An Effectiveness and Safety Study of Intravenous Golimumab in Patients With Active Rheumatoid Arthritis Despite Treatment With Methotrexate Therapy

• Sponsor: Centocor, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00973479
• Collaborator: Schering-Plough (Industry)
• Enrollment: 592
• Locations: 91
• Arms: 2
• Duration (Months): 41
• Patients Per Site: 6.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate clinical effectiveness and safety of golimumab with methotrexate (MTX) in the treatment of rheumatoid arthritis (RA) when compared to MTX alone.

Condition or Disease	Intervention/Treatment	Phase
Arthritis, Rheumatoid	Drug: Golimumab; Other: Placebo; Drug: methotrexate (MTX)	Phase 3

Detailed Description

This is a randomized (study medication is assigned by chance), double-blind (neither physician nor participants knows the treatment that the participant receives), placebo-controlled (an inactive substance is compared with a medication to test whether the medication has a real effect in a clinical study), multicenter, 2-arm (2 groups) study of golimumab in participants with active RA despite concurrent MTX therapy. Approximately 564 participants will be randomly allocated to 1 of 2 treatment groups in a 2:1 ratio ie, Group 1(approximately 376 participants will receive golimumab + MTX) and Group 2 (approximately 188 participants will receive MTX + placebo). Total duration of study for each participant is 112 weeks. Safety will be evaluated by assessment of adverse events, tuberculosis testing and blood testing.

Study Design

• Study Type: Interventional
• Actual Enrollment: 592 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-blind, Placebo-controlled Trial of Golimumab, an Anti-TNFalpha Monoclonal Antibody, Administered Intravenously, in Patients With Active Rheumatoid Arthritis Despite Methotrexate Therapy
• Study Start Date: Sep 1, 2009
• Actual Primary Completion Date: Mar 1, 2011
• Actual Study Completion Date: Feb 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group I: Placebo + Methotrexate (MTX) 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; 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).; Other: Placebo; Participants will receive placebo intravenous infusion over 30 ± 10 minutes as: Group I: at Week 16 and 24; Group II: at Weeks 0, 4, 12, 16, and 20; and for early escape: at Week 24.; Drug: methotrexate (MTX); Participants will be maintained on their stable dose of commercial MTX (between 15 to 25 mg/week) throughout the study.
Placebo Comparator: Group II: Golimumab + Methotrexate (MTX) 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; 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).; Other: Placebo; Participants will receive placebo intravenous infusion over 30 ± 10 minutes as: Group I: at Week 16 and 24; Group II: at Weeks 0, 4, 12, 16, and 20; and for early escape: at Week 24.; Drug: methotrexate (MTX); Participants will be maintained on their stable dose of commercial MTX (between 15 to 25 mg/week) throughout the study.

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

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

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

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of rheumatoid arthritis (RA) for at least 3 months prior to screening

• Have been treated with and tolerated methotrexate (MTX) at a dose of at least 15 mg/week for at least 3 months prior to screening, and have been on a stable MTX dose of 15 mg/week to 25 mg/week for at least 4 weeks prior to screening

• Have an active RA, as defined by disease activity with at least 6 swollen and 6 tender joints, at the time of screening and at baseline

• C-Reactive Protein greater than or equal to 1.0 mg/dL at screening

• No history of latent or active tuberculosis prior to screening

Exclusion Criteria:

• Other inflammatory diseases, including but not limited to psoriatic arthritis, ankylosing spondylitis, systemic lupus erythematosus, or lyme disease

• Treated with disease modifying agents (other than methotrexate)/systemic immunosuppressives (eg, D-penicillamine, hydroxychloroquine, chloroquine, oral or parenteral gold, sulfasalazine, leflunomide, azathioprine, cyclosporine, mycophenolate mofetil) during the 4 weeks prior to first administration of study agent

• Received intra-articular (in the joint), intramuscular (in the muscle), or intravenous corticosteroids, including adrenocorticotropic hormone, during the 4 weeks prior to first administration of study agent

