Study Comparing 80 mg of Adalimumab With Placebo, and Dem... | NCT00647270 | Trialant
NCT00647270
Sponsor
Abbott
Status
Completed
Last Update Posted
Apr 11, 2011Estimated
Enrollment
420Actual
Phase
Phase 3
Conditions
Rheumatoid Arthritis
Interventions
adalimumab
Placebo
adalimumab
Countries
United States
Australia
Canada
Germany
Puerto Rico
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT00647270
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
M10-261
Secondary IDs
Not provided
Brief Title
Study Comparing 80 mg of Adalimumab With Placebo, and Demonstrating the Non-inferiority of Monthly 80 mg Adalimumab Dosing Compared With 40 mg Adalimumab Every Other Week Dosing
Official Title
A Multi-center, Randomized, Double-blind,Placebo-controlled Study Comparing 80 mg of Adalimumab With Placebo, and Demonstrating the Non-inferiority of Monthly 80 mg Adalimumab Dosing Compared With 40 mg Adalimumab Every Other Week Dosing
Acronym
Not provided
Organization
AbbottINDUSTRY
Status Module
Record Verification Date
Apr 2011
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Dec 2007
Primary Completion Date
Apr 2009Actual
Completion Date
Apr 2009Actual
First Submitted Date
Mar 27, 2008
First Submission Date that Met QC Criteria
Mar 28, 2008
First Posted Date
Mar 31, 2008Estimated
Results Waived
Not provided
Results First Submitted Date
Apr 14, 2010
Results First Submitted that Met QC Criteria
Apr 14, 2010
Results First Posted Date
May 10, 2010Estimated
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Apr 7, 2011
Last Update Posted Date
Apr 11, 2011Estimated
Sponsor/Collaborators Module
Responsible Party, by Official Title
Not provided
Lead Sponsor
AbbottINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
No
Is FDA Regulated Drug
Not provided
Is FDA Regulated Device
Not provided
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
To demonstrate the efficacy of 80 mg adalimumab monthly dosing compared with placebo and demonstrate the non-inferiority of monthly dosing of 80 mg adalimumab compared with dosing of 40 mg adalimumab every other week.
Detailed Description
The objective of this study is to demonstrate the efficacy of 80 mg adalimumab monthly dosing compared with placebo as measured by ACR20 response criteria following 12 weeks of therapy. The study is also designed to demonstrate the non-inferiority of monthly dosing of 80 mg adalimumab compared with dosing of 40 mg adalimumab eow as measured by ACR20 response criteria at Week 12.
The Number of Responders According to the American College of Rheumatology (ACR) 20 Response Criteria at Week 12 Involving the Comparison of Adalimumab 80 mg Monthly Dose Versus Placebo and Adalimumab 40 mg Every Other Week (Eow)
Comparison of adalimumab 80 mg monthly dose versus placebo and adalimumab 40 mg eow in the number of responders with ACR criteria improvement consisting of 20%, (ACR20) reduction in tender or swollen joint counts (TJC or SJC, respectively) and 20% improvement in 3 of the following 5 criteria: [1] physician's global assessment of disease activity (PGA), [2] subject's assessment of disease activity, [3] subject's assessment of pain, [4] subject's assessment of physical disability via a health assessment questionnaire disability index(HAQ-DI), and [5] C-reactive protein (CRP) at each visit
Week 12
Secondary Outcomes
Measure
Description
Time Frame
Within Group Mean Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 (Observed)
The HAQ-DI is a self-reported subject measure of physical function calculated as the mean of 8 category scores: Dressing and Grooming, Rising, Eating, Walking, Hygiene, Reach, Grip, and Activities. Each category score is calculated as the maximum of the scores for the questions within the category. The HAQ-DI is expressed on a scale of 0 (without any difficulty) to 3 (unable to do) representing an average score across the category. Scores for at least 6 categories are needed to compute the HAQ score. Changes to lower scores indicate improvement in physical function.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Subject > 18 years of age
Subject has a diagnosis of RA as defined by the 1987-revised ACR-classification criteria and has a disease duration for a minimum of three months
Subject must meet the following two criteria: a) At least 6 swollen joints out of 66 assessed, or b) At least 6 tender joints out of 68 assessed
If a subject is on MTX, the doses must be stable for at least 4 weeks prior to Screening blood draw and follow standard recommendations for MTX treatment
Subject is judged to be in generally good health as determined by the principal investigator
Exclusion Criteria:
Subject has previous exposure to any systemic anti-TNF therapy (eg, infliximab, etanercept, certolizumab pegol or golimumab) including adalimumab
Subject has a history of acute inflammatory joint disease of different origin other than RA
Subject has been treated with any investigational biologic agents
Subject considered by the investigator, for any reason, to be an unsuitable candidate for the study
Female subject who is pregnant or breast-feeding or considering becoming pregnant
Burmester GR, Landewe R, Genovese MC, Friedman AW, Pfeifer ND, Varothai NA, Lacerda AP. Adalimumab long-term safety: infections, vaccination response and pregnancy outcomes in patients with rheumatoid arthritis. Ann Rheum Dis. 2017 Feb;76(2):414-417. doi: 10.1136/annrheumdis-2016-209322. Epub 2016 Jun 23.
