A Study of the Safety and Efficacy of Ustekinumab (CNTO 1275) in Participants With Crohn's Disease

• Sponsor: Centocor, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00265122
• Collaborator: (none)
• Enrollment: 131
• Locations: 57
• Arms: 6
• Duration (Months): 30
• Patients Per Site: 2.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to examine the safety and efficacy of CNTO 1275 in participants with active Crohn's Disease.

Condition or Disease	Intervention/Treatment	Phase
Crohn Disease	Drug: Ustekinumab 90 mg; Drug: Ustekinumab 4.5 mg/kg; Drug: Placebo SC; Drug: Placebo IV	Phase 2

Detailed Description

This is a multicenter, randomized study of IL-12p40 (CNTO 1275), hereafter referred to as ustekinumab, in 2 populations of participants with moderately to severely active Crohn's disease of at least 6 weeks duration. A total of approximately 120 volunteers will participate in this study in Canada, Belgium, and the United States. Two separate groups of participants (Population 1 and Population 2) will be evaluated. The primary population of participants (Population 1) will consist of approximately 100 participants with Crohn's disease despite treatment with standard Crohn's disease medications (includes agents to decrease intestinal inflammation such as 5-ASA medications such as PENTASA, ASACOL), corticosteroids such as prednisone and/or other drugs known to suppress the immune system called immunomodulators such as azathioprine, 6-mercaptopurine, methotrexate, infliximab or adalimumab [marketed under the trade name of HUMMIRA]). Participants in Population 1 will be randomly assigned (assigned by chance, like "flipping a coin") to double-blind treatment (participants and study staff will not know the identity of the treatments) with ustekinumab and placebo (inactive substance) in 1 of 4 treatment groups as follows: (1) 4 weeks of treatment with ustekinumab 90 mg followed by 4 weeks of treatment with placebo injected subcutaneously (SC, under the skin), (II) 4 weeks of placebo followed by 4 weeks of ustekinumab 90 mg injected SC, (III) 1 intravenous (IV, in the vein) infusion of ustekinumab 4.5 mg/kg followed by 1 IV infusion of placebo, and (IV) 1 IV infusion of placebo followed by 1 IV infusion of ustekinumab 4.5 mg/kg. Population 2 consists of approximately 20 participants who failed to respond to previous therapy with infliximab (trade name REMICADE), a type of antibody that decreases inflammation in patients with moderate to severe Crohn's disease). All participants in Population 2 will receive open-label (un-blinded) treatment with ustekinumab 4.5 mg/kg administered SC for 4 weeks or as one IV infusion. Placebo will not be given to participants in Population 2. The duration of the study for each participant is 28 weeks (not including a screening period of up to 2 weeks) with participants returning at Week 54 to have blood samples collected to assess the concentration of ustekinumab and antibodies to ustekinumab. Adverse events (side-effects) as a measure of safety and tolerability and results from routine laboratory tests will be monitored and reported throughout the study from the time that informed consent is documented up to 3 days after the final blood sample collection at Week 54. Note: doses of ustekinumab used in the study were adjusted by a factor of 0.9 to be consistent with the corrected absorptivity constant for ustekinumab. Therefore, ustekinumab doses of 100 mg and 5 mg/kg previously stated in the study protocol have been restated as 90 mg and 4.5 mg/kg, respectively. No change was made to the amount of ustekinumab given to participants in this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 131 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Phase 2a Study of Human Monoclonal Antibody to IL-12p40 (CNTO 1275) in Subjects With Moderately to Severely Active Crohn's Disease
• Study Start Date: Apr 1, 2004
• Actual Primary Completion Date: Nov 1, 2005
• Actual Study Completion Date: Oct 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Population 1: Placebo SC followed by ustekinumab SC Placebo injected subcutaneously (SC) once a week for 4 weeks (Weeks 0-3) during Intervention Period 1 followed by ustekinumab 90 mg SC once a week for 4 weeks (Weeks 8-11) during Intervention Period 2.	Drug: Ustekinumab 90 mg; one 90 mg SC injection each week for 4 weeks (Weeks 0-3 during Intervention Period 1 or Weeks 8-11 during Intervention Period 2 for Population 1 or Weeks 0-3 during Intervention Period 1 for Population 2); Other Names: CNTO 1275 ; Drug: Placebo SC; one SC injection each week for 4 weeks (Weeks 0-3 in Intervention Period 1 or Weeks 8-11 in Intervention Period 2 for Population 1 or at Weeks 0-3 in Intervention Period 1 for Population 2)
Experimental: Population 1: Ustekinumab SC followed by Placebo SC: Ustekinumab 90 mg injected subcutaneously (SC) once a week for 4 weeks (Weeks 0-3) during Intervention Period 1 followed by ustekinumab 90 mg SC once a week for 4 weeks (Weeks 8-11) during Intervention Period 2.	Drug: Ustekinumab 90 mg; one 90 mg SC injection each week for 4 weeks (Weeks 0-3 during Intervention Period 1 or Weeks 8-11 during Intervention Period 2 for Population 1 or Weeks 0-3 during Intervention Period 1 for Population 2); Other Names: CNTO 1275 ; Drug: Placebo SC; one SC injection each week for 4 weeks (Weeks 0-3 in Intervention Period 1 or Weeks 8-11 in Intervention Period 2 for Population 1 or at Weeks 0-3 in Intervention Period 1 for Population 2)
Experimental: Population 1: Placebo IV followed by ustekinumab IV Placebo given as 1 intravenous (IV) infusion at Week 0 during Intervention Period 1 and ustekinumab 4.5 mg/kg given as one IV infusion at Week 8 during Intervention Period 2.	Drug: Ustekinumab 4.5 mg/kg; one IV infusion of 4.5 mg/kg over a period of not less than 2 hours at Week 0 in Intervention Period 1 or Week 8 in Intervention Period 2 for Population 1 or at Week 0 in Intervention Period 1 for Population 2; Other Names: CNTO 1275 ; Drug: Placebo IV; one IV infusion over a period of not less than 2 hours at Week 0 in Intervention Period 1 for Population 1 and Population 2 or at Week 8 in Intervention Period 2 for Population 1
Experimental: Population 1: Ustekinumab IV followed by Placebo IV: Ustekinumab 4.5 mg/kg given as one intravenous(IV) infusion at Week 0 during Intervention Period 1 followed by placebo given as one IV infusion at Week 8 during Intervention Period 2.	Drug: Ustekinumab 4.5 mg/kg; one IV infusion of 4.5 mg/kg over a period of not less than 2 hours at Week 0 in Intervention Period 1 or Week 8 in Intervention Period 2 for Population 1 or at Week 0 in Intervention Period 1 for Population 2; Other Names: CNTO 1275 ; Drug: Placebo IV; one IV infusion over a period of not less than 2 hours at Week 0 in Intervention Period 1 for Population 1 and Population 2 or at Week 8 in Intervention Period 2 for Population 1
Experimental: Population 2: Ustekinumab SC Ustekinumab 90 mg injected subcutaneously (SC) once a week at Weeks 0-3 during Intervention Period 1. No intervention given during Intervention Period 2.	Drug: Ustekinumab 90 mg; one 90 mg SC injection each week for 4 weeks (Weeks 0-3 during Intervention Period 1 or Weeks 8-11 during Intervention Period 2 for Population 1 or Weeks 0-3 during Intervention Period 1 for Population 2); Other Names: CNTO 1275
Experimental: Population 2: Ustekinumab IV Ustekinumab 4.5 mg given as one intravenous (IV) infusion at Week 0 during Intervention Period 1. No intervention given during Intervention Period 2.	Drug: Ustekinumab 4.5 mg/kg; one IV infusion of 4.5 mg/kg over a period of not less than 2 hours at Week 0 in Intervention Period 1 or Week 8 in Intervention Period 2 for Population 1 or at Week 0 in Intervention Period 1 for Population 2; Other Names: CNTO 1275

