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

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03963232
• Collaborator: (none)
• Enrollment: 520
• Locations: 40
• Arms: 2
• Actual Duration (Months): 31.4
• Patients Per Site: 13
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The reason for this study is to see if the drug galcanezumab is safe and effective in participants with episodic migraine. The study will last about 53 weeks and may include up to 12 visits.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 520 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 the Efficacy and Safety of Galcanezumab in Patients With Episodic Migraine-the Persist Study
• Actual Study Start Date: Jul 30, 2019
• Actual Primary Completion Date: Jul 27, 2021
• Actual Study Completion Date: Mar 11, 2022

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Double-blind treatment phase: Participants received placebo once per month subcutaneously (SC) for 3 months. Open-label treatment phase: After completion of double-blind phase, participants could enter open-label treatment phase where they receive 240 milligram (mg) loading dose of galcanezumab SC (2 injections of 120 mg) in the first month followed by 120 mg per month for 2 months. Follow-up phase: After completion or discontinuation from double-blind or open-label treatment phases, participants enter follow-up phase where they are observed for 4 months. No treatments administered.	Drug: Placebo; Administered SC
Experimental: Galcanezumab 120 mg Double-blind treatment phase: Participants received 240 mg loading dose of galcanezumab SC (2 injections of 120 mg) in the first month followed by 120 mg per month for 2 months. Open-label treatment phase: After completion of double-blind phase, participants could enter open-label treatment phase where they continue to receive 120 mg galcanezumab SC per month for 3 months. Follow-up phase: After completion or discontinuation from double-blind or open-label treatment phases, participants enter follow-up phase where they are observed for 4 months. No treatments administered.	Drug: Galcanezumab; Administered SC; Other Names: LY2951742

Outcome Measures

Primary Outcome Measures

1. Overall Mean Change From Baseline in the Number of Monthly Migraine Headache Days (MHDs) During the Double-blind Treatment Phase. [Baseline, 3 Months]

   MHD is a calendar day on which a migraine or probable migraine (a headache missing 1 of the migraine features) occurred. Per International Headache Society [IHS] International Classification of Headache Disorders 3rd edition [ICHD-3], migraine is defined as a headache, with or without aura, of ≥30 minutes duration with the following required features (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 (B) During headache at least 1 of the following: Nausea and/or vomiting; Photophobia and phonophobia. Overall mean is derived from the average of months 1 to 3 with Least square (LS) mean change calculated using mixed model repeat measures (MMRM) model with fixed categorical effects of treatment, country, month, and treatment-by-month interaction, and the continuous fixed covariates of baseline value and baseline value-by-visit interaction.

Secondary Outcome Measures

1. Overall Mean Percentage of Participants With ≥30%, ≥50%, ≥75%, 100% Reduction From Baseline in Monthly Migraine Headache Days (MHDs) During the Double-blind Treatment Phase. [3 Months]

   Participant having: 30% or greater reduction in the total number of MHDs relative to baseline in a 30-day period is considered to have 30% response rate to treatment or "30% responder." 50% or greater reduction in the total number of MHDs relative to baseline in a 30-day period is considered to have 50% response rate to treatment or "50% responder." 75% or greater reduction in the total number of MHDs relative to baseline in a 30-day period is considered to have 75% response rate to treatment or "75% responder." 100% reduction in the total number of MHDs relative to baseline in a 30-day period is considered to have 100% response rate to treatment or "100% responder." Overall mean is derived from the average of months 1 to 3 using generalized linear mixed model (GLIMMIX) with the fixed categorical effects of treatment, month, and treatment-by-month interaction, as well as the continuous, fixed covariate of baseline value.

2. Overall Mean Change From Baseline in the Role Function-Restrictive Domain Score of the Migraine-Specific Quality-of-Life Questionnaire Version 2.1 (MSQ v2.1) During the Double-blind Treatment Phase. [Baseline, 3 Months]

   MSQ v2.1 is a self-administered instrument that was developed to address physical, emotional limitations of specific concern to individuals with migraine. It consists of 14 items that address 3 domains: Role Function-Restrictive (items 1-7), Role Function- Preventive (items 8-11) and Emotional Function (items 12-14). All item responses ranges from 1 (none of the time) to 6 (all of the time). Total raw scores for each domain is the sum of the raw scores of each item in that domain. After the total raw score is computed for each domain, they are transformed to a 0-100 scale with higher scores indicating a better health status & a positive change in scores reflecting functional improvement. Overall mean is derived from the average of months 1 to 3 with LS mean change calculated using MMRM model with fixed categorical effects of treatment, country, month, and treatment-by-month interaction, and the continuous fixed covariates of baseline value and baseline value-by-visit interaction.

