Rheumatoid Arthritis Dose Ranging Study - Study Results

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Investigator); Primary Purpose: Treatment
Condition:	Rheumatoid Arthritis
Interventions:	Drug: etoricoxib Drug: Comparator: placebo Drug: Comparator: diclofenac

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
90 multicenter rheumatologists: US (71), Canada (14), Colombia (3), Switzerland (2), recruited 761 study patients from their patient pool and through advertising. First Patient In 04-Jan-2006, Last Patient Last Visit 26-Mar-2008.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Patients must have taken Non Steroidal Anti-inflammatory Drugs (NSAIDs) at a therapeutic labeled dose on a regular basis and demonstrated a clinical response in the past and at screening. Following a protocol-specified "washout," patients must have demonstrated disease activity and worsening in symptoms of Rheumatoid Arthritis from the screening.

Reporting Groups

	Description
Placebo	Treatment I: Placebo orally once daily
Etoricoxib 10 mg	Treatment I: Etoricoxib 10 mg orally once daily
Etoricoxib 30 mg	Treatment I: Etoricoxib 30 mg orally once daily
Etoricoxib 60 mg	Treatment I: Etoricoxib 60 mg orally once daily
Etoricoxib 90 mg	Treatment I and II: Etoricoxib 90 mg orally once daily
Diclofenac 150 mg (Treatment II)	Treatment II: Diclofenac 75 mg orally twice daily

Participant Flow for 2 periods

Period 1: Treatment I Period

	Placebo	Etoricoxib 10 mg	Etoricoxib 30 mg	Etoricoxib 60 mg	Etoricoxib 90 mg
STARTED	161	154	151	140	155
COMPLETED	63 ^[1]	71 ^[1]	74 ^[1]	68 ^[1]	99 ^[1]
NOT COMPLETED	98	83	77	72	56
Adverse Event	3	6	3	5	7
Laboratory Adverse Event	0	0	0	1	0
Lack of Efficacy	6	2	8	0	1
Lost to Follow-up	1	0	0	1	1
Protocol Violation	2	2	0	0	0
Withdrawal by Subject	2	0	0	2	2
Patient out of town for an extended time	0	1	0	0	0
Unblinded due to Serious Adverse Event	0	0	1	0	0
Reassigned to Treatment II Period	84	72	65	63	45

[1]	Randomized to Treatment I period and remained on Treatment I period during course of study

Period 2: Treatment II Period

	Etoricoxib 90 mg	Diclofenac 150 mg (Treatment II)
STARTED	180 ^[1]	149 ^[2]
COMPLETED	147	116
NOT COMPLETED	33	33
Adverse Event	9	9
Laboratory Adverse Event	0	1
Lack of Efficacy	20	19
Lost to Follow-up	1	1
Withdrawal by Subject	3	2
Pre-scheduled total hip replacement	0	1

[1]	Etoricoxib 10 mg (38), 30 mg (28), 60 mg (33), 90 mg (45) and placebo (36) reassigned to 90 mg (180)
[2]	Etoricoxib 10 mg (34), 30 mg (37), 60 mg (29), and placebo (49) reassigned to diclofenac (149)

Baseline Characteristics

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Reporting Groups

	Description
Placebo	Treatment I: Placebo orally once daily
Etoricoxib 10 mg	Treatment I: Etoricoxib 10 mg orally once daily
Etoricoxib 30 mg	Treatment I: Etoricoxib 30 mg orally once daily
Etoricoxib 60 mg	Treatment I: Etoricoxib 60 mg orally once daily
Etoricoxib 90 mg	Treatment I: Etoricoxib 90 mg orally once daily