Outcome Measures

Primary Outcome Measures

1. Number of Participants in Population 1 With a Clinical Response at Week 8 [Week 8]

   The table below provides the number of participants in Population 1 with a clinical response at Week 8 defined as a reduction from baseline in the CDAI (Crohn's disease activity index) score of >= 25% and >= 70 points at Week 8. A reduction in CDAI score correlates with improvement in the severity of illness. The CDAI is derived as a weighted sum of 8 different Crohn's disease related variables: extra-intestinal manifestations, abdominal mass, weight, hematocrit, total number of liquid stools (or bags emptied for participants with a stoma), abdominal pain/cramping, use of antidiarrheal drug(s) and/or opiates, and general well being. The primary endpoint analysis was based on the comparison between the combined SC and IV Placebo and combined SC and IV ustekinumab treatment groups in Population 1.

Secondary Outcome Measures

1. Number of Participants in Population 2 With a Clinical Response at Week 8 [Week 8]

   The table below provides the number of participants in Population 2 with a clinical response at Week 8 defined as a reduction from baseline in the CDAI (Crohn's disease activity index) score of >= 25% and >= 70 points at Week 8. A reduction in CDAI score correlates with improvement in the severity of illness. The CDAI is derived as a weighted sum of 8 different Crohn's disease related variables: extra-intestinal manifestations, abdominal mass, weight, hematocrit, total number of liquid stools (or bags emptied for participants with a stoma), abdominal pain/cramping, use of antidiarrheal drug(s) and/or opiates, and general well-being.

2. Number of Participants in Population 1 With Clinical Remission at Week 8 [Week 8]

   The table below shows the number of participants in Population 1 with clinical remission at Week 8 defined a CDAI (Crohn's disease activity index) score < 150 points at Week 8. A reduction in CDAI score correlates with improvement in the severity of illness. The CDAI is derived as a weighted sum of 8 different Crohn's disease related variables: extra-intestinal manifestations, abdominal mass, weight, hematocrit, total number of liquid stools (or bags emptied for participants with a stoma), abdominal pain/cramping, use of antidiarrheal drug(s) and/or opiates, and general well-being.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Have moderately to severly active Crohn's disease or fistulizing Crohn's disease for at least 6 weeks' duration with a Crohn's disease activity index (CDAI) score of >=220 and <=450

• In Population 1, participants must have had active disease despite treatment with 5-ASA compounds, antibiotics, corticosteroids, and/or immunomodulators, including anti-TNF agents. In Population 2, participants must have had active disease and have failed to respond to infliximab at the maximum approved dose and treatment regimen for Crohn's disease as defined in the US package insert.

Exclusion Criteria:

• Have local manifestations of Crohn's disease such as strictures, abscesses, or other disease complications for which surgery might be indicated

• Had intra-abdominal surgery within 6 months prior to entering the study

• Have received treatment with parenteral nutrition (ie, introduction of nutrition into the body via a route other than the mouth) (total parenteral nutrition [TPN]) within 6 weeks of baseline

