A Study to Evaluate the Efficacy and Safety of TEV-48125 (Fremanezumab) for the Prevention of Episodic Cluster Headache (ECH)

• ClinicalTrials.gov Identifier: NCT02945046
• Recruitment Status: Terminated
• First Posted: October 26, 2016
• Results First Posted: April 13, 2020
• Last Update Posted: November 9, 2021
• Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
• Information provided by (Responsible Party): Teva Branded Pharmaceutical Products R&D, Inc.

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Episodic Cluster Headache
• Interventions: Drug: Fremanezumab; Drug: Placebo
• Enrollment: 169

Participant Flow

Recruitment Details
Pre-assignment Details	A total of 169 participants were randomized in a 1:1:1 ratio to placebo, fremanezumab 675 milligrams (mg)/placebo/placebo, or fremanezumab 900/225/225 mg groups.

Arm/Group Title	Placebo	Fremanezumab 675 mg/Placebo/Placebo	Fremanezumab 900/225/225 mg
Arm/Group Description	Participants received placebo administered via an approximately 1-hour intravenous infusion and as 3 subcutaneous injections at Week 0 followed by placebo administered as single subcutaneous injection at Weeks 4 and 8, respectively.	Participants received placebo as an approximately 1-hour intravenous infusion followed by fremanezumab at 675 milligrams (mg) administered as 3 subcutaneous injections (225 mg/1.5 milliliters [mL]) at Week 0 and placebo administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively.	Participants received fremanezumab at 900 mg administered via an approximately 1-hour intravenous infusion followed by 3 placebo subcutaneous injections at Week 0 and fremanezumab at 225 mg administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively.
Period Title: Overall Study
Started [1]	59	55	55
Safety Analysis Set [2]	59	55	55
Full Analysis Set [3]	57	53	55
Completed	46	42	40
Not Completed	13	13	15
Reason Not Completed
Adverse Event	1	0	2
Withdrawal by Subject	3	3	3
Protocol Violation	2	3	2
Lost to Follow-up	1	1	0
Lack of Efficacy	1	2	1
Other than specified	5	4	7
[1] Intent-to-treat (ITT) analysis set: all randomized participants.; [2] All randomized participants who received at least 1 dose of investigational medicinal product (IMP).; [3] Received ≥1 dose of IMP; had ≥10 days of postbaseline efficacy assessment on primary endpoint.

Baseline Characteristics

Arm/Group Title		Placebo	Fremanezumab 675 mg/Placebo/Placebo	Fremanezumab 900/225/225 mg	Total
Arm/Group Description		Participants received placebo administered via an approximately 1-hour intravenous infusion and as 3 subcutaneous injections at Week 0 followed by placebo administered as single subcutaneous injection at Weeks 4 and 8, respectively.	Participants received placebo as an approximately 1-hour intravenous infusion followed by fremanezumab at 675 mg administered as 3 subcutaneous injections (225 mg/1.5 mL) at Week 0 and placebo administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively.	Participants received fremanezumab at 900 mg administered via an approximately 1-hour intravenous infusion followed by 3 placebo subcutaneous injections at Week 0 and fremanezumab at 225 mg administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively.	Total of all reporting groups
Overall Number of Baseline Participants		59	55	55	169
Baseline Analysis Population Description		ITT analysis set included all randomized participants.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	59 participants	55 participants	55 participants	169 participants
		43.1 (10.39)	45.4 (11.23)	43.5 (11.48)	43.9 (11.01)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	59 participants	55 participants	55 participants	169 participants
	Female	16 27.1%	17 30.9%	17 30.9%	50 29.6%
	Male	43 72.9%	38 69.1%	38 69.1%	119 70.4%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	59 participants	55 participants	55 participants	169 participants
	Hispanic or Latino	2 3.4%	3 5.5%	5 9.1%	10 5.9%
	Not Hispanic or Latino	56 94.9%	52 94.5%	49 89.1%	157 92.9%
	Unknown or Not Reported	1 1.7%	0 0.0%	1 1.8%	2 1.2%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	59 participants	55 participants	55 participants	169 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Asian	1 1.7%	0 0.0%	1 1.8%	2 1.2%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Black or African American	3 5.1%	0 0.0%	2 3.6%	5 3.0%
	White	54 91.5%	55 100.0%	51 92.7%	160 94.7%
	More than one race	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	1 1.7%	0 0.0%	1 1.8%	2 1.2%
Number of CH Attacks [1]; Mean (Standard Deviation); Unit of measure: CH attacks
	Number Analyzed	59 participants	55 participants	55 participants	169 participants
		14.8 (10.50)	15.9 (9.18)	14.5 (7.55)	15.1 (9.15)
		[1] Measure Description: A CH attack was defined as a severe or very severe unilateral orbital, supraorbital, and/or temporal pain lasting 15 to 180 minutes with either or both of the following 2 categories: 1) at least 1 of the following symptoms or signs, ipsilateral to the headache: -conjunctival injection and/or lacrimation; -nasal congestion and/or rhinorrhea; -eyelid edema; -forehead and facial sweating; -forehead and facial flushing; -sensation of fullness in the ear; -miosis and/or ptosis. 2) a sense of restlessness or agitation.

