Study Evaluating Efficacy / Safety of Etanercept + Methotrexate Compared to Usual Treatment in Moderate RA Subjects

• Sponsor: Wyeth is now a wholly owned subsidiary of Pfizer (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00706797
• Collaborator: (none)
• Enrollment: 141
• Locations: 49
• Arms: 2
• Duration (Months): 19.9
• Patients Per Site: 2.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

To assess comparative radiographic efficacy, clinical efficacy and safety of etanercept (ETN)

• methotrexate (MTX) with usual disease-modifying anti-rheumatic drug (DMARD) treatment in subjects with moderate RA who were treated with MTX monotherapy, but continue to have moderate disease activity.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: etanercept (EnbrelTM); Drug: methotrexate	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 141 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Randomized Study to Evaluate the Radiographic Efficacy and Safety of Enbrel™ (Etanercept) Added to Methotrexate in Comparison With Usual Treatment in Subjects With Moderate Rheumatoid Arthritis Disease Activity
• Study Start Date: Sep 1, 2008
• Actual Primary Completion Date: Dec 1, 2009
• Actual Study Completion Date: May 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Usual care Utilized Disease-Modifying Antirheumatic Drugs (DMARDs) from a list of the 6 most commonly prescribed in the participating countries (Methotrexate, sulfasalazine, hydroxychloroquine, leflunomide, cyclosporine A and gold).	Drug: methotrexate
Active Comparator: ETN + MTX Etanercept (ETN) 50 milligrams (mg) sub-cutaneous (SC) injection once weekly (pre-filled syringe) plus continuation of current dose of Methotrexate (MTX) either oral (PO), SC, or intramuscular (IM).	Drug: etanercept (EnbrelTM); Drug: methotrexate

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Modified Total Sharp Score (TSS) at Week 52 [Baseline, Week 52]

   Modified TSS is a measure of change in joint health. TSS is defined as joint space narrowing score (range 0 [no narrowing] to 168 [high narrowing]) plus (+) erosion score (range is from 0 [no erosion] to 280 [high erosion]). The modified TSS range is from 0 (no damage) to 448 (bad joint status). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement.

Secondary Outcome Measures

1. Change From Baseline in Erosions at Week 52 [Baseline, Week 52]

   Erosion score (a component of the modified TSS) is a measure of change in joint health. Erosion score range is from 0 (no erosion) to 280 (high erosion). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement.

2. Change From Baseline in Joint Space Narrowing at Week 52 [Baseline, Week 52]

   Joint space narrowing score (a component of the modified TSS) is a measure of change in joint health. Joint space narrowing score range is 0 (no narrowing) to 168 (high narrowing). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement.

3. Percentage of Participants Showing no Radiographic Progression (TSS Change <0.5) at Week 52 [Baseline, Week 52, Last observation carried forward (LOCF)]

   Radiographic non-progression determined based on TSS change <0.5 using the dichotomous response Yes / No. The modified TSS range is from 0 (no damage) to 448 (bad joint status). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement.

4. Percentage of Participants Achieving >1.2 Improvement in Disease Activity Score Based on a 28-joint Count (DAS28) [Baseline, Week 12, Week 24, and Week 52]

   Disease activity score based on 28 painful joint counts, 28 swollen joint counts, erythrocyte sedimentation rate (ESR) in millimeters per hour (mm/hr), and general health (GH) using Visual Analog Scale (VAS); range 0 (very well) to 100 (extremely bad). DAS28 score calculated as 0.56 square root (√) (28 painful joint count) + 0.28 √ (28 swollen joint count) + 0.70 (ln ESR mm/hr) + 0.014 GH; range 0 to 10. DAS28 score >5.1=higher disease activity; <3.2=low disease activity; <2.6=clinical remission. Achievement of >1.2 improvement defined as decrease in DAS28 >1.2 (change in DAS28 < -1.2).

5. Percentage of Participants Achieving Remission (DAS28 <2.60) [Week 12, Week 24, and Week 52]

   Disease activity score based on 28 painful joint counts, 28 swollen joint counts, erythrocyte sedimentation rate (ESR) mm/hr, and general health (GH) using a visual analog scale (VAS); VAS range: 0 (very well) to 100 (extremely bad). DAS28 score calculated as 0.56 √ (28 painful joint count) + 0.28 √ (28 swollen joint count) + 0.70 (ln ESR mm/hr) + 0.014 GH; range 0 to 10. DAS28 score >5.10=higher disease activity; <3.20=low disease activity; <2.60=clinical remission.

6. Percentage of Participants Achieving Low Disease Activity (DAS28 ≤3.20) [Week 12, Week 24, and Week 52]

   Disease activity score based on 28 painful joint counts, 28 swollen joint counts, erythrocyte sedimentation rate (ESR) mm/hr, and general health (GH) using a visual analog scale (VAS); VAS range: 0 (very well) to 100 (extremely bad). DAS28 score calculated as 0.56 √ (28 painful joint count) + 0.28 √ (28 swollen joint count) + 0.70 (ln ESR mm/hr) + 0.014 GH; range 0 to 10. DAS28 score >5.10=higher disease activity; <3.20=low disease activity; <2.60=clinical remission.

7. Percentage of Participants Achieving a >0.6 Disease Activity Score (DAS)28 Response [Week 12, Week 24, and Week 52]

   Disease activity score based on 28 painful joint counts, 28 swollen joint counts, erythrocyte sedimentation rate (ESR) mm/hr, and participant's assessment of general health (GH) using a visual analog scale (VAS); VAS range: 0 (very well) to 100 (extremely bad). DAS28 score calculated as 0.56 √ (28 painful joint count) + 0.28 √ (28 swollen joint count) + 0.70 (ln ESR mm/hr) + 0.014 GH; range 0 to 10. DAS28 score >5.10=higher disease activity; <3.20=low disease activity; <2.60=clinical remission. DAS28 response of >0.6 defined as decrease in DAS28 >0.6 (change in DAS28 < -0.6).

