A Study of Gastrointestinal Emptying Time in Adult Participants With Migraine Before and After Start of a mAb CGRP Antagonist

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04294147
• Collaborator: (none)
• Enrollment: 65
• Locations: 3
• Arms: 2
• Actual Duration (Months): 4.9
• Patients Per Site: 21.7
• Patients Per Site Per Month: 4.4

Study Details

Study Description

Brief Summary

The purpose of this study is to measure the gastrointestinal emptying time using the wireless motility capsule (WMC) technology (FDA approved SmartPill™) in adult participants with migraine who are taking a monoclonal antibody (mAb) calcitonin gene-related peptide (CGRP) antagonist called galcanezumab or erenumab.

Condition or Disease	Intervention/Treatment	Phase
Migraine	Drug: Galcanezumab; Drug: Erenumab	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 65 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: A Phase 4 Single-Blind Study of Gastrointestinal Transit Time in Adult Patients With Migraine Before and After Initiation of a mAb CGRP Antagonist
• Actual Study Start Date: Oct 6, 2020
• Actual Primary Completion Date: Mar 5, 2021
• Actual Study Completion Date: Mar 5, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Galcanezumab Participants received a single subcutaneous (SC) dose of 240 milligram (mg) Galcanezumab.	Drug: Galcanezumab; Administered SC; Other Names: LY2951742
Active Comparator: Erenumab Participants received a single SC dose of 140 mg Erenumab.	Drug: Erenumab; Administered SC

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Colonic Transit Time (CTT) at Week 2 [Baseline, Week 2]

   Least squares (LS) mean change from baseline was calculated using analysis of covariance (ANCOVA) model with categorical effects of treatment, pooled investigative site, Body mass index (BMI) category (<30kg/m2, ≥30 kg/m2) and baseline migraine frequency (<8 migraine headache days, ≥8 migraine headache days) as well as the continuous baseline CTT (hours). A negative change from baseline indicates a decrease in CTT and a positive change from baseline indicate an increase in CTT.

Secondary Outcome Measures

1. Change From Baseline in Whole Gut Transit Time (WGTT) at Week 2 [Baseline, Week 2]

   Least squares (LS) mean change from baseline was calculated using ANCOVA model with categorical effects of treatment, pooled investigative site, Body mass index (BMI) category (<30kg/m2, ≥30 kg/m2) and baseline migraine frequency (<8 migraine headache days, ≥8 migraine headache days) as well as the continuous baseline WGTT (hours). A negative change from baseline indicates a decrease in WGTT and a positive change from baseline indicate an increase in WGTT.

2. Change From Baseline in Gastric Emptying Time (GET) at Week 2 [Baseline, Week 2]

   Least squares (LS) mean change from baseline was calculated using ANCOVA model with categorical effects of treatment, pooled investigative site, Body mass index (BMI) category (<30kg/m2, ≥30 kg/m2) and baseline migraine frequency (<8 migraine headache days, ≥8 migraine headache days) as well as the continuous baseline GET (hours). A negative change from baseline indicates a decrease in GET and a positive change from baseline indicate an increase in GET.

3. Change From Baseline in Small Intestine Bowel Transit Time (SBTT) at Week 2 [Baseline, Week 2]

   Least squares (LS) mean change from baseline was calculated using ANCOVA model with categorical effects of treatment, pooled investigative site, Body mass index (BMI) category (<30kg/m2, ≥30 kg/m2) and baseline migraine frequency (<8 migraine headache days, ≥8 migraine headache days) as well as the continuous baseline SBTT (hours). A negative change from baseline indicates a decrease in SBTT and a positive change from baseline indicate an increase in SBTT.

4. Change From Baseline in Combined Small and Large Intestine Bowel Transit Time (SLBTT) at Week 2 [Baseline, Week 2]

   Least squares (LS) mean change from baseline was calculated using ANCOVA model with categorical effects of treatment, pooled investigative site, Body mass index (BMI) category (<30kg/m2, ≥30 kg/m2) and baseline migraine frequency (<8 migraine headache days, ≥8 migraine headache days) as well as the continuous baseline SLBTT (hours). A negative change from baseline indicates a decrease in SLBTT and a positive change from baseline indicate an increase in SLBTT.

