Etoricoxib and placebo in patients with rheumatoid arthritis

• Register: EUCTR
• Last refreshed on: 7 October 2014
• Main ID: EUCTR2010-019871-31-AT
• Date of registration: 01/09/2010
• Prospective Registration: Yes
• Primary sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
• Public title: Etoricoxib and placebo in patients with rheumatoid arthritis
• Scientific 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
• Date of first enrolment: 03/11/2010
• Target sample size: 1800
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-019871-31
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 4

Countries of recruitment

Argentina, Austria, Belgium, Canada, Colombia, Czech Republic, Finland, Germany, India, Lithuania, Mexico, Poland, Romania, Russian Federation, Slovakia, South Africa, Taiwan, United Kingdom, United States

Contacts

• Name: Steven Hildemann
• Affiliation: MSD Regional Business Support Center GmbH

• Name: Steven Hildemann
• Affiliation: MSD Regional Business Support Center GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patient is a male or female = 18 years of age on the day of signing informed consent.
2. Patient understands the study procedures, the alternative treatments available, the risks involved with the study, and voluntarily agrees to participate by giving written informed consent.
3. Patient is able to read, understand and complete study questionnaires, including
questions requiring a visual analog scale (VAS) response.
4. Female patients of reproductive potential must demonstrate a serum ß-hCG level
consistent with a nongravid state at the prestudy visit and agree to remain abstinent, use oral, barrier, intramuscular, or implanted contraceptives from the prestudy Visit 1 until 28 days after the last dose of study medication. Women who are postmenopausal or have had a hysterectomy or bilateral tubal ligation or bilateral oophorectomy are exempt from this requirement. (Postmenopausal is defined as no menses for the previous 1 year).
Note: Serum FSH sample will be obtained only from women with cessation of menses within 1 year prior to Visit 1. If a patient’s Visit 1 FSH result is not within the postmenopausal range (as defined by the central laboratory), serum ß-hCG must be tested. The patient must demonstrate a serum ß-hCG level consistent with a nongravid state at the screening to continue in the study.
5. Patient is willing to limit alcohol intake to 2 drinks or equivalent per day for the duration of the study and follow-up period (one drink is defined as 2 oz. of hard alcohol, 5 oz. of wine, or 12 oz. of beer) and avoid unaccustomed physical activity (e.g., weight lifting) for the duration of the study.
6. Excepting RA, patient is judged to be in otherwise general good health based on
medical history, physical examination, and routine laboratory tests.
7. Patient has satisfied (for RA diagnosis) at least 4 of 7 ARA 1987 revised criteria for
the diagnosis of RA.
8. Patient is ACR Functional Class I, II, or III.
9. Patient has had a diagnosis of RA made at least 6 months prior to study start and was = 16 years of age when diagnosed.
10. Patient global assessment of disease activity (VAS of 100 mm) at Visit 1 is less than 80 mm.
11. Patient has a history of positive therapeutic benefit with NSAIDs and has taken an NSAID on a regular basis and at a therapeutic dose level (see Appendix 6.1) prior to study enrollment ( basis is defined as greater than 20 of the previous 30
days, including 7 of the last 10 days).
12. If patient is currently using anti-rheumatic therapy othen than NSAIDs, patient's approved nonstudy antirheumatic therapy has been at stable dosing relative to Visit 2 for the required time periods listed below AND is not anticipated to undergo a change during the study. Similarly, patients must not have discontinued such therapy within the timeframe given below.
Abatacept: 3 months; Adalimumab: 3 months; Anakinra: 2 months; Antimalarials: 6 weeks; Azathioprine: 3 months; Certolizumab pegol: 3 months; Cyclosporin A: 3 months; d-Penicillamine: 3 months; Etanercept: 3 months; Gold salts (oral or injectable): 3 months; Golimumab: 3 months; Infliximab: 3 months; Leflunomide: 3 months; Methotrexate: 2 months; Sulfasalazine: 6 weeks; Tocilizumab: 3 months;
Note: Treatment with rituximab or epratuzumab is not allowed within 6 months
prior to enrollment. Note: The use of other locally approved RA medications will be considered on a case-by-case basis and require prior discussion with the SPONSOR (or its delegates) before the patient i
Exclusion criteria:
Previous or Concurrent Diseases
1. Patient is legally incompetent (e.g., a minor or mentally incapacitated), or has active psychosis, or significant emotional problems at the time of the study which in the view of the investigator are sufficient to interfere with the conduct of the study.
2. Patient has a concurrent medical/arthritic disease that could confound or interfere with evaluation of efficacy including, but not limited to: inflammatory arthritis (e.g., systemic lupus erythematosus, spondyloarthropathy, polymyalgia rheumatica), recent acute attacks of gout or pseudogout, Paget’s disease affecting the study joint, a history of septic arthritis or intra-articular fracture of the study joint, osteochondritis desiccans or osteonecrosis of the study joint, Wilson’s disease, hemachromomatosis,
ochronosis, or primary osteochondromatosis and inflammatory muscle diseases (e.g. polymyositis, dermatomyositis). Note: Rheumatoid subjects with secondary Sjoegren's syndrome are allowed to participate in the study.
3. Patient has a history of gastric or biliary surgery (including gastric bypass surgery) or small intestine surgery that causes clinical malabsorption. Note: Patients who have had gastric banding or patients with cholecystectomy not resulting in malabsorbtion are allowed to participate.
4. Patient has an active peptic (gastric or duodenal) ulcer or history of inflammatory bowel disease.
5. Patient has a confirmed medical diagnosis of ischemic heart disease, cerebrovascular disease, or peripheral artery occlusive disease. In countries in which the use of selective COX-2 inhibitors has not been contraindicated in patients with these conditions, patients can otherwise participate (with the exception of those patients who have undergone coronary artery bypass graft surgery, angioplasty, or had a cerebrovascular accident or transient ischemic attack within the past 6 months).
6. Patient has class II-IV congestive heart failure (See Appendix 6.5).
7. Patient has uncontrolled hypertension (systolic >160 mm Hg or diastolic > 90 mm Hg) at Visit 1 or Visit 2. Investigators are encouraged to maximize blood pressure control according to local guidelines. Note: Local product labeling should be followed. In countries where the use of etoricoxib is contraindicated in patients with blood pressure values that are persistently elevated above 140/90 mm Hg, this definition of uncontrolled hypertension should be used. Note: Patients may be rescreened one time if blood pressure at Visit 1 is outside of the ranges listed above; patients must be excluded if blood pressure at Visit 2 is outside of the ranges listed above.
8. Patient has a history of neoplastic disease; Exceptions: (1) patients with adequately treated basal cell carcinoma or carcinoma in situ of the cervix may participate; (2) patients with other malignancies which have been successfully treated = 5 years prior to screening, where in the judgment of both the investigator and treating physician, appropriate follow-up has revealed no evidence of recurrence from the time of treatment through the time of screening. However, patients with a history of leukemia, lymphoma, malignant melanoma, and myeloproliferative disease are ineligible for the study regardless of the time since treatment, and in such cases, no exceptions will apply.
9. Patient is allergic to, or has a history of a significant clinical or laboratory adverse experience associated with etoricoxib; has hypersensitivity (e.g., bronch