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Scottsdale	Arizona	United States
2		Anaheim	California	United States
3		Sacramento	California	United States
4		San Francisco	California	United States
5		Bristol	Connecticut	United States
6		New Haven	Connecticut	United States
7		Jacksonville	Florida	United States
8		Miami	Florida	United States
9		Indianapolis	Indiana	United States
10		Topeka	Kansas	United States
11		Lexington	Kentucky	United States
12		Louisville	Kentucky	United States
13		Baton Rouge	Louisiana	United States
14		Metairie	Louisiana	United States
15		New Orleans	Louisiana	United States
16		Laurel	Maryland	United States
17		Chesterfield	Michigan	United States
18		Troy	Michigan	United States
19		Rochester	Minnesota	United States
20		Omaha	Nebraska	United States
21		Great Neck	New York	United States
22		New York	New York	United States
23		Chapel Hill	North Carolina	United States
24		Charlotte	North Carolina	United States
25		Cincinnati	Ohio	United States
26		Cleveland	Ohio	United States
27		Columbus	Ohio	United States
28		Oklahoma City	Oklahoma	United States
29		Portland	Oregon	United States
30		Beaver Falls	Pennsylvania	United States
31		Pittsburgh	Pennsylvania	United States
32		Providence	Rhode Island	United States
33		Columbia	South Carolina	United States
34		Germantown	Tennessee	United States
35		Knoxville	Tennessee	United States
36		Memphis	Tennessee	United States
37		Nashville	Tennessee	United States
38		Austin	Texas	United States
39		Dallas	Texas	United States
40		Houston	Texas	United States
41		Ogden	Utah	United States
42		Salt Lake City	Utah	United States
43		Charlottesville	Virginia	United States
44		Christiansburg	Virginia	United States
45		Richmond	Virginia	United States
46		Everett	Washington	United States
47		Seattle	Washington	United States
48		Tacoma	Washington	United States
49		Madison	Wisconsin	United States
50		Milwaukee	Wisconsin	United States
51		Leuven		Belgium
52		Edmonton	Alberta	Canada
53		Vancouver	British Columbia	Canada
54		Winnipeg	Manitoba	Canada
55		Toronto	Ontario	Canada
56		Hamilton		Canada
57		London		Canada

Sponsors and Collaborators

• Centocor, Inc.

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Centocor, Inc.
• ClinicalTrials.gov Identifier: NCT00265122
• Other Study ID Numbers: CR005287; C0379T07
• First Posted: Dec 14, 2005
• Last Update Posted: Feb 13, 2014
• Last Verified: Jan 1, 2014

• Keywords provided by Centocor, Inc.: Crohn Disease; Biologic; Infusion; Injection; CNTO 1275; Ustekinumab; C01275; IL-12p40
• Additional relevant MeSH terms: Crohn Disease; Ustekinumab

Study Results

Participant Flow

Recruitment Details	A total of 131 participants (104 in Population 1 and 27 in Population 2) were enrolled among 42 study centers (35 centers in the US, 6 in Canada, and 1 in Belgium) to receive treatment with placebo or ustekinumab (CNTO 1275) administered subcutaeously (injected under the skin [SC]) or intravenously (infused in a vein [IV]).
Pre-assignment Detail	Participants with moderate to severe active Crohn's Disease despite treatment with 5-ASA compounds, antibiotics, corticosteroids, and/or immunomodulators, including anti-TNF agents were enrolled and referred to as Population 1 and those with active disease who failed to respond to infliximab were enrolled and referred to as Population 2.

Arm/Group Title	Population 1: Placebo SC Followed by Ustekinumab SC	Population 1: Ustekinumab 90 mg SC Followed by Placebo SC	Population 1: Placebo IV Followed by Ustekinumab 4.5 mg/kg IV	Population 1: Ustekinumab 4.5 mg/kg IV Followed by Placebo IV	Population 2: Ustekinumab 90 mg SC	Population 2: Ustekinumab 4.5 mg/kg IV
Arm/Group Description	Placebo injected subcutaneously (SC) once a week for 4 weeks (Weeks 0-3) during Intervention Period 1 followed by ustekinumab 90 mg SC once a week for 4 weeks (Weeks 8-11) during Intervention Period 2.	Ustekinumab 90 mg injected subcutaneously (SC) once a week for 4 weeks (Weeks 0-3) during Intervention Period 1 followed by placebo SC once a week for 4 weeks (Weeks 8-11) during Intervention Period 2.	Placebo given as 1 intravenous (IV) infusion at Week 0 during Intervention Period 1 and ustekinumab 4.5 mg/kg given as one IV infusion at Week 8 during Intervention Period 2.	Ustekinumab 4.5 mg/kg given as one intravenous(IV) infusion at Week 0 during Intervention Period 1 followed by placebo given as one IV infusion at Week 8 during Intervention Period 2.	Ustekinumab 90 mg injected subcutaneously (SC) once a week at Weeks 0-3 during Intervention Period 1. No intervention given during Intervention Period 2.	Ustekinumab 4.5 mg given as one intravenous (IV) infusion at Week 0 during Intervention Period 1. No intervention given during Intervention Period 2.
Period Title: Intervention Period 1 (Weeks 0 to 8):
STARTED	26	25	27	26	14	13
COMPLETED	24	23	22	24	13	13
NOT COMPLETED	2	2	5	2	1	0
Period Title: Intervention Period 1 (Weeks 0 to 8):
STARTED	24	23	22	24	13	13
COMPLETED	17	22	18	20	8	12
NOT COMPLETED	7	1	4	4	5	1

Baseline Characteristics

Arm/Group Title	Population 1: Placebo SC Followed by Ustekinumab SC	Population 1: Ustekinumab 90 mg SC Followed by Placebo SC	Population 1: Placebo IV Followed by Ustekinumab 4.5 mg/kg IV	Population 1: Ustekinumab 4.5 mg/kg IV Followed by Placebo IV	Population 2: Ustekinumab 90 mg SC	Population 2: Ustekinumab 4.5 mg/kg IV	Total
Arm/Group Description	Placebo injected subcutaneously (SC) once a week for 4 weeks (Weeks 0-3) during Intervention Period 1 followed by ustekinumab 90 mg SC once a week for 4 weeks (Weeks 8-11) during Intervention Period 2.	Ustekinumab 90 mg injected subcutaneously (SC) once a week for 4 weeks (Weeks 0-3) during Intervention Period 1 followed by placebo SC once a week for 4 weeks (Weeks 8-11) during Intervention Period 2.	Placebo given as 1 intravenous (IV) infusion at Week 0 during Intervention Period 1 and ustekinumab 4.5 mg/kg given as one IV infusion at Week 8 during Intervention Period 2.	Ustekinumab 4.5 mg/kg given as one intravenous(IV) infusion at Week 0 during Intervention Period 1 followed by placebo given as one IV infusion at Week 8 during Intervention Period 2.	Ustekinumab 90 mg injected subcutaneously (SC) once a week at Weeks 0-3 during Intervention Period 1. No intervention given during Intervention Period 2.	Ustekinumab 4.5 mg given as one intravenous (IV) infusion at Week 0 during Intervention Period 1. No intervention given during Intervention Period 2.	Total of all reporting groups
Overall Participants	26	25	27	26	14	13	131
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	36.7 (13.99)	36.5 (13.17)	43.5 (11.39)	43.1 (12.23)	46.9 (13.63)	42.7 (11.27)	40.0 (12.97)
Sex: Female, Male (Count of Participants)
Female	11 42.3%	10 40%	14 51.9%	12 46.2%	6 42.9%	8 61.5%	61 46.6%
Male	15 57.7%	15 60%	13 48.1%	14 53.8%	8 57.1%	5 38.5%	70 53.4%

