Trial Outcomes & Findings for A Proof of Concept and Dose Ranging Study in Patients With Rheumatoid Arthritis (NCT NCT00713544)
NCT ID: NCT00713544
Last Updated: 2011-10-03
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 12 Weeks' treatment.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
373 participants
Primary outcome timeframe
12 weeks
Results posted on
2011-10-03
Participant Flow
The first participant enrolled on 01 July 2008, and the last participant completed the study on 08 April 2009. Participants were recruited from 61 centres in 14 countries in Europe, Southern Africa and South America.
Male or female adult patients with active rheumatoid arthritis (on background treatment of methotrexate) were randomly assigned to receive AZD5672 at 20, 50, 100 or 150 mg once daily, placebo or etanercept. It was planned to randomise approx 360 patients in total, 60 to the open-label etanercept arm and 300 in total to the AZD5672 or placebo arms.
Participant milestones
| Measure |
AZD5672 20 mg
AZD5672 20 mg, oral tablets, once daily, double-blinded
|
AZD5672 50 mg
AZD5672 50 mg, oral tablets, once daily, double-blinded
|
AZD5672 100 mg
AZD5672 100 mg, oral tablets, once daily, double-blinded
|
AZD5672 150 mg
AZD5672 150 mg, oral tablets, once daily, double-blinded
|
Placebo
Placebo to AZD5672, oral tablets, once daily, double-blinded
|
Etanercept
Etanercept 50 mg, subcutaneous injection, once weekly, open-label
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
52
|
52
|
52
|
76
|
65
|
76
|
|
Overall Study
COMPLETED
|
45
|
46
|
41
|
66
|
57
|
67
|
|
Overall Study
NOT COMPLETED
|
7
|
6
|
11
|
10
|
8
|
9
|
Reasons for withdrawal
| Measure |
AZD5672 20 mg
AZD5672 20 mg, oral tablets, once daily, double-blinded
|
AZD5672 50 mg
AZD5672 50 mg, oral tablets, once daily, double-blinded
|
AZD5672 100 mg
AZD5672 100 mg, oral tablets, once daily, double-blinded
|
AZD5672 150 mg
AZD5672 150 mg, oral tablets, once daily, double-blinded
|
Placebo
Placebo to AZD5672, oral tablets, once daily, double-blinded
|
Etanercept
Etanercept 50 mg, subcutaneous injection, once weekly, open-label
|
|---|---|---|---|---|---|---|
|
Overall Study
Adverse Event
|
5
|
3
|
7
|
7
|
3
|
5
|
|
Overall Study
Withdrawal by Subject
|
2
|
0
|
3
|
2
|
3
|
1
|
|
Overall Study
Protocol Violation
|
0
|
0
|
0
|
0
|
0
|
1
|
|
Overall Study
Physician Decision
|
0
|
0
|
0
|
0
|
0
|
2
|
|
Overall Study
Lack of Efficacy
|
0
|
1
|
0
|
1
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
0
|
0
|
1
|
0
|
0
|
0
|
|
Overall Study
AZ decision - Hepatitis C ab reactive
|
0
|
1
|
0
|
0
|
0
|
0
|
|
Overall Study
Incorrect enrollment
|
0
|
1
|
0
|
0
|
0
|
0
|
|
Overall Study
Hepatotoxicity - not an AE
|
0
|
0
|
0
|
0
|
1
|
0
|
Baseline Characteristics
A Proof of Concept and Dose Ranging Study in Patients With Rheumatoid Arthritis
Baseline characteristics by cohort
| Measure |
AZD5672 20 mg
n=52 Participants
AZD5672 20 mg, oral tablets, once daily, double-blinded
|
AZD5672 50 mg
n=52 Participants
AZD5672 50 mg, oral tablets, once daily, double-blinded
|
AZD5672 100 mg
n=51 Participants
AZD5672 100 mg, oral tablets, once daily, double-blinded
|
AZD5672 150 mg
n=76 Participants
AZD5672 150 mg, oral tablets, once daily, double-blinded
|
Placebo
n=65 Participants
Placebo to AZD5672, oral tablets, once daily, double-blinded
|
Etanercept
n=75 Participants
Etanercept 50 mg, subcutaneous injection, once weekly, open-label
|
Total
n=371 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Disease Activity Score (based on 28 joint counts) (DAS28)
|
6.6 Units on a scale
STANDARD_DEVIATION 0.80 • n=5 Participants
|
6.5 Units on a scale
STANDARD_DEVIATION 0.87 • n=7 Participants