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis (RA)
MedDRA version: 15.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Trade Name: ARCOXIA
Product Name: Etoricoxib
Product Code: MK-0663
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: ETORICOXIB
CAS Number: 202409-33-4
Current Sponsor code: MK-0663
Other descriptive name: 5-Chlor-6'-methyl- 3-[4-(methylsulfonyl)phenyl]- 2,3'-bipyridin
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 90-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: ARCOXIA
Product Name: Etoricoxib
Product Code: MK-0663
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: ETORICOXIB
CAS Number: 202409-33-4
Current Sponsor code: MK-0663
Other descriptive name: 5-Chlor-6'-methyl- 3-[4-(methylsulfonyl)phenyl]- 2,3'-bipyridin
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 60-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): The Primary Hypotheses 1 and 2 will be evaluated by comparing etoricoxib (90 mg,
60 mg) to placebo on the proportion of patients achieving the ACR20 Responder Index Criteria and completing Part I, and the time-weighted average change from baseline over the 6 weeks in Part I in Patient Global Assessment of Pain (VAS). An etoricoxib dose (90 mg, 60 mg) will be declared superior to placebo if it demonstrates significantly greater efficacy than placebo in both of these endpoints (alpha= 0.05, 2-sided).

Main Objective: Objective 1: To compare the effects of etoricoxib 90 mg vs. placebo after 6 weeks of
treatment
Objective 2: To compare the effects of etoricoxib 60 mg vs. placebo after 6 weeks of
treatment in Part I
Obejctive 3: To assess the safety and tolerability profile of etoricoxib 60 mg and 90 mg in the treatment of RA

Secondary Objective: Objective 1: To compare the effects between etoricoxib 90 mg and etoricoxib 60 mg
daily after 6 weeks of treatment in Part I
Objective 2: To evaluate the incremental benefit in those who are considered nonresponders to etoricoxib 60 mg in Part I, and who subsequently increase their dose to etoricoxib 90 mg in Part II, to those non-responders on etoricoxib 60 mg in Part I who subsequently remain on etoricoxib 60 mg in Part II

Timepoint(s) of evaluation of this end point: Assessment according to protocol

Secondary Outcome(s)

Secondary end point(s): Average change from week 6 in Patient Global Assessment of Pain (VAS) over weeks 10 and 12 among pain non-responders.

Timepoint(s) of evaluation of this end point: Assessment according to protocol

Secondary ID(s)

MK-0663-107

2010-019871-31-FI

Source(s) of Monetary Support

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.