HER-MES: Head-to-head Study of Erenumab Against Topiramate in Patients With Episodic and Chronic Migraine

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03828539
• Collaborator: (none)
• Enrollment: 777
• Locations: 79
• Arms: 2
• Actual Duration (Months): 17.2
• Patients Per Site: 9.8
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

This study used a single-cohort, 2-treatment arm, parallel-group randomized, double-blind, double-dummy design in adult patients with episodic migraine and chronic migraine, who had to be either naïve or not suitable for or could have failed up to three prophylactic treatments out of: propranolol/metoprolol, amitriptyline, flunarizine. Patients were stratified into groups according to their number of migraine days during the baseline period.

Condition or Disease	Intervention/Treatment	Phase
Migraine	Biological: Erenumab; Drug: Topiramate; Biological: Erenumab matching placebo; Drug: Topiramate matching placebo	Phase 4

Detailed Description

All patients completing the Baseline period and fulfilling baseline eligibility criteria were invited to participate to the Double-blind, double-dummy Treatment Epoch (DBTE, 24 weeks) .

Eligible patients were randomized to one of two treatment arms. DBTE started with a titration phase for topiramate of a maximum of 6 weeks to determine the maximal tolerated dose and aimed to reach the recommended treatment dose of 100 mg according to the German SmPC. After the titration phase, maintenance phase started (18 weeks). Topiramate dose had to be maintained until the end of the DBTE. Erenumab dose at beginning of the DBTE was determined patient individually by the investigator based on the guidance provided in the SmPC and was either 70 mg or 140 mg. Dose escalation from 70 mg to 140 mg in case of insufficient response was considered at anytime during the DBTE.

Dose reduction of topiramate and erenumab was not allowed during DBTE (Week 0 to Week 24). After Week 24 or if the patient discontinued study drug, a one week double-blind taper off phase followed to ensure proper down titration for topiramate. At the end of the DBTE (24 weeks) the final assessment occurred to address the objectives.

A Follow-Up Visit 4 weeks after last study visit (or 8 weeks after last IMP injection for discontinued patients) was required as part of routine safety monitoring. The primary analysis was triggered when all patients had completed their respective last visit of the DBTE.

The End of study occurred when the last patient completed last visit (LPLV).

Study Design

• Study Type: Interventional
• Actual Enrollment: 777 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: Head-to-head Study of Erenumab Against topiRamate-a Double-blind, Double Dummy Migraine Study to Assess Tolerability and Efficacy in a patiEnt -Centered Setting
• Actual Study Start Date: Feb 22, 2019
• Actual Primary Completion Date: Jul 29, 2020
• Actual Study Completion Date: Jul 29, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Erenumab 70 mg and 140 mg Erenumab	Biological: Erenumab; 70mg/1mL (70 mg) or 2x70mg/1mL (140 mg) in pre-filled syringe, administered every 4 weeks; Other Names: AMG334 ; Biological: Erenumab matching placebo; Erenumab matching placebo pre-filled syringue administered every 4 weeks
Active Comparator: Topiramate Topiramate in the highest tolerated dose (50 - 100 mg/day)	Drug: Topiramate; Film-coated tablet taken orally: 25 mg administered once daily (first week of titration phase). After the first week, titration was done according to the summary of product characteristics (SmPC) in 25 mg increments each week and aimed to reach the recommended daily treatment dose of 100 mg (50/75/100 mg). 50/75/100 mg were administered twice daily during titration phase and maintenance phase.; Other Names: Topamax ; Drug: Topiramate matching placebo; Topiramate matching placebo administered daily

Outcome Measures

Primary Outcome Measures

1. Proportion of Patients With Treatment Discontinuation Due to an Adverse Event (AE) During the Double-blind Treatment Epoch/Period (DBTE) [24 Weeks]

   The primary objective was to demonstrate the tolerability of 70 mg and 140 mg erenumab compared to topiramate in the highest tolerated dose assessed by the rate of patients discontinuing treatment due to AE during the double-blind epoch of the study.

Secondary Outcome Measures

1. Number of Patients With at Least 50% Reduction From Baseline in Monthly Migraine Days (MMD) Over the Last Three Months (Month 4, 5, and 6) [Baseline, Last three months (month 4, 5, and 6)]

   The secondary objective of this study was to evaluate the effect of erenumab compared to topiramate on the proportion of patients with at least 50% reduction from baseline in MMDs. The Baseline period was defined as the period between Week -4 and the day prior to first dose. This was analyzed by logistic regression over the last 3 months (months 4, 5, and 6) of treatment. All the subjects' data collected regarding 50% response in MMD was used in the analysis regardless of whether subjects discontinue study treatment or not. Subjects with missing response information on this endpoint were imputed as non-response (non-responder imputation).