8. Percentage of Participants Achieving Moderate or Good Response on European League Against Rheumatism (EULAR) Response Criteria [Week 12, Week 24, Week 52]

   Response to treatment assessed by EULAR response criteria. Participants were characterized as good, moderate, or non-responders based on both Disease Activity Score (DAS) level attained and change in DAS. Good response defined as >1.2 improvement in DAS from Baseline and DAS attained during follow-up of ≤2.4. Non-responders = participants with improvement of ≤0.6 or participants with improvement of >0.6 but ≤1.2 and DAS attained during follow-up of >5.1. Remaining participants were classified as moderate. Scores of good and moderate were considered to have therapeutic response.

9. Percentage of Participants With American College of Rheumatology 20% (ACR20) Response [Week 12, Week 24, Week 52]

   American College of Rheumatology 20% (ACR20) response: responder = ≥ 20% improvement in tender joint count; ≥ 20% improvement in swollen joint count; and ≥ 20% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and erythrocyte sedimentation rate (ESR). Subjects withdrawing early were non-responders.

10. Percentage of Participants With American College of Rheumatology 50% (ACR50) Response [Week 12, Week 24, Week 52]

    American College of Rheumatology 50% (ACR50) response: responder = ≥ 50% improvement in tender joint count; ≥ 50% improvement in swollen joint count; and ≥ 50% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and erythrocyte sedimentation rate (ESR). Subjects withdrawing early were non-responders.

11. Percentage of Participants With American College of Rheumatology 70% (ACR70) Response [Week 12, Week 24, Week 52]

    American College of Rheumatology 70% (ACR70) response: responder = ≥ 70% improvement in tender joint count; ≥ 70% improvement in swollen joint count; and ≥ 70% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and erythrocyte sedimentation rate (ESR) . Subjects withdrawing early were non-responders.

12. Percentage of Participants With American College of Rheumatology 90% (ACR90) Response [Week 12, Week 24, Week 52]

    American College of Rheumatology 90% (ACR 90) response: responder = ≥ 90% improvement in tender joint count; ≥ 90% improvement in swollen joint count; and ≥ 90% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and erythrocyte sedimentation rate (ESR). Subjects withdrawing early were non-responders.

13. Change From Baseline in Mean Daily Dose of Corticosteroids to Manage Flare-ups Across the 52-week Treatment Period [Week 4, Week 12, Week 24, Week 40, Week 52]

    Mean daily dose of corticosteroids to manage flare-ups (temporary increases in corticosteroid dose or use of intra-articular steroids) during treatment period. Daily dose of equivalent prednisone derived in mg/day: oral corticosteroids: 5 mg of prednisone = 5 mg of prednisolone = 25 mg of cortisone = 20 mg of hydrocortisone = 4 mg of methylprednisolone = 4 mg of triamcinolone = 2mg of paramethasone = 0.75 mg of betamethasone = 0.75 of dexamethasone = 0.3 of cortivazol.

14. Percentage of Participants Achieving a Minimal Clinically Important Improvement (MCII) [Week 12, Week 52]

    Participants were asked how their pain had been during the last 48 hours compared to baseline. Participants that reported improvement assessed how important this improvement was to them; range: very important, moderately important, slightly important, or not at all important. Binary response options: 1=improved very important, or improved moderately important; 2=slightly important, not at all important, no change, or worse-more pain.

15. Percentage of Participants Achieving a Patient Acceptable Symptom State (PASS) [Week 4, Week 12, Week 24, Week 40, Week 52]

    Percentage of participants reporting acceptable symptom state: acceptance to remain for the rest of their lives with the level of pain they had during the last 48 hours; and unacceptable symptom state: not able to remain for the rest of their lives with the level of pain they had during the last 48 hours.

16. Health Related Quality of Life: EuroQol-5D Health Index [Baseline, Week 12, Week 24, and Week 52]

    EQ-5D is a self-administered questionnaire to assess health-related quality of life in 5 domains (mobility, self care, usual activities, pain or discomfort, and anxiety or depression). Scores from the 5 domains are used to calculate the Health State Profile Score as a single index value; range: 0.0 (death) to 1.0 (perfect health); higher scores indicate a better health state.

17. Health Related Quality of Life: EuroQol-5D Health State Visual Analog Scale (VAS) [Baseline, Week 12, Week 24, and Week 52]

    EQ-5D: subject rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health state.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Meet the 1987 ACR Revised Criteria for Rheumatoid Arthritis.

• Documented evidence, confirmed by a blinded 3rd party assessor, of at least one erosion observed by X-ray at randomization based on X-ray taken at the screening visit.

• Have received MTX as stable dose for 28 days prior to the screening visit.

Exclusion Criteria:

• Previous treatment with ETN, infliximab, adalimumab, other Tumor necrosis factor (TNF) -a inhibitors, anakinra or other biological agents.

