Continuation Study With Budesonide Oral Suspension (BOS)... | NCT03245840

Status Module

Name	Class
Takeda Development Center Americas, Inc.	INDUSTRY

Label	Type	Description	Intervention Names
Budesonide Oral Suspension	Experimental	Participants received 10 milliliters (mL) of budesonide oral suspension at a concentration of 0.2 milligram per milliliter (mg/mL), twice daily, for up to 4 years 5 months.	Drug: Budesonide oral suspension

Name	Type	Description	Arm Group Labels	Other Names
Budesonide oral suspension	Drug	BOS 10 mL twice daily.	Budesonide Oral Suspension

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs	An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. A Serious Adverse Event (SAE) was any untoward medical occurrence (whether considered to be related to investigational product or not) that at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital abnormality/birth defect, and is an important medical event. Both serious and Non-serious TEAEs were reported in this outcome measure. TEAEs were defined as AEs with a start date on or after the first dose of investigational product or a start date before the date of the first dose of investigational product that increased in severity or after the date of the first dose.	From start of study drug administration up to End of study (EOS) (Up to Month 53)
Number of Participants With Clinically Significant Physical Examination Findings	Number of participants with clinically significant physical examination findings were reported. Clinical significance was determined by investigator.	From start of study drug administration up to EOS (Up to Month 53)
Number of Participants With Clinically Significant Change From Baseline in Vital Signs	Participants were assessed by investigator for any clinically significant changes in vital parameters like temperature, systolic and diastolic blood pressure, pulse, respiratory rate, BMI, and weight. Vital signs were assessed after the participant had been in a supine position for at least 5 minutes immediately prior to the assessment. The criteria for clinically significant change was as per the investigators discretion.	From start of study drug administration up to EOS (Up to Month 53)
Change From Baseline in Bone Mineral Density (BMD) For Adolescents Assessed by Dual-Energy X-ray Absorptiometry (DXA) Scan at Month 12

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Participant completed the SHP621-302 (NCT02736409) extension study and is considered by the investigator to potentially benefit from continued BOS investigational treatment.
Participant is able to provide written informed consent (participant, parent or legal guardian and, as appropriate, participant assent) to participate in the study before completing any study-related procedures.
Females of childbearing potential must agree to continue acceptable birth control measures (example (e.g.): abstinence, surgically sterile male partner, stable oral contraceptives, or double-barrier methods) throughout study participation.
Participant is willing and has an understanding and ability to fully comply with study procedures and restrictions as defined in protocol.

Exclusion Criteria:

Participant has changes in medications or diet during the SHP621-302 (NCT02736409) study that could affect participation in this continuation study.
Participant anticipates using swallowed topical corticosteroid for EoE or systemic corticosteroid for any condition during the treatment period; any temporary use (less than or equal to [≤] 7 days) or initiation of new steroid treatment during the study should be documented and discussed with the medical monitor prospectively but should be avoided within 4 weeks of the scheduled esophagogastroduodenoscopy (EGDs).
Participant anticipates use of Cytochrome P450 3A4 inhibitors (e.g., ketoconazole, grapefruit juice) during the continuation study.
Participant has an appearance at the EGD at the final treatment evaluation visit of SHP621-302 (NCT02736409) (Visit 8) of an esophageal stricture (high grade), as defined by the presence of a lesion that does not allow passage of a diagnostic adult upper endoscope (e.g., with an insertion tube diameter of greater than (>) 9 millimeter [mm]).
Participant has presence of esophageal varices at the EGD at the final treatment evaluation visit (Visit 8) of the SHP621-302 (NCT02736409) study.
Participant has any current disease of the gastrointestinal tract, aside from EoE, including eosinophilic gastritis, enteritis, colitis, or proctitis, inflammatory bowel disease, or celiac disease.
Participant has other diseases causing or associated with esophageal eosinophilia, including hypereosinophilic syndrome, collagen vascular disease, vasculitis, achalasia, or parasitic infection.
Participant has oropharyngeal or esophageal candidiasis that failed to respond to previous treatment. Diagnosis with oropharyngeal or esophageal candidiasis at or since the final treatment evaluation visit (Visit 8) of the SHP621-302 (NCT02736409) study is not an exclusion as long as the participant is expected to respond to treatment.
Participant has a potentially serious acute or chronic infection or immunodeficiency condition, including tuberculosis, fungal, bacterial, viral/parasite infection, ocular herpes simplex, or chicken pox/measles.
Participant has upper gastrointestinal bleeding identified at the EGD at the final treatment evaluation visit (Visit 8) of the SHP621-302 (NCT02736409) study.
Participant has evidence of active infection with Helicobacter pylori.
Participant has evidence of unstable asthma.
Participant is female and pregnant or nursing.
Participant has a history of intolerance, hypersensitivity, or idiosyncratic reaction to budesonide (or any other corticosteroids), or to any other ingredients of the study medication.
Participant has a history or high risk of noncompliance with treatment or regular clinic visits.