3. Overall Mean Change From Baseline in the Number of Monthly Migraine Headache Days Requiring Medication for the Acute Treatment of Headache During the Double-blind Treatment Phase. [Baseline, 3 Months]

   Number of monthly migraine headache days requiring medication for the acute treatment of headache is defined as the number of calendar days in a 30-day period on which migraine or probable migraine occurs and acute medication is used. Overall mean is derived from the average of months 1 to 3 with LS mean change calculated using MMRM model with fixed categorical effects of treatment, country, month, and treatment-by-month interaction, and the continuous fixed covariates of baseline value and baseline value-by-visit interaction.

4. Overall Mean Change From Baseline in the Number of Monthly Headache Days During the Double-blind Treatment Phase. [Baseline, 3 Months]

   Number of monthly headache days is the number of calendar days in a 30-day period on which a headache occurs. Overall mean is derived from the average of months 1 to 3 with LS mean change calculated using MMRM model with fixed categorical effects of treatment, country, month, and treatment-by-month interaction, and the continuous fixed covariates of baseline value and baseline value-by-visit interaction.

5. Percentage of Participants Who Maintain 50% Response Criteria During the Double-blind Treatment Phase. [Month 1 to Month 3]

   Percentage of participants who maintained 50% response rate to treatment in all 3 months of the double-blind treatment phase.

6. Overall Mean Change From Baseline in Number of Monthly Migraine Attacks During the Double-blind Treatment Phase. [Baseline, 3 Months]

   Number of monthly migraine attacks is the number of sets of consecutive days with migraine or probable migraine separated by at least one migraine-free day in a 30-day period day. Overall mean is derived from the average of months 1 to 3 with LS mean change calculated using MMRM model with fixed categorical effects of treatment, country, month, and treatment-by-month interaction, and the continuous fixed covariates of baseline value and baseline value-by-visit interaction.

7. Overall Mean Change From Baseline in Number of Monthly Migraine Headache Hours During the Double-blind Treatment Phase. [Baseline, 3 Months]

   Number of monthly migraine headache hours is the total number of headache hours in a 30-day period on days when a migraine or probable migraine occurs. Overall mean is derived from the average of months 1 to 3 with LS mean change calculated using MMRM model with fixed categorical effects of treatment, country, month, and treatment-by-month interaction, and the continuous fixed covariates of baseline value and baseline value-by-visit interaction.

8. Overall Mean Change From Baseline in Number of Monthly Headache Hours During the Double-blind Treatment Phase. [Baseline, 3 Months]

   Number of monthly headache hours is the total number of headache hours in a 30-day period on which a headache occurred. Overall mean is derived from the average of months 1 to 3 with LS mean change calculated using MMRM model with fixed categorical effects of treatment, country, month, and treatment-by-month interaction, and the continuous fixed covariates of baseline value and baseline value-by-visit interaction.

9. Overall Mean Change From Baseline in Severity of Migraine Headaches During the Double-blind Treatment Phase. [Baseline, 3 Months]

   Severity of Migraine Headache was measured on a headache severity scale ranging from 1 to 3 with 1=mild, 2=moderate, and 3=severe. The mean severity of migraine headache for each month will be calculated as: sum of severity of migraine headache days divided by number of migraine headache days. Overall mean is derived from the average of months 1 to 3 with LS mean change calculated using MMRM model with fixed categorical effects of treatment, country, month, and treatment-by-month interaction, and the continuous fixed covariates of baseline value and baseline value-by-visit interaction.

10. Mean Change From Baseline in the Patient Global Impression of Severity (PGI-S) Score at Month 3 During the Double-blind Treatment Phase. [Baseline, Month 3]

    PGI-S is a 7-point scale that measures participants own global impression of their illness severity. The participant was instructed as follows: "Considering migraine as a chronic condition, how would you rate your level of illness?" Response options range from 1 ("normal, not at all ill") to 7 ("extremely ill"). LS mean change was calculated using analysis of variance (ANCOVA) model with fixed categorical effects of treatment, country, and the continuous fixed covariates of baseline value and baseline value-by-visit interaction.

11. Mean Change From Baseline on the Migraine Disability Assessment Test (MIDAS) Total Score at Month 3 During the Double-blind Treatment Phase. [Baseline, Month 3]

    The MIDAS was designed to quantify headache-related disability over a 3-month period. This instrument consists of 5 items that measures the impact that migraine headaches have on migraineurs' life, including days of work/school missed, days with productivity at work/school reduced to half or more, days with household work missed, days with productivity in household work reduced to half or more, and days missed family/social/leisure activities. Each item has a numeric response range from 0 to 90 days; if days are missed from work/school or household work they are not counted as days with reduced productivity at work/school or household work. The numeric responses are summed to produce a total score ranging from 0 to 270. A higher value is indicative of more disability. LS mean change was calculated using ANCOVA model with fixed categorical effects of treatment, country, and the continuous fixed covariates of baseline value and baseline value-by-visit interaction.

