A Study of LY2951742 (Galcanezumab) in Japanese Participants With Episodic Migraine

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02959177
• Collaborator: (none)
• Enrollment: 459
• Locations: 47
• Arms: 3
• Actual Duration (Months): 26.3
• Patients Per Site: 9.8
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The main purpose of this study is to determine the efficacy of the study drug Galcanezumab in Japanese participants with episodic migraine.

Condition or Disease	Intervention/Treatment	Phase
Migraine	Drug: Galcanezumab; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 459 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-Controlled Study of LY2951742 (Galcanezumab) in Japanese Patients With Episodic Migraine
• Actual Study Start Date: Nov 9, 2016
• Actual Primary Completion Date: Jan 18, 2019
• Actual Study Completion Date: Jan 18, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 120 milligrams (mg) Galcanezumab 120 mg galcanezumab (LY2951742) administered subcutaneously (SC) once a month for 6 months.	Drug: Galcanezumab; Administered SC; Other Names: LY2951742
Experimental: 240 mg Galcanezumab 120 mg galcanezumab (LY2951742) administered SC once a month for 6 months.	Drug: Galcanezumab; Administered SC; Other Names: LY2951742
Placebo Comparator: Placebo Placebo administered SC once a month for 6 months.	Drug: Placebo; Administered SC

Outcome Measures

Primary Outcome Measures

1. Overall Mean Change From Baseline in the Number of Monthly Migraine Headache Days (MHD) [Baseline, Month 1 through Month 6]

   Migraine Headache Day (MHD):A calendar day on which a migraine headache or probable migraine headache occurred. Migraine Headache : A headache, with or without aura, of ≥30 minutes duration with both of the following required features (A and B): A) At least 2 of the following headache characteristics: Unilateral location; Pulsatile quality; Moderate or severe pain intensity; Aggravation by or causing avoidance of routine physical activity; AND B) During headache at least one of the following: Nausea and/or vomiting; Photophobia and phonophobia; The overall mean is derived from the average of months 1 to 6 from mixed model repeat measures (MMRM) model. Least Square Mean (LSMEAN) was calculated using MMRM models with fixed categorical effects of treatment, month, and treatment-by-month interaction, as well as the continuous, fixed covariates of baseline value and baseline-by-month interaction.

Secondary Outcome Measures

1. Percentage of Participants With a 50% or Greater Reduction From Baseline in Monthly Migraine Headache Days [Baseline, Month 1 through Month 6]

   Migraine Headache Day (MHD): A calendar day on which a migraine headache or probable migraine headache occurred. A 50% responder in a particular month is any participant who has a ≥50% reduction from baseline in the monthly number of migraine headache attacks in a 30-day interval. It is derived from the average of months 1 to 6 from generalized linear mixed model repeated measures. Mean percentages of participants were calculated with a generalized linear mixed model repeated measures method with treatment, month and treatment by month, and baseline MHD category as fixed factors.

2. Percentage of Participants With a 75% or Greater Reduction From Baseline in Monthly Migraine Headache Days [Baseline, Month 1 through Month 6]

   Migraine Headache Day (MHD): A calendar day on which a migraine headache or probable migraine headache occurred. A 75% responder in a particular month is any participant who has a ≥75% reduction from baseline in the monthly number of migraine headache attacks in a 30-day interval. It is derived from the average of months 1 to 6 from generalized linear mixed model repeated measures. Mean percentages of participants were calculated with a generalized linear mixed model repeated measures method with treatment, month and treatment by month, and baseline MHD category as fixed factors.

3. Percentage of Participants With a 100% Reduction From Baseline in Monthly Migraine Headache Days [Baseline, Month 1 through Month 6]

   Migraine Headache Day (MHD): A calendar day on which a migraine headache or probable migraine headache occurred. A 100% responder in a particular month is any participant who has a 100% reduction from baseline in the monthly number of migraine headache attacks in a 30-day interval. It is derived from the average of months 1 to 6 from generalized linear mixed model repeated measures. Mean percentages of participants were calculated with a generalized linear mixed model repeated measures method with treatment, month and treatment by month, and baseline MHD category as fixed factors.

4. Overall Mean Change From Baseline on the Migraine-Specific Quality (MSQ) of Life Questionnaire [Baseline, Month 4 through Month 6]

   MSQ version 2.1 is a health status instrument consists of 14 items addressing 3 domains:(1)Role Function-Restrictive (items 1-7);(2)Role Function- Preventive (items 8-11);&(3)Emotional Function (items 12-14).Response options range from "none of the time" (value 1) to "all of the time" (value 6), & are reverse-recoded (value 6 to 1) before the domain scores are calculated. Total raw scores for each domain is the sum of the final item value for all of the items in that domain. After total raw score is computed for each domain & total score, they are transformed to a 0-100 scale with higher scores indicating a better health status & a positive change in scores reflecting functional improvement. The overall mean is derived from the average of months 4 to 6 from MMRM model. LSMean was calculated using MMRM model with treatment, month, treatment by month, baseline by month and baseline MHD category as fixed factors.

5. Overall Mean Change From Baseline in Number of Migraine Headache Days With Acute Medication Use [Baseline, Month 1 through Month 6]

   Migraine Headache Day (MHD) with Acute Medication Use: Calendar days on which migraine or probable migraine occurs, requiring acute medication. The overall mean is derived from the average of months 1 to 6 from MMRM model. LSMean was calculated using MMRM model with treatment, month, treatment by month, baseline, baseline by month, and baseline MHD category as fixed effects.

6. Mean Change From Baseline in the Patient Global Impression of Severity (PGI-S) Score [Baseline, Month 4 through Month 6]

   The PGI-S scale is a patient-rated instrument that measures patients own global impression of their illness severity. The patient was instructed as follows: "Considering migraine as a chronic condition, how would you rate your level of illness?" Response options were from 1 ("normal, not at all ill") to 7 ("extremely ill"). Mean is derived from the average of months 4 to 6 from MMRM model. Least square mean (LSM) was calculated using an MMRM model with treatment, month, treatment by month, baseline, baseline by month, and baseline MHD category as fixed effects.

7. Overall Mean Change From Baseline in Headache Hours [Baseline, Month 1 through Month 6]

   Headache Hours is calculated as the total number of headache hours on which a headache occurred. Overall mean is derived from the average of months 1 to 6 from MMRM model. LSMean was calculated using the MMRM model with treatment, month, treatment by month, baseline, baseline by month and baseline MHD category.

8. Mean Change From Baseline on the Migraine Disability Assessment Test (MIDAS) Total Score [Baseline, Month 6]

   The MIDAS is a participant-rated scale which was designed to quantify headache-related disability over a 3-month period. This instrument consists of five items that reflect the number of days reported as missing or with reduced productivity at work or home, and the number of days of missed social events. Each item has a numeric response range from 0 to 90 days, if days are missed from work or home they are not counted as days with reduced productivity at work or home. The numeric responses are summed to produce a total score ranging from 0 to 270, in which a higher value is indicative of more disability. LSMean was calculated using MMRM model with treatment, month, treatment by month, baseline, baseline by month, and baseline MHD category as fixed factors.

