Open Label Long-Term Safety Study of Certolizumab Pegol (CZP) for Patients With Rheumatoid Arthritis

• Sponsor: UCB Pharma (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00160693
• Collaborator: (none)
• Enrollment: 402
• Locations: 61
• Arm: 1
• Duration (Months): 95.1
• Patients Per Site: 6.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The primary purpose of this study is to obtain long-term safety data with CZP in patients with Rheumatoid Arthritis (RA). Additional objectives are to assess the dose and type of Arthritis medication(s) utilized by patients, and to assess the long-term impact of CZP on physical function. Treatment will continue up to approval of a marketing application for this product.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Biological: Certolizumab Pegol	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 402 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III, Multicenter, Open-Label Long-Term Study to Assess the Safety and Tolerability of CDP870 400 mg Subcutaneously Every 4 Weeks, in Subjects With Rheumatoid Arthritis
• Study Start Date: Mar 1, 2003
• Actual Primary Completion Date: Feb 1, 2011
• Actual Study Completion Date: Feb 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Certolizumab Pegol	Biological: Certolizumab Pegol; 400 mg of Certolizumab Pegol subcutaneously every 4 Weeks; Other Names: Cimzia

Outcome Measures

Primary Outcome Measures

1. Percentage of Subjects With at Least One Adverse Event (AE) During the Study Period of 8 Years [From first dose of CZP up to 8 years]

   An AE is any untoward medical occurrence in a subject or trial subject that is administered a drug or biologic (medicinal product) or that is using a medical device. The event does not necessarily have a causal relationship with that treatment or usage. First dose of CZP was at Baseline of one of the feeder studies C87011 [NCT00548834] or C87014 [NCT00544154] for subjects randomized to CZP, or at First Visit (Week 0) of this study for subjects randomized to Placebo.

2. Percentage of Subjects Who Withdrew Due to an Adverse Event (AE) During the Study Period of 8 Years [From First Visit (Week 0 in this study) up to 8 years]

   An AE is any untoward medical occurrence in a subject or trial subject that is administered a drug or biologic (medicinal product) or that is using a medical device. The event does not necessarily have a causal relationship with that treatment or usage. The results of this Primary Outcome Measure are summarized from the Adverse Event pages of the Case Report Forms.

Secondary Outcome Measures

1. Percentage of Subjects Meeting the American College of Rheumatology 20% Response Criteria (ACR20) at Week 52 [From Baseline to Week 52]

   The assessments are based on a 20% or greater improvement from Baseline to Week 52 in the number of tender joints, a 20% or more improvement in the number of swollen joints, and a 20% or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the respective feeder study.

2. Percentage of Subjects Meeting the American College of Rheumatology 20% Response Criteria (ACR20) at Week 100 [From Baseline to Week 100]

   The assessments are based on a 20% or greater improvement from Baseline to Week 100 in the number of tender joints, a 20% or more improvement in the number of swollen joints, and a 20% or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the respective feeder study.

3. Percentage of Subjects Meeting the American College of Rheumatology 20% Response Criteria (ACR20) at Week 160 [From Baseline to Week 160]

   The assessments are based on a 20% or greater improvement from Baseline to Week 160 in the number of tender joints, a 20% or more improvement in the number of swollen joints, and a 20% or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the respective feeder study.

4. Percentage of Subjects Meeting the American College of Rheumatology 20% Response Criteria (ACR20) at Week 208 [From Baseline to Week 208]

   The assessments are based on a 20% or greater improvement from Baseline to Week 208 in the number of tender joints, a 20% or more improvement in the number of swollen joints, and a 20% or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the respective feeder study.

5. Percentage of Subjects Meeting the American College of Rheumatology 20% Response Criteria (ACR20) at Week 256 [From Baseline to Week 256]

   The assessments are based on a 20% or greater improvement from Baseline to Week 256 in the number of tender joints, a 20% or more improvement in the number of swollen joints, and a 20% or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the respective feeder study.

6. Percentage of Subjects Meeting the American College of Rheumatology 20% Response Criteria (ACR20) at Week 316 [From Baseline to Week 316]

   The assessments are based on a 20% or greater improvement from Baseline to Week 316 in the number of tender joints, a 20% or more improvement in the number of swollen joints, and a 20% or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the respective feeder study.

7. Percentage of Subjects Meeting the American College of Rheumatology 20% Response Criteria (ACR20) at Completion Visit or Early Withdrawal Visit [From Baseline to Completion Visit/ early Withdrawal Visit, up to 8 years]

   The assessments are based on a 20% or greater improvement from Baseline to the Completion Visit or early Withdrawal Visit in the number of tender joints, a 20% or more improvement in the number of swollen joints, and a 20% or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP).

8. Percentage of Subjects Meeting the American College of Rheumatology 50% Response Criteria (ACR50) at Completion Visit or Early Withdrawal Visit [From Baseline to Completion Visit/ early Withdrawal Visit, up to 8 years]

   The assessments are based on a 50% or greater improvement from Baseline to the Completion Visit or early Withdrawal Visit in the number of tender joints, a 50% or more improvement in the number of swollen joints, and a 50% or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP).

9. Percentage of Subjects Meeting the American College of Rheumatology 70% Response Criteria (ACR70) at Completion Visit or Early Withdrawal Visit [From Baseline to Completion Visit/ early Withdrawal Visit, up to 8 years]

   The assessments are based on a 70% or greater improvement from Baseline to the Completion Visit or early Withdrawal Visit in the number of tender joints, a 70% or more improvement in the number of swollen joints, and a 70% or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP).

10. Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ- DI) at Completion Visit or Early Withdrawal Visit [From Baseline to Completion Visit/ early Withdrawal Visit, up to 8 years]

    The HAQ-DI assesses the degree of difficulty experienced in eight domains (Dressing and Grooming, Arising, Eating, Walking, Hygiene, Reach, Gripping, Other Activities) of daily living activities using 20 questions. The HAQ-DI is calculated by summing the domain scores and dividing them by the number of domains. It ranges from 0 (no difficulty) to 3 (unable to do). Negative values indicate an improvement from Baseline to the Post-Baseline Visit with larger negative values showing a better improvement.

11. Percentage of Subjects Who Withdrew Due to Lack of Efficacy During the Study Period of 8 Years [From First Visit (Week 0 in this study) up to 8 years]

12. Percentage of Subjects Utilizing Common Additional Arthritis Medications During the Study Period of 8 Years [From First Visit (Week 0 in this study) up to 8 years]

    This Secondary Outcome Measure shows additional arthritis medications received by at least 20% of subjects during the 8-year study.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Participation in CZP trial C87014 or C87011

• If female and of childbearing potential, she agrees to participate in this study by providing written informed consent, has been using adequate contraception since her last menses, will use adequate contraception during the study and for 12 weeks after the last dose of study drug (or longer if required by local regulations), is not lactating, and has had a negative urine pregnancy test on the day of receiving the first dose of study drug

• Must have provided written informed consent before undergoing any study procedures

Exclusion Criteria:

• History (Hx) of chronic infection, serious or life-threatening infection - (including Herpes Zoster) within 6 months prior, or any current symptom indicating infection

• Current or recent Hx of severe, progressive and/or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological or cerebral disease

• Any finding indicative of Tuberculosis at end of previous study

• Known HIV infection

• Persistently abnormal AST (Aspartate Aminotransferase) or ALT (Alanine Aminotransferase) results (> 2 times upper limit of normal)

• Hemoglobin (Hgb) levels < 9 g/dL or Hematocrit < 30 %

• Total White Blood Cell (WBC) count of < 3.0 x 100/L (< 3000/mm^3)

• Platelet count < 100 x 100 L (100,000/mm^3)

• Serum creatinine > 1.5 times upper limit of normal based on patient age and sex

• Receipt of any biological therapies for RA in 6 months prior to study entry or any prior treatment (tx) with Tumor Necrosis Factor (TNF) blocking agent (excluding CDP870)

• Receipt of any vaccination (live, attenuated or killed) in 8 weeks prior to Baseline

• Any other condition which the Principal Investigator judges would make patient unsuitable for study participation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Huntsville	Alabama	United States
2		Paradise Valley	Arizona	United States
3		Washington	District of Columbia	United States
4		Aventura	Florida	United States
5		Clearwater	Florida	United States
6		Ocala	Florida	United States
7		Orlando	Florida	United States
8		Tampa	Florida	United States
9		Coeur d'Alene	Idaho	United States
10		Springfield	Illinois	United States
11		Wichita	Kansas	United States
12		Wheaton	Maryland	United States
13		Fall River	Massachusetts	United States
14		Saint Louis	Missouri	United States
15		Lincoln	Nebraska	United States
16		Charlotte	North Carolina	United States
17		Cleveland	Ohio	United States
18		Dayton	Ohio	United States
19		Erie	Pennsylvania	United States
20		West Reading	Pennsylvania	United States
21		Charleston	South Carolina	United States
22		Memphis	Tennessee	United States
23		Austin	Texas	United States
24		Dallas	Texas	United States
25		Duncanville	Texas	United States
26		Lubbock	Texas	United States
27		San Antonio	Texas	United States
28		San Diego	Texas	United States
29		Everett	Washington	United States
30		Graz		Austria
31		Klagenfurt		Austria
32		Vienna		Austria
33		Antwerpen		Belgium
34		Diepenbeek		Belgium
35		Liege		Belgium
36		Merksem		Belgium
37		Ceske Budejovice		Czechia
38		Liberec		Czechia
39		Ostrava Trebovice		Czechia
40		Prague 2		Czechia
41		Praha4 -krc		Czechia
42		Uherske Hradiste		Czechia
43		Berlin		Germany
44		Gortlitz		Germany
45		Hamburg		Germany
46		Jena		Germany
47		Koln		Germany
48		Leipzig		Germany
49		Ratingen		Germany
50		Dublin		Ireland
51		Waterford		Ireland
52		Birmingham		United Kingdom
53		Cannock		United Kingdom
54		Colchester		United Kingdom
55		Glasgow		United Kingdom
56		Harrogate		United Kingdom
57		London		United Kingdom
58		Manchester		United Kingdom
59		Oxford		United Kingdom
60		Peterborough		United Kingdom
61		Wirral		United Kingdom

Sponsors and Collaborators

• UCB Pharma

Investigators

• Study Director: UCB Clinical Trial Call Center, [phone] (UCB)

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Product Information
• FDA Safety Alerts and Recalls

Publications

None provided.