See Also Links
Not provided
Available IPD Information
Not provided
IPD Sharing Statement Module
No data available
No data is available for this block.
Results Section
Participant Flow Module
Pre-assignment Details
A total of 432 subjects were enrolled, randomized, and received at least 1 dose of study drug. A total of 420 subjects were defined as the Full analysis set (FAS), which excluded the 12 subjects enrolled at a non-compliant site. A total of 48 subjects were switched from placebo to adalimumab 40 mg eow and participated in Period 2.
Recruitment Details
The study was conducted at 72 sites in the United States, Canada, Puerto Rico, Germany, the United Kingdom, and Australia. Subjects received over the course of 24 weeks either 80 mg adalimumab monthly, 40 mg adalimumab every other week (eow), or placebo (12 weeks) followed by 40 mg adalimumab eow (12 weeks).
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Placebo
Placebo 40 mg every other week (eow) for 12 weeks for Period 1; Adalimumab 40 mg eow for remaining 12 weeks for Period 2
Within Group Mean Change From Baseline in the Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 (Last Observation Carried Forward [LOCF])
The HAQ-DI is a self-reported subject measure of physical function calculated as the mean of 8 category scores: Dressing and Grooming, Rising, Eating, Walking, Hygiene, Reach, Grip, and Activities. Each category score is calculated as the maximum of the scores for the questions within the category. The HAQ-DI is expressed on a scale of 0 (without any difficulty) to 3 (unable to do) representing an average score across the category. Scores for at least 6 categories are needed to compute the HAQ score. Changes to lower scores indicate improvement in physical function.
Baseline and Week 12
Between Group Mean Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 (Observed)
The HAQ-DI is a self-reported subject measure of physical function calculated as the mean of 8 category scores: Dressing and Grooming, Rising, Eating, Walking, Hygiene, Reach, Grip, and Activities. Each category score is calculated as the maximum of the scores for the questions within the category. The HAQ-DI is expressed on a scale of 0 (without any difficulty) to 3 (unable to do) representing an average score across the category. Scores for at least 6 categories are needed to compute the HAQ score. Changes to lower scores indicate improvement in physical function.
Baseline and Week 12
Between Group Mean Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 (Last Observation Carried Forward [LOCF])
The HAQ-DI is a self-reported subject measure of physical function calculated as the mean of 8 category scores: Dressing and Grooming, Rising, Eating, Walking, Hygiene, Reach, Grip, and Activities. Each category score is calculated as the maximum of the scores for the questions within the category. The HAQ-DI is expressed on a scale of 0 (without any difficulty) to 3 (unable to do) representing an average score across the category. Scores for at least 6 categories are needed to compute the HAQ score. Changes to lower scores indicate improvement in physical function.
Adalimumab 80 mg monthly for Period 1 and Period 2
FG00056 subjectsPlacebo subjects in Period 1 received adalimumab 40 mg every other week in Period 2.