Outcome Measures

1. Primary Outcome

Title	Number of Participants in Population 1 With a Clinical Response at Week 8
Description	The table below provides the number of participants in Population 1 with a clinical response at Week 8 defined as a reduction from baseline in the CDAI (Crohn's disease activity index) score of >= 25% and >= 70 points at Week 8. A reduction in CDAI score correlates with improvement in the severity of illness. The CDAI is derived as a weighted sum of 8 different Crohn's disease related variables: extra-intestinal manifestations, abdominal mass, weight, hematocrit, total number of liquid stools (or bags emptied for participants with a stoma), abdominal pain/cramping, use of antidiarrheal drug(s) and/or opiates, and general well being. The primary endpoint analysis was based on the comparison between the combined SC and IV Placebo and combined SC and IV ustekinumab treatment groups in Population 1.
Time Frame	Week 8

Outcome Measure Data

Analysis Population Description

The analysis included all randomized patients (ITT), regardless of whether they had any protocol deviations.

Arm/Group Title	Population 1: Placebo SC Followed by Ustekinumab SC	Population 1: Ustekinumab 90 mg SC Followed by Placebo SC	Population 1: Placebo IV Followed by Ustekinumab 4.5 mg/kg IV	Population 1: Ustekinumab 4.5 mg/kg IV Followed by Placebo IV	Population 1: Placebo SC and IV Combined	Population 1: Ustekinumab SC and IV Combined
Arm/Group Description	Placebo injected subcutaneously (SC) once a week for 4 weeks (Weeks 0-3) during Intervention Period 1 followed by ustekinumab 90 mg SC once a week for 4 weeks (Weeks 8-11) during Intervention Period 2.	Ustekinumab 90 mg injected subcutaneously (SC) once a week for 4 weeks (Weeks 0-3) during Intervention Period 1 followed by placebo SC once a week for 4 weeks (Weeks 8-11) during Intervention Period 2.	Placebo given as 1 intravenous (IV) infusion at Week 0 during Intervention Period 1 and ustekinumab 4.5 mg/kg given as one IV infusion at Week 8 during Intervention Period 2.	Ustekinumab 4.5 mg/kg given as one intravenous(IV) infusion at Week 0 during Intervention Period 1 followed by placebo given as one IV infusion at Week 8 during Intervention Period 2.	All particpants who received Placebo SC and Placebo IV	All participants who received Ustekinumab 90 mg SC and Ustekinumab 4.5 mg/kg IV
Measure Participants	26	25	27	26	53	51
Number [participants]	13 50%	12 48%	8 29.6%	13 50%	21 150%	25 192.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Population 1: Placebo SC and IV Combined, Population 1: Ustekinumab SC and IV Combined
	Comments	Null hypothesis: No difference between ustekinumab and placebo at a significant level of 0.05.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.337
	Comments	The P-Value is from a Cochran-Mantel-Haenszel (CMH) test stratified by the route of administration.
	Method	Cochran-Mantel-Haenszel
	Comments

2. Secondary Outcome

Title	Number of Participants in Population 2 With a Clinical Response at Week 8
Description	The table below provides the number of participants in Population 2 with a clinical response at Week 8 defined as a reduction from baseline in the CDAI (Crohn's disease activity index) score of >= 25% and >= 70 points at Week 8. A reduction in CDAI score correlates with improvement in the severity of illness. The CDAI is derived as a weighted sum of 8 different Crohn's disease related variables: extra-intestinal manifestations, abdominal mass, weight, hematocrit, total number of liquid stools (or bags emptied for participants with a stoma), abdominal pain/cramping, use of antidiarrheal drug(s) and/or opiates, and general well-being.
Time Frame	Week 8

Outcome Measure Data

Analysis Population Description

The analysis included all randomized patients (ITT), regardless of whether they had any protocol deviations.

Arm/Group Title	Population 2: Ustekinumab 90 SC	Population 2: Ustekinumab 4.5 mg/kg IV
Arm/Group Description	Paticipants received ustekinumab 90 mg subcutaneously (SC) at Weeks 0, 1, 2, and 3 (Intervention Period 1: Weeks 0-8), and did not receive any study agent from Week 8 onward (Intervention Period 2: Weeks 8-28)	Ustekinumab 4.5 mg given as one intravenous (IV) infusion at Week 0 during Intervention Period 1. No intervention given during Intervention Period 2.
Measure Participants	14	13
Number [participants]	6 23.1%	7 28%

3. Secondary Outcome

Title	Number of Participants in Population 1 With Clinical Remission at Week 8
Description	The table below shows the number of participants in Population 1 with clinical remission at Week 8 defined a CDAI (Crohn's disease activity index) score < 150 points at Week 8. A reduction in CDAI score correlates with improvement in the severity of illness. The CDAI is derived as a weighted sum of 8 different Crohn's disease related variables: extra-intestinal manifestations, abdominal mass, weight, hematocrit, total number of liquid stools (or bags emptied for participants with a stoma), abdominal pain/cramping, use of antidiarrheal drug(s) and/or opiates, and general well-being.
Time Frame	Week 8

Outcome Measure Data

Analysis Population Description

The analysis included all randomized patients (ITT), regardless of whether they had any protocol deviations.