• Responsible Party: UCB Pharma
• ClinicalTrials.gov Identifier: NCT00160693
• Other Study ID Numbers: C87015; 2005-002617-21
• First Posted: Sep 12, 2005
• Last Update Posted: Aug 1, 2018
• Last Verified: Mar 1, 2018

• Keywords provided by UCB Pharma: Rheumatoid Arthritis; America College of Rheumatology; Disease modifying anti-rheumatic drug; Certolizumab Pegol (CDP870)
• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid; Certolizumab Pegol

Study Results

Participant Flow

Recruitment Details	Subjects must have participated in CZP trial C87011 [NCT00548834] or C87014 [NCT00544154] for at least 12 weeks to be eligible to enter the study. All enrolled subjects who received at least one dose of study medication are included in the Safety Set (SS).
Pre-assignment Detail	Participant Flow and Baseline Characteristics refer to the Safety Set (SS). Baseline Characteristics were measured at Baseline of the respective feeder study.

Arm/Group Title	Certolizumab Pegol
Arm/Group Description	400 mg of Certolizumab Pegol subcutaneously every 4 Weeks.
Period Title: Overall Study
STARTED	402
COMPLETED	167
NOT COMPLETED	235

Baseline Characteristics

Arm/Group Title	Certolizumab Pegol
Arm/Group Description	400 mg of Certolizumab Pegol subcutaneously every 4 Weeks.
Overall Participants	402
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	327 81.3%
>=65 years	75 18.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.4 (12.1)
Sex: Female, Male (Count of Participants)
Female	303 75.4%
Male	99 24.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	3 0.7%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	19 4.7%
White	363 90.3%
More than one race	0 0%
Unknown or Not Reported	17 4.2%
Region of Enrollment (participants) [Number]
United States	160 39.8%
Czech Republic	81 20.1%
Belgium	11 2.7%
Ireland	8 2%
Austria	19 4.7%
Germany	87 21.6%
United Kingdom	36 9%
Weight (kilogram (kg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram (kg)]	78.00 (17.88)
Height (centimeter (cm)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeter (cm)]	166.4 (8.6)
Body Mass Index (BMI) (kilogram/ meter^2 (kg / m^2)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram/ meter^2 (kg / m^2)]	28.20 (6.34)
Disease Duration (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	9.46 (8.13)

Outcome Measures

1. Primary Outcome

Title	Percentage of Subjects With at Least One Adverse Event (AE) During the Study Period of 8 Years
Description	An AE is any untoward medical occurrence in a subject or trial subject that is administered a drug or biologic (medicinal product) or that is using a medical device. The event does not necessarily have a causal relationship with that treatment or usage. First dose of CZP was at Baseline of one of the feeder studies C87011 [NCT00548834] or C87014 [NCT00544154] for subjects randomized to CZP, or at First Visit (Week 0) of this study for subjects randomized to Placebo.
Time Frame	From first dose of CZP up to 8 years

Outcome Measure Data

Analysis Population Description

Safety Set (SS).

Arm/Group Title	Certolizumab Pegol
Arm/Group Description	400 mg of Certolizumab Pegol subcutaneously every 4 Weeks.
Measure Participants	402
Number [percentage of subjects]	93.5

2. Primary Outcome

Title	Percentage of Subjects Who Withdrew Due to an Adverse Event (AE) During the Study Period of 8 Years
Description	An AE is any untoward medical occurrence in a subject or trial subject that is administered a drug or biologic (medicinal product) or that is using a medical device. The event does not necessarily have a causal relationship with that treatment or usage. The results of this Primary Outcome Measure are summarized from the Adverse Event pages of the Case Report Forms.
Time Frame	From First Visit (Week 0 in this study) up to 8 years

Outcome Measure Data

Analysis Population Description

Safety Set (SS).

Arm/Group Title	Certolizumab Pegol
Arm/Group Description	400 mg of Certolizumab Pegol subcutaneously every 4 Weeks.
Measure Participants	402
Number [percentage of subjects]	24.9

3. Secondary Outcome

Title	Percentage of Subjects Meeting the American College of Rheumatology 20% Response Criteria (ACR20) at Week 52
Description	The assessments are based on a 20% or greater improvement from Baseline to Week 52 in the number of tender joints, a 20% or more improvement in the number of swollen joints, and a 20% or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the respective feeder study.
Time Frame	From Baseline to Week 52

Outcome Measure Data

Analysis Population Description

Of the 402 subjects in the Safety Set (SS), 370 subjects are included in this analysis, because they had available data at Baseline and Week 52.

Arm/Group Title	Certolizumab Pegol
Arm/Group Description	400 mg of Certolizumab Pegol subcutaneously every 4 Weeks.
Measure Participants	370
Number (95% Confidence Interval) [percentage of subjects]	58.1

4. Secondary Outcome

Title	Percentage of Subjects Meeting the American College of Rheumatology 20% Response Criteria (ACR20) at Week 100
Description	The assessments are based on a 20% or greater improvement from Baseline to Week 100 in the number of tender joints, a 20% or more improvement in the number of swollen joints, and a 20% or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the respective feeder study.
Time Frame	From Baseline to Week 100

Outcome Measure Data

Analysis Population Description

Of the 402 subjects in the Safety Set (SS), 275 subjects are included in this analysis, because they had available data at Baseline and Week 100.

