ENFORCE: A Study to Explore the Long-Term Safety and Efficacy of Fremanezumab (TEV-48125) for the Prevention of Cluster Headache

• Sponsor: Teva Branded Pharmaceutical Products R&D, Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03107052
• Collaborator: (none)
• Enrollment: 275
• Locations: 83
• Arms: 3
• Actual Duration (Months): 25.5
• Patients Per Site: 3.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a 68-week study to evaluate the long-term safety and efficacy of fremanezumab in participants with cluster headache (CH). Participants who complete the pivotal studies TV48125-CNS-30056 (NCT02945046) and TV48125-CNS-30057 (NCT02964338) and enroll into the current study will visit the investigational center for investigational medicinal product (IMP) administration, safety and efficacy assessments, and blood and urine collections for pharmacokinetics, immunogenicity (anti-drug antibodies [ADAs]), and biomarker analyses. Participants will return to the investigational center for a follow-up visit to evaluate ADAs, fremanezumab concentrations, biomarkers, and safety (adverse events and concomitant medications) approximately 7.5 months after the last dose of IMP.

Condition or Disease	Intervention/Treatment	Phase
Cluster Headache	Drug: Fremanezumab	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 275 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Double-Blind, Double-Dummy Study to Explore the Long-Term Safety and Efficacy of TEV-48125 for the Prevention of Cluster Headache
• Actual Study Start Date: Apr 27, 2017
• Actual Primary Completion Date: Jun 11, 2019
• Actual Study Completion Date: Jun 11, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fremanezumab 225 mg Monthly Participants with ECH or CCH who received fremanezumab at 900 mg intravenous (IV) infusion at Week 0 and fremanezumab at 225 mg subcutaneous (SC) injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30056 or TV48125-CNS-30057, and participants with CCH who received fremanezumab at 675 mg SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30057; will receive fremanezumab at 225 mg SC injection monthly (approximately every 4 weeks, administered as single SC injection of fremanezumab at 225 mg [225 mg/1.5 milliliter {mL}] at Week 0 and 36; and 2 placebo SC injections at Weeks 0, 12, 24, and 36 for blinding in participants rolled over from Study TV48125-CNS-30056; fremanezumab at 225 mg as a single SC injection (225 mg/1.5 mL) at Week 0, 12, 24, and 36; 2 SC injections of placebo at Week 0 for blinding in participants rolled over from Study TV48125-CNS-30057) through Week 36 in this study.	Drug: Fremanezumab; Fremanezumab; Other Names: TEV-48125
Experimental: Fremanezumab 675/225 mg Monthly Participants with CCH who received placebo IV infusion and SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30057; will receive fremanezumab 675 mg SC injection as loading dose (administered as 3 SC injections of fremanezumab at 225 mg [225 mg/1.5 mL] at Week 0) followed by monthly (approximately every 4 weeks) fremanezumab at 225 mg SC injection (administered as single SC injection of fremanezumab at 225 mg [225 mg/1.5 mL] at Weeks 12, 24, and 36) through Week 36.	Drug: Fremanezumab; Fremanezumab; Other Names: TEV-48125
Experimental: Fremanezumab 675 mg Quarterly Participants with ECH who received fremanezumab at 675 mg SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study; or placebo IV infusion and SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30056; will receive fremanezumab at 675 mg SC injection quarterly (approximately every 12 weeks, administered as 3 SC injections of fremanezumab at 225 mg [225 mg/1.5 mL] at Weeks 0 an 36; and single placebo SC injections at Weeks 4, 8, 16, 20, 28, and 32 for blinding) through Week 36.	Drug: Fremanezumab; Fremanezumab; Other Names: TEV-48125

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events (AEs) [Baseline up to follow-up (Week 68)]

   An 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. 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 participant and required medical intervention to prevent the previously listed serious outcomes. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. Baseline refers to the baseline values from the pivotal studies.

2. Number of Participants With Potentially Clinically Significant Abnormal Laboratory Results: Serum Chemistry [Baseline up to end of treatment (Week 40)]

   Serum chemistry tests with potentially clinically significant abnormal findings included: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), lactate dehydrogenase (LDH) each ≥3*upper limit of normal (ULN); Blood urea nitrogen (BUN) ≥10.71 millimole (mmol)/L; Bilirubin (Total) ≥34.2 micromole/liter (umol/L); and Creatinine ≥177 umol/L. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. Baseline refers to the baseline values from the pivotal studies.

3. Number of Participants With Potentially Clinically Significant Abnormal Laboratory Results: Hematology [Baseline up to end of treatment (Week 40)]

   Hematology tests with potentially clinically significant abnormal findings included: hemoglobin less than or equal to (≤)115 grams (g)/L (males) or ≤95 g/L (females), leukocytes count ≥20*10^9/L or ≤3*10^9/L, eosinophils ≥10%, hematocrit <0.37 L/L (males) and <0.32 L/L (females), platelets count ≥700*10^9/L or ≤75*10^9/L, absolute neutrophil count (ANC) ≤1*10^9/L. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. Baseline refers to the baseline values from the pivotal studies.

4. Number of Participants With Potentially Clinically Significant Abnormal Laboratory Results: Urinalysis [Baseline up to end of treatment (Week 40)]

   Urinalysis laboratory tests with potentially clinically significant abnormal findings included: haemoglobin, urine glucose, ketones, urine total protein each ≥2 unit (U) increase from baseline. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. Baseline refers to the baseline values from the pivotal studies.

5. Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Coagulation Laboratory Test Results [Baseline up to end of treatment (Week 40)]

   Coagulation parameters included: prothrombin time (PT) (seconds) and prothrombin international normalized ratio (INR). Shifts represented as Baseline - endpoint value (last observed post-baseline value). Shifts from baseline to endpoint were summarized using participant counts grouped into three categories: - Low (below normal range) - Normal (within the normal range of 9.4 to 12.5 seconds) - High (above normal range). Missing PT and prothrombin INR shift data are also presented. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. Baseline refers to the baseline values from the pivotal studies.

6. Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Values [Baseline up to follow-up (Week 68)]

   Potentially clinically significant abnormal vital signs findings included: Pulse rate ≥120 beats per minute (bpm) and increase from baseline of ≥15 bpm, or ≤50 bpm and decrease from baseline of ≥15 bpm; Systolic blood pressure ≤90 millimeters of mercury (mmHg) and decrease from baseline of ≥20 mmHg, or ≥180 mmHg and increase from baseline of ≥20 mmHg; Diastolic blood pressure ≤50 mmHg and decrease from baseline of ≥15 mmHg, or ≥105 mmHg and increase from baseline of ≥15 mmHg; Temperature >38.3 degrees celsius (°C). A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. Baseline refers to the baseline values from the pivotal studies.

7. Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters [Baseline up to follow-up (Week 68)]

   ECG parameters included: heart rate, PR interval, QRS interval, QT interval corrected using the Fridericia formula (QTcF), QT interval corrected using the Bazett's formula (QTcB) and RR interval. Shifts represented as Baseline - endpoint value (last observed post-baseline value). Abnormal NCS indicated an abnormal but not clinically significant finding. Abnormal CS indicated an abnormal and clinically significant finding. Missing ECG shift data are also presented. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. Baseline refers to the baseline values from the pivotal studies.

8. Number of Participants With Abnormal Physical Examination Findings [Baseline up to follow-up (Week 68)]

   A complete physical examination included the following organ systems: general appearance; head, eyes, ears, nose, and throat; chest and lungs; heart; abdomen; musculoskeletal; skin; lymph nodes; and neurological. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. Baseline refers to the baseline values from the pivotal studies.

