Kathleen Sanner

Utility and Sensitivity of the Sore Throat Pain Model: Results of a Randomized Controlled Trial on the COX‐2 Selective Inhibitor Valdecoxib

The sore throat pain model was employed in this randomized, placebo‐controlled trial to examine the sensitivity of the model in testing the efficacy of valdecoxib as an acute analgesic drug. Changes were made to the study design by employing a different diagnostic index for tonsillo‐pharyngitis, a different rating scale (derived from Lasagnas pain thermometer), and alternative analyses, individual responder rates. Under double‐blind conditions, 197 patients with painful pharyngitis were randomly allocated to valdecoxib 20 mg bid (n = 65), valdecoxib 40 mg qd (n = 66), or placebo (n = 66) for 24 hours. The expanded Tonsillo‐Pharyngitis Assessment and the Lasagna Pain Scale were validated as sensitive study instruments. Both dosage regimens provided significantly greater pain relief compared with placebo on standard efficacy measures over the 24‐hour study (all P < .05). Tests for individual response (eg, percentage of patients with at least moderate relief) confirmed these results, and other response rates identified the high sensitivity of the model itself (eg, only 5% of placebo‐treated patients achieved ≥50% of maximum total pain relief over 6 hours). These findings indicate that sore throat is a sensitive model to assess analgesic efficacy.

Onset of action of a lozenge containing flurbiprofen 8.75 mg: A randomized, double-blind, placebo-controlled trial with a new method for measuring onset of analgesic activity

Summary Using frequent measurements and analyses based on definite drug response, a new onset‐of‐action model identified the early onset of action of a flurbiprofen 8.75‐mg lozenge. ABSTRACT A new onset‐of‐action model was utilized to distinguish the pharmacologic activity of flurbiprofen 8.75 mg delivered in a lozenge from the demulcent effect of the lozenge base. In a randomized, double‐blind, placebo‐controlled trial, patients with sore throat rated pain on a Sore Throat Pain Intensity Scale before taking one flurbiprofen or placebo lozenge and at frequent (2‐minute) intervals over the first hour after treatment. Further ratings of the Sore Throat Pain Intensity Scale and other patient‐reported outcomes (difficulty swallowing, swollen throat, pain relief) were obtained at varying intervals over 6 hours. Onset of pharmacologic activity was defined as the median time of first perceived pain reduction if a patient reported clinically meaningful (at least moderate) relief. The conventional method of comparing mean treatment responses at each time point was also implemented. Demulcent action was detected at the first 2‐minute assessment. By the new method, 102 flurbiprofen‐treated patients were identified as first perceiving pain relief at 12 minutes, compared with >120 minutes by 102 patients using placebo (P < 0.001). By the conventional method, mean percentage pain reduction for flurbiprofen 8.75 mg was first significantly differentiated from placebo at 26 minutes (P < 0.05). Efficacy of flurbiprofen lozenge was demonstrated for 3.5‐4 hours on the 4 patient‐reported outcomes (all P < 0.05 compared with placebo). There were no serious adverse events. This patient‐centered onset‐of‐action model identifies the initiation of pain relief in patients who are definite drug responders, here demonstrating that a flurbiprofen 8.75‐mg lozenge provides early relief of sore throat.

Efficacy of Low-Dose Celecoxib in Patients With Acute Pain

UNLABELLED The sore throat pain model was used to evaluate single-dose effects of celecoxib 50 and 100 mg over 6 hours in the treatment of acute pharyngeal pain. Multiple-dose effects of 50-mg bid and 100 mg followed by 50 mg over 6 to 24 hours were also evaluated. Under double-blind, randomized, placebo-controlled conditions, 269 adults with confirmed acute pharyngitis rated throat pain intensity, throat soreness, difficulty swallowing, and sore throat pain relief over 24 hours. For the primary efficacy analysis (SPID2), patients receiving celecoxib 100 mg during the first 2 hours after the first dose had significantly higher mean scores than patients in the placebo group (P < .0003). Efficacy was also demonstrated for celecoxib 50 and 100 mg compared with placebo for all end points (including total pain relief, summed pain intensity differences, total reduction of throat soreness, and difficulty swallowing) at all time points after the first dose and after the second 50-mg dose (P < .01). There were no differences between the dosage regimens, although a supplementary 50-mg dose of celecoxib 6 to 12 hours after the first dose appeared to provide additional efficacy over 24 hours. No serious adverse events (AEs) or discontinuations due to an AE were reported. The results of this study demonstrate that in this pain model, celecoxib is a well tolerated and efficacious analgesic in 50- and 100-mg doses. PERSPECTIVE In a double-blind, randomized, placebo-controlled trial utilizing the sore throat pain model, low-dose celecoxib (50- and 100-mg doses) was well tolerated and provided effective analgesia in patients with acute pain.