FG001159 subjects
FG002205 subjects
COMPLETED
FG00048 subjects
FG001146 subjects
FG002182 subjects
NOT COMPLETED
FG0008 subjects
FG00113 subjects
FG00223 subjects
Type
Comment
Reasons
Adverse Event
FG0002 subjects
FG0017 subjects
FG0027 subjects
Lost to Follow-up
FG0000 subjects
FG0011 subjects
FG0021 subjects
Withdrawal by Subject
FG0002 subjects
FG0011 subjects
FG0027 subjects
Other
FG0004 subjects
FG0014 subjects
FG0028 subjects
Period 2, Placebo Switched to Adalimumab
Type
Comment
Milestone Data
STARTED
FG00048 subjectsPlacebo subjects in Period 1 received adalimumab 40 mg eow in Period 2
FG001146 subjects
FG002182 subjects
COMPLETED
FG00045 subjects
FG001137 subjects
FG002175 subjects
NOT COMPLETED
FG0003 subjects
FG0019 subjects
FG0027 subjects
Type
Comment
Reasons
Adverse Event
FG0001 subjects
FG0013 subjects
FG0023 subjects
Withdrawal by Subject
FG000
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Placebo
Placebo 40 mg every other week (eow) for 12 weeks for Period 1; Adalimumab 40 mg eow for remaining 12 weeks for Period 2
BG001
Adalimumab 40 mg Eow
Adalimumab 40 mg eow for Period 1 and Period 2
BG002
Adalimumab 80 mg Monthly
Adalimumab 80 mg monthly for Period 1 and Period 2
BG003
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00056
BG001159
BG002205
BG003420
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Customized
Number
participants
Title
Denominators
Categories
< 65 years
Title
Measurements
BG00043
BG001113
BG002148
BG003
Age Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00054.4± 12.46
BG00157.2± 12.79
BG002
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00043
BG001122
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
The Number of Responders According to the American College of Rheumatology (ACR) 20 Response Criteria at Week 12 Involving the Comparison of Adalimumab 80 mg Monthly Dose Versus Placebo and Adalimumab 40 mg Every Other Week (Eow)
Comparison of adalimumab 80 mg monthly dose versus placebo and adalimumab 40 mg eow in the number of responders with ACR criteria improvement consisting of 20%, (ACR20) reduction in tender or swollen joint counts (TJC or SJC, respectively) and 20% improvement in 3 of the following 5 criteria: [1] physician's global assessment of disease activity (PGA), [2] subject's assessment of disease activity, [3] subject's assessment of pain, [4] subject's assessment of physical disability via a health assessment questionnaire disability index(HAQ-DI), and [5] C-reactive protein (CRP) at each visit
Full Analysis Set (FAS) - a subset of the intent to treat population used in all efficacy analyses excluding subjects from an Abbott identified Investigator who was non-compliant with the protocol requirements. The FAS of subjects who received at least 1 dose of study drug during Period 2 of the study was used for Period 2 efficacy analyses.
Posted
Number
participants
Week 12
ID
Title
Description
OG000
Placebo
Placebo 40 mg every other week (eow) for 12 weeks for Period 1; Adalimumab 40 mg eow for remaining 12 weeks for Period 2
OG001
Adalimumab 40 mg Eow
Adalimumab 40 mg eow for Period 1 and Period 2
OG002
Adalimumab 80 mg Monthly
Adalimumab 80 mg monthly for Period 1 and Period 2
Units
Counts
Participants
OG00056
OG001159
OG002205
Title
Denominators
Categories
Responders
Title
Measurements
OG00019
OG00180
OG00297
Nonresponders
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG002
Adalimumab 80 mg monthly versus placebo: The null hypothesis associated with this comparison stated that adalimumab 80 mg monthly would be inferior to placebo with respect to ACR20 response percentage; the alternative hypothesis was that adalimumab 80 mg monthly would be superior to placebo with respect to ACR20 response.
Chi-squared
0.074
Mean Difference (Final Values)
-3.0
2-Sided
95
-13.3
7.4
Treatment difference between adalimumab 80 mg monthly and placebo divided by the difference between adalimumab 40 mg eow and placebo.
No
Superiority or Other
Secondary
Within Group Mean Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 (Observed)
The HAQ-DI is a self-reported subject measure of physical function calculated as the mean of 8 category scores: Dressing and Grooming, Rising, Eating, Walking, Hygiene, Reach, Grip, and Activities. Each category score is calculated as the maximum of the scores for the questions within the category. The HAQ-DI is expressed on a scale of 0 (without any difficulty) to 3 (unable to do) representing an average score across the category. Scores for at least 6 categories are needed to compute the HAQ score. Changes to lower scores indicate improvement in physical function.
Full Analysis Set (FAS)-a subset of the intent to treat population used in all efficacy analyses excluding subjects from an Abbott identified Investigator who was non-compliant with protocol requirements. The FAS of subjects who received at least 1 dose of study drug during Period 2 of the study was used for Period 2 efficacy analyses (observed).