9. Percentage of Participants With Positive Responses on Patient Satisfaction With Medication Questionnaire-Modified (PSMQ-M) [Month 6]

   The PSMQ-M is a self-rated scale which measures participants level of satisfaction with study medication.The scale has been modified for use in this study, assessing 3 items related to the clinical trial treatment over the past 4 weeks: satisfaction, preference, and side effects. Satisfaction responses range from "very unsatisfied" to "very satisfied" with the current treatment. Preference compares the current study medication to previous medications, with responses from "much rather prefer my previous medication" to "much rather prefer the medication administered to me during the study"

10. Number of Participants With Suicidal Ideations Collected by Columbia - Suicide Severity Rating Scale (C-SSRS) [Month 1 through Month 6]

    C-SSRS captures the occurrence, severity, and frequency of suicide-related thoughts during the assessment period. The scale includes suggested questions to solicit the type of information needed to determine if a suicide-related thoughts occurred. Some questions are binary responses (yes/no) and some are on a scale of 1 (low severity) to 5 (high severity). Suicidal ideation (SI): a "yes" answer to any of 5 suicidal ideation questions: wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods without intent to act, active suicidal ideation with some intent to act without specific plan, active suicidal ideation with specific plan and intent

11. Number of Participants With Suicidal Behaviors Assessed by Columbia - Suicide Severity Rating Scale (C-SSRS) [Month 1 through Month 6]

    C -SSRS captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal behavior is defined as a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation is defined as a "yes" answer to any one of 5 suicidal ideation questions: wish to be dead, and 4 different categories of active suicidal ideation.

12. Percentage of Participants Developing Anti-Drug Antibodies (ADA) to Galcanezumab [Baseline through Month 6]

    Treatment emergent ADA will be defined as any of the following: A negative baseline result and a positive post-baseline ADA result with a titer ≥20. This is also called treatment-induced ADA. A positive baseline result and a positive post-baseline ADA result with a ≥4-fold increase in titers (for example, baseline titer of 10 increasing to ≥40 post-baseline). This is called treatment-boosted ADA.

13. Pharmacokinetics (PK): Serum Concentration of Galcanezumab [Month 6]

    Pharmacokinetics (PK): Serum Concentration of Galcanezumab

14. Total Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP) [Month 6]

    Total Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP)

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Have a diagnosis of migraine as defined by International Headache Society (IHS) International Classification of Headache Disorders (ICHD)-3 beta guidelines (1.1 or 1.2) (ICHD-3 2013), with a history of migraine headaches of at least 1 year prior to screening, and migraine onset prior to age 50.

Exclusion Criteria:

• Are currently enrolled in or have participated within the last 30 days or within 5 half-lives (whichever is longer) in a clinical trial involving an investigational product.

• Current use or prior exposure to Galcanezumab or other antibodies to CGRP or its receptor.

• Known hypersensitivity to multiple drugs, monoclonal antibodies or other therapeutic proteins, or to Galcanezumab and the excipients in the investigational product.

• History of persistent daily headache, cluster headache or migraine subtypes including hemiplegic (sporadic or familial) migraine, ophthalmoplegic migraine, and migraine with brainstem aura (basilar-type migraine) defined by IHS ICHD-3 beta.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Chiba		Japan	275-0026
2	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Chofu-shi		Japan	182-0006
3	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Fukui		Japan	918 8503
4	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Fukui		Japan	9188503
5	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Fukuoka		Japan	816 0824
6	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Higashioka		Japan	578-8588
7	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Hiroshima		Japan	730-0031
8	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Iruma-Gun		Japan	350-0495
9	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Kagoshima		Japan	892-0842
10	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Kasaoka-shi		Japan	714-0043
11	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Kawasaki		Japan	211-8588
12	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Kawasaki		Japan	2118588
13	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Kobe		Japan	658-0064
14	For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.	Kobe		Japan	6580064
15	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Kochi		Japan	780-8011
16	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Kyoto		Japan	600-8811
17	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Kyoto		Japan	606-0851
18	For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.	Kōchi		Japan	780-0051
19	"For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician."	Matsuyama		Japan	790-0925
20	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Matsuyama		Japan	790-0925
21	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Minato-Ku		Japan	108-8642
22	For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.	Minatoku		Japan	1088642
23	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Morioka		Japan	020-0034
24	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Morioka		Japan	020-8505
25	For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.	Morioka		Japan	0200034
26	For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.	Niigata		Japan	9493193
27	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Nishinomiya		Japan	663-8014
28	"For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician."	Nishinomiya		Japan	663-8204
29	For additional information regarding investigative sites for this trial, contact 1-888-545-5972 Mon - Fri, 9 AM to 4 PM or 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time or speak with your personal physician.	Nishinomiya		Japan	663-8204
30	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Oita		Japan	870-0831
31	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Okayama-shi		Japan	700-8557
32	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Osaka-Shi		Japan	556-0015
33	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Ota-shi		Japan	373-8585
34	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Saijo-shi		Japan	793-0030
35	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Saitama		Japan	338 8577
36	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Sapporo		Japan	003-0003
37	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Sapporo		Japan	060-8570
38	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Sendai		Japan	982-0014
39	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Shibuya-ku		Japan	151-0051
40	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Shinjuku-ku		Japan	160-0017
41	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Shizuoka		Japan	420-0853
42	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Tachikawa-shi		Japan	190-8531
43	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Tokyo		Japan	160-8582
44	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Tōyama		Japan	9300803
45	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Yamaguchi		Japan	754-0002
46	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Yamanashi		Japan	400-0124
47	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Yamanashi		Japan	4000124

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

• Study Protocol - Aug 30, 2016
• Statistical Analysis Plan - Nov 15, 2018

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT02959177
• Other Study ID Numbers: 15796; I5Q-JE-CGAN
• First Posted: Nov 8, 2016
• Last Update Posted: Apr 27, 2021
• Last Verified: Feb 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Eli Lilly and Company: prevention; prophylaxis; headache
• Additional relevant MeSH terms: Migraine Disorders

Study Results

Participant Flow

Pre-assignment Detail	Participants were randomized to a Treatment Phase with double-blind treatment arms and then could enter a Follow-up Post Treatment Phase.

Arm/Group Title	120 mg Galcanezumab	240 mg Galcanezumab	Placebo
Arm/Group Description	Participants received loading dose of 240mg (2 injections of 120mg each) galcanezumab at first dosing visit followed by 120mg galcanezumab once a month for 5 months by subcutaneous (SC)injection.	Participants received 240 mg galcanezumab administered SC once a month for 6 months.	Placebo administered SC once a month for 6 months.
Period Title: Double-Blind Treatment Phase
STARTED	115	114	230
Received at Least 1 Dose of Study Drug	115	114	230
COMPLETED	104	111	225
NOT COMPLETED	11	3	5
Period Title: Double-Blind Treatment Phase
STARTED	52	52	100
COMPLETED	51	51	98
NOT COMPLETED	1	1	2

Baseline Characteristics

Arm/Group Title	120 mg Galcanezumab	240 mg Galcanezumab	Placebo	Total
Arm/Group Description	Participants received loading dose of 240mg (2 injections of 120mg each) galcanezumab at first dosing visit followed by 120mg galcanezumab once a month for 5 months by subcutaneous injection.	Participants received 240 mg galcanezumab administered SC once a month for 6 months.	Participants were administered placebo SC once a month for 6 months..	Total of all reporting groups
Overall Participants	115	114	230	459
Age, Customized (Count of Participants)
Less than 20 years old	1 0.9%	0 0%	1 0.4%	2 0.4%
Greater than 20 years old	114 99.1%	114 100%	229 99.6%	457 99.6%
Sex: Female, Male (Count of Participants)
Female	95 82.6%	96 84.2%	196 85.2%	387 84.3%
Male	20 17.4%	18 15.8%	34 14.8%	72 15.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	115 100%	114 100%	230 100%	459 100%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	115 100%	114 100%	230 100%	459 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
Japan	115 100%	114 100%	230 100%	459 100%
Migraine Headache Days (MHD) per month (days per month) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [days per month]	8.6 (2.8)	9.0 (3.0)	8.6 (3.0)	8.8 (2.9)

Outcome Measures

1. Primary Outcome

Title	Overall Mean Change From Baseline in the Number of Monthly Migraine Headache Days (MHD)
Description	Migraine Headache Day (MHD):A calendar day on which a migraine headache or probable migraine headache occurred. Migraine Headache : A headache, with or without aura, of ≥30 minutes duration with both of the following required features (A and B): A) At least 2 of the following headache characteristics: Unilateral location; Pulsatile quality; Moderate or severe pain intensity; Aggravation by or causing avoidance of routine physical activity; AND B) During headache at least one of the following: Nausea and/or vomiting; Photophobia and phonophobia; The overall mean is derived from the average of months 1 to 6 from mixed model repeat measures (MMRM) model. Least Square Mean (LSMEAN) was calculated using MMRM models with fixed categorical effects of treatment, month, and treatment-by-month interaction, as well as the continuous, fixed covariates of baseline value and baseline-by-month interaction.
Time Frame	Baseline, Month 1 through Month 6

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had baseline and at least one post baseline value.

