robenacoxib and Osteoarthritis

The main objective of this pilot clinical trial was to evaluate outcome measures for the assessment of the nonsteroidal anti-inflammatory drug (NSAID) robenacoxib in cats with degenerative joint disease-associated pain (DJD-pain). Otherwise healthy cats (n = 109) with DJD-pain entered a parallel group, randomized, blinded clinical trial. Cats received placebo (P) or robenacoxib (R) for two consecutive 3-week periods. Treatment groups were PP, RR, and RP. Actimetry and owner-assessment data were collected. Data were analyzed using mixed-effects and generalized mixed-effects linear models. Activity data showed high within-cat and between-cat variability, and 82.4% of the values were zero. Compared to placebo, mean total activity was higher (5.7%) in robenacoxib-treated cats (p = 0.24); for the 80th percentile of activity, more robenacoxib-treated cats had a > 10% increase in activity after 3 (p = 0.046) and 6 weeks (p = 0.026). Robenacoxib treatment significantly decreased owner-assessed disability, (p = 0.01; 49% reduction in disability; effect size ~ 0.3), and improved temperament (p = 0.0039) and happiness (p = 0.021) after 6 weeks. More robenacoxib-treated cats were successes at 6 weeks (p = 0.018; NNT: 3.8). Adverse effect frequencies were similar across groups. Results identified suitable endpoints for confirmatory studies, while also indicating efficacy of robenacoxib in cats with DJD-pain.

Topics: Animals; Cat Diseases; Cats; Diphenylamine; Female; Joint Diseases; Male; Osteoarthritis; Pain; Pain Management; Phenylacetates; Pilot Projects; Placebos

The objective of this study was to evaluate the clinical safety of the non-steroidal anti-inflammatory drug (NSAID) robenacoxib in cats with osteoarthritis. Degenerative joint disease, including osteoarthritis, is highly prevalent in cats and many cases have associated pain and impaired mobility. Although NSAIDs are used routinely to control pain and inflammation in cats with osteoarthritis, there are safety concerns because of the high concurrent prevalence of chronic kidney disease (CKD) and the paucity of data on the safety of these drugs in target clinical populations.. A total of 194 cats with osteoarthritis were recruited and randomly allocated to receive either robenacoxib at a dosage of 1.0-2.4 mg/kg (n = 95) or placebo (n = 99) tablets PO q24h for 28 days. Safety was assessed in 193 cats, including a subgroup of 40 animals with concurrent CKD, defined as serum creatinine concentration ⩾1.6 mg/dl and urine specific gravity <1.030. Safety endpoints included reports of adverse events, results of clinical examinations, including body weight, and clinical chemistry and hematology variables.. In all 193 cats and the subgroup of 40 animals with concurrent CKD, there were no differences between groups in frequencies of reported adverse events, body weight change or results of serum or urine chemistry or hematology variables.. Robenacoxib was well tolerated when administered daily for 1 month in cats with osteoarthritis, including cats with evidence of concurrent CKD. There was no clinical indication of damage to the gastrointestinal tract, kidney or liver.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cat Diseases; Cats; Diphenylamine; Osteoarthritis; Phenylacetates

Robenacoxib is a member of the coxib class of nonsteroidal anti-inflammatory drugs (NSAID), with high selectivity for the cyclooxygenase (COX)-2 isoform of COX. In this study, the efficacy and tolerability of robenacoxib were compared with those of carprofen in canine osteoarthritis in a multi-centre, prospective, randomized, blinded, positive-controlled noninferiority clinical trial. Both drugs were administered orally once daily at recommended dosages: robenacoxib at 1-2 mg/kg (n = 125 dogs) and racemic carprofen at 2-4 mg/kg (n = 63 dogs) for a total of 12 weeks. The efficacy of the test compounds was assessed by veterinary investigators and owners using numerical rating scales at baseline and days 7, 14, 28, 56 and 84. In both groups, all scores were significantly (P < 0.0001) improved compared with baseline at all time points (days 7-84). Robenacoxib had noninferior efficacy to carprofen for the primary endpoint, the global functional disability, both for all dogs and for the subgroup of dogs in which robenacoxib was not administered during meals. Noninferiority was also demonstrated for three of six veterinary investigator secondary endpoints and four of six owner efficacy endpoints. For haematology and clinical chemistry variables, there were some significant differences from baseline levels but no differences between groups. There were no differences between groups in the frequencies of adverse events, which were reported in 46% dogs with robenacoxib and 52% with carprofen (P = 0.44), which were most frequently mild events affecting the gastrointestinal tract. In conclusion, noninferior efficacy and tolerability of robenacoxib compared with carprofen was demonstrated in dogs with osteoarthritis.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Carbazoles; Diphenylamine; Dog Diseases; Dogs; Female; Male; Osteoarthritis; Phenylacetates

