Selective Inhibition of Na1.8 with VX-548 for Acute Pain.

Background: The Na1.8 voltage-gated sodium channel, expressed in peripheral nociceptive neurons, plays a role in transmitting nociceptive signals. The effect of VX-548, an oral, highly selective inhibitor of Na1.

Opioid-Free Recovery from Bunionectomy with HTX-011, a Dual-Acting Local Anesthetic Combining Bupivacaine and Meloxicam, as the Foundation of Non-Opioid Multimodal Analgesia.

Background: There is a need for postoperative pain control that minimizes or eliminates opioid use during the first 72 hours following surgery, when pain is most severe. HTX-011 is an extended-release, dual-acting local anesthetic that demonstrated superior 72-hour analgesia over standard of care bupivacaine hydrochloride (HCl) and saline placebo in a phase 3 bunionectomy study (EPOCH-1). Having shown HTX-011 monotherapy is superior to bupivacaine HCl in reducing postoperative pain intensity and opioid use, this follow-on study evaluated the safety and efficacy of HTX-011 as the foundation of a multimodal analgesia (MMA) regimen using over-the-counter medications recommended by practice guidelines for pain management.

Efficacy and Safety of Intravenously Administered Tramadol in Patients with Moderate to Severe Pain Following Bunionectomy: A Randomized, Double-Blind, Placebo-Controlled, Dose-Finding Study.

Introduction: This 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.

Methods: This 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.

HTX-011 Reduced Pain and Opioid Use After Primary Total Knee Arthroplasty: Results of a Randomized Phase 2b Trial.

Background: HTX-011 is an extended-release, dual-acting local anesthetic consisting of bupivacaine and low-dose meloxicam in a novel polymer that is administered by needle-free application during surgery. The active ingredients are released from the polymer by controlled diffusion over 72 hours.

Methods: This phase 2b, double-blind, placebo-controlled and active-controlled trial enrolled patients undergoing primary unilateral total knee arthroplasty under general anesthesia.

Mechanism of action of HTX-011: a novel, extended-release, dual-acting local anesthetic formulation for postoperative pain.

Background And Objectives: Obtaining consistent efficacy beyond 12-24 hours with local anesthetics, including extended-release formulations, has been a challenging goal. Inflammation resulting from surgery lowers the pH of affected tissues, reducing neuronal penetration of local anesthetics. HTX-011, an investigational, nonopioid, extended-release dual-acting local anesthetic combining bupivacaine and low-dose meloxicam, was developed to reduce postsurgical pain through 72 hours using novel extended-release polymer technology.

Efficacy and Safety of Intravenous Meloxicam in Patients With Moderate-to-Severe Pain Following Bunionectomy: A Randomized, Double-Blind, Placebo-controlled Trial.

Objective: To evaluate the analgesic efficacy and safety of a novel intravenous (IV) formulation of meloxicam (30 mg) in patients with moderate-to-severe pain following a standardized, unilateral bunionectomy with first metatarsal osteotomy and internal fixation.

Materials And Methods: Patients who met the criteria for moderate-to-severe postoperative pain were randomized to receive bolus injections of meloxicam IV 30 mg (n=100) or placebo (n=101) administered once daily. The primary efficacy endpoint was the Summed Pain Intensity Difference over 48 hours (SPID48).

Long-Term Follow-up of Onychomycosis Patients Treated With Efinaconazole.

Background: Onychomycosis is a common disease that remains difficult to treat despite the introduction of new topical agents. Clinical trials on efinaconazole and tavaborole included 48 weeks' daily treatment regimens with a 4-week follow-up. It has been suggested that either a longer treatment regimen or longer follow-up would lead to even better results, primarily due to the time taken for the diseased nail to grow out, especially in those patients with more severe disease.

Safety and efficacy of intramuscular human placenta-derived mesenchymal stromal-like cells (cenplacel [PDA-002]) in patients who have a diabetic foot ulcer with peripheral arterial disease.