12. Percentage of Participants With Treatment Emergent Anti-Drug Antibodies (TE-ADA) During the Double-blind Treatment Phase. [Baseline to Month 3]

    A TE-ADA evaluable participant is considered to be TE-ADA positive if the participant 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 positive if there is at least one post baseline result of ADA Present with titer >= 20.

13. Pharmacokinetics (PK): Serum Concentration of Galcanezumab During the Double-blind Treatment Phase. [Month 3]

    PK: Serum concentration of galcanezumab

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Participants must have a diagnosis of migraine as defined by International Headache Society (IHS) International Classification of Headache Disorders (ICHD)-3 (1.1 or 1.2) (ICHD-3 2018) with a history of migraine of at least 1 year prior to screening and migraine onset prior to age 50

• Prior to screening, participants must have a history of 4-14 migraine headache days and at least 2 migraine attacks per month on average within the past 3 months

Exclusion Criteria:

• Are currently enrolled in any other clinical trial involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study

• Current use or prior exposure to galcanezumab or another calcitonin gene-related peptide (CGRP) antibody, including those who have previously completed or withdrawn from this study or any other study investigating a CGRP antibody

• Participants who are taking, or are expected to take, therapeutic antibodies during the course of the study (for example, adalimumab, infliximab, trastuzumab, bevacizumab, etc.)

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

• Women who are pregnant or nursing

• History of chronic migraine, daily persistent headache, cluster headache, medication overuse headache, migraine with brainstem aura, or hemiplegic migraine

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Xuanwu Hospital-Capital Medical University	Beijing	Beijing	China	100053
2	Chinese PLA General Hospital	Beijing	Beijing	China	100853
3	The First Affiliated Hospital Chongqing Medical University	Chongqing	Chongqing	China	400016
4	Guangzhou First People's Hospital	Guangzhou	Guangdong	China	510180
5	The Affiliated Hospital of Guiyang Medical College	Guiyang	Guizhou	China	550004
6	The First Affiliated Hospital of Zhengzhou Universtiy	Zhengzhou	Henan	China	450052
7	Tongji Hosp Tongji Med Col Huazhong Univ of Sci & Tech	Wu Han	Hubei	China	430030
8	Wuhan Union Hospital	Wuhan	Hubei	China	430022
9	Xiangya Hospital, Central South University	Changsha	Hunan	China	410008
10	The First Affliated Hospital of Soochow University	Suzhou	Jiangsu	China	215000
11	Affiliated Hospital of Jiangsu University	Zhenjiang	Jiangsu	China	212000
12	Pingxiang People's Hospital	Pingxiang	Jiangxi	China	337000
13	No.2 Hospital Affiliated to Jilin University	Changchun City	Jilin	China	130041
14	Tianjin Huanhu Hospital	Tianjin	Jinnan District	China	300350
15	Jiangsu Province Hospital	Nanjing	Nanjing	China	210029
16	First Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shaanxi	China	710061
17	Jinan Central Hospital	Jinan	Shandong	China	250013
18	People's hospital of Rizhao	Rizhao	Shandong	China	276826
19	Shanghai East Hospital	Shanghai	Shanghai	China	20000
20	Zhongshan Hospital, Fudan University	Shanghai	Shanghai	China	200032
21	HuaShan Hospital Affiliated To Fudan University	Shanghai	Shanghai	China	20040
22	West China Hospital Sichuan University	Cheng Du	Sichuan	China	610041
23	Tianjin Medical University General Hospital	Tianjin	Tianjin	China	300052
24	First Affiliated Hospital of Kunming Medical University	Kunming	Yunnan	China	650032
25	Zhejiang Hospital	Hangzhou	Zhejiang	China	310013
26	Bao Tou Central Hospital	Baotou	Zizhiqu	China	014040
27	All India Institute of Medical Sciences	New Delhi	Delhi	India	110029
28	Sir Ganga Ram Hospital	New Delhi	Delhi	India	110060
29	Apollo Hospitals International Ltd.	Ahmedabad	Gujarat	India	382428
30	Artemis Hospital	Gurgaon	Haryana	India	122001
31	Mangala Hospitals & Mangala Kidney Foundation	Mangalore	Karnataka	India	575003
32	CHL - Apollo Hospital	Indore	Madh Prad	India	452008
33	Getwell Hospital & Research Institute	Nagpur	Maharashtra	India	440012
34	HCG Manavata Cancer Centre	Nashik	Maharashtra	India	422001
35	Deenanath Mangeshkar Hospital & Research Centre	Pune	Maharashtra	India	411004
36	Gobind Ballabh Pant Hospital	New Delhi		India	110002
37	First Moscow State Medical University n.a. Sechenov	Moscow		Russian Federation	119991
38	University Headache Clinic	Moscow		Russian Federation	121467
39	OOO "Medis"	Nizhny Novgorod		Russian Federation	603137
40	Academician I.P. Pavlov First St-Petersburg State Medical University	St-Petersburg		Russian Federation	197022