Other Outcome Measures

1. EXPLORATORY ENDPOINT: Proportion of Patients Achieving at Least a 5 Points Reduction in the Headache Impact Test (HIT-6) From Baseline to Week 24 [Baseline, Week 24]

   The HIT-6 is a widely used patient-reported outcome measure that assesses the negative effects of headaches on normal activity. Six items assess the frequency of pain severity, headaches limiting daily activity (household, work, school, and social), wanting to lie down when headache is experienced, feeling too tired to work or do daily activities because of headache, feeling "fed up" or irritated because of headache, and headaches limiting ability to concentrate or work on daily activities. Each of the 6 questions is responded to using 1 of 5 response categories: "never," "rarely," "sometimes," "very often," or "always." For each HIT-6 item, 6, 8, 10, 11, or 13 points, respectively, are assigned to the response provided. These points are summed to produce a total HIT-6 score that ranges from 36 to 78. HIT-6 scores are categorized into 4 grades: little or no impact (49 or less), some impact (50 - 55), substantial impact (56 - 59), and severe impact (60 - 78) due to headache.

2. EXPLORATORY ENDPOINT: Proportion of Patients Achieving at Least a 5 Points Increase in the Medical Outcome Short Form Health Survey Version 2 (SF-36) From Baseline to Week 24 [Baseline, Week 24]

   The SF-36 is a widely used and extensively studied instrument to measure health-related quality of life (HRQoL) among healthy subjects and patients with acute and chronic conditions. It consists of eight subscales that can be scored individually: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. Two overall summary scores, the Physical Component Summary (PCS) and the Mental Component Summary (MCS) also can be computed. The SF-36 has proven useful in monitoring general and specific populations, comparing the relative burden of different disease, differentiating the health benefits produced by different treatments, and in screening individual patients. The purpose of the SF-36 in this study was to assess the HRQoL of patients. Given the nature of this disease and the 4-weekly assessment, the SF-36 version 2, with a 4-week recall period, was used in this study.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

1. Documented history of migraine in the 12 months prior to screen

2. at least 4 days per month of migraine symptoms

3. =80% diary compliance during the Baseline period

4. Patients must be either naïve or not suitable or have failed previous migraine prophylactic treatments

Key Exclusion Criteria:

