Pooled Dosing and Efficacy Analysis of the Sufentanil Sublingual Tablet 30 mcg Across Demographic Subgroups for the Management of Moderate-to-Severe Acute Pain.

PURPOSE: To aid nurses in dosing sufentanil sublingual tablet (SST) 30 mcg administered via a single-dose applicator, dosing requirements and efficacy of SST 30 mcg were analyzed across age, sex, race, and body mass index subgroups. DESIGN: Patient characteristics were pooled from three postoperative studies (two placebo-controlled and one open-label) and one open-label emergency department study. Drug dosing and efficacy data were pooled from the postoperative studies. METHODS: Efficacy was assessed through summed pain intensity difference to baseline during 12 hours across subgroups. FINDINGS: Mean (standard deviation) drug doses administered from 0 to 12 hours was 3.9 (2.0) for SST 30 mcg and was less frequent for older (≥65 years) versus younger patients. The summed pain intensity difference to baseline during 12 hours was superior with SST 30 mcg versus placebo across all subgroups. CONCLUSIONS: SST 30 mcg is a sublingual opioid analgesic with efficacy across demographic subgroups.

Pooled Phase III safety analysis of sufentanil sublingual tablets for short-term treatment of moderate-to-severe acute pain.

Aim: To evaluate the pooled safety of sufentanil sublingual tablets (SSTs) administered at 30-mcg dose equivalents over ≤72 h for moderate-to-severe acute pain management in medically supervised settings. Patients & methods: Safety data from SST 30 mcg Phase III studies were pooled with an additional patient subset from studies in which two SST 15 mcg were self-administered within 20-25 min (30-mcg dose-equivalent). Results: Analyses included 804 patients. Median (range) SST 30-mcg dosing over 24 h was 7.0 (1-15) tablets. Adverse events (AEs) were experienced by 60.5% (SST) and 61.4% (placebo) and treatment-related AEs by 43.8% (SST) and 33.5% (placebo; 10.3% difference; 95% CI: 2.0-18.6) of patients. No dose-dependent increase in oxygen desaturation was observed with SST. Conclusion: SST was well-tolerated, with most AEs considered mild or moderate in severity.

Sufentanil sublingual tablet 30mcg for moderate-to-severe acute pain in the ED.

BACKGROUND: Pharmacological properties of the sufentanil sublingual tablet 30mcg (SST 30mcg) could offer potential analgesic advantages in settings requiring noninvasive, acute pain management. The feasibility of using SST 30mcg for moderate-to-severe pain management in the emergency department (ED) was evaluated. METHODS: This open-label, multicenter feasibility study included patients aged ≥18years who presented to the ED with moderate-to-severe pain (≥4 on the numeric rating scale of pain intensity (NRS); opioid-tolerant patients were excluded. Patients received a single SST 30-mcg dose (single-dose cohort) or, upon request, ≤3 additional doses ≥60min apart (multiple-dose cohort) and were evaluated over 1 or 2h. Effectiveness was assessed by patient-reported pain scores (11-point NRS; 5-point pain relief scale). Safety and tolerability were also assessed. RESULTS: Overall, 76 patients enrolled into the single-dose (n=40) and multiple-dose (n=36) cohorts. In the first hour (combined cohorts), mean pain intensity was significantly lower 15-min post-dosing (P<0.001; clinically meaningful within 30-minutes post-dosing) and continued to decrease during the first hour (P<0.001 for each 15-minute interval). Mean pain intensity (multiple-dose cohort) decreased from 7.6 at baseline to 4.5 at 1h and to 4.6 at 2h (P<0.001 for both); mean pain relief increased from baseline to 1.9 at 1h (P<0.001) and to 2.0 at 2h (P<0.001). Most (79%) patients had no adverse events (AEs), and there were no severe AEs. CONCLUSIONS: SST 30mcg was feasible for managing moderate-to-severe acute pain in an ED setting.

An Open-Label Study of Sufentanil Sublingual Tablet 30 Mcg in Patients with Postoperative Pain.

Objective: To evaluate sufentanil sublingual tablet 30 mcg (SST 30 mcg) for postoperative pain in an older patient population with comorbidities. Design: Multicenter, open-label, single-arm study. Setting: Nine hospitals across the United States. Subjects: Adults aged ≥40 years who had undergone a surgical procedure. Methods: Patients with a postoperative pain intensity score ≥4 on an 11-point numeric rating scale (NRS) were allowed to enter the study and receive SST 30 mcg as requested for pain (minimum 60-minute redosing interval) over the 12-hour study period. Efficacy was assessed by patient reports of pain intensity on the NRS and a five-point pain relief scale. Safety was monitored throughout the study; plasma sufentanil concentrations were also measured. The primary efficacy endpoint was the time-weighted summed pain intensity difference (SPID) to baseline over 12 hours (SPID12). Results: Of the 140 patients enrolled, 69% were American Society of Anesthesiologists Physical Class II or III, 44% had a body mass index (BMI) ≥30 mg/kg2, and 29% had hepatic and/or renal impairment. Average age was 54.7 years (SD = 9.9 years), and average baseline pain intensity was 6.2 (SD = 1.9). The most common surgeries were abdominal (59%) and orthopedic (20%). The mean SPID12 was 36.0 (standard error of the mean = 2.2); mean scores were similar, regardless of age, sex, race, and BMI. From baseline, mean pain intensity decreased significantly starting 30 minutes postdose, and mean pain relief increased significantly starting 15 minutes postdose, remaining relatively stable through 12 hours (P < 0.001 at each time point). Four (3%) patients discontinued due to inadequate analgesia, and 45 (32%) patients had one or more adverse events that were considered possibly or probably related to the study drug. Mean plasma sufentanil concentrations were generally similar regardless of age, sex, BMI, or organ impairment status. Conclusions: SST 30 mcg was effective and well tolerated for the management of moderate-to-severe acute postoperative pain.