Baseline Measures

	Placebo	Etoricoxib 10 mg	Etoricoxib 30 mg	Etoricoxib 60 mg	Etoricoxib 90 mg	Total
Number of Participants [units: participants]	161	154	151	140	155	761
Age [units: years] Mean ± Standard Deviation	57.4 ± 11.80	58.7 ± 11.92	56.2 ± 11.17	57.7 ± 10.96	54.9 ± 12.54	57.0 ± 11.75
Gender [units: participants]
Female	136	117	126	112	122	613
Male	25	37	25	28	33	148
American Rheumatism Association Functional Class ^[1] [units: Participants]
Class I	44	49	49	41	38	221
Class II	102	83	83	73	98	439
Class III	15	22	19	26	19	101
Corticosteroid User [units: Participants]
Yes	50	50	42	41	49	232
No	111	104	109	99	106	529
Disease Modifying Antirheumatic Drug User [units: Participants]
Yes	133	129	122	114	131	629
No	28	25	29	26	24	132
Disease Modifying Antirheumatic Drug or Corticosteroid User [units: Participants]
Yes	139	134	126	119	136	654
No	22	20	25	21	19	107
Methotrexate User [units: Participants]
Yes	99	91	96	93	93	472
No	62	63	55	47	62	289
Race/Ethnicity [units: participants]
Asian	1	0	1	1	1	4
Black	5	8	3	7	6	29
White	114	106	121	96	112	549
Hispanic	41	39	25	34	36	175
Native American	0	0	1	2	0	3
Indian	0	1	0	0	0	1
Rheumatoid Factor [units: Participants]
Positive	120	117	121	120	121	599
Negative	40	37	30	20	34	161
Not Reported	1	0	0	0	0	1
Smoking Status [units: Participants]
Current	27	28	29	23	22	129
Ex-User	53	46	42	39	40	220
Non-User	81	80	80	78	93	412
Body Weight [units: Kilograms] Mean ± Standard Deviation	76.42 ± 16.54	76.12 ± 18.48	77.36 ± 20.00	75.72 ± 19.54	77.97 ± 18.61	76.73 ± 18.58
Duration of Rheumatoid Arthritis (Years) [units: Years] Mean ± Standard Deviation	10.0 ± 9.78	10.1 ± 9.76	11.2 ± 8.40	10.3 ± 10.18	9.9 ± 9.98	10.3 ± 9.62
Height [units: Centimeters] Mean ± Standard Deviation	161.93 ± 9.71	163.63 ± 8.55	164.57 ± 9.13	162.96 ± 9.22	163.49 ± 10.04	163.30 ± 9.37
Investigator Global Assessment of Disease Activity (0 to 4 - Likert Scale) ^[2] [units: units on a scale] Mean ± Standard Deviation	2.71 ± 0.61	2.71 ± 0.67	2.75 ± 0.66	2.69 ± 0.63	2.73 ± 0.65	2.72 ± 0.64
Patient Global Assessment of Disease Activity (0-To- 100 Millimeter Visual Analog Scale) ^[3] [units: units on a scale] Mean ± Standard Deviation	66.08 ± 18.67	69.28 ± 19.37	66.56 ± 20.47	66.60 ± 19.58	65.42 ± 18.45	66.79 ± 19.30
Patient Global Assessment of Pain (0- To- 100-mm Visual Analog Scale) ^[3] [units: units on a scale] Mean ± Standard Deviation	72.66 ± 16.03	72.42 ± 17.32	70.95 ± 16.67	69.54 ± 18.24	71.08 ± 17.55	71.38 ± 17.14
Swollen Joint Count (Out of 66 Joints) [units: Number of Swollen Joints] Mean ± Standard Deviation	16.05 ± 9.79	17.75 ± 10.86	16.74 ± 10.11	15.79 ± 9.40	16.30 ± 10.05	16.53 ± 10.06
Tender Joint Count (Out of 68 Joints) [units: Number of Tender Joints] Mean ± Standard Deviation	26.91 ± 14.17	28.33 ± 15.42	27.19 ± 14.97	26.76 ± 14.37	27.25 ± 16.11	27.30 ± 15.00

[1]	Class I: Completely able to perform usual activities of daily living (self care, vocational, and avocational), Class II: Able to perform usual self-care and vocational activities, but limited in avocational activities, Class III: Able to perform usual self-care activities, but limited in vocational and avocational activities
[2]	(0 to 4 - Likert Scale) 0=Very Well, 1=Well, 2=Fair, 3=Poor, 4=Very Poor
[3]	(0- to 100-mm Visual Analog Scale) 0 mm= No pain, 100 mm= Extreme pain

Outcome Measures

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1. Primary:

Proportion of Patients Who Met the ACR20 Responder Index Criteria [ Time Frame: 12 weeks ]

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2. Secondary:

Tender Joint Count (Out of 68 Joints) Time-Weighted Average Change From Baseline (Flare/Randomization Visit) in the 12-Week Treatment Period (All Patients-Treated Population) [ Time Frame: Time-weighted average change from baseline across Weeks 2, 7, and 12 ]

Show Outcome Measure 2

3. Secondary:

Swollen Joint Count (Out of 66 Joints) Time-Weighted Average Change From Baseline (Flare/Randomization Visit) in the 12-Week Treatment Period (All Patients-Treated Population) [ Time Frame: Time-weighted average change from baseline across Weeks 2, 7, and 12 ]

Show Outcome Measure 3

4. Secondary:

Patient Global Assessment of Disease Activity (0- to 100-mm Visual Analog Scale) Time Weighted Average Change From Baseline (Flare/Randomization Visit) in the 12-Week Treatment I Period (All Patients-Treated Population) [ Time Frame: Time-weighted average change from baseline across Weeks 2, 7, and 12 ]

Show Outcome Measure 4

5. Secondary:

Investigator Global Assessment of Disease Activity (0- to 4-Likert Scale) Time Weighted Average Change From Baseline (Flare/Randomization Visit) in the 12-Week Treatment I Period (All Patients-Treated Population) [ Time Frame: Time-weighted average change from baseline across Weeks 2, 7, and 12 ]

Show Outcome Measure 5

6. Secondary:

Patient Global Assessment of Pain (0- to 100-mm Visual Analog Scale) Time Weighted Average Change From Baseline (Flare/Randomization Visit) in the 12-Week Treatment I Period (All Patients-Treated Population) [ Time Frame: Time-weighted average change from baseline across Weeks 2, 7, and 12 ]

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Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact:

Name/Title: Executive Vice President, Clinical and Quantitative Sciences
Organization: Merck Sharp & Dohme Corp
phone: 1-800-672-6372

No publications provided

Responsible Party:	Executive Vice President, Clinical and Quantitative Sciences, Merck Sharp & Dohme Corp
ClinicalTrials.gov Identifier:	NCT00264147 History of Changes
Other Study ID Numbers:	2005_077, MK0663-086
Study First Received:	December 9, 2005
Results First Received:	March 19, 2009
Last Updated:	April 14, 2010
Health Authority:	United States: Food and Drug Administration