9. Number of Participants With Injection Site Reactions [Baseline up to Week 36]

   Number of participants who reported treatment-emergent injection site reactions are summarized. Preferred terms from Medical Dictionary for Regulatory Activities (MedDRA) version 18.1 were offered without a threshold applied. Injection site reactions included injection site erythema, induration, pain, haemorrhage, bruising, rash, warmth, and pruritus. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. Baseline refers to the baseline values from the pivotal studies.

10. Number of Participants With Hypersensitivity/Anaphylaxis Reactions [Baseline up to Week 36]

    A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. Baseline refers to the baseline values from the pivotal studies.

11. Number of Participants Who Received Concomitant Medications [Baseline up to follow-up (Week 68)]

    Concomitant medications included: agents acting on the renin-angiotensin system, all other therapeutic products (homeopathic), allergens, analgesics, anesthetics, anti-parkinson drugs, antianemic preparations, antibacterials, antibiotics and chemotherapeutics for dermatological use, antidiarrheals, intestinal antiinflammatory/antiinfective agents, antiemetic, antiepileptics, antifungals for dermatologiocal use, antigout preparations, antihemorrhagics, antihistamines for systemic use, antihypertensives, antiinflammatory and antirheumatic products, antimycotics for systemic use, antipruritics, antipsoriatics, antivirals for systemic use, beta blocking agents, blood substitutes and perfusion solutions, cardiac therapy, corticosteroids, cough and cold preparations, diagnostic radiopharmaceuticals, diuretics, thyroid therapy, urologicals, vaccines, psycoleptics, psycoanaleptics, ophthalmologicals, muscle relaxants, drugs used in diabetes. Baseline refers to values from the pivotal studies.

12. Number of Participants With Suicidal Ideation and Suicidal Behavior as Assessed by the Electronic Columbia Suicide Severity Rating Scale (eC-SSRS) [Baseline up to follow-up (Week 68)]

    eC-SSRS is a questionnaire to assess suicidal ideation and suicidal behavior. Suicidal behavior was defined as a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation was defined as a "yes" answer to any one of 5 suicidal ideation questions: wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent, any self-injurious behavior with no suicidal intent. Baseline refers to the baseline values from the pivotal studies.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• The participant completes either the Phase 3 pivotal study for ECH (Study TV48125-CNS-30056) or the Phase 3 pivotal study for CCH (Study TV48125-CNS-30057) without important protocol deviations related to participant safety and participant compliance.

• Prior to 15 June 2018, participants from the ECH study and the CCH study were enrolled. After 15 June 2018, only participants who participated in the ECH study (Study TV48125-CNS-30056) will be enrolled for active treatment.

• In addition, participants who do not complete the pivotal efficacy studies, and participants who complete the pivotal efficacy studies but will not continue treatment during this long-term safety study, will be offered to enroll in this study for the purpose of evaluating ADAs, and safety (adverse events and concomitant medications) approximately 7.5 months after administration of the last dose of the IMP.

• Additional criteria apply, please contact the investigator for more information

Exclusion Criteria:

• Any finding that, in the judgment of the investigator, is a clinically significant abnormality, including serum chemistry, hematology, coagulation, and urinalysis test values (abnormal tests may be repeated for confirmation)

• Additional criteria apply, please contact the investigator for more information

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Teva Investigational Site 13834	Phoenix	Arizona	United States	85018
2	Teva Investigational Site 13819	Canoga Park	California	United States	91303
3	Teva Investigational Site 13811	Santa Monica	California	United States	90404
4	Teva Investigational Site 13823	Stanford	California	United States	94305
5	Teva Investigational Site 13837	Aurora	Colorado	United States	80045
6	Teva Investigational Site 13814	Colorado Springs	Colorado	United States	80918
7	Teva Investigational Site 13836	Denver	Colorado	United States	80218
8	Teva Investigational Site 13813	Englewood	Colorado	United States	80113
9	Teva Investigational Site 13821	New Haven	Connecticut	United States	06510-2483
10	Teva Investigational Site 13812	Stamford	Connecticut	United States	06905
11	Teva Investigational Site 13810	Gainesville	Florida	United States	32607
12	Teva Investigational Site 13815	Orlando	Florida	United States	32806
13	Teva Investigational Site 13829	Ormond Beach	Florida	United States	32174
14	Teva Investigational Site 13830	Saint Petersburg	Florida	United States	33709
15	Teva Investigational Site 13842	Tampa	Florida	United States	33612
16	Teva Investigational Site 13840	Tampa	Florida	United States	33634
17	Teva Investigational Site 13833	Columbus	Georgia	United States	31904
18	Teva Investigational Site 13826	Chicago	Illinois	United States	60614
19	Teva Investigational Site 13818	Ann Arbor	Michigan	United States	48104
20	Teva Investigational Site 13835	Las Vegas	Nevada	United States	89106
21	Teva Investigational Site 13832	Las Vegas	Nevada	United States	89113
22	Teva Investigational Site 13831	Lebanon	New Hampshire	United States	03756
23	Teva Investigational Site 13820	Princeton	New Jersey	United States	08540
24	Teva Investigational Site 13827	Albuquerque	New Mexico	United States	87102
25	Teva Investigational Site 13816	Amherst	New York	United States	14226
26	Teva Investigational Site 13817	New York	New York	United States	10019
27	Teva Investigational Site 13809	Raleigh	North Carolina	United States	27607
28	Teva Investigational Site 13839	Salisbury	North Carolina	United States	28144
29	Teva Investigational Site 13825	Cleveland	Ohio	United States	44195
30	Teva Investigational Site 13824	Philadelphia	Pennsylvania	United States	19107
31	Teva Investigational Site 13841	Richmond	Texas	United States	77307
32	Teva Investigational Site 13822	Virginia Beach	Virginia	United States	23454
33	Teva Investigational Site 78120	Auchenflower		Australia	4066
34	Teva Investigational Site 78118	Clayton		Australia	3168
35	Teva Investigational Site 78123	Melbourne		Australia	3004
36	Teva Investigational Site 78122	Parkville		Australia	3050
37	Teva Investigational Site 78121	Randwick		Australia	2031
38	Teva Investigational Site 11132	Newmarket	Ontario	Canada	L3Y5G8
39	Teva Investigational Site 11130	Calgary		Canada
40	Teva Investigational Site 40030	Helsinki		Finland	00180
41	Teva Investigational Site 40031	Oulu		Finland	90100
42	Teva Investigational Site 40029	Turku		Finland	20100
43	Teva Investigational Site 32666	Berlin		Germany	10117
44	Teva Investigational Site 32667	Bochum		Germany	44787
45	Teva Investigational Site 32660	Essen		Germany	45147
46	Teva Investigational Site 32665	Hamburg		Germany	20246
47	Teva Investigational Site 32662	Kiel		Germany	24149
48	Teva Investigational Site 32661	Konigstein im Taunus		Germany	61462
49	Teva Investigational Site 32663	Rostock		Germany	18147
50	Teva Investigational Site 80124	Ashkelon		Israel	7830604
51	Teva Investigational Site 80122	Hadera		Israel	3810101
52	Teva Investigational Site 80125	Holon		Israel	58100
53	Teva Investigational Site 80121	Jerusalem		Israel	9112001
54	Teva Investigational Site 80123	Netanya		Israel	4244916
55	Teva Investigational Site 80120	Ramat Gan		Israel	5265601
56	Teva Investigational Site 80127	Tel Aviv		Israel	64239
57	Teva Investigational Site 80126	Tel-Aviv		Israel	6812509
58	Teva Investigational Site 30190	Milan		Italy	20133
59	Teva Investigational Site 30192	Modena		Italy	41124
60	Teva Investigational Site 30194	Napoli		Italy	80131
61	Teva Investigational Site 30193	Pavia		Italy	27100
62	Teva Investigational Site 30191	Rome		Italy	00161
63	Teva Investigational Site 30189	Rome		Italy	00163
64	Teva Investigational Site 38118	Leiden		Netherlands	2333 ZA
65	Teva Investigational Site 38119	Nijmegen		Netherlands	6532 SZ
66	Teva Investigational Site 38117	Zwolle		Netherlands	8025 AB
67	Teva Investigational Site 53380	Bialystok		Poland	15-402
68	Teva Investigational Site 53383	Krakow		Poland	31-505
69	Teva Investigational Site 53379	Krakow		Poland	33-332
70	Teva Investigational Site 53382	Lodz		Poland	90-338
71	Teva Investigational Site 53381	Szczecin		Poland	70-111
72	Teva Investigational Site 31211	Galdakao.		Spain	48960
73	Teva Investigational Site 31214	Madrid		Spain	28034
74	Teva Investigational Site 31213	Sevilla		Spain	41013
75	Teva Investigational Site 31212	Valladolid		Spain	47003
76	Teva Investigational Site 31215	Zaragoza		Spain	50009
77	Teva Investigational Site 42047	Huddinge		Sweden	141 86
78	Teva Investigational Site 42045	Vallingby		Sweden	162 68
79	Teva Investigational Site 34224	Glasgow		United Kingdom	G51 4TF
80	Teva Investigational Site 34222	Liverpool		United Kingdom	L9 7LJ
81	Teva Investigational Site 34223	London		United Kingdom	SE1 9RT
82	Teva Investigational Site 34220	London		United Kingdom	W6 8RF
83	Teva Investigational Site 34221	Oxford		United Kingdom	OX3 9DU

