CM or EM received 3 injections of placebo 1.5 mL SC on Day 0 and single injection of placebo 1.5 mL SC on Days 28 and 56. | DB period: Participants with CM or EM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of placebo 1.5 mL for 2 months (on Days 28 and 56). | DB period: Participants with CM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). Participants with EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL and 2 injections of placebo 1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). |
| Measure Participants | 271 | 268 | 278 |
| Count of Participants [Participants] |
11
3.9%
|
12
4.3%
|
3
1.1%
|
| Title | OL Period: Number of Participants With Potentially Clinically Significant Abnormal Hematology Results |
|---|---|
| Description | Criteria for potentially clinically significant abnormal hematology values included: hemoglobin: <115 g/L (in men) or ≤95 g/L (in women), hematocrit: <0.37 L/L (in men) or <0.32 L/L (in women), leukocytes: ≥20*10^9/L or ≤3*10^9/L, eosinophils: >=10%, platelets: ≥700*10^9/L or ≤75*10^9/L, and ANC: ≤1*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 | Week 12 up to Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| OL safety analysis set included all participants who received at least 1 dose of study drug during the OL treatment period. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. |
| Arm/Group Title | Placebo | Fremanezumab Quarterly | Fremanezumab Monthly |
|---|---|---|---|
| Arm/Group Description | OL period: Participants with CM or EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. | OL period: Participants with CM or EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. | OL period: Participants with CM or EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. |
| Measure Participants | 259 | 270 | 273 |
| Count of Participants [Participants] |
9
3.2%
|
11
4%
|
5
1.8%
|
| Title | DB Period: Number of Participants With Potentially Clinically Significant Abnormal Coagulation Laboratory Test Results |
|---|---|
| Description | Criteria for potentially clinically significant abnormal coagulation values included: prothrombin international normalized ratio (INR): greater than (>) 1.5. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. |
| Time Frame | Baseline up to Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. |
| Arm/Group Title | Placebo | Fremanezumab Quarterly | Fremanezumab Monthly |
|---|---|---|---|
| Arm/Group Description | DB period: Participants with CM or EM received 3 injections of placebo 1.5 mL SC on Day 0 and single injection of placebo 1.5 mL SC on Days 28 and 56. | DB period: Participants with CM or EM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of placebo 1.5 mL for 2 months (on Days 28 and 56). | DB period: Participants with CM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). Participants with EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL and 2 injections of placebo 1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). |
| Measure Participants | 269 | 267 | 277 |
| Count of Participants [Participants] |
2
0.7%
|
4
1.4%
|
4
1.4%
|
| Title | OL Period: Number of Participants With Potentially Clinically Significant Abnormal Coagulation Laboratory Test Results |
|---|---|
| Description | Criteria for potentially clinically significant abnormal coagulation values included: prothrombin INR: >1.5. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. |
| Time Frame | Week 12 up to Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| OL safety analysis set included all participants who received at least 1 dose of study drug during the OL treatment period. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. |
| Arm/Group Title | Placebo | Fremanezumab Quarterly | Fremanezumab Monthly |
|---|---|---|---|