• Known allergy to human immunoglobulin proteins or other components of golimumab

• Received any commercial or investigational anti-tumor necrosis factor alpha therapy such as but not exclusively infliximab, golimumab, adalimumab or etanercept

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Daytona Beach	Florida	United States
2		Miami	Florida	United States
3		Palm Harbor	Florida	United States
4		Moline	Illinois	United States
5		Wheaton	Maryland	United States
6		Worcester	Massachusetts	United States
7		Lincoln	Nebraska	United States
8		Cincinnati	Ohio	United States
9		Lubbock	Texas	United States
10		Buenos Aires N/A		Argentina
11		Buenos Aires		Argentina
12		Cordoba		Argentina
13		Rosario		Argentina
14		San Juan		Argentina
15		San Miguel De Tucuman		Argentina
16		Santa Fe		Argentina
17		Cairns		Australia
18		Maroochydore		Australia
19		Melbourne		Australia
20		Woodville		Australia
21		Woolloongabba		Australia
22		Antioquia		Colombia
23		Barranquilla		Colombia
24		Bogota		Colombia
25		Cali Valley Del Cauca		Colombia
26		Medellin		Colombia
27		Budapest		Hungary
28		Debrecen		Hungary
29		Eger		Hungary
30		Gyor		Hungary
31		Gyula		Hungary
32		Szombathely		Hungary
33		Veszprem		Hungary
34		Anyang		Korea, Republic of
35		Dae-Gu		Korea, Republic of
36		Daejeon		Korea, Republic of
37		Incheon		Korea, Republic of
38		Pusan		Korea, Republic of
39		Seoul		Korea, Republic of
40		Alytus		Lithuania
41		Kaunas		Lithuania
42		Klaipeda		Lithuania
43		Siauliai		Lithuania
44		Vilnius		Lithuania
45		Georgetown		Malaysia
46		Ipoh		Malaysia
47		Johor Bahru		Malaysia
48		Kota Kinabalu		Malaysia
49		Kuantan		Malaysia
50		Kuching		Malaysia
51		Precinct 7		Malaysia
52		Selangor Darul Ehasan		Malaysia
53		Seremban		Malaysia
54		Guadalajara		Mexico
55		Leon		Mexico
56		Mexico		Mexico
57		Mex		Mexico
58		Monterrey		Mexico
59		Auckland		New Zealand
60		Takapuna Auckland		New Zealand
61		Timaru		New Zealand
62		Bialystok		Poland
63		Bydgoszcz		Poland
64		Dzialdowo		Poland
65		Elblag		Poland
66		Katowice		Poland
67		Lublin		Poland
68		Poznan		Poland
69		Sopot		Poland
70		Szczecin		Poland
71		Warszawa		Poland
72		Wloszczowa		Poland
73		Wrocław		Poland
74		Chelyabinsk		Russian Federation
75		Ekaterinburg		Russian Federation
76		Krasnoyarsk		Russian Federation
77		Moscow N/A		Russian Federation
78		Moscow		Russian Federation
79		Petrozavodsk		Russian Federation
80		Saint Petersburg		Russian Federation
81		Saratov		Russian Federation
82		St.Petersburg		Russian Federation
83		Donetsk		Ukraine
84		Ivano-Frankovsk		Ukraine
85		Kharkiv		Ukraine
86		Kyiv		Ukraine
87		Odessa		Ukraine
88		Simferopol		Ukraine
89		Ternopil		Ukraine
90		Vinnitsa		Ukraine
91		Zaporizhzhya		Ukraine

Sponsors and Collaborators

• Centocor, Inc.
• Schering-Plough

Investigators

• Study Director: Centocor, Inc. Clinical Trial, Centocor, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Centocor, Inc.
• ClinicalTrials.gov Identifier: NCT00973479
• Other Study ID Numbers: CR015784; CNTO148ART3001; 2008-006064-11
• First Posted: Sep 9, 2009
• Last Update Posted: Dec 25, 2013
• Last Verified: Nov 1, 2013

