An Effectiveness and Safety Study of Intravenous Golimuma... | NCT00973479

NCT00973479

ID	Type	Description	Link
CNTO148ART3001	Other Identifier	Centocor, Inc
2008-006064-11	EudraCT Number

Status Module

Name	Class
Schering-Plough	INDUSTRY

Oversight Module

Description Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Group I: Placebo + Methotrexate (MTX)	Experimental	Participants will receive placebo at Weeks 0, 4, 12, and 16. Participants will cross over to golimumab at Week 24, and receive administrations at Weeks 24, 28, and every 8 weeks thereafter. They will be maintained on their stable dose of commercial methotrexate throughout the study. Participants will be eligible for early escape (receive golimumab) at Week 16 if they demonstrate a less than 10 percent improvement in both tender and swollen joint count. These participants will receive golimumab at Weeks 16, 20, and every 8 weeks thereafter.	Drug: Golimumab Other: Placebo Drug: methotrexate (MTX)
Group II: Golimumab + Methotrexate (MTX)	Placebo Comparator	Participants will receive golimumab at Weeks 0, 4, and every 8 weeks thereafter. They will be maintained on their stable dose of commercial methotrexate throughout the study. Participants will receive a placebo infusion at Week 16 and Week 24 to maintain the blind.	Drug: Golimumab Other: Placebo Drug: methotrexate (MTX)

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Golimumab	Drug	Participants will receive 2 mg/kg of golimumab intravenously over 30 ± 10 minutes. Group 1: at Weeks 0, 4, and every 8 weeks thereafter (up to Week 100). Group II: Weeks 24, 28, and every 8 weeks thereafter (up to Week 100); Early escape: at Week 16, 20 and every 8 weeks thereafter (up to Week 100).

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Proportion of Participants With an American College of Rheumatology (ACR) 20 Response at Week 14	An ACR 20 response is defined as a greater than or equal to 20 percent improvement from baseline in: 1. Swollen (66 joints) and tender (68 joints) joint counts; 2. greater than or equal to 20 percentage improvement in at least 3 of the following 5 assessments: a. Participant's assessment of pain by Visual Analog Scale (VAS), (0 [no pain] to 10 [worst pain]) b. Participant's global assessment of disease activity by VAS c. Physician's global assessment of disease activity by VAS d. Participant's assessment of physical function as measured by the Health Assessment Questionnaire (HAQ) e. C-reactive protein.	Week 14

Secondary Outcomes

Measure	Description	Time Frame
Proportion of Participants With Moderate or Good Response in Disease Activity Index Score 28 (DAS28) Using C-reactive Protein (CRP) at Week 14	DAS28 using CRP is an index to measure the disease activity in participants with rheumatoid arthritis combining tender joints (28 joints), swollen joints (28 joints), CRP, and participant's global assessment of disease activity. The DAS28 score ranges from 0 (best) to 10 (worst). DAS28 score above 5.1 means high disease activity whereas a DAS28 below 3.2 indicates low disease activity. Higher scores indicate worsening. A decrease in DAS28 score >1.2 is being referred to as a "good response" and a decrease of 0.6-1.2 as a "moderate response".

Eligibility Module

Name	Affiliation	Role
Centocor, Inc. Clinical Trial	Centocor, Inc.	Study Director

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
35313978	Derived	Husni ME, Deodhar A, Schwartzman S, Chakravarty SD, Hsia EC, Leu JH, Zhou Y, Lo KH, Kavanaugh A. Pooled safety results across phase 3 randomized trials of intravenous golimumab in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. Arthritis Res Ther. 2022 Mar 21;24(1):73. doi: 10.1186/s13075-022-02753-6.
35183373