• Receipt of any DMARD, other than MTX, within 28 days before screening.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Ostrava		Czech Republic	722 00
2		Prague		Czech Republic	128-50
3		Prague		Czech Republic	140-59
4		Amiens cedex 1		France	80054
5		Amiens		France	80054
6		Echirolles		France	38130
7		Metz		France	57077
8		Montpellier		France	34295
9		Paris cedex 13		France	75651
10		Paris cedex 14		France	75679
11		Paris		France	75651
12		Paris		France	75679
13		Rouen		France	76031
14		Tours cedex 9		France	37044
15		Tours		France	37044
16		Berlin		Germany	10117
17		Frankfurt		Germany	60590
18		Hamburg-Eilbeck		Germany	22081
19		Homburg		Germany	66424
20		Koeln		Germany	50924
21		Mainz		Germany	55131
22		Budapest		Hungary	1023
23		Budapest		Hungary	1036
24		Miskolc		Hungary	3529
25		Rijeka		Hungary	51000
26		Split		Hungary	21000
27		Zagreb		Hungary	10000
28		Jesi (Ancona)		Italy	60035
29		Reggio Calabria		Italy	89100
30		Bytom		Poland	41-902
31		Krakow		Poland	31-531
32		Ustron		Poland	43-450
33		Warszawa		Poland	00-909
34		Warszawa		Poland	02-637
35		Wroclaw		Poland	50-088
36		Santander	Cantabria	Spain	39008
37		Getafe	Madrid	Spain	28902
38		Bilbao	Vizcaya	Spain	48013
39		Barcelona		Spain	08035
40		Madrid		Spain	28006
41		Madrid		Spain	28040
42		Madrid		Spain	28046
43		Valencia		Spain	46010
44		Izmir		Turkey	35340
45		Cambridge	Cambs	United Kingdom	CB2 2QQ
46		Birmingham	West Midlands	United Kingdom	WS11 5XY
47		Aintree		United Kingdom	L9 7AL
48		Newcastle		United Kingdom	NE7 7DN
49		Wirral		United Kingdom	CH49 5PE

Sponsors and Collaborators

• Wyeth is now a wholly owned subsidiary of Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Wyeth is now a wholly owned subsidiary of Pfizer

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00706797
• Other Study ID Numbers: 0881X1-4437
• First Posted: Jun 30, 2008
• Last Update Posted: Jun 21, 2011
• Last Verified: Jun 1, 2011

• Keywords provided by , ,: Moderate Rheumatoid Arthritis
• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid; Etanercept; Methotrexate

Study Results

Participant Flow

Pre-assignment Detail	141 participants were randomized, 1 participant performed all the planned visits, and 140 participants were discontinued before completion of the study; 115 participants prematurely withdrew due to discontinuation of the study by the sponsor.

Arm/Group Title	Usual Care	ETN + MTX
Arm/Group Description	Utilized Disease-Modifying Antirheumatic Drugs (DMARDs) from a list of the 6 most commonly prescribed in the participating countries (Methotrexate, sulfasalazine, hydroxychloroquine, leflunomide, cyclosporine A and gold).	Etanercept (ETN) 50 milligrams (mg) sub-cutaneous (SC) injection once weekly (pre-filled syringe) plus continuation of current dose of Methotrexate (MTX) either oral (PO), SC, or intramuscular (IM).
Period Title: Overall Study
STARTED	70	71
Safety Population	63	71
COMPLETED	1	0
NOT COMPLETED	69	71

Baseline Characteristics

Arm/Group Title	Usual Care	ETN + MTX	Total
Arm/Group Description	Utilized Disease-Modifying Antirheumatic Drugs (DMARDs) from a list of the 6 most commonly prescribed in the participating countries (Methotrexate, sulfasalazine, hydroxychloroquine, leflunomide, cyclosporine A and gold).	Etanercept (ETN) 50 milligrams (mg) sub-cutaneous (SC) injection once weekly (pre-filled syringe) plus continuation of current dose of Methotrexate (MTX) either oral (PO), SC, or intramuscular (IM).	Total of all reporting groups
Overall Participants	63	71	134
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.3 (12.1)	53.8 (13.1)	55.5 (12.7)
Sex: Female, Male (Count of Participants)
Female	50 79.4%	56 78.9%	106 79.1%
Male	13 20.6%	15 21.1%	28 20.9%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Modified Total Sharp Score (TSS) at Week 52
Description	Modified TSS is a measure of change in joint health. TSS is defined as joint space narrowing score (range 0 [no narrowing] to 168 [high narrowing]) plus (+) erosion score (range is from 0 [no erosion] to 280 [high erosion]). The modified TSS range is from 0 (no damage) to 448 (bad joint status). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat (mITT) population including all participants with an erosion at randomization confirmed by the blinded expert assessor, received at least 1 dose of subject treatment, and had data for randomization and 1 post randomization X-ray. Efficacy data not analyzed due to early termination of the study.

Arm/Group Title	Usual Care	ETN + MTX
Arm/Group Description	Utilized Disease-Modifying Antirheumatic Drugs (DMARDs) from a list of the 6 most commonly prescribed in the participating countries (Methotrexate, sulfasalazine, hydroxychloroquine, leflunomide, cyclosporine A and gold).	Etanercept (ETN) 50 milligrams (mg) sub-cutaneous (SC) injection once weekly (pre-filled syringe) plus continuation of current dose of Methotrexate (MTX) either oral (PO), SC, or intramuscular (IM).
Measure Participants	0	0

2. Secondary Outcome

Title	Change From Baseline in Erosions at Week 52
Description	Erosion score (a component of the modified TSS) is a measure of change in joint health. Erosion score range is from 0 (no erosion) to 280 (high erosion). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

mITT; efficacy data not analyzed due to early termination of the study.

Arm/Group Title	Usual Care	ETN + MTX
Arm/Group Description	Utilized Disease-Modifying Antirheumatic Drugs (DMARDs) from a list of the 6 most commonly prescribed in the participating countries (Methotrexate, sulfasalazine, hydroxychloroquine, leflunomide, cyclosporine A and gold).	Etanercept (ETN) 50 milligrams (mg) sub-cutaneous (SC) injection once weekly (pre-filled syringe) plus continuation of current dose of Methotrexate (MTX) either oral (PO), SC, or intramuscular (IM).
Measure Participants	0	0

3. Secondary Outcome

Title	Change From Baseline in Joint Space Narrowing at Week 52
Description	Joint space narrowing score (a component of the modified TSS) is a measure of change in joint health. Joint space narrowing score range is 0 (no narrowing) to 168 (high narrowing). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

mITT; efficacy data not analyzed due to early termination of the study.