Arm/Group Title	Population 1:Placebo SC Followed by Ustekinumab 90 mg SC	Population 1: Ustekinumab 90 mg SC Followed by Placebo SC	Population 1: Placebo IV Followed by Ustekinumab 4.5 mg/kg IV	Population 1: Ustekinumab 4.5 mg/kg IV Followed by Placebo IV	Population 1: Placebo SC and IV Combined	Population 1: Ustekinumab SC and IV Combined
Arm/Group Description	Participants received subcutaneous (SC) injections of placebo at Weeks 0, 1, 2, 3 (Intervention Period 1: Weeks 0-8), and 90 mg ustekinumab SC at Weeks 8, 9, 10 and 11 (Intervention Period 2: Weeks 8-28)	Ustekinumab 90 mg injected subcutaneously (SC) once a week for 4 weeks (Weeks 0-3) during Intervention Period 1 followed by placebo SC once a week for 4 weeks (Weeks 8-11) during Intervention Period 2.	Placebo given as 1 intravenous (IV) infusion at Week 0 during Intervention Period 1 and ustekinumab 4.5 mg/kg given as one IV infusion at Week 8 during Intervention Period 2.	Ustekinumab 4.5 mg/kg given as one intravenous(IV) infusion at Week 0 during Intervention Period 1 followed by placebo given as one IV infusion at Week 8 during Intervention Period 2.	All participants who received Placebo SC and Placebo IV	All participants who received Ustekinumab SC and Ustekinumab IV
Measure Participants	26	25	27	26	53	51
Number [participants]	6 23.1%	6 24%	3 11.1%	7 26.9%	9 64.3%	13 100%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Population 1: Placebo SC and IV Combined, Population 1: Ustekinumab SC and IV Combined
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.292
	Comments	The P-Value is from a CMH test stratified by the route of administration.
	Method	Cochran-Mantel-Haenszel
	Comments