1. Older than 50 years of age at migraine onset

2. Pregnant or nursing

3. History of cluster or hemiplegic headache

4. History or evidence of major psychiatric disorder

5. Score of 19 or higher on Beck Depression Inventory (BDI)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Stuttgart	Baden Wuertemberg	Germany	70178
2	Novartis Investigative Site	Hannover	Niedersachsen	Germany	30159
3	Novartis Investigative Site	Aachen	Nordrhein-Westfalen	Germany	52062
4	Novartis Investigative Site	Alzenau		Germany	63755
5	Novartis Investigative Site	Bad Homburg		Germany	61348
6	Novartis Investigative Site	Bad Honnef		Germany	53604
7	Novartis Investigative Site	Bad Saarow		Germany	15526
8	Novartis Investigative Site	Bayreuth		Germany	95445
9	Novartis Investigative Site	Bergen		Germany	18528
10	Novartis Investigative Site	Berlin		Germany	10713
11	Novartis Investigative Site	Berlin		Germany	120999
12	Novartis Investigative Site	Berlin		Germany	12101
13	Novartis Investigative Site	Berlin		Germany	12163
14	Novartis Investigative Site	Berlin		Germany	12627
15	Novartis Investigative Site	Berlin		Germany	13156
16	Novartis Investigative Site	Berlin		Germany	13353
17	Novartis Investigative Site	Berlin		Germany	14169
18	Novartis Investigative Site	Bielefeld		Germany	D 33647
19	Novartis Investigative Site	Boblingen		Germany	71032
20	Novartis Investigative Site	Bochum		Germany	44791
21	Novartis Investigative Site	Bonn		Germany	53111
22	Novartis Investigative Site	Bonn		Germany	53177
23	Novartis Investigative Site	Celle		Germany	29223
24	Novartis Investigative Site	Chemnitz		Germany	09117
25	Novartis Investigative Site	Dillingen		Germany	66763
26	Novartis Investigative Site	Erbach		Germany	64711
27	Novartis Investigative Site	Essen		Germany	45133
28	Novartis Investigative Site	Essen		Germany	45147
29	Novartis Investigative Site	Frankfurt		Germany	60313
30	Novartis Investigative Site	Freiburg		Germany	79098
31	Novartis Investigative Site	Gelsenkirchen		Germany	45879
32	Novartis Investigative Site	Greifswald		Germany	17475
33	Novartis Investigative Site	Haar		Germany	85540
34	Novartis Investigative Site	Halle		Germany	06120
35	Novartis Investigative Site	Hamburg		Germany	20253
36	Novartis Investigative Site	Heidelberg		Germany	69120
37	Novartis Investigative Site	Heidenheim		Germany	89518
38	Novartis Investigative Site	Hoppegarten		Germany	15366
39	Novartis Investigative Site	Ibbenbueren		Germany	49477
40	Novartis Investigative Site	Jena		Germany	07740
41	Novartis Investigative Site	Juelich		Germany	52428
42	Novartis Investigative Site	Kassel		Germany	34121
43	Novartis Investigative Site	Kassel		Germany
44	Novartis Investigative Site	Kiel		Germany	24149
45	Novartis Investigative Site	Koln		Germany	50935
46	Novartis Investigative Site	Königstein im Taunus		Germany	61462
47	Novartis Investigative Site	Leipzig		Germany	04103
48	Novartis Investigative Site	Leipzig		Germany	04107
49	Novartis Investigative Site	Luenen		Germany	44534
50	Novartis Investigative Site	Mannheim		Germany	66163
51	Novartis Investigative Site	Marburg Wehrda		Germany	35041
52	Novartis Investigative Site	Mittweida		Germany	09648
53	Novartis Investigative Site	Muenchen		Germany	81377
54	Novartis Investigative Site	Muenchen		Germany	81675
55	Novartis Investigative Site	Muenster		Germany	48149
56	Novartis Investigative Site	Neu-Ulm		Germany	89231
57	Novartis Investigative Site	Neuburg an der Donau		Germany	86633
58	Novartis Investigative Site	Osnabrück		Germany	49074
59	Novartis Investigative Site	Pforzheim		Germany	75172
60	Novartis Investigative Site	Quakenbrueck		Germany	49610
61	Novartis Investigative Site	Regensburg		Germany	93059
62	Novartis Investigative Site	Rostock		Germany	18057
63	Novartis Investigative Site	Ruelzheim		Germany	76761
64	Novartis Investigative Site	Schwerin		Germany	19053
65	Novartis Investigative Site	Schwerin		Germany	19055
66	Novartis Investigative Site	Seesen		Germany	38723
67	Novartis Investigative Site	Siegen		Germany	57076
68	Novartis Investigative Site	Sindelfingen		Germany	71065
69	Novartis Investigative Site	Stadtroda		Germany	07646
70	Novartis Investigative Site	Stuttgart		Germany	70174
71	Novartis Investigative Site	Stuttgart		Germany	70178
72	Novartis Investigative Site	Stuttgart		Germany	70182
73	Novartis Investigative Site	Trier		Germany	54292
74	Novartis Investigative Site	Tübingen		Germany	72076
75	Novartis Investigative Site	Ulm		Germany	89073
76	Novartis Investigative Site	Unterhaching		Germany	82008
77	Novartis Investigative Site	Westerstede/Oldenburg		Germany	26655
78	Novartis Investigative Site	Wiesbaden		Germany	65191
79	Novartis Investigative Site	Wuerzburg		Germany	97080

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

• Study Protocol - Jun 6, 2019
• Statistical Analysis Plan - Oct 1, 2020

More Information

Additional Information:

• A Plain Language Trial Summary is available on novartisclinicaltrials.com

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03828539
• Other Study ID Numbers: CAMG334ADE01; 2018-000943-15
• First Posted: Feb 4, 2019
• Last Update Posted: Oct 11, 2021
• Last Verified: Oct 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Novartis Pharmaceuticals: Migraine; Episodic migraine; Chronic migraine; Headache; erenumab; topiramate; CAMG 334; Calcitonin Gene-related Peptide; CGRP; CGRP receptor agonist; monoclonal antibody; treatment failure
• Additional relevant MeSH terms: Migraine Disorders; Topiramate; Erenumab; Antibodies, Monoclonal

Study Results

Participant Flow

Recruitment Details	82 centers in Germany enrolled patients.
Pre-assignment Detail	A total of 777 patients were randomized to receive either erenumab (389 patients) or topiramate (388 patients).

