A Two-Part 26-Week Study of Etoricoxib as Treatment for Ankylosing Spondylitis (AS) (MK-0663-108)
Primary Purpose
Spondylitis, Ankylosing
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Part I - etoricoxib 60 mg
Part I - etoricoxib 90 mg
Part I- naproxen 1000 mg
Part I - Placebo to naproxen 500 mg
Part II- etoricoxib 60 mg
Part II- etoricoxib 90 mg
Part II- naproxen 1000 mg
Part I - Placebo to etoricoxib 60 mg
Part I - Placebo to etoricoxib 90 mg
Part II- Placebo to etoricoxib 60 mg
Part II - Placebo to etoricoxib 90 mg
Part II- Placebo to naproxen 500 mg
Sponsored by
About this trial
This is an interventional treatment trial for Spondylitis, Ankylosing
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Active Comparator
Arm Label
etoricoxib 60 mg/etoricoxib 60 mg
etoricoxib 60 mg/etoricoxib 90 mg
etoricoxib 90 mg/etoricoxib 90 mg
naproxen 1000 mg/naproxen 1000 mg
Arm Description
The etoricoxib 60 mg/etoricoxib 60 mg treatment sequence will receive etoricoxib 60 mg in Part I and Part II
The etoricoxib 60 mg/etoricoxib 90 mg treatment sequence will receive etoricoxib 60 mg in Part I and etoricoxib 90 mg in Part II
The etoricoxib 90 mg/etoricoxib 90 mg treatment sequence will receive etoricoxib 90 mg in Part I and Part II
The naproxen 1000 mg/naproxen 1000 mg treatment sequence will receive naproxen 1000 mg in Part I and Part II
Outcomes
Primary Outcome Measures
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.
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.
Number of Participants Discontinuing Study Treatment Due to an Adverse Event
Secondary Outcome Measures
Time-Weighted Average Change From Baseline in the Spinal Pain Intensity in Study Part 1: Etoricoxib 90 mg vs. Etoricoxib 60 mg
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.
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)
Spinal Pain Intensity is measured using a visual analog scale (VAS) from 0-100 mm with a lower value representing a better response. Average change from Week 6 in Spinal Pain Intensity (VAS) over Weeks 10 and 12 is calculated as the average Spinal pain Intensity (VAS) value over Weeks 10 and 12 minus the Spinal Pain Intensity (VAS) at Week 6.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01208207
Brief Title
A Two-Part 26-Week Study of Etoricoxib as Treatment for Ankylosing Spondylitis (AS) (MK-0663-108)
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
February 2022
Overall Recruitment Status
Completed
Study Start Date
September 27, 2010 (Actual)
Primary Completion Date
November 12, 2014 (Actual)
Study Completion Date
November 12, 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Organon and Co
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Spondylitis, Ankylosing
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
1015 (Actual)
8. Arms, Groups, and Interventions
Arm Title
etoricoxib 60 mg/etoricoxib 60 mg
Arm Type
Experimental
Arm Description
The etoricoxib 60 mg/etoricoxib 60 mg treatment sequence will receive etoricoxib 60 mg in Part I and Part II
Arm Title
etoricoxib 60 mg/etoricoxib 90 mg
Arm Type
Experimental
Arm 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
Arm Title
etoricoxib 90 mg/etoricoxib 90 mg
Arm Type
Experimental
Arm Description
The etoricoxib 90 mg/etoricoxib 90 mg treatment sequence will receive etoricoxib 90 mg in Part I and Part II
Arm Title
naproxen 1000 mg/naproxen 1000 mg
Arm Type
Active Comparator
Arm Description
The naproxen 1000 mg/naproxen 1000 mg treatment sequence will receive naproxen 1000 mg in Part I and Part II
Intervention Type
Drug
Intervention Name(s)
Part I - etoricoxib 60 mg
Other Intervention Name(s)
MK-0663
Intervention Description
etoricoxib 60 mg oral tablet once daily for 6 weeks
Intervention Type