• Keywords provided by Centocor, Inc.: Arthritis, Rheumatoid; Active rheumatoid arthritis; Golimumab; CNTO148; Anti-TNFalpha monoclonal antibody; Methotrexate; Intravenous
• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid; Golimumab; Methotrexate

Study Results

Participant Flow

Recruitment Details	This study evaluated the efficacy and safety of intravenous administration of Golimumab 2mg/kg + methotrexate (MTX) in patients with Active Rheumatoid Arthritis despite treatment with MTX therapy. It was conducted between 14 September 2009 and 08 February 2013 and recruited participants at 92 sites in 13 countries worldwide.
Pre-assignment Detail	592 participants were randomly allocated to 2 treatment arms. At Week 16 some participants in Placebo arm switched to Golimumab earlier than the rest at Week 24. Thus, the Adverse Events are presented based upon the time when participants began to receive Golimumab in the following manner: Golimumab from Day 0, from Week 16 and from Week 24.

Arm/Group Title	Group I: Placebo + Methotrexate (MTX)	Group II: Golimumab 2 mg/kg + Methotrexate (MTX)
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	197	395
COMPLETED	160	326
NOT COMPLETED	37	69

Baseline Characteristics

Arm/Group Title	Group I: Placebo + Methotrexate (MTX)	Group II: Golimumab 2 mg/kg + Methotrexate (MTX)	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	197	395	592
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.4 (11.26)	51.9 (12.55)	51.8 (12.13)
Sex: Female, Male (Count of Participants)
Female	157 79.7%	326 82.5%	483 81.6%
Male	40 20.3%	69 17.5%	109 18.4%
Region of Enrollment (participants) [Number]
Argentina	28 14.2%	54 13.7%	82 13.9%
Australia	3 1.5%	6 1.5%	9 1.5%
Columbia	12 6.1%	25 6.3%	37 6.3%
Hungary	10 5.1%	21 5.3%	31 5.2%
Korea, Republic of	4 2%	12 3%	16 2.7%
Lithuania	20 10.2%	44 11.1%	64 10.8%
Malaysia	8 4.1%	18 4.6%	26 4.4%
Mexico	13 6.6%	25 6.3%	38 6.4%
New Zealand	2 1%	4 1%	6 1%
Poland	36 18.3%	65 16.5%	101 17.1%
Russian Federation	23 11.7%	46 11.6%	69 11.7%
Ukraine	32 16.2%	58 14.7%	90 15.2%
United States	6 3%	17 4.3%	23 3.9%

Outcome Measures

1. Primary Outcome

Title	Proportion of Participants With an American College of Rheumatology (ACR) 20 Response at Week 14
Description	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.
Time Frame	Week 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Group I: Placebo + Methotrexate (MTX)	Group II: Golimumab 2 mg/kg + Methotrexate (MTX)
Arm/Group Description	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.	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.
Measure Participants	197	395
Number [Percentage of Participants]	24.9 12.6%	58.5 14.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group I: Placebo + Methotrexate (MTX), Group II: Golimumab 2 mg/kg + Methotrexate (MTX)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Group I: Placebo + Methotrexate (MTX)	Group II: Golimumab 2 mg/kg + Methotrexate (MTX)
Arm/Group Description	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.	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.
Measure Participants	197	395
Number [Percentage of Participants]	40.1 20.4%	81.3 20.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group I: Placebo + Methotrexate (MTX), Group II: Golimumab 2 mg/kg + Methotrexate (MTX)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

3. Secondary Outcome

Title	Change From Baseline in Health Assessment Questionnaire (HAQ) Score at Week 14
Description	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.
Time Frame	Week 14

