A Study Of Galcanezumab In Participants With Episodic Cluster Headache

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02397473
• Collaborator: (none)
• Enrollment: 109
• Locations: 47
• Arms: 2
• Actual Duration (Months): 36.4
• Patients Per Site: 2.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The main purpose of this study is to evaluate the efficacy and safety of the study drug known as Galcanezumab in participants with episodic cluster headaches.

Condition or Disease	Intervention/Treatment	Phase
Episodic Cluster Headache	Drug: Galcanezumab; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 109 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study of LY2951742 in Patients With Episodic Cluster Headache
• Actual Study Start Date: May 22, 2015
• Actual Primary Completion Date: Feb 12, 2018
• Actual Study Completion Date: Jun 4, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Galcanezumab 300mg Galcanezumab 300mg administered subcutaneously (SC) every 30 days during an 8 week treatment period.	Drug: Galcanezumab; Administered SC; Other Names: LY2951742
Placebo Comparator: Placebo Placebo administered SC every 30 days during an 8 week treatment period.	Drug: Placebo; Administered SC

Outcome Measures

Primary Outcome Measures

1. Overall Mean Change From Baseline in Number of Weekly Cluster Headache Attacks [Baseline, Week 1 through Week 3]

   Number of cluster headache attacks was recorded daily by study participants in their ePRO Diary. Overall mean change from baseline is derived from the average of weeks 1 to 3 from mixed model repeated measures (MMRM) analysis. Least Square (LS) means were calculated using MMRM model with treatment, sex, pooled investigative site, week, baseline, and treatment by week as fixed effects.

Secondary Outcome Measures

1. Percentage of Participants With 50% or Greater Reduction From Baseline in the Weekly Number of Cluster Headache Attacks [Baseline, Week 3]

   Number of cluster headache attacks was recorded daily by study participants in their ePRO Diary. Percentage of participants with 50% or greater reduction from baseline at week 3 was analyzed using Koch's nonparametric randomization-based analysis of covariance method. This method adjusted for pooled investigative site by including it as a stratification variable. It also adjusted for sex and baseline value.

2. Overall Mean Change From Baseline in Number of Weekly Cluster Headache Attacks [Baseline, Week 1 through Week 8]

   Number of cluster headache attacks was recorded daily by study participants in their ePRO Diary. Overall mean change from baseline is derived from the average of weeks 1 to 8 from MMRM analysis. Least Square (LS) means were calculated using MMRM model with treatment, sex, pooled investigative site, week, baseline, and treatment by week as fixed effects.

3. Percentage of Participants Reporting a Score of 1 or 2 on the Patient Global Impression of Improvement (PGI-I) [Week 4]

   PGI-I requests participants to mark the box that best describes their cluster headache condition since they started taking the medicine. The options in the displayed boxes are represented on a 7-point scale, with 1 = very much better, 2 = much better, 3 = a little better, 4 = no change, 5 = a little worse, 6 = much worse, and 7 = very much worse. Percentage of participants were derived with a generalized linear mixed model repeated measures method with treatment, sex, baseline cluster headache attack category, month, and treatment by month as fixed effects.

4. Percentage of Participants Reporting a Score of 1 or 2 on the Patient Global Impression of Improvement (PGI-I) [Week 8]

   PGI-I requests participants to mark the box that best describes their cluster headache condition since they started taking the medicine. The options in the displayed boxes are represented on a 7-point scale, with 1 = very much better, 2 = much better, 3 = a little better, 4 = no change, 5 = a little worse, 6 = much worse, and 7 = very much worse. Percentage of participants were derived with a generalized linear mixed model repeated measures method with treatment, sex, baseline cluster headache attack category, month, and treatment by month as fixed effects.