| Arm/Group Description | OL period: Participants with CM or EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. | OL period: Participants with CM or EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. | OL period: Participants with CM or EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. |
| Measure Participants | 257 | 270 | 272 |
| Count of Participants [Participants] |
3
1.1%
|
1
0.4%
|
3
1.1%
|
| Title | DB Period: Number of Participants With Potentially Clinically Significant Abnormal Urinalysis Laboratory Tests Results |
|---|---|
| Description | Criteria for potentially clinically significant abnormal urinalysis values included: urine glucose (milligrams/deciliter [mg/dL]): ≥2 unit increase from baseline, ketones (mg/dL): ≥2 unit increase from baseline, urine total protein (mg/dL): ≥2 unit increase from baseline, and haemoglobin ≥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 up to Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. |
| Arm/Group Title | Placebo | Fremanezumab Quarterly | Fremanezumab Monthly |
|---|---|---|---|
| Arm/Group Description | DB period: Participants with CM or EM received 3 injections of placebo 1.5 mL SC on Day 0 and single injection of placebo 1.5 mL SC on Days 28 and 56. | DB period: Participants with CM or EM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of placebo 1.5 mL for 2 months (on Days 28 and 56). | DB period: Participants with CM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). Participants with EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL and 2 injections of placebo 1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). |
| Measure Participants | 277 | 276 | 285 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
| Title | OL Period: Number of Participants With Potentially Clinically Significant Abnormal Urinalysis Laboratory Tests Results |
|---|---|
| Description | Criteria for potentially clinically significant abnormal urinalysis values included: urine glucose (mg/dL): ≥2 unit increase from baseline, ketones (mg/dL): ≥2 unit increase from baseline, urine total protein (mg/dL): ≥2 unit increase from baseline, and haemoglobin ≥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 | Week 12 up to Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| OL safety analysis set included all participants who received at least 1 dose of study drug during the OL treatment period. |
| Arm/Group Title | Placebo | Fremanezumab Quarterly | Fremanezumab Monthly |
|---|---|---|---|
| Arm/Group Description | OL period: Participants with CM or EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. | OL period: Participants with CM or EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. | OL period: Participants with CM or EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. |
| Measure Participants | 262 | 271 | 274 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
| Title | DB Period: Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Values |
|---|---|
| Description | Criteria for potentially clinically significant abnormal vital signs values 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 celsius and change of ≥1.1 degrees celsius. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. |
| Time Frame | Baseline up to Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. |
| Arm/Group Title | Placebo | Fremanezumab Quarterly | Fremanezumab Monthly |
|---|---|---|---|
| Arm/Group Description | DB period: Participants with CM or EM received 3 injections of placebo 1.5 mL SC on Day 0 and single injection of placebo 1.5 mL SC on Days 28 and 56. | DB period: Participants with CM or EM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of placebo 1.5 mL for 2 months (on Days 28 and 56). | DB period: Participants with CM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). Participants with EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL and 2 injections of placebo 1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). |