Outcome Measures

1. Primary Outcome

Title	Mean Change From Baseline in the Weekly Average Number of Cluster Headache (CH) Attacks During the 4-Week Period After Administration of the First Dose of the IMP
Description	A CH attack was defined as a severe or very severe unilateral orbital, supraorbital, and/or temporal pain lasting 15 to 180 minutes with either or both of the following 2 categories: 1) at least 1 of the following symptoms or signs, ipsilateral to the headache: -conjunctival injection and/or lacrimation; -nasal congestion and/or rhinorrhea; -eyelid edema; -forehead and facial sweating; -forehead and facial flushing; -sensation of fullness in the ear; -miosis and/or ptosis. 2) a sense of restlessness or agitation. Least Squares (LS) mean calculated using analysis of covariance (ANCOVA) model with baseline preventive medication use (yes or no), sex, region (United States [US]/Canada or other), and treatment as fixed effects and the baseline number of CH attacks as a covariate. Change from baseline in the overall weekly average number of CH attacks during the 4-week period after administration of the first dose of study drug (based on Week 0 to 4 data) is reported.
Time Frame	Baseline (Week 0), up to Week 4

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomized participants who received at least 1 dose of IMP and had at least 10 days of postbaseline efficacy assessment in the first 4 weeks on the primary endpoint.

Arm/Group Title	Placebo	Fremanezumab 675 mg/Placebo/Placebo	Fremanezumab 900/225/225 mg
Arm/Group Description:	Participants received placebo administered via an approximately 1-hour intravenous infusion and as 3 subcutaneous injections at Week 0 followed by placebo administered as single subcutaneous injection at Weeks 4 and 8, respectively.	Participants received placebo as an approximately 1-hour intravenous infusion followed by fremanezumab at 675 mg administered as 3 subcutaneous injections (225 mg/1.5 mL) at Week 0 and placebo administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively.	Participants received fremanezumab at 900 mg administered via an approximately 1-hour intravenous infusion followed by 3 placebo subcutaneous injections at Week 0 and fremanezumab at 225 mg administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively.
Overall Number of Participants Analyzed	57	53	55
Least Squares Mean (Standard Error); Unit of Measure: CH attacks/week
	-5.7 (1.00)	-5.8 (1.02)	-7.6 (1.01)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Fremanezumab 675 mg/Placebo/Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.9093
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -2.72 to 2.42
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.30
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Fremanezumab 900/225/225 mg
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1345
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-1.9
	Confidence Interval	(2-Sided) 95%; -4.49 to 0.61
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.29
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Percentage of Participants With a ≥50% Reduction From Baseline in the Weekly Average Number of CH Attacks During the 4-Week Period After the First Dose of the IMP
Description	A CH attack was defined as a severe or very severe unilateral orbital, supraorbital, and/or temporal pain lasting 15 to 180 minutes with either or both of the following 2 categories: 1) at least 1 of the following symptoms or signs, ipsilateral to the headache: -conjunctival injection and/or lacrimation; -nasal congestion and/or rhinorrhea; -eyelid edema; -forehead and facial sweating; -forehead and facial flushing; -sensation of fullness in the ear; -miosis and/or ptosis. 2) a sense of restlessness or agitation.
Time Frame	Baseline (Week 0), up to Week 4

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomized participants who received at least 1 dose of IMP and had at least 10 days of postbaseline efficacy assessment in the first 4 weeks on the primary endpoint.

Arm/Group Title	Placebo	Fremanezumab 675 mg/Placebo/Placebo	Fremanezumab 900/225/225 mg
Arm/Group Description:	Participants received placebo administered via an approximately 1-hour intravenous infusion and as 3 subcutaneous injections at Week 0 followed by placebo administered as single subcutaneous injection at Weeks 4 and 8, respectively.	Participants received placebo as an approximately 1-hour intravenous infusion followed by fremanezumab at 675 mg administered as 3 subcutaneous injections (225 mg/1.5 mL) at Week 0 and placebo administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively.	Participants received fremanezumab at 900 mg administered via an approximately 1-hour intravenous infusion followed by 3 placebo subcutaneous injections at Week 0 and fremanezumab at 225 mg administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively.
Overall Number of Participants Analyzed	57	53	55
Measure Type: Number; Unit of Measure: percentage of participants
	60	55	75

3. Secondary Outcome

Title	Mean Change From Baseline in Weekly Average Number of CH Attacks During the 12-Week Period After Administration of the First Dose of the IMP
Description	A CH attack was defined as a severe or very severe unilateral orbital, supraorbital, and/or temporal pain lasting 15 to 180 minutes with either or both of the following 2 categories: 1) at least 1 of the following symptoms or signs, ipsilateral to the headache: -conjunctival injection and/or lacrimation; -nasal congestion and/or rhinorrhea; -eyelid edema; -forehead and facial sweating; -forehead and facial flushing; -sensation of fullness in the ear; -miosis and/or ptosis. 2) a sense of restlessness or agitation. LS mean calculated using mixed model for repeated measures (MMRM) with baseline preventive medication use (yes or no), gender, region (US/Canada or other), treatment, month, and month-by-treatment interaction as fixed effects and baseline number of CH attacks as a covariate. Change from baseline in the overall weekly average number of CH attacks during the 12-week period after administration of the first dose of study drug (based on Week 0 to 12 data) is reported.
Time Frame	Baseline (Week 0), up to Week 12

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomized participants who received at least 1 dose of IMP and had at least 10 days of postbaseline efficacy assessment in the first 4 weeks on the primary endpoint.