Arm/Group Title	Erenumab	Topiramate
Arm/Group Description	70 mg and 140 mg Erenumab	Topiramate in the highest tolerated dose (50 - 100 mg/day)
Period Title: Overall Study
STARTED	389	388
Full Analysis Set (FAS)	388	388
Safety Analysis Set (SAF)	388	388
COMPLETED	373	366
NOT COMPLETED	16	22

Baseline Characteristics

Arm/Group Title	Erenumab	Topiramate	Total
Arm/Group Description	70 mg and 140 mg Erenumab	Topiramate in the highest tolerated dose (50 - 100 mg/day)	Total of all reporting groups
Overall Participants	388	388	776
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	40.8 (12.4)	40.7 (12.4)	40.7 (12.4)
Sex: Female, Male (Count of Participants)
Female	331 85.3%	335 86.3%	666 85.8%
Male	57 14.7%	53 13.7%	110 14.2%
Race/Ethnicity, Customized (Number) [Number]
Caucasian	383 98.7%	387 99.7%	770 99.2%
Asian	1 0.3%	0 0%	1 0.1%
Unknown	1 0.3%	0 0%	1 0.1%
Other	3 0.8%	1 0.3%	4 0.5%
Baseline Monthly Migraine Days (MMDs) categories (Count of Participants)
< 4 days	2 0.5%	0 0%	2 0.3%
4 to 7 days	94 24.2%	92 23.7%	186 24%
8 to 14 days	248 63.9%	254 65.5%	502 64.7%
>= 15 days	43 11.1%	42 10.8%	85 11%
Missing	1 0.3%	0 0%	1 0.1%

Outcome Measures

1. Primary Outcome

Title	Proportion of Patients With Treatment Discontinuation Due to an Adverse Event (AE) During the Double-blind Treatment Epoch/Period (DBTE)
Description	The primary objective was to demonstrate the tolerability of 70 mg and 140 mg erenumab compared to topiramate in the highest tolerated dose assessed by the rate of patients discontinuing treatment due to AE during the double-blind epoch of the study.
Time Frame	24 Weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS)

Arm/Group Title	Erenumab	Topiramate
Arm/Group Description	70 mg and 140 mg Erenumab	Topiramate in the highest tolerated dose (50 - 100 mg/day)
Measure Participants	388	388
Count of Participants [Participants]	41 10.6%	151 38.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Erenumab, Topiramate
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments
	Method	Regression, Logistic
	Comments	Odds ratio is obtained from a logistic regression model that includes treatment group and stratification factor (MMD at baseline)
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.19
	Confidence Interval	(2-Sided) 95%; 0.13 to 0.27
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Number of Patients With at Least 50% Reduction From Baseline in Monthly Migraine Days (MMD) Over the Last Three Months (Month 4, 5, and 6)
Description	The secondary objective of this study was to evaluate the effect of erenumab compared to topiramate on the proportion of patients with at least 50% reduction from baseline in MMDs. The Baseline period was defined as the period between Week -4 and the day prior to first dose. This was analyzed by logistic regression over the last 3 months (months 4, 5, and 6) of treatment. All the subjects' data collected regarding 50% response in MMD was used in the analysis regardless of whether subjects discontinue study treatment or not. Subjects with missing response information on this endpoint were imputed as non-response (non-responder imputation).
Time Frame	Baseline, Last three months (month 4, 5, and 6)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS)

Arm/Group Title	Erenumab	Topiramate
Arm/Group Description	70 mg and 140 mg Erenumab	Topiramate in the highest tolerated dose (50 - 100 mg/day)
Measure Participants	388	388
Count of Participants [Participants]	215 55.4%	121 31.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Erenumab, Topiramate
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments
	Method	Regression, Logistic
	Comments	Odds ratio is obtained from a logistic regression model that includes treatment group and stratification factor (MMD at baseline)
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.76
	Confidence Interval	(2-Sided) 95%; 2.06 to 3.71
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Other Pre-specified Outcome