Arm/Group Title	120 mg Galcanezumab	240 mg Galcanezumab	Placebo
Arm/Group Description	Participants received loading dose of 240mg (2 injections of 120mg each) galcanezumab at first dosing visit followed by 120mg galcanezumab once a month for 5 months by subcutaneous injection.	Participants received 240 mg galcanezumab administered SC once a month for 6 months.	Participants were administered placebo SC once a month for 6 months.
Measure Participants	115	114	230
Least Squares Mean (95% Confidence Interval) [Days]	-3.60	-3.36	-0.59

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	120 mg Galcanezumab, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	-3.01
	Confidence Interval	(2-Sided) 95%; -3.80 to -2.22
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	240 mg Galcanezumab, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.7
	Confidence Interval	(2-Sided) 95%; -3.53 to -1.94
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Participants With a 50% or Greater Reduction From Baseline in Monthly Migraine Headache Days
Description	Migraine Headache Day (MHD): A calendar day on which a migraine headache or probable migraine headache occurred. A 50% responder in a particular month is any participant who has a ≥50% reduction from baseline in the monthly number of migraine headache attacks in a 30-day interval. It is derived from the average of months 1 to 6 from generalized linear mixed model repeated measures. Mean percentages of participants were calculated with a generalized linear mixed model repeated measures method with treatment, month and treatment by month, and baseline MHD category as fixed factors.
Time Frame	Baseline, Month 1 through Month 6

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had baseline and at least one post baseline value.

Arm/Group Title	120 mg Galcanezumab	240 mg Galcanezumab	Placebo
Arm/Group Description	Participants received loading dose of 240mg (2 injections of 120mg each) galcanezumab at first dosing visit followed by 120mg galcanezumab once a month for 5 months by subcutaneous injection.	Participants received 240 mg galcanezumab administered SC once a month for 6 months.	Participants were administered placebo SC once a month for 6 months.
Measure Participants	115	114	230
Mean (Standard Error) [percentage of participants]	49.8 (3.4) 43.3%	48.2 (3.5) 42.3%	20.3 (2.0) 8.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	120 mg Galcanezumab, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.89
	Confidence Interval	(2-Sided) 95%; 2.71 to 5.57
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	240 mg Galcanezumab, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.664
	Confidence Interval	(2-Sided) 95%; 2.54 to 5.23
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Participants With a 75% or Greater Reduction From Baseline in Monthly Migraine Headache Days
Description	Migraine Headache Day (MHD): A calendar day on which a migraine headache or probable migraine headache occurred. A 75% responder in a particular month is any participant who has a ≥75% reduction from baseline in the monthly number of migraine headache attacks in a 30-day interval. It is derived from the average of months 1 to 6 from generalized linear mixed model repeated measures. Mean percentages of participants were calculated with a generalized linear mixed model repeated measures method with treatment, month and treatment by month, and baseline MHD category as fixed factors.
Time Frame	Baseline, Month 1 through Month 6

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had baseline and at least one post baseline value.

Arm/Group Title	120 mg Galcanezumab	240 mg Galcanezumab	Placebo
Arm/Group Description	Participants received loading dose of 240mg (2 injections of 120mg each) galcanezumab at first dosing visit followed by 120mg galcanezumab once a month for 5 months by subcutaneous injection.	Participants received 240 mg galcanezumab administered SC once a month for 6 months.	Participants were administered placebo SC once a month for 6 months.
Measure Participants	115	114	230
Mean (Standard Error) [percentage of participants]	25.5 (2.8) 22.2%	25.0 (2.8) 21.9%	9.6 (1.3) 4.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	120 mg Galcanezumab, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.24
	Confidence Interval	(2-Sided) 95%; 2.14 to 4.89
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	240 mg Galcanezumab, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.16
	Confidence Interval	(2-Sided) 95%; 2.08 to 4.80
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Percentage of Participants With a 100% Reduction From Baseline in Monthly Migraine Headache Days
Description	Migraine Headache Day (MHD): A calendar day on which a migraine headache or probable migraine headache occurred. A 100% responder in a particular month is any participant who has a 100% reduction from baseline in the monthly number of migraine headache attacks in a 30-day interval. It is derived from the average of months 1 to 6 from generalized linear mixed model repeated measures. Mean percentages of participants were calculated with a generalized linear mixed model repeated measures method with treatment, month and treatment by month, and baseline MHD category as fixed factors.
Time Frame	Baseline, Month 1 through Month 6

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had baseline and at least one post baseline value.

Arm/Group Title	120 mg Galcanezumab	240 mg Galcanezumab	Placebo
Arm/Group Description	Participants received loading dose of 240mg (2 injections of 120mg each) galcanezumab at first dosing visit followed by 120mg galcanezumab once a month for 5 months by subcutaneous injection.	Participants received 240 mg galcanezumab administered SC once a month for 6 months.	Participants were administered placebo SC once a month for 6 months.
Measure Participants	115	114	230
Mean (Standard Error) [percentage of participants]	9.0 (1.5) 7.8%	8.1 (1.5) 7.1%	2.8 (0.6) 1.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	120 mg Galcanezumab, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.47
	Confidence Interval	(2-Sided) 95%; 2.03 to 5.93
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	240 mg Galcanezumab, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.13
	Confidence Interval	(2-Sided) 95%; 1.79 to 5.44
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Overall Mean Change From Baseline on the Migraine-Specific Quality (MSQ) of Life Questionnaire
Description	MSQ version 2.1 is a health status instrument consists of 14 items addressing 3 domains:(1)Role Function-Restrictive (items 1-7);(2)Role Function- Preventive (items 8-11);&(3)Emotional Function (items 12-14).Response options range from "none of the time" (value 1) to "all of the time" (value 6), & are reverse-recoded (value 6 to 1) before the domain scores are calculated. Total raw scores for each domain is the sum of the final item value for all of the items in that domain. After total raw score is computed for each domain & total score, they are transformed to a 0-100 scale with higher scores indicating a better health status & a positive change in scores reflecting functional improvement. The overall mean is derived from the average of months 4 to 6 from MMRM model. LSMean was calculated using MMRM model with treatment, month, treatment by month, baseline by month and baseline MHD category as fixed factors.
Time Frame	Baseline, Month 4 through Month 6

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had baseline and at least one post baseline value.