Drug
Intervention Name(s)
Part I - etoricoxib 90 mg
Other Intervention Name(s)
Mk-0663
Intervention Description
etoricoxib 90 mg oral tablet once daily for 6 weeks
Intervention Type
Drug
Intervention Name(s)
Part I- naproxen 1000 mg
Intervention Description
naproxen 500 mg oral tablet twice daily for 6 weeks
Intervention Type
Drug
Intervention Name(s)
Part I - Placebo to naproxen 500 mg
Intervention Description
Placebo to naproxen 500 mg oral tablet twice daily for 6 weeks
Intervention Type
Drug
Intervention Name(s)
Part II- etoricoxib 60 mg
Other Intervention Name(s)
MK-0663
Intervention Description
etoricoxib 60 mg oral tablet once daily for 20 weeks
Intervention Type
Drug
Intervention Name(s)
Part II- etoricoxib 90 mg
Other Intervention Name(s)
MK-0663
Intervention Description
etoricoxib 90 mg oral tablet once daily for 20 weeks
Intervention Type
Drug
Intervention Name(s)
Part II- naproxen 1000 mg
Intervention Description
naproxen 500 mg oral tablet twice daily for 20 weeks
Intervention Type
Drug
Intervention Name(s)
Part I - Placebo to etoricoxib 60 mg
Intervention Description
Placebo to etoricoxib 60 mg oral tablet once daily for 6 weeks.
Intervention Type
Drug
Intervention Name(s)
Part I - Placebo to etoricoxib 90 mg
Intervention Description
Placebo to etoricoxib 90 mg oral tablet once daily for 6 weeks.
Intervention Type
Drug
Intervention Name(s)
Part II- Placebo to etoricoxib 60 mg
Intervention Description
Placebo to etoricoxib 60 mg oral tablet once daily for 20 weeks.
Intervention Type
Drug
Intervention Name(s)
Part II - Placebo to etoricoxib 90 mg
Intervention Description
Placebo to etoricoxib 90 mg oral tablet once daily for 20 weeks.
Intervention Type
Drug
Intervention Name(s)
Part II- Placebo to naproxen 500 mg
Intervention Description
Placebo to naproxen 500 mg orally twice daily for 20 weeks.
Primary Outcome Measure Information:
Title
Time-Weighted Average Change From Baseline in the Spinal Pain Intensity in Study Part 1: Etoricoxib 90 mg vs. Naproxen
Description
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.
Time Frame
Baseline and up to Week 6
Title
Time-Weighted Average Change From Baseline in the Spinal Pain Intensity in Study Part 1: Etoricoxib 60 mg vs. Naproxen
Description
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.
Time Frame
Baseline and up to Week 6
Title
Number of Participants Discontinuing Study Treatment Due to an Adverse Event
Time Frame
Up to 26 weeks
Secondary Outcome Measure Information:
Title
Time-Weighted Average Change From Baseline in the Spinal Pain Intensity in Study Part 1: Etoricoxib 90 mg vs. Etoricoxib 60 mg
Description
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.
Time Frame
Baseline and up to Week 6
Title
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)
Description
Spinal Pain Intensity is measured using a visual analog scale (VAS) from 0-100 mm with a lower value representing a better response. Average change from Week 6 in Spinal Pain Intensity (VAS) over Weeks 10 and 12 is calculated as the average Spinal pain Intensity (VAS) value over Weeks 10 and 12 minus the Spinal Pain Intensity (VAS) at Week 6.
Time Frame
Week 6 to Week 10 and Week 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Citations:
PubMed Identifier
27737664
Citation
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.
Results Reference
result
Available IPD and Supporting Information:
Available IPD/Information Type
CSR Synopsis
Available IPD/Information URL
http://www.merck.com/clinical-trials/study.html?id=0663-108&kw=0663-108&tab=access
Learn more about this trial
A Two-Part 26-Week Study of Etoricoxib as Treatment for Ankylosing Spondylitis (AS) (MK-0663-108)
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