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Group I: Placebo + Methotrexate (MTX)	Participants randomized to receive their stable dose of commercial MTX (between 15-25 mg/week) and placebo IV infusions at Weeks 0, 4, 12, 16, and 20. Participants will be crossed over to Golimumab 2 mg/kg at Week 24, and receive administrations at Weeks 24, 28 and q8 weeks thereafter up to Week 100. Subjects randomized to Group I (Placebo + MTX) will have the opportunity to enter early escape at Week 16 and initiate Golimumab 2 mg/kg infusions (Weeks 16, 20, and q8 weeks up to Week 100) if they demonstrate a < 10% improvement in both tender and swollen joint count.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Group I: Placebo + Methotrexate (MTX)	Participants randomized to receive their stable dose of commercial MTX (between 15-25 mg/week) and placebo IV infusions at Weeks 0, 4, 12, 16, and 20. Participants will be crossed over to Golimumab 2 mg/kg at Week 24, and receive administrations at Weeks 24, 28 and q8 weeks thereafter up to Week 100. Subjects randomized to Group I (Placebo + MTX) will have the opportunity to enter early escape at Week 16 and initiate Golimumab 2 mg/kg infusions (Weeks 16, 20, and q8 weeks up to Week 100) if they demonstrate a < 10% improvement in both tender and swollen joint count.
BG001	Group II: Golimumab 2 mg/kg + Methotrexate (MTX)	Participants randomized to receive 2 mg/kg of Golimumab intravenously at Weeks 0, 4, and q8 weeks up to Week 100. Participants will be maintained on their stable dose of commercial MTX (between 15 and 25 mg/week) throughout the study. Participants will receive a placebo infusion at Week 16 and Week 24 to maintain the blind.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00051.4± 11.26 BG00151.9± 12.55 BG00251.8± 12.13

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000157 BG001326 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

Argentina

Title	Measurements
	BG00028 BG00154 BG002

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

Proportion of Participants With an American College of Rheumatology (ACR) 20 Response at Week 14

An ACR 20 response is defined as a greater than or equal to 20 percent improvement from baseline in: 1. Swollen (66 joints) and tender (68 joints) joint counts; 2. greater than or equal to 20 percentage improvement in at least 3 of the following 5 assessments: a. Participant's assessment of pain by Visual Analog Scale (VAS), (0 [no pain] to 10 [worst pain]) b. Participant's global assessment of disease activity by VAS c. Physician's global assessment of disease activity by VAS d. Participant's assessment of physical function as measured by the Health Assessment Questionnaire (HAQ) e. C-reactive protein.

Intent-to-treat: all patients analyzed according to the treatment for which they were randomized.

Posted

Number

Percentage of Participants

Week 14

ID	Title	Description
OG000	Group I: Placebo + Methotrexate (MTX)	Participants randomized to receive their stable dose of commercial MTX (between 15-25 mg/week) and placebo IV infusions at Weeks 0, 4, 12, 16, and 20. Participants will be crossed over to Golimumab 2 mg/kg at Week 24, and receive administrations at Weeks 24, 28 and q8 weeks thereafter up to Week 100. Subjects randomized to Group I (Placebo + MTX) will have the opportunity to enter early escape at Week 16 and initiate Golimumab 2 mg/kg infusions (Weeks 16, 20, and q8 weeks up to Week 100) if they demonstrate a < 10% improvement in both tender and swollen joint count.
OG001	Group II: Golimumab 2 mg/kg + Methotrexate (MTX)	Participants randomized to receive 2 mg/kg of Golimumab intravenously at Weeks 0, 4, and q8 weeks up to Week 100. Participants will be maintained on their stable dose of commercial MTX (between 15 and 25 mg/week) throughout the study. Participants will receive a placebo infusion at Week 16 and Week 24 to maintain the blind.

Units	Counts
Participants	OG000197 OG001395

Title

Denominators

Categories

Title	Measurements
	OG00024.9 OG00158.5

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Cochran-Mantel-Haenszel		<0.001													No	Superiority or Other

Secondary

Proportion of Participants With Moderate or Good Response in Disease Activity Index Score 28 (DAS28) Using C-reactive Protein (CRP) at Week 14

DAS28 using CRP is an index to measure the disease activity in participants with rheumatoid arthritis combining tender joints (28 joints), swollen joints (28 joints), CRP, and participant's global assessment of disease activity. The DAS28 score ranges from 0 (best) to 10 (worst). DAS28 score above 5.1 means high disease activity whereas a DAS28 below 3.2 indicates low disease activity. Higher scores indicate worsening. A decrease in DAS28 score >1.2 is being referred to as a "good response" and a decrease of 0.6-1.2 as a "moderate response".