Arm/Group Title	120 mg Galcanezumab	240 mg Galcanezumab	Placebo
Arm/Group Description	Participants received loading dose of 240mg (2 injections of 120mg each) galcanezumab at first dosing visit followed by 120mg galcanezumab once a month for 5 months by subcutaneous injection.	Participants received 240 mg galcanezumab administered SC once a month for 6 months.	Participants were administered placebo SC once a month for 6 months.
Measure Participants	112	112	228
Least Squares Mean (95% Confidence Interval) [units on a scale]	17.13	15.91	10.12

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	120 mg Galcanezumab, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LSMean difference
	Estimated Value	7.00
	Confidence Interval	(2-Sided) 95%; 4.54 to 9.46
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	240 mg Galcanezumab, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.01
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	5.79
	Confidence Interval	(2-Sided) 95%; 3.33 to 8.24
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Overall Mean Change From Baseline in Number of Migraine Headache Days With Acute Medication Use
Description	Migraine Headache Day (MHD) with Acute Medication Use: Calendar days on which migraine or probable migraine occurs, requiring acute medication. The overall mean is derived from the average of months 1 to 6 from MMRM model. LSMean was calculated using MMRM model with treatment, month, treatment by month, baseline, baseline by month, and baseline MHD category as fixed effects.
Time Frame	Baseline, Month 1 through Month 6

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had baseline and at least one post baseline value.

Arm/Group Title	120 mg Galcanezumab	240 mg Galcanezumab	Placebo
Arm/Group Description	Participants received loading dose of 240mg (2 injections of 120mg each) galcanezumab at first dosing visit followed by 120mg galcanezumab once a month for 5 months by subcutaneous injection.	Participants received 240 mg galcanezumab administered SC once a month for 6 months.	Participants were administered placebo SC once a month for 6 months.
Measure Participants	115	114	230
Least Squares Mean (95% Confidence Interval) [MDHs with medication use]	-3.02	-2.81	-0.12

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	120 mg Galcanezumab, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LSMean difference
	Estimated Value	-2.90
	Confidence Interval	(2-Sided) 95%; -3.61 to -2.19
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	240 mg Galcanezumab, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LSMean difference
	Estimated Value	-2.70
	Confidence Interval	(2-Sided) 95%; -3.41 to -1.99
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Mean Change From Baseline in the Patient Global Impression of Severity (PGI-S) Score
Description	The PGI-S scale is a patient-rated instrument that measures patients own global impression of their illness severity. The patient was instructed as follows: "Considering migraine as a chronic condition, how would you rate your level of illness?" Response options were from 1 ("normal, not at all ill") to 7 ("extremely ill"). Mean is derived from the average of months 4 to 6 from MMRM model. Least square mean (LSM) was calculated using an MMRM model with treatment, month, treatment by month, baseline, baseline by month, and baseline MHD category as fixed effects.
Time Frame	Baseline, Month 4 through Month 6

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had baseline and at least one post baseline value.

Arm/Group Title	120 mg Galcanezumab	240 mg Galcanezumab	Placebo
Arm/Group Description	Participants received loading dose of 240mg (2 injections of 120mg each) galcanezumab at first dosing visit followed by 120mg galcanezumab once a month for 5 months by subcutaneous injection.	Participants received 240 mg galcanezumab administered SC once a month for 6 months.	Participants were administered placebo SC once a month for 6 months.
Measure Participants	112	112	228
Least Squares Mean (95% Confidence Interval) [units on a scale]	-0.25	-0.41	-0.15

8. Secondary Outcome

Title	Overall Mean Change From Baseline in Headache Hours
Description	Headache Hours is calculated as the total number of headache hours on which a headache occurred. Overall mean is derived from the average of months 1 to 6 from MMRM model. LSMean was calculated using the MMRM model with treatment, month, treatment by month, baseline, baseline by month and baseline MHD category.
Time Frame	Baseline, Month 1 through Month 6

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had baseline and at least one post baseline value.

Arm/Group Title	120 mg Galcanezumab	240 mg Galcanezumab	Placebo
Arm/Group Description	Participants received loading dose of 240mg (2 injections of 120mg each) galcanezumab at first dosing visit followed by 120mg galcanezumab once a month for 5 months by subcutaneous injection.	Participants received 240 mg galcanezumab administered SC once a month for 6 months.	Participants were administered placebo SC once a month for 6 months.
Measure Participants	115	114	230
Least Squares Mean (95% Confidence Interval) [hours per month]	-14.56	-16.46	-2.73

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	120 mg Galcanezumab, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	-11.82
	Confidence Interval	(2-Sided) 95%; -16.14 to -7.51
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	240 mg Galcanezumab, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LSMean difference
	Estimated Value	-13.73
	Confidence Interval	(2-Sided) 95%; -18.05 to -9.40
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Mean Change From Baseline on the Migraine Disability Assessment Test (MIDAS) Total Score
Description	The MIDAS is a participant-rated scale which was designed to quantify headache-related disability over a 3-month period. This instrument consists of five items that reflect the number of days reported as missing or with reduced productivity at work or home, and the number of days of missed social events. Each item has a numeric response range from 0 to 90 days, if days are missed from work or home they are not counted as days with reduced productivity at work or home. The numeric responses are summed to produce a total score ranging from 0 to 270, in which a higher value is indicative of more disability. LSMean was calculated using MMRM model with treatment, month, treatment by month, baseline, baseline by month, and baseline MHD category as fixed factors.
Time Frame	Baseline, Month 6

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had baseline and at least one post baseline value.

Arm/Group Title	120 mg Galcanezumab	240 mg Galcanezumab	Placebo
Arm/Group Description	Participants received loading dose of 240mg (2 injections of 120mg each) galcanezumab at first dosing visit followed by 120mg galcanezumab once a month for 5 months by subcutaneous injection.	Participants received 240 mg galcanezumab administered SC once a month for 6 months.	Participants were administered placebo SC once a month for 6 months.
Measure Participants	114	113	229
Least Squares Mean (95% Confidence Interval) [units on a scale]	-7.06	-5.13	-2.16

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	120 mg Galcanezumab, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	-4.90
	Confidence Interval	(2-Sided) 95%; -8.06 to -1.73
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	240 mg Galcanezumab, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	-2.97
	Confidence Interval	(2-Sided) 95%; -6.08 to 0.14
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Percentage of Participants With Positive Responses on Patient Satisfaction With Medication Questionnaire-Modified (PSMQ-M)
Description	The PSMQ-M is a self-rated scale which measures participants level of satisfaction with study medication.The scale has been modified for use in this study, assessing 3 items related to the clinical trial treatment over the past 4 weeks: satisfaction, preference, and side effects. Satisfaction responses range from "very unsatisfied" to "very satisfied" with the current treatment. Preference compares the current study medication to previous medications, with responses from "much rather prefer my previous medication" to "much rather prefer the medication administered to me during the study"
Time Frame	Month 6

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had Month 6 PSMQ-M measurement.

Arm/Group Title	120 mg Galcanezumab	240 mg Galcanezumab	Placebo
Arm/Group Description	Participants received loading dose of 240mg (2 injections of 120mg each) galcanezumab at first dosing visit followed by 120mg galcanezumab once a month for 5 months by subcutaneous injection.	Participants received 240 mg galcanezumab administered SC once a month for 6 months.	Participants were administered placebo SC once a month for 6 months.
Measure Participants	104	111	225
Satisfaction: Very satisfied	35.58 30.9%	44.14 38.7%	7.56 3.3%
Satisfaction: Somewhat satisfied	26.92 23.4%	23.42 20.5%	27.11 11.8%
Side effects: Much less side effects	35.58 30.9%	28.83 25.3%	24.89 10.8%
Side effects: Less side effects	22.12 19.2%	33.33 29.2%	25.78 11.2%
Preference: Prefer study medication	40.38 35.1%	34.23 30%	28.00 12.2%
Preference: Much Prefer study medication	22.12 19.2%	27.03 23.7%	3.11 1.4%

11. Secondary Outcome

Title	Number of Participants With Suicidal Ideations Collected by Columbia - Suicide Severity Rating Scale (C-SSRS)
Description	C-SSRS captures the occurrence, severity, and frequency of suicide-related thoughts during the assessment period. The scale includes suggested questions to solicit the type of information needed to determine if a suicide-related thoughts occurred. Some questions are binary responses (yes/no) and some are on a scale of 1 (low severity) to 5 (high severity). Suicidal ideation (SI): a "yes" answer to any of 5 suicidal ideation questions: wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods without intent to act, active suicidal ideation with some intent to act without specific plan, active suicidal ideation with specific plan and intent
Time Frame	Month 1 through Month 6

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had at least one post baseline C-SSRS assessment.