Sufentanil Sublingual Tablet 30 mcg for the Management of Pain Following Abdominal Surgery: A Randomized, Placebo-Controlled, Phase-3 Study.

BACKGROUND: Results from a phase-3, prospective, randomized, double-blind, placebo-controlled trial evaluating sufentanil sublingual tablet 30 mcg (SST) for the management of pain after ambulatory abdominal surgery are presented. METHODS: Adults with American Society of Anesthesiologists status 1 to 3 scheduled to undergo abdominoplasty, open tension-free inguinal hernioplasty, or laparoscopic abdominal surgery under general or spinal anesthesia that did not include intrathecal opioids during the operation were eligible. Opioid-tolerant patients were excluded. The primary endpoint was the time-weighted summed pain intensity difference to baseline (SPID) over 12 hours. Secondary endpoints included SPID over 24 and 48 hours, total pain relief, and patient and healthcare professional (HCP) global assessments. RESULTS: Overall, 161 patients were randomized to SST (N = 107) or placebo (N = 54); pain scores were recorded for up to 48 hours. SPID 12 was higher (greater pain intensity reduction from baseline) in the SST group compared with placebo (25.8 vs. 13.1; P < 0.001, with a difference of 12.7 [95% confidence interval 7.16, 18.23]). In the SST group, a greater proportion of patients and HCPs responded "good" or "excellent" on the global assessments compared with placebo (P < 0.001 for both). There was a numerically, but not statistically, higher incidence of nausea and headache in the SST group. CONCLUSIONS: In patients following abdominal surgery in an ambulatory care setting, SST was an effective opioid analgesic in postoperative pain management. In addition, SST was well tolerated with mild-to-moderate side effects, similar to those found in placebo-treated patients.

A randomized, double-blind, placebo-controlled study of an oral, extended-release formulation of phentermine/topiramate for the treatment of obstructive sleep apnea in obese adults.

STUDY OBJECTIVES: To evaluate safety and efficacy of phentermine 15 mg plus extended-release topiramate 92 mg for treatment of moderate to severe obstructive sleep apnea (OSA) in obese adults. DESIGN: This phase 2, randomized, double-blind, placebo-controlled study included 2-week screening and 28-week treatment periods. Overnight polysomnography was performed at baseline, Week 8, and Week 28. SETTING: Single-center study conducted from August 2008 to September 2009. PARTICIPANTS: Forty-five subjects with moderate to severe OSA not receiving positive airway pressure (PAP) treatment with body mass index of 30-40 kg/m(2). INTERVENTIONS: Subjects were randomized to receive placebo (n = 23) or phentermine 15 mg plus extended-release topiramate 92 mg (n = 22). Both groups received lifestyle-modification counseling. MEASUREMENTS AND RESULTS: Primary endpoint, change in apnea-hypopnea index (AHI), significantly favored phentermine 15 mg plus extended-release topiramate 92 mg (-31.5 events/h, 95% CI: -40.0, -22.9) over placebo (-16.6 events/h, 95% CI: -25.0, -8.2) at Week 28 (P =0.0084). At Week 28, there was a 10.2% (95% CI: -12.7, -7.6; 10.8 kg, 95% CI: -13.5, -8.0) mean decrease in weight in the phentermine 15 mg plus extended-release topiramate 92 mg group compared with 4.3% (95% CI: -6.6, -2.0; 4.7 kg, 95% CI: -7.2, -2.2) in the placebo group (P = 0.0006) and a positive, significant (P = 0.0003) correlation between percent change in weight and change in AHI. Significant improvements in overnight oxygen saturation and reduction in blood pressure compared with placebo were observed. Phentermine 15 mg plus extended-release topiramate 92 mg was well tolerated with low adverse event rates. CONCLUSIONS: Phentermine 15 mg plus extended-release topiramate 92 mg induced significant weight reductions and concomitant improvements in OSA and related symptoms vs placebo. This suggests weight loss mediated by phentermine 15 mg plus extended-release topiramate 92 mg may be useful in treatment of moderate to severe OSA in obese subjects unable or unwilling to comply with PAP treatment.