Name	Affiliation	Role
Study Director	Shire	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Children's Hospital		Birmingham	Alabama	35233	United States
Phoenix Childrens Hospital

PubMed Identifier	Type	Citation	Retractions
39954913	Derived	Dellon ES, Katzka DA, Mukkada VA, Collins MH, Falk GW, Richmond CA, Terreri B, Thakur M, Boules M, Goodwin B, Hirano I. Long-term Safety and Efficacy of Budesonide Oral Suspension for Eosinophilic Esophagitis: A 4-Year, Phase 3, Open-Label Study. Clin Gastroenterol Hepatol. 2025 Nov;23(12):2155-2166.e5. doi: 10.1016/j.cgh.2024.12.024. Epub 2025 Feb 13.

Label	URL
To obtain more information on the study, click here/on this link	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	BOS-BOS	Participants who were randomized to budesonide oral suspension (BOS) and placebo (PBO) in Study SHP621-301 (NCT02605837) and to BOS in Study SHP621-302 (NCT02736409), were enrolled in Study SHP621-303 to receive 10 milliliters (mL) of BOS at a concentration of 0.2 milligram per milliliter (mg/mL), twice daily, for up to 4 years 5 months.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jun 21, 2021	Sep 21, 2022

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs

An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. A Serious Adverse Event (SAE) was any untoward medical occurrence (whether considered to be related to investigational product or not) that at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital abnormality/birth defect, and is an important medical event. Both serious and Non-serious TEAEs were reported in this outcome measure. TEAEs were defined as AEs with a start date on or after the first dose of investigational product or a start date before the date of the first dose of investigational product that increased in severity or after the date of the first dose.

The safety set consisted of all participants who received at least 1 dose of BOS.

Posted

Count of Participants

Participants

From start of study drug administration up to End of study (EOS) (Up to Month 53)

ID	Title	Description
OG000	BOS-BOS	Participants who were randomized to BOS and PBO in Study SHP621-301 (NCT02605837) and to BOS in Study SHP621-302 (NCT02736409), were enrolled in Study SHP621-303 to receive 10 mL of BOS at a concentration of 0.2 mg/mL, twice daily, for up to 4 years 5 months.
OG001	PBO-BOS	Participants who were randomized to and fully responded to BOS treatment in Study SHP621-301 (NCT02605837), were randomized to PBO in Study SHP621-302 (NCT02736409) and enrolled in Study SHP621-303 to receive 10 mL of BOS at a concentration of 0.2 mg/mL, twice daily, for up to 4 years 5 months.

Units	Counts
Participants	OG000121 OG00110

Title

Denominators

Categories

TEAEs

Title	Measurements
	OG00093 OG0017

Serious TEAEs

Title	Measurements
	OG000

Primary

Number of Participants With Clinically Significant Physical Examination Findings

Number of participants with clinically significant physical examination findings were reported. Clinical significance was determined by investigator.

The safety set consisted of all participants who received at least 1 dose of BOS.

