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

NCT01208207 | Completed Phase 3 Results

• 1 other identifier: 0663-108
• Study Type: interventional
• Target: 1,015
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Spondylitis, Ankylosing

Outcome Measures

Primary Outcomes (3)

• Time-Weighted Average Change From Baseline in the Spinal Pain Intensity in Study Part 1: Etoricoxib 90 mg vs. Naproxen

  Spinal Pain Intensity is measured using a visual analog scale (VAS) from 0-100 mm with a lower value representing a better response. The time-weighted average change is calculated by taking the time between adjacent observations divided by the time from the randomization visit to the last observation in the period of interest, and using it as the weight for computation of the average.

  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

  Spinal Pain Intensity is measured using a visual analog scale (VAS) from 0-100 mm with a lower value representing a better response. The time-weighted average change is calculated by taking the time between adjacent observations divided by the time from the randomization visit to the last observation in the period of interest, and using it as the weight for computation of the average.

  Baseline and up to Week 6

• Number of Participants Discontinuing Study Treatment Due to an Adverse Event

  Up to 26 weeks

Secondary Outcomes (2)

• 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

Study Arms (4)

etoricoxib 60 mg/etoricoxib 60 mg

EXPERIMENTAL

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

Drug: Part I - etoricoxib 60 mg; Drug: Part I - Placebo to naproxen 500 mg; Drug: Part II- etoricoxib 60 mg; Drug: Part I - Placebo to etoricoxib 90 mg; Drug: Part II - Placebo to etoricoxib 90 mg; Drug: Part II- Placebo to naproxen 500 mg

etoricoxib 60 mg/etoricoxib 90 mg

EXPERIMENTAL

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

Drug: Part I - etoricoxib 60 mg; Drug: Part I - Placebo to naproxen 500 mg; Drug: Part II- etoricoxib 90 mg; Drug: Part I - Placebo to etoricoxib 90 mg; Drug: Part II- Placebo to etoricoxib 60 mg; Drug: Part II- Placebo to naproxen 500 mg

etoricoxib 90 mg/etoricoxib 90 mg

EXPERIMENTAL

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

Drug: Part I - etoricoxib 90 mg; Drug: Part I - Placebo to naproxen 500 mg; Drug: Part II- etoricoxib 90 mg; Drug: Part I - Placebo to etoricoxib 60 mg; Drug: Part II- Placebo to etoricoxib 60 mg; Drug: Part II- Placebo to naproxen 500 mg

naproxen 1000 mg/naproxen 1000 mg

ACTIVE COMPARATOR

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

Drug: Part I- naproxen 1000 mg; Drug: Part II- naproxen 1000 mg; Drug: Part I - Placebo to etoricoxib 60 mg; Drug: Part I - Placebo to etoricoxib 90 mg; Drug: Part II- Placebo to etoricoxib 60 mg; Drug: Part II - Placebo to etoricoxib 90 mg

Interventions

Part I - etoricoxib 60 mg DRUG

etoricoxib 60 mg oral tablet once daily for 6 weeks

Also known as: MK-0663

etoricoxib 60 mg/etoricoxib 60 mg; etoricoxib 60 mg/etoricoxib 90 mg

Part I - etoricoxib 90 mg DRUG

etoricoxib 90 mg oral tablet once daily for 6 weeks

Also known as: Mk-0663

etoricoxib 90 mg/etoricoxib 90 mg

Part I- naproxen 1000 mg DRUG

naproxen 500 mg oral tablet twice daily for 6 weeks

naproxen 1000 mg/naproxen 1000 mg

Part I - Placebo to naproxen 500 mg DRUG

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

etoricoxib 60 mg/etoricoxib 60 mg; etoricoxib 60 mg/etoricoxib 90 mg; etoricoxib 90 mg/etoricoxib 90 mg

Part II- etoricoxib 60 mg DRUG

etoricoxib 60 mg oral tablet once daily for 20 weeks

Also known as: MK-0663

etoricoxib 60 mg/etoricoxib 60 mg

Part II- etoricoxib 90 mg DRUG

etoricoxib 90 mg oral tablet once daily for 20 weeks

Also known as: MK-0663

etoricoxib 60 mg/etoricoxib 90 mg; etoricoxib 90 mg/etoricoxib 90 mg

Part II- naproxen 1000 mg DRUG

naproxen 500 mg oral tablet twice daily for 20 weeks

naproxen 1000 mg/naproxen 1000 mg

Part I - Placebo to etoricoxib 60 mg DRUG

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

etoricoxib 90 mg/etoricoxib 90 mg; naproxen 1000 mg/naproxen 1000 mg

Part I - Placebo to etoricoxib 90 mg DRUG

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

etoricoxib 60 mg/etoricoxib 60 mg; etoricoxib 60 mg/etoricoxib 90 mg; naproxen 1000 mg/naproxen 1000 mg

Part II- Placebo to etoricoxib 60 mg DRUG

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

etoricoxib 60 mg/etoricoxib 90 mg; etoricoxib 90 mg/etoricoxib 90 mg; naproxen 1000 mg/naproxen 1000 mg

Part II - Placebo to etoricoxib 90 mg DRUG

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

etoricoxib 60 mg/etoricoxib 60 mg; naproxen 1000 mg/naproxen 1000 mg

Part II- Placebo to naproxen 500 mg DRUG

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

etoricoxib 60 mg/etoricoxib 60 mg; etoricoxib 60 mg/etoricoxib 90 mg; etoricoxib 90 mg/etoricoxib 90 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Organon and Co: lead

Related Publications (1)

• Balazcs E, Sieper J, Bickham K, Mehta A, Frontera N, Stryszak P, Popmihajlov Z, Peloso PM. A randomized, clinical trial to assess the relative efficacy and tolerability of two doses of etoricoxib versus naproxen in patients with ankylosing spondylitis. BMC Musculoskelet Disord. 2016 Oct 13;17(1):426. doi: 10.1186/s12891-016-1275-5.

  PMID: 27737664 RESULT

MeSH Terms

Conditions

Spondylitis, Ankylosing

Interventions

Etoricoxib

Condition Hierarchy (Ancestors)

Axial Spondyloarthritis; Spondylarthropathies; Spondylarthritis; Spondylitis; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Ankylosis; Joint Diseases; Arthritis

Intervention Hierarchy (Ancestors)

Sulfones; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 22, 2010
• First Posted: September 23, 2010
• Study Start: September 27, 2010
• Primary Completion: November 12, 2014
• Study Completion: November 12, 2014
• Last Updated: June 18, 2024
• Results First Posted: July 2, 2015

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share