5. Percentage of Participants With 50% or Greater Reduction From Baseline in Number of Weekly Cluster Headache Attacks [Baseline, Week 1 through Week 8]

   Number of cluster headache attacks was recorded daily by study participants in their ePRO Diary. Mean percentage of participants is derived from the average of weeks 1 to 8 from generalized linear mixed model repeated measures method with treatment, sex, week, treatment by week, and baseline as fixed effects.

6. Percentage of Participants With 30% or Greater Reduction From Baseline in Number of Weekly Cluster Headache Attacks [Baseline, Week 1 through Week 8]

   Number of cluster headache attacks was recorded daily by study participants in their ePRO Diary. Mean percentage of participants is derived from the average of weeks 1 to 8 from generalized linear mixed model repeated measures with treatment, sex, week, treatment by week and baseline as fixed effects.

7. Pharmacokinetics (PK): Serum Concentration of Galcanezumab [Week 4]

8. Pharmacokinetics (PK): Serum Concentration of Galcanezumab [Week 8]

9. Percentage of Participants Developing Anti-Drug Antibodies (ADA) to Galcanezumab [Baseline through Week 8]

   Treatment emergent (TE) ADA evaluable participant is considered to be TE ADA+ if the subject has at least one post-baseline titer that is a 4-fold or greater increase in titer from baseline measurement. If baseline result is ADA Not Present, then the participant is TE ADA+ if there is at least one post-baseline result of ADA present with titer >= 1: 20.

10. Percentage of Participants With Suicidal Ideation Assessed 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 and behaviors during the assessment period. The scale includes suggested questions to solicit the type of information needed to determine if a suicide-related thought or behavior occurred. Some questions are binary responses (yes/no) and some are on a scale of 1 (low severity) to 5 (high severity). Suicidal ideation: 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. Percentage of Participants With Suicidal Behaviors Assessed 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 and behaviors during the assessment period. The scale includes suggested questions to solicit the type of information needed to determine if a suicide-related thought or behavior occurred. Some questions are binary responses (yes/no) and some are on a scale of 1 (low severity) to 5 (high severity). Suicidal behavior: a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide.

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 cluster headache as defined by International Headache Society (IHS) International Classification of Headache Disorders (ICHD)-3 beta guidelines with a history of episodic cluster headache with at least two cluster periods lasting from 7 days to 1 year (when untreated) and separated by pain-free remission periods of >=1 month.

• Participants are able to distinguish cluster headache attacks from other headaches.

Exclusion Criteria:

• Current enrollment in or discontinuation within the last 30 days from, a clinical trial involving any investigational drug or device.

• Current use or any prior exposure to any calcitonin-gene-related peptide (CGRP) antibody, any antibody to the CGRP receptor, or antibody to nerve growth factor (NGF).

• Are taking indomethacin and/or are suspected of having another distinct trigeminal autonomic cephalalgia.

• A history of migraine variants that could implicate or could be confused with ischemia.

• Known hypersensitivity to multiple drugs, monoclonal antibodies or other therapeutic proteins.

• A history or presence of other medical illness that indicates a medical problem that would preclude study participation.

• Evidence of significant active or unstable psychiatric disease, in the opinion of the investigator.