Arm/Group Title	Placebo	Fremanezumab 675 mg/Placebo/Placebo	Fremanezumab 900/225/225 mg
Arm/Group Description:	Participants received placebo administered via an approximately 1-hour intravenous infusion and as 3 subcutaneous injections at Week 0 followed by placebo administered as single subcutaneous injection at Weeks 4 and 8, respectively.	Participants received placebo as an approximately 1-hour intravenous infusion followed by fremanezumab at 675 mg administered as 3 subcutaneous injections (225 mg/1.5 mL) at Week 0 and placebo administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively.	Participants received fremanezumab at 900 mg administered via an approximately 1-hour intravenous infusion followed by 3 placebo subcutaneous injections at Week 0 and fremanezumab at 225 mg administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively.
Overall Number of Participants Analyzed	57	53	55
Least Squares Mean (Standard Error); Unit of Measure: CH attacks/week
	-8.4 (0.66)	-8.9 (0.68)	-9.6 (0.67)

4. Secondary Outcome

Title	Mean Change From Baseline in Weekly Average Number of CH Attacks During the 4-Week Period After Administration of the Third Dose of the IMP
Description	A CH attack was defined as a severe or very severe unilateral orbital, supraorbital, and/or temporal pain lasting 15 to 180 minutes with either or both of the following 2 categories: 1) at least 1 of the following symptoms or signs, ipsilateral to the headache: -conjunctival injection and/or lacrimation; -nasal congestion and/or rhinorrhea; -eyelid edema; -forehead and facial sweating; -forehead and facial flushing; -sensation of fullness in the ear; -miosis and/or ptosis. 2) a sense of restlessness or agitation. LS mean calculated using MMRM with baseline preventive medication use (yes or no), gender, region (US/Canada or other), treatment, month, and month-by-treatment interaction as fixed effects and baseline number of CH attacks as a covariate. Change from baseline in the overall weekly average number of CH attacks during the 4-week period after administration of the first dose of study drug (based on Week 8 to 12 data) is reported.
Time Frame	Baseline (Week 0), Week 8 up to Week 12

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomized participants who received at least 1 dose of IMP and had at least 10 days of postbaseline efficacy assessment in the first 4 weeks on the primary endpoint. Here, 'overall number of participants analyzed'=participants evaluable for this outcome measure.

Arm/Group Title	Placebo	Fremanezumab 675 mg/Placebo/Placebo	Fremanezumab 900/225/225 mg
Arm/Group Description:	Participants received placebo administered via an approximately 1-hour intravenous infusion and as 3 subcutaneous injections at Week 0 followed by placebo administered as single subcutaneous injection at Weeks 4 and 8, respectively.	Participants received placebo as an approximately 1-hour intravenous infusion followed by fremanezumab at 675 mg administered as 3 subcutaneous injections (225 mg/1.5 mL) at Week 0 and placebo administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively.	Participants received fremanezumab at 900 mg administered via an approximately 1-hour intravenous infusion followed by 3 placebo subcutaneous injections at Week 0 and fremanezumab at 225 mg administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively.
Overall Number of Participants Analyzed	46	42	40
Least Squares Mean (Standard Error); Unit of Measure: CH attacks/week
	-10.8 (0.75)	-10.8 (0.78)	-10.9 (0.78)

5. Secondary Outcome

Title	Mean Change From Baseline in the Weekly Average Number of Days With Use of Cluster-Specific Acute Headache Medications (Triptans and Ergot Compounds) During the 12-Week Period After the First Dose of the IMP
Description	A maximum of 2 concomitant preventive medications for CH were allowed during the study. Participants must have been on a stable dose and regimen of the concomitant medication for at least 2 weeks before screening and throughout the study. LS mean calculated using ANCOVA model with baseline preventive medication use (yes or no), gender, region (US/Canada or other), and treatment as fixed effects and the baseline number of cluster headache attacks as a covariate. Baseline data and the mean change from baseline in the overall weekly average number of days with the use of cluster-specific acute headache medications (triptans and ergot compounds) during the 12-week period after administration of the first dose of study drug (based on Week 0 to 12 data) is reported.
Time Frame	Baseline (Week 0), up to Week 12

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomized participants who received at least 1 dose of IMP and had at least 10 days of postbaseline efficacy assessment in the first 4 weeks on the primary endpoint.