Arm/Group Title	Usual Care	ETN + MTX
Arm/Group Description	Utilized Disease-Modifying Antirheumatic Drugs (DMARDs) from a list of the 6 most commonly prescribed in the participating countries (Methotrexate, sulfasalazine, hydroxychloroquine, leflunomide, cyclosporine A and gold).	Etanercept (ETN) 50 milligrams (mg) sub-cutaneous (SC) injection once weekly (pre-filled syringe) plus continuation of current dose of Methotrexate (MTX) either oral (PO), SC, or intramuscular (IM).
Measure Participants	0	0

4. Secondary Outcome

Title	Percentage of Participants Showing no Radiographic Progression (TSS Change <0.5) at Week 52
Description	Radiographic non-progression determined based on TSS change <0.5 using the dichotomous response Yes / No. The modified TSS range is from 0 (no damage) to 448 (bad joint status). Increase from baseline represents disease progression and / or joint worsening; no change represents halting of disease progression; a decrease represents improvement.
Time Frame	Baseline, Week 52, Last observation carried forward (LOCF)

Outcome Measure Data

Analysis Population Description

mITT; efficacy data not analyzed due to early termination of the study.

Arm/Group Title	Usual Care	ETN + MTX
Arm/Group Description	Utilized Disease-Modifying Antirheumatic Drugs (DMARDs) from a list of the 6 most commonly prescribed in the participating countries (Methotrexate, sulfasalazine, hydroxychloroquine, leflunomide, cyclosporine A and gold).	Etanercept (ETN) 50 milligrams (mg) sub-cutaneous (SC) injection once weekly (pre-filled syringe) plus continuation of current dose of Methotrexate (MTX) either oral (PO), SC, or intramuscular (IM).
Measure Participants	0	0

5. Secondary Outcome

Title	Percentage of Participants Achieving >1.2 Improvement in Disease Activity Score Based on a 28-joint Count (DAS28)
Description	Disease activity score based on 28 painful joint counts, 28 swollen joint counts, erythrocyte sedimentation rate (ESR) in millimeters per hour (mm/hr), and general health (GH) using Visual Analog Scale (VAS); range 0 (very well) to 100 (extremely bad). DAS28 score calculated as 0.56 square root (√) (28 painful joint count) + 0.28 √ (28 swollen joint count) + 0.70 (ln ESR mm/hr) + 0.014 GH; range 0 to 10. DAS28 score >5.1=higher disease activity; <3.2=low disease activity; <2.6=clinical remission. Achievement of >1.2 improvement defined as decrease in DAS28 >1.2 (change in DAS28 < -1.2).
Time Frame	Baseline, Week 12, Week 24, and Week 52

Outcome Measure Data

Analysis Population Description

mITT; efficacy data not analyzed due to early termination of the study.

Arm/Group Title	Usual Care	ETN + MTX
Arm/Group Description	Utilized Disease-Modifying Antirheumatic Drugs (DMARDs) from a list of the 6 most commonly prescribed in the participating countries (Methotrexate, sulfasalazine, hydroxychloroquine, leflunomide, cyclosporine A and gold).	Etanercept (ETN) 50 milligrams (mg) sub-cutaneous (SC) injection once weekly (pre-filled syringe) plus continuation of current dose of Methotrexate (MTX) either oral (PO), SC, or intramuscular (IM).
Measure Participants	0	0

6. Secondary Outcome

Title	Percentage of Participants Achieving Remission (DAS28 <2.60)
Description	Disease activity score based on 28 painful joint counts, 28 swollen joint counts, erythrocyte sedimentation rate (ESR) mm/hr, and general health (GH) using a visual analog scale (VAS); VAS range: 0 (very well) to 100 (extremely bad). DAS28 score calculated as 0.56 √ (28 painful joint count) + 0.28 √ (28 swollen joint count) + 0.70 (ln ESR mm/hr) + 0.014 GH; range 0 to 10. DAS28 score >5.10=higher disease activity; <3.20=low disease activity; <2.60=clinical remission.
Time Frame	Week 12, Week 24, and Week 52

Outcome Measure Data

Analysis Population Description

mITT; efficacy data not analyzed due to early termination of the study.

Arm/Group Title	Usual Care	ETN + MTX
Arm/Group Description	Utilized Disease-Modifying Antirheumatic Drugs (DMARDs) from a list of the 6 most commonly prescribed in the participating countries (Methotrexate, sulfasalazine, hydroxychloroquine, leflunomide, cyclosporine A and gold).	Etanercept (ETN) 50 milligrams (mg) sub-cutaneous (SC) injection once weekly (pre-filled syringe) plus continuation of current dose of Methotrexate (MTX) either oral (PO), SC, or intramuscular (IM).
Measure Participants	0	0

7. Secondary Outcome

Title	Percentage of Participants Achieving Low Disease Activity (DAS28 ≤3.20)
Description	Disease activity score based on 28 painful joint counts, 28 swollen joint counts, erythrocyte sedimentation rate (ESR) mm/hr, and general health (GH) using a visual analog scale (VAS); VAS range: 0 (very well) to 100 (extremely bad). DAS28 score calculated as 0.56 √ (28 painful joint count) + 0.28 √ (28 swollen joint count) + 0.70 (ln ESR mm/hr) + 0.014 GH; range 0 to 10. DAS28 score >5.10=higher disease activity; <3.20=low disease activity; <2.60=clinical remission.
Time Frame	Week 12, Week 24, and Week 52

Outcome Measure Data

Analysis Population Description

mITT; efficacy data not analyzed due to early termination of the study.

