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Efficacy and safety of single-dose DFN-15 for treatment of acute postsurgical dental pain: a randomized, double-blind, placebo-controlled study.

ABSTRACT:

Abstract

The analgesic efficacy and safety of DFN-15, a new oral liquid formulation of celecoxib with more rapid absorption than the capsule, were evaluated in the treatment of acute pain in adult patients after dental surgery. In this randomized, double-blind, placebo-controlled, dose-ranging study, 120 otherwise healthy adults who underwent the extraction of bilateral impacted mandibular third molar teeth and experienced moderate to severe pain postsurgery were randomly assigned, in a 1:1:1:1 ratio, to receive one dose of either placebo or DFN-15 at 3 doses: 62.5, 125, and 250 mg. Participants were evaluated at prespecified time points over 8 hours after study drug administration, using several instruments, including the 11-point Numerical Pain Rating Scale, 5-point Pain Relief Scale, and 5-point Treatment Satisfaction Scale. Rescue analgesic (oxycodone / acetaminophen) was permitted. The primary endpoint was the summed pain intensity difference (SPID) over the 6-hour postdose period (SPID6), which was compared between each DFN-15 dose and placebo using analysis of covariance. Other assessments of pain relief, use of rescue medication, and safety were also analyzed. All 3 doses of DFN-15 were significantly superior to placebo in SPID6 (least square mean difference over placebo: -756.6, -1120.7, and -1355.1, P < 0.0001 for all comparisons). In addition, DFN-15 was generally superior to placebo in other endpoints, including reduction of pain intensity, speed and magnitude of pain relief, treatment satisfaction, and rescue medication use. DFN-15 was similar to placebo in the incidence of adverse events with no apparent dose-related effects.

SUBMITTER: Singla N

PROVIDER: S-EPMC8675044 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveThe objective of this study was to evaluate the efficacy, tolerability, and safety of 120 mg DFN-15 vs placebo for the acute treatment of migraine.BackgroundCertain nonsteroidal anti-inflammatory drugs (NSAIDs) are guideline-recommended therapies for the acute treatment of migraine, but patients who use them may have issues with gastrointestinal tolerability. Celecoxib, a selective inhibitor of cyclooxygenase-2, produces analgesia similar to nonselective NSAIDs. DFN-15 is an oral, ready-made liquid solution of celecoxib being investigated for the acute treatment of migraine.MethodsA randomized, double-blind, placebo-controlled, efficacy, tolerability, and safety study in adults with migraine was conducted. Subjects treated a single migraine attack with 120 mg DFN-15 or placebo as soon as possible after the onset of pain of moderate to severe intensity. The 2 independent coprimary efficacy endpoints were the proportion of subjects with freedom from pain and the absence of the most bothersome symptom (MBS) at 2 hours postdose. A second double-blind treatment period followed the first, but did not contribute to the primary outcomes and will be reported elsewhere.ResultsThere were 622 subjects randomized (1:1) to double-blind treatment with either 120 mg DFN-15 or placebo, and 567 (91.2%) treated a migraine with study drug (n = 285 DFN-15; n = 282 placebo). Groups were balanced in demographic characteristics; the mean age was 40, and most subjects were female (87% [494/567]). At 2 hours postdose, DFN-15 was significantly superior to placebo for pain freedom (35.6% [98/275] vs 21.7% [57/263], P < .001), with an odds ratio (95% CI) of 2.00 (1.36, 2.94) and for freedom from the MBS (57.8% [134/232] vs 44.8% [104/232], P = .007), with an odds ratio (95% CI) of 1.68 (1.17, 2.43). A total of 13.3% (38/285) of DFN-15-treated subjects and 8.9% (25/282) of placebo-treated subjects reported a treatment-emergent adverse event (TEAE). Study drug-related TEAEs were reported by 9.1% (26/285) of DFN-15 subjects and 6.0% (17/282) of placebo subjects, the most common of which were dysgeusia (4.2% [12/285] vs 1.4% [4/282]) and nausea (3.2% [9/285] vs 1.8% [5/282]). No subjects treated with DFN-15 reported TEAEs that were severe or led to withdrawal, and no serious TEAEs or deaths were reported in the study.ConclusionsDFN-15 was significantly more effective than placebo for the acute treatment of migraine, with a generally favorable tolerability and safety profile.