Posted
Mean
Standard Deviation
units on a score
Baseline and Week 12
ID
Title
Description
OG000
Placebo
Placebo 40 mg every other week (eow) for 12 weeks for Period 1; Adalimumab 40 mg eow for remaining 12 weeks for Period 2
OG001
Adalimumab 40 mg Eow
Adalimumab 40 mg eow for Period 1 and Period 2
OG002
Secondary
Within Group Mean Change From Baseline in the Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 (Last Observation Carried Forward [LOCF])
The HAQ-DI is a self-reported subject measure of physical function calculated as the mean of 8 category scores: Dressing and Grooming, Rising, Eating, Walking, Hygiene, Reach, Grip, and Activities. Each category score is calculated as the maximum of the scores for the questions within the category. The HAQ-DI is expressed on a scale of 0 (without any difficulty) to 3 (unable to do) representing an average score across the category. Scores for at least 6 categories are needed to compute the HAQ score. Changes to lower scores indicate improvement in physical function.
Full Analysis Set (FAS)-a subset of the intent to treat population used in all efficacy analyses excluding subjects from an Abbott identified Investigator who was non-compliant with protocol requirements. The FAS of subjects who received at least 1 dose of study drug during Period 2 of the study was used for Period 2 efficacy analyses (LOCF).
Posted
Mean
Standard Deviation
units on a score
Baseline and Week 12
ID
Title
Description
OG000
Placebo
Placebo 40 mg every other week (eow) for 12 weeks for Period 1; Adalimumab 40 mg eow for remaining 12 weeks for Period 2
OG001
Adalimumab 40 mg Eow
Adalimumab 40 mg eow for Period 1 and Period 2
Secondary
Between Group Mean Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 (Observed)
The HAQ-DI is a self-reported subject measure of physical function calculated as the mean of 8 category scores: Dressing and Grooming, Rising, Eating, Walking, Hygiene, Reach, Grip, and Activities. Each category score is calculated as the maximum of the scores for the questions within the category. The HAQ-DI is expressed on a scale of 0 (without any difficulty) to 3 (unable to do) representing an average score across the category. Scores for at least 6 categories are needed to compute the HAQ score. Changes to lower scores indicate improvement in physical function.
Full Analysis Set (FAS) - a subset of the intent to treat population used in all efficacy analyses excluding subjects from an Abbott identified Investigator who was non-compliant with the protocol requirements. The FAS of subjects who received at least 1 dose of study drug during Period 2 of the study was used for Period 2 efficacy analyses.
Posted
Least Squares Mean
Standard Error
units on a score
Baseline and Week 12
ID
Title
Description
OG000
Placebo
Placebo 40 mg every other week (eow) for 12 weeks for Period 1; Adalimumab 40 mg eow for remaining 12 weeks for Period 2
OG001
Adalimumab 40 mg Eow
Adalimumab 40 mg eow for Period 1 and Period 2
Secondary
Between Group Mean Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 (Last Observation Carried Forward [LOCF])
The HAQ-DI is a self-reported subject measure of physical function calculated as the mean of 8 category scores: Dressing and Grooming, Rising, Eating, Walking, Hygiene, Reach, Grip, and Activities. Each category score is calculated as the maximum of the scores for the questions within the category. The HAQ-DI is expressed on a scale of 0 (without any difficulty) to 3 (unable to do) representing an average score across the category. Scores for at least 6 categories are needed to compute the HAQ score. Changes to lower scores indicate improvement in physical function.
Full Analysis Set (FAS) - a subset of the intent to treat population used in all efficacy analyses excluding subjects from an Abbott identified Investigator who was non-compliant with the protocol requirements. The FAS of subjects who received at least 1 dose of study drug during Period 2 of the study was used for Period 2 efficacy analyses.