| Measure Participants | 277 | 276 | 283 |
| Count of Participants [Participants] |
9
3.2%
|
8
2.9%
|
8
2.8%
|
| Title | OL Period: Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Values |
|---|---|
| Description | Criteria for potentially clinically significant abnormal vital signs values included: pulse rate: ≤50 bpm and decrease of ≥15 bpm, or ≥120 bpm and increase of ≥15 bpm; systolic blood pressure: ≤90 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 celsius and change of ≥1.1 degrees celsius. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. |
| Time Frame | Week 12 up to Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| OL safety analysis set included all participants who received at least 1 dose of study drug during the OL treatment period. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. |
| Arm/Group Title | Placebo | Fremanezumab Quarterly | Fremanezumab Monthly |
|---|---|---|---|
| Arm/Group Description | OL period: Participants with CM or EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. | OL period: Participants with CM or EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. | OL period: Participants with CM or EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. |
| Measure Participants | 261 | 270 | 273 |
| Count of Participants [Participants] |
10
3.6%
|
14
5.1%
|
8
2.8%
|
| Title | DB Period: Number of Participants With Shift From Baseline to Week 12 in Electrocardiogram (ECG) Parameters |
|---|---|
| Description | ECG parameters included: heart rate, PR interval, QRS interval, QT interval corrected using the Fridericia formula (QTcF), QT interval corrected using the Bazett's formula (QTcB) and RR interval. Shifts represented as Baseline - Week 12 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, Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. Here, 'Overall number of participants analyzed' = participants with both baseline and Week 12 ECG findings. |
| Arm/Group Title | Placebo | Fremanezumab Quarterly | Fremanezumab Monthly |
|---|---|---|---|
| Arm/Group Description | DB period: Participants with CM or EM received 3 injections of placebo 1.5 mL SC on Day 0 and single injection of placebo 1.5 mL SC on Days 28 and 56. | DB period: Participants with CM or EM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of placebo 1.5 mL for 2 months (on Days 28 and 56). | DB period: Participants with CM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). Participants with EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL and 2 injections of placebo 1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). |
| Measure Participants | 258 | 271 | 270 |
| Normal - Normal |
199
71.3%
|
218
79%
|
212
74.9%
|
| Normal - Abnormal NCS |
21
7.5%
|
14
5.1%
|
15
5.3%
|
| Normal - Abnormal CS |
0
0%
|
0
0%
|
0
0%
|
| Abnormal NCS - Normal |
10
3.6%
|
19
6.9%
|
12
4.2%
|
| Abnormal NCS - Abnormal NCS |
28
10%
|
20
7.2%
|
31
11%
|
| Abnormal NCS - Abnormal CS |
0
0%
|
0
0%
|
0
0%
|
| Abnormal CS - Normal |
0
0%
|
0
0%
|
0
0%
|
| Abnormal CS - Abnormal NCS |
0
0%
|
0
0%
|
0
0%
|
| Abnormal CS - Abnormal CS |
0
0%
|
0
0%
|
0
0%
|
| Title | OL Period: Number of Participants With Shift From Baseline to Week 24 in ECG Parameters |
|---|---|
| Description | ECG parameters included: heart rate, PR interval, QRS interval, QT interval corrected using the Fridericia formula (QTcF), QT interval corrected using the Bazett's formula (QTcB) and RR interval. Shifts represented as Baseline - Week 24 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, Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| OL safety analysis set included all participants who received at least 1 dose of study drug during the OL treatment period. Here, 'Overall number of participants analyzed' = participants with both baseline and Week 24 ECG findings. |
| Arm/Group Title | Placebo | Fremanezumab Quarterly | Fremanezumab Monthly |