The efficacy and tolerability of robenacoxib for the treatment of osteoarthritis in dogs were evaluated in a prospective, multicenter, randomized, noninferiority design clinical trial. A total of 32 dogs presenting with osteoarthritis were allocated randomly to receive, orally once daily for 28 days, either 1-2 mg/kg robenacoxib (n=21) or 3.5-5 mg/kg carprofen (n=11). Dogs were assessed by clinicians and owners using numerical rating scale scores at baseline and days 14 and 28. The primary efficacy endpoint was the global functional disability score, which was the sum of clinician scores for standing posture, lameness at walk, lameness at trot, willingness to raise the contralateral limb and pain at palpation. There was a good to excellent level of efficacy in both treatment groups. Differences between days 14 and 28 compared to day 0 were significant for all 11 clinician and owner scores for robenacoxib, and for 6 of 11 scores for carprofen. The efficacy of robenacoxib was numerically superior to carprofen for all 13 endpoints, but differences were not statistically significant. For the global functional disability score, the estimated efficacy of robenacoxib was 1.244 (95% confidence interval 0.555-2.493) relative to carprofen. The tolerability of both treatments was good as assessed from adverse events, clinical signs, and hematology and serum biochemistry variables. In conclusion, once daily administration of robenacoxib tablets had noninferior efficacy and tolerability compared to carprofen for the treatment of the clinical signs of osteoarthritis in dogs.

Topics: Administration, Oral; Analysis of Variance; Animals; Carbazoles; Diphenylamine; Dog Diseases; Dogs; Japan; Osteoarthritis; Phenylacetates; Prospective Studies; Statistics, Nonparametric; Treatment Outcome

Robenacoxib is a novel and highly selective inhibitor of COX-2 in dogs and cats and because of its acidic nature is regarded as being tissue-selective. Thirty four dogs with stifle osteoarthritis secondary to failure of the cranial cruciate ligament were recruited into this study. Lameness, radiographic features, synovial cytology and C-reactive protein concentrations in serum and synovial fluid were assessed before and 28 days after commencing a course of Robenacoxib at a dose of 1 mg/kg SID.. There was a significant reduction in the lameness score (P < 0.01) and an increase in the radiographic score (P < 0.05) between pre- and post-treatment assessments. There was no difference between pre- (median 1.49 mg/l; Q1-Q3 0.56-4.24 mg/L) and post - (1.10 mg/L; 0.31-1.78 mg/L) treatment serum C-reactive protein levels although synovial fluid levels were significantly reduced (pre- : 0.44 mg/L; 0.23-1.62 mg/L; post- : 0.17 mg/L; 0.05-0.49 mg/L) (P < 0.05). There was no correlation between C-reactive protein concentrations in serum and matched synovial fluid samples.. Robenacoxib proved effective in reducing lameness in dogs with failure of the cranial cruciate ligament and osteoarthritis of the stifle joint. The drug also reduced levels of C-reactive protein in the synovial fluid taken from the affected stifle joint. Robenacoxib appears to reduce articular inflammation as assessed by C-reactive protein which supports the concept that Robenacoxib is a tissue-selective non-steroidal anti-inflammatory drug.

Topics: Animals; C-Reactive Protein; Cyclooxygenase Inhibitors; Diphenylamine; Dog Diseases; Dogs; Female; Lameness, Animal; Male; Osteoarthritis; Phenylacetates; Radiography; Stifle; Synovial Fluid

The purpose of this analysis was to investigate whether the recommended daily dosage of 1-2mg/kg robenacoxib provides consistent exposure when administered to dogs with chronic osteoarthritis (OA), and the need for dose adjustment in special patient populations. Data from three prospective, multi-center field studies in 208 OA dogs were analyzed using non-linear mixed effects modeling. A model based assessment was performed with stepwise inclusion and exclusion of population characteristics to explain between-subject variability, and assess the according necessity for dose adjustment. Only the influence of bodyweight on both apparent clearance and volume were found to be significant (p<0.01). No significant influence of sex, age and breed, or kidney and liver variables was identified in this representative sample of OA dogs. The population pharmacokinetic analysis performed showed that the 1-2mg/kg dosage chosen provided consistent robenacoxib exposure in a wide range of canine patients. No other dose adjustment seems necessary.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Body Weight; Chronic Disease; Diphenylamine; Dog Diseases; Dogs; Female; Male; Osteoarthritis; Phenylacetates; Sex Factors

The purpose of this population analysis was to characterize the pharmacokinetic properties of robenacoxib in blood and stifle joint synovial fluid of dogs.. Data were obtained from two studies: 1) 8 healthy Beagle dogs in which an acute inflammation was induced by injection of urate crystals into one joint; 2) 95 dogs from various breeds diagnosed with osteoarthritis (OA). Robenacoxib concentrations in blood and synovial fluid were measured using a validated HPLC-UV and LC-MS method. Non-linear mixed effects modeling was performed using NONMEM6.. A two-compartment pharmacokinetic model with linear elimination was developed to describe blood concentrations of robenacoxib. Blood clearance in healthy animals was found to be 75% higher than in OA dogs. Synovial fluid concentrations were modeled using an effect-compartment-type model predicting longer residence times in OA dogs compared to healthy Beagles (e.g. concentrations above the IC(50) for COX-2, respectively, 16 h vs. 10 h at 1.5 mg/kg).. Robenacoxib was found to reside longer at the effect site (inflamed joint) compared to blood in both healthy and OA dogs. These results may explain the good efficacy observed with once-daily dosing in clinical trials and the high safety index of robenacoxib in dogs.

Topics: Animals; Chromatography, High Pressure Liquid; Cyclooxygenase 2 Inhibitors; Diphenylamine; Dogs; Mass Spectrometry; Models, Biological; Osteoarthritis; Phenylacetates; Spectrophotometry, Ultraviolet