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 - Jan 10, 2020
• Statistical Analysis Plan - Aug 24, 2021

More Information

Additional Information:

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

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT03963232
• Other Study ID Numbers: 17054; I5Q-MC-CGAX
• First Posted: May 24, 2019
• Last Update Posted: Aug 19, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Eli Lilly and Company: prevention; prophylactic
• Additional relevant MeSH terms: Migraine Disorders

Study Results

Participant Flow

Recruitment Details

The study was designed to be conducted in three phases: a 3-month double-blind treatment phase, an optional 3-month open-label treatment phase and a 4-month follow-up phase. Current results reporting is for primary outcome i.e., double-blind treatment phase. Open-label treatment phase and follow-up phase data analysis are ongoing and will be presented at the time of final results reporting i.e., no later than March 11, 2023.

Arm/Group Title	Placebo - Double-Blind Treatment Phase	Galcanezumab 120mg - Double-Blind Treatment Phase
Arm/Group Description	Participants received placebo once per month subcutaneously (SC) for 3 months.	Participants received 240 mg loading dose of galcanezumab SC (2 injections of 120 mg) in the first month followed by 120 mg per month for 2 months.
Period Title: Overall Study
STARTED	259	261
Received at Least One Dose of Study Drug	259	261
COMPLETED	242	245
NOT COMPLETED	17	16

Baseline Characteristics

Arm/Group Title	Placebo	Galcanezumab 120 mg	Total
Arm/Group Description	Double-blind treatment phase: Participants received placebo once per month SC for 3 months during this phase. Open-label treatment phase: After completion of double-blind phase, participants could enter open-label treatment phase where they receive 240 mg loading dose of galcanezumab SC (2 injections of 120 mg) in the first month followed by 120 mg per month for 2 months. Follow-up phase: After completion or discontinuation from double-blind or open-label treatment phases, participants enter follow-up phase where they are observed for 4 months. No treatments administered.	Double-blind treatment phase: Participants received 240 mg loading dose of galcanezumab SC (2 injections of 120 mg) in the first month followed by 120 mg per month for 2 months. Open-label treatment phase: After completion of double-blind phase, participants could enter open-label treatment phase where they continue to receive 120 mg galcanezumab SC per month for 3 months. Follow-up phase: After completion or discontinuation from double-blind or open-label treatment phases, participants enter follow-up phase where they are observed for 4 months. No treatments administered.	Total of all reporting groups
Overall Participants	259	261	520
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	36.80 (9.83)	37.20 (9.33)	37.00 (9.57)
Sex: Female, Male (Count of Participants)
Female	196 75.7%	188 72%	384 73.8%
Male	63 24.3%	73 28%	136 26.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	239 92.3%	239 91.6%	478 91.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	20 7.7%	22 8.4%	42 8.1%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
China	198 76.4%	198 75.9%	396 76.2%
India	41 15.8%	41 15.7%	82 15.8%
Russia	20 7.7%	22 8.4%	42 8.1%
Monthly Migraine Headache Days (MHD) (days per month) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [days per month]	8.34 (2.70)	8.16 (2.83)	8.25 (2.76)

Outcome Measures

1. Primary Outcome

Title	Overall Mean Change From Baseline in the Number of Monthly Migraine Headache Days (MHDs) During the Double-blind Treatment Phase.
Description	MHD is a calendar day on which a migraine or probable migraine (a headache missing 1 of the migraine features) occurred. Per International Headache Society [IHS] International Classification of Headache Disorders 3rd edition [ICHD-3], migraine is defined as a headache, with or without aura, of ≥30 minutes duration with the following required features (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 (B) During headache at least 1 of the following: Nausea and/or vomiting; Photophobia and phonophobia. Overall mean is derived from the average of months 1 to 3 with Least square (LS) mean change calculated using mixed model repeat measures (MMRM) model with fixed categorical effects of treatment, country, month, and treatment-by-month interaction, and the continuous fixed covariates of baseline value and baseline value-by-visit interaction.
Time Frame	Baseline, 3 Months

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo - Double-Blind Treatment Phase	Galcanezumab 120mg - Double-Blind Treatment Phase
Arm/Group Description	Participants received placebo once per month SC for 3 months.	Participants received 240 mg loading dose of galcanezumab SC (2 injections of 120 mg) in the first month followed by 120 mg per month for 2 months.
Measure Participants	258	260
Least Squares Mean (Standard Error) [days per month]	-1.99 (0.23)	-3.81 (0.23)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo - Double-Blind Treatment Phase, Galcanezumab 120mg - Double-Blind Treatment Phase
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.82
	Confidence Interval	(2-Sided) 95%; -2.32 to -1.32
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.26
	Estimation Comments

