A walking model to assess the onset of analgesia in osteoarthritis knee pain.
OBJECTIVE
To assess a walking model utilizing a set of standardized treadmill walks to measure acute analgesic response in osteoarthritis (OA) of the knee.


METHODS
Randomized, double-blind, placebo-controlled, multiple dose, three-period crossover study. Patients > or =45 years of age (N=22) with symptomatic knee OA were randomized to naproxen 500 mg bid, tramadol/acetaminophen 37.5 mg/325 mg in forced titration, or placebo in each of three periods. Patients performed multiple 20-minute treadmill walks on Day 1 and Day 3 at a consistent self-selected pace predetermined at screening. Pain intensity (PI) during the walks was assessed on an 11-point numerical rating scale at 0, 3, 6, 9, 12, 15, 18, and 20 min. The primary endpoint was the time-weighted average (TWA) change from baseline PI on Day 3 for the two self-paced walks for the active treatments vs placebo. Time to moderate pain (TTMP) was a key secondary endpoint.


RESULTS
Compared with placebo, the TWA change from baseline PI on Day 3 was significantly better with tramadol/acetaminophen (P=0.043) but not with naproxen (P=0.089). TWA change from baseline on Day 1 was also significantly better with both tramadol/acetaminophen (P=0.001) and naproxen (P=0.048) compared with placebo. TTMP was significantly better for tramadol/acetaminophen and naproxen than placebo (P<0.001 to P=0.015) for walks on Day 1 after a single dose and on Day 3.


CONCLUSIONS
This novel OA pain model was able to discriminate both tramadol/acetaminophen and naproxen from placebo after single and multiple doses. ClinicalTrials.gov identifier: NCT00772967.
Peeva
E
E
Clinical Research, Merck Research Laboratories, Rahway, NJ 07065, United States. elena_peeva@merck.com
Beals
C R
CR
Bolognese
J A
JA
Kivitz
A J
AJ
Taber
L
L
Harman
A
A
Smugar
S S
SS
Moskowitz
R W
RW
D000082:Acetaminophen / Q000008:administration & dosage / Q000627:therapeutic use*; D000368:Aged; D000700:Analgesics / Q000008:administration & dosage / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004338:Drug Combinations; D005080:Exercise Test / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009288:Naproxen / Q000627:therapeutic use*; D020370:Osteoarthritis, Knee / Q000188:drug therapy* / Q000503:physiopathology; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement; D014147:Tramadol / Q000008:administration & dosage / Q000627:therapeutic use*; D016138:Walking
D000700:Analgesics; D004338:Drug Combinations; D000082:Acetaminophen; D014147:Tramadol; D009288:Naproxen