A Two-Part, 12-Week Study of Etoricoxib as a Treatment for Rheumatoid Arthritis (RA) (MK-0663-107)

Arthritis, Rheumatoid Clinical Trial

Official title:

A Phase III, Two-Part, Randomized, Double-Blind, Placebo-Controlled, Multicenter Clinical Trial to Assess the Relative Efficacy and Tolerability of Two Doses of MK-0663/Etoricoxib in Patients With Rheumatoid Arthritis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01208181
• Other study ID #: 0663-107
• Secondary ID: 2010-019871-31
• Status: Completed
• Phase: Phase 3
• Start date: September 27, 2010
• Est. completion date: July 29, 2014

Study information

• Verified date: February 2022
• Source: Organon and Co
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a 2-part (6 weeks duration for each part), randomized, double-blind, placebo-controlled study in participants with rheumatoid arthritis. The hypothesis is that etoricoxib (60 mg and 90 mg) administration will demonstrate superior efficacy compared to placebo after 6 weeks of treatment, as measured by the greater mean improvement from baseline in the Disease Activity Score C-Reactive Protein (DAS-28 CRP), and by the greater mean improvement in Patient Global Assessment of Pain (PGAP) from baseline over 6 weeks of treatment. Additionally, the added benefit of increasing the dose of etoricoxib from 60 mg to 90 mg will be assessed in the second part of the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1404
• Est. completion date: July 29, 2014
• Est. primary completion date: June 9, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Is male or female = 18 years of age in general good health (other than RA)

• Has an American College of Rheumatology Rheumatoid Clinical Response Criteria (ACR) Functional Class I, II, or III

• Has a diagnosis of RA at least 6 months ago and was at least 16 years of age when diagnosed

• Has a history of positive therapeutic benefit with nonsteroidal anti-inflammatory drugs (NSAIDs) and is taking an NSAID on a regular basis and at a therapeutic dose level and is not anticipated to undergo a change during the study

Exclusion Criteria:

• Has a concurrent medical/arthritic disease that could confound or interfere with evaluation of efficacy

• Has a history of gastric or biliary surgery (including gastric bypass surgery) or small intestine surgery that causes clinical malabsorption

• Has an active peptic (gastric or duodenal) ulcer or history of inflammatory bowel disease

• Has a confirmed medical diagnosis of ischemic heart disease, cerebrovascular disease, or peripheral artery occlusive disease

• Class II-IV congestive heart failure

• Has uncontrolled hypertension (systolic >160 mm Hg or diastolic > 90 mm Hg) at Visit 1 or Visit 2

• Has a clinical diagnosis of hepatic insufficiency defined as Child-Pugh score =5

• Has estimated glomerular filtration rate =30 mL/min

• Has a history of neoplastic disease within 5 years (exceptions: basal cell carcinoma or carcinoma in situ of the cervix)

• Is allergic to etoricoxib; history of a significant clinical or laboratory adverse experience associated with etoricoxib; hypersensitivity to aspirin or NSAIDs; or allergy to acetaminophen/paracetamol

• Has a personal or family history of an inherited or acquired bleeding disorder

• Requires oral corticosteroid therapy in excess of the equivalent of 10 mg daily of prednisone and/or have not been on a stable dose for at least 4 weeks prior to Visit 1 and/or whose dose is not expected to remain stable during the study

• Treated with B-cell depleting therapies within the past 6 months or anticipate this treatment during this trial

• Is a recreational or illicit drug use, or history within 5 years of drug or alcohol abuse/dependence;

• Is morbidly obese (defined as body mass index =40 kg/m^2)

• Is pregnant or breast feeding

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid

Intervention

Drug:
• Etoricoxib 60 mg
One tablet orally once daily for 6 weeks.
• Etoricoxib 90 mg
One tablet orally once daily for 6 weeks.
• Placebo to Etoricoxib 60 mg
One tablet orally once daily for 6 weeks.
• Placebo to Etoricoxib 90 mg
One tablet orally once daily for 6 weeks

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Organon and Co

References & Publications (1)