5. Change From Baseline in Motility Index by Quartile in the Colon at Week 2 [Baseline, Week 2]

   Motility index (MI) is a calculated outcome, based on the formula: In (Number of contractions x Σpressure amplitudes +1) where ln = natural logorithm, Σ = Sum. Least squares (LS) mean change from baseline was calculated using ANCOVA model with categorical effects of treatment, pooled investigative site, Body mass index (BMI) category (<30kg/m2, ≥30 kg/m2) and baseline migraine frequency (<8 migraine headache days, ≥8 migraine headache days) as well as the continuous baseline MI. A negative change from baseline indicates a decrease in colonic contractions or pressure or both, and a positive change from baseline indicates an increase in colonic contractions or pressure or both.

6. Change From Baseline in Gastrointestinal (GI) Symptom Rating Scale (GSRS) at Weeks 2 and 4 [Baseline, Week 2, Week 4]

   GSRS is a validated 15-item questionnaire that evaluates the common symptoms of GI disorders. It has five subscales: abdominal pain (abdominal pain, hunger pains, nausea), reflux (heartburn, acid reflux), indigestion (rumbling, bloating, belching, and increased flatus/breaking wind), constipation (constipation, hard stools, and sensation of not completely emptying the bowels), and diarrhea (diarrhea, loose stools, urgent need to have a bowel movement) syndromes. Subscale scores range from 1 to 7. Higher scores indicate greater severity of symptoms. LS mean change from baseline was calculated using mixed effects model for repeated measures (MMRM) with fixed categorical effects of treatment, pooled investigative site, BMI category (<30kg/m2, ≥30 kg/m2), baseline migraine frequency (<8 migraine headache days, ≥8 migraine headache days), week, and treatment-by-week interaction, as well as the continuous fixed covariates of baseline value and baseline-by-week interaction.

7. Change From Baseline in Bristol Stool Form Scale (BSFS) at Weeks 2 and 4 [Baseline, Week 2, Week 4]

   The BSFS is a 7-point ordinal scale which classifies the type of bowel movement based on the appearance of stool. Score 1, 2 indicate constipation (harder stools); 6, 7 indicate diarrhea (loose/liquid stools ); 3 to 5 are considered normal. A better score would trend toward the middle of the scale (3 to 5), while scores at either end of the scale correspond to worse outcomes. LS mean change from baseline was calculated using mixed effects model for repeated measures (MMRM) with fixed categorical effects of treatment, pooled investigative site, BMI category (<30kg/m2, ≥30 kg/m2), baseline migraine frequency (<8 migraine headache days, ≥8 migraine headache days), week, and treatment-by-week interaction, as well as the continuous fixed covariates of baseline value and baseline-by-week interaction.

8. Change From Baseline in the Weekly Spontaneous Bowel Movements (SBMs) at Weeks 2 and 4 [Baseline, Week 2, Week 4]

   Weekly SBM is the number of spontaneous (un-aided by laxatives, enemas, or suppositories) bowel movements that a participant has had in the past 7 days. LS mean change from baseline was calculated using mixed effects model for repeated measures (MMRM) with fixed categorical effects of treatment, pooled investigative site, BMI category (<30kg/m2, ≥30 kg/m2), baseline migraine frequency (<8 migraine headache days, ≥8 migraine headache days), week, and treatment-by-week interaction, as well as the continuous fixed covariates of baseline value and baseline-by-week interaction. A negative change from baseline indicates a decrease in weekly SBMs, and a positive change from baseline indicates an increase in weekly SBMs.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Have a diagnosis of migraine, with or without aura, as determined by the study investigator and in consideration of International Headache Society International Classification of Headache Disorders - 3rd edition guidelines (ICHD-3 2018)

• Have a frequency of less than 15 monthly headache days of which up to 14 can be migraine headache days.

• Participants can be on no more than 1 other migraine preventive treatment (except for tricyclic antidepressants and verapamil which are not allowed) as long as: that participant has had a stable dose of the oral migraine preventive treatment for a minimum of 2 months or participants have received onabotulinumtoxinA for a minimum of 2 cycles prior to screening

Exclusion Criteria:

• Participants with a history of gastric bezoars, swallowing disorders, severe dysphagia to food or pills, suspected or known strictures, fistulas, or physiological/mechanical GI obstruction

• History of any abdominal surgery within the past 3 months or GI surgery with the exception of cholecystectomy, appendectomy, or Nissen fundoplication

• History of irritable bowel syndrome (IBS), chronic constipation, Crohn's disease, celiac disease, ulcerative colitis, or diverticulitis