Arm/Group Title	120 mg Galcanezumab	240 mg Galcanezumab	Placebo
Arm/Group Description	Participants received loading dose of 240mg (2 injections of 120mg each) galcanezumab at first dosing visit followed by 120mg galcanezumab once a month for 5 months by subcutaneous injection.	Participants received 240 mg galcanezumab administered SC once a month for 6 months.	Participants were administered placebo SC once a month for 6 months.
Measure Participants	115	114	230
Wish to be dead	1 0.9%	0 0%	0 0%
Non-specific active suicidal thoughts	0 0%	0 0%	0 0%
Active SI with no intent	0 0%	0 0%	0 0%
Active SI with some intent	0 0%	0 0%	0 0%
Active SI with specific plan and intent	0 0%	0 0%	0 0%

12. Secondary Outcome

Title	Number of Participants With Suicidal Behaviors Assessed by Columbia - Suicide Severity Rating Scale (C-SSRS)
Description	C -SSRS captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal behavior is defined as a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation is defined as a "yes" answer to any one of 5 suicidal ideation questions: wish to be dead, and 4 different categories of active suicidal ideation.
Time Frame	Month 1 through Month 6

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug.

Arm/Group Title	120 mg Galcanezumab	240 mg Galcanezumab	Placebo
Arm/Group Description	Participants received loading dose of 240mg (2 injections of 120mg each) galcanezumab at first dosing visit followed by 120mg galcanezumab once a month for 5 months by subcutaneous injection..	Participants received 240 mg galcanezumab administered SC once a month for 6 months.	Participants were administered placebo SC once a month for 6 months.
Measure Participants	115	114	230
Preparatory acts or behavior	0 0%	0 0%	0 0%
Aborted attempt	0 0%	0 0%	0 0%
Non-fatal suicide attempt	0 0%	0 0%	0 0%
Completed suicide	0 0%	0 0%	0 0%

13. Secondary Outcome

Title	Percentage of Participants Developing Anti-Drug Antibodies (ADA) to Galcanezumab
Description	Treatment emergent ADA will be defined as any of the following: A negative baseline result and a positive post-baseline ADA result with a titer ≥20. This is also called treatment-induced ADA. A positive baseline result and a positive post-baseline ADA result with a ≥4-fold increase in titers (for example, baseline titer of 10 increasing to ≥40 post-baseline). This is called treatment-boosted ADA.
Time Frame	Baseline through Month 6

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug and had evaluable immunogenicity data.

Arm/Group Title	120 mg Galcanezumab	240 mg Galcanezumab	Placebo
Arm/Group Description	Participants received loading dose of 240mg (2 injections of 120mg each) galcanezumab at first dosing visit followed by 120mg galcanezumab once a month for 5 months by subcutaneous injection.	Participants received 240 mg galcanezumab administered SC once a month for 6 months.	Participants were administered placebo SC once a month for 6 months.
Measure Participants	115	114	230
Number [percentage of participants]	9.57 8.3%	10.53 9.2%	1.30 0.6%

14. Secondary Outcome

Title	Pharmacokinetics (PK): Serum Concentration of Galcanezumab
Description	Pharmacokinetics (PK): Serum Concentration of Galcanezumab
Time Frame	Month 6

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had measurable serum concentrations.

Arm/Group Title	120 mg Galcanezumab	240 mg Galcanezumab
Arm/Group Description	Participants received loading dose of 240mg (2 injections of 120mg each) galcanezumab at first dosing visit followed by 120mg galcanezumab once a month for 5 months by subcutaneous injection.	Participants received 240 mg galcanezumab administered SC once a month for 6 months.
Measure Participants	104	111
Mean (Standard Deviation) [nanograms per milliliter]	20400 (7490)	40600 (18400)

15. Secondary Outcome

Title	Total Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP)
Description	Total Plasma Concentration of Calcitonin Gene-Related Peptide (CGRP)
Time Frame	Month 6

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had measurable CGRP concentrations.

Arm/Group Title	120 mg Galcanezumab	240 mg Galcanezumab	Placebo
Arm/Group Description	Participants received loading dose of 240mg (2 injections of 120mg each) galcanezumab at first dosing visit followed by 120mg galcanezumab once a month for 5 months by subcutaneous injection.	Participants received 240 mg galcanezumab administered SC once a month for 6 months.	Participants were administered placebo SC once a month for 6 months.
Measure Participants	104	110	25
Mean (Standard Deviation) [nanograms per milliliter]	4.35 (1.25)	5.40 (1.53)	0.634 (1.36)