• Women who are pregnant or nursing.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cedars Sinai Medical Center	Los Angeles	California	United States	90048
2	Stanford University Hospital	Palo Alto	California	United States	94304
3	California Medical Clinic for Headache	Santa Monica	California	United States	90404
4	Colorado Neurological Institute	Englewood	Colorado	United States	80113
5	New England Institute for Clinical Research	Stamford	Connecticut	United States	06905
6	Mayo Clinic-Jacksonville	Jacksonville	Florida	United States	32224
7	University of Miami	Miami	Florida	United States	33136
8	St. Anthony's Hospital	Saint Petersburg	Florida	United States	33705
9	Tampa General Hospital	Tampa	Florida	United States	33606
10	Atlanta Center of Medical Research	Atlanta	Georgia	United States	30331
11	Michigan Head, Pain, and Neurological Institute	Ann Arbor	Michigan	United States	48104
12	ClinVest	Springfield	Missouri	United States	65807
13	Dent Neurological Institute	Amherst	New York	United States	14226
14	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
15	Clinical Trials of South Carolina	Charleston	South Carolina	United States	29406
16	Northwest Clinical Research Center	Bellevue	Washington	United States	98007-4209
17	West Virginia University Hospital	Morgantown	West Virginia	United States	26506
18	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	Gent		Belgium	9000
19	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	Liege		Belgium	4000
20	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.	Montreal		Canada	H2L 4M1
21	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.	Toronto		Canada	M4S IY2
22	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	Glostrup		Denmark	2600
23	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	Helsinki		Finland	00930
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.	Jyväskylä		Finland	40100
25	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	Turku		Finland	20100
26	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	Lille		France	59037
27	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	Nice		France	06003
28	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	Paris		France	75010
29	"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."	Paris		France	75475
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.	Saint Etienne Cedex 2		France	42055
31	Uniklinikum Essen AöR	Essen		Germany	45147
32	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	Hamburg		Germany	20246
33	Migräne- und Kopfschmerzklinik GmbH & Co. KG	Konigstein		Germany	61462
34	Klinikum der Universität München Campus Großhadern	Munchen		Germany	81377
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.	Athens		Greece	11525
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.	Athens		Greece	11528
37	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	Firenze		Italy	50134
38	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	Milano		Italy	20133
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.	Pavia		Italy	27100
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.	Amsterdam		Netherlands	1078 VV
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.	Nijmegen		Netherlands	6532 SZ
42	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	Barcelona		Spain	08035
43	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	La Coruna		Spain	15706
44	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	Valencia		Spain	46010
45	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	Hull		United Kingdom	HU3 2JZ
46	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	Liverpool		United Kingdom	L9 7LJ
47	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri, 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) or speak with your personal physician.	London		United Kingdom	SE5 9RS

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)

• Statistical Analysis Plan - Apr 5, 2018
• Study Protocol - Mar 29, 2018

More Information

Additional Information:

• Click here for more information about this study: A Study of LY2951742 in Participants With Episodic Cluster Headache

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT02397473
• Other Study ID Numbers: 15780; I5Q-MC-CGAL; 2015-000149-22
• First Posted: Mar 25, 2015
• Last Update Posted: Sep 9, 2019
• Last Verified: Aug 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Additional relevant MeSH terms: Cluster Headache; Headache

Study Results

Participant Flow

Arm/Group Title	Placebo	Galcanezumab 300mg
Arm/Group Description	Participants received placebo once a month for 2 months by subcutaneous (SC) injection. Participants did not receive any intervention during post treatment follow-up phase.	Participants received Galcanezumab 300mg once a month for two months by subcutaneous (SC) injection. Participants did not receive any intervention during post treatment follow-up phase.
Period Title: Treatment Phase
STARTED	57	52
Received at Least One Dose of Study Drug	57	49
COMPLETED	45	45
NOT COMPLETED	12	7
Period Title: Treatment Phase
STARTED	50	47
COMPLETED	47	45
NOT COMPLETED	3	2