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)

• Study Protocol - Aug 28, 2018
• Statistical Analysis Plan - Jul 15, 2019

More Information

Publications

None provided.

• Responsible Party: Teva Branded Pharmaceutical Products R&D, Inc.
• ClinicalTrials.gov Identifier: NCT03107052
• Other Study ID Numbers: TV48125-CNS-30058; 2016-003172-43
• First Posted: Apr 11, 2017
• Last Update Posted: Nov 9, 2021
• Last Verified: Nov 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Cluster Headache; Headache

Study Results

Participant Flow

Recruitment Details	A total of 275 participants with episodic cluster headache (ECH) or chronic cluster headache (CCH) were enrolled in this study.
Pre-assignment Detail	Participants were assigned to receive treatments in fremanezumab 225 milligrams (mg) monthly, fremanezumab 675/225 mg monthly, or fremanezumab 675 mg quarterly groups; based on their randomization in the pivotal studies TV48125-CNS-30056 (NCT02945046) and TV48125-CNS-30057 (NCT02964338).

Arm/Group Title	Fremanezumab 225 mg Monthly	Fremanezumab 675/225 mg Monthly	Fremanezumab 675 mg Quarterly
Arm/Group Description	Participants with ECH or CCH who received fremanezumab at 900 mg intravenous (IV) infusion at Week 0 and fremanezumab at 225 mg subcutaneous (SC) injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30056 or TV48125-CNS-30057, and participants with CCH who received fremanezumab at 675 mg SC injection at Week 0 and fremanezumab at 225 mg SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30057; received fremanezumab at 225 mg SC injection monthly (approximately every 4 weeks, administered as single SC injection of fremanezumab at 225 mg [225 mg/1.5 milliliter {mL}] at Week 0 and 36; and 2 placebo SC injections at Weeks 0, 12, 24, and 36 for blinding in participants rolled over from Study TV48125-CNS-30056; fremanezumab at 225 mg as a single SC injection [225 mg/1.5 mL] at Week 0, 12, 24, and 36; 2 SC injections of placebo at Week 0 for blinding in participants rolled over from Study TV48125-CNS-30057) through Week 36 in this study.	Participants with CCH who received placebo IV infusion and SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30057; received fremanezumab 675 mg SC injection as loading dose (administered as 3 SC injections of fremanezumab at 225 mg [225 mg/1.5 mL] at Week 0) followed by monthly (approximately every 4 weeks) fremanezumab at 225 mg SC injection (administered as single SC injection of fremanezumab at 225 mg [225 mg/1.5 mL] at Weeks 12, 24, and 36) through Week 36.	Participants with ECH who received fremanezumab at 675 mg SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study; or placebo IV infusion and SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30056; received fremanezumab at 675 mg SC injection quarterly (approximately every 12 weeks, administered as 3 SC injections of fremanezumab at 225 mg [225 mg/1.5 mL] at Weeks 0 and 36; and single placebo SC injection at Weeks 4, 8, 16, 20, 28, and 32 for blinding) through Week 36.
Period Title: Overall Study
STARTED	145	60	70
Safety Analysis Set	144	60	71
COMPLETED	26	14	29
NOT COMPLETED	119	46	41

Baseline Characteristics

Arm/Group Title	Fremanezumab 225 mg Monthly	Fremanezumab 675/225 mg Monthly	Fremanezumab 675 mg Quarterly	Total
Arm/Group Description	Participants with ECH or CCH who received fremanezumab at 900 mg IV infusion at Week 0 and fremanezumab at 225 mg SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30056 or TV48125-CNS-30057, and participants with CCH who received fremanezumab at 675 mg SC injection at Week 0 and fremanezumab at 225 mg SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30057; received fremanezumab at 225 mg SC injection monthly (approximately every 4 weeks, administered as single SC injection of fremanezumab at 225 mg [225 mg/1.5 mL] at Week 0 and 36; and 2 placebo SC injections at Weeks 0, 12, 24, and 36 for blinding in participants rolled over from Study TV48125-CNS-30056; fremanezumab at 225 mg as a single SC injection [225 mg/1.5 mL] at Week 0, 12, 24, and 36; 2 SC injections of placebo at Week 0 for blinding in participants rolled over from Study TV48125-CNS-30057) through Week 36 in this study.	Participants with CCH who received placebo IV infusion and SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30057; received fremanezumab 675 mg SC injection as loading dose (administered as 3 SC injections of fremanezumab at 225 mg [225 mg/1.5 mL] at Week 0) followed by monthly (approximately every 4 weeks) fremanezumab at 225 mg SC injection (administered as single SC injection of fremanezumab at 225 mg [225 mg/1.5 mL] at Weeks 12, 24, and 36) through Week 36.	Participants with ECH who received fremanezumab at 675 mg SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study; or placebo IV infusion and SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30056; received fremanezumab at 675 mg SC injection quarterly (approximately every 12 weeks, administered as 3 SC injections of fremanezumab at 225 mg [225 mg/1.5 mL] at Weeks 0 and 36; and single placebo SC injection at Weeks 4, 8, 16, 20, 28, and 32 for blinding) through Week 36.	Total of all reporting groups
Overall Participants	145	60	70	275
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.2 (12.25)	46.1 (11.14)	43.2 (11.40)	44.9 (11.81)
Sex: Female, Male (Count of Participants)
Female	51 35.2%	20 33.3%	25 35.7%	96 34.9%
Male	94 64.8%	40 66.7%	45 64.3%	179 65.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	9 6.2%	3 5%	2 2.9%	14 5.1%
White	136 93.8%	56 93.3%	68 97.1%	260 94.5%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	1 1.7%	0 0%	1 0.4%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events (AEs)
Description	An 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. 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 participant and required medical intervention to prevent the previously listed serious outcomes. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. Baseline refers to the baseline values from the pivotal studies.
Time Frame	Baseline up to follow-up (Week 68)

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of study drug.