Posted

Count of Participants

Participants

From start of study drug administration up to EOS (Up to Month 53)

ID	Title	Description
OG000	BOS-BOS	Participants who were randomized to BOS and PBO in Study SHP621-301 (NCT02605837) and to BOS in Study SHP621-302 (NCT02736409), were enrolled in Study SHP621-303 to receive 10 mL of BOS at a concentration of 0.2 mg/mL, twice daily, for up to 4 years 5 months.
OG001	PBO-BOS	Participants who were randomized to and fully responded to BOS treatment in Study SHP621-301 (NCT02605837), were randomized to PBO in Study SHP621-302 (NCT02736409) and enrolled in Study SHP621-303 to receive 10 mL of BOS at a concentration of 0.2 mg/mL, twice daily, for up to 4 years 5 months.

Units	Counts
Participants

Primary

Number of Participants With Clinically Significant Change From Baseline in Vital Signs

Participants were assessed by investigator for any clinically significant changes in vital parameters like temperature, systolic and diastolic blood pressure, pulse, respiratory rate, BMI, and weight. Vital signs were assessed after the participant had been in a supine position for at least 5 minutes immediately prior to the assessment. The criteria for clinically significant change was as per the investigators discretion.

The safety set consisted of all participants who received at least 1 dose of BOS.

Posted

Count of Participants

Participants

From start of study drug administration up to EOS (Up to Month 53)

ID	Title	Description
OG000	BOS-BOS	Participants who were randomized to BOS and PBO in Study SHP621-301 (NCT02605837) and to BOS in Study SHP621-302 (NCT02736409), were enrolled in Study SHP621-303 to receive 10 mL of BOS at a concentration of 0.2 mg/mL, twice daily, for up to 4 years 5 months.
OG001	PBO-BOS	Participants who were randomized to and fully responded to BOS treatment in Study SHP621-301 (NCT02605837), were randomized to PBO in Study SHP621-302 (NCT02736409) and enrolled in Study SHP621-303 to receive 10 mL of BOS at a concentration of 0.2 mg/mL, twice daily, for up to 4 years 5 months.

Primary

Change From Baseline in Bone Mineral Density (BMD) For Adolescents Assessed by Dual-Energy X-ray Absorptiometry (DXA) Scan at Month 12

The sites for DXA measurement were the lumbar spine at lumbar vertebrae 1 to 4 (L1-L4) and whole body. DXA scans for determination of BMD and body composition was performed in participants aged 11-17 years. Z-score indicates the number of standard deviations away from a reference population in the same age range and with the same sex. In this study, the BMD Z-score is considered abnormal when the z-score is less than (<) -2, suggesting a worse outcome (i.e., osteoporosis). Change from baseline in BMD for adolescents assessed by DXA Scan at Month 12 was reported.

The safety set consisted of all participants who received at least 1 dose of BOS. Here, overall number of participants analyzed signified participants who were evaluable for this outcome measure and number analyzed signifies participants who were evaluable for given categories. DXA was performed for participants aged 11-17 years only and no participants of this age range were present in PBO-BOS group.

Posted

Mean

Standard Deviation

Z-score

Baseline, Month 12

ID	Title	Description
OG000	BOS-BOS	Participants who were randomized to BOS and PBO in Study SHP621-301 (NCT02605837) and to BOS in Study SHP621-302 (NCT02736409), were enrolled in Study SHP621-303 to receive 10 mL of BOS at a concentration of 0.2 mg/mL, twice daily, for up to 4 years 5 months.

Primary

Change From Baseline in BMD For Adolescents Assessed by DXA Scan at Month 24

The sites for DXA measurement were the lumbar spine at lumbar vertebrae 1 to 4 (L1-L4) and whole body. DXA scans for determination of BMD and body composition was performed in participants aged 11-17 years. Z-score indicates the number of standard deviations away from a reference population in the same age range and with the same sex. In this study, the BMD Z-score is considered abnormal when the z-score is <-2, suggesting a worse outcome (i.e., osteoporosis) and vice versa. Change from baseline in BMD for adolescents assessed by DXA Scan at Month 24 was reported.

Posted

Mean

Standard Deviation

Z-score

Baseline, Month 24

ID	Title	Description
OG000	BOS-BOS	Participants who were randomized to BOS and PBO in Study SHP621-301 (NCT02605837) and to BOS in Study SHP621-302 (NCT02736409), were enrolled in Study SHP621-303 to receive 10 mL of BOS at a concentration of 0.2 mg/mL, twice daily, for up to 4 years 5 months.