Adverse Events

Time Frame	Week 28
Adverse Event Reporting Description	The number of participants at risk for adverse events was based on actual treatment received which differs from the number of participants randomized to treatment reported in Participant flow. Adverse events following the first administration of ustekinumab are included in the table.
Arm/Group Title	Population 1: Placebo SC Followed by Ustekinumab SC		Population 1: Ustekinumab 90 mg SC Followed by Placebo SC		Population 1: Placebo IV Followed by Ustekinumab 4.5 mg/kg IV		Population 1: Ustekinumab 4.5 mg/kg IV Followed by Placebo IV		Population 2: Ustekinumab 90 mg SC		Population 2: Ustekinumab 4.5 mg/kg IV
Arm/Group Description	Placebo injected subcutaneously (SC) once a week for 4 weeks (Weeks 0-3) during Intervention Period 1 followed by ustekinumab 90 mg SC once a week for 4 weeks (Weeks 8-11) during Intervention Period 2. NOTE: 4 of 26 participants randomized to this treatment group received placebo only and were excluded from the "Total # at Risk by any Serious Adverse Event" and "Total # at Risk by any Other Adverse Event" listed below.		Ustekinumab 90 mg injected subcutaneously (SC) once a week for 4 weeks (Weeks 0-3) during Intervention Period 1 followed by placebo SC once a week for 4 weeks (Weeks 8-11) during Intervention Period 2.		Placebo given as 1 intravenous (IV) infusion at Week 0 during Intervention Period 1 and ustekinumab 4.5 mg/kg given as one IV infusion at Week 8 during Intervention Period 2. NOTE: 8 of 27 participants randomized to this treatment group were excluded from the "Total # at Risk by any Serious Adverse Event" and "Total # at Risk by any Other Adverse Event" listed below for the following reasons: 7 participants received placebo only were excluded from the analysis of adverse events and 1 participant received ustekinumab IV at Week 0 and was included in the analysis of adverse events in the treatment group labelled "Ustekinumab 4.5 mg/kg IV followed by Placebo IV."		Ustekinumab 4.5 mg/kg given as one intravenous(IV) infusion at Week 0 during Intervention Period 1 followed by placebo given as one IV infusion at Week 8 during Intervention Period 2. NOTE: 26 participants randomized to this treatment group + 1 participant randomized to treatment with "Placebo IV followed by Ustekinumab 4.5 mg/kg IV" who received ustekinumab IV at Week 0 was included in the "Total # at Risk by any Serious Adverse Event" and "Total # at Risk by any Other Adverse Event" listed below.		Ustekinumab 90 mg injected subcutaneously (SC) once a week at Weeks 0-3 during Intervention Period 1. No intervention given during Intervention Period 2.		Ustekinumab 4.5 mg given as one intravenous (IV) infusion at Week 0 during Intervention Period 1. No intervention given during Intervention Period 2.
All Cause Mortality
	Population 1: Placebo SC Followed by Ustekinumab SC		Population 1: Ustekinumab 90 mg SC Followed by Placebo SC		Population 1: Placebo IV Followed by Ustekinumab 4.5 mg/kg IV		Population 1: Ustekinumab 4.5 mg/kg IV Followed by Placebo IV		Population 2: Ustekinumab 90 mg SC		Population 2: Ustekinumab 4.5 mg/kg IV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Population 1: Placebo SC Followed by Ustekinumab SC		Population 1: Ustekinumab 90 mg SC Followed by Placebo SC		Population 1: Placebo IV Followed by Ustekinumab 4.5 mg/kg IV		Population 1: Ustekinumab 4.5 mg/kg IV Followed by Placebo IV		Population 2: Ustekinumab 90 mg SC		Population 2: Ustekinumab 4.5 mg/kg IV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0%)		1/25 (4%)		2/19 (10.5%)		3/27 (11.1%)		2/14 (14.3%)		2/13 (15.4%)
Cardiac disorders
Coronary artery disease	0/22 (0%)		0/25 (0%)		0/19 (0%)		1/27 (3.7%)		0/14 (0%)		0/13 (0%)
Gastrointestinal disorders
Crohn's disease	0/22 (0%)		1/25 (4%)		1/19 (5.3%)		0/27 (0%)		0/14 (0%)		2/13 (15.4%)
Colonic stenosis	0/22 (0%)		0/25 (0%)		1/19 (5.3%)		0/27 (0%)		0/14 (0%)		0/13 (0%)
Small intestinal obstruction	0/22 (0%)		0/25 (0%)		0/19 (0%)		2/27 (7.4%)		0/14 (0%)		0/13 (0%)
Infections and infestations
Gastroenteritis	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		1/14 (7.1%)		0/13 (0%)
Histoplasmosis disseminated	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		0/14 (0%)		1/13 (7.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer	0/22 (0%)		0/25 (0%)		0/19 (0%)		1/27 (3.7%)		0/14 (0%)		0/13 (0%)
Nervous system disorders
Syncope	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		0/14 (0%)		1/13 (7.7%)
Renal and urinary disorders
Nephrolithiasis	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		1/14 (7.1%)		0/13 (0%)
Respiratory, thoracic and mediastinal disorders
Pneumothorax	0/22 (0%)		0/25 (0%)		1/19 (5.3%)		0/27 (0%)		0/14 (0%)		0/13 (0%)
Other (Not Including Serious) Adverse Events
	Population 1: Placebo SC Followed by Ustekinumab SC		Population 1: Ustekinumab 90 mg SC Followed by Placebo SC		Population 1: Placebo IV Followed by Ustekinumab 4.5 mg/kg IV		Population 1: Ustekinumab 4.5 mg/kg IV Followed by Placebo IV		Population 2: Ustekinumab 90 mg SC		Population 2: Ustekinumab 4.5 mg/kg IV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/22 (72.7%)		23/25 (92%)		16/19 (84.2%)		21/27 (77.8%)		12/14 (85.7%)		10/13 (76.9%)
Blood and lymphatic system disorders
Anaemia	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		1/14 (7.1%)		1/13 (7.7%)
Cardiac disorders
Atrial flutter	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		1/14 (7.1%)		0/13 (0%)
Tachycardia	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		0/14 (0%)		1/13 (7.7%)
Ear and labyrinth disorders
Ear pain	0/22 (0%)		2/25 (8%)		0/19 (0%)		0/27 (0%)		0/14 (0%)		2/13 (15.4%)
Ear congestion	0/22 (0%)		0/25 (0%)		1/19 (5.3%)		0/27 (0%)		0/14 (0%)		0/13 (0%)
Eye disorders
Conjunctivitis	0/22 (0%)		0/25 (0%)		1/19 (5.3%)		0/27 (0%)		0/14 (0%)		0/13 (0%)