Arm/Group Title	Usual Care	ETN + MTX
Arm/Group Description	Utilized Disease-Modifying Antirheumatic Drugs (DMARDs) from a list of the 6 most commonly prescribed in the participating countries (Methotrexate, sulfasalazine, hydroxychloroquine, leflunomide, cyclosporine A and gold).	Etanercept (ETN) 50 milligrams (mg) sub-cutaneous (SC) injection once weekly (pre-filled syringe) plus continuation of current dose of Methotrexate (MTX) either oral (PO), SC, or intramuscular (IM).
Measure Participants	0	0

8. Secondary Outcome

Title	Percentage of Participants Achieving a >0.6 Disease Activity Score (DAS)28 Response
Description	Disease activity score based on 28 painful joint counts, 28 swollen joint counts, erythrocyte sedimentation rate (ESR) mm/hr, and participant's assessment of general health (GH) using a visual analog scale (VAS); VAS range: 0 (very well) to 100 (extremely bad). DAS28 score calculated as 0.56 √ (28 painful joint count) + 0.28 √ (28 swollen joint count) + 0.70 (ln ESR mm/hr) + 0.014 GH; range 0 to 10. DAS28 score >5.10=higher disease activity; <3.20=low disease activity; <2.60=clinical remission. DAS28 response of >0.6 defined as decrease in DAS28 >0.6 (change in DAS28 < -0.6).
Time Frame	Week 12, Week 24, and Week 52

Outcome Measure Data

Analysis Population Description

mITT; efficacy data not analyzed due to early termination of the study.

Arm/Group Title	Usual Care	ETN + MTX
Arm/Group Description	Utilized Disease-Modifying Antirheumatic Drugs (DMARDs) from a list of the 6 most commonly prescribed in the participating countries (Methotrexate, sulfasalazine, hydroxychloroquine, leflunomide, cyclosporine A and gold).	Etanercept (ETN) 50 milligrams (mg) sub-cutaneous (SC) injection once weekly (pre-filled syringe) plus continuation of current dose of Methotrexate (MTX) either oral (PO), SC, or intramuscular (IM).
Measure Participants	0	0

9. Secondary Outcome

Title	Percentage of Participants Achieving Moderate or Good Response on European League Against Rheumatism (EULAR) Response Criteria
Description	Response to treatment assessed by EULAR response criteria. Participants were characterized as good, moderate, or non-responders based on both Disease Activity Score (DAS) level attained and change in DAS. Good response defined as >1.2 improvement in DAS from Baseline and DAS attained during follow-up of ≤2.4. Non-responders = participants with improvement of ≤0.6 or participants with improvement of >0.6 but ≤1.2 and DAS attained during follow-up of >5.1. Remaining participants were classified as moderate. Scores of good and moderate were considered to have therapeutic response.
Time Frame	Week 12, Week 24, Week 52

Outcome Measure Data

Analysis Population Description

mITT; efficacy data not analyzed due to early termination of the study.

Arm/Group Title	Usual Care	ETN + MTX
Arm/Group Description	Utilized Disease-Modifying Antirheumatic Drugs (DMARDs) from a list of the 6 most commonly prescribed in the participating countries (Methotrexate, sulfasalazine, hydroxychloroquine, leflunomide, cyclosporine A and gold).	Etanercept (ETN) 50 milligrams (mg) sub-cutaneous (SC) injection once weekly (pre-filled syringe) plus continuation of current dose of Methotrexate (MTX) either oral (PO), SC, or intramuscular (IM).
Measure Participants	0	0

10. Secondary Outcome

Title	Percentage of Participants With American College of Rheumatology 20% (ACR20) Response
Description	American College of Rheumatology 20% (ACR20) response: responder = ≥ 20% improvement in tender joint count; ≥ 20% improvement in swollen joint count; and ≥ 20% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and erythrocyte sedimentation rate (ESR). Subjects withdrawing early were non-responders.
Time Frame	Week 12, Week 24, Week 52

Outcome Measure Data

Analysis Population Description

mITT; efficacy data not analyzed due to early termination of the study.

Arm/Group Title	Usual Care	ETN + MTX
Arm/Group Description	Utilized Disease-Modifying Antirheumatic Drugs (DMARDs) from a list of the 6 most commonly prescribed in the participating countries (Methotrexate, sulfasalazine, hydroxychloroquine, leflunomide, cyclosporine A and gold).	Etanercept (ETN) 50 milligrams (mg) sub-cutaneous (SC) injection once weekly (pre-filled syringe) plus continuation of current dose of Methotrexate (MTX) either oral (PO), SC, or intramuscular (IM).
Measure Participants	0	0

11. Secondary Outcome

Title	Percentage of Participants With American College of Rheumatology 50% (ACR50) Response
Description	American College of Rheumatology 50% (ACR50) response: responder = ≥ 50% improvement in tender joint count; ≥ 50% improvement in swollen joint count; and ≥ 50% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and erythrocyte sedimentation rate (ESR). Subjects withdrawing early were non-responders.
Time Frame	Week 12, Week 24, Week 52

Outcome Measure Data

Analysis Population Description

mITT; efficacy data not analyzed due to early termination of the study.

Arm/Group Title	Usual Care	ETN + MTX
Arm/Group Description	Utilized Disease-Modifying Antirheumatic Drugs (DMARDs) from a list of the 6 most commonly prescribed in the participating countries (Methotrexate, sulfasalazine, hydroxychloroquine, leflunomide, cyclosporine A and gold).	Etanercept (ETN) 50 milligrams (mg) sub-cutaneous (SC) injection once weekly (pre-filled syringe) plus continuation of current dose of Methotrexate (MTX) either oral (PO), SC, or intramuscular (IM).
Measure Participants	0	0

12. Secondary Outcome

Title	Percentage of Participants With American College of Rheumatology 70% (ACR70) Response
Description	American College of Rheumatology 70% (ACR70) response: responder = ≥ 70% improvement in tender joint count; ≥ 70% improvement in swollen joint count; and ≥ 70% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and erythrocyte sedimentation rate (ESR) . Subjects withdrawing early were non-responders.
Time Frame	Week 12, Week 24, Week 52

Outcome Measure Data

Analysis Population Description

mITT; efficacy data not analyzed due to early termination of the study.