Adverse Events

Time Frame	10 months
Adverse Event Reporting Description	All randomized participants who received at least 1 dose of study drug during treatment phase and remained in follow-up phase. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
Arm/Group Title	Treatment Phase Placebo		Treatment Phase 120 mg Galcanezumab		Treatment Phase 240 mg Galcanezumab		Follow-up Phase Placebo		Follow-up 120 mg Galcanezumab		Follow-up Phase 240 mg Galcanezumab
Arm/Group Description	Participants were administered placebo SC once a month for 6 months.		Participants received loading dose of 240mg (2 injections of 120mg each) galcanezumab at first doing visit followed by 120mg galcanezumab once a month for 5 months by subcutaneous injection.		Participants received 240 mg galcanezumab administered SC once a month for 6 months.		Participants did not receive study drug		Participants did not receive study drug		Participants did not receive study drug
All Cause Mortality
	Treatment Phase Placebo		Treatment Phase 120 mg Galcanezumab		Treatment Phase 240 mg Galcanezumab		Follow-up Phase Placebo		Follow-up 120 mg Galcanezumab		Follow-up Phase 240 mg Galcanezumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/230 (0%)		0/115 (0%)		0/114 (0%)		0/100 (0%)		0/52 (0%)		0/52 (0%)
Serious Adverse Events
	Treatment Phase Placebo		Treatment Phase 120 mg Galcanezumab		Treatment Phase 240 mg Galcanezumab		Follow-up Phase Placebo		Follow-up 120 mg Galcanezumab		Follow-up Phase 240 mg Galcanezumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/230 (0%)		3/115 (2.6%)		1/114 (0.9%)		1/100 (1%)		0/52 (0%)		0/52 (0%)
Ear and labyrinth disorders
Sudden hearing loss	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Gastrointestinal disorders
Tooth impacted	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Infections and infestations
Pneumonia	0/230 (0%)	0	0/115 (0%)	0	0/114 (0%)	0	1/100 (1%)	1	0/52 (0%)	0	0/52 (0%)	0
Injury, poisoning and procedural complications
Meniscus injury	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Respiratory, thoracic and mediastinal disorders
Nasal septum deviation	0/230 (0%)	0	0/115 (0%)	0	1/114 (0.9%)	1	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Other (Not Including Serious) Adverse Events
	Treatment Phase Placebo		Treatment Phase 120 mg Galcanezumab		Treatment Phase 240 mg Galcanezumab		Follow-up Phase Placebo		Follow-up 120 mg Galcanezumab		Follow-up Phase 240 mg Galcanezumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	149/230 (64.8%)		98/115 (85.2%)		93/114 (81.6%)		30/100 (30%)		21/52 (40.4%)		20/52 (38.5%)
Blood and lymphatic system disorders
Anaemia	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Cardiac disorders
Tachycardia	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Ventricular extrasystoles	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Ear and labyrinth disorders
Eustachian tube patulous	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Eustachian tube stenosis	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Meniere's disease	0/230 (0%)	0	0/115 (0%)	0	1/114 (0.9%)	1	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Motion sickness	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Sudden hearing loss	0/230 (0%)	0	1/115 (0.9%)	2	2/114 (1.8%)	2	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Tinnitus	3/230 (1.3%)	3	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Vertigo	1/230 (0.4%)	1	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Vertigo positional	0/230 (0%)	0	0/115 (0%)	0	1/114 (0.9%)	1	1/100 (1%)	1	1/52 (1.9%)	1	0/52 (0%)	0
Endocrine disorders
Autoimmune thyroiditis	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Goitre	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Eye disorders
Asthenopia	0/230 (0%)	0	0/115 (0%)	0	1/114 (0.9%)	1	1/100 (1%)	1	0/52 (0%)	0	0/52 (0%)	0
Cataract	2/230 (0.9%)	2	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Chalazion	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Conjunctival hyperaemia	0/230 (0%)	0	0/115 (0%)	0	1/114 (0.9%)	1	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Conjunctivitis allergic	2/230 (0.9%)	2	1/115 (0.9%)	1	2/114 (1.8%)	2	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Corneal disorder	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Dry eye	2/230 (0.9%)	2	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	1/52 (1.9%)	1
Eye pruritus	0/230 (0%)	0	0/115 (0%)	0	1/114 (0.9%)	1	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Foreign body sensation in eyes	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Glaucoma	0/230 (0%)	0	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	1/52 (1.9%)	1
Ocular hypertension	0/230 (0%)	0	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	1/52 (1.9%)	1
Gastrointestinal disorders
Abdominal discomfort	2/230 (0.9%)	3	1/115 (0.9%)	1	2/114 (1.8%)	2	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Abdominal pain	1/230 (0.4%)	2	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Abdominal pain upper	8/230 (3.5%)	9	0/115 (0%)	0	3/114 (2.6%)	3	1/100 (1%)	1	1/52 (1.9%)	1	0/52 (0%)	0
Abdominal wall haemorrhage	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Allergic stomatitis	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Aphthous ulcer	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Barrett's oesophagus	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Chapped lips	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Cheilitis granulomatosa	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Chronic gastritis	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Colitis	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	1/100 (1%)	1	0/52 (0%)	0	0/52 (0%)	0
Colitis ischaemic	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Constipation	3/230 (1.3%)	3	4/115 (3.5%)	4	1/114 (0.9%)	1	0/100 (0%)	0	0/52 (0%)	0	1/52 (1.9%)	1
Dental caries	5/230 (2.2%)	5	7/115 (6.1%)	8	5/114 (4.4%)	5	1/100 (1%)	1	1/52 (1.9%)	1	0/52 (0%)	0
Diarrhoea	7/230 (3%)	7	4/115 (3.5%)	6	3/114 (2.6%)	4	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Dyspepsia	0/230 (0%)	0	0/115 (0%)	0	1/114 (0.9%)	1	0/100 (0%)	0	0/52 (0%)	0	1/52 (1.9%)	1
Enterocolitis	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Erosive duodenitis	0/230 (0%)	0	0/115 (0%)	0	0/114 (0%)	0	1/100 (1%)	1	0/52 (0%)	0	0/52 (0%)	0
Flatulence	0/230 (0%)	0	0/115 (0%)	0	1/114 (0.9%)	1	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Gastric polyps	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Gastritis	4/230 (1.7%)	5	1/115 (0.9%)	1	2/114 (1.8%)	2	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Gastroenteritis eosinophilic	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Gastrooesophageal reflux disease	1/230 (0.4%)	1	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	1/52 (1.9%)	1	0/52 (0%)	0
Gingival pain	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Gingival swelling	0/230 (0%)	0	0/115 (0%)	0	1/114 (0.9%)	1	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Haematochezia	1/230 (0.4%)	1	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Haemorrhoids	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Hypoaesthesia oral	1/230 (0.4%)	2	0/115 (0%)	0	1/114 (0.9%)	1	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Irritable bowel syndrome	0/230 (0%)	0	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	1/52 (1.9%)	1	0/52 (0%)	0
Large intestine polyp	1/230 (0.4%)	1	0/115 (0%)	0	1/114 (0.9%)	1	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Nausea	3/230 (1.3%)	3	1/115 (0.9%)	1	1/114 (0.9%)	1	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Oroantral fistula	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Periodontal disease	0/230 (0%)	0	0/115 (0%)	0	1/114 (0.9%)	1	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Stomatitis	2/230 (0.9%)	2	1/115 (0.9%)	1	1/114 (0.9%)	1	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Tooth disorder	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Tooth impacted	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Tooth loss	1/230 (0.4%)	1	0/115 (0%)	0	1/114 (0.9%)	1	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Toothache	4/230 (1.7%)	5	5/115 (4.3%)	5	1/114 (0.9%)	1	0/100 (0%)	0	1/52 (1.9%)	1	0/52 (0%)	0
Vomiting	2/230 (0.9%)	2	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
General disorders
Asthenia	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Chest discomfort	0/230 (0%)	0	0/115 (0%)	0	1/114 (0.9%)	1	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Fatigue	2/230 (0.9%)	2	2/115 (1.7%)	2	1/114 (0.9%)	1	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Hangover	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	1/100 (1%)	1	0/52 (0%)	0	0/52 (0%)	0