Dry eye	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		1/14 (7.1%)		0/13 (0%)
Eyelid oedema	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		1/14 (7.1%)		0/13 (0%)
Glaucoma	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		1/14 (7.1%)		0/13 (0%)
Lacrimation increased	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		0/14 (0%)		1/13 (7.7%)
Gastrointestinal disorders
Nausea	5/22 (22.7%)		2/25 (8%)		2/19 (10.5%)		3/27 (11.1%)		3/14 (21.4%)		2/13 (15.4%)
Abdominal pain	3/22 (13.6%)		2/25 (8%)		0/19 (0%)		5/27 (18.5%)		2/14 (14.3%)		0/13 (0%)
Abdominal distension	1/22 (4.5%)		2/25 (8%)		0/19 (0%)		3/27 (11.1%)		1/14 (7.1%)		0/13 (0%)
Dyspepsia	2/22 (9.1%)		3/25 (12%)		0/19 (0%)		1/27 (3.7%)		2/14 (14.3%)		1/13 (7.7%)
Vomiting	1/22 (4.5%)		2/25 (8%)		1/19 (5.3%)		2/27 (7.4%)		0/14 (0%)		1/13 (7.7%)
Abdominal pain lower	0/22 (0%)		2/25 (8%)		0/19 (0%)		2/27 (7.4%)		0/14 (0%)		0/13 (0%)
Abdominal pain upper	1/22 (4.5%)		0/25 (0%)		1/19 (5.3%)		1/27 (3.7%)		1/14 (7.1%)		0/13 (0%)
Diarrhoea	0/22 (0%)		1/25 (4%)		1/19 (5.3%)		1/27 (3.7%)		1/14 (7.1%)		0/13 (0%)
Flatulence	0/22 (0%)		2/25 (8%)		0/19 (0%)		1/27 (3.7%)		0/14 (0%)		0/13 (0%)
Abdominal hernia	0/22 (0%)		0/25 (0%)		1/19 (5.3%)		0/27 (0%)		0/14 (0%)		0/13 (0%)
Bowel sounds abnormal	0/22 (0%)		0/25 (0%)		1/19 (5.3%)		0/27 (0%)		0/14 (0%)		0/13 (0%)
Gastrointestinal disorder	0/22 (0%)		0/25 (0%)		1/19 (5.3%)		0/27 (0%)		0/14 (0%)		0/13 (0%)
Intestinal fistula	0/22 (0%)		0/25 (0%)		1/19 (5.3%)		0/27 (0%)		0/14 (0%)		0/13 (0%)
Aphthous stomatitis	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		0/14 (0%)		1/13 (7.7%)
Constipation	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		1/14 (7.1%)		0/13 (0%)
Dry mouth	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		1/14 (7.1%)		0/13 (0%)
Faecal incontinence	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		0/14 (0%)		1/13 (7.7%)
Food poisoning	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		0/14 (0%)		1/13 (7.7%)
Glossitis	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		1/14 (7.1%)		0/13 (0%)
Haemorrhoids	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		0/14 (0%)		1/13 (7.7%)
Mouth ulceration	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		1/14 (7.1%)		0/13 (0%)
Spigelian hernia	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		1/14 (7.1%)		0/13 (0%)
Crohn's disease	6/22 (27.3%)		4/25 (16%)		4/19 (21.1%)		7/27 (25.9%)		4/14 (28.6%)		4/13 (30.8%)
General disorders
Pyrexia	0/22 (0%)		4/25 (16%)		0/19 (0%)		3/27 (11.1%)		1/14 (7.1%)		3/13 (23.1%)
Fatigue	1/22 (4.5%)		1/25 (4%)		1/19 (5.3%)		2/27 (7.4%)		0/14 (0%)		2/13 (15.4%)
Pain	1/22 (4.5%)		2/25 (8%)		0/19 (0%)		0/27 (0%)		0/14 (0%)		0/13 (0%)
Influenza like illness	0/22 (0%)		0/25 (0%)		0/19 (0%)		2/27 (7.4%)		0/14 (0%)		0/13 (0%)
Chest discomfort	0/22 (0%)		0/25 (0%)		1/19 (5.3%)		0/27 (0%)		0/14 (0%)		0/13 (0%)
Infusion site erythema	0/22 (0%)		0/25 (0%)		1/19 (5.3%)		0/27 (0%)		0/14 (0%)		0/13 (0%)
Infusion site pruritus	0/22 (0%)		0/25 (0%)		1/19 (5.3%)		0/27 (0%)		0/14 (0%)		0/13 (0%)
Chest pain	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		1/14 (7.1%)		2/13 (15.4%)
Adverse drug reaction	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		1/14 (7.1%)		0/13 (0%)
Chills	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		1/14 (7.1%)		0/13 (0%)
Feeling cold	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		1/14 (7.1%)		0/13 (0%)
Malaise	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		0/14 (0%)		1/13 (7.7%)
Vessel puncture site bruise	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		0/14 (0%)		1/13 (7.7%)
Infections and infestations
Upper respiratory tract infection	6/22 (27.3%)		5/25 (20%)		3/19 (15.8%)		4/27 (14.8%)		1/14 (7.1%)		3/13 (23.1%)
Nasopharyngitis	1/22 (4.5%)		3/25 (12%)		1/19 (5.3%)		1/27 (3.7%)		1/14 (7.1%)		2/13 (15.4%)
Influenza	0/22 (0%)		3/25 (12%)		0/19 (0%)		2/27 (7.4%)		1/14 (7.1%)		0/13 (0%)
Gastroenteritis viral	0/22 (0%)		1/25 (4%)		2/19 (10.5%)		1/27 (3.7%)		0/14 (0%)		3/13 (23.1%)
Sinusitis	1/22 (4.5%)		0/25 (0%)		2/19 (10.5%)		1/27 (3.7%)		1/14 (7.1%)		0/13 (0%)
Urinary tract infection	0/22 (0%)		0/25 (0%)		1/19 (5.3%)		1/27 (3.7%)		1/14 (7.1%)		2/13 (15.4%)
Ear infection	0/22 (0%)		0/25 (0%)		1/19 (5.3%)		0/27 (0%)		0/14 (0%)		1/13 (7.7%)
Viral infection	0/22 (0%)		0/25 (0%)		1/19 (5.3%)		0/27 (0%)		0/14 (0%)		0/13 (0%)
Oral candidiasis	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		1/14 (7.1%)		1/13 (7.7%)
Clostridial infection	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		0/14 (0%)		1/13 (7.7%)
Gastrointestinal infection	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		0/14 (0%)		1/13 (7.7%)
Lower respiratory tract infection	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		0/14 (0%)		1/13 (7.7%)
Nail infection	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		1/14 (7.1%)		0/13 (0%)
Pneumonia	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		1/14 (7.1%)		0/13 (0%)
Tooth abscess	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		0/14 (0%)		1/13 (7.7%)
Vaginal candidiasis	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		0/14 (0%)		1/13 (7.7%)
Injury, poisoning and procedural complications
Muscle strain	0/22 (0%)		0/25 (0%)		1/19 (5.3%)		0/27 (0%)		0/14 (0%)		0/13 (0%)
Transmission of drug via semen	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		0/14 (0%)		1/13 (7.7%)
Investigations
Alanine aminotransferase increased	0/22 (0%)		2/25 (8%)		0/19 (0%)		0/27 (0%)		0/14 (0%)		0/13 (0%)
Platelet count increased	1/22 (4.5%)		0/25 (0%)		1/19 (5.3%)		0/27 (0%)		0/14 (0%)		0/13 (0%)
Blood glucose decreased	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		0/14 (0%)		1/13 (7.7%)
Blood glucose increased	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		0/14 (0%)		1/13 (7.7%)