Demonstration of the Analgesic Efficacy and Dose-Response of Acetylsalicylic Acid With Pseudoephedrine

To determine acute analgesia by acetylsalicylic acid (ASA) when combined with pseudoephedrine (PSE) in patients with upper respiratory tract infection (URTI), we used the sore throat pain model to measure single‐dose effects of ASA 500 mg/PSE 30 mg, ASA 1000 mg/PSE 60 mg, and acetaminophen (APAP) 1000 mg/PSE 60 mg (serving as a positive control). Under double‐blind, randomized, placebo‐controlled conditions, 640 adult patients with confirmed acute pharyngitis and rhinosinusitis associated with URTI rated throat pain intensity and relief at intervals over 6 hours. Efficacy was demonstrated for both doses of ASA/PSE compared with placebo for all end points, including total pain relief and summed pain intensity differences, beginning at 20 minutes on both scales (all P < .05), and the efficacy of APAP/PSE compared with placebo was confirmed (P < .01). Greater differences in pain relief and intensity were also demonstrated between the higher and lower doses of ASA/PSE (P < .05), in particular, among 329 patients with severe pain, as well as between ASA 1000 mg/PSE 60 mg and APAP 1000 mg/PSE 60 mg (P < .05). No serious adverse events were reported. This study demonstrates that ASA is a well‐tolerated and effective analgesic in 500‐ and 1000‐mg doses when combined with pseudoephedrine.

Efficacy of flurbiprofen 8.75 mg lozenge in patients with a swollen and inflamed sore throat

Abstract Objective: Sore throat is often over-treated with antibiotics, therefore there is a need for non-antibiotic treatments that provide effective relief. From the patient’s point of view, symptoms of pharyngeal inflammation such as a “swollen” and “inflamed” throat are often considered the most bothersome; so, a non-steroidal anti-inflammatory drug could be an appropriate treatment. We investigated the efficacy and safety of flurbiprofen 8.75 mg lozenge in adults with a swollen and inflamed throat. Research design and methods: We enrolled adults with moderate-to-severe sore throat and evidence of tonsillo-pharyngitis into a randomized, double-blind study. Patients received flurbiprofen 8.75 mg or placebo lozenges every 3–6 hours as needed (up to five lozenges in 24 hours) and rated their symptoms (sore throat pain, difficulty swallowing and the sensation of a swollen throat) on standard linear scales regularly over 24 hours. The efficacy of flurbiprofen lozenge was determined in patients reporting a swollen and inflamed throat at baseline, as well as those with relatively severe symptoms. Clinical trial registration: ClinicalTrials.gov NCT01049334. Main outcome measures: The main outcome measures were the time-weighted summed differences in patient-reported sore throat pain, difficulty swallowing and swollen throat over 24 hours. Results: Out of 204 patients, 124 (60.8%) described their throats as swollen and inflamed at baseline. Flurbiprofen lozenges provided greater relief than placebo over 24 hours: 79.8%, 99.6% and 69.3% (for sore throat pain, difficulty swallowing and swollen throat, respectively, all P ≤ 0.01). These outcomes were more substantial in patients with relatively severe symptoms. No serious or unexpected adverse events occurred. Conclusions: Flurbiprofen 8.75 mg lozenge appears to provide effective, well-tolerated relief of sore throat, difficulty swallowing and swollen throat in adults with a swollen and inflamed throat, as well as those with relatively severe symptoms. A limitation of these findings is that, while predetermined, these are secondary outcomes derived from a targeted sub-group of patients, not the entire study population.