Arm/Group Title	Fremanezumab 225 mg Monthly	Fremanezumab 675/225 mg Monthly	Fremanezumab 675 mg Quarterly
Arm/Group Description	Participants with ECH or CCH who received fremanezumab at 900 mg IV infusion at Week 0 and fremanezumab at 225 mg SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30056 or TV48125-CNS-30057, and participants with CCH who received fremanezumab at 675 mg SC injection at Week 0 and fremanezumab at 225 mg SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30057; received fremanezumab at 225 mg SC injection monthly (approximately every 4 weeks, administered as single SC injection of fremanezumab at 225 mg [225 mg/1.5 mL] at Week 0 and 36; and 2 placebo SC injections at Weeks 0, 12, 24, and 36 for blinding in participants rolled over from Study TV48125-CNS-30056; fremanezumab at 225 mg as a single SC injection [225 mg/1.5 mL] at Week 0, 12, 24, and 36; 2 SC injections of placebo at Week 0 for blinding in participants rolled over from Study TV48125-CNS-30057) through Week 36 in this study.	Participants with CCH who received placebo IV infusion and SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30057; received fremanezumab 675 mg SC injection as loading dose (administered as 3 SC injections of fremanezumab at 225 mg [225 mg/1.5 mL] at Week 0) followed by monthly (approximately every 4 weeks) fremanezumab at 225 mg SC injection (administered as single SC injection of fremanezumab at 225 mg [225 mg/1.5 mL] at Weeks 12, 24, and 36) through Week 36.	Participants with ECH who received fremanezumab at 675 mg SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study; or placebo IV infusion and SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30056; received fremanezumab at 675 mg SC injection quarterly (approximately every 12 weeks, administered as 3 SC injections of fremanezumab at 225 mg [225 mg/1.5 mL] at Weeks 0 and 36; and single placebo SC injection at Weeks 4, 8, 16, 20, 28, and 32 for blinding) through Week 36.
Measure Participants	144	60	71
Any AEs	87 60%	31 51.7%	42 60%
Treatment-related AEs	26 17.9%	6 10%	10 14.3%
Serious AEs	8 5.5%	2 3.3%	1 1.4%
AEs leading to discontinuation	6 4.1%	1 1.7%	2 2.9%

2. Primary Outcome

Title	Number of Participants With Potentially Clinically Significant Abnormal Laboratory Results: Serum Chemistry
Description	Serum chemistry tests with potentially clinically significant abnormal findings included: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), lactate dehydrogenase (LDH) each ≥3*upper limit of normal (ULN); Blood urea nitrogen (BUN) ≥10.71 millimole (mmol)/L; Bilirubin (Total) ≥34.2 micromole/liter (umol/L); and Creatinine ≥177 umol/L. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. Baseline refers to the baseline values from the pivotal studies.
Time Frame	Baseline up to end of treatment (Week 40)

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of study drug. Here, 'Overall number of participants analyzed' signifies participants with a laboratory result.

Arm/Group Title	Fremanezumab 225 mg Monthly	Fremanezumab 675/225 mg Monthly	Fremanezumab 675 mg Quarterly
Arm/Group Description	Participants with ECH or CCH who received fremanezumab at 900 mg IV infusion at Week 0 and fremanezumab at 225 mg SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30056 or TV48125-CNS-30057, and participants with CCH who received fremanezumab at 675 mg SC injection at Week 0 and fremanezumab at 225 mg SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30057; received fremanezumab at 225 mg SC injection monthly (approximately every 4 weeks, administered as single SC injection of fremanezumab at 225 mg [225 mg/1.5 mL] at Week 0 and 36; and 2 placebo SC injections at Weeks 0, 12, 24, and 36 for blinding in participants rolled over from Study TV48125-CNS-30056; fremanezumab at 225 mg as a single SC injection [225 mg/1.5 mL] at Week 0, 12, 24, and 36; 2 SC injections of placebo at Week 0 for blinding in participants rolled over from Study TV48125-CNS-30057) through Week 36 in this study.	Participants with CCH who received placebo IV infusion and SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30057; received fremanezumab 675 mg SC injection as loading dose (administered as 3 SC injections of fremanezumab at 225 mg [225 mg/1.5 mL] at Week 0) followed by monthly (approximately every 4 weeks) fremanezumab at 225 mg SC injection (administered as single SC injection of fremanezumab at 225 mg [225 mg/1.5 mL] at Weeks 12, 24, and 36) through Week 36.	Participants with ECH who received fremanezumab at 675 mg SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study; or placebo IV infusion and SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30056; received fremanezumab at 675 mg SC injection quarterly (approximately every 12 weeks, administered as 3 SC injections of fremanezumab at 225 mg [225 mg/1.5 mL] at Weeks 0 and 36; and single placebo SC injection at Weeks 4, 8, 16, 20, 28, and 32 for blinding) through Week 36.
Measure Participants	129	55	67
Count of Participants [Participants]	2 1.4%	0 0%	1 1.4%

3. Primary Outcome

Title	Number of Participants With Potentially Clinically Significant Abnormal Laboratory Results: Hematology
Description	Hematology tests with potentially clinically significant abnormal findings included: hemoglobin less than or equal to (≤)115 grams (g)/L (males) or ≤95 g/L (females), leukocytes count ≥20*10^9/L or ≤3*10^9/L, eosinophils ≥10%, hematocrit <0.37 L/L (males) and <0.32 L/L (females), platelets count ≥700*10^9/L or ≤75*10^9/L, absolute neutrophil count (ANC) ≤1*10^9/L. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. Baseline refers to the baseline values from the pivotal studies.
Time Frame	Baseline up to end of treatment (Week 40)

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of study drug. Here, 'Overall number of participants analyzed' signifies participants with a laboratory result.

Arm/Group Title	Fremanezumab 225 mg Monthly	Fremanezumab 675/225 mg Monthly	Fremanezumab 675 mg Quarterly
Arm/Group Description	Participants with ECH or CCH who received fremanezumab at 900 mg IV infusion at Week 0 and fremanezumab at 225 mg SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30056 or TV48125-CNS-30057, and participants with CCH who received fremanezumab at 675 mg SC injection at Week 0 and fremanezumab at 225 mg SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30057; received fremanezumab at 225 mg SC injection monthly (approximately every 4 weeks, administered as single SC injection of fremanezumab at 225 mg [225 mg/1.5 mL] at Week 0 and 36; and 2 placebo SC injections at Weeks 0, 12, 24, and 36 for blinding in participants rolled over from Study TV48125-CNS-30056; fremanezumab at 225 mg as a single SC injection [225 mg/1.5 mL] at Week 0, 12, 24, and 36; 2 SC injections of placebo at Week 0 for blinding in participants rolled over from Study TV48125-CNS-30057) through Week 36 in this study.	Participants with CCH who received placebo IV infusion and SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30057; received fremanezumab 675 mg SC injection as loading dose (administered as 3 SC injections of fremanezumab at 225 mg [225 mg/1.5 mL] at Week 0) followed by monthly (approximately every 4 weeks) fremanezumab at 225 mg SC injection (administered as single SC injection of fremanezumab at 225 mg [225 mg/1.5 mL] at Weeks 12, 24, and 36) through Week 36.	Participants with ECH who received fremanezumab at 675 mg SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study; or placebo IV infusion and SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30056; received fremanezumab at 675 mg SC injection quarterly (approximately every 12 weeks, administered as 3 SC injections of fremanezumab at 225 mg [225 mg/1.5 mL] at Weeks 0 and 36; and single placebo SC injection at Weeks 4, 8, 16, 20, 28, and 32 for blinding) through Week 36.
Measure Participants	129	55	67
Count of Participants [Participants]	6 4.1%	3 5%	0 0%

4. Primary Outcome

Title	Number of Participants With Potentially Clinically Significant Abnormal Laboratory Results: Urinalysis
Description	Urinalysis laboratory tests with potentially clinically significant abnormal findings included: haemoglobin, urine glucose, ketones, urine total protein each ≥2 unit (U) increase from baseline. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. Baseline refers to the baseline values from the pivotal studies.
Time Frame	Baseline up to end of treatment (Week 40)

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of study drug. Here, 'Overall number of participants analyzed' signifies participants with a laboratory result.