Blood potassium decreased	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		0/14 (0%)		1/13 (7.7%)
Blood pressure decreased	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		0/14 (0%)		1/13 (7.7%)
Occult blood positive	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		0/14 (0%)		1/13 (7.7%)
Metabolism and nutrition disorders
Anorexia	0/22 (0%)		0/25 (0%)		0/19 (0%)		2/27 (7.4%)		0/14 (0%)		0/13 (0%)
Decreased appetite	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		0/14 (0%)		1/13 (7.7%)
Hypokalaemia	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		0/14 (0%)		1/13 (7.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/22 (0%)		5/25 (20%)		3/19 (15.8%)		3/27 (11.1%)		1/14 (7.1%)		2/13 (15.4%)
Back pain	0/22 (0%)		3/25 (12%)		0/19 (0%)		2/27 (7.4%)		2/14 (14.3%)		1/13 (7.7%)
Fistula	0/22 (0%)		0/25 (0%)		1/19 (5.3%)		0/27 (0%)		0/14 (0%)		0/13 (0%)
Joint swelling	0/22 (0%)		0/25 (0%)		1/19 (5.3%)		0/27 (0%)		0/14 (0%)		0/13 (0%)
Musculoskeletal stiffness	0/22 (0%)		0/25 (0%)		1/19 (5.3%)		0/27 (0%)		0/14 (0%)		0/13 (0%)
Fibromyalgia	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		0/14 (0%)		1/13 (7.7%)
Muscle spasms	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		0/14 (0%)		1/13 (7.7%)
Musculoskeletal chest pain	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		1/14 (7.1%)		0/13 (0%)
Myalgia	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		1/14 (7.1%)		0/13 (0%)
Neck pain	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		1/14 (7.1%)		0/13 (0%)
Temporomandibular joint syndrome	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		0/14 (0%)		1/13 (7.7%)
Nervous system disorders
Headache	0/22 (0%)		6/25 (24%)		3/19 (15.8%)		4/27 (14.8%)		3/14 (21.4%)		3/13 (23.1%)
Dizziness	1/22 (4.5%)		1/25 (4%)		2/19 (10.5%)		1/27 (3.7%)		0/14 (0%)		0/13 (0%)
Migraine	3/22 (13.6%)		0/25 (0%)		0/19 (0%)		1/27 (3.7%)		0/14 (0%)		0/13 (0%)
Cervical root pain	0/22 (0%)		0/25 (0%)		1/19 (5.3%)		0/27 (0%)		0/14 (0%)		0/13 (0%)
Neuralgia	0/22 (0%)		0/25 (0%)		1/19 (5.3%)		0/27 (0%)		0/14 (0%)		0/13 (0%)
Burning sensation	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		1/14 (7.1%)		0/13 (0%)
Neuropathy peripheral	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		1/14 (7.1%)		0/13 (0%)
Paraesthesia	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		1/14 (7.1%)		0/13 (0%)
Syncope	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		0/14 (0%)		1/13 (7.7%)
Syncope vasovagal	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		1/14 (7.1%)		0/13 (0%)
Psychiatric disorders
Anxiety	0/22 (0%)		2/25 (8%)		0/19 (0%)		1/27 (3.7%)		0/14 (0%)		1/13 (7.7%)
Insomnia	0/22 (0%)		0/25 (0%)		1/19 (5.3%)		1/27 (3.7%)		1/14 (7.1%)		1/13 (7.7%)
Depression	0/22 (0%)		0/25 (0%)		1/19 (5.3%)		1/27 (3.7%)		0/14 (0%)		0/13 (0%)
Restlessness	0/22 (0%)		0/25 (0%)		1/19 (5.3%)		0/27 (0%)		0/14 (0%)		0/13 (0%)
Disorientation	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		0/14 (0%)		1/13 (7.7%)
Stress	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		0/14 (0%)		1/13 (7.7%)
Renal and urinary disorders
Nephrolithiasis	1/22 (4.5%)		0/25 (0%)		1/19 (5.3%)		1/27 (3.7%)		1/14 (7.1%)		0/13 (0%)
Reproductive system and breast disorders
Menorrhagia	0/22 (0%)		0/25 (0%)		1/19 (5.3%)		0/27 (0%)		0/14 (0%)		0/13 (0%)
Menstruation irregular	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		0/14 (0%)		1/13 (7.7%)
Respiratory, thoracic and mediastinal disorders
Cough	0/22 (0%)		3/25 (12%)		0/19 (0%)		0/27 (0%)		1/14 (7.1%)		2/13 (15.4%)
Dyspnoea	0/22 (0%)		1/25 (4%)		1/19 (5.3%)		1/27 (3.7%)		0/14 (0%)		0/13 (0%)
Epistaxis	0/22 (0%)		0/25 (0%)		1/19 (5.3%)		0/27 (0%)		0/14 (0%)		0/13 (0%)
Pharyngolaryngeal pain	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		1/14 (7.1%)		1/13 (7.7%)
Pleurisy	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		1/14 (7.1%)		0/13 (0%)
Pleuritic pain	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		1/14 (7.1%)		0/13 (0%)
Sinus congestion	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		1/14 (7.1%)		0/13 (0%)
Skin and subcutaneous tissue disorders
Rash	1/22 (4.5%)		3/25 (12%)		1/19 (5.3%)		3/27 (11.1%)		0/14 (0%)		0/13 (0%)
Pruritus	0/22 (0%)		0/25 (0%)		1/19 (5.3%)		3/27 (11.1%)		0/14 (0%)		1/13 (7.7%)
Dermal cyst	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		1/14 (7.1%)		0/13 (0%)
Hyperhidrosis	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		1/14 (7.1%)		0/13 (0%)
Night sweats	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		1/14 (7.1%)		0/13 (0%)
Skin disorder	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		0/14 (0%)		1/13 (7.7%)
Skin lesion	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		1/14 (7.1%)		0/13 (0%)
Urticaria	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		1/14 (7.1%)		0/13 (0%)
Surgical and medical procedures
Tooth extraction	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		0/14 (0%)		1/13 (7.7%)
Vascular disorders
Flushing	0/22 (0%)		0/25 (0%)		0/19 (0%)		2/27 (7.4%)		0/14 (0%)		0/13 (0%)
Hypertension	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		0/14 (0%)		1/13 (7.7%)
Intermittent claudication	0/22 (0%)		0/25 (0%)		0/19 (0%)		0/27 (0%)		1/14 (7.1%)		0/13 (0%)

Limitations/Caveats

The count of patients with any nonserious adverse events (NAE) excludes patients who only had NAE that occurred in <=5% of patients. This information may vary from existing approved labeling and publications due to the requirement of this website.

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Certain Agreements

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

Generally, the only disclosure restriction on the PI is that the sponsor has 60 days to review results communications prior to public release and can embargo communications regarding trial results for a period that does not exceed 180 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.