Arm/Group Title	Certolizumab Pegol
Arm/Group Description	400 mg of Certolizumab Pegol subcutaneously every 4 Weeks.
Measure Participants	275
Number (95% Confidence Interval) [percentage of subjects]	60.0

5. Secondary Outcome

Title	Percentage of Subjects Meeting the American College of Rheumatology 20% Response Criteria (ACR20) at Week 160
Description	The assessments are based on a 20% or greater improvement from Baseline to Week 160 in the number of tender joints, a 20% or more improvement in the number of swollen joints, and a 20% or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the respective feeder study.
Time Frame	From Baseline to Week 160

Outcome Measure Data

Analysis Population Description

Of the 402 subjects in the Safety Set (SS), 247 subjects are included in this analysis, because they had available data at Baseline and Week 160.

Arm/Group Title	Certolizumab Pegol
Arm/Group Description	400 mg of Certolizumab Pegol subcutaneously every 4 Weeks.
Measure Participants	247
Number (95% Confidence Interval) [percentage of subjects]	68.4

6. Secondary Outcome

Title	Percentage of Subjects Meeting the American College of Rheumatology 20% Response Criteria (ACR20) at Week 208
Description	The assessments are based on a 20% or greater improvement from Baseline to Week 208 in the number of tender joints, a 20% or more improvement in the number of swollen joints, and a 20% or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the respective feeder study.
Time Frame	From Baseline to Week 208

Outcome Measure Data

Analysis Population Description

Of the 402 subjects in the Safety Set (SS), 223 subjects are included in this analysis, because they had available data at Baseline and Week 208.

Arm/Group Title	Certolizumab Pegol
Arm/Group Description	400 mg of Certolizumab Pegol subcutaneously every 4 Weeks.
Measure Participants	223
Number (95% Confidence Interval) [percentage of subjects]	72.6

7. Secondary Outcome

Title	Percentage of Subjects Meeting the American College of Rheumatology 20% Response Criteria (ACR20) at Week 256
Description	The assessments are based on a 20% or greater improvement from Baseline to Week 256 in the number of tender joints, a 20% or more improvement in the number of swollen joints, and a 20% or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the respective feeder study.
Time Frame	From Baseline to Week 256

Outcome Measure Data

Analysis Population Description

Of the 402 subjects in the Safety Set (SS), 211 subjects are included in this analysis, because they had available data at Baseline and Week 256.

Arm/Group Title	Certolizumab Pegol
Arm/Group Description	400 mg of Certolizumab Pegol subcutaneously every 4 Weeks.
Measure Participants	211
Number (95% Confidence Interval) [percentage of subjects]	75.4

8. Secondary Outcome

Title	Percentage of Subjects Meeting the American College of Rheumatology 20% Response Criteria (ACR20) at Week 316
Description	The assessments are based on a 20% or greater improvement from Baseline to Week 316 in the number of tender joints, a 20% or more improvement in the number of swollen joints, and a 20% or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP). Baseline is Baseline of the respective feeder study.
Time Frame	From Baseline to Week 316

Outcome Measure Data

Analysis Population Description

Of the 402 subjects in the Safety Set (SS), 140 subjects are included in this analysis, because they had available data at Baseline and Week 316.

Arm/Group Title	Certolizumab Pegol
Arm/Group Description	400 mg of Certolizumab Pegol subcutaneously every 4 Weeks.
Measure Participants	140
Number (95% Confidence Interval) [percentage of subjects]	76.4

9. Secondary Outcome

Title	Percentage of Subjects Meeting the American College of Rheumatology 20% Response Criteria (ACR20) at Completion Visit or Early Withdrawal Visit
Description	The assessments are based on a 20% or greater improvement from Baseline to the Completion Visit or early Withdrawal Visit in the number of tender joints, a 20% or more improvement in the number of swollen joints, and a 20% or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP).
Time Frame	From Baseline to Completion Visit/ early Withdrawal Visit, up to 8 years

Outcome Measure Data

Analysis Population Description

Safety Set (SS).

Arm/Group Title	Certolizumab Pegol
Arm/Group Description	400 mg of Certolizumab Pegol subcutaneously every 4 Weeks.
Measure Participants	402
Number (95% Confidence Interval) [percentage of subjects]	57.2

10. Secondary Outcome

Title	Percentage of Subjects Meeting the American College of Rheumatology 50% Response Criteria (ACR50) at Completion Visit or Early Withdrawal Visit
Description	The assessments are based on a 50% or greater improvement from Baseline to the Completion Visit or early Withdrawal Visit in the number of tender joints, a 50% or more improvement in the number of swollen joints, and a 50% or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP).
Time Frame	From Baseline to Completion Visit/ early Withdrawal Visit, up to 8 years

Outcome Measure Data

Analysis Population Description

Safety Set (SS).

Arm/Group Title	Certolizumab Pegol
Arm/Group Description	400 mg of Certolizumab Pegol subcutaneously every 4 Weeks.
Measure Participants	402
Number (95% Confidence Interval) [percentage of subjects]	27.6

11. Secondary Outcome

Title	Percentage of Subjects Meeting the American College of Rheumatology 70% Response Criteria (ACR70) at Completion Visit or Early Withdrawal Visit
Description	The assessments are based on a 70% or greater improvement from Baseline to the Completion Visit or early Withdrawal Visit in the number of tender joints, a 70% or more improvement in the number of swollen joints, and a 70% or greater improvement in 3 of the 5 remaining core set measures: Patient's Global Assessment of Disease Activity (PtGADA), Physician's Global Assessment of Disease Activity (PhGADA), Patient's Assessment of Arthritis Pain (PtAAP), physical function as assessed by the Health Assessment Questionnaire - Disability Index (HAQ-DI) and C-Reactive Protein (CRP).
Time Frame	From Baseline to Completion Visit/ early Withdrawal Visit, up to 8 years

Outcome Measure Data

Analysis Population Description

Safety Set (SS).