Units	Counts

Primary

Change From Baseline in BMD For Adolescents Assessed by DXA Scan at Month 36

The sites for DXA measurement were the lumbar spine at lumbar vertebrae 1 to 4 (L1-L4) and whole body. DXA scans for determination of BMD and body composition was performed in participants aged 11-17 years. Z-score indicates the number of standard deviations away from a reference population in the same age range and with the same sex. In this study, the BMD Z-score is considered abnormal when the z-score is < -2, suggesting a worse outcome (i.e., osteoporosis) and vice versa. Change from baseline in BMD for adolescents assessed by DXA Scan at Month 36 was reported.

Posted

Mean

Standard Deviation

Z-score

Baseline, Month 36

ID	Title	Description
OG000	BOS-BOS	Participants who were randomized to BOS and PBO in Study SHP621-301 (NCT02605837) and to BOS in Study SHP621-302 (NCT02736409), were enrolled in Study SHP621-303 to receive 10 mL of BOS at a concentration of 0.2 mg/mL, twice daily, for up to 4 years 5 months.

Units	Counts

Primary

Change From Baseline in BMD For Adolescents Assessed by DXA Scan at Month 48

The sites for DXA measurement were the lumbar spine at lumbar vertebrae 1 to 4 (L1-L4) and whole body. DXA scans for determination of BMD and body composition was performed in participants aged 11-17 years. Z-score indicates the number of standard deviations away from a reference population in the same age range and with the same sex. In this study, the BMD Z-score is considered abnormal when the z-score is < -2, suggesting a worse outcome (i.e., osteoporosis) and vice versa. Change from baseline in BMD for adolescents assessed by DXA Scan at Month 48 was reported.

Posted

Mean

Standard Deviation

Z-score

Baseline, Month 48

ID	Title	Description
OG000	BOS-BOS	Participants who were randomized to BOS and PBO in Study SHP621-301 (NCT02605837) and to BOS in Study SHP621-302 (NCT02736409), were enrolled in Study SHP621-303 to receive 10 mL of BOS at a concentration of 0.2 mg/mL, twice daily, for up to 4 years 5 months.

Units	Counts

Primary

Change From Baseline in BMD For Adolescents Assessed by DXA Scan at EOS (Up to Month 53)

The sites for DXA measurement were the lumbar spine at lumbar vertebrae 1 to 4 (L1-L4) and whole body. DXA scans for determination of BMD and body composition was performed in participants aged 11-17 years. Z-score indicates the number of standard deviations away from a reference population in the same age range and with the same sex. In this study, the BMD Z-score is considered abnormal when the z-score is < -2, suggesting a worse outcome (i.e., osteoporosis) and vice versa. Change from baseline in BMD for adolescents assessed by DXA Scan at EOS (up to Month 53) was reported.

Posted

Mean

Standard Deviation

Z-score

Baseline, EOS (Up to Month 53)

ID	Title	Description
OG000	BOS-BOS	Participants who were randomized to BOS and PBO in Study SHP621-301 (NCT02605837) and to BOS in Study SHP621-302 (NCT02736409), were enrolled in Study SHP621-303 to receive 10 mL of BOS at a concentration of 0.2 mg/mL, twice daily, for up to 4 years 5 months.

Units

Primary

Change From Baseline in Cortisol Level After Adrenocorticotropic Hormone (ACTH) Stimulation at Month 12

ACTH testing was a standard procedure to measure the levels of cortisol in the blood following the injection of a synthetic form of ACTH (250 microgram [mcg]). The type of synthetic and route of administration was per investigator discretion. The change from baseline in cortisol levels was calculated at Month 12 and reported in this outcome measure.