Title	EXPLORATORY ENDPOINT: Proportion of Patients Achieving at Least a 5 Points Reduction in the Headache Impact Test (HIT-6) From Baseline to Week 24
Description	The HIT-6 is a widely used patient-reported outcome measure that assesses the negative effects of headaches on normal activity. Six items assess the frequency of pain severity, headaches limiting daily activity (household, work, school, and social), wanting to lie down when headache is experienced, feeling too tired to work or do daily activities because of headache, feeling "fed up" or irritated because of headache, and headaches limiting ability to concentrate or work on daily activities. Each of the 6 questions is responded to using 1 of 5 response categories: "never," "rarely," "sometimes," "very often," or "always." For each HIT-6 item, 6, 8, 10, 11, or 13 points, respectively, are assigned to the response provided. These points are summed to produce a total HIT-6 score that ranges from 36 to 78. HIT-6 scores are categorized into 4 grades: little or no impact (49 or less), some impact (50 - 55), substantial impact (56 - 59), and severe impact (60 - 78) due to headache.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS)

Arm/Group Title	Erenumab	Topiramate
Arm/Group Description	70 mg and 140 mg Erenumab	Topiramate in the highest tolerated dose (50 - 100 mg/day)
Measure Participants	388	388
Count of Participants [Participants]	280 72.2%	209 53.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Erenumab, Topiramate
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments
	Method	Regression, Logistic
	Comments	Odds ratio is obtained from a logistic regression model that includes treatment group and stratification factor (MMD at baseline)
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.30
	Confidence Interval	(2-Sided) 95%; 1.70 to 3.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Other Pre-specified Outcome

Title	EXPLORATORY ENDPOINT: Proportion of Patients Achieving at Least a 5 Points Increase in the Medical Outcome Short Form Health Survey Version 2 (SF-36) From Baseline to Week 24
Description	The SF-36 is a widely used and extensively studied instrument to measure health-related quality of life (HRQoL) among healthy subjects and patients with acute and chronic conditions. It consists of eight subscales that can be scored individually: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. Two overall summary scores, the Physical Component Summary (PCS) and the Mental Component Summary (MCS) also can be computed. The SF-36 has proven useful in monitoring general and specific populations, comparing the relative burden of different disease, differentiating the health benefits produced by different treatments, and in screening individual patients. The purpose of the SF-36 in this study was to assess the HRQoL of patients. Given the nature of this disease and the 4-weekly assessment, the SF-36 version 2, with a 4-week recall period, was used in this study.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS)