• Participants with type 1 or type 2 diabetes

• Participants with cardiac pacemakers or other implanted or portable electromechanical device

• Participants with a body mass index of ≥40 kilograms per square meter (kg/m²)

• Women who are pregnant or nursing

• Participants currently on mAb CGRP antagonists or have received a mAb CGRP antagonist within the past 6 months prior to visit 1

• Participants who have received an oral CGRP antagonist (gepant) in the last 14 days prior to Visit 1

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Research Institute LLC	Los Angeles	California	United States	90048
2	Pharmacology Research Institute	Newport Beach	California	United States	92660
3	CMR of Greater New Haven	Waterbury	Connecticut	United States	06708

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 - May 19, 2020
• Statistical Analysis Plan - Sep 29, 2020

More Information

Additional Information:

• A Study of Gastrointestinal Emptying Time in Adult Participants With Migraine Before and After Start of a CGRP Antagonist

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT04294147
• Other Study ID Numbers: 17590; I5Q-MC-CGBC
• First Posted: Mar 3, 2020
• Last Update Posted: Mar 22, 2022
• Last Verified: Feb 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
• Keywords provided by Eli Lilly and Company: prevention; prophylaxis; headache
• Additional relevant MeSH terms: Migraine Disorders; Erenumab

Study Results

Participant Flow

Arm/Group Title	140 mg Erenumab SC	240 mg Galcanezumab SC
Arm/Group Description	Participants received a single subcutaneous (SC) dose of 140 milligram (mg) Erenumab.	Participants received a single SC dose of 240 mg Galcanezumab.
Period Title: Overall Study
STARTED	32	33
Received at Least One Dose of Study Drug	32	33
COMPLETED	30	33
NOT COMPLETED	2	0

Baseline Characteristics

Arm/Group Title	140 mg Erenumab SC	240 mg Galcanezumab SC	Total
Arm/Group Description	Participants received a single SC dose of 140 mg Erenumab.	Participants received a single SC dose of 240 mg Galcanezumab.	Total of all reporting groups
Overall Participants	32	33	65
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	40.7 (11.4)	38 (9.5)	39.3 (10.5)
Sex: Female, Male (Count of Participants)
Female	27 84.4%	28 84.8%	55 84.6%
Male	5 15.6%	5 15.2%	10 15.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	12 37.5%	15 45.5%	27 41.5%
Not Hispanic or Latino	19 59.4%	18 54.5%	37 56.9%
Unknown or Not Reported	1 3.1%	0 0%	1 1.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 6.3%	0 0%	2 3.1%
Asian	0 0%	1 3%	1 1.5%
Native Hawaiian or Other Pacific Islander	1 3.1%	0 0%	1 1.5%
Black or African American	4 12.5%	6 18.2%	10 15.4%
White	23 71.9%	26 78.8%	49 75.4%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	2 6.3%	0 0%	2 3.1%
Region of Enrollment (Count of Participants)
United States	32 100%	33 100%	65 100%
Colonic transit time (hours) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [hours]	31.5 (28.1)	28.3 (24.1)	29.9 (26.0)
Whole Gut Transit Time (hours) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [hours]	41.9 (30.3)	42.3 (29.8)	42.1 (29.8)
Gastric Emptying Time (hours) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [hours]	5.3 (6.3)	9.3 (17.4)	7.3 (13.2)
Small Intestine Bowel Transit Time (hours) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [hours]	5.1 (1.6)	4.7 (2.2)	4.9 (1.9)
Combined Small and Large Intestine Bowel Transit Time (hours) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [hours]	36.6 (28.6)	33.0 (24.7)	34.8 (26.6)
Motility Index (MI) by Quartile in the Colon (motility index) [Mean (Standard Deviation) ]
Quartile 1 of Colon	12.352 (2.8544)	12.201 (2.7862)	12.2765 (2.8203)
Quartile 2 of Colon	12.869 (3.0315)	12.444 (3.0525)	12.6565 (3.042)
Quartile 3 of Colon	12.408 (4.0960)	12.318 (3.9021)	12.363 (3.99905)
Quartile 4 of Colon	14.381 (2.1097)	13.245 (2.2947)	13.813 (2.2022)
Gastrointestinal Symptom Rating Scale (score on a scale) [Mean (Standard Deviation) ]
Abdominal pain syndrome	1.2 (0.5)	1.2 (0.3)	1.2 (0.4)
Reflux syndrome	1.1 (0.3)	1.1 (0.3)	1.1 (0.3)
Indigestion syndrome	1.2 (0.3)	1.3 (0.5)	1.2 (0.4)
Constipation syndrome	1.1 (0.1)	1.1 (0.2)	1.1 (0.2)
Diarrhea syndrome	1.1 (0.3)	1.2 (0.4)	1.2 (0.4)
Bristol Stool Form Scale (score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score on a scale]	3.6 (0.9)	3.8 (1.1)	3.7 (1.0)
Weekly spontaneous bowel movements (SBMs) (SBMs per week) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [SBMs per week]	8.6 (3.7)	9.2 (5.7)	8.9 (4.8)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Colonic Transit Time (CTT) at Week 2
Description	Least squares (LS) mean change from baseline was calculated using analysis of covariance (ANCOVA) model with categorical effects of treatment, pooled investigative site, Body mass index (BMI) category (<30kg/m2, ≥30 kg/m2) and baseline migraine frequency (<8 migraine headache days, ≥8 migraine headache days) as well as the continuous baseline CTT (hours). A negative change from baseline indicates a decrease in CTT and a positive change from baseline indicate an increase in CTT.
Time Frame	Baseline, Week 2