Posted

Mean

Standard Deviation

micrograms per deciliter (mcg/dL)

Baseline, Month 12

ID	Title	Description
OG000	BOS-BOS	Participants who were randomized to BOS and PBO in Study SHP621-301 (NCT02605837) and to BOS in Study SHP621-302 (NCT02736409), were enrolled in Study SHP621-303 to receive 10 mL of BOS at a concentration of 0.2 mg/mL, twice daily, for up to 4 years 5 months.
OG001	PBO-BOS	Participants who were randomized to and fully responded to BOS treatment in Study SHP621-301 (NCT02605837), were randomized to PBO in Study SHP621-302 (NCT02736409) and enrolled in Study SHP621-303 to receive 10 mL of BOS at a concentration of 0.2 mg/mL, twice daily, for up to 4 years 5 months.

Primary

Change From Baseline in Cortisol Level After ACTH Stimulation at Month 24

Posted

Mean

Standard Deviation

mcg/dL

Baseline, Month 24

ID	Title	Description
OG000	BOS-BOS	Participants who were randomized to BOS and PBO in Study SHP621-301 (NCT02605837) and to BOS in Study SHP621-302 (NCT02736409), were enrolled in Study SHP621-303 to receive 10 mL of BOS at a concentration of 0.2 mg/mL, twice daily, for up to 4 years 5 months.
OG001	PBO-BOS	Participants who were randomized to and fully responded to BOS treatment in Study SHP621-301 (NCT02605837), were randomized to PBO in Study SHP621-302 (NCT02736409) and enrolled in Study SHP621-303 to receive 10 mL of BOS at a concentration of 0.2 mg/mL, twice daily, for up to 4 years 5 months.

Primary

Change From Baseline in Cortisol Level After ACTH Stimulation at Month 36

Posted

Mean

Standard Deviation

mcg/dL

Baseline, Month 36

ID	Title	Description
OG000	BOS-BOS	Participants who were randomized to BOS and PBO in Study SHP621-301 (NCT02605837) and to BOS in Study SHP621-302 (NCT02736409), were enrolled in Study SHP621-303 to receive 10 mL of BOS at a concentration of 0.2 mg/mL, twice daily, for up to 4 years 5 months.
OG001	PBO-BOS	Participants who were randomized to and fully responded to BOS treatment in Study SHP621-301 (NCT02605837), were randomized to PBO in Study SHP621-302 (NCT02736409) and enrolled in Study SHP621-303 to receive 10 mL of BOS at a concentration of 0.2 mg/mL, twice daily, for up to 4 years 5 months.

Primary

Change From Baseline in Cortisol Level After ACTH Stimulation at Month 48

Posted

Mean

Standard Deviation

mcg/dL

Baseline, Month 48

ID	Title	Description
OG000	BOS-BOS	Participants who were randomized to BOS and PBO in Study SHP621-301 (NCT02605837) and to BOS in Study SHP621-302 (NCT02736409), were enrolled in Study SHP621-303 to receive 10 mL of BOS at a concentration of 0.2 mg/mL, twice daily, for up to 4 years 5 months.
OG001	PBO-BOS	Participants who were randomized to and fully responded to BOS treatment in Study SHP621-301 (NCT02605837), were randomized to PBO in Study SHP621-302 (NCT02736409) and enrolled in Study SHP621-303 to receive 10 mL of BOS at a concentration of 0.2 mg/mL, twice daily, for up to 4 years 5 months.

Primary

Change From Baseline in Cortisol Level After ACTH Stimulation at EOS (Up to Month 53)

Posted

Mean

Standard Deviation

mcg/dL

Baseline, EOS (Up to Month 53)

ID	Title	Description
OG000	BOS-BOS	Participants who were randomized to BOS and PBO in Study SHP621-301 (NCT02605837) and to BOS in Study SHP621-302 (NCT02736409), were enrolled in Study SHP621-303 to receive 10 mL of BOS at a concentration of 0.2 mg/mL, twice daily, for up to 4 years 5 months.
OG001	PBO-BOS	Participants who were randomized to and fully responded to BOS treatment in Study SHP621-301 (NCT02605837), were randomized to PBO in Study SHP621-302 (NCT02736409) and enrolled in Study SHP621-303 to receive 10 mL of BOS at a concentration of 0.2 mg/mL, twice daily, for up to 4 years 5 months.