2. Secondary Outcome

Title	Overall Mean Percentage of Participants With ≥30%, ≥50%, ≥75%, 100% Reduction From Baseline in Monthly Migraine Headache Days (MHDs) During the Double-blind Treatment Phase.
Description	Participant having: 30% or greater reduction in the total number of MHDs relative to baseline in a 30-day period is considered to have 30% response rate to treatment or "30% responder." 50% or greater reduction in the total number of MHDs relative to baseline in a 30-day period is considered to have 50% response rate to treatment or "50% responder." 75% or greater reduction in the total number of MHDs relative to baseline in a 30-day period is considered to have 75% response rate to treatment or "75% responder." 100% reduction in the total number of MHDs relative to baseline in a 30-day period is considered to have 100% response rate to treatment or "100% responder." Overall mean is derived from the average of months 1 to 3 using generalized linear mixed model (GLIMMIX) with the fixed categorical effects of treatment, month, and treatment-by-month interaction, as well as the continuous, fixed covariate of baseline value.
Time Frame	3 Months

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo - Double-Blind Treatment Phase	Galcanezumab 120mg - Double-Blind Treatment Phase
Arm/Group Description	Participants received placebo once per month SC for 3 months.	Participants received 240 mg loading dose of galcanezumab SC (2 injections of 120 mg) in the first month followed by 120 mg per month for 2 months.
Measure Participants	258	260
30% responder	50.3 (2.4) 19.4%	73.0 (2.1) 28%
50% responder	32.9 (2.3) 12.7%	54.9 (2.4) 21%
75% responder	12.7 (1.6) 4.9%	29.2 (2.1) 11.2%
100% responder	3.9 (0.9) 1.5%	11.9 (1.4) 4.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo - Double-Blind Treatment Phase, Galcanezumab 120mg - Double-Blind Treatment Phase
	Comments	30% responder
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	GLIMMIX
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.674
	Confidence Interval	(2-Sided) 95%; 2.010 to 3.557
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo - Double-Blind Treatment Phase, Galcanezumab 120mg - Double-Blind Treatment Phase
	Comments	50% responder
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	GLIMMIX
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.481
	Confidence Interval	(2-Sided) 95%; 1.869 to 3.293
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo - Double-Blind Treatment Phase, Galcanezumab 120mg - Double-Blind Treatment Phase
	Comments	75% responder
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	GLIMMIX
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.824
	Confidence Interval	(2-Sided) 95%; 2.007 to 3.972
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo - Double-Blind Treatment Phase, Galcanezumab 120mg - Double-Blind Treatment Phase
	Comments	100% responder
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	GLIMMIX
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.309
	Confidence Interval	(2-Sided) 95%; 1.989 to 5.504
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Overall Mean Change From Baseline in the Role Function-Restrictive Domain Score of the Migraine-Specific Quality-of-Life Questionnaire Version 2.1 (MSQ v2.1) During the Double-blind Treatment Phase.
Description	MSQ v2.1 is a self-administered instrument that was developed to address physical, emotional limitations of specific concern to individuals with migraine. It consists of 14 items that address 3 domains: Role Function-Restrictive (items 1-7), Role Function- Preventive (items 8-11) and Emotional Function (items 12-14). All item responses ranges from 1 (none of the time) to 6 (all of the time). Total raw scores for each domain is the sum of the raw scores of each item in that domain. After the total raw score is computed for each domain, they are transformed to a 0-100 scale with higher scores indicating a better health status & a positive change in scores reflecting functional improvement. Overall mean is derived from the average of months 1 to 3 with LS mean change calculated using MMRM model with fixed categorical effects of treatment, country, month, and treatment-by-month interaction, and the continuous fixed covariates of baseline value and baseline value-by-visit interaction.
Time Frame	Baseline, 3 Months

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo - Double-Blind Treatment Phase	Galcanezumab 120mg - Double-Blind Treatment Phase
Arm/Group Description	Participants received placebo once per month SC for 3 months.	Participants received 240 mg loading dose of galcanezumab SC (2 injections of 120 mg) in the first month followed by 120 mg per month for 2 months.
Measure Participants	248	260
Least Squares Mean (Standard Error) [score on a scale]	13.94 (0.88)	21.01 (0.85)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo - Double-Blind Treatment Phase, Galcanezumab 120mg - Double-Blind Treatment Phase
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	7.07
	Confidence Interval	(2-Sided) 95%; 5.20 to 8.95
	Parameter Dispersion	Type: Standard Deviation; Value: 0.95
	Estimation Comments

4. Secondary Outcome

Title	Overall Mean Change From Baseline in the Number of Monthly Migraine Headache Days Requiring Medication for the Acute Treatment of Headache During the Double-blind Treatment Phase.
Description	Number of monthly migraine headache days requiring medication for the acute treatment of headache is defined as the number of calendar days in a 30-day period on which migraine or probable migraine occurs and acute medication is used. Overall mean is derived from the average of months 1 to 3 with LS mean change calculated using MMRM model with fixed categorical effects of treatment, country, month, and treatment-by-month interaction, and the continuous fixed covariates of baseline value and baseline value-by-visit interaction.
Time Frame	Baseline, 3 Months