|
6.4 Units on a scale
STANDARD_DEVIATION 0.72 • n=5 Participants
|
6.3 Units on a scale
STANDARD_DEVIATION 0.79 • n=4 Participants
|
6.6 Units on a scale
STANDARD_DEVIATION 0.74 • n=21 Participants
|
6.7 Units on a scale
STANDARD_DEVIATION 0.80 • n=8 Participants
|
6.5 Units on a scale
STANDARD_DEVIATION 0.79 • n=8 Participants
|
|
Age Continuous
|
53 Year
STANDARD_DEVIATION 12.7 • n=5 Participants
|
53 Year
STANDARD_DEVIATION 12 • n=7 Participants
|
54 Year
STANDARD_DEVIATION 10.8 • n=5 Participants
|
53 Year
STANDARD_DEVIATION 10.2 • n=4 Participants
|
53 Year
STANDARD_DEVIATION 10.6 • n=21 Participants
|
54 Year
STANDARD_DEVIATION 9.6 • n=8 Participants
|
53 Year
STANDARD_DEVIATION 10.8 • n=8 Participants
|
|
Sex: Female, Male
Female
|
45 Participants
n=5 Participants
|
45 Participants
n=7 Participants
|
45 Participants
n=5 Participants
|
67 Participants
n=4 Participants
|
54 Participants
n=21 Participants
|
66 Participants
n=8 Participants
|
322 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
11 Participants
n=21 Participants
|
9 Participants
n=8 Participants
|
49 Participants
n=8 Participants
|
|
Duration of rheumatoid arthritis
Duration of rheumatoid arthritis > 5 years
|
23 participants
n=5 Participants
|
30 participants
n=7 Participants
|
25 participants
n=5 Participants
|
39 participants
n=4 Participants
|
36 participants
n=21 Participants
|
48 participants
n=8 Participants
|
201 participants
n=8 Participants
|
|
Duration of rheumatoid arthritis
Duration of rheumatoid arthritis <= 5years
|
29 participants
n=5 Participants
|
22 participants
n=7 Participants
|
26 participants
n=5 Participants
|
37 participants
n=4 Participants
|
29 participants
n=21 Participants
|
27 participants
n=8 Participants
|
170 participants
n=8 Participants
|
PRIMARY outcome
Timeframe: 12 weeksThe 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 12 Weeks' treatment.
Outcome measures
| Measure |
AZD5672 20 mg
n=52 Participants
AZD5672 20 mg, oral tablets, once daily, double-blinded
|
AZD5672 50 mg
n=52 Participants
AZD5672 50 mg, oral tablets, once daily, double-blinded
|
AZD5672 100 mg
n=51 Participants
AZD5672 100 mg, oral tablets, once daily, double-blinded
|
AZD5672 150 mg
n=76 Participants
AZD5672 150 mg, oral tablets, once daily, double-blinded
|
Placebo
n=65 Participants
Placebo to AZD5672, oral tablets, once daily, double-blinded
|
Etanercept
n=75 Participants
Etanercept 50 mg, subcutaneous injection, once weekly, open-label
|
|---|---|---|---|---|---|---|
|
American College of Rheumatology 20 Response (ACR20)
|
20 Participants
|
15 Participants
|
17 Participants
|
34 Participants
|
25 Participants
|
58 Participants
|
SECONDARY outcome
Timeframe: 12 weeksThe 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 12 Weeks' treatment.
Outcome measures
| Measure |
AZD5672 20 mg
n=52 Participants
AZD5672 20 mg, oral tablets, once daily, double-blinded
|
AZD5672 50 mg
n=52 Participants
AZD5672 50 mg, oral tablets, once daily, double-blinded
|
AZD5672 100 mg
n=51 Participants
AZD5672 100 mg, oral tablets, once daily, double-blinded
|
AZD5672 150 mg
n=76 Participants
AZD5672 150 mg, oral tablets, once daily, double-blinded
|
Placebo
n=65 Participants
Placebo to AZD5672, oral tablets, once daily, double-blinded
|
Etanercept
n=75 Participants
Etanercept 50 mg, subcutaneous injection, once weekly, open-label
|
|---|---|---|---|---|---|---|
|
American College of Rheumatology 50 Response (ACR50)
|
10 Participants
|
5 Participants
|
6 Participants
|
11 Participants
|
6 Participants
|
35 Participants
|
SECONDARY outcome
Timeframe: 12 weeksThe 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 12 Weeks' treatment.