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had baseline, post-baseline CTT assessments.

Arm/Group Title	140 mg Erenumab SC	240 mg Galcanezumab SC
Arm/Group Description	Participants received a single SC dose of 140 mg Erenumab.	Participants received a single SC dose of 240 mg Galcanezumab.
Measure Participants	28	31
Least Squares Mean (Standard Error) [hours]	5.752 (5.7234)	-5.348 (5.4177)

2. Secondary Outcome

Title	Change From Baseline in Whole Gut Transit Time (WGTT) at Week 2
Description	Least squares (LS) mean change from baseline was calculated using ANCOVA model with categorical effects of treatment, pooled investigative site, Body mass index (BMI) category (<30kg/m2, ≥30 kg/m2) and baseline migraine frequency (<8 migraine headache days, ≥8 migraine headache days) as well as the continuous baseline WGTT (hours). A negative change from baseline indicates a decrease in WGTT and a positive change from baseline indicate an increase in WGTT.
Time Frame	Baseline, Week 2

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had baseline, post-baseline WGTT assessments.

Arm/Group Title	140 mg Erenumab SC	240 mg Galcanezumab SC
Arm/Group Description	Participants received a single SC dose of 140 mg Erenumab.	Participants received a single SC dose of 240 mg Galcanezumab.
Measure Participants	28	31
Least Squares Mean (Standard Error) [hours]	4.123 (5.9808)	-7.043 (5.6307)

3. Secondary Outcome

Title	Change From Baseline in Gastric Emptying Time (GET) at Week 2
Description	Least squares (LS) mean change from baseline was calculated using ANCOVA model with categorical effects of treatment, pooled investigative site, Body mass index (BMI) category (<30kg/m2, ≥30 kg/m2) and baseline migraine frequency (<8 migraine headache days, ≥8 migraine headache days) as well as the continuous baseline GET (hours). A negative change from baseline indicates a decrease in GET and a positive change from baseline indicate an increase in GET.
Time Frame	Baseline, Week 2

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had baseline, post-baseline GET assessments.

Arm/Group Title	140 mg Erenumab SC	240 mg Galcanezumab SC
Arm/Group Description	Participants received a single SC dose of 140 mg Erenumab.	Participants received a single SC dose of 240 mg Galcanezumab.
Measure Participants	28	31
Least Squares Mean (Standard Error) [hours]	-1.320 (1.0299)	-0.582 (0.9691)

4. Secondary Outcome

Title	Change From Baseline in Small Intestine Bowel Transit Time (SBTT) at Week 2
Description	Least squares (LS) mean change from baseline was calculated using ANCOVA model with categorical effects of treatment, pooled investigative site, Body mass index (BMI) category (<30kg/m2, ≥30 kg/m2) and baseline migraine frequency (<8 migraine headache days, ≥8 migraine headache days) as well as the continuous baseline SBTT (hours). A negative change from baseline indicates a decrease in SBTT and a positive change from baseline indicate an increase in SBTT.
Time Frame	Baseline, Week 2

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had baseline, post-baseline SBTT assessments.