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo - Double-Blind Treatment Phase	Galcanezumab 120mg - Double-Blind Treatment Phase
Arm/Group Description	Participants received placebo once per month SC for 3 months.	Participants received 240 mg loading dose of galcanezumab SC (2 injections of 120 mg) in the first month followed by 120 mg per month for 2 months.
Measure Participants	258	260
Least Squares Mean (Standard Error) [days per month]	-0.71 (0.22)	-2.49 (0.22)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo - Double-Blind Treatment Phase, Galcanezumab 120mg - Double-Blind Treatment Phase
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.78
	Confidence Interval	(2-Sided) 95%; -2.25 to -1.31
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.24
	Estimation Comments

5. Secondary Outcome

Title	Overall Mean Change From Baseline in the Number of Monthly Headache Days During the Double-blind Treatment Phase.
Description	Number of monthly headache days is the number of calendar days in a 30-day period on which a headache occurs. Overall mean is derived from the average of months 1 to 3 with LS mean change calculated using MMRM model with fixed categorical effects of treatment, country, month, and treatment-by-month interaction, and the continuous fixed covariates of baseline value and baseline value-by-visit interaction.
Time Frame	Baseline, 3 Months

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo - Double-Blind Treatment Phase	Galcanezumab 120mg - Double-Blind Treatment Phase
Arm/Group Description	Participants received placebo once per month SC for 3 months.	Participants received 240 mg loading dose of galcanezumab SC (2 injections of 120 mg) in the first month followed by 120 mg per month for 2 months.
Measure Participants	258	260
Least Squares Mean (Standard Error) [days per month]	-2.09 (0.24)	-3.91 (0.24)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo - Double-Blind Treatment Phase, Galcanezumab 120mg - Double-Blind Treatment Phase
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.82
	Confidence Interval	(2-Sided) 95%; -2.35 to -1.29
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.27
	Estimation Comments

6. Secondary Outcome

Title	Percentage of Participants Who Maintain 50% Response Criteria During the Double-blind Treatment Phase.
Description	Percentage of participants who maintained 50% response rate to treatment in all 3 months of the double-blind treatment phase.
Time Frame	Month 1 to Month 3

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo - Double-Blind Treatment Phase	Galcanezumab 120mg - Double-Blind Treatment Phase
Arm/Group Description	Participants received placebo once per month SC for 3 months.	Participants received 240 mg loading dose of galcanezumab SC (2 injections of 120 mg) in the first month followed by 120 mg per month for 2 months.
Measure Participants	258	260
Number [percentage of participants]	12.4 4.8%	29.6 11.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo - Double-Blind Treatment Phase, Galcanezumab 120mg - Double-Blind Treatment Phase
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.04
	Confidence Interval	(2-Sided) 95%; 1.92 to 4.81
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Overall Mean Change From Baseline in Number of Monthly Migraine Attacks During the Double-blind Treatment Phase.
Description	Number of monthly migraine attacks is the number of sets of consecutive days with migraine or probable migraine separated by at least one migraine-free day in a 30-day period day. Overall mean is derived from the average of months 1 to 3 with LS mean change calculated using MMRM model with fixed categorical effects of treatment, country, month, and treatment-by-month interaction, and the continuous fixed covariates of baseline value and baseline value-by-visit interaction.
Time Frame	Baseline, 3 Months

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo - Double-Blind Treatment Phase	Galcanezumab 120mg - Double-Blind Treatment Phase
Arm/Group Description	Participants received placebo once per month SC for 3 months.	Participants received 240 mg loading dose of galcanezumab SC (2 injections of 120 mg) in the first month followed by 120 mg per month for 2 months.
Measure Participants	258	260
Least Squares Mean (Standard Error) [migraine attacks per month]	-1.57 (0.12)	-2.46 (0.12)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo - Double-Blind Treatment Phase, Galcanezumab 120mg - Double-Blind Treatment Phase
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.89
	Confidence Interval	(2-Sided) 95%; -1.15 to -0.62
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

8. Secondary Outcome

Title	Overall Mean Change From Baseline in Number of Monthly Migraine Headache Hours During the Double-blind Treatment Phase.
Description	Number of monthly migraine headache hours is the total number of headache hours in a 30-day period on days when a migraine or probable migraine occurs. Overall mean is derived from the average of months 1 to 3 with LS mean change calculated using MMRM model with fixed categorical effects of treatment, country, month, and treatment-by-month interaction, and the continuous fixed covariates of baseline value and baseline value-by-visit interaction.
Time Frame	Baseline, 3 Months

