A Two-Part 26-Week Study of Etoricoxib as Treatment for Ankylosing Spondylitis (AS) (MK-0663-108)

A Phase III, Two-Part, Randomized, Double-Blind, Active Comparator-Controlled, Multicenter Clinical Trial to Study the Relative Efficacy and Tolerability of Two Doses of MK-0663/Etoricoxib in Patients With Ankylosing Spondylitis

Sponsors

Lead Sponsor: Merck Sharp & Dohme Corp.

Source Merck Sharp & Dohme Corp.
Brief Summary

The purpose of the study is to evaluate the efficacy and tolerability of two doses of etoricoxib compared to naproxen in the treatment of ankylosing spondylitis (AS). The primary objectives are to evaluate the improvement in Spinal Pain Intensity over 6 weeks of treatment with etoricoxib 90 mg or 60 mg compared to naproxen; and to evaluate the improvement in Spinal Pain Intensity over 6 weeks of treatment with etoricoxib 90 mg compared with etoricoxib 60 mg. 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. The primary hypothesis is that the improvement in Spinal Pain Intensity visual analog scale (VAS) as measured by the time-weighted average (TWA) change from baseline over 6 weeks of treatment in Part I for etoricoxib 90 mg or 60 mg once daily is not inferior to naproxen 1000 mg.

Overall Status Completed
Start Date September 27, 2010
Completion Date November 12, 2014
Primary Completion Date November 12, 2014
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Time-Weighted Average Change From Baseline in the Spinal Pain Intensity in Study Part 1: Etoricoxib 90 mg vs. Naproxen Baseline and up to Week 6
Time-Weighted Average Change From Baseline in the Spinal Pain Intensity in Study Part 1: Etoricoxib 60 mg vs. Naproxen Baseline and up to Week 6
Number of Participants Discontinuing Study Treatment Due to an Adverse Event Up to 26 weeks
Secondary Outcome
Measure Time Frame
Time-Weighted Average Change From Baseline in the Spinal Pain Intensity in Study Part 1: Etoricoxib 90 mg vs. Etoricoxib 60 mg Baseline and up to Week 6
Average Change From Week 6 in the Spinal Pain Intensity Over Weeks 10 and 12 in Study Part 2: Etoricoxib 60/90 mg vs. Etoricoxib 60mg (Non-responders From Part I) Week 6 to Week 10 and Week 12
Enrollment 1015
Condition
Intervention

Intervention Type: Drug

Intervention Name: Part I - etoricoxib 60 mg

Description: etoricoxib 60 mg oral tablet once daily for 6 weeks

Other Name: MK-0663

Intervention Type: Drug

Intervention Name: Part I - etoricoxib 90 mg

Description: etoricoxib 90 mg oral tablet once daily for 6 weeks

Arm Group Label: etoricoxib 90 mg/etoricoxib 90 mg

Other Name: Mk-0663

Intervention Type: Drug

Intervention Name: Part I- naproxen 1000 mg

Description: naproxen 500 mg oral tablet twice daily for 6 weeks

Arm Group Label: naproxen 1000 mg/naproxen 1000 mg

Intervention Type: Drug

Intervention Name: Part I - Placebo to naproxen 500 mg

Description: Placebo to naproxen 500 mg oral tablet twice daily for 6 weeks

Intervention Type: Drug

Intervention Name: Part II- etoricoxib 60 mg

Description: etoricoxib 60 mg oral tablet once daily for 20 weeks

Arm Group Label: etoricoxib 60 mg/etoricoxib 60 mg

Other Name: MK-0663

Intervention Type: Drug

Intervention Name: Part II- etoricoxib 90 mg

Description: etoricoxib 90 mg oral tablet once daily for 20 weeks

Other Name: MK-0663

Intervention Type: Drug

Intervention Name: Part II- naproxen 1000 mg

Description: naproxen 500 mg oral tablet twice daily for 20 weeks

Arm Group Label: naproxen 1000 mg/naproxen 1000 mg

Intervention Type: Drug

Intervention Name: Part I - Placebo to etoricoxib 60 mg

Description: Placebo to etoricoxib 60 mg oral tablet once daily for 6 weeks.