|---|---|---|---|
| Arm/Group Description | OL period: Participants with CM or EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. | OL period: Participants with CM or EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. | OL period: Participants with CM or EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. |
| Measure Participants | 247 | 257 | 261 |
| Normal - Normal |
194
69.5%
|
215
77.9%
|
204
72.1%
|
| Normal - Abnormal NCS |
15
5.4%
|
5
1.8%
|
15
5.3%
|
| Normal - Abnormal CS |
0
0%
|
0
0%
|
1
0.4%
|
| Abnormal NCS - Normal |
14
5%
|
20
7.2%
|
16
5.7%
|
| Abnormal NCS - Abnormal NCS |
24
8.6%
|
17
6.2%
|
25
8.8%
|
| Abnormal NCS - Abnormal CS |
0
0%
|
0
0%
|
0
0%
|
| Abnormal CS - Normal |
0
0%
|
0
0%
|
0
0%
|
| Abnormal CS - Abnormal NCS |
0
0%
|
0
0%
|
0
0%
|
| Abnormal CS - Abnormal CS |
0
0%
|
0
0%
|
0
0%
|
| Title | DB Period: Number of Participants Who Received Concomitant Medications for Adverse Events |
|---|---|
| Description | Concomitant medications included: agents acting on the renin-angiotensin system, all other therapeutic products (for example: homeopathic preparation), allergens, analgesics, anesthetics, anti-parkinson drugs, antianemic preparations, antibacterials for systemic use, antibiotics and chemotherapeutics for dermatological use, antidiarrheals, intestinal antiinflammatory/antiinfective agents, antiemetic, antiepileptics, antifungals for dermatologiocal use, antigout preparations, antihemorrhagics, antihistamines for systemic use, antihypertensives, antiinflammatory and antirheumatic products, antimycotics for systemic use, antipruritics, antipsoriatics, antivirals for systemic use, beta blocking agents, blood substitutes and perfusion solutions, cardiac therapy, corticosteroids, cough and cold preparations, diagnostic radiopharmaceuticals, diuretics, thyroid therapy, urologicals, vaccines, psycoleptics, psycoanaleptics, ophthalmologicals, muscle relaxants, drugs used in diabetes etc. |
| Time Frame | Baseline up to Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| DB safety analysis set included all randomized participants who received at least 1 dose of study drug during the DB treatment period. |
| Arm/Group Title | Placebo | Fremanezumab Quarterly | Fremanezumab Monthly |
|---|---|---|---|
| Arm/Group Description | DB period: Participants with CM or EM received 3 injections of placebo 1.5 mL SC on Day 0 and single injection of placebo 1.5 mL SC on Days 28 and 56. | DB period: Participants with CM or EM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of placebo 1.5 mL for 2 months (on Days 28 and 56). | DB period: Participants with CM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). Participants with EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL and 2 injections of placebo 1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). |
| Measure Participants | 277 | 276 | 285 |
| Count of Participants [Participants] |
274
98.2%
|
269
97.5%
|
280
98.9%
|
| Title | OL Period: Number of Participants Who Received Concomitant Medications for Adverse Events |
|---|---|
| Description | Concomitant medications included: agents acting on the renin-angiotensin system, all other therapeutic products (for example: homeopathic preparation), allergens, analgesics, anesthetics, anti-parkinson drugs, antianemic preparations, antibacterials for systemic use, antibiotics and chemotherapeutics for dermatological use, antidiarrheals, intestinal antiinflammatory/antiinfective agents, antiemetic, antiepileptics, antifungals for dermatologiocal use, antigout preparations, antihemorrhagics, antihistamines for systemic use, antihypertensives, antiinflammatory and antirheumatic products, antimycotics for systemic use, antipruritics, antipsoriatics, antivirals for systemic use, beta blocking agents, blood substitutes and perfusion solutions, cardiac therapy, corticosteroids, cough and cold preparations, diagnostic radiopharmaceuticals, diuretics, thyroid therapy, urologicals, vaccines, psycoleptics, psycoanaleptics, ophthalmologicals, muscle relaxants, drugs used in diabetes etc. |