Intent-to-treat: all patients analyzed according to the treatment for which they were randomized.

Posted

Number

Percentage of Participants

Week 14

ID	Title	Description
OG000	Group I: Placebo + Methotrexate (MTX)	Participants randomized to receive their stable dose of commercial MTX (between 15-25 mg/week) and placebo IV infusions at Weeks 0, 4, 12, 16, and 20. Participants will be crossed over to Golimumab 2 mg/kg at Week 24, and receive administrations at Weeks 24, 28 and q8 weeks thereafter up to Week 100. Subjects randomized to Group I (Placebo + MTX) will have the opportunity to enter early escape at Week 16 and initiate Golimumab 2 mg/kg infusions (Weeks 16, 20, and q8 weeks up to Week 100) if they demonstrate a < 10% improvement in both tender and swollen joint count.
OG001	Group II: Golimumab 2 mg/kg + Methotrexate (MTX)

Secondary

Change From Baseline in Health Assessment Questionnaire (HAQ) Score at Week 14

The HAQ is 20-question instrument that assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0 (no difficulty), to 3 (inability to perform a task in that area). HAQscore on a scale ranges from 0 (no disability) to 3 (completely disabled). Higher scores indicate worsening.

Intent-to-treat: all patients analyzed according to the treatment for which they were randomized.

Posted

Mean

Standard Deviation

Scores on a scale

Week 14

ID	Title	Description
OG000	Group I: Placebo + Methotrexate (MTX)	Participants randomized to receive their stable dose of commercial MTX (between 15-25 mg/week) and placebo IV infusions at Weeks 0, 4, 12, 16, and 20. Participants will be crossed over to Golimumab 2 mg/kg at Week 24, and receive administrations at Weeks 24, 28 and q8 weeks thereafter up to Week 100. Subjects randomized to Group I (Placebo + MTX) will have the opportunity to enter early escape at Week 16 and initiate Golimumab 2 mg/kg infusions (Weeks 16, 20, and q8 weeks up to Week 100) if they demonstrate a < 10% improvement in both tender and swollen joint count.
OG001	Group II: Golimumab 2 mg/kg + Methotrexate (MTX)	Participants randomized to receive 2 mg/kg of Golimumab intravenously at Weeks 0, 4, and q8 weeks up to Week 100. Participants will be maintained on their stable dose of commercial MTX (between 15 and 25 mg/week) throughout the study. Participants will receive a placebo infusion at Week 16 and Week 24 to maintain the blind.

Secondary

Proportion of Participants Who Achieved American College of Rheumatology (ACR) 50 Response at Week 24

An ACR 50 response is defined as a greater than or equal to 50 percent improvement from baseline in: 1. Swollen (66 joints) and tender (68 joints) joint counts; 2. greater than or equal to 50 percentage improvement in 3 of the following 5 assessments: a. Participant's assessment of pain by Visual Analog Scale (VAS) (0-10 cm) b. Participant's global assessment of disease activity by VAS (0-10 cm) c. Physician's global assessment of disease activity by VAS (0-10 cm) d. Participant's assessment of physical function as measured by the Health Assessment Questionnaire (HAQ) e. C reactive protein.

Intent-to-treat: all patients analyzed according to the treatment for which they were randomized.

Posted

Number

Percentage of Participants

Week 24

ID	Title	Description
OG000	Group I: Placebo + Methotrexate (MTX)	Participants randomized to receive their stable dose of commercial MTX (between 15-25 mg/week) and placebo IV infusions at Weeks 0, 4, 12, 16, and 20. Participants will be crossed over to Golimumab 2 mg/kg at Week 24, and receive administrations at Weeks 24, 28 and q8 weeks thereafter up to Week 100. Subjects randomized to Group I (Placebo + MTX) will have the opportunity to enter early escape at Week 16 and initiate Golimumab 2 mg/kg infusions (Weeks 16, 20, and q8 weeks up to Week 100) if they demonstrate a < 10% improvement in both tender and swollen joint count.
OG001	Group II: Golimumab 2 mg/kg + Methotrexate (MTX)

Secondary

Change From Baseline in Total Van Der Heijde Modified Sharp (vdH-S) Score at Week 24.