Posted
Least Squares Mean
Standard Error
units on a score
Baseline and Week 12
ID
Title
Description
OG000
Placebo
Placebo 40 mg every other week (eow) for 12 weeks for Period 1; Adalimumab 40 mg eow for remaining 12 weeks for Period 2
OG001
Adalimumab 40 mg Eow
Adalimumab 40 mg eow for Period 1 and Period 2
Time Frame
24 Weeks
Description
Not provided
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Placebo Every Other Week (Eow)-Period 1
Placebo eow for 12 weeks for Period 1 Adalimumab 40 mg eow for remaining 12 weeks for Period 2
5
57
13
57
EG001
Adalimumab 40 mg Eow -Period 1
Adalimumab 40 mg eow for Period 1 and Period 2
8
164
29
164
EG002
Adalimumab 80 mg Monthly-Period 1
Adalimumab 80 mg monthly for Period 1 and Period 2
4
211
38
211
EG003
Placebo/Adalimumab 40 mg Eow-Period 2
Placebo 40 mg eow for Period 1 (weeks 1-12) Subjects switched to Adalimumab 40 mg eow for remaining 12 weeks for Period 2
1
49
6
49
EG004
Adalimumab 40 mg Eow-Period 2
Adalimumab 40 mg eow for Period 1 and Period 2
5
151
14
151
EG005
Adalimumab 80 mg Monthly - Period 2
Adalimumab 80 mg monthly for Period 1 and Period 2
12
188
11
188
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Abdominal adhesions
Gastrointestinal disorders
MedDRA 12.0
Non-systematic Assessment
EG0000 affected57 at risk
EG0011 affected164 at risk
EG0020 affected211 at risk
EG0030 affected49 at risk
EG0040 affected151 at risk
EG0050 affected188 at risk
Small intestinal stenosis
Gastrointestinal disorders
MedDRA 12.0
Non-systematic Assessment
EG0000 affected57 at risk
EG0011 affected164 at risk
EG0020 affected211 at risk
EG003
Oedema peripheral
General disorders
MedDRA 12.0
Non-systematic Assessment
EG0000 affected57 at risk
EG0011 affected164 at risk
EG0020 affected211 at risk
EG003
Cellulitis
Infections and infestations
MedDRA 12.0
Non-systematic Assessment
EG0000 affected57 at risk
EG0010 affected164 at risk
EG0022 affected211 at risk
EG003
Gastroenteritis
Infections and infestations
MedDRA 12.0
Non-systematic Assessment
EG0000 affected57 at risk
EG0011 affected164 at risk
EG0020 affected211 at risk
EG003
Meningitis meningococcal
Infections and infestations
MedDRA 12.0
Non-systematic Assessment
EG0000 affected57 at risk
EG0010 affected164 at risk
EG0021 affected211 at risk
EG003
Pneumonia
Infections and infestations
MedDRA 12.0
Non-systematic Assessment
EG0000 affected57 at risk
EG0014 affected164 at risk
EG0020 affected211 at risk
EG003
Septic shock
Infections and infestations
MedDRA 12.0
Non-systematic Assessment
EG0000 affected57 at risk
EG0011 affected164 at risk
EG0020 affected211 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA 12.0
Non-systematic Assessment
EG0000 affected57 at risk
EG0012 affected164 at risk
EG0020 affected211 at risk
EG003
Cervical vertebral fracture
Injury, poisoning and procedural complications
MedDRA 12.0
Non-systematic Assessment
EG0000 affected57 at risk
EG0010 affected164 at risk
EG0021 affected211 at risk
EG003
Drug toxicity
Injury, poisoning and procedural complications
MedDRA 12.0
Non-systematic Assessment
EG0001 affected57 at risk
EG0010 affected164 at risk
EG0020 affected211 at risk
EG003
Femur fracture
Injury, poisoning and procedural complications
MedDRA 12.0
Non-systematic Assessment
EG0001 affected57 at risk
EG0010 affected164 at risk
EG0020 affected211 at risk
EG003
Head injury
Injury, poisoning and procedural complications
MedDRA 12.0
Non-systematic Assessment
EG0000 affected57 at risk
EG0010 affected164 at risk
EG0021 affected211 at risk
EG003
Humerus fracture
Injury, poisoning and procedural complications
MedDRA 12.0
Non-systematic Assessment
EG0000 affected57 at risk
EG0011 affected164 at risk
EG0020 affected211 at risk
EG003
Limb injury
Injury, poisoning and procedural complications
MedDRA 12.0
Non-systematic Assessment
EG0000 affected57 at risk
EG0010 affected164 at risk
EG0021 affected211 at risk
EG003
Patella fracture
Injury, poisoning and procedural complications
MedDRA 12.0
Non-systematic Assessment
EG0001 affected57 at risk
EG0010 affected164 at risk
EG0020 affected211 at risk
EG003
Pubic rami fracture
Injury, poisoning and procedural complications
MedDRA 12.0
Non-systematic Assessment