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Group I: Placebo + Methotrexate (MTX)	Group II: Golimumab 2 mg/kg + Methotrexate (MTX)
Arm/Group Description	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.	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.
Measure Participants	197	395
Mean (Standard Deviation) [Scores on a scale]	0.1250 (0.55770)	0.5000 (0.57706)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group I: Placebo + Methotrexate (MTX), Group II: Golimumab 2 mg/kg + Methotrexate (MTX)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANOVA of van der Waerden scores
	Comments

4. Secondary Outcome

Title	Proportion of Participants Who Achieved American College of Rheumatology (ACR) 50 Response at Week 24
Description	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.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Group I: Placebo + Methotrexate (MTX)	Group II: Golimumab 2 mg/kg + Methotrexate (MTX)
Arm/Group Description	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.	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.
Measure Participants	197	395
Number [Percentage of Participants]	13.2 6.7%	34.9 8.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group I: Placebo + Methotrexate (MTX), Group II: Golimumab 2 mg/kg + Methotrexate (MTX)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Group I: Placebo + Methotrexate (MTX)	Group II: Golimumab 2 mg/kg + Methotrexate (MTX)
Arm/Group Description	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.	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.
Measure Participants	197	395
Mean (Standard Deviation) [Scores on a scale]	1.09 (3.194)	0.03 (1.899)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group I: Placebo + Methotrexate (MTX), Group II: Golimumab 2 mg/kg + Methotrexate (MTX)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANOVA of van der Waerden scores
	Comments

