Diclofenac potassium liquid-filled soft gelatin capsules in the management of patients with postbunionectomy pain: a Phase III, multicenter, randomized, double-blind, placebo-controlled study conducted over 5 days.

BACKGROUND: Diclofenac potassium liquid-filled soft gelatin capsule (DPSGC) is a rapidly absorbed formulation of diclofenac potassium developed for the treatment of mild to moderate acute pain. OBJECTIVE: The present study was conducted to assess the efficacy and safety profile of DPSGC 25 mg in patients with pain after first-metatarsal bunionectomy. METHODS: This was a Phase III, multicenter, randomized, double-blind, parallel-group, placebo-controlled study conducted over 5 days. Patients experiencing the requisite level of pain (score > or = 4 on an 11-point numeric pain rating scale [NPRS] from 0 = no pain to 10 = worst possible pain) on the day after bunionectomy were randomized to receive DPSGC 25 mg or matching placebo. A second dose was given when patients requested additional medication for pain. Subsequent doses were given every 6 hours over a 48-hour inpatient multiple-dose period and continued over an additional 48-hour outpatient multiple-dose period. Opioid rescue medication was available as needed after the second dose of study medication. The primary efficacy end point was the mean NPRS score over the 48-hour inpatient multiple-dose period. Additional measures included NPRS scores at predefined times over 48 hours, the summed pain intensity difference over 48 hours (SPID48), the time-weighted sum of pain relief scores over the first 8 hours, the mean dosing interval (the time from dosing to the time rescue medication or the next dose of study medication was administered, whichever was less), the proportion of patients requiring rescue medication, and the onset of perceptible and meaningful pain relief (2-stopwatch method). Tolerability was assessed based on physician monitoring and patient reporting of adverse events (AEs) and the results of standard laboratory tests. RESULTS: Of 201 randomized patients (102 DPSGC 25 mg, 99 placebo; 86.6% female; 58.2% white; mean [SD] age, 45.2 [11.5] years; weight range, 49.4-108.0 kg), 198 completed the study. Mean baseline NPRS scores did not differ significantly between the DPSGC and placebo groups (6.9 and 7.3, respectively). DPSGC was associated with significant improvements compared with placebo in mean NPRS score over 48 hours (2.5 vs 5.6, respectively; P < 0.001), mean SPID48 (210.0 vs 90.3; P < 0.001), and overall mean dosing interval (331.5 vs 263.9 min; P < 0.001). Significant differences in NPRS scores between DPSGC 25 mg and placebo were noted at all time points from baseline through 48 hours (P < 0.001). The proportion of patients requiring rescue medication was significantly lower in the DPSGC group compared with the placebo group (39.2% vs 87.9% on day 1; 21.6% vs 64.6% on day 2; both, P < 0.001). Patients receiving DPSGC had a significantly faster onset of meaningful pain relief compared with those receiving placebo (P = 0.008). The most commonly reported AEs were nausea (7.8% vs 18.2%), headache (5.9% vs 9.1%), vomiting (3.9% vs 9.1%), and constipation (3.9% vs 2.0%). The overall incidence of AEs occurring in > or = 2% of patients was significantly lower in the DPSGC group than in the placebo group (20.6% vs 44.4%; P < 0.05); no patient receiving DPSGC had a serious AE. CONCLUSIONS: DPSGC 25 mg taken every 6 hours was effective in reducing postbunionectomy pain in the patients studied. DPSGC was well tolerated, suggesting that it may be a practicable option for the treatment of mild to moderate acute pain. ClinicalTrials. gov identifier: NCT00366444.

Tolerability and patient acceptance of sodium phosphate tablets compared with 4-L PEG solution in colon cleansing: combined results of 2 identically designed, randomized, controlled, parallel group, multicenter phase 3 trials.

GOALS: Evaluate patient tolerance and acceptance of a sodium phosphate (NaP) tablet purgative compared with a 4-L polyethylene glycol (PEG) solution. BACKGROUND: Characteristics and side effects of bowel purgatives deter patients from undergoing screening colonoscopy. Published data demonstrated comparable bowel cleansing with NaP tablets and a 4-L PEG solution in 2 phase for 3 studies. This report presents data on patient tolerability and acceptance. STUDY: Two identically designed, randomized, investigator-blinded, and multicenter trials were performed. Tolerability and patient acceptance were based on purgative regimen compliance, incidence of gastrointestinal adverse events, and patient responses to questionnaires. RESULTS: Eight hundred forty-five patients were assessed (420 and 425 in the tablet and PEG solution groups, respectively). Patient compliance with the tablet regimen was greater: 94% of patients took all the tablets compared with 57% completing the PEG solution regimen (P<0.0001). Nausea, vomiting, and bloating occurred significantly less often in patients taking NaP tablets (P<0.0001). Among patients taking tablets, 88.4% rated them "easy" or "slightly difficult" to take, compared with 60.6% of patients taking the PEG solution. The preparation's taste was rated "barely tolerable" or "not tolerable" by 1% of patients treated with NaP tablets and 23.6% treated with PEG solution. Drinking the required volume of clear liquid for the tablet or PEG preparation was rated "easy" or "slightly difficult" by 92.2% and 66.9% of patients, respectively. Almost all (90.7%) patients taking the tablets indicated they would take the same preparation in the future, compared with 67.1% of patients taking the PEG solution (P<0.0001 for each comparison). CONCLUSIONS: Tolerability and patient acceptance of a NaP tablet purgative were superior to 4-L PEG solution.