EG0000 affected57 at risk
EG0011 affected164 at risk
EG0020 affected211 at risk
EG003
Hypovolaemia
Metabolism and nutrition disorders
MedDRA 12.0
Non-systematic Assessment
EG0000 affected57 at risk
EG0011 affected164 at risk
EG0020 affected211 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA 12.0
Non-systematic Assessment
EG0000 affected57 at risk
EG0011 affected164 at risk
EG0020 affected211 at risk
EG003
Prostate cancer
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 12.0
Non-systematic Assessment
EG0000 affected57 at risk
EG0011 affected164 at risk
EG0020 affected211 at risk
EG003
Dizziness
Nervous system disorders
MedDRA 12.0
Non-systematic Assessment
EG0000 affected57 at risk
EG0011 affected164 at risk
EG0021 affected211 at risk
EG003
Renal failure acute
Renal and urinary disorders
MedDRA 12.0
Non-systematic Assessment
EG0000 affected57 at risk
EG0011 affected164 at risk
EG0020 affected211 at risk
EG003
Arteriosclerosis
Vascular disorders
MedDRA 12.0
Non-systematic Assessment
EG0001 affected57 at risk
EG0010 affected164 at risk
EG0020 affected211 at risk
EG003
Haematoma
Vascular disorders
MedDRA 12.0
Non-systematic Assessment
EG0001 affected57 at risk
EG0010 affected164 at risk
EG0020 affected211 at risk
EG003
Neutropenia
Blood and lymphatic system disorders
MedDRA 12.0
Non-systematic Assessment
EG0000 affected57 at risk
EG0010 affected164 at risk
EG0020 affected211 at risk
EG003
Cardiac failure congestive
Cardiac disorders
MedDRA 12.0
Non-systematic Assessment
EG0000 affected57 at risk
EG0010 affected164 at risk
EG0020 affected211 at risk
EG003
Coronary artery disease
Cardiac disorders
MedDRA 12.0
Non-systematic Assessment
EG0000 affected57 at risk
EG0010 affected164 at risk
EG0020 affected211 at risk
EG003
Myocardial infaection
Cardiac disorders
MedDRA 12.0
Non-systematic Assessment
EG0000 affected57 at risk
EG0010 affected164 at risk
EG0020 affected211 at risk
EG003
Abdominal pain
Cardiac disorders
MedDRA 12.0
Non-systematic Assessment
EG0000 affected57 at risk
EG0010 affected164 at risk
EG0020 affected211 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA 12.0
Non-systematic Assessment
EG0000 affected57 at risk
EG0010 affected164 at risk
EG0020 affected211 at risk
EG003
Death
General disorders
MedDRA 12.0
Non-systematic Assessment
EG0000 affected57 at risk
EG0010 affected164 at risk
EG0020 affected211 at risk
EG003
Diverticulitis
Infections and infestations
MedDRA 12.0
Non-systematic Assessment
EG0000 affected57 at risk
EG0010 affected164 at risk
EG0020 affected211 at risk
EG003
Meningitis
Infections and infestations
MedDRA 12.0
Non-systematic Assessment
EG0000 affected57 at risk
EG0010 affected164 at risk
EG0020 affected211 at risk
EG003
Staphylococcal infection
Infections and infestations
MedDRA 12.0
Non-systematic Assessment
EG0000 affected57 at risk
EG0010 affected164 at risk
EG0020 affected211 at risk
EG003
Ankle fracture
Injury, poisoning and procedural complications
MedDRA 12.0
Non-systematic Assessment
EG0000 affected57 at risk
EG0010 affected164 at risk
EG0020 affected211 at risk
EG003
Fibula fracture
Injury, poisoning and procedural complications
MedDRA 12.0
Non-systematic Assessment
EG0000 affected57 at risk
EG0010 affected164 at risk
EG0020 affected211 at risk
EG003
Splenic haematoma
Infections and infestations
MedDRA 12.0
Non-systematic Assessment
EG0000 affected57 at risk
EG0010 affected164 at risk
EG0020 affected211 at risk
EG003
Hypokalamia
Metabolism and nutrition disorders
MedDRA 12.0
Non-systematic Assessment
EG0000 affected57 at risk
EG0010 affected164 at risk
EG0020 affected211 at risk
EG003
Rheumatoid arthritis
Musculoskeletal and connective tissue disorders
MedDRA 12.0
Non-systematic Assessment
EG0000 affected57 at risk
EG0010 affected164 at risk
EG0020 affected211 at risk
EG003
Spinal osteoarthritis
Musculoskeletal and connective tissue disorders
MedDRA 12.0
Non-systematic Assessment
EG0000 affected57 at risk
EG0010 affected164 at risk
EG0020 affected211 at risk
EG003
Breast cancer
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 12.0
Non-systematic Assessment
EG0000 affected57 at risk
EG0010 affected164 at risk
EG0020 affected211 at risk
EG003
