The Experts below are selected from a list of 915 Experts worldwide ranked by ideXlab platform
Stephen E. Daniels - One of the best experts on this subject based on the ideXlab platform.
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a randomized phase 2 study investigating trv130 a biased ligand of the μ opioid receptor for the intravenous treatment of acute pain
Pain, 2016Co-Authors: Eugene R. Viscusi, Stephen E. Daniels, Lynn R Webster, Michael E Kuss, James A Bolognese, Seth Zuckerman, David G Soergel, Ruth Ann Subach, Emily Cook, Franck SkobierandaAbstract:Efficacy of conventional opioids can be limited by adverse events (AEs). TRV130 is a structurally novel biased ligand of the μ-opioid receptor that activates G protein signaling with little β-arrestin recruitment. In this phase 2, randomized, placebo- and active-controlled study, we investigated the efficacy and tolerability of TRV130 in acute pain after Bunionectomy. We used an adaptive study design in which 144 patients experiencing moderate-to-severe acute pain after Bunionectomy were randomized to receive double-blind TRV130, placebo, or morphine in a pilot phase. After pilot phase analysis, 195 patients were randomized to receive double-dummy TRV130 0.5, 1, 2, or 3 mg every 3 hours (q3h); placebo; or morphine 4 mg q4h intravenously. The primary end point was the time-weighted average change in numeric rating scale pain intensity over the 48-hour treatment period. Secondary end points included stopwatch and categorical assessments of pain relief. Safety and tolerability were also assessed. TRV130 2 and 3 mg q3h, and morphine 4 mg q4h produced statistically greater mean reductions in pain intensity than placebo over 48 hours (P < 0.005). TRV130 at 2 and 3 mg produced significantly greater categorical pain relief than morphine (P < 0.005) after the first dose, with meaningful pain relief occurring in under 5 minutes. TRV130 produced no serious AEs, with tolerability similar to morphine. These results demonstrate that TRV130 rapidly produces profound analgesia in moderate-to-severe acute pain, suggesting that G-protein-biased μ-opioid receptor activation is a promising target for development of novel analgesics.
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A phase 3, randomized, placebo-controlled trial of DepoFoam® bupivacaine (extended-release bupivacaine local analgesic) in Bunionectomy.
Advances in therapy, 2011Co-Authors: Michael Golf, Stephen E. Daniels, Erol OnelAbstract:Background DepoFoam® bupivacaine (Pacira Pharmaceuticals, Inc., San Diego, CA, USA), an extended-release liposomal bupivacaine-based analgesic, was compared with placebo for the prevention of pain after Bunionectomy in a randomized, multicenter, double-blind phase 3 clinical study.
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efficacy and safety of oxycodone hcl niacin tablets for the treatment of moderate to severe postoperative pain following Bunionectomy surgery
Current Medical Research and Opinion, 2011Co-Authors: Stephen E. Daniels, Ron J. Spivey, Sonia Singla, Michael Golf, Francis ClarkAbstract:AbstractObjective:To evaluate the efficacy and safety of two dose strengths of oxycodone hydrochloride (HCl)/niacin tablets for the treatment of moderate-to-severe postoperative pain following Bunionectomy surgery.Research design and methods:Randomized, double-blind, placebo-controlled, US multicenter, repeat-dose study (Clinicaltrials.gov: NCT00654069). A total of 606 patients aged ≥18 years with moderate-to-severe pain post-Bunionectomy were screened, and 405 patients were randomized to receive placebo, 2 × 5/30 mg oxycodone HCl/niacin tablets, or 2 × 7.5/30 mg oxycodone HCl/niacin tablets administered every 6 hours for 48 hours. Ketorolac tromethamine was available as rescue medication.Main outcome measures:Primary efficacy endpoint was the sum of pain-intensity difference scores during the 48 hours (SPID48) following the initial dose of study drug. Secondary efficacy endpoints included a responder analysis and use of rescue medication. Safety evaluations included adverse events (AEs), vital signs, and...
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Efficacy and safety of oxycodone HCl/niacin tablets for the treatment of moderate-to-severe postoperative pain following Bunionectomy surgery.