Primary

Number of Participants With Clinically Significant Changes in Clinical Laboratory Assessments

Clinical laboratory parameters included hematology, chemistry, urinalysis; urine pregnancy test. Number of participants with potential clinically significant changes in laboratory parameters which were deemed clinically meaningful by the investigator were reported.

The safety set consisted of all participants who received at least 1 dose of BOS.

Posted

Count of Participants

Participants

From start of study drug administration up to EOS (Up to Month 53)

ID	Title	Description
OG000	BOS-BOS	Participants who were randomized to BOS and PBO in Study SHP621-301 (NCT02605837) and to BOS in Study SHP621-302 (NCT02736409), were enrolled in Study SHP621-303 to receive 10 mL of BOS at a concentration of 0.2 mg/mL, twice daily, for up to 4 years 5 months.
OG001	PBO-BOS	Participants who were randomized to and fully responded to BOS treatment in Study SHP621-301 (NCT02605837), were randomized to PBO in Study SHP621-302 (NCT02736409) and enrolled in Study SHP621-303 to receive 10 mL of BOS at a concentration of 0.2 mg/mL, twice daily, for up to 4 years 5 months.

Units	Counts

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Cardiogenic shock	Cardiac disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected121 at risk EG0010 events0 affected10 at risk
Myocardial infarction	Cardiac disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected121 at risk EG0010 events0 affected10 at risk
Oesophageal perforation	Gastrointestinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected121 at risk EG0010 events0 affected10 at risk
Anaphylactic reaction	Immune system disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected121 at risk EG0010 events0 affected10 at risk
Appendicitis	Infections and infestations	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected121 at risk EG0010 events0 affected10 at risk
Overdose	Injury, poisoning and procedural complications	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected121 at risk EG0010 events0 affected10 at risk
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected121 at risk EG0010 events0 affected10 at risk
Obesity	Metabolism and nutrition disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected121 at risk EG0010 events0 affected10 at risk
Rhabdomyolysis	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected121 at risk EG0010 events0 affected10 at risk
Petit mal epilepsy	Nervous system disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected121 at risk EG0010 events0 affected10 at risk
Abortion spontaneous	Pregnancy, puerperium and perinatal conditions	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected121 at risk EG0010 events0 affected10 at risk
Completed suicide	Psychiatric disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected121 at risk EG0010 events0 affected10 at risk
Depression	Psychiatric disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected121 at risk EG0010 events0 affected10 at risk
Pneumomediastinum	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected121 at risk EG0010 events0 affected10 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Mitral valve incompetence	Cardiac disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected121 at risk EG0011 events1 affected10 at risk
Tricuspid valve incompetence	Cardiac disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected121 at risk EG0011 events1 affected10 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0008 events8 affected121 at risk EG0010 events0 affected10 at risk
Nausea	Gastrointestinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0005 events4 affected121 at risk EG0011 events1 affected10 at risk
Oesophageal food impaction	Gastrointestinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0009 events5 affected121 at risk EG0011 events1 affected10 at risk
Oesophageal stenosis	Gastrointestinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0004 events2 affected121 at risk EG0011 events1 affected10 at risk
Fatigue	General disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected121 at risk EG0011 events1 affected10 at risk
Drug hypersensitivity	Immune system disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected121 at risk EG0011 events1 affected10 at risk
Seasonal allergy	Immune system disorders	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected121 at risk EG0011 events1 affected10 at risk
Bronchitis	Infections and infestations	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected121 at risk EG0011 events1 affected10 at risk
Cellulitis	Infections and infestations	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected121 at risk EG0011 events1 affected10 at risk
Corona virus infection	Infections and infestations	MedDRA 18.0	Non-systematic Assessment	EG00010 events10 affected121 at risk EG0011 events1 affected10 at risk
Diverticulitis	Infections and infestations	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected121 at risk EG0011 events1 affected10 at risk
Herpes zoster	Infections and infestations	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected121 at risk EG0011 events1 affected10 at risk
Influenza	Infections and infestations	MedDRA 18.0	Non-systematic Assessment	EG0007 events7 affected121 at risk EG0010 events0 affected10 at risk
Nasopharyngitis	Infections and infestations	MedDRA 18.0	Non-systematic Assessment	EG0009 events8 affected121 at risk EG0010 events0 affected10 at risk
Oesophageal candidiasis	Infections and infestations	MedDRA 18.0	Non-systematic Assessment	EG0005 events4 affected121 at risk EG0011 events1 affected10 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 18.0	Non-systematic Assessment	EG00011 events10 affected121 at risk EG0011 events1 affected10 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDRA 18.0	Non-systematic Assessment	EG0002 events2 affected121 at risk EG0011 events1 affected10 at risk
Hand fracture	Injury, poisoning and procedural complications	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected121 at risk EG0011 events1 affected10 at risk
Radius fracture	Injury, poisoning and procedural complications	MedDRA 18.0	Non-systematic Assessment	EG0000 events0 affected121 at risk EG0011 events1 affected10 at risk
ACTH stimulation test abnormal	Investigations	MedDRA 18.0	Non-systematic Assessment	EG00016 events14 affected121 at risk EG0010 events0 affected10 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected121 at risk EG0011 events1 affected10 at risk
Dizziness	Nervous system disorders	MedDRA 18.0	Non-systematic Assessment	EG0002 events1 affected121 at risk EG0011 events1 affected10 at risk
Anxiety	Psychiatric disorders	MedDRA 18.0	Non-systematic Assessment	EG0003 events3 affected121 at risk EG0011 events1 affected10 at risk
Depression	Psychiatric disorders	MedDRA 18.0	Non-systematic Assessment	EG00012 events10 affected121 at risk EG0011 events1 affected10 at risk
Insomnia	Psychiatric disorders	MedDRA 18.0	Non-systematic Assessment	EG0003 events3 affected121 at risk EG0011 events1 affected10 at risk
Obsessive-compulsive disorder	Psychiatric disorders	MedDRA 18.0	Non-systematic Assessment	EG0001 events1 affected121 at risk EG0011 events1 affected10 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 18.0	Non-systematic Assessment	EG0004 events3 affected121 at risk EG0011 events1 affected10 at risk
Hypertension	Vascular disorders	MedDRA 18.0	Non-systematic Assessment	EG0007 events7 affected121 at risk EG0011 events1 affected10 at risk