Arm/Group Title	140 mg Erenumab SC	240 mg Galcanezumab SC
Arm/Group Description	Participants received a single SC dose of 140 mg Erenumab.	Participants received a single SC dose of 240 mg Galcanezumab.
Measure Participants	28	31
Least Squares Mean (Standard Error) [hours]	-0.551 (0.3138)	-0.719 (0.2935)

5. Secondary Outcome

Title	Change From Baseline in Combined Small and Large Intestine Bowel Transit Time (SLBTT) at Week 2
Description	Least squares (LS) mean change from baseline was calculated using ANCOVA model with categorical effects of treatment, pooled investigative site, Body mass index (BMI) category (<30kg/m2, ≥30 kg/m2) and baseline migraine frequency (<8 migraine headache days, ≥8 migraine headache days) as well as the continuous baseline SLBTT (hours). A negative change from baseline indicates a decrease in SLBTT and a positive change from baseline indicate an increase in SLBTT.
Time Frame	Baseline, Week 2

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had baseline, post-baseline SLBTT assessments.

Arm/Group Title	140 mg Erenumab SC	240 mg Galcanezumab SC
Arm/Group Description	Participants received a single SC dose of 140 mg Erenumab.	Participants received a single SC dose of 240 mg Galcanezumab.
Measure Participants	28	31
Least Squares Mean (Standard Error) [hours]	5.150 (5.6590)	-5.957 (5.3549)

6. Secondary Outcome

Title	Change From Baseline in Motility Index by Quartile in the Colon at Week 2
Description	Motility index (MI) is a calculated outcome, based on the formula: In (Number of contractions x Σpressure amplitudes +1) where ln = natural logorithm, Σ = Sum. Least squares (LS) mean change from baseline was calculated using ANCOVA model with categorical effects of treatment, pooled investigative site, Body mass index (BMI) category (<30kg/m2, ≥30 kg/m2) and baseline migraine frequency (<8 migraine headache days, ≥8 migraine headache days) as well as the continuous baseline MI. A negative change from baseline indicates a decrease in colonic contractions or pressure or both, and a positive change from baseline indicates an increase in colonic contractions or pressure or both.
Time Frame	Baseline, Week 2

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had baseline, post-baseline MI assessments for each quartile in the colon.

Arm/Group Title	140 mg Erenumab SC	240 mg Galcanezumab SC
Arm/Group Description	Participants received a single SC dose of 140 mg Erenumab.	Participants received a single SC dose of 240 mg Galcanezumab.
Measure Participants	28	31
Quartile 1 of Colon	1.111 (0.5226)	0.367 (0.4912)
Quartile 2 of Colon	0.218 (0.7258)	-0.251 (0.6813)
Quartile 3 of Colon	0.926 (0.7477)	-0.298 (0.7016)
Quartile 4 of Colon	0.489 (0.4723)	-0.035 (0.4445)

7. Secondary Outcome

Title	Change From Baseline in Gastrointestinal (GI) Symptom Rating Scale (GSRS) at Weeks 2 and 4
Description	GSRS is a validated 15-item questionnaire that evaluates the common symptoms of GI disorders. It has five subscales: abdominal pain (abdominal pain, hunger pains, nausea), reflux (heartburn, acid reflux), indigestion (rumbling, bloating, belching, and increased flatus/breaking wind), constipation (constipation, hard stools, and sensation of not completely emptying the bowels), and diarrhea (diarrhea, loose stools, urgent need to have a bowel movement) syndromes. Subscale scores range from 1 to 7. Higher scores indicate greater severity of symptoms. LS mean change from baseline was calculated using mixed effects model for repeated measures (MMRM) with fixed categorical effects of treatment, pooled investigative site, BMI category (<30kg/m2, ≥30 kg/m2), baseline migraine frequency (<8 migraine headache days, ≥8 migraine headache days), week, and treatment-by-week interaction, as well as the continuous fixed covariates of baseline value and baseline-by-week interaction.
Time Frame	Baseline, Week 2, Week 4

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had baseline, post-baseline GSRS assessments.