Adverse Events

Time Frame	Adverse events data were collected for the duration of study (100 weeks) and follow-up (12 weeks).
Adverse Event Reporting Description	The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table is based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Arm/Group Title	Placebo + MTX -> Golimumab 2 mg/kg + MTX at Week 16		Placebo + MTX -> Golimumab 2 mg/kg + MTX at Week 24		Golimumab 2 mg/kg + MTX		Combined Golimumab
Arm/Group Description	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.		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.		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.		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.
All Cause Mortality
	Placebo + MTX -> Golimumab 2 mg/kg + MTX at Week 16		Placebo + MTX -> Golimumab 2 mg/kg + MTX at Week 24		Golimumab 2 mg/kg + MTX		Combined Golimumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo + MTX -> Golimumab 2 mg/kg + MTX at Week 16		Placebo + MTX -> Golimumab 2 mg/kg + MTX at Week 24		Golimumab 2 mg/kg + MTX		Combined Golimumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/68 (16.2%)		17/121 (14%)		78/395 (19.7%)		106/584 (18.2%)
Blood and lymphatic system disorders
Anaemia	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Lymphadenopathy	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Cardiac disorders
Acute coronary syndrome	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Acute myocardial infarction	0/68 (0%)		1/121 (0.8%)		0/395 (0%)		1/584 (0.2%)
Angina pectoris	1/68 (1.5%)		0/121 (0%)		1/395 (0.3%)		2/584 (0.3%)
Angina unstable	0/68 (0%)		1/121 (0.8%)		0/395 (0%)		1/584 (0.2%)
Atrial fibrillation	1/68 (1.5%)		0/121 (0%)		1/395 (0.3%)		2/584 (0.3%)
Cor pulmonale chronic	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Myocardial infarction	1/68 (1.5%)		0/121 (0%)		1/395 (0.3%)		2/584 (0.3%)
Myocardial ischaemia	0/68 (0%)		1/121 (0.8%)		2/395 (0.5%)		3/584 (0.5%)
Sick sinus syndrome	1/68 (1.5%)		0/121 (0%)		0/395 (0%)		1/584 (0.2%)
Ear and labyrinth disorders
Vertigo	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Endocrine disorders
Hyperthyroidism	0/68 (0%)		1/121 (0.8%)		0/395 (0%)		1/584 (0.2%)
Eye disorders
Cataract	0/68 (0%)		0/121 (0%)		3/395 (0.8%)		3/584 (0.5%)
Gastrointestinal disorders
Abdominal pain upper	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Acute abdomen	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Diverticulum intestinal	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Duodenogastric reflux	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Gastric disorder	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Gastritis	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Gastrooesophageal reflux disease	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Haemorrhoids	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Hiatus hernia	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Pancreatitis acute	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Pancreatitis chronic	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
General disorders
Cyst	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Pyrexia	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Sudden death	0/68 (0%)		1/121 (0.8%)		0/395 (0%)		1/584 (0.2%)
Hepatobiliary disorders
Bile duct stone	0/68 (0%)		1/121 (0.8%)		0/395 (0%)		1/584 (0.2%)
Cholecystitis	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Cholecystitis acute	0/68 (0%)		1/121 (0.8%)		0/395 (0%)		1/584 (0.2%)
Cholelithiasis	0/68 (0%)		1/121 (0.8%)		0/395 (0%)		1/584 (0.2%)
Hepatitis toxic	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Jaundice	0/68 (0%)		1/121 (0.8%)		0/395 (0%)		1/584 (0.2%)
Infections and infestations
Appendicitis	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Arthritis bacterial	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Bacteraemia	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Bronchitis	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Cellulitis	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Device related infection	1/68 (1.5%)		0/121 (0%)		0/395 (0%)		1/584 (0.2%)
Empyema	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Endophthalmitis	1/68 (1.5%)		0/121 (0%)		0/395 (0%)		1/584 (0.2%)
Erysipelas	0/68 (0%)		0/121 (0%)		2/395 (0.5%)		2/584 (0.3%)
Gastroenteritis	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Infective spondylitis	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Intervertebral discitis	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Lobar pneumonia	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Lung abscess	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Pelvic inflammatory disease	0/68 (0%)		1/121 (0.8%)		0/395 (0%)		1/584 (0.2%)
Pharyngitis	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Pneumonia	1/68 (1.5%)		0/121 (0%)		4/395 (1%)		5/584 (0.9%)
Pneumonia cryptococcal	0/68 (0%)		1/121 (0.8%)		0/395 (0%)		1/584 (0.2%)
Rectal abscess	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Sepsis	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Sepsis syndrome	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Septic shock	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Tuberculosis	0/68 (0%)		1/121 (0.8%)		0/395 (0%)		1/584 (0.2%)
Tuberculous pleurisy	0/68 (0%)		1/121 (0.8%)		0/395 (0%)		1/584 (0.2%)
Upper respiratory tract infection	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Urinary tract infection	0/68 (0%)		1/121 (0.8%)		3/395 (0.8%)		4/584 (0.7%)
Urosepsis	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Vestibular neuronitis	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Injury, poisoning and procedural complications
Ankle fracture	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Concussion	1/68 (1.5%)		0/121 (0%)		0/395 (0%)		1/584 (0.2%)