Baseline Characteristics

Arm/Group Title	Placebo	Galcanezumab 300mg	Total
Arm/Group Description	Participants received placebo once a month for 2 months by SC injection. Participants did not receive any intervention during post treatment follow-up phase.	Participants received Galcanezumab 300mg once a month for two months by SC injection. Participants did not receive any intervention during post treatment follow-up phase.	Total of all reporting groups
Overall Participants	57	49	106
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.40 (11.32)	47.49 (10.74)	46.37 (11.05)
Sex: Female, Male (Count of Participants)
Female	10 17.5%	8 16.3%	18 17%
Male	47 82.5%	41 83.7%	88 83%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 7%	3 6.1%	7 6.6%
Not Hispanic or Latino	45 78.9%	41 83.7%	86 81.1%
Unknown or Not Reported	8 14%	5 10.2%	13 12.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 1.8%	1 2%	2 1.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	4 7%	2 4.1%	6 5.7%
White	47 82.5%	43 87.8%	90 84.9%
More than one race	5 8.8%	3 6.1%	8 7.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
Greece	1 1.8%	2 4.1%	3 2.8%
Canada	1 1.8%	1 2%	2 1.9%
Netherlands	1 1.8%	2 4.1%	3 2.8%
Belgium	4 7%	4 8.2%	8 7.5%
United States	18 31.6%	16 32.7%	34 32.1%
Finland	2 3.5%	1 2%	3 2.8%
Denmark	2 3.5%	1 2%	3 2.8%
Italy	11 19.3%	9 18.4%	20 18.9%
United Kingdom	1 1.8%	1 2%	2 1.9%
France	5 8.8%	4 8.2%	9 8.5%
Germany	4 7%	2 4.1%	6 5.7%
Spain	7 12.3%	6 12.2%	13 12.3%
Weekly Cluster Headache Attacks (Cluster Headache Attacks per week) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Cluster Headache Attacks per week]	17.30 (10.05)	17.82 (10.12)	17.54 (10.04)
Lifetime suicidal ideation prior to screening (Count of Participants)
Count of Participants [Participants]	5 8.8%	9 18.4%	14 13.2%
Lifetime suicidal behavior prior to screening (Count of Participants)
Count of Participants [Participants]	0 0%	1 2%	1 0.9%

Outcome Measures

1. Primary Outcome

Title	Overall Mean Change From Baseline in Number of Weekly Cluster Headache Attacks
Description	Number of cluster headache attacks was recorded daily by study participants in their ePRO Diary. Overall mean change from baseline is derived from the average of weeks 1 to 3 from mixed model repeated measures (MMRM) analysis. Least Square (LS) means were calculated using MMRM model with treatment, sex, pooled investigative site, week, baseline, and treatment by week as fixed effects.
Time Frame	Baseline, Week 1 through Week 3

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 measurement.

Arm/Group Title	Placebo	Galcanezumab 300mg
Arm/Group Description	Participants received placebo once a month for two months by SC injection. Participants did not receive any intervention during post treatment follow-up phase.	Participants received Galcanezumab 300mg once a month for two months by SC injection. Participants did not receive any intervention during post treatment follow-up phase.
Measure Participants	57	49
Least Squares Mean (Standard Error) [Cluster Headache Attacks per Week]	-5.22 (1.33)	-8.69 (1.42)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galcanezumab 300mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.036
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	-3.47
	Confidence Interval	(2-Sided) 95%; -6.72 to -0.23
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.63
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Participants With 50% or Greater Reduction From Baseline in the Weekly Number of Cluster Headache Attacks
Description	Number of cluster headache attacks was recorded daily by study participants in their ePRO Diary. Percentage of participants with 50% or greater reduction from baseline at week 3 was analyzed using Koch's nonparametric randomization-based analysis of covariance method. This method adjusted for pooled investigative site by including it as a stratification variable. It also adjusted for sex and baseline value.
Time Frame	Baseline, Week 3

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 measurement.

Arm/Group Title	Placebo	Galcanezumab 300mg
Arm/Group Description	Participants received placebo once a month for two months by SC injection. Participants did not receive any intervention during post treatment follow-up phase.	Participants received Galcanezumab 300mg once a month for two months by SC injection. Participants did not receive any intervention during post treatment follow-up phase.
Measure Participants	57	49
Number [percentage of participants]	52.63 92.3%	71.43 145.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galcanezumab 300mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.046
	Comments
	Method	ANCOVA
	Comments	Koch's nonparametric randomization-based ANCOVA.