Arm/Group Title	Fremanezumab 225 mg Monthly	Fremanezumab 675/225 mg Monthly	Fremanezumab 675 mg Quarterly
Arm/Group Description	Participants with ECH or CCH who received fremanezumab at 900 mg IV infusion at Week 0 and fremanezumab at 225 mg SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30056 or TV48125-CNS-30057, and participants with CCH who received fremanezumab at 675 mg SC injection at Week 0 and fremanezumab at 225 mg SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30057; received fremanezumab at 225 mg SC injection monthly (approximately every 4 weeks, administered as single SC injection of fremanezumab at 225 mg [225 mg/1.5 mL] at Week 0 and 36; and 2 placebo SC injections at Weeks 0, 12, 24, and 36 for blinding in participants rolled over from Study TV48125-CNS-30056; fremanezumab at 225 mg as a single SC injection [225 mg/1.5 mL] at Week 0, 12, 24, and 36; 2 SC injections of placebo at Week 0 for blinding in participants rolled over from Study TV48125-CNS-30057) through Week 36 in this study.	Participants with CCH who received placebo IV infusion and SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30057; received fremanezumab 675 mg SC injection as loading dose (administered as 3 SC injections of fremanezumab at 225 mg [225 mg/1.5 mL] at Week 0) followed by monthly (approximately every 4 weeks) fremanezumab at 225 mg SC injection (administered as single SC injection of fremanezumab at 225 mg [225 mg/1.5 mL] at Weeks 12, 24, and 36) through Week 36.	Participants with ECH who received fremanezumab at 675 mg SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study; or placebo IV infusion and SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30056; received fremanezumab at 675 mg SC injection quarterly (approximately every 12 weeks, administered as 3 SC injections of fremanezumab at 225 mg [225 mg/1.5 mL] at Weeks 0 and 36; and single placebo SC injection at Weeks 4, 8, 16, 20, 28, and 32 for blinding) through Week 36.
Measure Participants	129	55	67
Count of Participants [Participants]	0 0%	0 0%	0 0%

5. Primary Outcome

Title	Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Coagulation Laboratory Test Results
Description	Coagulation parameters included: prothrombin time (PT) (seconds) and prothrombin international normalized ratio (INR). Shifts represented as Baseline - endpoint value (last observed post-baseline value). Shifts from baseline to endpoint were summarized using participant counts grouped into three categories: - Low (below normal range) - Normal (within the normal range of 9.4 to 12.5 seconds) - High (above normal range). Missing PT and prothrombin INR shift data are also presented. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. Baseline refers to the baseline values from the pivotal studies.
Time Frame	Baseline up to end of treatment (Week 40)

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of study drug.

Arm/Group Title	Fremanezumab 225 mg Monthly	Fremanezumab 675/225 mg Monthly	Fremanezumab 675 mg Quarterly
Arm/Group Description	Participants with ECH or CCH who received fremanezumab at 900 mg IV infusion at Week 0 and fremanezumab at 225 mg SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30056 or TV48125-CNS-30057, and participants with CCH who received fremanezumab at 675 mg SC injection at Week 0 and fremanezumab at 225 mg SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30057; received fremanezumab at 225 mg SC injection monthly (approximately every 4 weeks, administered as single SC injection of fremanezumab at 225 mg [225 mg/1.5 mL] at Week 0 and 36; and 2 placebo SC injections at Weeks 0, 12, 24, and 36 for blinding in participants rolled over from Study TV48125-CNS-30056; fremanezumab at 225 mg as a single SC injection [225 mg/1.5 mL] at Week 0, 12, 24, and 36; 2 SC injections of placebo at Week 0 for blinding in participants rolled over from Study TV48125-CNS-30057) through Week 36 in this study.	Participants with CCH who received placebo IV infusion and SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30057; received fremanezumab 675 mg SC injection as loading dose (administered as 3 SC injections of fremanezumab at 225 mg [225 mg/1.5 mL] at Week 0) followed by monthly (approximately every 4 weeks) fremanezumab at 225 mg SC injection (administered as single SC injection of fremanezumab at 225 mg [225 mg/1.5 mL] at Weeks 12, 24, and 36) through Week 36.	Participants with ECH who received fremanezumab at 675 mg SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study; or placebo IV infusion and SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30056; received fremanezumab at 675 mg SC injection quarterly (approximately every 12 weeks, administered as 3 SC injections of fremanezumab at 225 mg [225 mg/1.5 mL] at Weeks 0 and 36; and single placebo SC injection at Weeks 4, 8, 16, 20, 28, and 32 for blinding) through Week 36.
Measure Participants	144	60	71
Low-Low	0 0%	0 0%	0 0%
Low-Normal	0 0%	0 0%	0 0%
Low-High	0 0%	0 0%	0 0%
Normal-Low	1 0.7%	0 0%	0 0%
Normal-Normal	103 71%	42 70%	61 87.1%
Normal-High	6 4.1%	4 6.7%	1 1.4%
High-Low	0 0%	0 0%	0 0%
High-Normal	7 4.8%	4 6.7%	3 4.3%
High-High	4 2.8%	2 3.3%	0 0%
Missing	23 15.9%	8 13.3%	6 8.6%
Low-Low	0 0%	0 0%	0 0%
Low-Normal	0 0%	0 0%	0 0%
Low-High	0 0%	0 0%	0 0%
Normal-Low	1 0.7%	0 0%	0 0%
Normal-Normal	99 68.3%	39 65%	59 84.3%
Normal-High	6 4.1%	5 8.3%	1 1.4%
High-Low	0 0%	0 0%	0 0%
High-Normal	11 7.6%	4 6.7%	5 7.1%
High-High	4 2.8%	4 6.7%	0 0%
Missing	23 15.9%	8 13.3%	6 8.6%

6. Primary Outcome

Title	Number of Participants With Potentially Clinically Significant Abnormal Vital Signs Values
Description	Potentially clinically significant abnormal vital signs findings included: Pulse rate ≥120 beats per minute (bpm) and increase from baseline of ≥15 bpm, or ≤50 bpm and decrease from baseline of ≥15 bpm; Systolic blood pressure ≤90 millimeters of mercury (mmHg) and decrease from baseline of ≥20 mmHg, or ≥180 mmHg and increase from baseline of ≥20 mmHg; Diastolic blood pressure ≤50 mmHg and decrease from baseline of ≥15 mmHg, or ≥105 mmHg and increase from baseline of ≥15 mmHg; Temperature >38.3 degrees celsius (°C). A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. Baseline refers to the baseline values from the pivotal studies.
Time Frame	Baseline up to follow-up (Week 68)

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of study drug. Here, 'Overall number of participants analyzed' signifies participants with a vital sign result.

