Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement

The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.


A Walking Model of Osteoarthritis (OA) Knee Pain: A Double-Blind, Placebo-Controlled, 3-Period Crossover Study to Evaluate the Analgesic Effects of Naproxen and Tramadol/Acetaminophen in Patients with OA of the Knee

Peeva1,  Elena, Beals1,  CR, Bolognese2,  JA, Kivitz3,  A., Taber4,  L., Harman1,  A., Chung1,  H.

Merck & Co., Inc., Rahway, NJ
Cytel, Inc., MA
Altoona Arthritis & Osteo Ctr, Duncansville, PA
Pivotal Research Ctrs, Peoria, AZ
University Hospitals, Beachwood, OH

Purpose:

New clinical trial designs for OA pain that can be conducted faster and with fewer patients would speed the testing of novel therapeutic agents. We developed a walking model of OA that takes advantage of the clinical observation that patients frequently report an increase in OA pain during and following exertion. The model is based on standardized series of controlled walks over a short period of time that are used to reproducibly elicit specific knee pain in patients with OA. The objective of this study was to validate the walking model in OA by evaluating the acute efficacy of an NSAID and a weak opiate in patients with OA.

Methods:

Randomized, placebo-controlled, 3-period balanced cross-over study comparing naproxen 500 mg bid and tramadol/acetaminophen 37.5/325 mg per tablet in titration over a three day period to full dose (75/650 mg/mg) in patients >=45 years with OA of the knee (N=21). Patients performed a set of standardized 20-minute treadmill walks at 2, 4, 5 and 6 hours post-drug administration on Day 1, and at 4, 5 and 6 hours post-dose on Day 3. The 2, 4 and 6-hour walks were identically paced at a speed set by the patient (self-pace) at pre-study; the 5-hour walks were at a pace 10–30% faster than the self-pace (high-pace). The primary endpoint was change from baseline in time-weighted average pain intensity (TWA PI), on a numerical scale from 0–10, for tramadol/acetaminophen and naproxen vs. placebo for the self-paced walks on Day 3. Time to moderate pain was also evaluated.

Results:

Results are shown in the Table. For the primary endpoint of TWA PI change from baseline for self-paced walks on Day 3, the comparison was statistically significant for tramadol/acetaminophen (p<0.05), but not for naproxen (p=0.089). When excluding an outlier patient with PI increase >3 standard deviations above the mean PI, both tramadol/acetaminophen (p<0.001) and naproxen (p<0.01) were significantly more effective than placebo for the primary endpoint.

EndpointTramadol/acetaminophenNaproxenPlacebo
TWA PI change from baseline, self-paced walks Day 1-1.5***-1.0*-0.4
TWA PI change from baseline, self-paced walks Day 3-1.7*-1.5-0.9
TWA PI change from baseline, self-paced walks Day 3 (outlier excluded)-2.0***-1.7**-0.7
TWA PI change from baseline, high-paced walks Day 1-1.0**-0.50.2
TWA PI change from baseline, high-paced walks Day 3-1.3**-1.1*-0.2
Time to moderate pain, Day 1, self-paced walks17.8 min***16.4 min*14.2 min
Time to moderate pain, Day 3, self-paced walks18.0 min**18.4 min***14.6 min
All values are least squares means
TWA PI: time-weighted average pain intensity
* p<0.05; ** p<0.01; *** p<0.001 vs. placebo

Conclusion:

The walking model is a promising method for identifying acute treatment effects of drugs for OA pain.

To cite this abstract, please use the following information:
Peeva, Elena, Beals, CR, Bolognese, JA, Kivitz, A., Taber, L., Harman, A., et al; A Walking Model of Osteoarthritis (OA) Knee Pain: A Double-Blind, Placebo-Controlled, 3-Period Crossover Study to Evaluate the Analgesic Effects of Naproxen and Tramadol/Acetaminophen in Patients with OA of the Knee [abstract]. Arthritis Rheum 2009;60 Suppl 10 :835
DOI: 10.1002/art.25915

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