Arm/Group Title	140 mg Erenumab SC	240 mg Galcanezumab SC
Arm/Group Description	Participants received a single SC dose of 140 mg Erenumab.	Participants received a single SC dose of 240 mg Galcanezumab.
Measure Participants	32	33
Abdominal pain syndrome - Week 2	-0.041 (0.0826)	0.022 (0.0799)
Abdominal pain syndrome - Week 4	-0.090 (0.0748)	0.071 (0.0713)
Reflux syndrome - Week 2	-0.042 (0.0756)	0.074 (0.0729)
Reflux syndrome - Week 4	0.078 (0.0862)	0.17 (0.082)
Indigestion syndrome - Week 2	0.026 (0.0844)	-0.011 (0.0814)
Indigestion syndrome - Week 4	0.005 (0.0955)	0.20 (0.091)
constipation syndrome - Week 2	0.41 (0.153)	0.38 (0.148)
constipation syndrome - Week 4	0.25 (0.161)	0.43 (0.153)
Diarrhea syndrome - Week 2	-0.076 (0.0367)	-0.063 (0.0352)
Diarrhea syndrome - Week 4	-0.057 (0.0852)	0.072 (0.0807)

8. Secondary Outcome

Title	Change From Baseline in Bristol Stool Form Scale (BSFS) at Weeks 2 and 4
Description	The BSFS is a 7-point ordinal scale which classifies the type of bowel movement based on the appearance of stool. Score 1, 2 indicate constipation (harder stools); 6, 7 indicate diarrhea (loose/liquid stools ); 3 to 5 are considered normal. A better score would trend toward the middle of the scale (3 to 5), while scores at either end of the scale correspond to worse outcomes. LS mean change from baseline was calculated using mixed effects model for repeated measures (MMRM) with fixed categorical effects of treatment, pooled investigative site, BMI category (<30kg/m2, ≥30 kg/m2), baseline migraine frequency (<8 migraine headache days, ≥8 migraine headache days), week, and treatment-by-week interaction, as well as the continuous fixed covariates of baseline value and baseline-by-week interaction.
Time Frame	Baseline, Week 2, Week 4

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had baseline, post-baseline BSFS assessments.

Arm/Group Title	140 mg Erenumab SC	240 mg Galcanezumab SC
Arm/Group Description	Participants received a single SC dose of 140 mg Erenumab.	Participants received a single SC dose of 240 mg Galcanezumab.
Measure Participants	32	33
Week 2	-0.44 (0.163)	-0.040 (0.1554)
Week 4	-0.48 (0.182)	0.023 (0.1710)

9. Secondary Outcome

Title	Change From Baseline in the Weekly Spontaneous Bowel Movements (SBMs) at Weeks 2 and 4
Description	Weekly SBM is the number of spontaneous (un-aided by laxatives, enemas, or suppositories) bowel movements that a participant has had in the past 7 days. LS mean change from baseline was calculated using mixed effects model for repeated measures (MMRM) with fixed categorical effects of treatment, pooled investigative site, BMI category (<30kg/m2, ≥30 kg/m2), baseline migraine frequency (<8 migraine headache days, ≥8 migraine headache days), week, and treatment-by-week interaction, as well as the continuous fixed covariates of baseline value and baseline-by-week interaction. A negative change from baseline indicates a decrease in weekly SBMs, and a positive change from baseline indicates an increase in weekly SBMs.
Time Frame	Baseline, Week 2, Week 4

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study drug and had baseline, post-baseline weekly SBM assessments.

Arm/Group Title	140 mg Erenumab SC	240 mg Galcanezumab SC
Arm/Group Description	Participants received a single SC dose of 140 mg Erenumab.	Participants received a single SC dose of 240 mg Galcanezumab.
Measure Participants	32	33
Week 2	-1.28 (0.537)	0.31 (0.517)
Week 4	-1.13 (0.511)	0.54 (0.484)

Adverse Events

Time Frame	Baseline to Follow-up (Up To 28 Days)
Adverse Event Reporting Description	All randomized participants who received at least one dose of study drug.
Arm/Group Title	140 mg Erenumab SC		240 mg Galcanezumab SC
Arm/Group Description	Participants received a single SC dose of 140 mg Erenumab.		Participants received a single SC dose of 240 mg Galcanezumab.
All Cause Mortality
	140 mg Erenumab SC		240 mg Galcanezumab SC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/32 (0%)		0/33 (0%)
Serious Adverse Events
	140 mg Erenumab SC		240 mg Galcanezumab SC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/32 (0%)		0/33 (0%)
Other (Not Including Serious) Adverse Events
	140 mg Erenumab SC		240 mg Galcanezumab SC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/32 (21.9%)		3/33 (9.1%)
Gastrointestinal disorders
Abdominal pain upper	0/32 (0%)	0	2/33 (6.1%)	3
Constipation	5/32 (15.6%)	5	1/33 (3%)	1
Infections and infestations
Covid-19	2/32 (6.3%)	2	0/33 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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