ID	Term
D004941	Esophagitis
D004935	Esophageal Diseases
D005767	Gastrointestinal Diseases
D004066	Digestive System Diseases
D005759	Gastroenteritis
D004802	Eosinophilia
D007960	Leukocyte Disorders
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D006969	Hypersensitivity, Immediate
D006967	Hypersensitivity
D007154	Immune System Diseases

ID	Title	Description
BG000	BOS-BOS	Participants who were randomized to BOS and PBO in Study SHP621-301 (NCT02605837) and to BOS in Study SHP621-302 (NCT02736409), were enrolled in Study SHP621-303 to receive 10 mL of BOS at a concentration of 0.2 mg/mL, twice daily, for up to 4 years 5 months.
BG001	PBO-BOS	Participants who were randomized to and fully responded to BOS treatment in Study SHP621-301 (NCT02605837), were randomized to PBO in Study SHP621-302 (NCT02736409) and enrolled in Study SHP621-303 to receive 10 mL of BOS at a concentration of 0.2 mg/mL, twice daily, for up to 4 years 5 months.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	BOS-BOS	Participants who were randomized to BOS and PBO in Study SHP621-301 (NCT02605837) and to BOS in Study SHP621-302 (NCT02736409), were enrolled in Study SHP621-303 to receive 10 mL of BOS at a concentration of 0.2 mg/mL, twice daily, for up to 4 years 5 months.	2	121	11	121	90	121
EG001	PBO-BOS	Participants who were randomized to and fully responded to BOS treatment in Study SHP621-301 (NCT02605837), were randomized to PBO in Study SHP621-302 (NCT02736409) and enrolled in Study SHP621-303 to receive 10 mL of BOS at a concentration of 0.2 mg/mL, twice daily, for up to 4 years 5 months.	0	10	0	10	7	10