An assessment of the efficacy and safety of diclofenac potassium liquid-filled capsules in patients with various levels of baseline pain intensity.

CONTEXT: Diclofenac potassium liquid-filled soft gelatin capsule (DPSGC; Zipsor*) is a novel formulation of diclofenac potassium used to treat mild to moderate acute pain. OBJECTIVE: To investigate whether DPSGC 25 mg provided significant reduction in pain intensity compared with placebo, regardless of baseline pain intensity, a post hoc analysis was performed of pooled data from two replicate randomized controlled trials (NCT00366444 and NCT00375934) that evaluated the safety and efficacy of DPSGC in postbunionectomy treatment. METHODS: Patients from the two randomized trials were assigned to one of two subgroups: patients with baseline numerical pain rating scale (NPRS) scores of 4 or greater to less than 7 and those with baseline NPRS scores of 7 or greater. Within each subgroup, efficacy and safety of DPSGC was compared with placebo. RESULTS: Across the two studies, 73 DPSGC- and 59 placebo-treated patients had baseline pain intensity scores ranging from 4 or greater to less than 7, while 128 DPSGC- and 141 placebo-treated patients had baseline pain intensity scores of 7 or greater. Significantly lower mean 48-hour NPRS scores were observed in the DPSGC group, regardless of baseline pain intensity (P < 0.0001). In both subgroups, at least twice as many patients treated with DPSGC rated the study drug as very good or excellent compared with patients taking placebo. Potential limitations for this post hoc analysis include study design and patient population. As with all studies investigating treatment for pain, the use of rescue medication may also be a potential limitation. CONCLUSIONS: DPSGC provided significantly greater improvements in pain compared with placebo following bunionectomy, regardless of patients' baseline pain level.

Onset of action of diclofenac potassium liquid-filled capsules in dental surgery patients.

OBJECTIVE: Diclofenac potassium soft gelatin capsules (DPSGC) are a low-dose, liquid-filled formulation that uses patented dispersion technology to facilitate rapid and consistent gastrointestinal absorption. Onset of pain relief experienced by patients receiving DPSGC was evaluated in two dental pain studies. Confirmed perceptible pain relief was evaluated in a post hoc analysis from these randomized controlled trials. RESEARCH DESIGN AND METHODS: Adult patients (n = 514) were enrolled in two multicenter, parallel group, double-blind, placebo-controlled studies. Patients undergoing third molar extraction and experiencing a requisite level of pain (≥50 mm on a 100-mm visual analog scale within 4 hours post-surgery) were randomized to receive single doses of DPSGC 25 mg, 50 mg, 100 mg, or placebo. Pain was assessed at baseline and during 6 hours after dosing. Times to onset of perceptible and meaningful pain relief were recorded using the two-stopwatch method. Confirmed perceptible pain relief was determined in the DPSGC and placebo groups by calculating the median time to onset of perceptible pain relief (first stopwatch) in only those individuals who reported meaningful pain relief (second stopwatch). RESULTS: More than 80% of patients achieved confirmed perceptible pain relief in the DPSGC groups compared with less than 30% of patients in the placebo group (Study 1 and Study 2, p < 0.0001). The median time to onset of confirmed perceptible pain relief in the two studies was less than 30 minutes for patients receiving any dose of DPSGC and more than 360 minutes in the placebo group (Study 1 and Study 2, p < 0.0001). DPSGC was well tolerated and no serious adverse events were reported. Study design limitations include the short duration of the trial and evaluation of a relatively limited patient population. CONCLUSIONS: These results indicate that DPSGC was efficacious in providing a rapid onset of confirmed perceptible pain relief within 30 minutes of administration in these single dose postoperative dental pain studies.

Diclofenac potassium liquid-filled soft gelatin capsules for the treatment of postbunionectomy pain.

OBJECTIVE: Diclofenac potassium liquid-filled soft gelatin capsule (DPSGC) is a rapidly absorbed formulation of diclofenac approved for the treatment of mild to moderate acute pain in adults (≥18 years of age). The objective of this study was to investigate the efficacy and safety of DPSGC 25 mg in a multicenter, randomized, double-blind, placebo-controlled study in patients experiencing pain following first metatarsal bunionectomy. RESEARCH DESIGN AND METHODS: Patients experiencing a requisite level of pain (≥4 based on an 11-point numeric pain rating scale [NPRS]; 0 = no pain, 10 = worst pain possible) on the day following surgery were randomized to receive DPSGC 25 mg or placebo. Patients received a second dose (remedication) on request or at 8 hours postdose followed by additional doses every 6 hours through the end of postsurgery Day 4. Rescue medication (hydrocodone/acetaminophen) was available as needed after the second dose. CLINICAL TRIAL REGISTRATION: NCT00375934. MAIN OUTCOME MEASURE: The primary efficacy endpoint was the average NPRS score over the 48 hour inpatient multiple-dose period. RESULTS: DPSGC provided a significant improvement in mean 48 hour NPRS scores over placebo (3.29 vs 5.74, respectively; p < 0.0001), as well as for summed pain intensity difference (203.1 vs 86.6; p < 0.0001). Patients treated with DPSGC experienced a faster onset of meaningful pain relief compared with placebo (p = 0.0034). Rescue medication use on Day 1 and Day 2 was reduced in the DPSGC group compared with placebo (53.5% vs 92.1% on Day 1; 30.3% vs 67.3% on Day 2; p < 0.0001). DPSGC was well tolerated and no patients treated with DPSGC reported serious adverse events. As with any study, there are potential limitations including study design and patient population. CONCLUSION: These results indicate that DPSGC reduced pain in patients who underwent bunionectomy and this novel formulation of diclofenac potassium may be a practical option for treating mild to moderate acute pain.