Contusion	1/68 (1.5%)		0/121 (0%)		0/395 (0%)		1/584 (0.2%)
Dislocation of vertebra	1/68 (1.5%)		0/121 (0%)		0/395 (0%)		1/584 (0.2%)
Femoral neck fracture	0/68 (0%)		1/121 (0.8%)		0/395 (0%)		1/584 (0.2%)
Femur fracture	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Hand fracture	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Head injury	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Humerus fracture	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Laceration	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Meniscus lesion	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Rib fracture	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Road traffic accident	0/68 (0%)		1/121 (0.8%)		0/395 (0%)		1/584 (0.2%)
Spinal compression fracture	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Upper limb fracture	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Metabolism and nutrition disorders
Dehydration	0/68 (0%)		1/121 (0.8%)		0/395 (0%)		1/584 (0.2%)
Electrolyte imbalance	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Hyponatraemia	0/68 (0%)		1/121 (0.8%)		0/395 (0%)		1/584 (0.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Foot deformity	0/68 (0%)		1/121 (0.8%)		1/395 (0.3%)		2/584 (0.3%)
Intervertebral disc protrusion	1/68 (1.5%)		0/121 (0%)		2/395 (0.5%)		3/584 (0.5%)
Muscular weakness	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Osteoarthritis	1/68 (1.5%)		1/121 (0.8%)		1/395 (0.3%)		3/584 (0.5%)
Osteonecrosis	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Rheumatoid arthritis	2/68 (2.9%)		0/121 (0%)		10/395 (2.5%)		12/584 (2.1%)
Synovitis	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Bowen's disease	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Breast cancer	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Cervix carcinoma stage 0	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Chronic lymphocytic leukaemia	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Fibroadenoma of breast	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Lung neoplasm	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Salivary gland adenoma	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Thyroid neoplasm	0/68 (0%)		1/121 (0.8%)		0/395 (0%)		1/584 (0.2%)
Nervous system disorders
Carotid artery stenosis	0/68 (0%)		1/121 (0.8%)		0/395 (0%)		1/584 (0.2%)
Cerebral infarction	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Cerebral ischaemia	0/68 (0%)		1/121 (0.8%)		1/395 (0.3%)		2/584 (0.3%)
Iiird nerve paresis	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Ischaemic stroke	0/68 (0%)		0/121 (0%)		2/395 (0.5%)		2/584 (0.3%)
Lacunar infarction	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Radiculopathy	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Subarachnoid haemorrhage	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Syncope	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Renal and urinary disorders
Calculus ureteric	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Nephrolithiasis	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Nephropathy	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Renal colic	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Reproductive system and breast disorders
Bartholinitis	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Breast disorder	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Metrorrhagia	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Uterine prolapse	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Asthma	0/68 (0%)		0/121 (0%)		2/395 (0.5%)		2/584 (0.3%)
Dyspnoea	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Hypoxia	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Interstitial lung disease	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Pleurisy	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Respiratory failure	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Skin and subcutaneous tissue disorders
Rash	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Vascular disorders
Arterial rupture	0/68 (0%)		1/121 (0.8%)		0/395 (0%)		1/584 (0.2%)
Deep vein thrombosis	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Hypotension	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Peripheral vascular disorder	0/68 (0%)		0/121 (0%)		1/395 (0.3%)		1/584 (0.2%)
Other (Not Including Serious) Adverse Events
	Placebo + MTX -> Golimumab 2 mg/kg + MTX at Week 16		Placebo + MTX -> Golimumab 2 mg/kg + MTX at Week 24		Golimumab 2 mg/kg + MTX		Combined Golimumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	34/68 (50%)		38/121 (31.4%)		199/395 (50.4%)		271/584 (46.4%)
Infections and infestations
Bronchitis	6/68 (8.8%)		9/121 (7.4%)		37/395 (9.4%)		52/584 (8.9%)
Nasopharyngitis	3/68 (4.4%)		8/121 (6.6%)		28/395 (7.1%)		39/584 (6.7%)
Pharyngitis	0/68 (0%)		7/121 (5.8%)		26/395 (6.6%)		33/584 (5.7%)
Upper respiratory tract infection	5/68 (7.4%)		8/121 (6.6%)		54/395 (13.7%)		67/584 (11.5%)
Urinary tract infection	3/68 (4.4%)		7/121 (5.8%)		26/395 (6.6%)		36/584 (6.2%)
Investigations
Alanine aminotransferase increased	8/68 (11.8%)		3/121 (2.5%)		27/395 (6.8%)		38/584 (6.5%)
Aspartate aminotransferase increased	5/68 (7.4%)		2/121 (1.7%)		18/395 (4.6%)		25/584 (4.3%)
Hepatic enzyme increased	4/68 (5.9%)		0/121 (0%)		6/395 (1.5%)		10/584 (1.7%)
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis	9/68 (13.2%)		3/121 (2.5%)		33/395 (8.4%)		45/584 (7.7%)
Nervous system disorders
Headache	5/68 (7.4%)		2/121 (1.7%)		27/395 (6.8%)		34/584 (5.8%)
Vascular disorders
Hypertension	8/68 (11.8%)		4/121 (3.3%)		27/395 (6.8%)		39/584 (6.7%)

Limitations/Caveats

[Not Specified]

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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 less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.