Arm/Group Title	Erenumab	Topiramate
Arm/Group Description	70 mg and 140 mg Erenumab	Topiramate in the highest tolerated dose (50 - 100 mg/day)
Measure Participants	388	388
Physical Component Summary (PCS)	185 47.7%	145 37.4%
Mental Component Summary (MCS)	98 25.3%	65 16.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Erenumab, Topiramate
	Comments	Physical Component Summary (PCS)
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments	Odds ratio is obtained from a logistic regression model that includes treatment group and stratification factor (MMD at baseline)
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.75
	Confidence Interval	(2-Sided) 95%; 1.26 to 2.43
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Erenumab, Topiramate
	Comments	Mental Component Summary (MCS)
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments
	Method	Regression, Logistic
	Comments	Odds ratio is obtained from a logistic regression model that includes treatment group and stratification factor (MMD at baseline)
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.79
	Confidence Interval	(2-Sided) 95%; 1.29 to 2.69
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Adverse events were collected from first dose of study treatment until 8 weeks after the last Investigational Medicinal product (IMP) injection, assessed up to approximately 33 weeks (treatment duration ranged from 4.0 to 25.1 weeks).
Adverse Event Reporting Description	Any sign or symptom that occurs during the study treatment until 8 weeks after the last Investigational Medicinal product (IMP) injection. Maximum exposure to study treatments = 25 weeks (Erenumab treatment group) and 25.1 weeks (Topiramate treatment group).
Arm/Group Title	Erenumab		Topiramate
Arm/Group Description	70 mg and 140 mg Erenumab		Topiramate in the highest tolerated dose (50 - 100 mg/day)
All Cause Mortality
	Erenumab		Topiramate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/388 (0%)		0/388 (0%)
Serious Adverse Events
	Erenumab		Topiramate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/388 (2.6%)		19/388 (4.9%)
Eye disorders
Angle closure glaucoma	0/388 (0%)		1/388 (0.3%)
Retinal detachment	0/388 (0%)		1/388 (0.3%)
Rhegmatogenous retinal detachment	0/388 (0%)		1/388 (0.3%)
Gastrointestinal disorders
Gastritis	0/388 (0%)		1/388 (0.3%)
Irritable bowel syndrome	0/388 (0%)		1/388 (0.3%)
Mechanical ileus	1/388 (0.3%)		0/388 (0%)
Obstructive defaecation	1/388 (0.3%)		0/388 (0%)
Hepatobiliary disorders
Cholelithiasis	0/388 (0%)		1/388 (0.3%)
Immune system disorders
Anaphylactic shock	0/388 (0%)		1/388 (0.3%)
Infections and infestations
Appendicitis	0/388 (0%)		1/388 (0.3%)
Bacteriuria	0/388 (0%)		1/388 (0.3%)
Gastroenteritis	0/388 (0%)		1/388 (0.3%)
Gastrointestinal infection	0/388 (0%)		1/388 (0.3%)
Influenza	0/388 (0%)		1/388 (0.3%)
Nasopharyngitis	0/388 (0%)		1/388 (0.3%)
Papilloma viral infection	1/388 (0.3%)		0/388 (0%)
Parasitic gastroenteritis	0/388 (0%)		1/388 (0.3%)
Pyelonephritis	0/388 (0%)		1/388 (0.3%)
Injury, poisoning and procedural complications
Ankle fracture	0/388 (0%)		1/388 (0.3%)
Concussion	0/388 (0%)		1/388 (0.3%)
Contusion	1/388 (0.3%)		0/388 (0%)
Fall	1/388 (0.3%)		0/388 (0%)
Ligament rupture	1/388 (0.3%)		0/388 (0%)
Limb injury	1/388 (0.3%)		0/388 (0%)
Skin laceration	1/388 (0.3%)		0/388 (0%)
Sternal fracture	1/388 (0.3%)		0/388 (0%)
Tendon injury	1/388 (0.3%)		0/388 (0%)
Investigations
Weight decreased	0/388 (0%)		1/388 (0.3%)
Metabolism and nutrition disorders
Decreased appetite	0/388 (0%)		1/388 (0.3%)
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	1/388 (0.3%)		0/388 (0%)
Lumbar spinal stenosis	0/388 (0%)		1/388 (0.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Fibroadenoma of breast	0/388 (0%)		1/388 (0.3%)
Nervous system disorders
Migraine	0/388 (0%)		1/388 (0.3%)
Migraine with aura	1/388 (0.3%)		0/388 (0%)
Syncope	0/388 (0%)		1/388 (0.3%)
Psychiatric disorders
Depression	0/388 (0%)		1/388 (0.3%)
Major depression	1/388 (0.3%)		0/388 (0%)
Reproductive system and breast disorders
Cervical dysplasia	1/388 (0.3%)		0/388 (0%)
Dysmenorrhoea	1/388 (0.3%)		0/388 (0%)
Endometriosis	0/388 (0%)		1/388 (0.3%)
Other (Not Including Serious) Adverse Events
	Erenumab		Topiramate
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	253/388 (65.2%)		331/388 (85.3%)
Ear and labyrinth disorders
Vertigo	20/388 (5.2%)		24/388 (6.2%)
Gastrointestinal disorders
Abdominal pain upper	22/388 (5.7%)		23/388 (5.9%)
Constipation	48/388 (12.4%)		12/388 (3.1%)
Diarrhoea	20/388 (5.2%)		29/388 (7.5%)
Nausea	36/388 (9.3%)		71/388 (18.3%)
General disorders
Fatigue	44/388 (11.3%)		74/388 (19.1%)
Infections and infestations
Nasopharyngitis	145/388 (37.4%)		150/388 (38.7%)
Investigations
Weight decreased	5/388 (1.3%)		22/388 (5.7%)
Metabolism and nutrition disorders
Decreased appetite	8/388 (2.1%)		39/388 (10.1%)
Musculoskeletal and connective tissue disorders
Back pain	21/388 (5.4%)		20/388 (5.2%)
Nervous system disorders
Disturbance in attention	18/388 (4.6%)		63/388 (16.2%)
Dizziness	28/388 (7.2%)		60/388 (15.5%)
Dysgeusia	3/388 (0.8%)		23/388 (5.9%)
Paraesthesia	17/388 (4.4%)		159/388 (41%)
Taste disorder	0/388 (0%)		26/388 (6.7%)
Psychiatric disorders
Sleep disorder	20/388 (5.2%)		8/388 (2.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.