Current medical research and opinion, 2011Co-Authors: Stephen E. Daniels, Ron J. Spivey, Sonia Singla, Michael Golf, Francis ClarkAbstract:AbstractObjective:To evaluate the efficacy and safety of two dose strengths of oxycodone hydrochloride (HCl)/niacin tablets for the treatment of moderate-to-severe postoperative pain following Bunionectomy surgery.Research design and methods:Randomized, double-blind, placebo-controlled, US multicenter, repeat-dose study (Clinicaltrials.gov: NCT00654069). A total of 606 patients aged ≥18 years with moderate-to-severe pain post-Bunionectomy were screened, and 405 patients were randomized to receive placebo, 2 × 5/30 mg oxycodone HCl/niacin tablets, or 2 × 7.5/30 mg oxycodone HCl/niacin tablets administered every 6 hours for 48 hours. Ketorolac tromethamine was available as rescue medication.Main outcome measures:Primary efficacy endpoint was the sum of pain-intensity difference scores during the 48 hours (SPID48) following the initial dose of study drug. Secondary efficacy endpoints included a responder analysis and use of rescue medication. Safety evaluations included adverse events (AEs), vital signs, and...
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A randomized, double-blind, phase III study comparing multiple doses of tapentadol IR, oxycodone IR, and placebo for postoperative (Bunionectomy) pain
Current medical research and opinion, 2009Co-Authors: Stephen E. Daniels, David Upmalis, A. Okamoto, Claudia Lange, J. HaeusslerAbstract:ABSTRACTObjective: This study evaluated tapentadol immediate release (IR) for pain relief following orthopedic Bunionectomy surgery.Methods: This randomized, double-blind, placebo- and active-controlled, phase III study included patients with moderate-to-severe pain following Bunionectomy. Randomized patients (N = 603) received tapentadol IR 50, 75, or 100 mg; oxycodone HCl IR 15 mg; or placebo orally every 4–6 hours over a 72-hour period following Bunionectomy. The primary endpoint was the sum of pain intensity difference (SPID) over 48 hours. Secondary endpoints included SPID over 12, 24, and 72 hours; total pain relief, and sum of total pain relief and sum of pain intensity difference (SPRID) over 12, 24, 48, and 72 hours; use of rescue medication; patient global impression of change; and onset of action assessment. Possible limitations of this study were that the intense dose monitoring and thorough nursing care were unlikely to represent actual use situations and could introduce similar bias across a...
Francis Clark - One of the best experts on this subject based on the ideXlab platform.
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efficacy and safety of oxycodone hcl niacin tablets for the treatment of moderate to severe postoperative pain following Bunionectomy surgery
Current Medical Research and Opinion, 2011Co-Authors: Stephen E. Daniels, Ron J. Spivey, Sonia Singla, Michael Golf, Francis ClarkAbstract:AbstractObjective:To evaluate the efficacy and safety of two dose strengths of oxycodone hydrochloride (HCl)/niacin tablets for the treatment of moderate-to-severe postoperative pain following Bunionectomy surgery.Research design and methods:Randomized, double-blind, placebo-controlled, US multicenter, repeat-dose study (Clinicaltrials.gov: NCT00654069). A total of 606 patients aged ≥18 years with moderate-to-severe pain post-Bunionectomy were screened, and 405 patients were randomized to receive placebo, 2 × 5/30 mg oxycodone HCl/niacin tablets, or 2 × 7.5/30 mg oxycodone HCl/niacin tablets administered every 6 hours for 48 hours. Ketorolac tromethamine was available as rescue medication.Main outcome measures:Primary efficacy endpoint was the sum of pain-intensity difference scores during the 48 hours (SPID48) following the initial dose of study drug. Secondary efficacy endpoints included a responder analysis and use of rescue medication. Safety evaluations included adverse events (AEs), vital signs, and...
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Efficacy and safety of oxycodone HCl/niacin tablets for the treatment of moderate-to-severe postoperative pain following Bunionectomy surgery.
Current medical research and opinion, 2011Co-Authors: Stephen E. Daniels, Ron J. Spivey, Sonia Singla, Michael Golf, Francis ClarkAbstract:AbstractObjective:To evaluate the efficacy and safety of two dose strengths of oxycodone hydrochloride (HCl)/niacin tablets for the treatment of moderate-to-severe postoperative pain following Bunionectomy surgery.Research design and methods:Randomized, double-blind, placebo-controlled, US multicenter, repeat-dose study (Clinicaltrials.gov: NCT00654069). A total of 606 patients aged ≥18 years with moderate-to-severe pain post-Bunionectomy were screened, and 405 patients were randomized to receive placebo, 2 × 5/30 mg oxycodone HCl/niacin tablets, or 2 × 7.5/30 mg oxycodone HCl/niacin tablets administered every 6 hours for 48 hours. Ketorolac tromethamine was available as rescue medication.Main outcome measures:Primary efficacy endpoint was the sum of pain-intensity difference scores during the 48 hours (SPID48) following the initial dose of study drug. Secondary efficacy endpoints included a responder analysis and use of rescue medication. Safety evaluations included adverse events (AEs), vital signs, and...
