Comparing Efficacy and Safety of 2 Dose Regimens of Subcutaneous Administration of TEV-48125 Versus Placebo for the Preventive Treatment of Chronic Migraine
Sponsor
Teva Branded Pharmaceutical Products R&D, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT02621931
Collaborator
(none)
1,130
273
3
12.6
4.1
0.3
Study Details
Study Description
Brief Summary
The study is being conducted to evaluate two doses of TEV-48125 in adult patients with chronic migraine
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
1130 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study Comparing the Efficacy and Safety of 2 Dose Regimens of Subcutaneous Administration of Fremanezumab (TEV-48125) Versus Placebo for the Preventive Treatment of Chronic Migraine
Actual Study Start Date
:
Mar 22, 2016
Actual Primary Completion Date
:
Apr 11, 2017
Actual Study Completion Date
:
Apr 11, 2017
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Placebo Matching Placebo |
Drug: Placebo
Placebo 1.5 mL pre-filled syringes identical in appearance to active intervention. Study drug was administered at the clinical site.
|
| Experimental: Fremanezumab 675 mg/placebo/placebo Participants randomized to the fremanezumab 675 mg/placebo/placebo treatment arm received 675 mg of fremanezumab as 3 active injections (225 mg/1.5 mL) on Day 0, and placebo as a single 1.5-mL injection on Days 28 and 56. |
Drug: Fremanezumab
Fremanezumab was provided as a sterile, unpreserved, aqueous solution for injection, 225 mg/1.5 mL pre-filled syringe for single-use administration. The 675 mg dose was given as 3 injections; doses of 225 mg were given as a single injection. Study drug was administered at the clinical site.
Other Names:
Drug: Placebo
Placebo 1.5 mL pre-filled syringes identical in appearance to active intervention. Study drug was administered at the clinical site.
|
| Experimental: Fremanezumab 675/225/225 mg Participants randomized to the fremanezumab 675/225/225 mg treatment arm received 675 mg of fremanezumab as 3 active injections (225 mg/1.5 mL) on Day 0 and 225 mg of fremanezumab as 1 active injection (225 mg/1.5 mL) on Days 28 and 56. |
Drug: Fremanezumab
Fremanezumab was provided as a sterile, unpreserved, aqueous solution for injection, 225 mg/1.5 mL pre-filled syringe for single-use administration. The 675 mg dose was given as 3 injections; doses of 225 mg were given as a single injection. Study drug was administered at the clinical site.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline in the Monthly Average Number of Headache Days of At Least Moderate Severity During the 12-Week Period After the First Dose of Study Drug [Baseline (Days -28 to Day -1), Treatment (Days 1 - Week 12)]
Headaches were subjectively rated by participants as mild, moderate or severe. A headache day of at least moderate severity was defined as a calendar day (00:00 to 23:59) where the patient (using the electronic headache diary device) reports: - a day with headache pain that lasts ≥4 hours with a peak severity of at least moderate severity or - a day when the patient used acute migraine-specific medication (triptans or ergots) to treat a headache of any severity or duration. Monthly averages are derived and normalized to 28 days equivalent by the following formula: (# days of efficacy variable over relevant period / # days with assessments recorded in the e-diary over the relevant period) * 28. The change is calculated as post-baseline value - baseline value.
- Participants With Treatment-Emergent Adverse Events (TEAEs) [Day 1 to Week 12]
An adverse event (AE) was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an AE which prevents usual activities. Relationship of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes.
Secondary Outcome Measures
- Change From Baseline in the Monthly Average Number of Migraine Days During the 12-Week Period After the First Dose of Study Drug [Baseline (Days -28 to Day -1), Treatment (Days 1 - 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 endorsing criteria for migraine with or without aura - a calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache endorsing criteria for probable migraine, a migraine subtype where only 1 migraine criterion is missing - a calendar day (0:00 to 23:59) demonstrating a headache of any duration that was treated with migraine-specific medications (triptans and ergot compounds). Monthly averages are derived and normalized to 28 days equivalent by the following formula: (# days of efficacy variable over relevant period / # days with assessments recorded in the e-diary over the relevant period) * 28. The change is calculated as post-baseline value - baseline value.
- Percentage of Participants With At Least 50% Reduction In Monthly Average Number of Headache Days of At Least Moderate Severity [Baseline (Days -28 to Day -1), Treatment: Month 1, Month 2, Month 3, Month 1-3 (Days 1 - Week 12)]
Responder rates were defined as the percentage of total subjects who reached at least a 50% reduction in the monthly average of headache days (as subjectively reported by participants in the study diary) of at least moderate severity relative to the baseline period. For the overall analysis (Month 1-3), patients who discontinued early were considered non-responders. Monthly averages are derived and normalized to 28 days equivalent by the following formula: (# days of efficacy variable over relevant period / # days with assessments recorded in the e-diary over the relevant period) * 28. The percentage reduction in monthly average is calculated as: ((baseline value - post-baseline value) / baseline value) * 100.
- Change From Baseline in the Monthly Average Number of Days of Use of Any Acute Headache Medicine During the 12 Week Period After the First Dose of Study Drug [Baseline (Days -28 to Day -1), Treatment (Days 1 - Week 12)]
Participants recorded any migraine medications (name of drug, number of tablets/capsules, and the dose in milligrams per tablet/capsule) taken on each day in their electronic headache diary device. Acute migraine-specific medication included triptans or ergots. Monthly averages are derived and normalized to 28 days equivalent by the following formula: (# days of efficacy variable over relevant period / # days with assessments recorded in the e-diary over the relevant period) * 28. The change is calculated as post-baseline value - baseline value.
- Change From Baseline in the Number of Headache Days of At Least Moderate Severity During the 4 Week Period After the First Dose of Study Drug [Baseline (Days -28 to Day -1), Treatment (Days 1 - Week 4)]
Headaches were subjectively rated by participants as mild, moderate or severe. A headache day of at least moderate severity was defined as a calendar day (00:00 to 23:59) where the patient (using the electronic headache diary device) reports: - a day with headache pain that lasts ≥4 hours with a peak severity of at least moderate severity or - a day when the patient used acute migraine-specific medication (triptans or ergots) to treat a headache of any severity or duration. The change is calculated as post-baseline value - baseline value.
- Change From Baseline in the Monthly Average Number of Headache Days of At Least Moderate Severity During the 12 Week Period After the First Dose of Study Medication in Patients Not Receiving Concomitant Preventive Migraine Medications [Baseline (Days -28 to Day -1), Treatment (Days 1 - Week 12)]
A subset of patients (specified in the protocol not to exceed 30%) were allowed to use 1 concomitant migraine preventive medication. This outcome only includes those participants who did not take concomitant preventive migraine medication during this study. Headaches were subjectively rated by participants as mild, moderate or severe. A headache day of >= moderate severity was defined as a calendar day where the patient (using the electronic headache diary device) reports: - a day with headache pain that lasts ≥4 hours with a peak severity of >= moderate severity or - a day when the patient used acute migraine-specific medication (triptans or ergots) to treat a headache of any severity or duration. Monthly averages are derived and normalized to 28 days equivalent by the following formula: (# days of efficacy variable over relevant period / # days with assessments recorded in the e-diary over the relevant period) * 28. Change is post-baseline value - baseline value.
- Change From Baseline in Migraine-Related Disability Score, As Measured by the 6-Item Headache Impact Test (HIT) At Week 12 [Baseline, 12 weeks]
The HIT-6 was developed by Kosinski et al (2003) as a short form for reliably assessing the adverse headache impact in clinical practice and clinical research settings. The questionnaire measures the adverse impact of headache on social functioning, role functioning, vitality, cognitive functioning, and psychological distress. It also assesses headache severity. Scores range from 36 to 78, where a higher score indicates a greater impact of headache on the daily life of the patient, i.e. scores ≤49 represent little or no impact, scores between 50 and 55 represent some impact, scores between 56 and 59 represent substantial impact; and scores ≥60 indicate severe impact. Negative change from baseline values indicate less adverse impact of headache.
- Electrocardiogram (ECG) Findings Shifts From Baseline to Overall [Baseline (Day 0), Treatment Week 12 (or endpoint)]
12-lead ECGs were performed before other assessments (eg, blood draws and administration of questionnaires) and performed in triplicate. The worst post-baseline finding for the participant is summarized. Only participants with both baseline and post-baseline ECGs are included. The ECG was evaluated by the investigator at the time of recording (signed and dated), and the printout was kept in the source documentation file. When potentially clinically significant findings were detected by the investigator, a cardiologist at a central diagnostic center was consulted for a definitive interpretation. Any ECG finding that was judged by the investigator as a potentially clinically significant change (worsening) compared with a baseline value was considered an adverse event. - NCS = abnormal, not clinically significant. - CS= abnormal, clinically significant. Shift format is: baseline finding / worst post-baseline finding.
- Participants With Vital Signs Potentially Clinically Significant Abnormal Values [Treatment Days 28, 56 and 84 (or endpoint). Changes from previous reading may reflect the baseline reading performed on Day 0.]
Vital signs were performed before other assessments (eg, blood draws and administration of questionnaires). Vital signs with potentially clinically significant abnormal findings included: - Pulse Rate High: >=120 and increase of >=15 beats per minute - Pulse Rate Low: <=50 and decrease of >=15 beats per minute - Systolic Blood Pressure Low: <=90 mmHg and decrease of >=20 mmHg - Diastolic Blood Pressure High: >=105 mmHg and increase of >=15 mmHg - Diastolic Blood Pressure Low: <=50 mmHg and decrease of >=15 mmHg - Respiratory Rate Low: <10 breaths / minute
- Participants With Serum Chemistry and Hematology Potentially Clinically Significant Abnormal Results [Treatment Days 28, 56 and 84 (or endpoint)]
Serum chemistry and hematology laboratory tests with potentially clinically significant abnormal findings included: - Blood Urea Nitrogen (BUN) High: >=10.71 mmol/L - Creatinine High: >=177 umol/L - Bilirubin High: >=34.2 umol/L - Alanine Aminotransferase (ALT): >=3*upper limit of normal (ULN) - Aspartate Aminotransferase (AST): >=3*upper limit of normal (ULN) - Gamma Glutamyl Transferase (GGT): >=3*upper limit of normal (ULN) - Hemoglobin: Male: <115 g/L or Female: <=95 g/L - Hematocrit: Male: <0.37 L/L or Female: <0.32 L/L - Leukocytes: >=20*10^9/L or <=3*10^9/L - Eosinophils/Leukocytes: >=10% - Platelets: >=700*10^9/L or <=75*10^9/L
- Participants With Urinalysis Laboratory Tests Potentially Clinically Significant Abnormal Results [Treatment Days 28, 56 and 84 (or endpoint). Changes from previous reading reflect the baseline reading performed on Day 0.]