Arm/Group Title	Usual Care	ETN + MTX
Arm/Group Description	Utilized Disease-Modifying Antirheumatic Drugs (DMARDs) from a list of the 6 most commonly prescribed in the participating countries (Methotrexate, sulfasalazine, hydroxychloroquine, leflunomide, cyclosporine A and gold).	Etanercept (ETN) 50 milligrams (mg) sub-cutaneous (SC) injection once weekly (pre-filled syringe) plus continuation of current dose of Methotrexate (MTX) either oral (PO), SC, or intramuscular (IM).
Measure Participants	0	0

13. Secondary Outcome

Title	Percentage of Participants With American College of Rheumatology 90% (ACR90) Response
Description	American College of Rheumatology 90% (ACR 90) response: responder = ≥ 90% improvement in tender joint count; ≥ 90% improvement in swollen joint count; and ≥ 90% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and erythrocyte sedimentation rate (ESR). Subjects withdrawing early were non-responders.
Time Frame	Week 12, Week 24, Week 52

Outcome Measure Data

Analysis Population Description

mITT; efficacy data not analyzed due to early termination of the study.

Arm/Group Title	Usual Care	ETN + MTX
Arm/Group Description	Utilized Disease-Modifying Antirheumatic Drugs (DMARDs) from a list of the 6 most commonly prescribed in the participating countries (Methotrexate, sulfasalazine, hydroxychloroquine, leflunomide, cyclosporine A and gold).	Etanercept (ETN) 50 milligrams (mg) sub-cutaneous (SC) injection once weekly (pre-filled syringe) plus continuation of current dose of Methotrexate (MTX) either oral (PO), SC, or intramuscular (IM).
Measure Participants	0	0

14. Secondary Outcome

Title	Change From Baseline in Mean Daily Dose of Corticosteroids to Manage Flare-ups Across the 52-week Treatment Period
Description	Mean daily dose of corticosteroids to manage flare-ups (temporary increases in corticosteroid dose or use of intra-articular steroids) during treatment period. Daily dose of equivalent prednisone derived in mg/day: oral corticosteroids: 5 mg of prednisone = 5 mg of prednisolone = 25 mg of cortisone = 20 mg of hydrocortisone = 4 mg of methylprednisolone = 4 mg of triamcinolone = 2mg of paramethasone = 0.75 mg of betamethasone = 0.75 of dexamethasone = 0.3 of cortivazol.
Time Frame	Week 4, Week 12, Week 24, Week 40, Week 52

Outcome Measure Data

Analysis Population Description

mITT; efficacy data not analyzed due to early termination of the study.

Arm/Group Title	Usual Care	ETN + MTX
Arm/Group Description	Utilized Disease-Modifying Antirheumatic Drugs (DMARDs) from a list of the 6 most commonly prescribed in the participating countries (Methotrexate, sulfasalazine, hydroxychloroquine, leflunomide, cyclosporine A and gold).	Etanercept (ETN) 50 milligrams (mg) sub-cutaneous (SC) injection once weekly (pre-filled syringe) plus continuation of current dose of Methotrexate (MTX) either oral (PO), SC, or intramuscular (IM).
Measure Participants	0	0

15. Secondary Outcome

Title	Percentage of Participants Achieving a Minimal Clinically Important Improvement (MCII)
Description	Participants were asked how their pain had been during the last 48 hours compared to baseline. Participants that reported improvement assessed how important this improvement was to them; range: very important, moderately important, slightly important, or not at all important. Binary response options: 1=improved very important, or improved moderately important; 2=slightly important, not at all important, no change, or worse-more pain.
Time Frame	Week 12, Week 52

Outcome Measure Data

Analysis Population Description

mITT; efficacy data not analyzed due to early termination of the study.

Arm/Group Title	Usual Care	ETN + MTX
Arm/Group Description	Utilized Disease-Modifying Antirheumatic Drugs (DMARDs) from a list of the 6 most commonly prescribed in the participating countries (Methotrexate, sulfasalazine, hydroxychloroquine, leflunomide, cyclosporine A and gold).	Etanercept (ETN) 50 milligrams (mg) sub-cutaneous (SC) injection once weekly (pre-filled syringe) plus continuation of current dose of Methotrexate (MTX) either oral (PO), SC, or intramuscular (IM).
Measure Participants	0	0

16. Secondary Outcome

Title	Percentage of Participants Achieving a Patient Acceptable Symptom State (PASS)
Description	Percentage of participants reporting acceptable symptom state: acceptance to remain for the rest of their lives with the level of pain they had during the last 48 hours; and unacceptable symptom state: not able to remain for the rest of their lives with the level of pain they had during the last 48 hours.
Time Frame	Week 4, Week 12, Week 24, Week 40, Week 52

Outcome Measure Data

Analysis Population Description

mITT; efficacy data not analyzed due to early termination of the study.

Arm/Group Title	Usual Care	ETN + MTX
Arm/Group Description	Utilized Disease-Modifying Antirheumatic Drugs (DMARDs) from a list of the 6 most commonly prescribed in the participating countries (Methotrexate, sulfasalazine, hydroxychloroquine, leflunomide, cyclosporine A and gold).	Etanercept (ETN) 50 milligrams (mg) sub-cutaneous (SC) injection once weekly (pre-filled syringe) plus continuation of current dose of Methotrexate (MTX) either oral (PO), SC, or intramuscular (IM).
Measure Participants	0	0

17. Secondary Outcome

Title	Health Related Quality of Life: EuroQol-5D Health Index
Description	EQ-5D is a self-administered questionnaire to assess health-related quality of life in 5 domains (mobility, self care, usual activities, pain or discomfort, and anxiety or depression). Scores from the 5 domains are used to calculate the Health State Profile Score as a single index value; range: 0.0 (death) to 1.0 (perfect health); higher scores indicate a better health state.
Time Frame	Baseline, Week 12, Week 24, and Week 52

Outcome Measure Data

Analysis Population Description

mITT; efficacy data not analyzed due to early termination of the study.