Arm/Group Title	Certolizumab Pegol
Arm/Group Description	400 mg of Certolizumab Pegol subcutaneously every 4 Weeks.
Measure Participants	402
Number (95% Confidence Interval) [percentage of subjects]	7.7

12. Secondary Outcome

Title	Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ- DI) at Completion Visit or Early Withdrawal Visit
Description	The HAQ-DI assesses the degree of difficulty experienced in eight domains (Dressing and Grooming, Arising, Eating, Walking, Hygiene, Reach, Gripping, Other Activities) of daily living activities using 20 questions. The HAQ-DI is calculated by summing the domain scores and dividing them by the number of domains. It ranges from 0 (no difficulty) to 3 (unable to do). Negative values indicate an improvement from Baseline to the Post-Baseline Visit with larger negative values showing a better improvement.
Time Frame	From Baseline to Completion Visit/ early Withdrawal Visit, up to 8 years

Outcome Measure Data

Analysis Population Description

Of the 402 subjects in the Safety Set (SS), 400 subjects are included in this analysis, because they had available data at Baseline and Completion or early Withdrawal Visit.

Arm/Group Title	Certolizumab Pegol
Arm/Group Description	400 mg of Certolizumab Pegol subcutaneously every 4 Weeks.
Measure Participants	400
Mean (Standard Deviation) [units on a scale]	-0.305 (0.620)

13. Secondary Outcome

Title	Percentage of Subjects Who Withdrew Due to Lack of Efficacy During the Study Period of 8 Years
Time Frame	From First Visit (Week 0 in this study) up to 8 years

Outcome Measure Data

Analysis Population Description

Safety Set (SS).

Arm/Group Title	Certolizumab Pegol
Arm/Group Description	400 mg of Certolizumab Pegol subcutaneously every 4 Weeks.
Measure Participants	402
Number [percentage of subjects]	7.5

14. Secondary Outcome

Title	Percentage of Subjects Utilizing Common Additional Arthritis Medications During the Study Period of 8 Years
Description	This Secondary Outcome Measure shows additional arthritis medications received by at least 20% of subjects during the 8-year study.
Time Frame	From First Visit (Week 0 in this study) up to 8 years

Outcome Measure Data

Analysis Population Description

Safety Set (SS).

Arm/Group Title	Certolizumab Pegol
Arm/Group Description	400 mg of Certolizumab Pegol subcutaneously every 4 Weeks.
Measure Participants	402
Acetylsalicylic acid	21.9
Celecoxib	22.9
Diclofenac	23.4
Folic acid	65.2
Ibuprofen	26.4
Methotrexate	60.9
Methylprednisolone	33.8
Other Immunosuppressive agents	25.9
Paracetamol	29.6
Prednisolone	20.4
Prednisone	39.3