Outcome measures
| Measure |
AZD5672 20 mg
n=52 Participants
AZD5672 20 mg, oral tablets, once daily, double-blinded
|
AZD5672 50 mg
n=52 Participants
AZD5672 50 mg, oral tablets, once daily, double-blinded
|
AZD5672 100 mg
n=51 Participants
AZD5672 100 mg, oral tablets, once daily, double-blinded
|
AZD5672 150 mg
n=76 Participants
AZD5672 150 mg, oral tablets, once daily, double-blinded
|
Placebo
n=65 Participants
Placebo to AZD5672, oral tablets, once daily, double-blinded
|
Etanercept
n=75 Participants
Etanercept 50 mg, subcutaneous injection, once weekly, open-label
|
|---|---|---|---|---|---|---|
|
American College of Rheumatology 70 Response (ACR70)
|
3 Participants
|
2 Participants
|
3 Participants
|
2 Participants
|
3 Participants
|
12 Participants
|
SECONDARY outcome
Timeframe: Baseline to 12 WeeksChange 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 12 Weeks' 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 |
AZD5672 20 mg
n=52 Participants
AZD5672 20 mg, oral tablets, once daily, double-blinded
|
AZD5672 50 mg
n=52 Participants
AZD5672 50 mg, oral tablets, once daily, double-blinded
|
AZD5672 100 mg
n=51 Participants
AZD5672 100 mg, oral tablets, once daily, double-blinded
|
AZD5672 150 mg
n=76 Participants
AZD5672 150 mg, oral tablets, once daily, double-blinded
|
Placebo
n=65 Participants
Placebo to AZD5672, oral tablets, once daily, double-blinded
|
Etanercept
n=75 Participants
Etanercept 50 mg, subcutaneous injection, once weekly, open-label
|
|---|---|---|---|---|---|---|
|
Disease Activity Score (Based on 28 Joint Count) (DAS28)
|
-1.3 Units on a scale
Standard Deviation 1.27
|
-1.1 Units on a scale
Standard Deviation 1.01
|
-1.3 Units on a scale
Standard Deviation 1.23
|
-1.3 Units on a scale
Standard Deviation 1.15
|
-1.1 Units on a scale
Standard Deviation 1.13
|
-2.6 Units on a scale
Standard Deviation 1.35
|
SECONDARY outcome
Timeframe: Baseline to 12 WeeksChange 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 12 Weeks 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 |
AZD5672 20 mg
n=52 Participants
AZD5672 20 mg, oral tablets, once daily, double-blinded
|
AZD5672 50 mg
n=52 Participants
AZD5672 50 mg, oral tablets, once daily, double-blinded
|
AZD5672 100 mg
n=51 Participants
AZD5672 100 mg, oral tablets, once daily, double-blinded
|
AZD5672 150 mg
n=76 Participants
AZD5672 150 mg, oral tablets, once daily, double-blinded
|
Placebo
n=65 Participants
Placebo to AZD5672, oral tablets, once daily, double-blinded
|
Etanercept
n=75 Participants
Etanercept 50 mg, subcutaneous injection, once weekly, open-label
|
|---|---|---|---|---|---|---|
|
Health Assessment Questionnaire - Disability Index (HAQ-DI)
|
-0.3 Units on a scale
Standard Deviation 0.47
|
-0.2 Units on a scale
Standard Deviation 0.48
|
-0.2 Units on a scale
Standard Deviation 0.40
|
-0.3 Units on a scale
Standard Deviation 0.33
|
-0.3 Units on a scale
Standard Deviation 0.47
|
-0.5 Units on a scale
Standard Deviation 0.49
|
Adverse Events
AZD5672 20 mg
Serious events: 0 serious events
Other events: 12 other events
Deaths: 0 deaths
AZD5672 50 mg
Serious events: 1 serious events
Other events: 11 other events
Deaths: 0 deaths
AZD5672 100 mg
Serious events: 2 serious events
Other events: 15 other events
Deaths: 0 deaths
AZD5672 150 mg
Serious events: 2 serious events
Other events: 21 other events
Deaths: 0 deaths
Placebo
Serious events: 1 serious events
Other events: 15 other events
Deaths: 0 deaths
Etanercept
Serious events: 0 serious events