Total vdH-S score is sum of joint erosion score and joint-space narrowing (JSN) score. Joint erosion score summarizes erosion severity in 32 joints of hands and 12 joints of feet. Each joint scored from 0 (no erosion) to 5 (extensive loss of bone from more than one half of the articulating bone). Maximal erosion score is 280. JSN score summarizes severity of JSN in 30 joints of hands and 12 joints of feet. Assessment of JSN, including subluxation, is scored from 0 (normal) to 4 (bony ankylosis or complete luxation). Maximal JSN score is 168. Thus, the worst possible vdH-S score is 448.

Intent-to-treat: all patients analyzed according to the treatment for which they were randomized.

Posted

Mean

Standard Deviation

Scores on a scale

Week 24

ID	Title	Description
OG000	Group I: Placebo + Methotrexate (MTX)	Participants randomized to receive their stable dose of commercial MTX (between 15-25 mg/week) and placebo IV infusions at Weeks 0, 4, 12, 16, and 20. Participants will be crossed over to Golimumab 2 mg/kg at Week 24, and receive administrations at Weeks 24, 28 and q8 weeks thereafter up to Week 100. Subjects randomized to Group I (Placebo + MTX) will have the opportunity to enter early escape at Week 16 and initiate Golimumab 2 mg/kg infusions (Weeks 16, 20, and q8 weeks up to Week 100) if they demonstrate a < 10% improvement in both tender and swollen joint count.
OG001	Group II: Golimumab 2 mg/kg + Methotrexate (MTX)

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo + MTX -> Golimumab 2 mg/kg + MTX at Week 16	Participants received placebo only through Week 16 and met early escape criteria or subjects who received first placebo and later inadvertently received Golimumab prior or at Week 16. The follow-up period for this treatment group begins once a participant switches to Golimumab 2 mg/kg. Participants may have missed one or more study agent doses.	11	68	34	68
EG001	Placebo + MTX -> Golimumab 2 mg/kg + MTX at Week 24	Participants received placebo only through Week 24 or subjects who received first placebo and later inadvertently received Golimumab after Week 16 through Week 24. The follow-up period for this treatment group begins once a participants switches to Golimumab 2 mg/kg. Participants may have missed one or more study agent doses.	17	121	38	121
EG002	Golimumab 2 mg/kg + MTX	Participants were assigned to Golimumab 2 mg/kg + MTX and received at least one 2 mg/kg Golimumab. The follow-up period for this treatment group begins with the first dose of Golimumab 2 mg/kg. Participants may have missed one or more Golimumab doses.	78	395	199	395
EG003	Combined Golimumab	Participants in the reporting groups: Placebo + MTX -> Golimumab 2 mg/kg + MTX at Week 16, Placebo + MTX -> Golimumab 2 mg/kg + MTX at Week 24, and Golimumab 2 mg/kg + MTX.	106	584	271	584