Urinalysis with potentially clinically significant abnormal findings included: - Blood: >=2 unit increase from baseline - Urine Glucose (mg/dL): >=2 unit increase from baseline - Ketones (mg/dL): >=2 unit increase from baseline - Urine Protein (mg/dL): >=2 unit increase from baseline
- Prothrombin Time Shifts From Baseline to Endpoint [Baseline (Day 0), Treatment Endpoint (Week 12)]
Shifts in prothrombin time from baseline to endpoint were summarized using patient counts grouped into three categories: - Low (below normal range) - Normal (within the normal range of 9.4 to 12.5 seconds) - High (above normal range) Shift format is: baseline finding / endpoint finding
- Injection Site Reaction Adverse Events [Day 1 to Week 12]
Counts of participants who reported treatment-emergent injection site reactions as AEs are summarized. Preferred terms from MedDRA version 18.1 are offered without a threshold applied.
- Participants With Positive Electronic Columbia Suicide Severity Rating Scale (eC-SSRS) Results After the First Dose of Study Drug [Baseline (Day 0), Treatment Days 28, 56, 84]
The electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) was used to assess the participant's suicidal ideation (severity and intensity) and behavior (Posner et al 2011). Suicidal behavior is defined as a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation is defined as a "yes" answer to any one of 5 suicidal ideation questions: wish to be dead, and 4 different categories of active suicidal ideation. The eC-SSRS Baseline/Screening version was completed by the participant at baseline, and the eC-SSRS Since Last Visit version was completed by the participant at all other time points. Any positive findings on the eC-SSRS Since Last Visit version required evaluation by a physician or doctoral-level psychologist. Findings after the first dose of study drug using the eC-SSRS Since Last Visit version are summarized.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 70 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Males or females aged 18 to 70 years, inclusive, with migraine onset at ≤50 years of age
-
Patient signs and dates the informed consent document
-
Patient has history of migraine according to International Classification of Headache Disorders, or clinical judgment suggests a migraine diagnosis
-
85% e-diary compliance
-
Total body weight between 99 and 250 lbs, inclusive
-
Additional criteria apply, please contact the investigator for more information
Exclusion Criteria:
-
Clinically significant hematological, cardiac, renal, endocrine, pulmonary, gastrointestinal, genitourinary, neurologic, hepatic, or ocular disease, at the discretion of the investigator
-
Evidence or medical history of clinically significant psychiatric issues, including any suicide attempt in the past, or suicidal ideation with a specific plan in the past 2 years
-
History of clinically significant cardiovascular disease or vascular ischemia (such as myocardial, neurological [eg, cerebral ischemia], peripheral extremity ischemia, or other ischemic event) or thromboembolic events (arterial or venous thrombotic or embolic events), such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism
-
Known infection or history of human immunodeficiency virus, tuberculosis, or chronic hepatitis B or C infection
-
Past or current history of cancer in the last 5 years, except for appropriately treated nonmelanoma skin carcinoma
-
Pregnant or nursing females
-
History of hypersensitivity reactions to injected proteins, including monoclonal antibodies
-
Participation in a clinical study of a new chemical entity or a prescription medicine within 2 months prior to study drug administration or 5 half-lives, whichever is longer
-
Additional criteria apply, please contact the investigator for more information
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Teva Investigational Site 13628 | Birmingham | Alabama | United States | 35211 |
| 2 | Teva Investigational Site 13577 | Birmingham | Alabama | United States | 35216 |
| 3 | Teva Investigational Site 13577 | Birmingham | Alabama | United States | |
| 4 | Teva Investigational Site 13628 | Birmingham | Alabama | United States | |
| 5 | Teva Investigational Site 13606 | Phoenix | Arizona | United States | 85018 |
| 6 | Teva Investigational Site 13579 | Phoenix | Arizona | United States | 85023 |
| 7 | Teva Investigational Site 13579 | Phoenix | Arizona | United States | |
| 8 | Teva Investigational Site 13606 | Phoenix | Arizona | United States | |
| 9 | Teva Investigational Site 13602 | Little Rock | Arkansas | United States | 72205 |
| 10 | Teva Investigational Site 13602 | Little Rock | Arkansas | United States | |
| 11 | Teva Investigational Site 13568 | Encino | California | United States | 91316 |
| 12 | Teva Investigational Site 13568 | Encino | California | United States | |
| 13 | Teva Investigational Site 13546 | Fullerton | California | United States | 92835 |
| 14 | Teva Investigational Site 13546 | Fullerton | California | United States | |
| 15 | Teva Investigational Site 13540 | Long Beach | California | United States | 90806 |
| 16 | Teva Investigational Site 13540 | Long Beach | California | United States | |
| 17 | Teva Investigational Site 13632 | Redlands | California | United States | 92374 |
| 18 | Teva Investigational Site 13632 | Redlands | California | United States | |
| 19 | Teva Investigational Site 13571 | Redondo Beach | California | United States | 90277 |
| 20 | Teva Investigational Site 13571 | Redondo Beach | California | United States | |
| 21 | Teva Investigational Site 13573 | San Diego | California | United States | 92103 |
| 22 | Teva Investigational Site 13573 | San Diego | California | United States | |
| 23 | Teva Investigational Site 13538 | Santa Monica | California | United States | 90404 |
| 24 | Teva Investigational Site 13538 | Santa Monica | California | United States | |
| 25 | Teva Investigational Site 13594 | Santa Rosa | California | United States | 95405 |
| 26 | Teva Investigational Site 13594 | Santa Rosa | California | United States | |
| 27 | Teva Investigational Site 13595 | Walnut Creek | California | United States | 94598 |
| 28 | Teva Investigational Site 13595 | Walnut Creek | California | United States | |
| 29 | Teva Investigational Site 13629 | Aurora | Colorado | United States | 80014 |
| 30 | Teva Investigational Site 13629 | Aurora | Colorado | United States | |
| 31 | Teva Investigational Site 13557 | Boulder | Colorado | United States | 80301 |
| 32 | Teva Investigational Site 13557 | Boulder | Colorado | United States | |
| 33 | Teva Investigational Site 13593 | Colorado Springs | Colorado | United States | 80918 |
| 34 | Teva Investigational Site 13593 | Colorado Springs | Colorado | United States | |
| 35 | Teva Investigational Site 13633 | Denver | Colorado | United States | 80210 |
| 36 | Teva Investigational Site 13612 | Denver | Colorado | United States | 80239 |
| 37 | Teva Investigational Site 13612 | Denver | Colorado | United States | |
| 38 | Teva Investigational Site 13633 | Denver | Colorado | United States | |
| 39 | Teva Investigational Site 13631 | Englewood | Colorado | United States | 80113 |
| 40 | Teva Investigational Site 13631 | Englewood | Colorado | United States | |
| 41 | Teva Investigational Site 13563 | East Hartford | Connecticut | United States | 06118 |
| 42 | Teva Investigational Site 13563 | East Hartford | Connecticut | United States | |
| 43 | Teva Investigational Site 13550 | Stamford | Connecticut | United States | 06905 |
| 44 | Teva Investigational Site 13550 | Stamford | Connecticut | United States | |
| 45 | Teva Investigational Site 13635 | Bradenton | Florida | United States | 34201 |
| 46 | Teva Investigational Site 13635 | Bradenton | Florida | United States | |
| 47 | Teva Investigational Site 13597 | Gainesville | Florida | United States | 32607 |
| 48 | Teva Investigational Site 13597 | Gainesville | Florida | United States | |
| 49 | Teva Investigational Site 13607 | Hialeah | Florida | United States | 33012 |
| 50 | Teva Investigational Site 13607 | Hialeah | Florida | United States | |
| 51 | Teva Investigational Site 13559 | Jacksonville | Florida | United States | 32205 |
| 52 | Teva Investigational Site 13559 | Jacksonville | Florida | United States | |
| 53 | Teva Investigational Site 13584 | Ocala | Florida | United States | 34471 |
| 54 | Teva Investigational Site 13584 | Ocala | Florida | United States | |
| 55 | Teva Investigational Site 13587 | Orlando | Florida | United States | 32806 |
| 56 | Teva Investigational Site 13599 | Orlando | Florida | United States | 32819 |
| 57 | Teva Investigational Site 13551 | Orlando | Florida | United States | |
| 58 | Teva Investigational Site 13555 | Orlando | Florida | United States | |
| 59 | Teva Investigational Site 13587 | Orlando | Florida | United States | |
| 60 | Teva Investigational Site 13599 | Orlando | Florida | United States | |
| 61 | Teva Investigational Site 13567 | Palm Beach Gardens | Florida | United States | 33410 |
| 62 | Teva Investigational Site 13567 | Palm Beach Gardens | Florida | United States | |
| 63 | Teva Investigational Site 13553 | Pembroke Pines | Florida | United States | 33026 |
| 64 | Teva Investigational Site 13553 | Pembroke Pines | Florida | United States | |
| 65 | Teva Investigational Site 13616 | Pinellas Park | Florida | United States | 33781 |
| 66 | Teva Investigational Site 13616 | Pinellas Park | Florida | United States | |
| 67 | Teva Investigational Site 13620 | Atlanta | Georgia | United States | 30312 |
| 68 | Teva Investigational Site 13537 | Atlanta | Georgia | United States | 30342 |
| 69 | Teva Investigational Site 13537 | Atlanta | Georgia | United States | |
| 70 | Teva Investigational Site 13620 | Atlanta | Georgia | United States | |
| 71 | Teva Investigational Site 13604 | Boise | Idaho | United States | |
| 72 | Teva Investigational Site 13604 | Meridian | Idaho | United States | 83642 |
| 73 | Teva Investigational Site 13585 | Chicago | Illinois | United States | 60607 |
| 74 | Teva Investigational Site 13621 | Chicago | Illinois | United States | 60654 |
| 75 | Teva Investigational Site 13585 | Chicago | Illinois | United States | |
| 76 | Teva Investigational Site 13621 | Chicago | Illinois | United States | |
| 77 | Teva Investigational Site 13627 | Evanston | Illinois | United States | 60201 |