Lung adenocarcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 12.0
Non-systematic Assessment
EG0000 affected57 at risk
EG0010 affected164 at risk
EG0020 affected211 at risk
EG003
Presyncope
Nervous system disorders
MedDRA 12.0
Non-systematic Assessment
EG0000 affected57 at risk
EG0010 affected164 at risk
EG0020 affected211 at risk
EG003
Depression
Psychiatric disorders
MedDRA 12.0
Non-systematic Assessment
EG0000 affected57 at risk
EG0010 affected164 at risk
EG0020 affected211 at risk
EG003
Acute respiratory distress syndrome
Respiratory, thoracic and mediastinal disorders
MedDRA 12.0
Non-systematic Assessment
EG0000 affected57 at risk
EG0010 affected164 at risk
EG0020 affected211 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA 12.0
Non-systematic Assessment
EG0000 affected57 at risk
EG0010 affected164 at risk
EG0020 affected211 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA 12.0
Non-systematic Assessment
EG0000 affected57 at risk
EG0010 affected164 at risk
EG0020 affected211 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
diarrhoea
Gastrointestinal disorders
MedDRA 12.0
Non-systematic Assessment
EG0004 affected57 at risk
EG0012 affected164 at risk
EG0024 affected211 at risk
EG0030 affected49 at risk
EG0040 affected151 at risk
EG0050 affected188 at risk
nausea
Gastrointestinal disorders
MedDRA 12.0
Non-systematic Assessment
EG0003 affected57 at risk
EG0019 affected164 at risk
EG00213 affected211 at risk
EG003
nasopharyngitis
Infections and infestations
MedDRA 12.0
Non-systematic Assessment
EG0003 affected57 at risk
EG0018 affected164 at risk
EG0022 affected211 at risk
EG003
upper respiratory tract infection
Infections and infestations
MedDRA 12.0
Non-systematic Assessment
EG0004 affected57 at risk
EG0015 affected164 at risk
EG00211 affected211 at risk
EG003
dizziness
Nervous system disorders
MedDRA 12.0
Non-systematic Assessment
EG0003 affected57 at risk
EG0014 affected164 at risk
EG0025 affected211 at risk
EG003
headache
Nervous system disorders
MedDRA 12.0
Non-systematic Assessment
EG0003 affected57 at risk
EG0018 affected164 at risk
EG00210 affected211 at risk
EG003
cough
Respiratory, thoracic and mediastinal disorders
MedDRA 12.0
Non-systematic Assessment
EG0003 affected57 at risk
EG0011 affected164 at risk
EG0021 affected211 at risk
EG003
Abbott identified Investigator non-compliance with the protocol requirements at one site and made the decision to exclude the data from this site from all efficacy analyses. Sample size was too small to demonstrate superiority and non-inferiority.
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
Abbott requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. Abbott requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if Abbott needs to secure patent or proprietary protection.
Point of Contact
Title
Organization
Phone
Extension
Email
Global Medical Services
Abbott
800-633-9110
ID
Term
D001172
Arthritis, Rheumatoid
Ancestor Terms
ID
Term
D001168
Arthritis
D007592
Joint Diseases
D009140
Musculoskeletal Diseases
D012216
Rheumatic Diseases
D003240
Connective Tissue Diseases
D017437
Skin and Connective Tissue Diseases
D001327
Autoimmune Diseases
D007154
Immune System Diseases
Browse Leaves
Not provided
Browse Branches
Not provided
ID
Term
D000068879
Adalimumab
Ancestor Terms
ID
Term
D061067
Antibodies, Monoclonal, Humanized
D000911
Antibodies, Monoclonal
D000906
Antibodies
D007136
Immunoglobulins
D007162
Immunoproteins
D001798
Blood Proteins
D011506
Proteins
D000602
Amino Acids, Peptides, and Proteins
D012712
Serum Globulins
D005916
Globulins
Browse Leaves
Not provided
Browse Branches
Not provided
0 subjects
FG0010 subjects
FG0024 subjects
Other
FG0002 subjects
FG0016 subjects
FG0020 subjects
304
>= 65 years
Title
Measurements
BG00013
BG00146
BG00257
BG003116
56.3
± 12.43
BG00356.4± 12.58
149
BG003314
Male
BG00013
BG00137
BG00256
BG003106
Title
Measurements
OG00037
OG00179
OG002108
OG001
OG002
The non-inferiority of adalimumab 80 mg monthly to adalimumab 40 mg every other week (eow) was to be claimed if at least 50% of the treatment effect of adalimumab 40 mg eow over placebo was to be achieved by adalimumab 80 mg monthly over placebo.