Intervention Type: Drug

Intervention Name: Part I - Placebo to etoricoxib 90 mg

Description: Placebo to etoricoxib 90 mg oral tablet once daily for 6 weeks.

Intervention Type: Drug

Intervention Name: Part II- Placebo to etoricoxib 60 mg

Description: Placebo to etoricoxib 60 mg oral tablet once daily for 20 weeks.

Intervention Type: Drug

Intervention Name: Part II - Placebo to etoricoxib 90 mg

Description: Placebo to etoricoxib 90 mg oral tablet once daily for 20 weeks.

Intervention Type: Drug

Intervention Name: Part II- Placebo to naproxen 500 mg

Description: Placebo to naproxen 500 mg orally twice daily for 20 weeks.

Eligibility

Criteria:

Inclusion Criteria:

- Has a definite diagnosis of Ankylosing Spondylitis (AS) per Modified New York Criteria made at least 6 months prior to screening

- Has a history of positive therapeutic benefit with non-steroidal anti-inflammatory drugs (NSAIDs) and regular use of NSAIDS for past 30 days

- Has a score on Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Question 2 at screening visit that is <77 mm

- Must demonstrate sufficient "flare" or worsening of AS pain

- Is in general good health (other than AS)

- Has had approved non-study antirheumatic therapy that has been at stable dosing AND is not anticipated to undergo a change within the first 6 weeks of the protocol

Exclusion Criteria:

- Has inflammatory arthritis (eg, rheumatoid arthritis, psoriatic arthritis, crystal-induced arthritis, spondyloarthropathy, diffuse idiopathic skeletal hyperostosis [DISH]), polymyalgia rheumatica, a history of septic arthritis or intra-articular fracture of the study joint, Wilson's disease, hemachromatosis, ochronosis, or primary osteochondromatosis

- Has acute peripheral articular disease (onset within 4 weeks prior to screening) of an active (painful or swollen) peripheral arthritis

- Has a history of gastric or biliary surgery, or small intestine surgery that causes clinical malabsorption

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

- Has undergone coronary artery bypass graft surgery (CABG), angioplasty, or has a cerebrovascular accident or transient ischemic attack within the past 6 months or has active ischemic heart disease, cerebrovascular disease, or peripheral vascular disease

- Has Class II-IV congestive heart failure

- Has uncontrolled hypertension

- Has a history of neoplastic disease, except adequately treated basal cell carcinoma or carcinoma in situ of the cervix, or malignancies that have been successfully treated ≥ 5 years prior to screening

- Has history of leukemia, lymphoma, malignant melanoma, and myeloproliferative disease

- Allergy to etoricoxib or naproxen, or history of a significant clinical or laboratory adverse experience associated with etoricoxib or naproxen

- Has a history or family history of an inherited or acquired bleeding disorder

- Is considered morbidly obese and demonstrates significant health problems stemming from obesity, which would confound study participation or interpretation of study results

- Is pregnant, breast-feeding, or expecting to conceive during the study

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

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Medical Director Study Director Merck Sharp & Dohme Corp.
Verification Date

September 2018

Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 4
Arm Group

Label: etoricoxib 60 mg/etoricoxib 60 mg

Type: Experimental

Description: The etoricoxib 60 mg/etoricoxib 60 mg treatment sequence will receive etoricoxib 60 mg in Part I and Part II

Label: etoricoxib 60 mg/etoricoxib 90 mg

Type: Experimental

Description: The etoricoxib 60 mg/etoricoxib 90 mg treatment sequence will receive etoricoxib 60 mg in Part I and etoricoxib 90 mg in Part II

Label: etoricoxib 90 mg/etoricoxib 90 mg

Type: Experimental

Description: The etoricoxib 90 mg/etoricoxib 90 mg treatment sequence will receive etoricoxib 90 mg in Part I and Part II

Label: naproxen 1000 mg/naproxen 1000 mg

Type: Active Comparator

Description: The naproxen 1000 mg/naproxen 1000 mg treatment sequence will receive naproxen 1000 mg in Part I and Part II

Patient Data Yes
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Triple (Participant, Investigator, Outcomes Assessor)

Source: ClinicalTrials.gov