Arm/Group Title	Usual Care	ETN + MTX
Arm/Group Description	Utilized Disease-Modifying Antirheumatic Drugs (DMARDs) from a list of the 6 most commonly prescribed in the participating countries (Methotrexate, sulfasalazine, hydroxychloroquine, leflunomide, cyclosporine A and gold).	Etanercept (ETN) 50 milligrams (mg) sub-cutaneous (SC) injection once weekly (pre-filled syringe) plus continuation of current dose of Methotrexate (MTX) either oral (PO), SC, or intramuscular (IM).
Measure Participants	0	0

18. Secondary Outcome

Title	Health Related Quality of Life: EuroQol-5D Health State Visual Analog Scale (VAS)
Description	EQ-5D: subject rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health state.
Time Frame	Baseline, Week 12, Week 24, and Week 52

Outcome Measure Data

Analysis Population Description

mITT; efficacy data not analyzed due to early termination of the study.

Arm/Group Title	Usual Care	ETN + MTX
Arm/Group Description	Utilized Disease-Modifying Antirheumatic Drugs (DMARDs) from a list of the 6 most commonly prescribed in the participating countries (Methotrexate, sulfasalazine, hydroxychloroquine, leflunomide, cyclosporine A and gold).	Etanercept (ETN) 50 milligrams (mg) sub-cutaneous (SC) injection once weekly (pre-filled syringe) plus continuation of current dose of Methotrexate (MTX) either oral (PO), SC, or intramuscular (IM).
Measure Participants	0	0