| Time Frame | Week 12 up to Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| OL safety analysis set included all participants who received at least 1 dose of study drug during the OL treatment period. |
| Arm/Group Title | Placebo | Fremanezumab Quarterly | Fremanezumab Monthly |
|---|---|---|---|
| Arm/Group Description | OL period: Participants with CM or EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. | OL period: Participants with CM or EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. | OL period: Participants with CM or EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. |
| Measure Participants | 262 | 271 | 274 |
| Count of Participants [Participants] |
262
93.9%
|
266
96.4%
|
270
95.4%
|
Adverse Events
| Time Frame | Baseline (Day 0) up to follow-up visit (Week 46) | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Safety analysis set included all participants who received at least 1 dose of study drug. AE data per system organ class (SOC) and preferred term (PT) were summarized collectively for both periods. 2 participants (1 with CM and 1 with EM) randomized to placebo but received Fremanezumab monthly dosing during double-blind treatment period. They were analyzed in the treatment arm per actual treatment received. | |||||
| Arm/Group Title | Placebo | Fremanezumab Quarterly | Fremanezumab Monthly | |||
| Arm/Group Description | DB period: Participants with CM or EM received 3 injections of placebo 1.5 mL SC on Day 0 and single injection of placebo 1.5 mL SC on Days 28 and 56. OL period: Participants with CM or EM received fremanezumab (TEV-48125) 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. | DB period: Participants with CM or EM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of placebo 1.5 mL for 2 months (on Days 28 and 56). OL period: Participants with CM or EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. | DB period: Participants with CM received fremanezumab 675 mg SC (3 injections of fremanezumab 225 mg/1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56). Participants with EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL and 2 injections of placebo 1.5 mL) on Day 0 followed by monthly SC administration of fremanezumab 225 mg (1 injection of fremanezumab 225 mg/1.5 mL) for 2 months (on Days 28 and 56).OL period: Participants with CM or EM received fremanezumab 225 mg SC (1 injection of fremanezumab 225 mg/1.5 mL) at Days 84, 112, and 140. | |||
All Cause Mortality |
||||||
| Placebo | Fremanezumab Quarterly | Fremanezumab Monthly | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/277 (0%) | 0/276 (0%) | 0/285 (0%) | |||
Serious Adverse Events |
||||||
| Placebo | Fremanezumab Quarterly | Fremanezumab Monthly | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 13/277 (4.7%) | 10/276 (3.6%) | 11/285 (3.9%) | |||
| Cardiac disorders | ||||||
| Atrial fibrillation | 0/277 (0%) | 0 | 0/276 (0%) | 0 | 1/285 (0.4%) | 1 |
| Palpitations | 1/277 (0.4%) | 1 | 0/276 (0%) | 0 | 0/285 (0%) | 0 |
| Congenital, familial and genetic disorders | ||||||
| Congenital diaphragmatic hernia | 1/277 (0.4%) | 1 | 0/276 (0%) | 0 | 0/285 (0%) | 0 |
| Eye disorders | ||||||
| Retinal tear | 0/277 (0%) | 0 | 0/276 (0%) | 0 | 1/285 (0.4%) | 1 |
| Gastrointestinal disorders | ||||||
| Anal polyp | 0/277 (0%) | 0 | 1/276 (0.4%) | 2 | 0/285 (0%) | 0 |
| Gastrooesophageal reflux disease | 0/277 (0%) | 0 | 1/276 (0.4%) | 1 | 0/285 (0%) | 0 |
| Inguinal hernia | 1/277 (0.4%) | 1 | 0/276 (0%) | 0 | 0/285 (0%) | 0 |
| Hepatobiliary disorders | ||||||
| Cholecystitis acute | 0/277 (0%) | 0 | 1/276 (0.4%) | 1 | 0/285 (0%) | 0 |
| Cholelithiasis | 0/277 (0%) | 0 | 1/276 (0.4%) | 1 | 1/285 (0.4%) | 1 |