Lowell Scott Weil - One of the best experts on this subject based on the ideXlab platform.
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The Radiographic Effects of the Scarf Bunionectomy on Rearfoot Alignment
Foot & ankle specialist, 2014Co-Authors: Nicholas G. Argerakis, Lowell Weil, Lowell Scott Weil, Dimitrios Anagnostopoulos, Catherine A. Feuerstein, Erin E. Klein, Ashley K. BoccioAbstract:Statement of Purpose. Excessive pronation of the rearfoot has been implicated as a destabilizing force in the progression of hallux abducto valgus. Although the scarf Bunionectomy has been shown to effectively correct the intermetatarsal angle associated with hallux valgus deformity, its effect on the rearfoot has yet to be established. The purpose of this case series is to demonstrate the effect of the scarf Bunionectomy on rearfoot alignment. Methodology. Medical records were reviewed to isolate patients who underwent unilateral or bilateral scarf bunionectomies (with or without akin osteotomy) who had complete medical records, follow-up of at least 12 months, and met the inclusion/exclusion criteria. Preoperative and postoperative radiographic measurements were analyzed at various postoperative time intervals. Standard deviations and statistical significance was obtained. Results. One hundred feet (71 patients) were included in this analysis. The long-term results of this study highlighted the scarf os...
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scarf osteotomy for correction of hallux valgus historical perspective surgical technique and results
Foot and Ankle Clinics of North America, 2000Co-Authors: Lowell Scott WeilAbstract:Abstract The Scarf osteotomy has proven to be a versatile and powerful procedure to correct various degrees of hallux valgus deformity. Through modifications of bone-cut lengths and in combination with a phalangeal osteotomy, most hallux valgus deformities can be addressed. In cases of extreme hypermobility of the first ray or arthrosis of the first metatarsocuneiform joint, the Lapidus operation may be more appropriate. Hallux valgus rigidus or hallux valgus with severe rheumatoid joint disease usually requires alternative procedures. The results of the Scarf osteotomy compare favorably with the results reported for other popular bunion surgeries. When choosing a procedure, the clinician should consider that the Scarf osteotomy allows the patient to ambulate postoperatively without a cast or the use of crutches, to return to bathing and a closed athletic shoe in one week, and to have bilateral surgery, which maintains cost-effectiveness and returns the patient to his or her desired lifestyle more quickly. It has been said that surgery is both a science and an art. The author often believes that bunion surgery is more art than science, hence the success of so many procedures in one surgeon's hands and the failure in another's hands. The Scarf Bunionectomy is a technically demanding procedure that has a large learning curve. Once mastered, however, the Scarf Bunionectomy can provide a predictable and satisfying outcome for both patient and foot surgeon.
Michael Golf - One of the best experts on this subject based on the ideXlab platform.
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A phase 3, randomized, placebo-controlled trial of DepoFoam® bupivacaine (extended-release bupivacaine local analgesic) in Bunionectomy.
Advances in therapy, 2011Co-Authors: Michael Golf, Stephen E. Daniels, Erol OnelAbstract:Background DepoFoam® bupivacaine (Pacira Pharmaceuticals, Inc., San Diego, CA, USA), an extended-release liposomal bupivacaine-based analgesic, was compared with placebo for the prevention of pain after Bunionectomy in a randomized, multicenter, double-blind phase 3 clinical study.
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efficacy and safety of oxycodone hcl niacin tablets for the treatment of moderate to severe postoperative pain following Bunionectomy surgery
Current Medical Research and Opinion, 2011Co-Authors: Stephen E. Daniels, Ron J. Spivey, Sonia Singla, Michael Golf, Francis ClarkAbstract:AbstractObjective:To evaluate the efficacy and safety of two dose strengths of oxycodone hydrochloride (HCl)/niacin tablets for the treatment of moderate-to-severe postoperative pain following Bunionectomy surgery.Research design and methods:Randomized, double-blind, placebo-controlled, US multicenter, repeat-dose study (Clinicaltrials.gov: NCT00654069). A total of 606 patients aged ≥18 years with moderate-to-severe pain post-Bunionectomy were screened, and 405 patients were randomized to receive placebo, 2 × 5/30 mg oxycodone HCl/niacin tablets, or 2 × 7.5/30 mg oxycodone HCl/niacin tablets administered every 6 hours for 48 hours. Ketorolac tromethamine was available as rescue medication.Main outcome measures:Primary efficacy endpoint was the sum of pain-intensity difference scores during the 48 hours (SPID48) following the initial dose of study drug. Secondary efficacy endpoints included a responder analysis and use of rescue medication. Safety evaluations included adverse events (AEs), vital signs, and...