Adverse Events

Arm/Group Title	Usual Care		ETN + MTX
Arm/Group Description	Utilized Disease-Modifying Antirheumatic Drugs (DMARDs) from a list of the 6 most commonly prescribed in the participating countries (Methotrexate, sulfasalazine, hydroxychloroquine, leflunomide, cyclosporine A and gold).		Etanercept (ETN) 50 milligrams (mg) sub-cutaneous (SC) injection once weekly (pre-filled syringe) plus continuation of current dose of Methotrexate (MTX) either oral (PO), SC, or intramuscular (IM).
All Cause Mortality
	Usual Care		ETN + MTX
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Usual Care		ETN + MTX
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/63 (6.3%)		5/71 (7%)
Cardiac disorders
Cardiac failure	1/63 (1.6%)		0/71 (0%)
Atrial fibrillation	0/63 (0%)		1/71 (1.4%)
Gastrointestinal disorders
Gastritis	1/63 (1.6%)		0/71 (0%)
Hiatus hernia	0/63 (0%)		1/71 (1.4%)
Infections and infestations
Bronchopneumonia	1/63 (1.6%)		0/71 (0%)
Pneumonia	0/63 (0%)		2/71 (2.8%)
Pyothorax	0/63 (0%)		1/71 (1.4%)
Musculoskeletal and connective tissue disorders
Bursitis	1/63 (1.6%)		0/71 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	0/63 (0%)		2/71 (2.8%)
Nervous system disorders
Transient ischaemic attack	0/63 (0%)		1/71 (1.4%)
Other (Not Including Serious) Adverse Events
	Usual Care		ETN + MTX
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	27/63 (42.9%)		37/71 (52.1%)
Blood and lymphatic system disorders
Anaemia	1/63 (1.6%)		0/71 (0%)
Leukopenia	1/63 (1.6%)		0/71 (0%)
Cardiac disorders
Atrial fibrillation	1/63 (1.6%)		1/71 (1.4%)
Mitral valve incompetence	1/63 (1.6%)		0/71 (0%)
Palpitations	0/63 (0%)		1/71 (1.4%)
Sick sinus syndrome	1/63 (1.6%)		0/71 (0%)
Endocrine disorders
Goitre	0/63 (0%)		1/71 (1.4%)
Eye disorders
Astigmatism	1/63 (1.6%)		0/71 (0%)
Cataract	1/63 (1.6%)		1/71 (1.4%)
Conjunctivitis	0/63 (0%)		2/71 (2.8%)
Myopia	0/63 (0%)		1/71 (1.4%)
Retinopathy	0/63 (0%)		1/71 (1.4%)
Gastrointestinal disorders
Abdominal pain	1/63 (1.6%)		0/71 (0%)
Abdominal pain upper	2/63 (3.2%)		0/71 (0%)
Aphthous stomatitis	2/63 (3.2%)		0/71 (0%)
Dental caries	0/63 (0%)		1/71 (1.4%)
Diarrhoea	1/63 (1.6%)		1/71 (1.4%)
Enteritis	1/63 (1.6%)		0/71 (0%)
Gastritis	1/63 (1.6%)		0/71 (0%)
Nausea	3/63 (4.8%)		0/71 (0%)
Reflux gastritis	1/63 (1.6%)		0/71 (0%)
Toothache	1/63 (1.6%)		1/71 (1.4%)
Vomiting	0/63 (0%)		1/71 (1.4%)
General disorders
Asthenia	1/63 (1.6%)		2/71 (2.8%)
Fatigue	0/63 (0%)		2/71 (2.8%)
Injection site erythema	0/63 (0%)		1/71 (1.4%)
Injection site joint inflammation	0/63 (0%)		1/71 (1.4%)
Injection site pruritus	0/63 (0%)		1/71 (1.4%)
Injection site rash	0/63 (0%)		4/71 (5.6%)
Injection site reaction	0/63 (0%)		3/71 (4.2%)
Oedema peripheral	1/63 (1.6%)		1/71 (1.4%)
Pyrexia	1/63 (1.6%)		0/71 (0%)
Hepatobiliary disorders
Hepatic cyst	1/63 (1.6%)		0/71 (0%)
Liver disorder	0/63 (0%)		1/71 (1.4%)
Immune system disorders
Hypersensitivity	0/63 (0%)		1/71 (1.4%)
Infections and infestations
Arthritis infective	0/63 (0%)		1/71 (1.4%)
Bronchitis	1/63 (1.6%)		1/71 (1.4%)
Diverticulitis	0/63 (0%)		1/71 (1.4%)
Gastroenteritis	1/63 (1.6%)		0/71 (0%)
Helicobacter infection	1/63 (1.6%)		0/71 (0%)
Herpes zoster	1/63 (1.6%)		0/71 (0%)
Influenza	1/63 (1.6%)		1/71 (1.4%)
Nasopharyngitis	0/63 (0%)		3/71 (4.2%)
Oral herpes	0/63 (0%)		1/71 (1.4%)
Pneumonia	0/63 (0%)		1/71 (1.4%)
Rash pustular	1/63 (1.6%)		0/71 (0%)
Rhinitis	0/63 (0%)		2/71 (2.8%)
Tooth infection	0/63 (0%)		1/71 (1.4%)
Upper respiratory tract infection	1/63 (1.6%)		3/71 (4.2%)
Urinary tract infection	2/63 (3.2%)		2/71 (2.8%)
Viral infection	0/63 (0%)		1/71 (1.4%)
Injury, poisoning and procedural complications
Contusion	1/63 (1.6%)		0/71 (0%)
Investigations
Alanine aminotransferase increased	0/63 (0%)		1/71 (1.4%)
Aspartate aminotransferase increased	1/63 (1.6%)		0/71 (0%)
Blood urea increased	1/63 (1.6%)		0/71 (0%)
Hepatitis b dna decreased	0/63 (0%)		1/71 (1.4%)
Transaminases abnormal	0/63 (0%)		1/71 (1.4%)
Transaminases increased	1/63 (1.6%)		2/71 (2.8%)
Weight decreased	1/63 (1.6%)		0/71 (0%)
Metabolism and nutrition disorders
Hyperlipidaemia	0/63 (0%)		1/71 (1.4%)
Type 2 diabetes mellitus	1/63 (1.6%)		0/71 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/63 (1.6%)		0/71 (0%)
Arthritis	1/63 (1.6%)		0/71 (0%)
Back pain	1/63 (1.6%)		2/71 (2.8%)
Osteoarthritis	0/63 (0%)		1/71 (1.4%)
Osteopenia	1/63 (1.6%)		1/71 (1.4%)
Osteoporosis	0/63 (0%)		1/71 (1.4%)
Pain in extremity	1/63 (1.6%)		1/71 (1.4%)
Rheumatoid arthritis	1/63 (1.6%)		1/71 (1.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma	0/63 (0%)		1/71 (1.4%)
Nervous system disorders
Dizziness	1/63 (1.6%)		0/71 (0%)
Dysgeusia	0/63 (0%)		1/71 (1.4%)
Headache	1/63 (1.6%)		1/71 (1.4%)
Hypoaesthesia	0/63 (0%)		2/71 (2.8%)
Intercostal neuralgia	0/63 (0%)		1/71 (1.4%)
Paraesthesia	0/63 (0%)		1/71 (1.4%)
Psychiatric disorders
Agitation	0/63 (0%)		1/71 (1.4%)
Depressed mood	0/63 (0%)		2/71 (2.8%)
Depression	1/63 (1.6%)		0/71 (0%)
Renal and urinary disorders
Dysuria	0/63 (0%)		1/71 (1.4%)
Haematuria	1/63 (1.6%)		0/71 (0%)
Leukocyturia	1/63 (1.6%)		0/71 (0%)
Nephrolithiasis	1/63 (1.6%)		0/71 (0%)
Nephropathy toxic	1/63 (1.6%)		0/71 (0%)
Urethral pain	0/63 (0%)		1/71 (1.4%)
Reproductive system and breast disorders
Breast pain	1/63 (1.6%)		0/71 (0%)
Menorrhagia	1/63 (1.6%)		0/71 (0%)
Prostatitis	0/63 (0%)		1/71 (1.4%)
Thelitis	0/63 (0%)		1/71 (1.4%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/63 (0%)		1/71 (1.4%)
Epistaxis	0/63 (0%)		1/71 (1.4%)
Skin and subcutaneous tissue disorders
Ecchymosis	2/63 (3.2%)		0/71 (0%)
Hyperkeratosis	0/63 (0%)		1/71 (1.4%)
Melanosis	0/63 (0%)		1/71 (1.4%)
Pruritus	0/63 (0%)		1/71 (1.4%)
Rash pruritic	0/63 (0%)		1/71 (1.4%)
Skin exfoliation	1/63 (1.6%)		0/71 (0%)
Skin ulcer	0/63 (0%)		1/71 (1.4%)
Surgical and medical procedures
Knee arthroplasty	1/63 (1.6%)		0/71 (0%)
Thyroidectomy	0/63 (0%)		1/71 (1.4%)
Tooth extraction	0/63 (0%)		1/71 (1.4%)
Vascular disorders
Aortic arteriosclerosis	0/63 (0%)		1/71 (1.4%)
Arteriosclerosis	0/63 (0%)		1/71 (1.4%)
Flushing	1/63 (1.6%)		0/71 (0%)
Haematoma	1/63 (1.6%)		0/71 (0%)
Hot flush	0/63 (0%)		1/71 (1.4%)
Hypertension	4/63 (6.3%)		2/71 (2.8%)
Hypotension	1/63 (1.6%)		0/71 (0%)

Limitations/Caveats

Following early termination of the study, only disposition of randomized participants, description of demographic data on safety population, and safety analyses were performed.

More Information

Certain Agreements

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

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.