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo - Double-Blind Treatment Phase	Galcanezumab 120mg - Double-Blind Treatment Phase
Arm/Group Description	Participants received placebo once per month SC for 3 months.	Participants received 240 mg loading dose of galcanezumab SC (2 injections of 120 mg) in the first month followed by 120 mg per month for 2 months.
Measure Participants	258	260
Least Squares Mean (Standard Error) [hours per month]	-12.83 (1.98)	-31.72 (1.96)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo - Double-Blind Treatment Phase, Galcanezumab 120mg - Double-Blind Treatment Phase
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-18.88
	Confidence Interval	(2-Sided) 95%; -23.21 to -14.56
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.20
	Estimation Comments

9. Secondary Outcome

Title	Overall Mean Change From Baseline in Number of Monthly Headache Hours During the Double-blind Treatment Phase.
Description	Number of monthly headache hours is the total number of headache hours in a 30-day period on which a headache occurred. Overall mean is derived from the average of months 1 to 3 with LS mean change calculated using MMRM model with fixed categorical effects of treatment, country, month, and treatment-by-month interaction, and the continuous fixed covariates of baseline value and baseline value-by-visit interaction.
Time Frame	Baseline, 3 Months

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo - Double-Blind Treatment Phase	Galcanezumab 120mg - Double-Blind Treatment Phase
Arm/Group Description	Participants received placebo once per month SC for 3 months.	Participants received 240 mg loading dose of galcanezumab SC (2 injections of 120 mg) in the first month followed by 120 mg per month for 2 months.
Measure Participants	258	260
Least Squares Mean (Standard Error) [hours per month]	-12.94 (2.06)	-32.18 (2.03)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo - Double-Blind Treatment Phase, Galcanezumab 120mg - Double-Blind Treatment Phase
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-19.24
	Confidence Interval	(2-Sided) 95%; -23.73 to -14.75
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.29
	Estimation Comments

10. Secondary Outcome

Title	Overall Mean Change From Baseline in Severity of Migraine Headaches During the Double-blind Treatment Phase.
Description	Severity of Migraine Headache was measured on a headache severity scale ranging from 1 to 3 with 1=mild, 2=moderate, and 3=severe. The mean severity of migraine headache for each month will be calculated as: sum of severity of migraine headache days divided by number of migraine headache days. Overall mean is derived from the average of months 1 to 3 with LS mean change calculated using MMRM model with fixed categorical effects of treatment, country, month, and treatment-by-month interaction, and the continuous fixed covariates of baseline value and baseline value-by-visit interaction.
Time Frame	Baseline, 3 Months

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo - Double-Blind Treatment Phase	Galcanezumab 120mg - Double-Blind Treatment Phase
Arm/Group Description	Participants received placebo once per month SC for 3 months.	Participants received 240 mg loading dose of galcanezumab SC (2 injections of 120 mg) in the first month followed by 120 mg per month for 2 months.
Measure Participants	256	253
Least Squares Mean (Standard Error) [score on a scale]	-0.03 (0.03)	-0.19 (0.03)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo - Double-Blind Treatment Phase, Galcanezumab 120mg - Double-Blind Treatment Phase
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.16
	Confidence Interval	(2-Sided) 95%; -0.22 to -0.10
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.03
	Estimation Comments

11. Secondary Outcome

Title	Mean Change From Baseline in the Patient Global Impression of Severity (PGI-S) Score at Month 3 During the Double-blind Treatment Phase.
Description	PGI-S is a 7-point scale that measures participants own global impression of their illness severity. The participant was instructed as follows: "Considering migraine as a chronic condition, how would you rate your level of illness?" Response options range from 1 ("normal, not at all ill") to 7 ("extremely ill"). LS mean change was calculated using analysis of variance (ANCOVA) model with fixed categorical effects of treatment, country, and the continuous fixed covariates of baseline value and baseline value-by-visit interaction.
Time Frame	Baseline, Month 3

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had baseline value, non-missing post baseline value at month 3.

Arm/Group Title	Placebo - Double-Blind Treatment Phase	Galcanezumab 120mg - Double-Blind Treatment Phase
Arm/Group Description	Participants received placebo once per month SC for 3 months.	Participants received 240 mg loading dose of galcanezumab SC (2 injections of 120 mg) in the first month followed by 120 mg per month for 2 months.
Measure Participants	238	252
Least Squares Mean (Standard Error) [score on a scale]	-0.610 (0.0961)	-0.834 (0.0930)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo - Double-Blind Treatment Phase, Galcanezumab 120mg - Double-Blind Treatment Phase
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0284
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.224
	Confidence Interval	(2-Sided) 95%; -0.43 to -0.02
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1021
	Estimation Comments

12. Secondary Outcome

Title	Mean Change From Baseline on the Migraine Disability Assessment Test (MIDAS) Total Score at Month 3 During the Double-blind Treatment Phase.
Description	The MIDAS was designed to quantify headache-related disability over a 3-month period. This instrument consists of 5 items that measures the impact that migraine headaches have on migraineurs' life, including days of work/school missed, days with productivity at work/school reduced to half or more, days with household work missed, days with productivity in household work reduced to half or more, and days missed family/social/leisure activities. Each item has a numeric response range from 0 to 90 days; if days are missed from work/school or household work they are not counted as days with reduced productivity at work/school or household work. The numeric responses are summed to produce a total score ranging from 0 to 270. A higher value is indicative of more disability. LS mean change was calculated using ANCOVA model with fixed categorical effects of treatment, country, and the continuous fixed covariates of baseline value and baseline value-by-visit interaction.
Time Frame	Baseline, Month 3

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had baseline value, non-missing post baseline value at month 3.