Arm/Group Title	Fremanezumab 225 mg Monthly	Fremanezumab 675/225 mg Monthly	Fremanezumab 675 mg Quarterly
Arm/Group Description	Participants with ECH or CCH who received fremanezumab at 900 mg IV infusion at Week 0 and fremanezumab at 225 mg SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30056 or TV48125-CNS-30057, and participants with CCH who received fremanezumab at 675 mg SC injection at Week 0 and fremanezumab at 225 mg SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30057; received fremanezumab at 225 mg SC injection monthly (approximately every 4 weeks, administered as single SC injection of fremanezumab at 225 mg [225 mg/1.5 mL] at Week 0 and 36; and 2 placebo SC injections at Weeks 0, 12, 24, and 36 for blinding in participants rolled over from Study TV48125-CNS-30056; fremanezumab at 225 mg as a single SC injection [225 mg/1.5 mL] at Week 0, 12, 24, and 36; 2 SC injections of placebo at Week 0 for blinding in participants rolled over from Study TV48125-CNS-30057) through Week 36 in this study.	Participants with CCH who received placebo IV infusion and SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30057; received fremanezumab 675 mg SC injection as loading dose (administered as 3 SC injections of fremanezumab at 225 mg [225 mg/1.5 mL] at Week 0) followed by monthly (approximately every 4 weeks) fremanezumab at 225 mg SC injection (administered as single SC injection of fremanezumab at 225 mg [225 mg/1.5 mL] at Weeks 12, 24, and 36) through Week 36.	Participants with ECH who received fremanezumab at 675 mg SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study; or placebo IV infusion and SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30056; received fremanezumab at 675 mg SC injection quarterly (approximately every 12 weeks, administered as 3 SC injections of fremanezumab at 225 mg [225 mg/1.5 mL] at Weeks 0 and 36; and single placebo SC injection at Weeks 4, 8, 16, 20, 28, and 32 for blinding) through Week 36.
Measure Participants	139	57	68
Count of Participants [Participants]	6 4.1%	4 6.7%	2 2.9%

7. Primary Outcome

Title	Number of Participants With Shift From Baseline to Endpoint (Last Assessment) in Electrocardiogram (ECG) Parameters
Description	ECG parameters included: heart rate, PR interval, QRS interval, QT interval corrected using the Fridericia formula (QTcF), QT interval corrected using the Bazett's formula (QTcB) and RR interval. Shifts represented as Baseline - endpoint value (last observed post-baseline value). Abnormal NCS indicated an abnormal but not clinically significant finding. Abnormal CS indicated an abnormal and clinically significant finding. Missing ECG shift data are also presented. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. Baseline refers to the baseline values from the pivotal studies.
Time Frame	Baseline up to follow-up (Week 68)

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of study drug.

Arm/Group Title	Fremanezumab 225 mg Monthly	Fremanezumab 675/225 mg Monthly	Fremanezumab 675 mg Quarterly
Arm/Group Description	Participants with ECH or CCH who received fremanezumab at 900 mg IV infusion at Week 0 and fremanezumab at 225 mg SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30056 or TV48125-CNS-30057, and participants with CCH who received fremanezumab at 675 mg SC injection at Week 0 and fremanezumab at 225 mg SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30057; received fremanezumab at 225 mg SC injection monthly (approximately every 4 weeks, administered as single SC injection of fremanezumab at 225 mg [225 mg/1.5 mL] at Week 0 and 36; and 2 placebo SC injections at Weeks 0, 12, 24, and 36 for blinding in participants rolled over from Study TV48125-CNS-30056; fremanezumab at 225 mg as a single SC injection [225 mg/1.5 mL] at Week 0, 12, 24, and 36; 2 SC injections of placebo at Week 0 for blinding in participants rolled over from Study TV48125-CNS-30057) through Week 36 in this study.	Participants with CCH who received placebo IV infusion and SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30057; received fremanezumab 675 mg SC injection as loading dose (administered as 3 SC injections of fremanezumab at 225 mg [225 mg/1.5 mL] at Week 0) followed by monthly (approximately every 4 weeks) fremanezumab at 225 mg SC injection (administered as single SC injection of fremanezumab at 225 mg [225 mg/1.5 mL] at Weeks 12, 24, and 36) through Week 36.	Participants with ECH who received fremanezumab at 675 mg SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study; or placebo IV infusion and SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30056; received fremanezumab at 675 mg SC injection quarterly (approximately every 12 weeks, administered as 3 SC injections of fremanezumab at 225 mg [225 mg/1.5 mL] at Weeks 0 and 36; and single placebo SC injection at Weeks 4, 8, 16, 20, 28, and 32 for blinding) through Week 36.
Measure Participants	144	60	71
Normal / Normal	76 52.4%	30 50%	46 65.7%
Normal / Abnormal NCS	16 11%	6 10%	4 5.7%
Normal / Abnormal CS	1 0.7%	0 0%	0 0%
Abnormal NCS / Normal	15 10.3%	7 11.7%	4 5.7%
Abnormal NCS / Abnormal NCS	23 15.9%	12 20%	12 17.1%
Abnormal NCS / Abnormal CS	0 0%	0 0%	0 0%
Abnormal CS / Normal	0 0%	0 0%	0 0%
Abnormal CS / Abnormal NCS	0 0%	0 0%	0 0%
Abnormal CS / Abnormal CS	0 0%	0 0%	0 0%
Missing	13 9%	5 8.3%	5 7.1%

8. Primary Outcome

Title	Number of Participants With Abnormal Physical Examination Findings
Description	A complete physical examination included the following organ systems: general appearance; head, eyes, ears, nose, and throat; chest and lungs; heart; abdomen; musculoskeletal; skin; lymph nodes; and neurological. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. Baseline refers to the baseline values from the pivotal studies.
Time Frame	Baseline up to follow-up (Week 68)

Outcome Measure Data

Analysis Population Description

ITT analysis set included all participants who were enrolled in this study for long-term safety evaluation, regardless if they received study treatment or not.

Arm/Group Title	Fremanezumab 225 mg Monthly	Fremanezumab 675/225 mg Monthly	Fremanezumab 675 mg Quarterly
Arm/Group Description	Participants with ECH or CCH who received fremanezumab at 900 mg IV infusion at Week 0 and fremanezumab at 225 mg SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30056 or TV48125-CNS-30057, and participants with CCH who received fremanezumab at 675 mg SC injection at Week 0 and fremanezumab at 225 mg SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30057; received fremanezumab at 225 mg SC injection monthly (approximately every 4 weeks, administered as single SC injection of fremanezumab at 225 mg [225 mg/1.5 mL] at Week 0 and 36; and 2 placebo SC injections at Weeks 0, 12, 24, and 36 for blinding in participants rolled over from Study TV48125-CNS-30056; fremanezumab at 225 mg as a single SC injection [225 mg/1.5 mL] at Week 0, 12, 24, and 36; 2 SC injections of placebo at Week 0 for blinding in participants rolled over from Study TV48125-CNS-30057) through Week 36 in this study.	Participants with CCH who received placebo IV infusion and SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30057; received fremanezumab 675 mg SC injection as loading dose (administered as 3 SC injections of fremanezumab at 225 mg [225 mg/1.5 mL] at Week 0) followed by monthly (approximately every 4 weeks) fremanezumab at 225 mg SC injection (administered as single SC injection of fremanezumab at 225 mg [225 mg/1.5 mL] at Weeks 12, 24, and 36) through Week 36.	Participants with ECH who received fremanezumab at 675 mg SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study; or placebo IV infusion and SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30056; received fremanezumab at 675 mg SC injection quarterly (approximately every 12 weeks, administered as 3 SC injections of fremanezumab at 225 mg [225 mg/1.5 mL] at Weeks 0 and 36; and single placebo SC injection at Weeks 4, 8, 16, 20, 28, and 32 for blinding) through Week 36.
Measure Participants	145	60	70
Count of Participants [Participants]	22 15.2%	8 13.3%	7 10%

9. Primary Outcome

Title	Number of Participants With Injection Site Reactions
Description	Number of participants who reported treatment-emergent injection site reactions are summarized. Preferred terms from Medical Dictionary for Regulatory Activities (MedDRA) version 18.1 were offered without a threshold applied. Injection site reactions included injection site erythema, induration, pain, haemorrhage, bruising, rash, warmth, and pruritus. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. Baseline refers to the baseline values from the pivotal studies.
Time Frame	Baseline up to Week 36

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of study drug.

Arm/Group Title	Fremanezumab 225 mg Monthly	Fremanezumab 675/225 mg Monthly	Fremanezumab 675 mg Quarterly
Arm/Group Description	Participants with ECH or CCH who received fremanezumab at 900 mg IV infusion at Week 0 and fremanezumab at 225 mg SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30056 or TV48125-CNS-30057, and participants with CCH who received fremanezumab at 675 mg SC injection at Week 0 and fremanezumab at 225 mg SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30057; received fremanezumab at 225 mg SC injection monthly (approximately every 4 weeks, administered as single SC injection of fremanezumab at 225 mg [225 mg/1.5 mL] at Week 0 and 36; and 2 placebo SC injections at Weeks 0, 12, 24, and 36 for blinding in participants rolled over from Study TV48125-CNS-30056; fremanezumab at 225 mg as a single SC injection [225 mg/1.5 mL] at Week 0, 12, 24, and 36; 2 SC injections of placebo at Week 0 for blinding in participants rolled over from Study TV48125-CNS-30057) through Week 36 in this study.	Participants with CCH who received placebo IV infusion and SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30057; received fremanezumab 675 mg SC injection as loading dose (administered as 3 SC injections of fremanezumab at 225 mg [225 mg/1.5 mL] at Week 0) followed by monthly (approximately every 4 weeks) fremanezumab at 225 mg SC injection (administered as single SC injection of fremanezumab at 225 mg [225 mg/1.5 mL] at Weeks 12, 24, and 36) through Week 36.	Participants with ECH who received fremanezumab at 675 mg SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study; or placebo IV infusion and SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30056; received fremanezumab at 675 mg SC injection quarterly (approximately every 12 weeks, administered as 3 SC injections of fremanezumab at 225 mg [225 mg/1.5 mL] at Weeks 0 and 36; and single placebo SC injection at Weeks 4, 8, 16, 20, 28, and 32 for blinding) through Week 36.
Measure Participants	144	60	71
Injection site induration	13 9%	4 6.7%	5 7.1%
Injection site pain	6 4.1%	1 1.7%	3 4.3%
Injection site erythema	7 4.8%	1 1.7%	1 1.4%
Injection site haemorrhage	2 1.4%	0 0%	0 0%
Injection site pruritus	2 1.4%	0 0%	0 0%
Injection site bruising	0 0%	1 1.7%	0 0%
Injection site rash	0 0%	0 0%	1 1.4%
Injection site warmth	1 0.7%	0 0%	0 0%

10. Primary Outcome

Title	Number of Participants With Hypersensitivity/Anaphylaxis Reactions
Description	A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. Baseline refers to the baseline values from the pivotal studies.
Time Frame	Baseline up to Week 36

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of study drug.

Arm/Group Title	Fremanezumab 225 mg Monthly	Fremanezumab 675/225 mg Monthly	Fremanezumab 675 mg Quarterly
Arm/Group Description	Participants with ECH or CCH who received fremanezumab at 900 mg IV infusion at Week 0 and fremanezumab at 225 mg SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30056 or TV48125-CNS-30057, and participants with CCH who received fremanezumab at 675 mg SC injection at Week 0 and fremanezumab at 225 mg SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30057; received fremanezumab at 225 mg SC injection monthly (approximately every 4 weeks, administered as single SC injection of fremanezumab at 225 mg [225 mg/1.5 mL] at Week 0 and 36; and 2 placebo SC injections at Weeks 0, 12, 24, and 36 for blinding in participants rolled over from Study TV48125-CNS-30056; fremanezumab at 225 mg as a single SC injection [225 mg/1.5 mL] at Week 0, 12, 24, and 36; 2 SC injections of placebo at Week 0 for blinding in participants rolled over from Study TV48125-CNS-30057) through Week 36 in this study.	Participants with CCH who received placebo IV infusion and SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30057; received fremanezumab 675 mg SC injection as loading dose (administered as 3 SC injections of fremanezumab at 225 mg [225 mg/1.5 mL] at Week 0) followed by monthly (approximately every 4 weeks) fremanezumab at 225 mg SC injection (administered as single SC injection of fremanezumab at 225 mg [225 mg/1.5 mL] at Weeks 12, 24, and 36) through Week 36.	Participants with ECH who received fremanezumab at 675 mg SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study; or placebo IV infusion and SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30056; received fremanezumab at 675 mg SC injection quarterly (approximately every 12 weeks, administered as 3 SC injections of fremanezumab at 225 mg [225 mg/1.5 mL] at Weeks 0 and 36; and single placebo SC injection at Weeks 4, 8, 16, 20, 28, and 32 for blinding) through Week 36.
Measure Participants	144	60	71
Count of Participants [Participants]	0 0%	0 0%	0 0%

11. Primary Outcome

Title	Number of Participants Who Received Concomitant Medications
Description	Concomitant medications included: agents acting on the renin-angiotensin system, all other therapeutic products (homeopathic), allergens, analgesics, anesthetics, anti-parkinson drugs, antianemic preparations, antibacterials, antibiotics and chemotherapeutics for dermatological use, antidiarrheals, intestinal antiinflammatory/antiinfective agents, antiemetic, antiepileptics, antifungals for dermatologiocal use, antigout preparations, antihemorrhagics, antihistamines for systemic use, antihypertensives, antiinflammatory and antirheumatic products, antimycotics for systemic use, antipruritics, antipsoriatics, antivirals for systemic use, beta blocking agents, blood substitutes and perfusion solutions, cardiac therapy, corticosteroids, cough and cold preparations, diagnostic radiopharmaceuticals, diuretics, thyroid therapy, urologicals, vaccines, psycoleptics, psycoanaleptics, ophthalmologicals, muscle relaxants, drugs used in diabetes. Baseline refers to values from the pivotal studies.
Time Frame	Baseline up to follow-up (Week 68)

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of study drug.

Arm/Group Title	Fremanezumab 225 mg Monthly	Fremanezumab 675/225 mg Monthly	Fremanezumab 675 mg Quarterly
Arm/Group Description	Participants with ECH or CCH who received fremanezumab at 900 mg IV infusion at Week 0 and fremanezumab at 225 mg SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30056 or TV48125-CNS-30057, and participants with CCH who received fremanezumab at 675 mg SC injection at Week 0 and fremanezumab at 225 mg SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30057; received fremanezumab at 225 mg SC injection monthly (approximately every 4 weeks, administered as single SC injection of fremanezumab at 225 mg [225 mg/1.5 mL] at Week 0 and 36; and 2 placebo SC injections at Weeks 0, 12, 24, and 36 for blinding in participants rolled over from Study TV48125-CNS-30056; fremanezumab at 225 mg as a single SC injection [225 mg/1.5 mL] at Week 0, 12, 24, and 36; 2 SC injections of placebo at Week 0 for blinding in participants rolled over from Study TV48125-CNS-30057) through Week 36 in this study.	Participants with CCH who received placebo IV infusion and SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30057; received fremanezumab 675 mg SC injection as loading dose (administered as 3 SC injections of fremanezumab at 225 mg [225 mg/1.5 mL] at Week 0) followed by monthly (approximately every 4 weeks) fremanezumab at 225 mg SC injection (administered as single SC injection of fremanezumab at 225 mg [225 mg/1.5 mL] at Weeks 12, 24, and 36) through Week 36.	Participants with ECH who received fremanezumab at 675 mg SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study; or placebo IV infusion and SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30056; received fremanezumab at 675 mg SC injection quarterly (approximately every 12 weeks, administered as 3 SC injections of fremanezumab at 225 mg [225 mg/1.5 mL] at Weeks 0 and 36; and single placebo SC injection at Weeks 4, 8, 16, 20, 28, and 32 for blinding) through Week 36.
Measure Participants	144	60	71
Count of Participants [Participants]	140 96.6%	56 93.3%	68 97.1%

12. Primary Outcome

Title	Number of Participants With Suicidal Ideation and Suicidal Behavior as Assessed by the Electronic Columbia Suicide Severity Rating Scale (eC-SSRS)
Description	eC-SSRS is a questionnaire to assess suicidal ideation and suicidal behavior. Suicidal behavior was defined as a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation was defined as a "yes" answer to any one of 5 suicidal ideation questions: wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent, any self-injurious behavior with no suicidal intent. Baseline refers to the baseline values from the pivotal studies.
Time Frame	Baseline up to follow-up (Week 68)

Outcome Measure Data

Analysis Population Description

ITT analysis set included all participants who were enrolled in this study for long-term safety evaluation, regardless if they received study treatment or not.