Bickham K, Kivitz AJ, Mehta A, Frontera N, Shah S, Stryszak P, Popmihajlov Z, Peloso PM. Evaluation of two doses of etoricoxib, a COX-2 selective non-steroidal anti-inflammatory drug (NSAID), in the treatment of Rheumatoid Arthritis in a double-blind, ran — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time-Weighted Average Change From Baseline in DAS28-CRP in Part 1 (Etoricoxib vs. Placebo)	Disease Activity Score Using C-Reactive Protein [DAS28-CRP] (0 - 10 Range). The DAS28-CRP index is a composite score of weighted components including tender joint counts of 28, swollen joint counts of 28, patient global assessment of disease activity, and C-reactive protein (CRP). For each observation (Baseline, Week 2, 4, 6, 10, 12), components were combined into a single DAS28-CRP score using the following algorithm: 0.56*square root (sqrt) (tender joint count [28])+0.28*sqrt(swollen joint count [28] )+0.36* ln(crp+1) + 0.014* Patient Global Assessment of Disease Activity + 0.96. The primary objectives of the study compared the efficacy of etoricoxib (90 mg, 60 mg) to placebo in Part 1 of this study so data for only these 3 arms are displayed.	Baseline and Week 6
Primary	Time-Weighted Average Change From Baseline in Patient Global Assessment of Pain in Part 1 (Etoricoxib vs. Placebo)	A participant overall assessment of pain on a visual analog scale (VAS) was assessed with a question concerning the amount of pain due to arthritis during the past 48 hours. Pain was assessed on an 100 mm VAS scale with a left-hand marker "no pain" (0 mm) or right-hand marker "extreme pain" (100 mm). The primary objectives of the study compared the efficacy of etoricoxib (90 mg, 60 mg) to placebo in Part 1 of this study so data for only these 3 arms are displayed.	Baseline and Week 6
Primary	Percentage of Participants Who Experienced at Least One Adverse Event (AE)	An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure.	Up to 112 days
Primary	Percentage of Participants Who Discontinued Study Drug Due to an AE	An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure.	Up to Week 12
Secondary	Time-Weighted Average Change From Baseline in DAS28-CRP in Part 1 (Etoricoxib 90 mg vs. Etoricoxib 60 mg)	Disease Activity Score Using C-Reactive Protein [DAS28-CRP] (0 - 10 Range). The DAS28-CRP index is a composite score of weighted components including tender joint counts of 28, swollen joint counts of 28, patient global assessment of disease activity, and C-reactive protein (CRP). For each observation (Baseline, Week 2, 4, 6, 10, 12), components were combined into a single DAS28-CRP score using the following algorithm: 0.56*square root (sqrt) (tender joint count [28])+0.28*sqrt(swollen joint count [28] )+0.36* ln(crp+1) + 0.014* Patient Global Assessment of Disease Activity + 0.96. The key secondary objectives compared the relative efficacy between etoricoxib 90 mg and 60 mg in Part 1 of this study so data for only these 2 arms are displayed.	Baseline and Week 6
Secondary	Time-Weighted Average Change From Baseline in Patient Global Assessment of Pain in Part 1 (Etoricoxib 90 mg vs. Etoricoxib 60 mg)	A participant overall assessment of pain on a visual analog scale (VAS) was assessed with a question concerning the amount of pain due to arthritis during the past 48 hours. Pain was assessed on an 100 mm VAS scale with a left-hand marker "no pain" (0 mm) or right-hand marker "extreme pain" (100 mm). The key secondary objectives compared the relative efficacy between etoricoxib 90 mg and 60 mg in Part 1 of this study so data for only these 2 arms are displayed.	Baseline and Week 6
Secondary	Average Change From Week 6 in Patient Global Assessment of Pain Over Weeks 10 and 12 in Part 2 Among Pain Inadequate Responders From Part 1	A participant overall assessment of pain on a visual analog scale (VAS) was assessed with a question concerning the amount of pain due to arthritis during the past 48 hours. Pain was assessed on an 100 mm VAS scale with a left-hand marker "no pain" (0 mm) or right-hand marker "extreme pain" (100 mm). In those participants who were considered inadequate responders to etoricoxib 60 mg in Part 1 (defined as a participant with <50% improvement from baseline in PGAP [VAS] at Week 6), the incremental benefit of increasing the etoricoxib dose from 60 mg (in Part 1) to 90 mg (in Part 2) compared to remaining on 60 mg in Part 2 was evaluated via average change from Week 6 over Weeks 10 and 12 in Patient Global Assessment of Pain score. Therefore, data for only these 2 arms are displayed.	Week 6 and Week 10 to Week 12