The objective of this study was to examine the safety of cenplacel (PDA-002) in patients with peripheral arterial disease (PAD) and a diabetic foot ulcer (DFU). Cenplacel is a mesenchymal-like cell population derived from full-term human placenta. This phase 1, dose-escalation study investigated cenplacel in diabetic patients with chronic DFUs (Wagner grade 1 or grade 2) and PAD [ankle-brachial index (ABI) >0·5 and ≤0·9], enrolled sequentially into each of four dose cohorts (3 × 10 , 10 × 10 , 30 × 10 and 100 × 10 cells; administered intramuscularly on study days 1 and 8 in combination with standard of care).

Defining the optimal formulation and schedule of a candidate toxoid vaccine against Clostridium difficile infection: A randomized Phase 2 clinical trial.

Background: Clostridium difficile, a major cause of nosocomial and antibiotic-associated diarrhea, carries a significant disease and cost burden. This study aimed to select an optimal formulation and schedule for a candidate toxoid vaccine against C. difficile toxins A and B.

Efinaconazole Topical Solution, 10%: Factors Contributing to Onychomycosis Success.

To provide an adequate therapeutic effect against onychomycosis, it has been suggested that topical drugs should have two properties: drug permeability through the nail plate and into the nail bed, and retention of their antifungal activity in the disease-affected areas. Only recently has the importance of other delivery routes (such as subungual) been discussed. Efinaconazole has been shown to have a more potent antifungal activity than the most commonly used onychomycosis treatments.

Efficacy and safety of tavaborole topical solution, 5%, a novel boron-based antifungal agent, for the treatment of toenail onychomycosis: Results from 2 randomized phase-III studies.

Background: Onychomycosis, a fungal nail infection, can impact quality of life.

Objective: We sought to evaluate the efficacy and safety of tavaborole topical solution, 5% for treatment of toenail onychomycosis.

Methods: In 2 phase-III trials, adults with distal subungual onychomycosis affecting 20% to 60% of a target great toenail were randomized 2:1 to tavaborole or vehicle once daily for 48 weeks.

Access of efinaconazole topical solution, 10%, to the infection site by spreading through the subungual space.

Objective: To evaluate the ability of efinaconazole vehicle to reach the site of toenail onychomycosis by spreading through the subungual space between the nail plate and nail bed. Lacquer-based vehicles are primarily limited to application on the nail plate and dependent on nail plate permeation.

Methods: 11 patients (mean age 48.

Efinaconazole topical solution, 10%: the development of a new topical treatment for toenail onychomycosis.

Background: Toenail onychomycosis is a common disease with limited treatment options; treatment failure and relapse are frequently encountered. Many patients experience long-standing disease affecting multiple toenails, with substantial discomfort and pain. Although some patients might prefer a topical therapy, efficacy with ciclopirox nail lacquer has been disappointing.

The efficacy and safety of tavaborole, a novel, boron-based pharmaceutical agent: phase 2 studies conducted for the topical treatment of toenail onychomycosis.

Objective: To assess the potential efficacy, safety, and optimal dosing concentration of tavaborole, a novel, boron-based pharmaceutical agent with broad-spectrum antifungal activity, for the treatment of onychomycosis of the toenail due to dermatophytes.

Methods: One double-blind, randomized, vehicle-controlled study (study 1) and two open-label studies (studies 2 and 3) examined the efficacy, safety, and optimal dosing concentration of tavaborole topical solution applied once daily or three times weekly for 180 days at concentrations of 1.0%, 2.

Efficacy of high-dose versus standard-dose influenza vaccine in older adults.

Background: As compared with a standard-dose vaccine, a high-dose, trivalent, inactivated influenza vaccine (IIV3-HD) improves antibody responses to influenza among adults 65 years of age or older. This study evaluated whether IIV3-HD also improves protection against laboratory-confirmed influenza illness.