Chi-squared
0.74
Non - inferiority of adalimumab 80 mg monthly compared with 40 mg eow could not be tested because the null hypothesis of the first comparison was not rejected.
95
Yes
Non-Inferiority or Equivalence
A sensitivity analysis was proposed for the non-inferiority comparison. If the lower confidence limit of θ80 - θ40 was greater than -0.1, then the non-inferiority of adalimumab 80 mg monthly to adalimumab 40 mg eow would be claimed
Adalimumab 80 mg Monthly
Adalimumab 80 mg monthly for Period 1 and Period 2
Units
Counts
Participants
OG00056
OG001159
OG002205
Title
Denominators
Categories
Title
Measurements
OG000-0.11± 0.488
OG001-0.41± 0.508
OG002-0.39± 0.536
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG002
Using a fixed-sequence multiple-testing approach at an alpha level of 0.05 to test the secondary endpoints, the testing of the null-hypothesis began with the first endpoint and stopped as soon as failure to reject a hypothesis occurred (i.e., P value > 0.05). Using this procedure, testing stopped after secondary endpoint number 1, change from Baseline in HAQ at Week 12.
ANCOVA
0.002
95
No
Superiority or Other
OG002
Adalimumab 80 mg Monthly
Adalimumab 80 mg monthly for Period 1 and Period 2
Units
Counts
Participants
OG00056
OG001159
OG002205
Title
Denominators
Categories
Title
Measurements
OG000-0.12± 0.484
OG001-0.40± 0.507
OG002-0.37± 0.537
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG002
Using a fixed-sequence multiple-testing approach at an alpha level of 0.05 to test the secondary endpoints, the testing of the null-hypothesis began with the first endpoint and stopped as soon as failure to reject a hypothesis occurred (i.e., P value > 0.05). Using this procedure, testing stopped after secondary endpoint number 1, change from Baseline in HAQ at Week 12.
ANCOVA
0.005
95
No
Superiority or Other
OG000
OG001
Using a fixed-sequence multiple-testing approach at an alpha level of 0.05 to test the secondary endpoints, the testing of the null-hypothesis began with the first endpoint and stopped as soon as failure to reject a hypothesis occurred (i.e., P value > 0.05). Using this procedure, testing stopped after secondary endpoint number 1, change from Baseline in HAQ at Week 12.
ANCOVA
0.002
95
No
Superiority or Other
OG002
Adalimumab 80 mg Monthly
Adalimumab 80 mg monthly for Period 1 and Period 2
Units
Counts
Participants
OG00056
OG001159
OG002205
Title
Denominators
Categories
Title
Measurements
OG0000± 0
OG001-0.26± 0.081
OG002-0.24± 0.079
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
OG002
Using a fixed-sequence multiple-testing approach at an alpha level of 0.05 to test the secondary endpoints, the testing of the null-hypothesis began with the first endpoint and stopped as soon as failure to reject a hypothesis occurred (i.e., P value > 0.05). Using this procedure, testing stopped after secondary endpoint number 1, change from Baseline in HAQ at Week 12.
ANCOVA
0.002
The ANCOVA Model was adjusted for the Baseline Measure.
95
No
Superiority or Other
OG002
Adalimumab 80 mg Monthly
Adalimumab 80 mg monthly for Period 1 and Period 2
Units
Counts
Participants
OG00056
OG001159
OG002205
Title
Denominators
Categories
Title
Measurements
OG0000± 0
OG001-0.24± 0.077
OG002-0.21± 0.075
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG002
Using a fixed-sequence multiple-testing approach at an alpha level of 0.05 to test the secondary endpoints, the testing of the null-hypothesis began with the first endpoint and stopped as soon as failure to reject a hypothesis occurred (i.e., P value > 0.05). Using this procedure, testing stopped after secondary endpoint number 1, change from Baseline in HAQ at Week 12.
ANCOVA
The ANCOVA Model was adjusted for Baseline Measure.
0.005
The ANCOVA Model was adjusted for Baseline Measure.