Arm/Group Title	Placebo - Double-Blind Treatment Phase	Galcanezumab 120mg - Double-Blind Treatment Phase
Arm/Group Description	Participants received placebo once per month SC for 3 months.	Participants received 240 mg loading dose of galcanezumab SC (2 injections of 120 mg) in the first month followed by 120 mg per month for 2 months.
Measure Participants	238	252
Least Squares Mean (Standard Error) [score on a scale]	-10.181 (3.0597)	-22.610 (2.9582)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo - Double-Blind Treatment Phase, Galcanezumab 120mg - Double-Blind Treatment Phase
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-12.429
	Confidence Interval	(2-Sided) 95%; -18.81 to -6.05
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.2484
	Estimation Comments

13. Secondary Outcome

Title	Percentage of Participants With Treatment Emergent Anti-Drug Antibodies (TE-ADA) During the Double-blind Treatment Phase.
Description	A TE-ADA evaluable participant is considered to be TE-ADA positive if the participant 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 positive if there is at least one post baseline result of ADA Present with titer >= 20.
Time Frame	Baseline to Month 3

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo - Double-Blind Treatment Phase	Galcanezumab 120mg - Double-Blind Treatment Phase
Arm/Group Description	Participants received placebo once per month SC for 3 months.	Participants received 240 mg loading dose of galcanezumab SC (2 injections of 120 mg) in the first month followed by 120 mg per month for 2 months.
Measure Participants	248	259
Number [percentage of participants]	1.2 0.5%	9.3 3.6%

14. Secondary Outcome

Title	Pharmacokinetics (PK): Serum Concentration of Galcanezumab During the Double-blind Treatment Phase.
Description	PK: Serum concentration of galcanezumab
Time Frame	Month 3

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of galcanezumab and had evaluable serum concentrations.

Arm/Group Title	Galcanezumab 120mg - Double-Blind Treatment Phase
Arm/Group Description	Participants received 240 mg loading dose of galcanezumab SC (2 injections of 120 mg) in the first month followed by 120 mg per month for 2 months.
Measure Participants	260
Mean (Standard Deviation) [Nanogram per milliliter (ng/mL)]	14696 (5675)

Adverse Events

Time Frame	Baseline to end of double-blind phase (Up To 3 Months).
Adverse Event Reporting Description	All randomized participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly. Per protocol, AE analysis was planned per treatment regimen received in each study phase. Open-label treatment phase and follow-up phase data analysis are ongoing and will be presented at the time of final results reporting i.e., no later than March 11, 2023.
Arm/Group Title	Placebo - Double-Blind Treatment Phase		Galcanezumab 120mg - Double-Blind Treatment Phase
Arm/Group Description	Participants received placebo once per month SC for 3 months.		Participants received 240 mg loading dose of galcanezumab SC (2 injections of 120 mg) in the first month followed by 120 mg per month for 2 months.
All Cause Mortality
	Placebo - Double-Blind Treatment Phase		Galcanezumab 120mg - Double-Blind Treatment Phase
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/259 (0%)		0/261 (0%)
Serious Adverse Events
	Placebo - Double-Blind Treatment Phase		Galcanezumab 120mg - Double-Blind Treatment Phase
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/259 (1.5%)		2/261 (0.8%)
Gastrointestinal disorders
Haemorrhoids	1/259 (0.4%)	1	0/261 (0%)	0
Infections and infestations
Covid-19 pneumonia	1/259 (0.4%)	1	0/261 (0%)	0
Gastroenteritis	0/259 (0%)	0	1/261 (0.4%)	1
Infected dermal cyst	0/259 (0%)	0	1/261 (0.4%)	1
Pregnancy, puerperium and perinatal conditions
Abortion threatened	1/196 (0.5%)	1	0/188 (0%)	0
Respiratory, thoracic and mediastinal disorders
Nasal septum deviation	1/259 (0.4%)	1	0/261 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo - Double-Blind Treatment Phase		Galcanezumab 120mg - Double-Blind Treatment Phase
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	29/259 (11.2%)		32/261 (12.3%)
General disorders
Injection site pain	16/259 (6.2%)	37	19/261 (7.3%)	47
Infections and infestations
Upper respiratory tract infection	13/259 (5%)	14	14/261 (5.4%)	15

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.