3. Secondary Outcome

Title	Overall Mean Change From Baseline in Number of Weekly Cluster Headache Attacks
Description	Number of cluster headache attacks was recorded daily by study participants in their ePRO Diary. Overall mean change from baseline is derived from the average of weeks 1 to 8 from MMRM analysis. Least Square (LS) means were calculated using MMRM model with treatment, sex, pooled investigative site, week, baseline, and treatment by week as fixed effects.
Time Frame	Baseline, Week 1 through Week 8

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 measurement.

Arm/Group Title	Placebo	Galcanezumab 300mg
Arm/Group Description	Participants received placebo once a month for two months by SC injection. Participants did not receive any intervention during post treatment follow-up phase.	Participants received Galcanezumab 300mg once a month for two months by SC injection. Participants did not receive any intervention during post treatment follow-up phase.
Measure Participants	57	49
Least Squares Mean (Standard Error) [Cluster Headache Attacks per Week]	-9.97 (0.95)	-10.80 (1.00)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galcanezumab 300mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.493
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LSMean Difference
	Estimated Value	-0.83
	Confidence Interval	(2-Sided) 95%; -3.23 to 1.57
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.20
	Estimation Comments

4. Secondary Outcome

Title	Percentage of Participants Reporting a Score of 1 or 2 on the Patient Global Impression of Improvement (PGI-I)
Description	PGI-I requests participants to mark the box that best describes their cluster headache condition since they started taking the medicine. The options in the displayed boxes are represented on a 7-point scale, with 1 = very much better, 2 = much better, 3 = a little better, 4 = no change, 5 = a little worse, 6 = much worse, and 7 = very much worse. Percentage of participants were derived with a generalized linear mixed model repeated measures method with treatment, sex, baseline cluster headache attack category, month, and treatment by month as fixed effects.
Time Frame	Week 4

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had PGI-I measurement at week4.

Arm/Group Title	Placebo	Galcanezumab 300mg
Arm/Group Description	Participants received placebo once a month for two months by SC injection. Participants did not receive any intervention during post treatment follow-up phase.	Participants received Galcanezumab 300mg once a month for two months by SC injection. Participants did not receive any intervention during post treatment follow-up phase.
Measure Participants	49	44
Number [percentage of participants]	46.4 81.4%	72.5 148%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galcanezumab 300mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.016
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.046
	Confidence Interval	(2-Sided) 95%; 1.242 to 7.469
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Percentage of Participants Reporting a Score of 1 or 2 on the Patient Global Impression of Improvement (PGI-I)
Description	PGI-I requests participants to mark the box that best describes their cluster headache condition since they started taking the medicine. The options in the displayed boxes are represented on a 7-point scale, with 1 = very much better, 2 = much better, 3 = a little better, 4 = no change, 5 = a little worse, 6 = much worse, and 7 = very much worse. Percentage of participants were derived with a generalized linear mixed model repeated measures method with treatment, sex, baseline cluster headache attack category, month, and treatment by month as fixed effects.
Time Frame	Week 8

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had PGI-I measurement at week 8.

Arm/Group Title	Placebo	Galcanezumab 300mg
Arm/Group Description	Participants received placebo once a month for two months by SC injection. Participants did not receive any intervention during post treatment follow-up phase.	Participants received Galcanezumab 300mg once a month for two months by SC injection. Participants did not receive any intervention during post treatment follow-up phase.
Measure Participants	40	38
Number [percentage of participants]	66.1 116%	71.9 146.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galcanezumab 300mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.575
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.312
	Confidence Interval	(2-Sided) 95%; .502 to 3.426
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Percentage of Participants With 50% or Greater Reduction From Baseline in Number of Weekly Cluster Headache Attacks
Description	Number of cluster headache attacks was recorded daily by study participants in their ePRO Diary. Mean percentage of participants is derived from the average of weeks 1 to 8 from generalized linear mixed model repeated measures method with treatment, sex, week, treatment by week, and baseline as fixed effects.
Time Frame	Baseline, Week 1 through Week 8

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 measurement.

Arm/Group Title	Placebo	Galcanezumab 300mg
Arm/Group Description	Participants received placebo once a month for two months by SC injection. Participants did not receive any intervention during post treatment follow-up phase.	Participants received Galcanezumab 300mg once a month for two months by SC injection. Participants did not receive any intervention during post treatment follow-up phase.
Measure Participants	57	49
Number [percentage of participants]	70.4 123.5%	69.6 142%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galcanezumab 300mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.910
	Comments
	Method	Mixed Models Analysis
	Comments	Pseudo-likelihood-based repeated measures.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	.965
	Confidence Interval	(2-Sided) 95%; .512 to 1.819
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Percentage of Participants With 30% or Greater Reduction From Baseline in Number of Weekly Cluster Headache Attacks
Description	Number of cluster headache attacks was recorded daily by study participants in their ePRO Diary. Mean percentage of participants is derived from the average of weeks 1 to 8 from generalized linear mixed model repeated measures with treatment, sex, week, treatment by week and baseline as fixed effects.
Time Frame	Baseline, Week 1 through Week 8

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 measurement.

Arm/Group Title	Placebo	Galcanezumab 300mg
Arm/Group Description	Participants received placebo once a month for two months by SC injection. Participants did not receive any intervention during post treatment follow-up phase.	Participants received Galcanezumab 300mg once a month for two months by SC injection. Participants did not receive any intervention during post treatment follow-up phase.
Measure Participants	57	49
Number [percentage of participants]	78.9 138.4%	77.7 158.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Galcanezumab 300mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.841
	Comments
	Method	Mixed Models Analysis
	Comments	Pseudolikelihood-based repeated measures model
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.929
	Confidence Interval	(2-Sided) 95%; 0.449 to 1.923
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Pharmacokinetics (PK): Serum Concentration of Galcanezumab
Time Frame	Week 4

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Galcanezumab 300mg
Arm/Group Description	Participants received Galcanezumab 300mg once a month for two months by SC injection. Participants did not receive any intervention during post treatment follow-up phase.
Measure Participants	45
Mean (Standard Deviation) [Nanogram per Milliliter (ng/mL)]	20200 (6880)

9. Secondary Outcome

Title	Pharmacokinetics (PK): Serum Concentration of Galcanezumab
Time Frame	Week 8

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Galcanezumab 300mg
Arm/Group Description	Participants received Galcanezumab 300mg once a month for two months by SC injection. Participants did not receive any intervention during post treatment follow-up phase.
Measure Participants	45
Mean (Standard Deviation) [Nanogram per Milliliter (ng/mL)]	26400 (11200)

10. Secondary Outcome

Title	Percentage of Participants Developing Anti-Drug Antibodies (ADA) to Galcanezumab
Description	Treatment emergent (TE) ADA evaluable participant is considered to be TE ADA+ if the subject has at least one post-baseline titer that is a 4-fold or greater increase in titer from baseline measurement. If baseline result is ADA Not Present, then the participant is TE ADA+ if there is at least one post-baseline result of ADA present with titer >= 1: 20.
Time Frame	Baseline through Week 8

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had non-missing baseline ADA result, and at least one non-missing post baseline ADA result.

Arm/Group Title	Placebo	Galcanezumab 300mg
Arm/Group Description	Participants received placebo once a month for two months by SC injection. Participants did not receive any intervention during post treatment follow-up phase.	Participants received Galcanezumab 300mg once a month for two months by SC injection. Participants did not receive any intervention during post treatment follow-up phase.
Measure Participants	53	48
Number [percentage of participants]	0 0%	0 0%

11. Secondary Outcome

Title	Percentage of Participants With Suicidal Ideation Assessed by Columbia - Suicide Severity Rating Scale (C-SSRS)
Description	C-SSRS captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. The scale includes suggested questions to solicit the type of information needed to determine if a suicide-related thought or behavior occurred. Some questions are binary responses (yes/no) and some are on a scale of 1 (low severity) to 5 (high severity). Suicidal ideation: 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	Placebo	Galcanezumab 300mg
Arm/Group Description	Participants received placebo once a month for two months by SC injection. Participants did not receive any intervention during post treatment follow-up phase.	Participants received Galcanezumab 300mg once a month for two months by SC injection. Participants did not receive any intervention during post treatment follow-up phase.
Measure Participants	54	49
Number [percentage of participants]	0 0%	0 0%

12. Secondary Outcome

Title	Percentage of Participants With Suicidal Behaviors Assessed by Columbia - Suicide Severity Rating Scale (C-SSRS)
Description	C-SSRS captures the occurrence, severity, and frequency of suicide-related thoughts and behaviors during the assessment period. The scale includes suggested questions to solicit the type of information needed to determine if a suicide-related thought or behavior occurred. Some questions are binary responses (yes/no) and some are on a scale of 1 (low severity) to 5 (high severity). Suicidal behavior: a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide.
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	Placebo	Galcanezumab 300mg
Arm/Group Description	Participants received placebo once a month for two months by SC injection. Participants did not receive any intervention during post treatment follow-up phase.	Participants received Galcanezumab 300mg once a month for two months by SC injection. Participants did not receive any intervention during post treatment follow-up phase.
Measure Participants	54	49
Number [percentage of participants]	0 0%	0 0%

Adverse Events

Time Frame	6 Months
Arm/Group Title	Placebo - Treatment Phase		Galcanezumab 300mg - Treatment Phase		Placebo - Post Treatment Phase		Galcanezumab 300mg - Post Treatment Phase
Arm/Group Description	Participants received placebo once a month for two months by SC injection.		Participants received Galcanezumab 300mg once a month for two months by SC injection.		Participants didn't receive any intervention.		Participants didn't receive any intervention.
All Cause Mortality
	Placebo - Treatment Phase		Galcanezumab 300mg - Treatment Phase		Placebo - Post Treatment Phase		Galcanezumab 300mg - Post Treatment Phase
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/57 (0%)		0/49 (0%)		0/50 (0%)		0/47 (0%)
Serious Adverse Events
	Placebo - Treatment Phase		Galcanezumab 300mg - Treatment Phase		Placebo - Post Treatment Phase		Galcanezumab 300mg - Post Treatment Phase
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/57 (0%)		0/49 (0%)		2/50 (4%)		0/47 (0%)
Nervous system disorders
Cluster headache	0/57 (0%)	0	0/49 (0%)	0	1/50 (2%)	1	0/47 (0%)	0
Renal and urinary disorders
Nephrolithiasis	0/57 (0%)	0	0/49 (0%)	0	1/50 (2%)	1	0/47 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo - Treatment Phase		Galcanezumab 300mg - Treatment Phase		Placebo - Post Treatment Phase		Galcanezumab 300mg - Post Treatment Phase
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/57 (7%)		7/49 (14.3%)		3/50 (6%)		1/47 (2.1%)
General disorders
Injection site pain	0/57 (0%)	0	4/49 (8.2%)	4	0/50 (0%)	0	0/47 (0%)	0
Infections and infestations
Nasopharyngitis	1/57 (1.8%)	1	3/49 (6.1%)	3	3/50 (6%)	3	1/47 (2.1%)	1
Musculoskeletal and connective tissue disorders
Back pain	3/57 (5.3%)	3	0/49 (0%)	0	0/50 (0%)	0	0/47 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

All information provided to Investigator &/or Institution by Lilly or Lilly-designated representatives, or generated by Investigator &/or institution in connection with Study, will be kept in confidence and not used for any purpose not expressly provided in the Agreement for at least 5 years after termination or conclusion of Study, except to the extent that Lilly gives Investigator &/or Institution written permission or particular information is required by laws or regulations to be disclosed.