Arm/Group Title	Placebo	Fremanezumab 675 mg/Placebo/Placebo	Fremanezumab 900/225/225 mg
Arm/Group Description:	Participants received placebo administered via an approximately 1-hour intravenous infusion and as 3 subcutaneous injections at Week 0 followed by placebo administered as single subcutaneous injection at Weeks 4 and 8, respectively.	Participants received placebo as an approximately 1-hour intravenous infusion followed by fremanezumab at 675 mg administered as 3 subcutaneous injections (225 mg/1.5 mL) at Week 0 and placebo administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively.	Participants received fremanezumab at 900 mg administered via an approximately 1-hour intravenous infusion followed by 3 placebo subcutaneous injections at Week 0 and fremanezumab at 225 mg administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively.
Overall Number of Participants Analyzed	57	53	55
Least Squares Mean (Standard Error); Unit of Measure: days of use/week
	-1.6 (0.36)	-2.4 (0.36)	-2.8 (0.36)

6. Secondary Outcome

Title	Mean Change From Baseline in the Weekly Average Number of Days Oxygen Was Used to Treat Episodic Cluster Headache (ECH) During the 12-Week Period After the First Dose of the IMP
Description	LS mean calculated using ANCOVA model with baseline preventive medication use (yes or no), gender, region (US/Canada or other), and treatment as fixed effects and the baseline number of cluster headache attacks as a covariate. Baseline data and the mean change from baseline in the overall weekly average number of days oxygen was used to treat ECH during the 12-week period after administration of the first dose of IMP (based on Week 0 to 12 data) is reported.
Time Frame	Baseline (Week 0), up to Week 12

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomized participants who received at least 1 dose of IMP and had at least 10 days of postbaseline efficacy assessment in the first 4 weeks on the primary endpoint.

Arm/Group Title	Placebo	Fremanezumab 675 mg/Placebo/Placebo	Fremanezumab 900/225/225 mg
Arm/Group Description:	Participants received placebo administered via an approximately 1-hour intravenous infusion and as 3 subcutaneous injections at Week 0 followed by placebo administered as single subcutaneous injection at Weeks 4 and 8, respectively.	Participants received placebo as an approximately 1-hour intravenous infusion followed by fremanezumab at 675 mg administered as 3 subcutaneous injections (225 mg/1.5 mL) at Week 0 and placebo administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively.	Participants received fremanezumab at 900 mg administered via an approximately 1-hour intravenous infusion followed by 3 placebo subcutaneous injections at Week 0 and fremanezumab at 225 mg administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively.
Overall Number of Participants Analyzed	57	53	55
Least Squares Mean (Standard Error); Unit of Measure: days of use/week
	-1.1 (0.30)	-1.5 (0.31)	-1.0 (0.30)

7. Secondary Outcome

Title	Number of Participants Who Perceived Improvement of CH-Associated Pain From Baseline as Measured by the Patient-Perceived Satisfactory Improvement (PPSI) Scale at Weeks 1, 4, 8, and 12
Description	The PPSI assessment was developed to measure pain intensity and was adjusted for CH symptoms improvement. Participants marked the level of CH-associated pain and indicated if pain is "1=much worse," "2=moderately worse," "3=slightly worse," "4=unchanged," "5=slightly improved," "6=moderately improved," or "7=much improved" compared with 4 weeks prior. PPSI was defined as the change in pain that corresponds with a minimal rating of "5=slightly improved." Data at Week 1 was recorded on Day 7 in the electronic diary device at home. Week 12 data also included assessment at the early withdrawal visit for participants who discontinued the study early.
Time Frame	Baseline, Weeks 1, 4, 8, and 12

Outcome Measure Data

Analysis Population Description

Full analysis set included all randomized participants who received at least 1 dose of IMP and had at least 10 days of postbaseline efficacy assessment in the first 4 weeks on the primary endpoint.

Arm/Group Title		Placebo	Fremanezumab 675 mg/Placebo/Placebo	Fremanezumab 900/225/225 mg
Arm/Group Description:		Participants received placebo administered via an approximately 1-hour intravenous infusion and as 3 subcutaneous injections at Week 0 followed by placebo administered as single subcutaneous injection at Weeks 4 and 8, respectively.	Participants received placebo as an approximately 1-hour intravenous infusion followed by fremanezumab at 675 mg administered as 3 subcutaneous injections (225 mg/1.5 mL) at Week 0 and placebo administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively.	Participants received fremanezumab at 900 mg administered via an approximately 1-hour intravenous infusion followed by 3 placebo subcutaneous injections at Week 0 and fremanezumab at 225 mg administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively.
Overall Number of Participants Analyzed		57	53	55
Measure Type: Count of Participants; Unit of Measure: Participants
Baseline	Much worse	10 17.5%	14 26.4%	7 12.7%
	Moderately worse	3 5.3%	5 9.4%	8 14.5%
	Slightly worse	3 5.3%	3 5.7%	3 5.5%
	Unchanged	37 64.9%	31 58.5%	28 50.9%
	Slightly improved	3 5.3%	0 0.0%	6 10.9%
	Moderately improved	1 1.8%	0 0.0%	1 1.8%
	Much improved	0 0.0%	0 0.0%	2 3.6%
	Missing	0 0.0%	0 0.0%	0 0.0%
Week 1	Much worse	2 3.5%	4 7.5%	1 1.8%
	Moderately worse	2 3.5%	2 3.8%	1 1.8%
	Slightly worse	5 8.8%	3 5.7%	2 3.6%
	Unchanged	19 33.3%	11 20.8%	9 16.4%
	Slightly improved	11 19.3%	8 15.1%	14 25.5%
	Moderately improved	5 8.8%	3 5.7%	6 10.9%
	Much improved	6 10.5%	12 22.6%	12 21.8%
	Missing	7 12.3%	10 18.9%	10 18.2%
Week 4	Much worse	1 1.8%	1 1.9%	2 3.6%
	Moderately worse	3 5.3%	0 0.0%	1 1.8%
	Slightly worse	4 7.0%	2 3.8%	0 0.0%
	Unchanged	8 14.0%	11 20.8%	5 9.1%
	Slightly improved	9 15.8%	9 17.0%	8 14.5%
	Moderately improved	5 8.8%	7 13.2%	8 14.5%
	Much improved	23 40.4%	19 35.8%	27 49.1%
	Missing	4 7.0%	4 7.5%	4 7.3%
Week 8	Much worse	1 1.8%	1 1.9%	0 0.0%
	Moderately worse	3 5.3%	0 0.0%	1 1.8%
	Slightly worse	0 0.0%	1 1.9%	1 1.8%
	Unchanged	13 22.8%	8 15.1%	12 21.8%
	Slightly improved	1 1.8%	6 11.3%	5 9.1%
	Moderately improved	7 12.3%	6 11.3%	7 12.7%
	Much improved	20 35.1%	20 37.7%	17 30.9%
	Missing	12 21.1%	11 20.8%	12 21.8%
Week 12	Much worse	3 5.3%	2 3.8%	2 3.6%
	Moderately worse	0 0.0%	0 0.0%	1 1.8%
	Slightly worse	2 3.5%	1 1.9%	0 0.0%
	Unchanged	16 28.1%	16 30.2%	16 29.1%
	Slightly improved	5 8.8%	5 9.4%	4 7.3%
	Moderately improved	8 14.0%	7 13.2%	5 9.1%
	Much improved	17 29.8%	19 35.8%	24 43.6%
	Missing	6 10.5%	3 5.7%	3 5.5%