Injection site bruising	4/230 (1.7%)	4	2/115 (1.7%)	2	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Injection site dermatitis	0/230 (0%)	0	0/115 (0%)	0	1/114 (0.9%)	2	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Injection site discolouration	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Injection site discomfort	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Injection site eczema	0/230 (0%)	0	0/115 (0%)	0	1/114 (0.9%)	1	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Injection site erythema	5/230 (2.2%)	9	17/115 (14.8%)	46	31/114 (27.2%)	84	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Injection site haemorrhage	1/230 (0.4%)	1	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Injection site induration	1/230 (0.4%)	1	3/115 (2.6%)	5	3/114 (2.6%)	3	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Injection site inflammation	0/230 (0%)	0	3/115 (2.6%)	4	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Injection site mass	0/230 (0%)	0	1/115 (0.9%)	2	1/114 (0.9%)	1	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Injection site pain	3/230 (1.3%)	3	7/115 (6.1%)	9	8/114 (7%)	14	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Injection site pruritus	0/230 (0%)	0	10/115 (8.7%)	24	23/114 (20.2%)	59	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Injection site rash	2/230 (0.9%)	3	0/115 (0%)	0	3/114 (2.6%)	6	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Injection site reaction	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Injection site swelling	3/230 (1.3%)	4	12/115 (10.4%)	22	12/114 (10.5%)	22	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Injection site urticaria	0/230 (0%)	0	1/115 (0.9%)	1	1/114 (0.9%)	4	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Injection site warmth	0/230 (0%)	0	2/115 (1.7%)	7	1/114 (0.9%)	4	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Malaise	0/230 (0%)	0	1/115 (0.9%)	1	1/114 (0.9%)	1	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Oedema	0/230 (0%)	0	1/115 (0.9%)	2	1/114 (0.9%)	1	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Oedema peripheral	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Papillitis	0/230 (0%)	0	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	1/52 (1.9%)	1	0/52 (0%)	0
Puncture site induration	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Pyrexia	0/230 (0%)	0	0/115 (0%)	0	2/114 (1.8%)	2	2/100 (2%)	2	0/52 (0%)	0	0/52 (0%)	0
Hepatobiliary disorders
Cholelithiasis	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Immune system disorders
Seasonal allergy	0/230 (0%)	0	0/115 (0%)	0	1/114 (0.9%)	1	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Infections and infestations
Acute sinusitis	0/230 (0%)	0	1/115 (0.9%)	1	1/114 (0.9%)	1	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Bacterial vulvovaginitis	0/196 (0%)	0	1/95 (1.1%)	1	0/96 (0%)	0	0/84 (0%)	0	0/43 (0%)	0	0/44 (0%)	0
Bronchitis	1/230 (0.4%)	1	3/115 (2.6%)	3	1/114 (0.9%)	2	1/100 (1%)	1	1/52 (1.9%)	1	0/52 (0%)	0
Cellulitis	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Conjunctivitis	0/230 (0%)	0	0/115 (0%)	0	1/114 (0.9%)	1	1/100 (1%)	1	0/52 (0%)	0	0/52 (0%)	0
Cystitis	2/230 (0.9%)	2	1/115 (0.9%)	1	3/114 (2.6%)	4	0/100 (0%)	0	0/52 (0%)	0	1/52 (1.9%)	1
Erysipelas	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Folliculitis	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Gastroenteritis	5/230 (2.2%)	5	7/115 (6.1%)	7	3/114 (2.6%)	3	1/100 (1%)	1	3/52 (5.8%)	3	0/52 (0%)	0
Gastroenteritis bacterial	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Gastroenteritis viral	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Gingivitis	0/230 (0%)	0	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	1/52 (1.9%)	1	0/52 (0%)	0
Helicobacter infection	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Herpes zoster	0/230 (0%)	0	2/115 (1.7%)	2	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	1/52 (1.9%)	1
Hordeolum	3/230 (1.3%)	3	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Infection	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Influenza	3/230 (1.3%)	3	9/115 (7.8%)	10	1/114 (0.9%)	1	1/100 (1%)	1	2/52 (3.8%)	2	1/52 (1.9%)	1
Laryngitis	0/230 (0%)	0	0/115 (0%)	0	1/114 (0.9%)	1	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Nasopharyngitis	76/230 (33%)	103	31/115 (27%)	43	28/114 (24.6%)	34	4/100 (4%)	5	4/52 (7.7%)	5	4/52 (7.7%)	5
Oesophageal candidiasis	0/230 (0%)	0	0/115 (0%)	0	0/114 (0%)	0	1/100 (1%)	1	0/52 (0%)	0	0/52 (0%)	0
Oral herpes	2/230 (0.9%)	3	2/115 (1.7%)	3	1/114 (0.9%)	1	0/100 (0%)	0	2/52 (3.8%)	2	0/52 (0%)	0
Otitis externa	1/230 (0.4%)	1	0/115 (0%)	0	1/114 (0.9%)	1	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Otitis media	0/230 (0%)	0	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	1/52 (1.9%)	1
Pericoronitis	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Periodontitis	2/230 (0.9%)	2	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Pharyngitis	9/230 (3.9%)	9	4/115 (3.5%)	4	3/114 (2.6%)	4	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Pneumonia	0/230 (0%)	0	0/115 (0%)	0	0/114 (0%)	0	1/100 (1%)	2	0/52 (0%)	0	0/52 (0%)	0
Postoperative wound infection	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Pulpitis dental	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Pyelonephritis	2/230 (0.9%)	2	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Rhinitis	1/230 (0.4%)	1	1/115 (0.9%)	1	1/114 (0.9%)	2	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Sinusitis	4/230 (1.7%)	5	1/115 (0.9%)	1	1/114 (0.9%)	1	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Tinea pedis	0/230 (0%)	0	0/115 (0%)	0	1/114 (0.9%)	1	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Tonsillitis	1/230 (0.4%)	3	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	1/52 (1.9%)	1	0/52 (0%)	0
Tooth abscess	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Upper respiratory tract infection	1/230 (0.4%)	1	2/115 (1.7%)	2	1/114 (0.9%)	1	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Urethritis	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Vulvitis	0/196 (0%)	0	0/95 (0%)	0	1/96 (1%)	1	0/84 (0%)	0	0/43 (0%)	0	0/44 (0%)	0
Vulvovaginal candidiasis	0/196 (0%)	0	0/95 (0%)	0	0/96 (0%)	0	0/84 (0%)	0	0/43 (0%)	0	1/44 (2.3%)	1
Injury, poisoning and procedural complications
Arthropod bite	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Arthropod sting	0/230 (0%)	0	0/115 (0%)	0	1/114 (0.9%)	1	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Chillblains	0/230 (0%)	0	2/115 (1.7%)	2	0/114 (0%)	0	1/100 (1%)	1	0/52 (0%)	0	0/52 (0%)	0
Contusion	4/230 (1.7%)	4	0/115 (0%)	0	0/114 (0%)	0	1/100 (1%)	1	0/52 (0%)	0	0/52 (0%)	0
Dental restoration failure	0/230 (0%)	0	0/115 (0%)	0	2/114 (1.8%)	2	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Fractured coccyx	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Fractured ischium	0/230 (0%)	0	0/115 (0%)	0	0/114 (0%)	0	1/100 (1%)	1	0/52 (0%)	0	0/52 (0%)	0
Heat illness	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Ligament sprain	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	1/100 (1%)	1	0/52 (0%)	0	0/52 (0%)	0
Meniscus injury	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Muscle rupture	0/230 (0%)	0	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	1/52 (1.9%)	1	0/52 (0%)	0
Muscle strain	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Post-traumatic neck syndrome	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Procedural pain	0/230 (0%)	0	1/115 (0.9%)	1	1/114 (0.9%)	1	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Rib fracture	0/230 (0%)	0	2/115 (1.7%)	2	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Thermal burn	3/230 (1.3%)	3	0/115 (0%)	0	1/114 (0.9%)	1	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Wound	0/230 (0%)	0	1/115 (0.9%)	1	2/114 (1.8%)	2	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Investigations
Blood bilirubin increased	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Blood creatine phosphokinase increased	1/230 (0.4%)	1	1/115 (0.9%)	1	0/114 (0%)	0	1/100 (1%)	1	0/52 (0%)	0	0/52 (0%)	0
Cardiac function test abnormal	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Liver function test increased	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Weight decreased	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
White blood cells urine	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Metabolism and nutrition disorders