Adverse Events

Time Frame	Adverse Events (AEs) were collected over the whole Study Period of 8 Years from first dose of study medication (Baseline of feeder study or First Visit of this study for subjects randomized to Placebo) to 24 Weeks post last dose (Last Follow-up Visit).
Adverse Event Reporting Description	AEs refer to the Safety Set (SS). SS includes all of the 402 enrolled subjects.
Arm/Group Title	Certolizumab Pegol
Arm/Group Description	400 mg of Certolizumab Pegol subcutaneously every 4 Weeks.
All Cause Mortality
	Certolizumab Pegol
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Certolizumab Pegol
	Affected / at Risk (%)	# Events
Total	184/402 (45.8%)
Blood and lymphatic system disorders
Anaemia	2/402 (0.5%)	3
Hilar lymphadenopathy	1/402 (0.2%)	1
Iron deficiency anaemia	1/402 (0.2%)	1
Lymphadenitis	2/402 (0.5%)	2
Thrombocytopenia	1/402 (0.2%)	1
Cardiac disorders
Acute coronary syndrome	1/402 (0.2%)	1
Acute myocardial infarction	2/402 (0.5%)	2
Angina pectoris	3/402 (0.7%)	3
Angina unstable	2/402 (0.5%)	2
Arrhythmia	1/402 (0.2%)	2
Atrial fibrillation	4/402 (1%)	5
Atrioventricular block	1/402 (0.2%)	1
Bradycardia	1/402 (0.2%)	1
Cardiac arrest	1/402 (0.2%)	1
Cardiac failure	4/402 (1%)	4
Coronary artery disease	6/402 (1.5%)	6
Coronary artery stenosis	2/402 (0.5%)	2
Myocardial infarction	5/402 (1.2%)	5
Myocardial ischaemia	2/402 (0.5%)	2
Sinus bradycardia	1/402 (0.2%)	1
Sinus tachycardia	1/402 (0.2%)	1
Endocrine disorders
Goitre	1/402 (0.2%)	1
Hyperthyroidism	2/402 (0.5%)	2
Eye disorders
Conjunctivitis	1/402 (0.2%)	1
Maculopathy	1/402 (0.2%)	1
Optic nerve disorder	1/402 (0.2%)	1
Gastrointestinal disorders
Abdominal adhesions	1/402 (0.2%)	1
Abdominal hernia	2/402 (0.5%)	2
Diarrhoea	1/402 (0.2%)	1
Diverticular perforation	1/402 (0.2%)	1
Diverticulum	1/402 (0.2%)	1
Diverticulum duodenal	1/402 (0.2%)	1
Gastric ulcer	1/402 (0.2%)	1
Gastritis	2/402 (0.5%)	2
Gastritis erosive	1/402 (0.2%)	1
Gastrointestinal haemorrhage	1/402 (0.2%)	1
Hiatus hernia	2/402 (0.5%)	2
Ileus paralytic	1/402 (0.2%)	1
Inflammatory bowel disease	1/402 (0.2%)	1
Inguinal hernia	2/402 (0.5%)	2
Leukoplakia oral	1/402 (0.2%)	1
Melaena	1/402 (0.2%)	1
Oedematous pancreatitis	1/402 (0.2%)	1
Oesophageal rupture	1/402 (0.2%)	1
Pancreatitis acute	1/402 (0.2%)	1
Peritonitis	1/402 (0.2%)	1
Rectal haemorrhage	1/402 (0.2%)	1
Stomatitis	1/402 (0.2%)	1
Subileus	1/402 (0.2%)	1
Umbilical hernia	1/402 (0.2%)	1
General disorders
Asthenia	1/402 (0.2%)	1
Chest pain	3/402 (0.7%)	4
Chills	1/402 (0.2%)	1
Impaired healing	2/402 (0.5%)	4
Malaise	1/402 (0.2%)	2
Multi-organ failure	1/402 (0.2%)	1
Non-cardiac chest pain	1/402 (0.2%)	1
Oedema	1/402 (0.2%)	1
Oedema peripheral	1/402 (0.2%)	1
Pyrexia	3/402 (0.7%)	3
Hepatobiliary disorders
Bile duct stone	2/402 (0.5%)	2
Cholangitis	2/402 (0.5%)	2
Cholecystitis	3/402 (0.7%)	3
Cholecystitis acute	1/402 (0.2%)	1
Cholecystitis chronic	1/402 (0.2%)	1
Cholelithiasis	3/402 (0.7%)	3
Hepatitis cholestatic	1/402 (0.2%)	1
Hepatotoxicity	1/402 (0.2%)	1
Liver disorder	1/402 (0.2%)	1
Perforation bile duct	1/402 (0.2%)	1
Immune system disorders
Drug hypersensitivity	1/402 (0.2%)	1
Infections and infestations
Abscess intestinal	1/402 (0.2%)	1
Abscess neck	1/402 (0.2%)	1
Arthritis infective	1/402 (0.2%)	1
Bronchitis	3/402 (0.7%)	3
Bronchitis acute	1/402 (0.2%)	1
Bronchopneumonia	2/402 (0.5%)	2
Cellulitis	4/402 (1%)	9
Cholangitis suppurative	1/402 (0.2%)	1
Cholecystitis infective	1/402 (0.2%)	1
Chronic sinusitis	1/402 (0.2%)	1
Chronic tonsillitis	1/402 (0.2%)	1
Clostridial infection	1/402 (0.2%)	1
Device related infection	1/402 (0.2%)	1
Diverticulitis	1/402 (0.2%)	1
Empyema	1/402 (0.2%)	1
Erysipelas	1/402 (0.2%)	1
Escherichia sepsis	1/402 (0.2%)	1
Gastroenteritis	3/402 (0.7%)	3
Gastroenteritis clostridial	1/402 (0.2%)	1
Gastroenteritis viral	1/402 (0.2%)	1
Herpes simplex	1/402 (0.2%)	1
Herpes zoster	2/402 (0.5%)	2
Histoplasmosis disseminated	1/402 (0.2%)	1
Infected skin ulcer	1/402 (0.2%)	1
Infection	1/402 (0.2%)	1
Liver abscess	1/402 (0.2%)	1