Project description:BACKGROUND:In a previous randomized, double-blind, proof-of-concept study in rapidly escalating migraine, a 3 mg dose of subcutaneous sumatriptan (DFN-11) was associated with fewer and shorter triptan sensations than a 6 mg dose. The primary objective of the study was to assess the efficacy and safety of acute treatment with DFN-11 compared with placebo in episodic migraine. METHODS:This was a multicenter, randomized, double-blind, placebo-controlled efficacy and safety study of DFN-11 in the acute treatment of adults with episodic migraine (study RESTOR). The primary endpoint was the proportion of subjects taking DFN-11 who were pain free at 2 h postdose in the double-blind period compared with placebo. Secondary endpoints included earlier postdose timepoints, assessments of pain relief and subjects' freedom from their most bothersome symptom (MBS) (among nausea, photophobia, and phonophobia). Safety and tolerability were assessed. RESULTS:A total of 392 subjects was screened, 268 (68.4%) were randomized, and 234 (87.3% of those randomized) completed the double-blind treatment period. The proportion of subjects who were pain free at 2 h postdose was significantly greater in the DFN-11 group than in the placebo group (51.0% vs 30.8%, P??=??0.0023). Compared with placebo, significantly higher proportions of subjects treated with DFN-11 were also pain free at 30, 60, and 90 min postdose (P?????0.0195). DFN-11 was significantly superior to placebo for pain relief at 60 min, 90 min, and 2 h postdose (P???0.0179). At 2 h postdose, DFN-11 was also significantly superior to placebo for freedom from photophobia (P??=??0.0056) and phonophobia (P??=??0.0167). Overall, 33.3% (37/111) who received DFN-11 and 13.4% (16/119) who received placebo experienced at least 1 treatment-emergent adverse event (TEAE), the most common of which were injection site swelling (7.2% vs 0.8%) and pain (7.2% vs 5.9%). Chest discomfort was about half as common in the DFN-11 treatment group as it was in the placebo group (0.9% vs 1.7%). CONCLUSIONS:This study met its primary endpoint, pain freedom at 2 h postdose, with DFN-11 significantly better than placebo, and the incidence of TEAEs and triptan sensations with DFN-11 was low. The 3 mg dose of sumatriptan in DFN-11 appears to be an effective alternative to a 6 mg SC dose of sumatriptan, with good safety and tolerability. ( clinicaltrials.gov : NCT02569853; registered 07 October 2015).

Project description:IntroductionThis study is part of the registrational program for intravenously administered (IV) tramadol in the USA and compared the analgesic benefit and tolerability of two doses of IV tramadol (50 mg and 25 mg) to placebo in adult patients undergoing bunionectomy, an orthopedic surgical model.MethodsThis was a phase 3, multicenter, double-blind, three-arm, randomized, placebo-controlled, multiple-dose, parallel-group trial to evaluate IV tramadol in the management of postoperative pain following bunionectomy. Eligible patients were randomized (1:1:1 ratio) to IV tramadol 50 mg, 25 mg, or placebo. Primary endpoint was summary of pain intensity differences over 48 h (SPID48). Key secondary endpoints included SPID24, total consumption of rescue analgesia, and patient global assessment of efficacy (PGA). Safety assessments included treatment emergent adverse events (TEAEs), clinical laboratory tests, vital signs, and electrocardiograms (ECGs). Assessment of the dose-response was an important objective of the study.ResultsThe study established a dose response, with IV tramadol 50 mg demonstrating statistically significant benefit (p < 0.05) over placebo for primary and all key secondary efficacy endpoints, whereas tramadol 25 mg demonstrated intermediate results between the 50 mg and placebo arms. IV tramadol 50 mg was well tolerated; most common TEAEs were nausea and vomiting; and there were no meaningful differences among treatments for vital signs, ECG, and laboratory assessments. The largest proportion of patients completed tramadol 50 mg (98.6%) compared to tramadol 25 mg (91.8%) and placebo (88.2%).ConclusionIV tramadol 50 mg was effective and well tolerated as treatment for postoperative pain following bunionectomy surgery, while IV tramadol 25 mg, although well tolerated, was judged an ineffective dose for the treatment of pain in this setting. IV tramadol 50 mg was further developed in the registrational program for the USA.Trial registrationClinicalTrials.gov identifier, NCT03290378.

Project description:IntroductionIbuprofen acid is poorly soluble in the stomach, thus reaching maximum plasma levels at approximately 90 min post-dose. Ibuprofen lysinate has been developed to accelerate absorption of ibuprofen to shorten the time to analgesic efficacy. This study compared analgesic efficacy and onset of effect of a single dose of ibuprofen lysinate or ibuprofen acid in patients undergoing third molar extraction.MethodsRandomized, double-blind, placebo-controlled, multi-center, parallel-group single-dose study. Adults (18-60 years) undergoing extraction of ≥ 1 third molar were randomized 2:2:1 to ibuprofen lysinate, ibuprofen acid, or placebo postoperatively. Pain relief (PAR, 5-point scale, 0 = none to 4 = complete pain relief) and pain intensity (PI, 100 mm visual analog scale) were assessed between 15 and 360 min post-dose. The primary endpoint was the weighted sum of PAR scores at 6 h (TOTPAR). Time to onset of effect, global assessment of efficacy, and adverse events were also assessed.ResultsOverall, 351 patients received ibuprofen lysinate (N = 141), ibuprofen acid (N = 139), or placebo (N = 71). Both active treatments significantly reduced pain compared with placebo, from 15 min post-dose to 6 h (TOTPAR: ibuprofen lysinate: 19.57; ibuprofen acid: 19.96; placebo: 8.27). Ibuprofen lysinate was significantly more effective than placebo, but non-inferior to ibuprofen acid, at providing pain relief over 6 h. There was no significant difference between ibuprofen lysinate and ibuprofen acid for onset of analgesia. Both ibuprofen formulations were well tolerated; all adverse events were mild to moderate and considered unrelated to treatment.ConclusionsA single dose of ibuprofen lysinate is non-inferior to ibuprofen acid in terms of analgesic efficacy, onset of action, and tolerability in patients who have recently undergone dental surgery.Trial registrationEudraCT No. 2006-006942-33. Plain language summary available for this article.

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Efficacy and safety of single-dose DFN-15 for treatment of acute postsurgical dental pain: a randomized, double-blind, placebo-controlled study.

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