8. Secondary 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.
Time Frame	Baseline up to Week 12

Outcome Measure Data

Analysis Population Description

Safety analysis set included all randomized participants who received at least 1 dose of the IMP.

Arm/Group Title	Placebo	Fremanezumab 675 mg/Placebo/Placebo	Fremanezumab 900/225/225 mg
Arm/Group Description:	Participants received placebo administered via an approximately 1-hour intravenous infusion and as 3 subcutaneous injections at Week 0 followed by placebo administered as single subcutaneous injection at Weeks 4 and 8, respectively.	Participants received placebo as an approximately 1-hour intravenous infusion followed by fremanezumab at 675 mg administered as 3 subcutaneous injections (225 mg/1.5 mL) at Week 0 and placebo administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively.	Participants received fremanezumab at 900 mg administered via an approximately 1-hour intravenous infusion followed by 3 placebo subcutaneous injections at Week 0 and fremanezumab at 225 mg administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively.
Overall Number of Participants Analyzed	59	55	55
Measure Type: Count of Participants; Unit of Measure: Participants
Any AEs	28 47.5%	26 47.3%	28 50.9%
Treatment-related AEs	8 13.6%	11 20.0%	13 23.6%
Serious AEs	5 8.5%	0 0.0%	1 1.8%
AEs leading to discontinuation	1 1.7%	0 0.0%	2 3.6%

9. Secondary Outcome

Title	Number of Participants With Potentially Clinically Significant Laboratory (Serum Chemistry, Hematology, and Urinalysis) Abnormal Results
Description	Serum chemistry, hematology, urinalysis laboratory tests with potentially clinically significant abnormal findings included: alanine aminotransferase (ALP), 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); Blood Urea Nitrogen ≥10.71 millimoles (mmol)/L; creatinine ≥177 umol/L; hemoglobin less than or equal to (≤)115 grams (g)/L (males) or ≤95 g/L (females); leukocytes ≥20*10^9/L or ≤3*10^9/L; eosinophils ≥10%; hematocrit <0.37 L/L (males) and <0.32 L/L (females); platelets ≥700*10^9/L or ≤75*10^9/L; 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.
Time Frame	Baseline up to Week 12

Outcome Measure Data

Analysis Population Description

Safety analysis set included all randomized participants who received at least 1 dose of the IMP. Here, 'overall number of participants analyzed'=participants evaluable for this outcome measure.

Arm/Group Title	Placebo	Fremanezumab 675 mg/Placebo/Placebo	Fremanezumab 900/225/225 mg
Arm/Group Description:	Participants received placebo administered via an approximately 1-hour intravenous infusion and as 3 subcutaneous injections at Week 0 followed by placebo administered as single subcutaneous injection at Weeks 4 and 8, respectively.	Participants received placebo as an approximately 1-hour intravenous infusion followed by fremanezumab at 675 mg administered as 3 subcutaneous injections (225 mg/1.5 mL) at Week 0 and placebo administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively.	Participants received fremanezumab at 900 mg administered via an approximately 1-hour intravenous infusion followed by 3 placebo subcutaneous injections at Week 0 and fremanezumab at 225 mg administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively.
Overall Number of Participants Analyzed	56	54	54
Measure Type: Count of Participants; Unit of Measure: Participants
With at least 1 serum chemistry abnormality	1 1.8%	1 1.9%	0 0.0%
With at least 1 hematology abnormality	4 7.1%	1 1.9%	4 7.4%
With at least 1 urinalysis abnormality	0 0.0%	0 0.0%	0 0.0%

10. Secondary Outcome

Title	Number of Participants With Shift From Baseline to Endpoint 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.
Time Frame	Baseline up to Week 12

Outcome Measure Data

Analysis Population Description

Safety analysis set included all randomized participants who received at least 1 dose of the IMP.