Methods: We conducted a phase IIIb-IV, multicenter, randomized, double-blind, active-controlled trial to compare IIV3-HD (60 μg of hemagglutinin per strain) with standard-dose trivalent, inactivated influenza vaccine (IIV3-SD [15 μg of hemagglutinin per strain]) in adults 65 years of age or older.

Efficacy and safety of once-daily luliconazole 1% cream in patients ≥12 years of age with interdigital tinea pedis: a phase 3, randomized, double-blind,vehicle-controlled study.

Background: Interdigital tinea pedis is one of the most common clinical presentations of dermatophytosis.

Objective: This phase 3 study evaluated the safety and efficacy of luliconazole cream 1% in patients with tinea pedis.

Methods: A total of 321 male and female patients aged ≥12 years with tinea pedis and eligible for modified intent-to-treat analysis were randomized 1:1 to receive luliconazole cream 1% (n=159) or vehicle (n=162) once daily for 14 days.

Efinaconazole 10% solution in the treatment of toenail onychomycosis: Two phase III multicenter, randomized, double-blind studies.

Background: Onychomycosis is a common nail infection, often resulting in nail plate damage and deformity. Topical lacquer treatments have negligible efficacy. Oral treatments, although more efficacious, are limited by drug interactions and potential hepatotoxicity.

Toenail assessment tool for quantitation of visibly infected mycotic nail plate in onychomycosis.

Typically, the amount of mycotic nail involvement in onychomycosis (fungal infection of the nail) before and after drug therapy is determined visually. Because there is an inherent element of subjectivity, it is difficult to accurately measure and compare results across clinical trials or to assess how much improvement has been achieved in response to therapy. We developed a simple tool for measuring mycotic nail involvement.

Treatment of toenail onychomycosis with oral terbinafine plus aggressive debridement: IRON-CLAD, a large, randomized, open-label, multicenter trial.

This study was conducted to investigate the efficacy of oral terbinafine with and without aggressive debridement for the treatment of toenail onychomycosis. Onychomycosis patients aged 18 to 75 years received 12 weeks of terbinafine, 250 mg/day, alone (n = 255) or with aggressive debridement (n = 249). Both groups showed marked improvement from baseline at all time points.

Analgesic efficacy of valdecoxib for acute postoperative pain after bunionectomy.

Two randomized, double-blind, placebo-controlled studies assessed the analgesic efficacy of valdecoxib in patients with moderate-to-severe pain after bunionectomy. Study 1 (N = 374) assessed the efficacy of two regimens of valdecoxib on the day after surgery (valdecoxib, 40 mg, with a 20-mg redose [n = 127]; valdecoxib, 40 mg, with a placebo redose [n = 122]; and placebo/placebo [n = 125]), and study 2 (N = 478) examined the efficacy of two different multiple-dose regimens on postoperative days 2 through 5 (valdecoxib, 20 mg, twice daily [n = 160]; valdecoxib, 20 mg, once daily [n = 159]; and placebo [n = 159]). Valdecoxib provided significant pain relief and reduced the use of opioid rescue medication.

An open-label, randomized study comparing efficacy and safety of intravenous piperacillin/tazobactam and ampicillin/sulbactam for infected diabetic foot ulcers.

Background: Soft tissue and bone infections of the lower limb continue to be a frequent and serious complication in patients with diabetes mellitus. The best choice of antimicrobial for the empiric treatment of moderate to severe diabetic foot infections has not been established clearly.

Methods: We conducted a prospective, randomized, open-label, multicenter trial comparing piperacillin/tazobactam (P/T) (4 g/0.

The efficacy and safety of Dermagraft in improving the healing of chronic diabetic foot ulcers: results of a prospective randomized trial.

Objective: To determine if a human fibroblast-derived dermal substitute could promote the healing of diabetic foot ulcers.

Research Design And Methods: A randomized, controlled, multicenter study was undertaken at 35 centers throughout the U.S.