Clinical trial NCT01208181: A Two-Part, 12-Week Study of Etoricoxib as a Treatment for Rheumatoid Arthritis (RA) (MK-0663-107)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Arthritis, Rheumatoid
Lead sponsor: Organon and Co
Sponsor class: INDUSTRY
First posted: 2010-09-23
Enrollment: 1404
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Time-Weighted Average Change From Baseline in DAS28-CRP in Part 1 (Etoricoxib vs. Placebo)
timeFrame: Baseline and Week 6
measure: Time-Weighted Average Change From Baseline in Patient Global Assessment of Pain in Part 1 (Etoricoxib vs. Placebo)
timeFrame: Baseline and Week 6
measure: Percentage of Participants Who Experienced at Least One Adverse Event (AE)
timeFrame: Up to 112 days
measure: Percentage of Participants Who Discontinued Study Drug Due to an AE
timeFrame: Up to Week 12
Secondary outcomes:
measure: Time-Weighted Average Change From Baseline in DAS28-CRP in Part 1 (Etoricoxib 90 mg vs. Etoricoxib 60 mg)
timeFrame: Baseline and Week 6
measure: Time-Weighted Average Change From Baseline in Patient Global Assessment of Pain in Part 1 (Etoricoxib 90 mg vs. Etoricoxib 60 mg)
timeFrame: Baseline and Week 6
measure: 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
timeFrame: Week 6 and Week 10 to Week 12
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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, randomized controlled trial. BMC Musculoskelet Disord. 2016 Aug 8;17:331. doi: 10.1186/s12891-016-1170-0.