Arm/Group Title		Placebo	Fremanezumab 675 mg/Placebo/Placebo	Fremanezumab 900/225/225 mg
Arm/Group Description:		Participants received placebo administered via an approximately 1-hour intravenous infusion and as 3 subcutaneous injections at Week 0 followed by placebo administered as single subcutaneous injection at Weeks 4 and 8, respectively.	Participants received placebo as an approximately 1-hour intravenous infusion followed by fremanezumab at 675 mg administered as 3 subcutaneous injections (225 mg/1.5 mL) at Week 0 and placebo administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively.	Participants received fremanezumab at 900 mg administered via an approximately 1-hour intravenous infusion followed by 3 placebo subcutaneous injections at Week 0 and fremanezumab at 225 mg administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively.
Overall Number of Participants Analyzed		59	55	55
Measure Type: Count of Participants; Unit of Measure: Participants
PT	Low-Low	0 0.0%	0 0.0%	0 0.0%
	Low-Normal	0 0.0%	0 0.0%	0 0.0%
	Low-High	0 0.0%	0 0.0%	0 0.0%
	Normal-Low	0 0.0%	0 0.0%	0 0.0%
	Normal-Normal	47 79.7%	46 83.6%	44 80.0%
	Normal-High	2 3.4%	2 3.6%	3 5.5%
	High-Low	0 0.0%	0 0.0%	0 0.0%
	High-Normal	4 6.8%	4 7.3%	4 7.3%
	High-High	1 1.7%	1 1.8%	2 3.6%
	Missing	5 8.5%	2 3.6%	2 3.6%
Prothrombin INR	Low-Low	0 0.0%	0 0.0%	0 0.0%
	Low-Normal	0 0.0%	0 0.0%	0 0.0%
	Low-High	0 0.0%	0 0.0%	0 0.0%
	Normal-Low	0 0.0%	0 0.0%	0 0.0%
	Normal-Normal	48 81.4%	48 87.3%	47 85.5%
	Normal-High	2 3.4%	2 3.6%	1 1.8%
	High-Low	0 0.0%	0 0.0%	0 0.0%
	High-Normal	3 5.1%	3 5.5%	3 5.5%
	High-High	1 1.7%	0 0.0%	2 3.6%
	Missing	5 8.5%	2 3.6%	2 3.6%

11. Secondary 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 of 15 bpm; systolic blood pressure ≤90 millimeters of mercury (mmHg) and decrease of 20 mmHg; diastolic blood pressure ≤50 mmHg and decrease of 15 mmHg, or ≥105 mmHg and increase of 15 mmHg. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Time Frame	Baseline up to Week 12

Outcome Measure Data

Analysis Population Description

Safety analysis set included all randomized participants who received at least 1 dose of the IMP. Here, 'overall number of participants analyzed'=participants evaluable for this outcome measure.

Arm/Group Title	Placebo	Fremanezumab 675 mg/Placebo/Placebo	Fremanezumab 900/225/225 mg
Arm/Group Description:	Participants received placebo administered via an approximately 1-hour intravenous infusion and as 3 subcutaneous injections at Week 0 followed by placebo administered as single subcutaneous injection at Weeks 4 and 8, respectively.	Participants received placebo as an approximately 1-hour intravenous infusion followed by fremanezumab at 675 mg administered as 3 subcutaneous injections (225 mg/1.5 mL) at Week 0 and placebo administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively.	Participants received fremanezumab at 900 mg administered via an approximately 1-hour intravenous infusion followed by 3 placebo subcutaneous injections at Week 0 and fremanezumab at 225 mg administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively.
Overall Number of Participants Analyzed	56	54	54
Measure Type: Count of Participants; Unit of Measure: Participants
	3 5.4%	0 0.0%	1 1.9%

12. Secondary 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.
Time Frame	Baseline up to Week 12

Outcome Measure Data

Analysis Population Description

Safety analysis set included all randomized participants who received at least 1 dose of the IMP.

Arm/Group Title	Placebo	Fremanezumab 675 mg/Placebo/Placebo	Fremanezumab 900/225/225 mg
Arm/Group Description:	Participants received placebo administered via an approximately 1-hour intravenous infusion and as 3 subcutaneous injections at Week 0 followed by placebo administered as single subcutaneous injection at Weeks 4 and 8, respectively.	Participants received placebo as an approximately 1-hour intravenous infusion followed by fremanezumab at 675 mg administered as 3 subcutaneous injections (225 mg/1.5 mL) at Week 0 and placebo administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively.	Participants received fremanezumab at 900 mg administered via an approximately 1-hour intravenous infusion followed by 3 placebo subcutaneous injections at Week 0 and fremanezumab at 225 mg administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively.
Overall Number of Participants Analyzed	59	55	55
Measure Type: Count of Participants; Unit of Measure: Participants
Normal / Normal	35 59.3%	33 60.0%	23 41.8%
Normal / Abnormal NCS	6 10.2%	1 1.8%	5 9.1%
Normal / Abnormal CS	0 0.0%	0 0.0%	0 0.0%
Abnormal NCS / Normal	4 6.8%	9 16.4%	4 7.3%
Abnormal NCS / Abnormal NCS	7 11.9%	9 16.4%	18 32.7%
Abnormal NCS / Abnormal CS	0 0.0%	0 0.0%	0 0.0%
Abnormal CS / Normal	0 0.0%	0 0.0%	0 0.0%
Abnormal CS / Abnormal NCS	0 0.0%	0 0.0%	0 0.0%
Abnormal CS / Abnormal CS	0 0.0%	0 0.0%	0 0.0%
Missing	7 11.9%	3 5.5%	5 9.1%

13. Secondary Outcome

Title	Number of Participants Who Received Concomitant Medications
Description	Concomitant medications included: agents acting on the renin-angiotensin system, all other therapeutic products (for example: homeopathic preparation), allergens, analgesics, anesthetics, anti-parkinson drugs, antianemic preparations, antibacterials for systemic use, antibiotics and chemotherapeutics for dermatological use, antidiarrheals, intestinal antiinflammatory/antiinfective agents, antiemetic, antiepileptics, antifungals for dermatologiocal use, antigout preparations, antihemorrhagics, antihistamines for systemic use, antihypertensives, antiinflammatory and antirheumatic products, antimycotics for systemic use, antipruritics, antipsoriatics, antivirals for systemic use, beta blocking agents, blood substitutes and perfusion solutions, cardiac therapy, corticosteroids, cough and cold preparations, diagnostic radiopharmaceuticals, diuretics, thyroid therapy, urologicals, vaccines, psycoleptics, psycoanaleptics, ophthalmologicals, muscle relaxants, drugs used in diabetes etc.
Time Frame	Baseline up to Week 12

Outcome Measure Data

Analysis Population Description

Safety analysis set included all randomized participants who received at least 1 dose of the IMP.

Arm/Group Title	Placebo	Fremanezumab 675 mg/Placebo/Placebo	Fremanezumab 900/225/225 mg
Arm/Group Description:	Participants received placebo administered via an approximately 1-hour intravenous infusion and as 3 subcutaneous injections at Week 0 followed by placebo administered as single subcutaneous injection at Weeks 4 and 8, respectively.	Participants received placebo as an approximately 1-hour intravenous infusion followed by fremanezumab at 675 mg administered as 3 subcutaneous injections (225 mg/1.5 mL) at Week 0 and placebo administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively.	Participants received fremanezumab at 900 mg administered via an approximately 1-hour intravenous infusion followed by 3 placebo subcutaneous injections at Week 0 and fremanezumab at 225 mg administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively.
Overall Number of Participants Analyzed	59	55	55
Measure Type: Count of Participants; Unit of Measure: Participants
	57 96.6%	52 94.5%	52 94.5%

14. Secondary 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, swelling, and pruritus. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Time Frame	Baseline up to Week 12

Outcome Measure Data

Analysis Population Description

Safety analysis set included all randomized participants who received at least 1 dose of the IMP.

Arm/Group Title	Placebo	Fremanezumab 675 mg/Placebo/Placebo	Fremanezumab 900/225/225 mg
Arm/Group Description:	Participants received placebo administered via an approximately 1-hour intravenous infusion and as 3 subcutaneous injections at Week 0 followed by placebo administered as single subcutaneous injection at Weeks 4 and 8, respectively.	Participants received placebo as an approximately 1-hour intravenous infusion followed by fremanezumab at 675 mg administered as 3 subcutaneous injections (225 mg/1.5 mL) at Week 0 and placebo administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively.	Participants received fremanezumab at 900 mg administered via an approximately 1-hour intravenous infusion followed by 3 placebo subcutaneous injections at Week 0 and fremanezumab at 225 mg administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively.
Overall Number of Participants Analyzed	59	55	55
Measure Type: Count of Participants; Unit of Measure: Participants
Injection site induration	1 1.7%	3 5.5%	6 10.9%
Injection site pain	4 6.8%	2 3.6%	6 10.9%
Injection site erythema	2 3.4%	0 0.0%	2 3.6%
Injection site haemorrhage	0 0.0%	0 0.0%	1 1.8%
Injection site pruritus	1 1.7%	0 0.0%	1 1.8%
Injection site swelling	0 0.0%	1 1.8%	0 0.0%

15. Secondary 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.
Time Frame	Baseline up to Week 12

Outcome Measure Data

Analysis Population Description

Safety analysis set included all randomized participants who received at least 1 dose of the IMP.

Arm/Group Title	Placebo	Fremanezumab 675 mg/Placebo/Placebo	Fremanezumab 900/225/225 mg
Arm/Group Description:	Participants received placebo administered via an approximately 1-hour intravenous infusion and as 3 subcutaneous injections at Week 0 followed by placebo administered as single subcutaneous injection at Weeks 4 and 8, respectively.	Participants received placebo as an approximately 1-hour intravenous infusion followed by fremanezumab at 675 mg administered as 3 subcutaneous injections (225 mg/1.5 mL) at Week 0 and placebo administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively.	Participants received fremanezumab at 900 mg administered via an approximately 1-hour intravenous infusion followed by 3 placebo subcutaneous injections at Week 0 and fremanezumab at 225 mg administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively.
Overall Number of Participants Analyzed	59	55	55
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	0 0.0%	0 0.0%

16. Secondary 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.
Time Frame	Baseline up to Week 12

Outcome Measure Data

Analysis Population Description

Safety analysis set included all randomized participants who received at least 1 dose of the IMP.