Lobar pneumonia	1/402 (0.2%)	1
Lower respiratory tract infection	1/402 (0.2%)	1
Lymph node tuberculosis	1/402 (0.2%)	1
Mastitis	1/402 (0.2%)	1
Necrotising fasciitis	1/402 (0.2%)	1
Neutropenic sepsis	1/402 (0.2%)	1
Pelvic abscess	1/402 (0.2%)	1
Pneumocystis jiroveci pneumonia	1/402 (0.2%)	1
Pneumonia	9/402 (2.2%)	10
Pneumonia legionella	1/402 (0.2%)	1
Pneumonia staphylococcal	1/402 (0.2%)	1
Pneumonia streptococcal	1/402 (0.2%)	1
Pulmonary tuberculosis	1/402 (0.2%)	1
Purulent synovitis	1/402 (0.2%)	1
Pyelonephritis	2/402 (0.5%)	2
Pyelonephritis acute	1/402 (0.2%)	1
Respiratory tract infection viral	1/402 (0.2%)	1
Sepsis	1/402 (0.2%)	1
Staphylococcal infection	1/402 (0.2%)	1
Subcutaneous abscess	2/402 (0.5%)	3
Tonsillitis	2/402 (0.5%)	2
Tracheobronchitis	1/402 (0.2%)	1
Tuberculosis	1/402 (0.2%)	1
Urinary tract infection	3/402 (0.7%)	3
Injury, poisoning and procedural complications
Brain contusion	1/402 (0.2%)	1
Contrast media reaction	1/402 (0.2%)	1
Contusion	1/402 (0.2%)	1
Device failure	1/402 (0.2%)	2
Fall	3/402 (0.7%)	4
Femoral neck fracture	1/402 (0.2%)	1
Femur fracture	1/402 (0.2%)	1
Forearm fracture	1/402 (0.2%)	1
Foreign body trauma	1/402 (0.2%)	1
Hip fracture	1/402 (0.2%)	1
Humerus fracture	2/402 (0.5%)	2
Incisional hernia	1/402 (0.2%)	1
Injury	2/402 (0.5%)	2
Joint dislocation	1/402 (0.2%)	1
Lumbar vertebral fracture	1/402 (0.2%)	1
Medical device complication	1/402 (0.2%)	1
Medication error	1/402 (0.2%)	1
Patella fracture	1/402 (0.2%)	1
Pelvic fracture	1/402 (0.2%)	1
Pubic rami fracture	1/402 (0.2%)	1
Radius fracture	2/402 (0.5%)	2
Spinal compression fracture	1/402 (0.2%)	1
Sternal fracture	1/402 (0.2%)	1
Subdural haematoma	1/402 (0.2%)	1
Synovial rupture	1/402 (0.2%)	1
Tendon injury	1/402 (0.2%)	1
Tendon rupture	1/402 (0.2%)	1
Tibia fracture	1/402 (0.2%)	1
Ulna fracture	1/402 (0.2%)	1
Upper limb fracture	1/402 (0.2%)	1
Wrist fracture	1/402 (0.2%)	1
XIth nerve injury	1/402 (0.2%)	1
Metabolism and nutrition disorders
Dehydration	1/402 (0.2%)	1
Diabetes mellitus	1/402 (0.2%)	2
Diabetic ketoacidosis	1/402 (0.2%)	1
Hypokalaemia	1/402 (0.2%)	1
Hyponatraemia	2/402 (0.5%)	2
Hypovolaemia	1/402 (0.2%)	1
Obesity	1/402 (0.2%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	2/402 (0.5%)	3
Arthritis	2/402 (0.5%)	2
Arthrofibrosis	1/402 (0.2%)	1
Back pain	2/402 (0.5%)	2
Bursitis	2/402 (0.5%)	2
Exostosis	1/402 (0.2%)	1
Finger deformity	1/402 (0.2%)	1
Fistula	2/402 (0.5%)	2
Groin pain	1/402 (0.2%)	1
Intervertebral disc degeneration	1/402 (0.2%)	1
Intervertebral disc disorder	1/402 (0.2%)	1
Intervertebral disc protrusion	4/402 (1%)	4
Joint destruction	1/402 (0.2%)	1
Joint swelling	1/402 (0.2%)	1
Lumbar spinal stenosis	1/402 (0.2%)	1
Myalgia	1/402 (0.2%)	1
Osteoarthritis	16/402 (4%)	21
Pain in extremity	1/402 (0.2%)	1
Rheumatoid arthritis	16/402 (4%)	20
Rheumatoid nodule	2/402 (0.5%)	2
Rotator cuff syndrome	1/402 (0.2%)	1
Spinal column stenosis	2/402 (0.5%)	2
Spinal osteoarthritis	1/402 (0.2%)	1
Synovial cyst	1/402 (0.2%)	1
Synovitis	2/402 (0.5%)	3
Tendon disorder	1/402 (0.2%)	1
Tenosynovitis	1/402 (0.2%)	1
Toe deformity	5/402 (1.2%)	5
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	4/402 (1%)	4
Breast cancer	3/402 (0.7%)	3
Cholesteatoma	1/402 (0.2%)	1
Colon adenoma	1/402 (0.2%)	1
Diffuse large B-cell lymphoma	1/402 (0.2%)	1
Lung adenocarcinoma	1/402 (0.2%)	1
Lung adenocarcinoma stage I	1/402 (0.2%)	1
Lung cancer metastatic	1/402 (0.2%)	1
Lung neoplasm malignant	1/402 (0.2%)	1
Lymphocytic leukaemia	1/402 (0.2%)	1
Malignant melanoma in situ	1/402 (0.2%)	1
Oncocytoma	1/402 (0.2%)	1
Ovarian cancer	1/402 (0.2%)	1
Parathyroid tumour benign	1/402 (0.2%)	1
Prostate cancer	1/402 (0.2%)	1
Prostatic adenoma	1/402 (0.2%)	1
Renal cell carcinoma stage I	1/402 (0.2%)	1
Squamous cell carcinoma of skin	1/402 (0.2%)	1
Thyroid gland cancer	1/402 (0.2%)	1
Thyroid neoplasm	1/402 (0.2%)	1
Tonsil cancer	1/402 (0.2%)	1
Uterine cancer	1/402 (0.2%)	1
Uterine leiomyoma	1/402 (0.2%)	1
Nervous system disorders
Cerebral ischaemia	1/402 (0.2%)	1