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Efficacy and safety of oxycodone HCl/niacin tablets for the treatment of moderate-to-severe postoperative pain following Bunionectomy surgery.
Current medical research and opinion, 2011Co-Authors: Stephen E. Daniels, Ron J. Spivey, Sonia Singla, Michael Golf, Francis ClarkAbstract:AbstractObjective:To evaluate the efficacy and safety of two dose strengths of oxycodone hydrochloride (HCl)/niacin tablets for the treatment of moderate-to-severe postoperative pain following Bunionectomy surgery.Research design and methods:Randomized, double-blind, placebo-controlled, US multicenter, repeat-dose study (Clinicaltrials.gov: NCT00654069). A total of 606 patients aged ≥18 years with moderate-to-severe pain post-Bunionectomy were screened, and 405 patients were randomized to receive placebo, 2 × 5/30 mg oxycodone HCl/niacin tablets, or 2 × 7.5/30 mg oxycodone HCl/niacin tablets administered every 6 hours for 48 hours. Ketorolac tromethamine was available as rescue medication.Main outcome measures:Primary efficacy endpoint was the sum of pain-intensity difference scores during the 48 hours (SPID48) following the initial dose of study drug. Secondary efficacy endpoints included a responder analysis and use of rescue medication. Safety evaluations included adverse events (AEs), vital signs, and...
Eugene R. Viscusi - One of the best experts on this subject based on the ideXlab platform.
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Oliceridine is Associated with Reduced Risk of Vomiting and Need for Rescue Antiemetics Compared to Morphine: Exploratory Analysis from Two Phase 3 Randomized Placebo and Active Controlled Trials
Pain and Therapy, 2020Co-Authors: Timothy L. Beard, Cathy Michalsky, Keith A. Candiotti, Paul Rider, Linda Wase, Ashraf S. Habib, Mark A. Demitrack, Michael J. Fossler, Eugene R. ViscusiAbstract:Introduction Use of parenteral opioids is a major risk factor for postoperative nausea and vomiting. Conventional opioids bind to µ-opioid receptors (MOR), stimulate both the G-protein signaling (achieving analgesia); and the β-arrestin pathway (associated with opioid-related adverse effects). Oliceridine, a next-generation IV opioid, is a G-protein selective MOR agonist, with limited recruitment of β-arrestin. In two randomized, placebo- and morphine-controlled phase 3 studies of patients with moderate-to-severe acute pain following Bunionectomy or abdominoplasty, oliceridine at demand doses of 0.1, 0.35, and 0.5 mg provided rapid and sustained analgesia vs. placebo with favorable gastrointestinal (GI) tolerability. In this exploratory analysis, we utilized a clinical endpoint assessing gastrointestinal tolerability, “complete GI response” defined as the proportion of patients with no vomiting and no use of rescue antiemetic to characterize the GI tolerability profile of oliceridine vs. morphine. Methods A logistic regression model was utilized to compare oliceridine (pooled regimens) vs. morphine, after controlling for analgesia (using the sum of pain intensity difference [SPID]-48/24 [Bunionectomy/abdominoplasty] with pre-rescue scores carried forward for 6 h). This analysis excluded patients receiving placebo and was performed for each study separately and for pooled data from both studies. Results In the unadjusted analysis, a significantly greater proportion of patients in the placebo (76.4%), oliceridine 0.1 mg (68.0%), and 0.35 mg (46.2%) demand dose achieved complete GI response vs. morphine 1 mg (30.8%), p ≤ 0.005. In the adjusted analysis, after controlling for analgesia, the odds ratio of experiencing a complete GI response with oliceridine (pooled regimens) vs. morphine was 3.14 (95% CI: 1.78, 5.56; p
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mechanism of action of htx 011 a novel extended release dual acting local anesthetic formulation for postoperative pain
Regional Anesthesia and Pain Medicine, 2020Co-Authors: Thomas Ottoboni, Barry D Quart, Jayne Pawasauskas, Joseph F Dasta, Richard A Pollak, Eugene R. ViscusiAbstract: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. Preclinical studies and a phase II clinical trial were conducted to confirm the mechanism of action of HTX-011. Methods In a validated postoperative pain pig model and a phase II Bunionectomy trial, the analgesic effects of HTX-011, oral meloxicam (preclinical only), liposomal bupivacaine (preclinical only) and saline placebo were evaluated. The optimal meloxicam:bupivacaine ratio for HTX-011 and the effect of HTX-011 on incisional tissue pH were also evaluated preclinically. Results Preclinical data demonstrate the ability of HTX-011 to address local tissue inflammation as demonstrated by a less acidic tissue pH, which was associated with potentiated and prolonged analgesic activity. In the phase II Bunionectomy study, HTX-011 achieved superior and sustained pain relief through 72 hours after surgery compared with each component in the polymer. Conclusions Preclinical animal and clinical results confirm that the low-dose meloxicam in HTX-011 normalizes the local pH in the incision, resulting in superior and synergistic analgesic activity compared with extended-release bupivacaine. HTX-011 represents an extended-release local anesthetic with a dual-acting mechanism of action that may provide an important advancement in the treatment of postoperative pain. Trial registration number NCT02762929.