Arm/Group Title	Placebo	Fremanezumab 675 mg/Placebo/Placebo	Fremanezumab 900/225/225 mg
Arm/Group Description:	Participants received placebo administered via an approximately 1-hour intravenous infusion and as 3 subcutaneous injections at Week 0 followed by placebo administered as single subcutaneous injection at Weeks 4 and 8, respectively.	Participants received placebo as an approximately 1-hour intravenous infusion followed by fremanezumab at 675 mg administered as 3 subcutaneous injections (225 mg/1.5 mL) at Week 0 and placebo administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively.	Participants received fremanezumab at 900 mg administered via an approximately 1-hour intravenous infusion followed by 3 placebo subcutaneous injections at Week 0 and fremanezumab at 225 mg administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively.
Overall Number of Participants Analyzed	59	55	55
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	1 1.8%	4 7.3%

Adverse Events

Time Frame	Baseline up to Week 12
Adverse Event Reporting Description	Safety analysis set included all randomized participants who received at least 1 dose of the IMP.
Arm/Group Title	Placebo		Fremanezumab 675 mg/Placebo/Placebo		Fremanezumab 900/225/225 mg
Arm/Group Description	Participants received placebo administered via an approximately 1-hour intravenous infusion and as 3 subcutaneous injections at Week 0 followed by placebo administered as single subcutaneous injection at Weeks 4 and 8, respectively.		Participants received placebo as an approximately 1-hour intravenous infusion followed by fremanezumab at 675 mg administered as 3 subcutaneous injections (225 mg/1.5 mL) at Week 0 and placebo administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively.		Participants received fremanezumab at 900 mg administered via an approximately 1-hour intravenous infusion followed by 3 placebo subcutaneous injections at Week 0 and fremanezumab at 225 mg administered as single subcutaneous injection (225 mg/1.5 mL) at Weeks 4 and 8, respectively.
All-Cause Mortality
	Placebo		Fremanezumab 675 mg/Placebo/Placebo		Fremanezumab 900/225/225 mg
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	0/59 (0.00%)		0/55 (0.00%)		0/55 (0.00%)
Serious Adverse Events
	Placebo		Fremanezumab 675 mg/Placebo/Placebo		Fremanezumab 900/225/225 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/59 (8.47%)		0/55 (0.00%)		1/55 (1.82%)
Ear and labyrinth disorders
Vertigo † 1	1/59 (1.69%)	1	0/55 (0.00%)	0	0/55 (0.00%)	0
Gastrointestinal disorders
Duodenitis † 1	1/59 (1.69%)	1	0/55 (0.00%)	0	0/55 (0.00%)	0
General disorders
Chest pain † 1	1/59 (1.69%)	2	0/55 (0.00%)	0	0/55 (0.00%)	0
Injury, poisoning and procedural complications
Lumbar vertebral fracture † 1	1/59 (1.69%)	1	0/55 (0.00%)	0	0/55 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer † 1	0/59 (0.00%)	0	0/55 (0.00%)	0	1/55 (1.82%)	1
Nervous system disorders
Cluster headache † 1	2/59 (3.39%)	3	0/55 (0.00%)	0	0/55 (0.00%)	0
1 Term from vocabulary, MedDRA 18.1; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Placebo		Fremanezumab 675 mg/Placebo/Placebo		Fremanezumab 900/225/225 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/59 (11.86%)		9/55 (16.36%)		16/55 (29.09%)
General disorders
Injection site induration † 1	1/59 (1.69%)	1	3/55 (5.45%)	7	6/55 (10.91%)	10
Injection site pain † 1	4/59 (6.78%)	6	2/55 (3.64%)	5	6/55 (10.91%)	17
Infections and infestations
Influenza † 1	2/59 (3.39%)	2	0/55 (0.00%)	0	3/55 (5.45%)	3
Nasopharyngitis † 1	1/59 (1.69%)	1	4/55 (7.27%)	5	4/55 (7.27%)	4
1 Term from vocabulary, MedDRA 18.1; † Indicates events were collected by systematic assessment

Limitations and Caveats

Study was terminated as a result of a pre-specified futility analysis at the interim of 150 participants completing the efficacy analysis of the study.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.

Results Point of Contact

• Name/Title: Director, Clinical Research
• Organization: Teva Branded Pharmaceutical Products, R&D Inc.
• Phone: 1-888-483-8279
• EMail: USMedInfo@tevapharm.com

• Responsible Party: Teva Branded Pharmaceutical Products R&D, Inc.
• ClinicalTrials.gov Identifier: NCT02945046
• Other Study ID Numbers: TV48125-CNS-30056; 2016-003278-42 ( EudraCT Number )
• First Submitted: October 25, 2016
• First Posted: October 26, 2016
• Results First Submitted: March 27, 2020
• Results First Posted: April 13, 2020
• Last Update Posted: November 9, 2021