Cerebrovascular accident	3/402 (0.7%)	6
Disturbance in attention	1/402 (0.2%)	1
Dizziness postural	1/402 (0.2%)	1
Epilepsy	1/402 (0.2%)	1
Global amnesia	1/402 (0.2%)	1
Grand mal convulsion	1/402 (0.2%)	1
Headache	1/402 (0.2%)	1
Ischaemic stroke	1/402 (0.2%)	1
Loss of consciousness	1/402 (0.2%)	1
Neuropathy peripheral	1/402 (0.2%)	1
Paraesthesia	1/402 (0.2%)	1
Subarachnoid haemorrhage	1/402 (0.2%)	1
Syncope	2/402 (0.5%)	3
Transient ischaemic attack	1/402 (0.2%)	1
Psychiatric disorders
Depression	1/402 (0.2%)	1
Panic disorder	1/402 (0.2%)	1
Post-traumatic stress disorder	1/402 (0.2%)	1
Renal and urinary disorders
Acute prerenal failure	1/402 (0.2%)	1
Incontinence	1/402 (0.2%)	1
Mixed incontinence	1/402 (0.2%)	1
Nephrolithiasis	4/402 (1%)	5
Renal colic	1/402 (0.2%)	1
Renal failure acute	1/402 (0.2%)	1
Stress incontinence	1/402 (0.2%)	1
Urinary incontinence	1/402 (0.2%)	1
Reproductive system and breast disorders
Benign prostatic hyperplasia	2/402 (0.5%)	2
Cystocele	1/402 (0.2%)	1
Endometriosis	1/402 (0.2%)	1
Menorrhagia	1/402 (0.2%)	1
Metrorrhagia	1/402 (0.2%)	1
Rectocele	1/402 (0.2%)	1
Vaginal prolapse	1/402 (0.2%)	1
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	1/402 (0.2%)	1
Chronic obstructive pulmonary disease	4/402 (1%)	4
Cough	1/402 (0.2%)	1
Pleurisy	1/402 (0.2%)	1
Pulmonary embolism	4/402 (1%)	4
Respiratory failure	3/402 (0.7%)	3
Skin and subcutaneous tissue disorders
Erythema	1/402 (0.2%)	2
Skin ulcer	1/402 (0.2%)	1
Surgical and medical procedures
Synovectomy	1/402 (0.2%)	2
Vascular disorders
Aortic aneurysm	1/402 (0.2%)	1
Arterial occlusive disease	1/402 (0.2%)	1
Arterial stenosis	1/402 (0.2%)	1
Circulatory collapse	1/402 (0.2%)	1
Deep vein thrombosis	4/402 (1%)	4
Embolism	1/402 (0.2%)	1
Hypertension	2/402 (0.5%)	2
Hypertensive crisis	1/402 (0.2%)	1
Hypotension	1/402 (0.2%)	1
Peripheral ischaemia	1/402 (0.2%)	1
Thrombophlebitis	1/402 (0.2%)	1
Varicose vein	1/402 (0.2%)	1
Venous thrombosis	1/402 (0.2%)	1
Other (Not Including Serious) Adverse Events
	Certolizumab Pegol
	Affected / at Risk (%)	# Events
Total	348/402 (86.6%)
Blood and lymphatic system disorders
Anaemia	25/402 (6.2%)	31
Eye disorders
Conjunctivitis	29/402 (7.2%)	34
Gastrointestinal disorders
Abdominal pain upper	22/402 (5.5%)	31
Constipation	24/402 (6%)	29
Diarrhoea	64/402 (15.9%)	135
Dyspepsia	41/402 (10.2%)	60
Nausea	49/402 (12.2%)	65
Vomiting	37/402 (9.2%)	58
General disorders
Fatigue	65/402 (16.2%)	86
Oedema peripheral	38/402 (9.5%)	54
Infections and infestations
Bronchitis	58/402 (14.4%)	89
Bronchitis acute	25/402 (6.2%)	45
Cystitis	33/402 (8.2%)	45
Herpes simplex	44/402 (10.9%)	70
Herpes zoster	24/402 (6%)	27
Influenza	40/402 (10%)	56
Lower respiratory tract infection	27/402 (6.7%)	65
Nasopharyngitis	141/402 (35.1%)	380
Pharyngitis	21/402 (5.2%)	36
Sinusitis	74/402 (18.4%)	123
Upper respiratory tract infection	93/402 (23.1%)	198
Urinary tract infection	84/402 (20.9%)	159
Viral infection	27/402 (6.7%)	42
Injury, poisoning and procedural complications
Contusion	30/402 (7.5%)	44
Fall	28/402 (7%)	42
Investigations
Alanine aminotransferase increased	27/402 (6.7%)	34
Musculoskeletal and connective tissue disorders
Arthralgia	65/402 (16.2%)	118
Back pain	90/402 (22.4%)	137
Bursitis	28/402 (7%)	40
Joint swelling	21/402 (5.2%)	39
Muscle spasms	27/402 (6.7%)	34
Neck pain	22/402 (5.5%)	26
Osteoarthritis	26/402 (6.5%)	49
Pain in extremity	46/402 (11.4%)	68
Rheumatoid arthritis	63/402 (15.7%)	109
Nervous system disorders
Dizziness	42/402 (10.4%)	59
Headache	86/402 (21.4%)	135
Paraesthesia	23/402 (5.7%)	29
Sciatica	28/402 (7%)	34
Psychiatric disorders
Depression	39/402 (9.7%)	49
Insomnia	36/402 (9%)	44
Respiratory, thoracic and mediastinal disorders
Cough	82/402 (20.4%)	126
Dyspnoea	22/402 (5.5%)	32
Pharyngolaryngeal pain	38/402 (9.5%)	52
Skin and subcutaneous tissue disorders
Rash	66/402 (16.4%)	104
Vascular disorders
Hypertension	78/402 (19.4%)	94

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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