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Tapentadol immediate release for moderate to severe acute post-surgery pain
Journal of opioid management, 2019Co-Authors: Eugene R. Viscusi, René Allard, Melanie Sohns, Mariëlle EerdekensAbstract:Objective: To investigate efficacy and tolerability of tapentadol immediate release (IR) in the treatment of moderate to severe acute pain in three surgical pain models. Design: Three randomized, double-blind, placebo- and active-controlled, multicenter, phase 3 trials were performed in total hip replacement surgery, abdominal hysterectomy, and Bunionectomy with trial medications administered every 4-6 hours as needed for up to 72 hours. Tapentadol IR was included in all trials, oxycodone IR in the total hip replacement trial, and morphine IR in the abdominal hysterectomy and Bunionectomy trials; active controls ensured assay sensitivity. Main outcome measures: The primary efficacy endpoint was the sum of pain intensity differences over the first 24 hours of treatment (SPID24) in the abdominal hysterectomy trial and SPID48 in the other two trials. Tolerability was assessed by adverse events reporting. Results: A total of 330, 832, and 285 patients with total hip replacement, abdominal hysterectomy, and Bunionectomy, respectively, were assessed for efficacy. All three trials demonstrated statistically significant improvements of tapentadol IR on the primary endpoint versus placebo and similar improvements compared to morphine IR or oxycodone IR. These findings were consistent with results of total pain relief assessments and patients’ global impressions of change in their overall health status after 72 hours (abdominal hysterectomy, Bunionectomy). The tolerability profile of tapentadol IR was as expected for a centrally acting analgesic in the post-surgery setting. Conclusions: Tapentadol IR has strong analgesic efficacy and is well tolerated in multiple post-surgery conditions of moderate to severe pain.
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a randomized phase 2 study investigating trv130 a biased ligand of the μ opioid receptor for the intravenous treatment of acute pain
Pain, 2016Co-Authors: Eugene R. Viscusi, Stephen E. Daniels, Lynn R Webster, Michael E Kuss, James A Bolognese, Seth Zuckerman, David G Soergel, Ruth Ann Subach, Emily Cook, Franck SkobierandaAbstract:Efficacy of conventional opioids can be limited by adverse events (AEs). TRV130 is a structurally novel biased ligand of the μ-opioid receptor that activates G protein signaling with little β-arrestin recruitment. In this phase 2, randomized, placebo- and active-controlled study, we investigated the efficacy and tolerability of TRV130 in acute pain after Bunionectomy. We used an adaptive study design in which 144 patients experiencing moderate-to-severe acute pain after Bunionectomy were randomized to receive double-blind TRV130, placebo, or morphine in a pilot phase. After pilot phase analysis, 195 patients were randomized to receive double-dummy TRV130 0.5, 1, 2, or 3 mg every 3 hours (q3h); placebo; or morphine 4 mg q4h intravenously. The primary end point was the time-weighted average change in numeric rating scale pain intensity over the 48-hour treatment period. Secondary end points included stopwatch and categorical assessments of pain relief. Safety and tolerability were also assessed. TRV130 2 and 3 mg q3h, and morphine 4 mg q4h produced statistically greater mean reductions in pain intensity than placebo over 48 hours (P < 0.005). TRV130 at 2 and 3 mg produced significantly greater categorical pain relief than morphine (P < 0.005) after the first dose, with meaningful pain relief occurring in under 5 minutes. TRV130 produced no serious AEs, with tolerability similar to morphine. These results demonstrate that TRV130 rapidly produces profound analgesia in moderate-to-severe acute pain, suggesting that G-protein-biased μ-opioid receptor activation is a promising target for development of novel analgesics.