Other events: 16 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
AZD5672 20 mg
n=52 participants at risk
AZD5672 20 mg, oral tablets, once daily, double-blinded
|
AZD5672 50 mg
n=52 participants at risk
AZD5672 50 mg, oral tablets, once daily, double-blinded
|
AZD5672 100 mg
n=51 participants at risk
AZD5672 100 mg, oral tablets, once daily, double-blinded
|
AZD5672 150 mg
n=76 participants at risk
AZD5672 150 mg, oral tablets, once daily, double-blinded
|
Placebo
n=65 participants at risk
Placebo to AZD5672, oral tablets, once daily, double-blinded
|
Etanercept
n=75 participants at risk
Etanercept 50 mg, subcutaneous injection, once weekly, open-label
|
|---|---|---|---|---|---|---|
|
Hepatobiliary disorders
Hepatitis Cholestatic
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/51
|
0.00%
0/76
|
1.5%
1/65
|
0.00%
0/75
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/52
|
1.9%
1/52
|
0.00%
0/51
|
0.00%
0/76
|
0.00%
0/65
|
0.00%
0/75
|
|
Infections and infestations
Pneumonia
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/51
|
1.3%
1/76
|
0.00%
0/65
|
0.00%
0/75
|
|
Infections and infestations
Sepsis
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/51
|
1.3%
1/76
|
0.00%
0/65
|
0.00%
0/75
|
|
Musculoskeletal and connective tissue disorders
Polymyositis
|
0.00%
0/52
|
0.00%
0/52
|
2.0%
1/51
|
0.00%
0/76
|
0.00%
0/65
|
0.00%
0/75
|
|
Skin and subcutaneous tissue disorders
Angioedema
|
0.00%
0/52
|
0.00%
0/52
|
2.0%
1/51
|
0.00%
0/76
|
0.00%
0/65
|
0.00%
0/75
|
Other adverse events
| Measure |
AZD5672 20 mg
n=52 participants at risk
AZD5672 20 mg, oral tablets, once daily, double-blinded
|
AZD5672 50 mg
n=52 participants at risk
AZD5672 50 mg, oral tablets, once daily, double-blinded
|
AZD5672 100 mg
n=51 participants at risk
AZD5672 100 mg, oral tablets, once daily, double-blinded
|
AZD5672 150 mg
n=76 participants at risk
AZD5672 150 mg, oral tablets, once daily, double-blinded
|
Placebo
n=65 participants at risk
Placebo to AZD5672, oral tablets, once daily, double-blinded
|
Etanercept
n=75 participants at risk
Etanercept 50 mg, subcutaneous injection, once weekly, open-label
|
|---|---|---|---|---|---|---|
|
Gastrointestinal disorders
ABDOMINAL PAIN UPPER
|
0.00%
0/52
|
3.8%
2/52
|
5.9%
3/51
|
2.6%
2/76
|
0.00%
0/65
|
0.00%
0/75
|
|
Gastrointestinal disorders
DYSPEPSIA
|
0.00%
0/52
|
1.9%
1/52
|
5.9%
3/51
|
1.3%
1/76
|
3.1%
2/65
|
0.00%
0/75
|
|
Infections and infestations
NASOPHARYNGITIS
|
5.8%
3/52
|
3.8%
2/52
|
7.8%
4/51
|
3.9%
3/76
|
6.2%
4/65
|
5.3%
4/75
|
|
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION
|
5.8%
3/52
|
1.9%
1/52
|
9.8%
5/51
|
6.6%
5/76
|
1.5%
1/65
|
1.3%
1/75
|
|
Infections and infestations
BRONCHITIS
|
1.9%
1/52
|
5.8%
3/52
|
2.0%
1/51
|
1.3%
1/76
|
1.5%
1/65
|
6.7%
5/75
|
|
Infections and infestations
VIRAL INFECTION
|
0.00%
0/52
|
0.00%
0/52
|
0.00%
0/51
|
5.3%
4/76
|
0.00%
0/65
|
2.7%
2/75
|
|
Infections and infestations
ALANINE AMINOTRANSFERASE INCREASED
|
7.7%
4/52
|
3.8%
2/52
|
5.9%
3/51
|
3.9%
3/76
|
4.6%
3/65
|
6.7%
5/75
|
|
Infections and infestations
ASPARTATE AMINOTRANSFERASE INCREASED
|
3.8%
2/52
|
1.9%
1/52
|
3.9%
2/51
|
3.9%
3/76
|
1.5%
1/65
|
5.3%
4/75
|
|
Musculoskeletal and connective tissue disorders
RHEUMATOID ARTHRITIS
|
3.8%
2/52
|
0.00%
0/52
|
3.9%
2/51
|
3.9%
3/76
|
7.7%
5/65
|
1.3%
1/75
|
|
Nervous system disorders
HEADACHE
|
1.9%
1/52
|
5.8%
3/52
|
3.9%
2/51
|
2.6%
2/76
|
1.5%
1/65
|
1.3%
1/75
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60