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG0031 affected584 at risk
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Acute coronary syndrome	Cardiac disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Acute myocardial infarction	Cardiac disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0011 affected121 at risk EG0020 affected395 at risk EG003
Angina pectoris	Cardiac disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Angina unstable	Cardiac disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0011 affected121 at risk EG0020 affected395 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Cor pulmonale chronic	Cardiac disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Myocardial infarction	Cardiac disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Myocardial ischaemia	Cardiac disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0011 affected121 at risk EG0022 affected395 at risk EG003
Sick sinus syndrome	Cardiac disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected68 at risk EG0010 affected121 at risk EG0020 affected395 at risk EG003
Vertigo	Ear and labyrinth disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Hyperthyroidism	Endocrine disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0011 affected121 at risk EG0020 affected395 at risk EG003
Cataract	Eye disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0023 affected395 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Acute abdomen	Gastrointestinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Diverticulum intestinal	Gastrointestinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Duodenogastric reflux	Gastrointestinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Gastric disorder	Gastrointestinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Haemorrhoids	Gastrointestinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Hiatus hernia	Gastrointestinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Pancreatitis acute	Gastrointestinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Pancreatitis chronic	Gastrointestinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Cyst	General disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Pyrexia	General disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Sudden death	General disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0011 affected121 at risk EG0020 affected395 at risk EG003
Bile duct stone	Hepatobiliary disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0011 affected121 at risk EG0020 affected395 at risk EG003
Cholecystitis	Hepatobiliary disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Cholecystitis acute	Hepatobiliary disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0011 affected121 at risk EG0020 affected395 at risk EG003
Cholelithiasis	Hepatobiliary disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0011 affected121 at risk EG0020 affected395 at risk EG003
Hepatitis toxic	Hepatobiliary disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Jaundice	Hepatobiliary disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0011 affected121 at risk EG0020 affected395 at risk EG003
Appendicitis	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Arthritis bacterial	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Bacteraemia	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Bronchitis	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Cellulitis	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Device related infection	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0001 affected68 at risk EG0010 affected121 at risk EG0020 affected395 at risk EG003
Empyema	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Endophthalmitis	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0001 affected68 at risk EG0010 affected121 at risk EG0020 affected395 at risk EG003
Erysipelas	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0022 affected395 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Infective spondylitis	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Intervertebral discitis	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Lobar pneumonia	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Lung abscess	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Pelvic inflammatory disease	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0011 affected121 at risk EG0020 affected395 at risk EG003
Pharyngitis	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Pneumonia	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0001 affected68 at risk EG0010 affected121 at risk EG0024 affected395 at risk EG003
Pneumonia cryptococcal	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0011 affected121 at risk EG0020 affected395 at risk EG003
Rectal abscess	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Sepsis	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Sepsis syndrome	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Septic shock	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Tuberculosis	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0011 affected121 at risk EG0020 affected395 at risk EG003
Tuberculous pleurisy	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0011 affected121 at risk EG0020 affected395 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0011 affected121 at risk EG0023 affected395 at risk EG003
Urosepsis	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Vestibular neuronitis	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Ankle fracture	Injury, poisoning and procedural complications	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Concussion	Injury, poisoning and procedural complications	MedDRA Version 15.1	Systematic Assessment	EG0001 affected68 at risk EG0010 affected121 at risk EG0020 affected395 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA Version 15.1	Systematic Assessment	EG0001 affected68 at risk EG0010 affected121 at risk EG0020 affected395 at risk EG003
Dislocation of vertebra	Injury, poisoning and procedural complications	MedDRA Version 15.1	Systematic Assessment	EG0001 affected68 at risk EG0010 affected121 at risk EG0020 affected395 at risk EG003
Femoral neck fracture	Injury, poisoning and procedural complications	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0011 affected121 at risk EG0020 affected395 at risk EG003
Femur fracture	Injury, poisoning and procedural complications	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Hand fracture	Injury, poisoning and procedural complications	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Head injury	Injury, poisoning and procedural complications	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Humerus fracture	Injury, poisoning and procedural complications	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Laceration	Injury, poisoning and procedural complications	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Meniscus lesion	Injury, poisoning and procedural complications	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Rib fracture	Injury, poisoning and procedural complications	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Road traffic accident	Injury, poisoning and procedural complications	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0011 affected121 at risk EG0020 affected395 at risk EG003