| 78 | Teva Investigational Site 13627 | Evanston | Illinois | United States | |
| 79 | Teva Investigational Site 13596 | Indianapolis | Indiana | United States | 46254 |
| 80 | Teva Investigational Site 13596 | Indianapolis | Indiana | United States | |
| 81 | Teva Investigational Site 13617 | Wichita | Kansas | United States | 67207 |
| 82 | Teva Investigational Site 13598 | Wichita | Kansas | United States | 67211 |
| 83 | Teva Investigational Site 13598 | Wichita | Kansas | United States | |
| 84 | Teva Investigational Site 13617 | Wichita | Kansas | United States | |
| 85 | Teva Investigational Site 13566 | Louisville | Kentucky | United States | 40207 |
| 86 | Teva Investigational Site 13566 | Louisville | Kentucky | United States | |
| 87 | Teva Investigational Site 13603 | Metairie | Louisiana | United States | 70006 |
| 88 | Teva Investigational Site 13603 | Metairie | Louisiana | United States | |
| 89 | Teva Investigational Site 13582 | Baltimore | Maryland | United States | |
| 90 | Teva Investigational Site 13582 | Pikesville | Maryland | United States | 21208 |
| 91 | Teva Investigational Site 13590 | Boston | Massachusetts | United States | 02131 |
| 92 | Teva Investigational Site 13590 | Boston | Massachusetts | United States | |
| 93 | Teva Investigational Site 13589 | New Bedford | Massachusetts | United States | 02301 |
| 94 | Teva Investigational Site 13589 | New Bedford | Massachusetts | United States | |
| 95 | Teva Investigational Site 13543 | Watertown | Massachusetts | United States | 02472 |
| 96 | Teva Investigational Site 13543 | Watertown | Massachusetts | United States | |
| 97 | Teva Investigational Site 13539 | Ann Arbor | Michigan | United States | 48104 |
| 98 | Teva Investigational Site 13539 | Ann Arbor | Michigan | United States | |
| 99 | Teva Investigational Site 13542 | Golden Valley | Minnesota | United States | 55422 |
| 100 | Teva Investigational Site 13542 | Golden Valley | Minnesota | United States | |
| 101 | Teva Investigational Site 13534 | Kansas City | Missouri | United States | 64114 |
| 102 | Teva Investigational Site 13534 | Kansas City | Missouri | United States | |
| 103 | Teva Investigational Site 13619 | Saint Louis | Missouri | United States | 63141 |
| 104 | Teva Investigational Site 13619 | Saint Louis | Missouri | United States | |
| 105 | Teva Investigational Site 13536 | Springfield | Missouri | United States | |
| 106 | Teva Investigational Site 13618 | Fremont | Nebraska | United States | 68025 |
| 107 | Teva Investigational Site 13618 | Fremont | Nebraska | United States | |
| 108 | Teva Investigational Site 13605 | Las Vegas | Nevada | United States | 89106 |
| 109 | Teva Investigational Site 13605 | Las Vegas | Nevada | United States | |
| 110 | Teva Investigational Site 13578 | Lebanon | New Hampshire | United States | 03756 |
| 111 | Teva Investigational Site 13578 | Lebanon | New Hampshire | United States | |
| 112 | Teva Investigational Site 13575 | Martinsville | New Jersey | United States | |
| 113 | Teva Investigational Site 13575 | Raritan | New Jersey | United States | 08869 |
| 114 | Teva Investigational Site 13588 | Albuquerque | New Mexico | United States | 87102 |
| 115 | Teva Investigational Site 13588 | Albuquerque | New Mexico | United States | |
| 116 | Teva Investigational Site 13576 | Amherst | New York | United States | 14226 |
| 117 | Teva Investigational Site 13576 | Amherst | New York | United States | |
| 118 | Teva Investigational Site 13565 | Plainview | New York | United States | 11803 |
| 119 | Teva Investigational Site 13565 | Plainview | New York | United States | |
| 120 | Teva Investigational Site 13544 | Greensboro | North Carolina | United States | 27401 |
| 121 | Teva Investigational Site 13574 | Greensboro | North Carolina | United States | 27408 |
| 122 | Teva Investigational Site 13544 | Greensboro | North Carolina | United States | |
| 123 | Teva Investigational Site 13574 | Greensboro | North Carolina | United States | |
| 124 | Teva Investigational Site 13545 | Raleigh | North Carolina | United States | 27607 |
| 125 | Teva Investigational Site 13545 | Raleigh | North Carolina | United States | |
| 126 | Teva Investigational Site 13609 | Akron | Ohio | United States | 44311 |
| 127 | Teva Investigational Site 13634 | Akron | Ohio | United States | 44311 |
| 128 | Teva Investigational Site 13609 | Akron | Ohio | United States | |
| 129 | Teva Investigational Site 13634 | Akron | Ohio | United States | |
| 130 | Teva Investigational Site 13533 | Cincinnati | Ohio | United States | 45227 |
| 131 | Teva Investigational Site 13624 | Cincinnati | Ohio | United States | 45249 |
| 132 | Teva Investigational Site 13533 | Cincinnati | Ohio | United States | |
| 133 | Teva Investigational Site 13624 | Cincinnati | Ohio | United States | |
| 134 | Teva Investigational Site 13569 | Cleveland | Ohio | United States | 44195 |
| 135 | Teva Investigational Site 13569 | Cleveland | Ohio | United States | |
| 136 | Teva Investigational Site 13626 | Columbus | Ohio | United States | 43212 |
| 137 | Teva Investigational Site 13626 | Columbus | Ohio | United States | |
| 138 | Teva Investigational Site 13625 | Mogadore | Ohio | United States | 44260 |
| 139 | Teva Investigational Site 13625 | Mogadore | Ohio | United States | |
| 140 | Teva Investigational Site 13561 | Oklahoma City | Oklahoma | United States | 73112 |
| 141 | Teva Investigational Site 13561 | Oklahoma City | Oklahoma | United States | |
| 142 | Teva Investigational Site 13601 | Eugene | Oregon | United States | 97401 |
| 143 | Teva Investigational Site 13601 | Eugene | Oregon | United States | |
| 144 | Teva Investigational Site 13591 | Jenkintown | Pennsylvania | United States | 19046 |
| 145 | Teva Investigational Site 13591 | Jenkintown | Pennsylvania | United States | |
| 146 | Teva Investigational Site 13554 | Philadelphia | Pennsylvania | United States | 19107 |
| 147 | Teva Investigational Site 13554 | Philadelphia | Pennsylvania | United States | |
| 148 | Teva Investigational Site 13608 | Uniontown | Pennsylvania | United States | 15401 |
| 149 | Teva Investigational Site 13608 | Uniontown | Pennsylvania | United States | |
| 150 | Teva Investigational Site 13615 | Greer | South Carolina | United States | 29650 |
| 151 | Teva Investigational Site 13615 | Greer | South Carolina | United States | |
| 152 | Teva Investigational Site 13556 | Mount Pleasant | South Carolina | United States | 29464 |
| 153 | Teva Investigational Site 13556 | Mount Pleasant | South Carolina | United States | |
| 154 | Teva Investigational Site 13560 | Bristol | Tennessee | United States | 37620 |
| 155 | Teva Investigational Site 13560 | Bristol | Tennessee | United States | |
| 156 | Teva Investigational Site 13532 | Nashville | Tennessee | United States | 37203 |
| 157 | Teva Investigational Site 13552 | Nashville | Tennessee | United States | 37203 |
| 158 | Teva Investigational Site 13532 | Nashville | Tennessee | United States | |
| 159 | Teva Investigational Site 13552 | Nashville | Tennessee | United States | |
| 160 | Teva Investigational Site 13541 | Austin | Texas | United States | 78731 |
| 161 | Teva Investigational Site 13541 | Austin | Texas | United States | |
| 162 | Teva Investigational Site 13623 | Dallas | Texas | United States | 75214 |
| 163 | Teva Investigational Site 13623 | Dallas | Texas | United States | |
| 164 | Teva Investigational Site 13611 | Plano | Texas | United States | 75024 |
| 165 | Teva Investigational Site 13611 | Plano | Texas | United States | |
| 166 | Teva Investigational Site 13572 | San Antonio | Texas | United States | 78229 |
| 167 | Teva Investigational Site 13572 | San Antonio | Texas | United States | |
| 168 | Teva Investigational Site 13614 | Murray | Utah | United States | 84107 |
| 169 | Teva Investigational Site 13614 | Murray | Utah | United States | |
| 170 | Teva Investigational Site 13581 | West Jordan | Utah | United States | 84088 |
| 171 | Teva Investigational Site 13581 | West Jordan | Utah | United States | |
| 172 | Teva Investigational Site 13630 | Virginia Beach | Virginia | United States | 23454 |
| 173 | Teva Investigational Site 13630 | Virginia Beach | Virginia | United States | |
| 174 | Teva Investigational Site 13564 | Seattle | Washington | United States | 98105 |
| 175 | Teva Investigational Site 13586 | Seattle | Washington | United States | 98105 |
| 176 | Teva Investigational Site 13564 | Seattle | Washington | United States | |
| 177 | Teva Investigational Site 13586 | Seattle | Washington | United States | |
| 178 | Teva Investigational Site 13600 | Morgantown | West Virginia | United States | 26506 |
| 179 | Teva Investigational Site 13600 | Morgantown | West Virginia | United States | |
| 180 | Teva Investigational Site 11124 | Hamilton | Ontario | Canada | L8N 1Y2 |
| 181 | Teva Investigational Site 11124 | Hamilton | Ontario | Canada | |
| 182 | Teva Investigational Site 11120 | Calgary | Canada | T3M 1M4 | |
| 183 | Teva Investigational Site 11120 | Calgary | Canada | ||
| 184 | Teva Investigational Site 11121 | Montreal | Canada | H2W 1V1 | |
| 185 | Teva Investigational Site 11121 | Montreal | Canada | ||
| 186 | Teva Investigational Site 11122 | Newmarket | Canada | L3Y5G8 | |
| 187 | Teva Investigational Site 11122 | Newmarket | Canada | ||
| 188 | Teva Investigational Site 11123 | Sarnia | Canada | N7T 4X3 | |
| 189 | Teva Investigational Site 11123 | Sarnia | Canada | ||
| 190 | Teva Investigational Site 54144 | Brno | Czechia | 602 00 | |
| 191 | Teva Investigational Site 54144 | Brno | Czechia | ||
| 192 | Teva Investigational Site 54141 | Kunratice | Czechia | 14800 | |
| 193 | Teva Investigational Site 54141 | Kunratice | Czechia | ||
| 194 | Teva Investigational Site 54145 | Pardubice | Czechia | 53002 | |
| 195 | Teva Investigational Site 54145 | Pardubice | Czechia | ||
| 196 | Teva Investigational Site 54142 | Prague 4 | Czechia | 140 59 | |
| 197 | Teva Investigational Site 54142 | Prague 4 | Czechia | ||
| 198 | Teva Investigational Site 54146 | Praha 3 | Czechia | 130 00 | |
| 199 | Teva Investigational Site 54146 | Praha 3 | Czechia | ||
| 200 | Teva Investigational Site 54143 | Praha | Czechia | 100 00 | |
| 201 | Teva Investigational Site 54143 | Praha | Czechia | ||
| 202 | Teva Investigational Site 40018 | Helsinki | Finland | 00100 | |
| 203 | Teva Investigational Site 40017 | Helsinki | Finland | 00930 | |
| 204 | Teva Investigational Site 40017 | Helsinki | Finland | ||
| 205 | Teva Investigational Site 40018 | Helsinki | Finland | ||
| 206 | Teva Investigational Site 40016 | Turku | Finland | 20100 | |
| 207 | Teva Investigational Site 40016 | Turku | Finland | ||
| 208 | Teva Investigational Site 80096 | Holon | Israel | 58100 | |
| 209 | Teva Investigational Site 80096 | Holon | Israel | ||
| 210 | Teva Investigational Site 80099 | Jerusalem | Israel | 9112001 | |
| 211 | Teva Investigational Site 80099 | Jerusalem | Israel | ||
| 212 | Teva Investigational Site 80098 | Nahariya | Israel | 221001 | |
| 213 | Teva Investigational Site 80097 | Netanya | Israel | 4244916 | |
| 214 | Teva Investigational Site 80097 | Netanya | Israel | ||
| 215 | Teva Investigational Site 80100 | Ramat Gan | Israel | 5262160 | |
| 216 | Teva Investigational Site 80100 | Ramat Gan | Israel | ||
| 217 | Teva Investigational Site 80095 | Tel Aviv | Israel | 64239 | |
| 218 | Teva Investigational Site 84072 | Chofu-shi | Japan | 182-0006 | |
| 219 | Teva Investigational Site 84064 | Chofu-shi | Japan | ||
| 220 | Teva Investigational Site 84072 | Chofu-shi | Japan | ||
| 221 | Teva Investigational Site 84066 | Kagoshima-shi | Japan | ||
| 222 | Teva Investigational Site 84066 | Kagoshima | Japan | 892-0844 | |
| 223 | Teva Investigational Site 84069 | Kai-shi | Japan | ||
| 224 | Teva Investigational Site 84069 | Kai | Japan | 400-0124 | |
| 225 | Teva Investigational Site 84073 | Kawasaki-shi | Japan | ||
| 226 | Teva Investigational Site 84073 | Kawasaki | Japan | 211-8588 | |
| 227 | Teva Investigational Site 84067 | Kyoto | Japan | 600-8811 | |
| 228 | Teva Investigational Site 84067 | Kyoto | Japan | ||
| 229 | Teva Investigational Site 84062 | Osaka-shi | Japan | 556-0015 | |
| 230 | Teva Investigational Site 84062 | Osaka-shi | Japan | ||
| 231 | Teva Investigational Site 84070 | Saitama-shi | Japan | ||
| 232 | Teva Investigational Site 84070 | Saitama | Japan | 338-8577 | |
| 233 | Teva Investigational Site 84061 | Sendai-shi | Japan | 982-0014 | |
| 234 | Teva Investigational Site 84061 | Sendai-shi | Japan | ||
| 235 | Teva Investigational Site 84065 | Shimotsuma | Japan | ||
| 236 | Teva Investigational Site 84068 | Shizuoka-shi | Japan | ||
| 237 | Teva Investigational Site 84068 | Shizuoka | Japan | 4200-853 | |
| 238 | Teva Investigational Site 84065 | Tochigi | Japan | 321-0293 | |
| 239 | Teva Investigational Site 84064 | Tokyo | Japan | 182-0006 | |
| 240 | Teva Investigational Site 84071 | Toyonaka-shi | Japan | ||
| 241 | Teva Investigational Site 84071 | Toyonaka | Japan | ||
| 242 | Teva Investigational Site 53364 | Krakow | Poland | 31-523 | |
| 243 | Teva Investigational Site 53363 | Krakow | Poland | 33-332 | |
| 244 | Teva Investigational Site 53363 | Krakow | Poland | ||
| 245 | Teva Investigational Site 53364 | Krakow | Poland | ||
| 246 | Teva Investigational Site 53366 | Lublin | Poland | 20-022 | |
| 247 | Teva Investigational Site 53366 | Lublin | Poland | ||
| 248 | Teva Investigational Site 53365 | Poznan | Poland | 60-529 | |
| 249 | Teva Investigational Site 53365 | Poznan | Poland | ||
| 250 | Teva Investigational Site 53367 | Warsaw | Poland | 04-730 | |
| 251 | Teva Investigational Site 53367 | Warsaw | Poland | ||
| 252 | Teva Investigational Site 50399 | Kazan | Russian Federation | 420012 | |
| 253 | Teva Investigational Site 50395 | Kazan | Russian Federation | 420021 | |
| 254 | Teva Investigational Site 50395 | Kazan | Russian Federation | ||
| 255 | Teva Investigational Site 50399 | Kazan | Russian Federation | ||
| 256 | Teva Investigational Site 50394 | Moscow | Russian Federation | 121467 | |
| 257 | Teva Investigational Site 50400 | Moscow | Russian Federation | 129128 | |
| 258 | Teva Investigational Site 50394 | Moscow | Russian Federation | ||
| 259 | Teva Investigational Site 50400 | Moscow | Russian Federation | ||
| 260 | Teva Investigational Site 50398 | Nizhniy Novgorod | Russian Federation | 603126 | |
| 261 | Teva Investigational Site 50396 | Nizhniy Novgorod | Russian Federation | 603137 | |
| 262 | Teva Investigational Site 50396 | Nizhniy Novgorod | Russian Federation | ||
| 263 | Teva Investigational Site 50398 | Nizhniy Novgorod | Russian Federation | ||
| 264 | Teva Investigational Site 50397 | Ufa | Russian Federation | 450007 | |
| 265 | Teva Investigational Site 50397 | Ufa | Russian Federation | ||
| 266 | Teva Investigational Site 31207 | Madrid | Spain | 28046 | |
| 267 | Teva Investigational Site 31207 | Madrid | Spain | ||
| 268 | Teva Investigational Site 31208 | Pamplona | Spain | 31008 | |
| 269 | Teva Investigational Site 31208 | Pamplona | Spain | ||
| 270 | Teva Investigational Site 31205 | Valladolid | Spain | 47003 | |
| 271 | Teva Investigational Site 31205 | Valladolid | Spain | ||
| 272 | Teva Investigational Site 31206 | Zaragoza | Spain | 50009 | |
| 273 | Teva Investigational Site 31206 | Zaragoza | Spain |
Sponsors and Collaborators
- Teva Branded Pharmaceutical Products R&D, Inc.
Investigators
- Study Director: Teva Medical Expert, MD, Teva Branded Pharmaceutical Products R&D, Inc.
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Teva Branded Pharmaceutical Products R&D, Inc.
ClinicalTrials.gov Identifier:
NCT02621931
Other Study ID Numbers:
- TV48125-CNS-30049
- 2015-004549-23
First Posted:
Dec 4, 2015
Last Update Posted:
Nov 9, 2021
Last Verified:
Nov 1, 2021
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | A total of 3148 patients with migraine provided written informed consent and were screened for entry into either Study TV48125-CNS-30049 or Study TV48125-CNS-30050. Of the 3148 screened, 1130 met entry criteria, including criteria for chronic migraine and diary compliance during the run-in period, and were randomized into this study. |
| Arm/Group Title | Placebo | Fremanezumab 675 mg/Placebo/Placebo | Fremanezumab 675/225/225 mg |
|---|---|---|---|
| Arm/Group Description | Participants randomized to the placebo treatment arm received three 1.5-mL placebo injections at Day 0 and a single 1.5-mL placebo injection at Days 28 and 56 . | Participants randomized to the fremanezumab 675 mg/placebo/placebo treatment arm received 675 mg of fremanezumab as 3 active injections (225 mg/1.5 mL) on Day 0, and placebo as a single 1.5-mL injection on Days 28 and 56. | Participants randomized to the fremanezumab 675/225/225 mg treatment arm received 675 mg of fremanezumab as 3 active injections (225 mg/1.5 mL) on Day 0 and 225 mg of fremanezumab as 1 active injection (225 mg/1.5 mL) on Days 28 and 56. |
| Period Title: Overall Study | |||
| STARTED | 375 | 376 | 379 |
| Safety and ITT Populations | 375 | 376 | 379 |
| Full Analysis Set | 371 | 375 | 375 |
| COMPLETED | 342 | 349 | 343 |
| NOT COMPLETED | 33 | 27 | 36 |
Baseline Characteristics
| Arm/Group Title | Placebo | Fremanezumab 675 mg/Placebo/Placebo | Fremanezumab 675/225/225 mg | Total |
|---|---|---|---|---|
| Arm/Group Description | Participants randomized to the placebo treatment arm received three 1.5-mL placebo injections at Day 0 and a single 1.5-mL placebo injection at Days 28 and 56 . | Participants randomized to the fremanezumab 675 mg/placebo/placebo treatment arm received 675 mg of fremanezumab as 3 active injections (225 mg/1.5 mL) on Day 0, and placebo as a single 1.5-mL injection on Days 28 and 56. | Participants randomized to the fremanezumab 675/225/225 mg treatment arm received 675 mg of fremanezumab as 3 active injections (225 mg/1.5 mL) on Day 0 and 225 mg of fremanezumab as 1 active injection (225 mg/1.5 mL) on Days 28 and 56. | Total of all reporting groups |
| Overall Participants | 375 | 376 | 379 | 1130 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
41.4
(12.03)
|
42.0
(12.37)
|
40.6
(11.95)
|
41.3
(12.12)
|
| Age, Customized (Count of Participants) | ||||
| 18-45 years |
229
61.1%
|
218
58%
|
248
65.4%
|
695
61.5%
|
| 46-65 years |
143
38.1%
|
149
39.6%
|
123
32.5%
|
415
36.7%
|
| >65 years |
3
0.8%
|
9
2.4%
|
8
2.1%
|
20
1.8%
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
330
88%
|
331
88%
|
330
87.1%
|
991
87.7%
|
| Male |
45
12%
|
45
12%
|
49
12.9%
|
139
12.3%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||
| White |
303
80.8%
|
293
77.9%
|
297
78.4%
|
893
79%
|
| Black |
29
7.7%
|
33
8.8%
|
37
9.8%
|
99
8.8%
|
| Asian |
40
10.7%
|
40
10.6%
|
41
10.8%
|
121
10.7%
|
| American Indian or Alaska Native |
0
0%
|
4
1.1%
|
2
0.5%
|
6
0.5%
|
| Native Hawaiian or Other Pacific Islander |
1
0.3%
|
2
0.5%
|
0
0%
|
3
0.3%
|
| Other |
2
0.5%
|
4
1.1%
|
2
0.5%
|
8
0.7%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||
| Not HIspanic or Latino |
343
91.5%
|
352
93.6%
|
338
89.2%
|
1033
91.4%
|
| Hispanic or Latino |
32
8.5%
|
22
5.9%
|
41
10.8%
|
95
8.4%
|
| Unknown |
0
0%
|
1
0.3%
|
0
0%
|
1
0.1%
|
| Not reported |
0
0%
|
1
0.3%
|
0
0%
|
1
0.1%
|
| Weight (kg) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [kg] |
72.6
(15.58)
|
72.4
(15.79)
|
72.5
(16.36)
|
72.5
(15.90)
|
| Time Since Initial Migraine Diagnosis (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
19.9
(12.86)
|
19.7
(12.84)
|
20.1
(11.98)
|
19.9
(12.55)
|
| Preventative Medication Use During Baseline Period (Count of Participants) | ||||
| Yes |
77
20.5%
|
77
20.5%
|
85
22.4%
|
239
21.2%
|
| No |
298
79.5%
|
299
79.5%
|
294
77.6%
|
891
78.8%
|
| Total Number of Headache Days of Any Duration And Any Severity During the 28 Day Baseline Period (days) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [days] |
20.3
(4.19)
|
20.4
(3.93)
|
20.3
(4.26)
|
20.3
(4.13)
|
| Number of Headache Days of At Least Moderate Severity (days) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [days] |
13.3
(5.82)
|
13.2
(5.47)
|
12.8
(5.80)
|
13.1
(5.70)
|
| Number of Migraine Days (days) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [days] |
16.4
(5.15)
|
16.2
(4.88)
|
16.0
(5.19)
|
16.2
(5.97)
|
| Number of Days of Use of Any Acute Headache Medications (days) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [days] |
13.0
(6.92)
|
13.1
(6.79)
|
13.1
(7.20)
|
13.1
(6.96)
|
| Headache Impact Test (HIT-6) Disability Score (units on a scale) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [units on a scale] |
64.1
(4.80)
|
64.3
(4.74)
|
64.6
(4.42)
|
64.3
(4.65)
|
Outcome Measures
| Title | Change From Baseline in the Monthly Average Number of Headache Days of At Least Moderate Severity During the 12-Week Period After the First Dose of Study Drug |
|---|---|
| Description | Headaches were subjectively rated by participants as mild, moderate or severe. A headache day of at least moderate severity was defined as a calendar day (00:00 to 23:59) where the patient (using the electronic headache diary device) reports: - a day with headache pain that lasts ≥4 hours with a peak severity of at least moderate severity or - a day when the patient used acute migraine-specific medication (triptans or ergots) to treat a headache of any severity or duration. Monthly averages are derived and normalized to 28 days equivalent by the following formula: (# days of efficacy variable over relevant period / # days with assessments recorded in the e-diary over the relevant period) * 28. The change is calculated as post-baseline value - baseline value. |
| Time Frame | Baseline (Days -28 to Day -1), Treatment (Days 1 - Week 12) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS) included those in the intent to treat (ITT) population who received at least 1 dose of study drug and had at least 10 days of post-baseline efficacy assessments on the primary endpoint. |
| Arm/Group Title | Placebo | Fremanezumab 675 mg/Placebo/Placebo | Fremanezumab 675/225/225 mg |
|---|---|---|---|
| Arm/Group Description | Participants randomized to the placebo treatment arm received three 1.5-mL placebo injections at Day 0 and a single 1.5-mL placebo injection at Days 28 and 56 . | Participants randomized to the fremanezumab 675 mg/placebo/placebo treatment arm received 675 mg of fremanezumab as 3 active injections (225 mg/1.5 mL) on Day 0, and placebo as a single 1.5-mL injection on Days 28 and 56. | Participants randomized to the fremanezumab 675/225/225 mg treatment arm received 675 mg of fremanezumab as 3 active injections (225 mg/1.5 mL) on Day 0 and 225 mg of fremanezumab as 1 active injection (225 mg/1.5 mL) on Days 28 and 56. |
| Measure Participants | 371 | 375 | 375 |
| Median (Inter-Quartile Range) [days] |
-2.5
|
-4.2
|
-4.5
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Fremanezumab 675 mg/Placebo/Placebo |
|---|---|---|
| Comments | Due to the deviation from the normal distribution assumption of the data, the primary analysis was conducted using the Wilcoxon rank-sum test as outlined in the statistical analysis plan (SAP). | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | 0.05 level of significance | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM difference from placebo |
| Estimated Value | -1.8 | |
| Confidence Interval |
(2-Sided) 95% -2.46 to -1.15 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.33 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Fremanezumab 675/225/225 mg |
|---|---|---|
| Comments | Due to the deviation from the normal distribution assumption of the data, the primary analysis was conducted using the Wilcoxon rank-sum test as outlined in the SAP. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | 0.05 level of significance | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM difference from placebo |
| Estimated Value | -2.1 | |
| Confidence Interval |
(2-Sided) 95% -2.76 to -1.45 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.33 |
|
| Estimation Comments | ||
| Title | Participants With Treatment-Emergent Adverse Events (TEAEs) |
|---|---|
| Description | An adverse event (AE) was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an AE which prevents usual activities. Relationship of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes. |
| Time Frame | Day 1 to Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population |
| Arm/Group Title | Placebo | Fremanezumab 675 mg/Placebo/Placebo | Fremanezumab 675/225/225 mg |
|---|---|---|---|
| Arm/Group Description | Participants randomized to the placebo treatment arm received three 1.5-mL placebo injections at Day 0 and a single 1.5-mL placebo injection at Days 28 and 56 . | Participants randomized to the fremanezumab 675 mg/placebo/placebo treatment arm received 675 mg of fremanezumab as 3 active injections (225 mg/1.5 mL) on Day 0, and placebo as a single 1.5-mL injection on Days 28 and 56. | Participants randomized to the fremanezumab 675/225/225 mg treatment arm received 675 mg of fremanezumab as 3 active injections (225 mg/1.5 mL) on Day 0 and 225 mg of fremanezumab as 1 active injection (225 mg/1.5 mL) on Days 28 and 56. |
| Measure Participants | 375 | 376 | 379 |
| Any TEAE |
240
64%
|
265
70.5%
|
270
71.2%
|
| Severe TEAE |
20
5.3%
|
14
3.7%
|
15
4%
|
| Treatment-related TEAE |
159
42.4%
|
186
49.5%
|
194
51.2%
|
| Serious TEAE |
6
1.6%
|
3
0.8%
|
5
1.3%
|
| Death |
0
0%
|
1
0.3%
|
0
0%
|
| TEAE leading to discontinuation |
8
2.1%
|
5
1.3%
|
7
1.8%
|
| Title | Change From Baseline in the Monthly Average Number of Migraine Days During the 12-Week Period After the First Dose of Study Drug |
|---|---|
| Description | A migraine day was defined as when at least 1 of the following situations occurred: - a calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache endorsing criteria for migraine with or without aura - a calendar day (0:00 to 23:59) demonstrating at least 4 consecutive hours of a headache endorsing criteria for probable migraine, a migraine subtype where only 1 migraine criterion is missing - a calendar day (0:00 to 23:59) demonstrating a headache of any duration that was treated with migraine-specific medications (triptans and ergot compounds). Monthly averages are derived and normalized to 28 days equivalent by the following formula: (# days of efficacy variable over relevant period / # days with assessments recorded in the e-diary over the relevant period) * 28. The change is calculated as post-baseline value - baseline value. |
| Time Frame | Baseline (Days -28 to Day -1), Treatment (Days 1 - Week 12) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS) |
| Arm/Group Title | Placebo | Fremanezumab 675 mg/Placebo/Placebo | Fremanezumab 675/225/225 mg |
|---|---|---|---|
| Arm/Group Description | Participants randomized to the placebo treatment arm received three 1.5-mL placebo injections at Day 0 and a single 1.5-mL placebo injection at Days 28 and 56 . | Participants randomized to the fremanezumab 675 mg/placebo/placebo treatment arm received 675 mg of fremanezumab as 3 active injections (225 mg/1.5 mL) on Day 0, and placebo as a single 1.5-mL injection on Days 28 and 56. | Participants randomized to the fremanezumab 675/225/225 mg treatment arm received 675 mg of fremanezumab as 3 active injections (225 mg/1.5 mL) on Day 0 and 225 mg of fremanezumab as 1 active injection (225 mg/1.5 mL) on Days 28 and 56. |
| Measure Participants | 371 | 375 | 375 |
| Least Squares Mean (Standard Error) [migraine days / month] |
-3.2
(0.35)
|
-4.9
(0.35)
|
-5.0
(0.35)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Fremanezumab 675 mg/Placebo/Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | 0.05 level of significance | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM difference from placebo |
| Estimated Value | -1.7 | |
| Confidence Interval |
(2-Sided) 95% -2.48 to -0.97 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.39 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Fremanezumab 675/225/225 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | 0.05 level of significance | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM difference from placebo |
| Estimated Value | -1.8 | |
| Confidence Interval |
(2-Sided) 95% -2.61 to -1.09 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.39 |
|
| Estimation Comments | ||
| Title | Percentage of Participants With At Least 50% Reduction In Monthly Average Number of Headache Days of At Least Moderate Severity |
|---|---|
| Description | Responder rates were defined as the percentage of total subjects who reached at least a 50% reduction in the monthly average of headache days (as subjectively reported by participants in the study diary) of at least moderate severity relative to the baseline period. For the overall analysis (Month 1-3), patients who discontinued early were considered non-responders. Monthly averages are derived and normalized to 28 days equivalent by the following formula: (# days of efficacy variable over relevant period / # days with assessments recorded in the e-diary over the relevant period) * 28. The percentage reduction in monthly average is calculated as: ((baseline value - post-baseline value) / baseline value) * 100. |
| Time Frame | Baseline (Days -28 to Day -1), Treatment: Month 1, Month 2, Month 3, Month 1-3 (Days 1 - Week 12) |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS. One participant in the Placebo and Fremanezumab 675/225/225 mg treatment arms had 0 headache days of >= moderate severity during baseline and treatment and therefore was not included. |
| Arm/Group Title | Placebo | Fremanezumab 675 mg/Placebo/Placebo | Fremanezumab 675/225/225 mg |
|---|---|---|---|
| Arm/Group Description | Participants randomized to the placebo treatment arm received three 1.5-mL placebo injections at Day 0 and a single 1.5-mL placebo injection at Days 28 and 56 . | Participants randomized to the fremanezumab 675 mg/placebo/placebo treatment arm received 675 mg of fremanezumab as 3 active injections (225 mg/1.5 mL) on Day 0, and placebo as a single 1.5-mL injection on Days 28 and 56. | Participants randomized to the fremanezumab 675/225/225 mg treatment arm received 675 mg of fremanezumab as 3 active injections (225 mg/1.5 mL) on Day 0 and 225 mg of fremanezumab as 1 active injection (225 mg/1.5 mL) on Days 28 and 56. |
| Measure Participants | 370 | 375 | 374 |
| Month 1 |
21.6
5.8%
|
41.3
11%
|
40.0
10.6%
|
| Month 2 |
24.3
6.5%
|
39.7
10.6%
|
41.9
11.1%
|
| Month 3 |
26.4
7%
|
40.5
10.8%
|
44.5
11.7%
|
| Overall - Months 1-3 |
18.1
4.8%
|
37.6
10%
|
40.8
10.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Fremanezumab 675 mg/Placebo/Placebo |
|---|---|---|
| Comments | Month 1: Active 675/placebo/placebo to Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | 0.05 level of significance. P-value based on Cochran-Mantel-Haenszel test stratified by baseline preventive medication use. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Fremanezumab 675/225/225 mg |
|---|---|---|
| Comments | Month 1: Active 675/225/225 to Placebo | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | 0.05 level of significance. P-value based on Cochran-Mantel-Haenszel test stratified by baseline preventive medication use. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Fremanezumab 675 mg/Placebo/Placebo |
|---|---|---|
| Comments | Month 2 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | 0.05 level of significance. P-value based on Cochran-Mantel-Haenszel test stratified by baseline preventive medication use. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Fremanezumab 675/225/225 mg |
|---|---|---|
| Comments | Month 2 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | 0.05 level of significance. P-value based on Cochran-Mantel-Haenszel test stratified by baseline preventive medication use. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Fremanezumab 675 mg/Placebo/Placebo |
|---|---|---|
| Comments | Month 3 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | 0.05 level of significance. P-value based on Cochran-Mantel-Haenszel test stratified by baseline preventive medication use. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Fremanezumab 675/225/225 mg |
|---|---|---|
| Comments | Month 3 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | 0.05 level of significance. P-value based on Cochran-Mantel-Haenszel test stratified by baseline preventive medication use. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Fremanezumab 675 mg/Placebo/Placebo |
|---|---|---|
| Comments | Overall | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | 0.05 level of significance. P-value based on Cochran-Mantel-Haenszel test stratified by baseline preventive medication use. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Fremanezumab 675/225/225 mg |
|---|---|---|
| Comments | Overall | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | 0.05 level of significance. P-value based on Cochran-Mantel-Haenszel test stratified by baseline preventive medication use. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Title | Change From Baseline in the Monthly Average Number of Days of Use of Any Acute Headache Medicine During the 12 Week Period After the First Dose of Study Drug |
|---|---|
| Description | Participants recorded any migraine medications (name of drug, number of tablets/capsules, and the dose in milligrams per tablet/capsule) taken on each day in their electronic headache diary device. Acute migraine-specific medication included triptans or ergots. Monthly averages are derived and normalized to 28 days equivalent by the following formula: (# days of efficacy variable over relevant period / # days with assessments recorded in the e-diary over the relevant period) * 28. The change is calculated as post-baseline value - baseline value. |
| Time Frame | Baseline (Days -28 to Day -1), Treatment (Days 1 - Week 12) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set |
| Arm/Group Title | Placebo | Fremanezumab 675 mg/Placebo/Placebo | Fremanezumab 675/225/225 mg |
|---|---|---|---|
| Arm/Group Description | Participants randomized to the placebo treatment arm received three 1.5-mL placebo injections at Day 0 and a single 1.5-mL placebo injection at Days 28 and 56. | Participants randomized to the fremanezumab 675 mg/placebo/placebo treatment arm received 675 mg of fremanezumab as 3 active injections (225 mg/1.5 mL) on Day 0, and placebo as a single 1.5-mL injection on Days 28 and 56. | Participants randomized to the fremanezumab 675/225/225 mg treatment arm received 675 mg of fremanezumab as 3 active injections (225 mg/1.5 mL) on Day 0 and 225 mg of fremanezumab as 1 active injection (225 mg/1.5 mL) on Days 28 and 56. |
| Measure Participants | 371 | 375 | 375 |
| Median (Inter-Quartile Range) [days] |
-2.0
|
-3.6
|
-4.2
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Fremanezumab 675 mg/Placebo/Placebo |
|---|---|---|
| Comments | Due to the deviation from the normal distribution assumption of the data, the primary analysis was conducted using the Wilcoxon rank-sum test as outlined in the SAP. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | 0.05 level of significance | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Fremanezumab 675/225/225 mg |
|---|---|---|
| Comments | Due to the deviation from the normal distribution assumption of the data, the primary analysis was conducted using the Wilcoxon rank-sum test as outlined in the SAP. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | 0.05 level of significance | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
| Title | Change From Baseline in the Number of Headache Days of At Least Moderate Severity During the 4 Week Period After the First Dose of Study Drug |
|---|---|
| Description | Headaches were subjectively rated by participants as mild, moderate or severe. A headache day of at least moderate severity was defined as a calendar day (00:00 to 23:59) where the patient (using the electronic headache diary device) reports: - a day with headache pain that lasts ≥4 hours with a peak severity of at least moderate severity or - a day when the patient used acute migraine-specific medication (triptans or ergots) to treat a headache of any severity or duration. The change is calculated as post-baseline value - baseline value. |
| Time Frame | Baseline (Days -28 to Day -1), Treatment (Days 1 - Week 4) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS) included those in the ITT population who received at least 1 dose of study drug and had at least 10 days of post-baseline efficacy assessments on the primary endpoint. |
| Arm/Group Title | Placebo | Fremanezumab 675 mg |
|---|---|---|
| Arm/Group Description | Participants randomized to the placebo treatment arm received three 1.5-mL placebo injections at Day 0 and a single 1.5-mL placebo injection at Days 28 and 56. | Participants randomized to both fremanezumab treatment arms received 675 mg of fremanezumab as 3 active injections (225 mg/1.5 mL) on Day 0. Later treatments are beyond the timeframe for this outcome. Therefore the data from both active treatment arms were combined for this comparison. |
| Measure Participants | 371 | 750 |
| Least Squares Mean (Standard Error) [days] |
-2.3
(0.33)
|
-4.6
(0.27)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Fremanezumab 675 mg/Placebo/Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | 0.05 level of significance | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LSM difference from placebo |
| Estimated Value | -2.3 | |
| Confidence Interval |
(2-Sided) 95% -2.95 to -1.73 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.31 |
|
| Estimation Comments | ||
| Title | Change From Baseline in the Monthly Average Number of Headache Days of At Least Moderate Severity During the 12 Week Period After the First Dose of Study Medication in Patients Not Receiving Concomitant Preventive Migraine Medications |
|---|---|
| Description | A subset of patients (specified in the protocol not to exceed 30%) were allowed to use 1 concomitant migraine preventive medication. This outcome only includes those participants who did not take concomitant preventive migraine medication during this study. Headaches were subjectively rated by participants as mild, moderate or severe. A headache day of >= moderate severity was defined as a calendar day where the patient (using the electronic headache diary device) reports: - a day with headache pain that lasts ≥4 hours with a peak severity of >= moderate severity or - a day when the patient used acute migraine-specific medication (triptans or ergots) to treat a headache of any severity or duration. Monthly averages are derived and normalized to 28 days equivalent by the following formula: (# days of efficacy variable over relevant period / # days with assessments recorded in the e-diary over the relevant period) * 28. Change is post-baseline value - baseline value. |
| Time Frame | Baseline (Days -28 to Day -1), Treatment (Days 1 - Week 12) |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS of participants who did not receive concomitant preventive migraine medications. |
| Arm/Group Title | Placebo | Fremanezumab 675 mg/Placebo/Placebo | Fremanezumab 675/225/225 mg |
|---|---|---|---|
| Arm/Group Description | Participants randomized to the placebo treatment arm received three 1.5-mL placebo injections at Day 0 and a single 1.5-mL placebo injection at Days 28 and 56. | Participants randomized to the fremanezumab 675 mg/placebo/placebo treatment arm received 675 mg of fremanezumab as 3 active injections (225 mg/1.5 mL) on Day 0, and placebo as a single 1.5-mL injection on Days 28 and 56. | Participants randomized to the fremanezumab 675/225/225 mg treatment arm received 675 mg of fremanezumab as 3 active injections (225 mg/1.5 mL) on Day 0 and 225 mg of fremanezumab as 1 active injection (225 mg/1.5 mL) on Days 28 and 56. |
| Measure Participants | 294 | 298 | 290 |
| Median (Inter-Quartile Range) [days] |
-2.4
|
-4.4
|
-4.6
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Fremanezumab 675 mg/Placebo/Placebo |
|---|---|---|
| Comments | Due to the deviation from the normal distribution assumption of the data, the primary analysis was conducted using the Wilcoxon rank-sum test as outlined in the SAP. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | 0.05 level of significance | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Fremanezumab 675/225/225 mg |
|---|---|---|
| Comments | Due to the deviation from the normal distribution assumption of the data, the primary analysis was conducted using the Wilcoxon rank-sum test as outlined in the SAP. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | 0.05 level of significance | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
| Title | Change From Baseline in Migraine-Related Disability Score, As Measured by the 6-Item Headache Impact Test (HIT) At Week 12 |
|---|---|
| Description | The HIT-6 was developed by Kosinski et al (2003) as a short form for reliably assessing the adverse headache impact in clinical practice and clinical research settings. The questionnaire measures the adverse impact of headache on social functioning, role functioning, vitality, cognitive functioning, and psychological distress. It also assesses headache severity. Scores range from 36 to 78, where a higher score indicates a greater impact of headache on the daily life of the patient, i.e. scores ≤49 represent little or no impact, scores between 50 and 55 represent some impact, scores between 56 and 59 represent substantial impact; and scores ≥60 indicate severe impact. Negative change from baseline values indicate less adverse impact of headache. |
| Time Frame | Baseline, 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set |
| Arm/Group Title | Placebo | Fremanezumab 675 mg/Placebo/Placebo | Fremanezumab 675/225/225 mg |
|---|---|---|---|
| Arm/Group Description | Participants randomized to the placebo treatment arm received three 1.5-mL placebo injections at Day 0 and a single 1.5-mL placebo injection at Days 28 and 56. | Participants randomized to the fremanezumab 675 mg/placebo/placebo treatment arm received 675 mg of fremanezumab as 3 active injections (225 mg/1.5 mL) on Day 0, and placebo as a single 1.5-mL injection on Days 28 and 56. | Participants randomized to the fremanezumab 675/225/225 mg treatment arm received 675 mg of fremanezumab as 3 active injections (225 mg/1.5 mL) on Day 0 and 225 mg of fremanezumab as 1 active injection (225 mg/1.5 mL) on Days 28 and 56. |
| Measure Participants | 371 | 375 | 375 |
| Median (Inter-Quartile Range) [units on a scale] |
-4.0
|
-5.0
|
-6.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Fremanezumab 675 mg/Placebo/Placebo |
|---|---|---|
| Comments | Due to the deviation from the normal distribution assumption of the data, the primary analysis was conducted using the Wilcoxon rank-sum test as outlined in the SAP. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0004 |
| Comments | 0.05 level of significance | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Fremanezumab 675/225/225 mg |
|---|---|---|
| Comments | Due to the deviation from the normal distribution assumption of the data, the primary analysis was conducted using the Wilcoxon rank-sum test as outlined in the SAP. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | 0.05 level of significance | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | ||
| Title | Electrocardiogram (ECG) Findings Shifts From Baseline to Overall |
|---|---|
| Description | 12-lead ECGs were performed before other assessments (eg, blood draws and administration of questionnaires) and performed in triplicate. The worst post-baseline finding for the participant is summarized. Only participants with both baseline and post-baseline ECGs are included. The ECG was evaluated by the investigator at the time of recording (signed and dated), and the printout was kept in the source documentation file. When potentially clinically significant findings were detected by the investigator, a cardiologist at a central diagnostic center was consulted for a definitive interpretation. Any ECG finding that was judged by the investigator as a potentially clinically significant change (worsening) compared with a baseline value was considered an adverse event. - NCS = abnormal, not clinically significant. - CS= abnormal, clinically significant. Shift format is: baseline finding / worst post-baseline finding. |
| Time Frame | Baseline (Day 0), Treatment Week 12 (or endpoint) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population of participants with both baseline and post-treatment ECGs. |
| Arm/Group Title | Placebo | Fremanezumab 675 mg/Placebo/Placebo | Fremanezumab 675/225/225 mg |
|---|---|---|---|
| Arm/Group Description | Participants randomized to the placebo treatment arm received three 1.5-mL placebo injections at Day 0 and a single 1.5-mL placebo injection at Days 28 and 56. | Participants randomized to the fremanezumab 675 mg/placebo/placebo treatment arm received 675 mg of fremanezumab as 3 active injections (225 mg/1.5 mL) on Day 0, and placebo as a single 1.5-mL injection on Days 28 and 56. | Participants randomized to the fremanezumab 675/225/225 mg treatment arm received 675 mg of fremanezumab as 3 active injections (225 mg/1.5 mL) on Day 0 and 225 mg of fremanezumab as 1 active injection (225 mg/1.5 mL) on Days 28 and 56. |
| Measure Participants | 360 | 361 | 362 |
| Normal / Normal |
215
57.3%
|
220
58.5%
|
223
58.8%
|
| Normal / NCS |
54
14.4%
|
48
12.8%
|
43
11.3%
|
| Normal / CS |
1
0.3%
|
0
0%
|
0
0%
|
| NCS / Normal |
31
8.3%
|
34
9%
|
34
9%
|
| NCS / NCS |
59
15.7%
|
59
15.7%
|
62
16.4%
|
| NCS / CS |
0
0%
|
0
0%
|
0
0%
|
| CS / Normal |
0
0%
|
0
0%
|
0
0%
|
| CS / NCS |
0
0%
|
0
0%
|
0
0%
|
| CS / CS |
0
0%
|
0
0%
|
0
0%
|
| Title | Participants With Vital Signs Potentially Clinically Significant Abnormal Values |
|---|---|
| Description | Vital signs were performed before other assessments (eg, blood draws and administration of questionnaires). Vital signs with potentially clinically significant abnormal findings included: - Pulse Rate High: >=120 and increase of >=15 beats per minute - Pulse Rate Low: <=50 and decrease of >=15 beats per minute - Systolic Blood Pressure Low: <=90 mmHg and decrease of >=20 mmHg - Diastolic Blood Pressure High: >=105 mmHg and increase of >=15 mmHg - Diastolic Blood Pressure Low: <=50 mmHg and decrease of >=15 mmHg - Respiratory Rate Low: <10 breaths / minute |
| Time Frame | Treatment Days 28, 56 and 84 (or endpoint). Changes from previous reading may reflect the baseline reading performed on Day 0. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population of participants with both baseline and post-treatment values for each vital sign. |
| Arm/Group Title | Placebo | Fremanezumab 675 mg/Placebo/Placebo | Fremanezumab 675/225/225 mg |
|---|---|---|---|
| Arm/Group Description | Participants randomized to the placebo treatment arm received three 1.5-mL placebo injections at Day 0 and a single 1.5-mL placebo injection at Days 28 and 56. | Participants randomized to the fremanezumab 675 mg/placebo/placebo treatment arm received 675 mg of fremanezumab as 3 active injections (225 mg/1.5 mL) on Day 0, and placebo as a single 1.5-mL injection on Days 28 and 56. | Participants randomized to the fremanezumab 675/225/225 mg treatment arm received 675 mg of fremanezumab as 3 active injections (225 mg/1.5 mL) on Day 0 and 225 mg of fremanezumab as 1 active injection (225 mg/1.5 mL) on Days 28 and 56. |
| Measure Participants | 366 | 373 | 372 |
| Participants with at least 1 abnormality |
7
1.9%
|
10
2.7%
|
14
3.7%
|
| Pulse Rate High |
0
0%
|
0
0%
|
1
0.3%
|
| Pulse Rate Low |
1
0.3%
|
1
0.3%
|
0
0%
|
| Systolic Blood Pressure Low |
2
0.5%
|
4
1.1%
|
6
1.6%
|
| Diastolic Blood Pressure High |
1
0.3%
|
2
0.5%
|
3
0.8%
|
| Diastolic Blood Pressure Low |
0
0%
|
1
0.3%
|
2
0.5%
|
| Respiratory Rate Low |
3
0.8%
|
2
0.5%
|
3
0.8%
|
| Title | Participants With Serum Chemistry and Hematology Potentially Clinically Significant Abnormal Results |
|---|---|
| Description | Serum chemistry and hematology laboratory tests with potentially clinically significant abnormal findings included: - Blood Urea Nitrogen (BUN) High: >=10.71 mmol/L - Creatinine High: >=177 umol/L - Bilirubin High: >=34.2 umol/L - Alanine Aminotransferase (ALT): >=3*upper limit of normal (ULN) - Aspartate Aminotransferase (AST): >=3*upper limit of normal (ULN) - Gamma Glutamyl Transferase (GGT): >=3*upper limit of normal (ULN) - Hemoglobin: Male: <115 g/L or Female: <=95 g/L - Hematocrit: Male: <0.37 L/L or Female: <0.32 L/L - Leukocytes: >=20*10^9/L or <=3*10^9/L - Eosinophils/Leukocytes: >=10% - Platelets: >=700*10^9/L or <=75*10^9/L |
| Time Frame | Treatment Days 28, 56 and 84 (or endpoint) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population of participants with at least one post-baseline result for the tests |
| Arm/Group Title | Placebo | Fremanezumab 675 mg/Placebo/Placebo | Fremanezumab 675/225/225 mg |
|---|---|---|---|
| Arm/Group Description | Participants randomized to the placebo treatment arm received three 1.5-mL placebo injections at Day 0 and a single 1.5-mL placebo injection at Days 28 and 56. | Participants randomized to the fremanezumab 675 mg/placebo/placebo treatment arm received 675 mg of fremanezumab as 3 active injections (225 mg/1.5 mL) on Day 0, and placebo as a single 1.5-mL injection on Days 28 and 56. | Participants randomized to the fremanezumab 675/225/225 mg treatment arm received 675 mg of fremanezumab as 3 active injections (225 mg/1.5 mL) on Day 0 and 225 mg of fremanezumab as 1 active injection (225 mg/1.5 mL) on Days 28 and 56. |
| Measure Participants | 366 | 373 | 371 |
| BUN |
1
0.3%
|
1
0.3%
|
1
0.3%
|
| Creatinine |
2
0.5%
|
0
0%
|
0
0%
|
| Bilirubin |
0
0%
|
2
0.5%
|
0
0%
|
| ALT |
2
0.5%
|
2
0.5%
|
7
1.8%
|
| AST |
0
0%
|
3
0.8%
|
4
1.1%
|
| GGT |
7
1.9%
|
7
1.9%
|
8
2.1%
|
| Hemoglobin |
2
0.5%
|
5
1.3%
|
3
0.8%
|
| Hematocrit |
8
2.1%
|
9
2.4%
|
7
1.8%
|
| Leukocytes |
2
0.5%
|
9
2.4%
|
5
1.3%
|
| Eosinophils/Leukocytes |
4
1.1%
|
5
1.3%
|
4
1.1%
|
| Platelets |
1
0.3%
|
2
0.5%
|
0
0%
|
| Title | Participants With Urinalysis Laboratory Tests Potentially Clinically Significant Abnormal Results |
|---|---|
| Description | Urinalysis with potentially clinically significant abnormal findings included: - Blood: >=2 unit increase from baseline - Urine Glucose (mg/dL): >=2 unit increase from baseline - Ketones (mg/dL): >=2 unit increase from baseline - Urine Protein (mg/dL): >=2 unit increase from baseline |
| Time Frame | Treatment Days 28, 56 and 84 (or endpoint). Changes from previous reading reflect the baseline reading performed on Day 0. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population of participants with at least one post-baseline result for the tests. |
| Arm/Group Title | Placebo | Fremanezumab 675 mg/Placebo/Placebo | Fremanezumab 675/225/225 mg |
|---|---|---|---|
| Arm/Group Description | Participants randomized to the placebo treatment arm received three 1.5-mL placebo injections at Day 0 and a single 1.5-mL placebo injection at Days 28 and 56. | Participants randomized to the fremanezumab 675 mg/placebo/placebo treatment arm received 675 mg of fremanezumab as 3 active injections (225 mg/1.5 mL) on Day 0, and placebo as a single 1.5-mL injection on Days 28 and 56. | Participants randomized to the fremanezumab 675/225/225 mg treatment arm received 675 mg of fremanezumab as 3 active injections (225 mg/1.5 mL) on Day 0 and 225 mg of fremanezumab as 1 active injection (225 mg/1.5 mL) on Days 28 and 56. |
| Measure Participants | 365 | 373 | 372 |
| Participants with at least 1 abnormality |
78
20.8%
|
57
15.2%
|
68
17.9%
|
| Blood |
33
8.8%
|
32
8.5%
|
35
9.2%
|
| Urine glucose |
7
1.9%
|
7
1.9%
|
5
1.3%
|
| Ketones |
7
1.9%
|
7
1.9%
|
7
1.8%
|
| Urine protein |
40
10.7%
|
19
5.1%
|
34
9%
|
| Title | Prothrombin Time Shifts From Baseline to Endpoint |
|---|---|
| Description | Shifts in prothrombin time from baseline to endpoint were summarized using patient counts grouped into three categories: - Low (below normal range) - Normal (within the normal range of 9.4 to 12.5 seconds) - High (above normal range) Shift format is: baseline finding / endpoint finding |
| Time Frame | Baseline (Day 0), Treatment Endpoint (Week 12) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population of participants with both baseline and post-treatment values |
| Arm/Group Title | Placebo | Fremanezumab 675 mg/Placebo/Placebo | Fremanezumab 675/225/225 mg |
|---|---|---|---|
| Arm/Group Description | Participants randomized to the placebo treatment arm received three 1.5-mL placebo injections at Day 0 and a single 1.5-mL placebo injection at Days 28 and 56. | Participants randomized to the fremanezumab 675 mg/placebo/placebo treatment arm received 675 mg of fremanezumab as 3 active injections (225 mg/1.5 mL) on Day 0, and placebo as a single 1.5-mL injection on Days 28 and 56. | Participants randomized to the fremanezumab 675/225/225 mg treatment arm received 675 mg of fremanezumab as 3 active injections (225 mg/1.5 mL) on Day 0 and 225 mg of fremanezumab as 1 active injection (225 mg/1.5 mL) on Days 28 and 56. |
| Measure Participants | 366 | 373 | 370 |
| Low / Low |
0
0%
|
0
0%
|
0
0%
|
| Low / Normal |
2
0.5%
|
0
0%
|
1
0.3%
|
| Low / High |
0
0%
|
0
0%
|
0
0%
|
| Normal / Low |
0
0%
|
1
0.3%
|
2
0.5%
|
| Normal / Normal |
330
88%
|
318
84.6%
|
327
86.3%
|
| Normal / High |
13
3.5%
|
17
4.5%
|
19
5%
|
| High / Low |
0
0%
|
0
0%
|
0
0%
|
| High / Normal |
14
3.7%
|
19
5.1%
|
12
3.2%
|
| High / High |
7
1.9%
|
18
4.8%
|
9
2.4%
|
| Title | Injection Site Reaction Adverse Events |
|---|---|
| Description | Counts of participants who reported treatment-emergent injection site reactions as AEs are summarized. Preferred terms from MedDRA version 18.1 are offered without a threshold applied. |
| Time Frame | Day 1 to Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population |
| Arm/Group Title | Placebo | Fremanezumab 675 mg/Placebo/Placebo | Fremanezumab 675/225/225 mg |
|---|---|---|---|
| Arm/Group Description | Participants randomized to the placebo treatment arm received three 1.5-mL placebo injections at Day 0 and a single 1.5-mL placebo injection at Days 28 and 56. | Participants randomized to the fremanezumab 675 mg/placebo/placebo treatment arm received 675 mg of fremanezumab as 3 active injections (225 mg/1.5 mL) on Day 0, and placebo as a single 1.5-mL injection on Days 28 and 56. | Participants randomized to the fremanezumab 675/225/225 mg treatment arm received 675 mg of fremanezumab as 3 active injections (225 mg/1.5 mL) on Day 0 and 225 mg of fremanezumab as 1 active injection (225 mg/1.5 mL) on Days 28 and 56. |
| Measure Participants | 375 | 376 | 379 |
| Participants with >= 1 injection site reaction |
151
40.3%
|
176
46.8%
|
183
48.3%
|
| Injection site pain |
104
27.7%
|
114
30.3%
|
99
26.1%
|
| Injection site induration |
68
18.1%
|
74
19.7%
|
90
23.7%
|
| Injection site erythema |
60
16%
|
80
21.3%
|
75
19.8%
|
| Injection site haemorrhage |
10
2.7%
|
7
1.9%
|
8
2.1%
|
| Injection site pruritus |
0
0%
|
6
1.6%
|
8
2.1%
|
| Injection site rash |
0
0%
|
4
1.1%
|
3
0.8%
|
| Injection site bruising |
2
0.5%
|
1
0.3%
|
2
0.5%
|
| Injection site swelling |
0
0%
|
2
0.5%
|
1
0.3%
|
| Injection site dermatitis |
0
0%
|
1
0.3%
|
0
0%
|
| Injection site discomfort |
0
0%
|
1
0.3%
|
0
0%
|
| Injection site haematoma |
0
0%
|
0
0%
|
1
0.3%
|
| Injection site hypoaesthesia |
0
0%
|
0
0%
|
1
0.3%
|
| Injection site inflammation |
0
0%
|
0
0%
|
1
0.3%
|
| Injection site oedema |
0
0%
|
1
0.3%
|
0
0%
|
| Injection site paraesthesia |
0
0%
|
0
0%
|
1
0.3%
|
| Injection site urticaria |
2
0.5%
|
0
0%
|
1
0.3%
|
| Injection site warmth |
2
0.5%
|
0
0%
|
1
0.3%
|
| Title | Participants With Positive Electronic Columbia Suicide Severity Rating Scale (eC-SSRS) Results After the First Dose of Study Drug |
|---|---|
| Description | The electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) was used to assess the participant's suicidal ideation (severity and intensity) and behavior (Posner et al 2011). Suicidal behavior is defined as a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation is defined as a "yes" answer to any one of 5 suicidal ideation questions: wish to be dead, and 4 different categories of active suicidal ideation. The eC-SSRS Baseline/Screening version was completed by the participant at baseline, and the eC-SSRS Since Last Visit version was completed by the participant at all other time points. Any positive findings on the eC-SSRS Since Last Visit version required evaluation by a physician or doctoral-level psychologist. Findings after the first dose of study drug using the eC-SSRS Since Last Visit version are summarized. |
| Time Frame | Baseline (Day 0), Treatment Days 28, 56, 84 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population |
| Arm/Group Title | Placebo | Fremanezumab 675 mg/Placebo/Placebo | Fremanezumab 675/225/225 mg |
|---|---|---|---|
| Arm/Group Description | Participants randomized to the placebo treatment arm received three 1.5-mL placebo injections at Day 0 and a single 1.5-mL placebo injection at Days 28 and 56. | Participants randomized to the fremanezumab 675 mg/placebo/placebo treatment arm received 675 mg of fremanezumab as 3 active injections (225 mg/1.5 mL) on Day 0, and placebo as a single 1.5-mL injection on Days 28 and 56. | Participants randomized to the fremanezumab 675/225/225 mg treatment arm received 675 mg of fremanezumab as 3 active injections (225 mg/1.5 mL) on Day 0 and 225 mg of fremanezumab as 1 active injection (225 mg/1.5 mL) on Days 28 and 56. |
| Measure Participants | 375 | 376 | 379 |
| Participants with positive eC-SSRS responses |
1
0.3%
|
1
0.3%
|
1
0.3%
|
| Specific finding: interrupted suicide attempt |
1
0.3%
|
1
0.3%
|
0
0%
|
| Specific finding: suicidal ideation |
0
0%
|
0
0%
|
1
0.3%
|
Adverse Events
| Time Frame | Day 1 to Week 12 | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | Placebo | Fremanezumab 675 mg/Placebo/Placebo | Fremanezumab 675/225/225 mg | |||
| Arm/Group Description | Participants randomized to receive placebo received three 1.5-mL placebo injections at Day 0 and a single 1.5-mL placebo injection at Days 28 and 56. | Participants randomized to receive fremanezumab 675 mg/placebo/placebo received 675 mg of fremanezumab as 3 active injections (225 mg/1.5 mL) on Day 0, and placebo as a single 1.5-mL injection on Days 28 and 56. | Participants randomized to receive fremanezumab 675/225/225 mg received 675 mg of fremanezumab as 3 active injections (225 mg/1.5 mL) on Day 0 and 225 mg of fremanezumab as 1 active injection (225 mg/1.5 mL) on Days 28 and 56. | |||
All Cause Mortality |
||||||
| Placebo | Fremanezumab 675 mg/Placebo/Placebo | Fremanezumab 675/225/225 mg | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/375 (0%) | 1/376 (0.3%) | 0/379 (0%) | |||
Serious Adverse Events |
||||||
| Placebo | Fremanezumab 675 mg/Placebo/Placebo | Fremanezumab 675/225/225 mg | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/375 (1.6%) | 3/376 (0.8%) | 5/379 (1.3%) | |||
| Eye disorders | ||||||
| Diplopia | 1/375 (0.3%) | 1 | 0/376 (0%) | 0 | 0/379 (0%) | 0 |
| General disorders | ||||||
| Oedema peripheral | 1/375 (0.3%) | 1 | 0/376 (0%) | 0 | 0/379 (0%) | 0 |
| Immune system disorders | ||||||
| Drug hypersensitivity | 1/375 (0.3%) | 1 | 0/376 (0%) | 0 | 0/379 (0%) | 0 |
| Infections and infestations | ||||||
| Pneumonia | 0/375 (0%) | 0 | 1/376 (0.3%) | 1 | 0/379 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||
| Accident | 1/375 (0.3%) | 1 | 0/376 (0%) | 0 | 0/379 (0%) | 0 |
| Clavicle fracture | 1/375 (0.3%) | 1 | 0/376 (0%) | 0 | 0/379 (0%) | 0 |
| Fall | 0/375 (0%) | 0 | 0/376 (0%) | 0 | 1/379 (0.3%) | 1 |
| Radius fracture | 0/375 (0%) | 0 | 0/376 (0%) | 0 | 1/379 (0.3%) | 1 |
| Road traffic accident | 0/375 (0%) | 0 | 1/376 (0.3%) | 1 | 0/379 (0%) | 0 |
| Ulna fracture | 0/375 (0%) | 0 | 0/376 (0%) | 0 | 1/379 (0.3%) | 1 |
| Wrist fracture | 0/375 (0%) | 0 | 1/376 (0.3%) | 1 | 0/379 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||
| Back pain | 0/375 (0%) | 0 | 0/376 (0%) | 0 | 1/379 (0.3%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Uterine leiomyoma | 1/375 (0.3%) | 1 | 0/376 (0%) | 0 | 0/379 (0%) | 0 |
| Nervous system disorders | ||||||
| Migraine | 1/375 (0.3%) | 1 | 0/376 (0%) | 0 | 0/379 (0%) | 0 |
| Psychiatric disorders | ||||||
| Suicidal ideation | 0/375 (0%) | 0 | 0/376 (0%) | 0 | 1/379 (0.3%) | 1 |
| Renal and urinary disorders | ||||||
| Calculus urinary | 0/375 (0%) | 0 | 0/376 (0%) | 0 | 1/379 (0.3%) | 1 |
| Nephrolithiasis | 1/375 (0.3%) | 1 | 0/376 (0%) | 0 | 0/379 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Asthma | 1/375 (0.3%) | 1 | 0/376 (0%) | 0 | 0/379 (0%) | 0 |
| Chronic obstructive pulmonary disease | 0/375 (0%) | 0 | 1/376 (0.3%) | 1 | 0/379 (0%) | 0 |
| Dyspnoea | 1/375 (0.3%) | 1 | 0/376 (0%) | 0 | 0/379 (0%) | 0 |
| Vascular disorders | ||||||
| Hypertensive crisis | 0/375 (0%) | 0 | 0/376 (0%) | 0 | 1/379 (0.3%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||
| Placebo | Fremanezumab 675 mg/Placebo/Placebo | Fremanezumab 675/225/225 mg | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 160/375 (42.7%) | 185/376 (49.2%) | 178/379 (47%) | |||
| General disorders | ||||||
| Injection site erythema | 60/375 (16%) | 129 | 80/376 (21.3%) | 172 | 75/379 (19.8%) | 166 |
| Injection site induration | 68/375 (18.1%) | 130 | 74/376 (19.7%) | 159 | 90/379 (23.7%) | 196 |
| Injection site pain | 104/375 (27.7%) | 288 | 114/376 (30.3%) | 296 | 99/379 (26.1%) | 271 |
| Infections and infestations | ||||||
| Nasopharyngitis | 20/375 (5.3%) | 24 | 19/376 (5.1%) | 20 | 15/379 (4%) | 16 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.
Results Point of Contact
| Name/Title | Director, Clinical Research |
|---|---|
| Organization | Teva Branded Pharmaceutical Products, R&D Inc |
| Phone | 1-888-483-8279 |
| USMedInfo@tevapharm.com |
Responsible Party:
Teva Branded Pharmaceutical Products R&D, Inc.
ClinicalTrials.gov Identifier:
NCT02621931
Other Study ID Numbers:
- TV48125-CNS-30049
- 2015-004549-23
First Posted:
Dec 4, 2015
Last Update Posted:
Nov 9, 2021
Last Verified:
Nov 1, 2021