| Immune system disorders | ||||||
| Anaphylactic reaction | 0/277 (0%) | 0 | 0/276 (0%) | 0 | 1/285 (0.4%) | 1 |
| Infections and infestations | ||||||
| Dengue fever | 1/277 (0.4%) | 1 | 0/276 (0%) | 0 | 0/285 (0%) | 0 |
| Diverticulitis | 0/277 (0%) | 0 | 1/276 (0.4%) | 1 | 0/285 (0%) | 0 |
| Peritonsillitis | 1/277 (0.4%) | 1 | 0/276 (0%) | 0 | 0/285 (0%) | 0 |
| Sinusitis | 1/277 (0.4%) | 1 | 0/276 (0%) | 0 | 0/285 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||
| Clavicle fracture | 0/277 (0%) | 0 | 1/276 (0.4%) | 1 | 0/285 (0%) | 0 |
| Foot fracture | 0/277 (0%) | 0 | 1/276 (0.4%) | 1 | 0/285 (0%) | 0 |
| Respiratory fume inhalation disorder | 0/277 (0%) | 0 | 0/276 (0%) | 0 | 1/285 (0.4%) | 1 |
| Rib fracture | 0/277 (0%) | 0 | 1/276 (0.4%) | 1 | 0/285 (0%) | 0 |
| Road traffic accident | 0/277 (0%) | 0 | 1/276 (0.4%) | 1 | 0/285 (0%) | 0 |
| Thoracic vertebral fracture | 1/277 (0.4%) | 1 | 0/276 (0%) | 0 | 0/285 (0%) | 0 |
| Investigations | ||||||
| Blood pressure increased | 1/277 (0.4%) | 1 | 0/276 (0%) | 0 | 0/285 (0%) | 0 |
| International normalised ratio abnormal | 0/277 (0%) | 0 | 1/276 (0.4%) | 1 | 0/285 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||
| Back pain | 0/277 (0%) | 0 | 1/276 (0.4%) | 1 | 0/285 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Angiomyxoma | 0/277 (0%) | 0 | 0/276 (0%) | 0 | 1/285 (0.4%) | 1 |
| Breast cancer | 1/277 (0.4%) | 1 | 0/276 (0%) | 0 | 0/285 (0%) | 0 |
| Thyroid adenoma | 1/277 (0.4%) | 1 | 0/276 (0%) | 0 | 0/285 (0%) | 0 |
| Uterine leiomyoma | 1/231 (0.4%) | 1 | 0/229 (0%) | 0 | 0/240 (0%) | 0 |
| Vulval cancer | 1/231 (0.4%) | 1 | 0/229 (0%) | 0 | 0/240 (0%) | 0 |
| Nervous system disorders | ||||||
| Hypoaesthesia | 1/277 (0.4%) | 1 | 0/276 (0%) | 0 | 0/285 (0%) | 0 |
| Intracranial aneurysm | 0/277 (0%) | 0 | 1/276 (0.4%) | 1 | 0/285 (0%) | 0 |
| Migraine | 1/277 (0.4%) | 1 | 0/276 (0%) | 0 | 0/285 (0%) | 0 |
| Multiple sclerosis | 0/277 (0%) | 0 | 0/276 (0%) | 0 | 1/285 (0.4%) | 1 |
| Optic neuritis | 0/277 (0%) | 0 | 0/276 (0%) | 0 | 1/285 (0.4%) | 1 |
| Renal and urinary disorders | ||||||
| Nephrolithiasis | 0/277 (0%) | 0 | 0/276 (0%) | 0 | 2/285 (0.7%) | 2 |
| Renal colic | 0/277 (0%) | 0 | 1/276 (0.4%) | 1 | 0/285 (0%) | 0 |
| Reproductive system and breast disorders | ||||||
| Dysmenorrhoea | 0/231 (0%) | 0 | 1/229 (0.4%) | 1 | 0/240 (0%) | 0 |
| Endometriosis | 0/231 (0%) | 0 | 0/229 (0%) | 0 | 1/240 (0.4%) | 1 |
| Menometrorrhagia | 0/231 (0%) | 0 | 0/229 (0%) | 0 | 1/240 (0.4%) | 1 |
| Menorrhagia | 0/231 (0%) | 0 | 1/229 (0.4%) | 1 | 0/240 (0%) | 0 |
| Metrorrhagia | 1/231 (0.4%) | 1 | 0/229 (0%) | 0 | 0/240 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Vocal cord thickening | 0/277 (0%) | 0 | 0/276 (0%) | 0 | 1/285 (0.4%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||
| Placebo | Fremanezumab Quarterly | Fremanezumab Monthly | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 88/277 (31.8%) | 90/276 (32.6%) | 81/285 (28.4%) | |||
| General disorders | ||||||
| Injection site erythema | 24/277 (8.7%) | 53 | 31/276 (11.2%) | 66 | 32/285 (11.2%) | 80 |
| Injection site induration | 16/277 (5.8%) | 52 | 19/276 (6.9%) | 41 | 18/285 (6.3%) | 65 |
| Injection site pain | 10/277 (3.6%) | 20 | 15/276 (5.4%) | 42 | 14/285 (4.9%) | 42 |
| Infections and infestations | ||||||
| Nasopharyngitis | 32/277 (11.6%) | 37 | 30/276 (10.9%) | 41 | 25/285 (8.8%) | 30 |
| Upper respiratory tract infection | 10/277 (3.6%) | 10 | 8/276 (2.9%) | 11 | 16/285 (5.6%) | 17 |
| Nervous system disorders | ||||||
| Migraine | 21/277 (7.6%) | 26 | 14/276 (5.1%) | 15 | 12/285 (4.2%) | 14 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.
Results Point of Contact
| Name/Title | Director, Clinical Research |
|---|---|
| Organization | Teva Branded Pharmaceutical Products, R&D Inc. |
| Phone | 1-888-483-8279 |
| USMedInfo@tevapharm.com |
- TV48125-CNS-30068
- 2017-002441-30