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Upper limb fracture	Injury, poisoning and procedural complications	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0011 affected121 at risk EG0020 affected395 at risk EG003
Electrolyte imbalance	Metabolism and nutrition disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0011 affected121 at risk EG0020 affected395 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Foot deformity	Musculoskeletal and connective tissue disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0011 affected121 at risk EG0021 affected395 at risk EG003
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected68 at risk EG0010 affected121 at risk EG0022 affected395 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA Version 15.1	Systematic Assessment	EG0001 affected68 at risk EG0011 affected121 at risk EG0021 affected395 at risk EG003
Osteonecrosis	Musculoskeletal and connective tissue disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Rheumatoid arthritis	Musculoskeletal and connective tissue disorders	MedDRA Version 15.1	Systematic Assessment	EG0002 affected68 at risk EG0010 affected121 at risk EG00210 affected395 at risk EG003
Synovitis	Musculoskeletal and connective tissue disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Bowen's disease	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Cervix carcinoma stage 0	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Chronic lymphocytic leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Fibroadenoma of breast	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Lung neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Salivary gland adenoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Thyroid neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0011 affected121 at risk EG0020 affected395 at risk EG003
Carotid artery stenosis	Nervous system disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0011 affected121 at risk EG0020 affected395 at risk EG003
Cerebral infarction	Nervous system disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Cerebral ischaemia	Nervous system disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0011 affected121 at risk EG0021 affected395 at risk EG003
Iiird nerve paresis	Nervous system disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Ischaemic stroke	Nervous system disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0022 affected395 at risk EG003
Lacunar infarction	Nervous system disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Radiculopathy	Nervous system disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Subarachnoid haemorrhage	Nervous system disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Syncope	Nervous system disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Calculus ureteric	Renal and urinary disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Nephrolithiasis	Renal and urinary disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Nephropathy	Renal and urinary disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Renal colic	Renal and urinary disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Bartholinitis	Reproductive system and breast disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Breast disorder	Reproductive system and breast disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Metrorrhagia	Reproductive system and breast disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Uterine prolapse	Reproductive system and breast disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Acute pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0022 affected395 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Pleurisy	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Arterial rupture	Vascular disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0011 affected121 at risk EG0020 affected395 at risk EG003
Deep vein thrombosis	Vascular disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Hypotension	Vascular disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003
Peripheral vascular disorder	Vascular disorders	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0010 affected121 at risk EG0021 affected395 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Bronchitis	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0006 affected68 at risk EG0019 affected121 at risk EG00237 affected395 at risk EG00352 affected584 at risk
Nasopharyngitis	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0003 affected68 at risk EG0018 affected121 at risk EG00228 affected395 at risk EG003
Pharyngitis	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0000 affected68 at risk EG0017 affected121 at risk EG00226 affected395 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0005 affected68 at risk EG0018 affected121 at risk EG00254 affected395 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA Version 15.1	Systematic Assessment	EG0003 affected68 at risk EG0017 affected121 at risk EG00226 affected395 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA Version 15.1	Systematic Assessment	EG0008 affected68 at risk EG0013 affected121 at risk EG00227 affected395 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA Version 15.1	Systematic Assessment	EG0005 affected68 at risk EG0012 affected121 at risk EG00218 affected395 at risk EG003
Hepatic enzyme increased	Investigations	MedDRA Version 15.1	Systematic Assessment	EG0004 affected68 at risk EG0010 affected121 at risk EG0026 affected395 at risk EG003
Rheumatoid arthritis	Musculoskeletal and connective tissue disorders	MedDRA Version 15.1	Systematic Assessment	EG0009 affected68 at risk EG0013 affected121 at risk EG00233 affected395 at risk EG003
Headache	Nervous system disorders	MedDRA Version 15.1	Systematic Assessment	EG0005 affected68 at risk EG0012 affected121 at risk EG00227 affected395 at risk EG003
Hypertension	Vascular disorders	MedDRA Version 15.1	Systematic Assessment	EG0008 affected68 at risk EG0014 affected121 at risk EG00227 affected395 at risk EG003

Facility	Status	City	State	ZIP	Country	Contacts
		Daytona Beach	Florida		United States

ID	Term
D001168	Arthritis
D007592	Joint Diseases
D009140	Musculoskeletal Diseases
D012216	Rheumatic Diseases
D003240	Connective Tissue Diseases
D017437	Skin and Connective Tissue Diseases
D001327	Autoimmune Diseases
D007154	Immune System Diseases

ID	Term
D000630	Aminopterin
D011622	Pterins
D011621	Pteridines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds