Trial Outcomes & Findings for A 6-month Randomised, Double-blind, Open Arm Comparator, Phase IIb, With AZD9056, in Patients With Rheumatoid Arthritis (RA) (NCT NCT00520572)
NCT ID: NCT00520572
Last Updated: 2013-02-04
Results Overview
The number of participants with greater to or equal to 20% improvement in the ACR composite score (a measure of RA symptoms including: joint swelling and tenderness; patient's assessment of pain, disease activity and physical function; physician's assessment of disease activity; and CRP) after 6 months' treatment
COMPLETED
PHASE2
385 participants
6 months
2013-02-04
Participant Flow
The first participant enrolled on 01 August 2007, the last participant completed the study on 08 April 2009. Participants were recruited from 59 centres in 12 countries in Australia, Canada, Europe, Russia, South America, and the USA.
Male/female participants with active rheumatoid arthritis (and on background methotrexate or sulphasalazine) were randomly assigned to receive AZD9056 at 50, 100, 200 or 400 mg once daily, placebo or etanercept. It was planned to randomise approximately 360 participants, 60 to the open-label etanercept arm and 300 to the AZD9056 or placebo arms
Participant milestones
| Measure |
AZD9056 50 mg
AZD9056 50 mg, oral tablets, once daily, double blinded
|
AZD9056 100 mg
AZD9056 100 mg, oral tablets, once daily, double blinded
|
AZD9056 200 mg
AZD9056 200 mg, oral tablets, once daily, double blinded
|
AZD9056 400 mg
AZD9056 400 mg, oral tablets, once daily, double blinded
|
Placebo
Placebo to AZD9056, oral tablets, once daily, double blinded
|
Etanercept
Etanercept 50 mg, subcutaneous injection, once weekly, open label
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
64
|
64
|
64
|
64
|
65
|
64
|
|
Overall Study
COMPLETED
|
52
|
50
|
49
|
50
|
53
|
62
|
|
Overall Study
NOT COMPLETED
|
12
|
14
|
15
|
14
|
12
|
2
|
Reasons for withdrawal
| Measure |
AZD9056 50 mg
AZD9056 50 mg, oral tablets, once daily, double blinded
|
AZD9056 100 mg
AZD9056 100 mg, oral tablets, once daily, double blinded
|
AZD9056 200 mg
AZD9056 200 mg, oral tablets, once daily, double blinded
|
AZD9056 400 mg
AZD9056 400 mg, oral tablets, once daily, double blinded
|
Placebo
Placebo to AZD9056, oral tablets, once daily, double blinded
|
Etanercept
Etanercept 50 mg, subcutaneous injection, once weekly, open label
|
|---|---|---|---|---|---|---|
|
Overall Study
Adverse Event
|
9
|
3
|
6
|
9
|
7
|
2
|
|
Overall Study
Withdrawal by Subject
|
0
|
9
|
5
|
2
|
2
|
0
|
|
Overall Study
Protocol Violation
|
0
|
0
|
1
|
0
|
0
|
0
|
|
Overall Study
Lack of Efficacy
|
1
|
1
|
1
|
2
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
0
|
0
|
0
|
0
|
1
|
0
|
|
Overall Study
Incorrect enrollment
|
1
|
0
|
1
|
0
|
1
|
0
|
|
Overall Study
Oral corticotherapy for acute urticaria
|
0
|
1
|
0
|
0
|
0
|
0
|
|
Overall Study
Long break in taking Medication
|
0
|
0
|
0
|
1
|
0
|
0
|
|
Overall Study
Did not receive Treatment
|
1
|
0
|
1
|
0
|
0
|
0
|
Baseline Characteristics
A 6-month Randomised, Double-blind, Open Arm Comparator, Phase IIb, With AZD9056, in Patients With Rheumatoid Arthritis (RA)
Baseline characteristics by cohort
| Measure |
AZD9056 50 mg
n=63 Participants
AZD9056 50 mg, oral tablets, once daily, double blinded
|
AZD9056 100 mg
n=64 Participants
AZD9056 100 mg, oral tablets, once daily, double blinded
|
AZD9056 200 mg
n=63 Participants
AZD9056 200 mg, oral tablets, once daily, double blinded
|
AZD9056 400 mg
n=64 Participants
AZD9056 400 mg, oral tablets, once daily, double blinded
|
Placebo
n=65 Participants
Placebo to AZD9056, oral tablets, once daily, double blinded
|
Etanercept
n=64 Participants
Etanercept 50 mg, subcutaneous injection, once weekly, open label
|
Total
n=383 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age Continuous
|
52 Years
STANDARD_DEVIATION 12.8 • n=5 Participants
|
54 Years
STANDARD_DEVIATION 11.5 • n=7 Participants
|
50 Years
STANDARD_DEVIATION 11.9 • n=5 Participants
|
52 Years
STANDARD_DEVIATION 11.8 • n=4 Participants
|
51 Years
STANDARD_DEVIATION 11.9 • n=21 Participants
|
51 Years
STANDARD_DEVIATION 10.8 • n=10 Participants
|
51.7 Years
STANDARD_DEVIATION 11.76 • n=115 Participants
|
|
Sex: Female, Male
Female
|
56 Participants
n=5 Participants
|
54 Participants
n=7 Participants
|
51 Participants
n=5 Participants
|
59 Participants
n=4 Participants
|
54 Participants
n=21 Participants
|
55 Participants
n=10 Participants
|
329 Participants
n=115 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
11 Participants
n=21 Participants
|
9 Participants
n=10 Participants
|
54 Participants
n=115 Participants
|
PRIMARY outcome
Timeframe: 6 monthsThe number of participants with greater to or equal to 20% improvement in the ACR composite score (a measure of RA symptoms including: joint swelling and tenderness; patient's assessment of pain, disease activity and physical function; physician's assessment of disease activity; and CRP) after 6 months' treatment
Outcome measures
| Measure |
AZD9056 50 mg
n=63 Participants
AZD9056 50 mg, oral tablets, once daily, double blinded
|
AZD9056 100 mg
n=64 Participants
AZD9056 100 mg, oral tablets, once daily, double blinded
|
AZD9056 200 mg
n=63 Participants
AZD9056 200 mg, oral tablets, once daily, double blinded
|
AZD9056 400 mg
n=64 Participants
AZD9056 400 mg, oral tablets, once daily, double blinded
|
Placebo
n=65 Participants
Placebo to AZD9056, oral tablets, once daily, double blinded
|
Etanercept
n=64 Participants
Etanercept 50 mg, subcutaneous injection, once weekly, open label
|
|---|---|---|---|---|---|---|
|
American College of Rheumatology 20 Response (ACR20) at 6 Months
|
23 Participants
|
26 Participants
|
23 Participants
|
21 Participants
|
21 Participants
|
42 Participants
|
SECONDARY outcome
Timeframe: 6 monthsThe number of participants with greater to or equal to 50% improvement in the ACR composite score (a measure of RA symptoms including: joint swelling and tenderness; patient's assessment of pain, disease activity and physical function; physician's assessment of disease activity; and CRP) after 6 months' treatment.
Outcome measures
| Measure |
AZD9056 50 mg
n=63 Participants
AZD9056 50 mg, oral tablets, once daily, double blinded
|
AZD9056 100 mg
n=64 Participants
AZD9056 100 mg, oral tablets, once daily, double blinded
|
AZD9056 200 mg
n=63 Participants
AZD9056 200 mg, oral tablets, once daily, double blinded
|
AZD9056 400 mg
n=64 Participants
AZD9056 400 mg, oral tablets, once daily, double blinded
|
Placebo
n=65 Participants
Placebo to AZD9056, oral tablets, once daily, double blinded
|
Etanercept
n=64 Participants
Etanercept 50 mg, subcutaneous injection, once weekly, open label
|
|---|---|---|---|---|---|---|
|
American College of Rheumatology 50 Response (ACR50) at 6 Months
|
13 Participants
|
8 Participants
|
9 Participants
|
13 Participants
|
11 Participants
|
30 Participants
|
SECONDARY outcome
Timeframe: 6 monthsThe number of participants with greater to or equal to 70% improvement in the ACR composite score (a measure of RA symptoms including: joint swelling and tenderness; patient's assessment of pain, disease activity and physical function; physician's assessment of disease activity; and CRP) after 6 months' treatment
Outcome measures
| Measure |
AZD9056 50 mg
n=63 Participants
AZD9056 50 mg, oral tablets, once daily, double blinded
|
AZD9056 100 mg
n=64 Participants
AZD9056 100 mg, oral tablets, once daily, double blinded
|
AZD9056 200 mg
n=63 Participants
AZD9056 200 mg, oral tablets, once daily, double blinded
|
AZD9056 400 mg
n=64 Participants
AZD9056 400 mg, oral tablets, once daily, double blinded
|
Placebo
n=65 Participants
Placebo to AZD9056, oral tablets, once daily, double blinded
|
Etanercept
n=64 Participants
Etanercept 50 mg, subcutaneous injection, once weekly, open label
|
|---|---|---|---|---|---|---|
|
American College of Rheumatology 70 Response (ACR70) at 6 Months
|
6 Participants
|
7 Participants
|
5 Participants
|
5 Participants
|
3 Participants
|
15 Participants
|
SECONDARY outcome
Timeframe: Baseline to 6 monthsChange from baseline in the DAS28 composite score (a measure of RA symptoms including: joint swelling and tenderness; patient's assessment of disease activity; and ESR) after 6 months' treatment. A change of zero indicates no effect of treatment and a negative change of 1.2 indicates a clinically important improvement in symptoms. (The DAS scale runs from 0 to 10, with the higher scores indicating worse RA symptoms).
Outcome measures
| Measure |
AZD9056 50 mg
n=63 Participants
AZD9056 50 mg, oral tablets, once daily, double blinded
|
AZD9056 100 mg
n=64 Participants
AZD9056 100 mg, oral tablets, once daily, double blinded
|
AZD9056 200 mg
n=63 Participants
AZD9056 200 mg, oral tablets, once daily, double blinded
|
AZD9056 400 mg
n=64 Participants
AZD9056 400 mg, oral tablets, once daily, double blinded
|
Placebo
n=65 Participants
Placebo to AZD9056, oral tablets, once daily, double blinded
|
Etanercept
n=64 Participants
Etanercept 50 mg, subcutaneous injection, once weekly, open label
|
|---|---|---|---|---|---|---|
|
Disease Activity Score (Based on 28 Joint Count) (DAS28) at 6 Months.
|
-1.2 Composite score
Standard Deviation 1.27
|
-1.4 Composite score
Standard Deviation 1.63
|
-1.1 Composite score
Standard Deviation 1.47
|
-1.4 Composite score
Standard Deviation 1.37
|
-1 Composite score
Standard Deviation 1.24
|
-2.3 Composite score
Standard Deviation 1.38
|
SECONDARY outcome
Timeframe: Baseline to 6 monthsChange from baseline in HAQ-DI (a measure of patients assessment of physical function scored between zero and 3) after 6 months' treatment, calculated as score at 6 months minus score at baseline. A change of zero indicates no effect of treatment and a negative change of 0.22 or greater indicates an improvement in symptoms. (The HAQ-DI scale runs from 0 to 3, with higher scores indicating greater disability).
Outcome measures
| Measure |
AZD9056 50 mg
n=63 Participants
AZD9056 50 mg, oral tablets, once daily, double blinded
|
AZD9056 100 mg
n=64 Participants
AZD9056 100 mg, oral tablets, once daily, double blinded
|
AZD9056 200 mg
n=63 Participants
AZD9056 200 mg, oral tablets, once daily, double blinded
|
AZD9056 400 mg
n=64 Participants
AZD9056 400 mg, oral tablets, once daily, double blinded
|
Placebo
n=65 Participants
Placebo to AZD9056, oral tablets, once daily, double blinded
|
Etanercept
n=64 Participants
Etanercept 50 mg, subcutaneous injection, once weekly, open label
|
|---|---|---|---|---|---|---|
|
Health Assessment Questionnaire - Disability Index (HAQ-DI) at 6 Months.
|
-0.3 Composite score
Standard Deviation 0.57
|
-0.3 Composite score
Standard Deviation 0.51
|
-0.2 Composite score
Standard Deviation 0.5
|
-0.3 Composite score
Standard Deviation 0.55
|
-0.3 Composite score
Standard Deviation 0.46
|
-0.6 Composite score
Standard Deviation 0.66
|
Adverse Events
AZD9056 50 mg
AZD9056 100 mg
AZD9056 200 mg
AZD9056 400 mg
Placebo
Etanercept
Serious adverse events
| Measure |
AZD9056 50 mg
n=63 participants at risk
AZD9056 50 mg, oral tablets, once daily, double blinded
|
AZD9056 100 mg
n=64 participants at risk
AZD9056 100 mg, oral tablets, once daily, double blinded
|
AZD9056 200 mg
n=63 participants at risk
AZD9056 200 mg, oral tablets, once daily, double blinded
|
AZD9056 400 mg
n=64 participants at risk
AZD9056 400 mg, oral tablets, once daily, double blinded
|
Placebo
n=65 participants at risk
Placebo to AZD9056, oral tablets, once daily, double blinded
|
Etanercept
n=64 participants at risk
Etanercept 50 mg, subcutaneous injection, once weekly, open label
|
|---|---|---|---|---|---|---|
|
Eye disorders
Visual Acuity Reduced
|
0.00%
0/63
|
0.00%
0/64
|
1.6%
1/63
|
0.00%
0/64
|
0.00%
0/37
|
0.00%
0/64
|
|
Eye disorders
Non-Cardiac Chest Pain
|
0.00%
0/63
|
0.00%
0/64
|
0.00%
0/63
|
1.6%
1/64
|
0.00%
0/65
|
0.00%
0/64
|
|
Injury, poisoning and procedural complications
Humerus Fracture
|
0.00%
0/63
|
0.00%
0/64
|
0.00%
0/63
|
0.00%
0/64
|
0.00%
0/65
|
1.6%
1/64
|
|
Injury, poisoning and procedural complications
Tibia Fracture
|
0.00%
0/63
|
0.00%
0/64
|
0.00%
0/63
|
0.00%
0/64
|
0.00%
0/65
|
1.6%
1/64
|
|
Musculoskeletal and connective tissue disorders
Joint Effusion
|
0.00%
0/63
|
0.00%
0/64
|
0.00%
0/63
|
0.00%
0/64
|
1.5%
1/65
|
0.00%
0/64
|
|
Renal and urinary disorders
Renal Colic
|
1.6%
1/63
|
0.00%
0/64
|
0.00%
0/63
|
0.00%
0/64
|
0.00%
0/65
|
0.00%
0/64
|
|
Renal and urinary disorders
Ureteral Polyp
|
0.00%
0/63
|
0.00%
0/64
|
0.00%
0/63
|
0.00%
0/64
|
0.00%
0/65
|
1.6%
1/64
|
|
Reproductive system and breast disorders
Uterine Polyp
|
1.6%
1/63
|
0.00%
0/64
|
0.00%
0/63
|
0.00%
0/64
|
0.00%
0/65
|
0.00%
0/64
|
Other adverse events
| Measure |
AZD9056 50 mg
n=63 participants at risk
AZD9056 50 mg, oral tablets, once daily, double blinded
|
AZD9056 100 mg
n=64 participants at risk
AZD9056 100 mg, oral tablets, once daily, double blinded
|
AZD9056 200 mg
n=63 participants at risk
AZD9056 200 mg, oral tablets, once daily, double blinded
|
AZD9056 400 mg
n=64 participants at risk
AZD9056 400 mg, oral tablets, once daily, double blinded
|
Placebo
n=65 participants at risk
Placebo to AZD9056, oral tablets, once daily, double blinded
|
Etanercept
n=64 participants at risk
Etanercept 50 mg, subcutaneous injection, once weekly, open label
|
|---|---|---|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
4.8%
3/63
|
10.9%
7/64
|
3.2%
2/63
|
10.9%
7/64
|
3.1%
2/65
|
1.6%
1/64
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
3.2%
2/63
|
0.00%
0/64
|
7.9%
5/63
|
10.9%
7/64
|
4.6%
3/65
|
1.6%
1/64
|
|
Gastrointestinal disorders
Diarrhoea
|
1.6%
1/63
|
0.00%
0/64
|
6.3%
4/63
|
9.4%
6/64
|
4.6%
3/65
|
0.00%
0/64
|
|
Infections and infestations
Bronchitis
|
4.8%
3/63
|
6.2%
4/64
|
0.00%
0/63
|
3.1%
2/64
|
3.1%
2/65
|
1.6%
1/64
|
|
Musculoskeletal and connective tissue disorders
Rheumatoid Atheritis
|
12.7%
8/63
|
9.4%
6/64
|
6.3%
4/63
|
9.4%
6/64
|
18.5%
12/65
|
3.1%
2/64
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
1.6%
1/63
|
4.7%
3/64
|
6.3%
4/63
|
4.7%
3/64
|
1.5%
1/65
|
3.1%
2/64
|
|
Nervous system disorders
Headache
|
4.8%
3/63
|
4.7%
3/64
|
11.1%
7/63
|
15.6%
10/64
|
6.2%
4/65
|
0.00%
0/64
|
|
Vascular disorders
Hypertension
|
3.2%
2/63
|
6.2%
4/64
|
3.2%
2/63
|
4.7%
3/64
|
0.00%
0/65
|
9.4%
6/64
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60