Controlled phase III clinical trial of diclofenac potassium liquid-filled soft gelatin capsule for treatment of postoperative dental pain.

PURPOSE: The purpose of the present study was to assess the safety and efficacy of oral diclofenac potassium liquid-filled soft gelatin capsule (DPSGC) that uses ProSorb dispersion technology (Xanodyne Pharmaceuticals, Inc, licensed from AAIPharma, Wilmington, NC), to treat adult patients with acute pain after third molar extraction. PATIENTS AND METHODS: In the present multicenter, randomized, double-blind, placebo-controlled trial, patients experiencing a baseline level of pain (≥ 50 mm on a 100-mm visual analog scale within 4 hours after surgery) were randomized to receive a single dose of DPSGC at 25, 50, or 100 mg or placebo. Pain intensity and relief were assessed for 6 hours after dosing. The efficacy endpoints included the summed pain intensity difference, total pain relief, and the median time to the onset of perceptible and meaningful pain relief (using the 2-stopwatch method). RESULTS: A total of 249 randomized patients had a significant increase in the summed pain intensity difference and total pain relief values at 3 and 6 hours across all DPSGC-treated groups compared with the placebo group (P < .0001). The onset of perceptible and meaningful pain relief was significantly faster in all DPSGC groups than in the placebo group, including the DPSGC 25-mg group (25 minutes [P = .0002] and 52 minutes [P < .0001] for perceptible and meaningful pain relief, respectively). Significantly fewer patients in the DPSGC groups required rescue medication compared with those in the placebo group (P < .0001). The global evaluation scores were significantly greater for the patients who received DPSGC than for those who received placebo (P < .0001), and more than 65% of DPSGC-treated patients rated the medication as good, very good, or excellent compared with 18% of the placebo-treated patients. DPSGC was generally well tolerated, and no serious adverse events were reported. CONCLUSIONS: The results from the present single-dose study of postoperative dental pain suggest that DPSGC offers significant pain relief compared with placebo and that the study medication provided was well tolerated by patients who required pain relief after third molar extraction.

A pharmacokinetic analysis of diclofenac potassium soft-gelatin capsule in patients after bunionectomy.

The clinical utility of diclofenac potassium, a nonsteroidal anti-inflammatory drug, may be lessened by inconsistent gastrointestinal absorption. Diclofenac potassium liquid filled soft-gelatin capsule (DPSGC) is an investigational formulation that uses ProSorb dispersion technology to facilitate rapid and consistent gastrointestinal absorption. In this study, the pharmacokinetic (PK) properties of DPSGC are investigated and compared with a commercially available oral diclofenac potassium tablet in patients after primary unilateral first metatarsal bunionectomy. In an open-label, randomized study, 53 patients received ProSorb-D 12.5 mg (the liquid equivalent of DPSGC), DPSGC 25 mg, DPSGC 50 mg, or immediate-release diclofenac potassium 50-mg tablet administered every 8 hours for a 24-hour inpatient period followed by 7 days of outpatient dosing. Diclofenac steady-state PK was evaluated over an 8-hour sampling period 4 days after surgery. Delayed and/or multiple peaks in the diclofenac plasma concentration-time course profiles occurred more frequently with the commercially available oral diclofenac potassium 50-mg tablet than with the other DPSGC formulations. PK data for ProSorb-D 12.5-mg liquid, DPSGC 25 mg, DPSGC 50 mg, and diclofenac potassium 50-mg tablet revealed mean peak plasma concentrations (Cmax) of 302, 749, 1006, and 902 ng/mL, respectively, whereas area under the plasma concentration curve values were 316, 595, 1029, and 1166 ng-hour/mL, respectively. Mean times to Cmax (tmax) were 0.49, 0.63, 0.95, and 1.26 h, respectively. When compared with absorption characteristics of diclofenac potassium 50-mg tablet, DPSGC was more rapidly and consistently absorbed after bunionectomy. These characteristics should be advantageous when rapid pain relief is desired.

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.