Arm/Group Title	Fremanezumab 225 mg Monthly	Fremanezumab 675/225 mg Monthly	Fremanezumab 675 mg Quarterly
Arm/Group Description	Participants with ECH or CCH who received fremanezumab at 900 mg IV infusion at Week 0 and fremanezumab at 225 mg SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30056 or TV48125-CNS-30057, and participants with CCH who received fremanezumab at 675 mg SC injection at Week 0 and fremanezumab at 225 mg SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30057; received fremanezumab at 225 mg SC injection monthly (approximately every 4 weeks, administered as single SC injection of fremanezumab at 225 mg [225 mg/1.5 mL] at Week 0 and 36; and 2 placebo SC injections at Weeks 0, 12, 24, and 36 for blinding in participants rolled over from Study TV48125-CNS-30056; fremanezumab at 225 mg as a single SC injection [225 mg/1.5 mL] at Week 0, 12, 24, and 36; 2 SC injections of placebo at Week 0 for blinding in participants rolled over from Study TV48125-CNS-30057) through Week 36 in this study.	Participants with CCH who received placebo IV infusion and SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30057; received fremanezumab 675 mg SC injection as loading dose (administered as 3 SC injections of fremanezumab at 225 mg [225 mg/1.5 mL] at Week 0) followed by monthly (approximately every 4 weeks) fremanezumab at 225 mg SC injection (administered as single SC injection of fremanezumab at 225 mg [225 mg/1.5 mL] at Weeks 12, 24, and 36) through Week 36.	Participants with ECH who received fremanezumab at 675 mg SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study; or placebo IV infusion and SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30056; received fremanezumab at 675 mg SC injection quarterly (approximately every 12 weeks, administered as 3 SC injections of fremanezumab at 225 mg [225 mg/1.5 mL] at Weeks 0 and 36; and single placebo SC injection at Weeks 4, 8, 16, 20, 28, and 32 for blinding) through Week 36.
Measure Participants	145	60	70
Count of Participants [Participants]	7 4.8%	1 1.7%	3 4.3%

Adverse Events

Time Frame	Baseline up to Week 68
Adverse Event Reporting Description	Safety population included all participants who received at least 1 dose of study drug.
Arm/Group Title	Fremanezumab 225 mg Monthly		Fremanezumab 675/225 mg Monthly		Fremanezumab 675 mg Quarterly
Arm/Group Description	Participants with ECH or CCH who received fremanezumab at 900 mg IV infusion at Week 0 and fremanezumab at 225 mg SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30056 or TV48125-CNS-30057, and participants with CCH who received fremanezumab at 675 mg SC injection at Week 0 and fremanezumab at 225 mg SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30057; received fremanezumab at 225 mg SC injection monthly (approximately every 4 weeks, administered as single SC injection of fremanezumab at 225 mg [225 mg/1.5 mL] at Week 0 and 36; and 2 placebo SC injections at Weeks 0, 12, 24, and 36 for blinding in participants rolled over from Study TV48125-CNS-30056; fremanezumab at 225 mg as a single SC injection [225 mg/1.5 mL] at Week 0, 12, 24, and 36; 2 SC injections of placebo at Week 0 for blinding in participants rolled over from Study TV48125-CNS-30057) through Week 36 in this study.		Participants with CCH who received placebo IV infusion and SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30057; received fremanezumab 675 mg SC injection as loading dose (administered as 3 SC injections of fremanezumab at 225 mg [225 mg/1.5 mL] at Week 0) followed by monthly (approximately every 4 weeks) fremanezumab at 225 mg SC injection (administered as single SC injection of fremanezumab at 225 mg [225 mg/1.5 mL] at Weeks 12, 24, and 36) through Week 36.		Participants with ECH who received fremanezumab at 675 mg SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study; or placebo IV infusion and SC injection at Week 0 and placebo SC injection at Weeks 4 and 8, respectively in the pivotal study TV48125-CNS-30056; received fremanezumab at 675 mg SC injection quarterly (approximately every 12 weeks, administered as 3 SC injections of fremanezumab at 225 mg [225 mg/1.5 mL] at Weeks 0 and 36; and single placebo SC injection at Weeks 4, 8, 16, 20, 28, and 32 for blinding) through Week 36.
All Cause Mortality
	Fremanezumab 225 mg Monthly		Fremanezumab 675/225 mg Monthly		Fremanezumab 675 mg Quarterly
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/144 (0%)		0/60 (0%)		0/71 (0%)
Serious Adverse Events
	Fremanezumab 225 mg Monthly		Fremanezumab 675/225 mg Monthly		Fremanezumab 675 mg Quarterly
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/144 (5.6%)		2/60 (3.3%)		1/71 (1.4%)
Cardiac disorders
Acute myocardial infarction	1/144 (0.7%)	1	0/60 (0%)	0	0/71 (0%)	0
Eye disorders
Amaurosis fugax	0/144 (0%)	0	0/60 (0%)	0	1/71 (1.4%)	1
Hepatobiliary disorders
Cholecystitis	1/144 (0.7%)	1	0/60 (0%)	0	0/71 (0%)	0
Cholelithiasis	1/144 (0.7%)	1	0/60 (0%)	0	0/71 (0%)	0
Infections and infestations
Influenza	0/144 (0%)	0	1/60 (1.7%)	1	0/71 (0%)	0
Injury, poisoning and procedural complications
Intentional overdose	1/144 (0.7%)	1	0/60 (0%)	0	0/71 (0%)	0
Lumbar vertebral fracture	1/144 (0.7%)	1	0/60 (0%)	0	0/71 (0%)	0
Road traffic accident	1/144 (0.7%)	1	0/60 (0%)	0	0/71 (0%)	0
Musculoskeletal and connective tissue disorders
Rotator cuff syndrome	0/144 (0%)	0	1/60 (1.7%)	1	0/71 (0%)	0
Nervous system disorders
Carotid artery stenosis	0/144 (0%)	0	0/60 (0%)	0	1/71 (1.4%)	1
Cluster headache	3/144 (2.1%)	3	0/60 (0%)	0	0/71 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	0/144 (0%)	0	1/60 (1.7%)	1	0/71 (0%)	0
Other (Not Including Serious) Adverse Events
	Fremanezumab 225 mg Monthly		Fremanezumab 675/225 mg Monthly		Fremanezumab 675 mg Quarterly
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	31/144 (21.5%)		11/60 (18.3%)		14/71 (19.7%)
Gastrointestinal disorders
Nausea	2/144 (1.4%)	3	3/60 (5%)	4	0/71 (0%)	0
General disorders
Injection site induration	13/144 (9%)	44	4/60 (6.7%)	13	5/71 (7%)	10
Oedema peripheral	0/144 (0%)	0	3/60 (5%)	3	0/71 (0%)	0
Infections and infestations
Nasopharyngitis	16/144 (11.1%)	18	5/60 (8.3%)	8	7/71 (9.9%)	8
Sinusitis	4/144 (2.8%)	4	3/60 (5%)	4	2/71 (2.8%)	2

Limitations/Caveats

The study was terminated after the ECH study (TV48125-CNS-30056) was terminated due to a pre specified futility analyses.

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.