A Single Center 2-way Crossover Study to Investigate the Mechanism of Action of Etoricoxib in Subjects With Osteoarthritis Knee Pain
|Osteoarthritis||Drug: Etoricoxib, followed by placebo (matching tablet, without active ingredient) Drug: Placebo (matching tablet, without active ingredient), followed by etoricoxib||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Basic Science
|Official Title:||A Single Center, Randomized, Double-blind, Placebo-controlled 2-way Crossover Study to Investigate the Mechanism of Action of Etoricoxib in Subjects With Osteoarthritis Knee Pain.|
- Change in Experimental mechanism based Pain Measures (EPMs)during two treatment periods of 4-weeks each [ Time Frame: The EPMs will be measured: at V3, prior to 1. treatment sequence w/ Medication/Placebo; at V5, after 4 weeks of treatment; at V6, prior to 2. treatment sequence w/ Medication/Placebo; at V8, after 4 weeks of treatment. ]
The following EPMs will be applied:
- Quantitative Sensory Testing (QST) of 3 knee joint pain locations
- Spreading sensitization
- Pain areas
- Wind-up like pain
- Descending noxious inhibitory control
- Cuff evoked pain
- Infrared thermography of both knees
- Change in Clinical Outcome measures during two treatment periods of 4-weeks each [ Time Frame: The Clinical Outcome measures will be measured at screening and throughout the two treatment sequences. The study period is in total 16 weeks. Some measures will be recorded daily, others only at study visits. ]
Change of pain severity as measured by the daily 24-hour average pain score (APS), night pain and worst daily pain, the following questionnaires: PQAS, BPI, IGIC, PGAC, WOMAC, Dolotest® and PDQ. Furthermore time and pain intensity from a 40 m self-paced walk test and from a 11 step stair climb test.
Fasting plasma, serum and urine samples will be collected and stored for potential further analysis of e.g. IL-6, IL-8, CTX1, CTX2, TNFα, CCL2, CO1, CO2, sCRP, CRP25, C1M, C2M, C3M, OC, MMP.
|Study Start Date:||July 2012|
|Study Completion Date:||July 2013|
|Primary Completion Date:||July 2013 (Final data collection date for primary outcome measure)|
Etoricoxib, followed by placebo
4 weeks of treatment with etoricoxib, followed by a wash out period of at least 6 days, followed by another 4 weeks of treatment with placebo.
Drug: Etoricoxib, followed by placebo (matching tablet, without active ingredient)
Sequence 1: 1 tablet of 60 mg etoricoxib daily for 4 weeks, for oral use. Sequence 2: 1 tablet of matching placebo daily for 4 weeks, for oral use.
Other Name: Acoxia®
Placebo, followed by etoricoxib
4 weeks of treatment with placebo, followed by a wash out period of at least 6 days, followed by another 4 weeks of treatment with etoricoxib.
Drug: Placebo (matching tablet, without active ingredient), followed by etoricoxib
Sequence 1: 1 tablet of matching placebo daily for 4 weeks, for oral use. Sequence 2: 1 tablet of 60 mg etoricoxib daily for 4 weeks, for oral use.
Other Name: Acoxia®
Study Rationale: The purpose of this study is to investigate which pain mechanisms in subjects with painful knee osteoarthritis can be affected by the peripheral and central actions of etoricoxib as compared to placebo during a 4 week treatment therapy period.
The present study will utilize a set of quantitative mechanism based pain biomarkers to assess peripheral and central pain manifestations in OA and the influence of etoricoxib on those individual manifestations in an attempt to understand and explain clinical pain alleviation.
Study Treatment: Subjects will be randomized to one of the 2 sequences of treatment: Sequence 1 (60 mg/day etoricoxib followed by placebo) or Sequence 2 (placebo followed by 60 mg/day etoricoxib). The two treatment periods of 4 weeks each are separated by a washout period of at least 6 days.
Primary Objective: To assess which pain mechanisms are modulated by 60 mg daily administration of etoricoxib compared to placebo in subjects with osteoarthritic (OA) knee pain during two treatment periods of 4-weeks each.
Secondary Objectives: To evaluate if changes in any of the mechanism based experimental pain assessment parameters can explain changes in clinical outcome parameters.
To profile drug responders- versus non-responders based on pain mechanisms involved.
To investigate if change in inflammatory, bone and cartilage related bio-chemical biomarkers can explain changes in either experimental or clinical pain parameters.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01619150
|Aalborg, Denmark, 9000|
|Study Director:||Hans Christian Hoeck, MD PhD||C4Pain|