Diabetes mellitus	1/230 (0.4%)	1	0/115 (0%)	0	1/114 (0.9%)	1	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Dyslipidaemia	1/230 (0.4%)	1	0/115 (0%)	0	1/114 (0.9%)	1	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Hyperlipidaemia	0/230 (0%)	0	0/115 (0%)	0	0/114 (0%)	0	1/100 (1%)	1	0/52 (0%)	0	0/52 (0%)	0
Hyperuricaemia	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	1/230 (0.4%)	1	3/115 (2.6%)	3	2/114 (1.8%)	2	1/100 (1%)	1	0/52 (0%)	0	1/52 (1.9%)	1
Arthritis	0/230 (0%)	0	0/115 (0%)	0	2/114 (1.8%)	2	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Back pain	3/230 (1.3%)	3	2/115 (1.7%)	2	6/114 (5.3%)	6	0/100 (0%)	0	1/52 (1.9%)	1	2/52 (3.8%)	2
Fasciitis	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Muscle spasms	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Musculoskeletal pain	1/230 (0.4%)	1	0/115 (0%)	0	1/114 (0.9%)	1	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Musculoskeletal stiffness	1/230 (0.4%)	1	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Myalgia	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Neck pain	1/230 (0.4%)	2	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Nodal osteoarthritis	0/230 (0%)	0	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	1/52 (1.9%)	1
Osteoarthritis	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Osteoporosis	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Pain in extremity	0/230 (0%)	0	0/115 (0%)	0	0/114 (0%)	0	1/100 (1%)	1	0/52 (0%)	0	0/52 (0%)	0
Periarthritis	0/230 (0%)	0	2/115 (1.7%)	2	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Rotator cuff syndrome	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Tendonitis	0/230 (0%)	0	0/115 (0%)	0	1/114 (0.9%)	1	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Tenosynovitis	1/230 (0.4%)	1	0/115 (0%)	0	1/114 (0.9%)	1	0/100 (0%)	0	0/52 (0%)	0	1/52 (1.9%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Kidney angiomyolipoma	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Lipoma	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Skin papilloma	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Nervous system disorders
Cervical radiculopathy	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Dizziness	2/230 (0.9%)	2	0/115 (0%)	0	2/114 (1.8%)	2	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Dysgeusia	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Facial spasm	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Headache	1/230 (0.4%)	1	1/115 (0.9%)	1	1/114 (0.9%)	1	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Intercostal neuralgia	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Migraine with aura	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Migraine without aura	0/230 (0%)	0	2/115 (1.7%)	2	0/114 (0%)	0	3/100 (3%)	3	0/52 (0%)	0	2/52 (3.8%)	2
Neuralgia	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Occipital neuralgia	1/230 (0.4%)	1	0/115 (0%)	0	1/114 (0.9%)	1	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Poor quality sleep	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Presyncope	1/230 (0.4%)	1	0/115 (0%)	0	1/114 (0.9%)	1	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Radial nerve palsy	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Sciatica	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	1/52 (1.9%)	1
Somnolence	1/230 (0.4%)	1	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Syncope	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Tension headache	0/230 (0%)	0	0/115 (0%)	0	1/114 (0.9%)	1	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Product Issues
Device failure	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Psychiatric disorders
Attention deficit/hyperactivity disorder	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Depression	0/230 (0%)	0	1/115 (0.9%)	1	1/114 (0.9%)	1	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Insomnia	3/230 (1.3%)	3	1/115 (0.9%)	1	1/114 (0.9%)	1	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Neurosis	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Renal and urinary disorders
Haematuria	1/230 (0.4%)	2	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	1/52 (1.9%)	1	0/52 (0%)	0
Nephrolithiasis	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Ureterolithiasis	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Reproductive system and breast disorders
Breast mass	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Cervical dysplasia	0/196 (0%)	0	0/95 (0%)	0	1/96 (1%)	1	0/84 (0%)	0	0/43 (0%)	0	0/44 (0%)	0
Dysmenorrhoea	1/196 (0.5%)	1	0/95 (0%)	0	1/96 (1%)	1	1/84 (1.2%)	2	0/43 (0%)	0	0/44 (0%)	0
Ovarian cyst	0/196 (0%)	0	0/95 (0%)	0	0/96 (0%)	0	1/84 (1.2%)	1	0/43 (0%)	0	0/44 (0%)	0
Premenstrual syndrome	0/196 (0%)	0	0/95 (0%)	0	0/96 (0%)	0	1/84 (1.2%)	1	0/43 (0%)	0	0/44 (0%)	0
Pruritus genital	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Uterine polyp	0/196 (0%)	0	1/95 (1.1%)	1	0/96 (0%)	0	0/84 (0%)	0	0/43 (0%)	0	0/44 (0%)	0
Withdrawal bleed	1/196 (0.5%)	1	0/95 (0%)	0	0/96 (0%)	0	0/84 (0%)	0	0/43 (0%)	0	0/44 (0%)	0
Respiratory, thoracic and mediastinal disorders
Asthma	2/230 (0.9%)	2	3/115 (2.6%)	4	2/114 (1.8%)	2	1/100 (1%)	1	0/52 (0%)	0	0/52 (0%)	0
Cough	2/230 (0.9%)	2	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Dyspnoea	2/230 (0.9%)	2	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Oropharyngeal pain	4/230 (1.7%)	4	1/115 (0.9%)	1	2/114 (1.8%)	5	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Rhinitis allergic	2/230 (0.9%)	2	0/115 (0%)	0	2/114 (1.8%)	2	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Upper respiratory tract inflammation	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Skin and subcutaneous tissue disorders
Acne	3/230 (1.3%)	3	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	1/52 (1.9%)	1	0/52 (0%)	0
Alopecia areata	0/230 (0%)	0	0/115 (0%)	0	1/114 (0.9%)	1	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Asteatosis	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Dermal cyst	0/230 (0%)	0	0/115 (0%)	0	1/114 (0.9%)	1	2/100 (2%)	2	0/52 (0%)	0	0/52 (0%)	0
Dermatitis	2/230 (0.9%)	2	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Dermatitis allergic	0/230 (0%)	0	0/115 (0%)	0	1/114 (0.9%)	1	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Dermatitis contact	2/230 (0.9%)	2	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Dry skin	1/230 (0.4%)	1	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Eczema	2/230 (0.9%)	3	1/115 (0.9%)	1	2/114 (1.8%)	2	0/100 (0%)	0	0/52 (0%)	0	1/52 (1.9%)	1
Haemorrhage subcutaneous	0/230 (0%)	0	0/115 (0%)	0	1/114 (0.9%)	1	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Hand dermatitis	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Onychoclasis	0/230 (0%)	0	0/115 (0%)	0	0/114 (0%)	0	1/100 (1%)	1	0/52 (0%)	0	0/52 (0%)	0
Pruritus	0/230 (0%)	0	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	1/52 (1.9%)	1
Rash	3/230 (1.3%)	3	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	1/52 (1.9%)	1	0/52 (0%)	0
Rosacea	0/230 (0%)	0	0/115 (0%)	0	1/114 (0.9%)	1	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Seborrhoeic dermatitis	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	1/52 (1.9%)	1
Skin hypertrophy	0/230 (0%)	0	0/115 (0%)	0	1/114 (0.9%)	1	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Solar dermatitis	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Urticaria	0/230 (0%)	0	2/115 (1.7%)	3	7/114 (6.1%)	7	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Xeroderma	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Social circumstances
Menopause	0/230 (0%)	0	0/115 (0%)	0	1/114 (0.9%)	1	0/84 (0%)	0	0/43 (0%)	0	0/44 (0%)	0
Surgical and medical procedures
Cyst removal	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Endodontic procedure	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Maxillary antrum operation	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Meniscus removal	0/230 (0%)	0	1/115 (0.9%)	1	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Nasal septal operation	0/230 (0%)	0	0/115 (0%)	0	1/114 (0.9%)	1	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Skin cyst excision	0/230 (0%)	0	0/115 (0%)	0	0/114 (0%)	0	1/100 (1%)	1	0/52 (0%)	0	0/52 (0%)	0
Tooth extraction	0/230 (0%)	0	2/115 (1.7%)	3	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Wisdom teeth removal	0/230 (0%)	0	2/115 (1.7%)	2	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Vascular disorders
Hot flush	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0
Hypertension	1/230 (0.4%)	1	0/115 (0%)	0	0/114 (0%)	0	0/100 (0%)	0	0/52 (0%)	0	0/52 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.