scholarly journals HTX-011 reduced pain intensity and opioid consumption versus bupivacaine HCl in bunionectomy: phase III results from the randomized EPOCH 1 study

2019 ◽  
Vol 44 (7) ◽  
pp. 700-706 ◽  
Author(s):  
Eugene Viscusi ◽  
Joseph S Gimbel ◽  
Richard A Pollack ◽  
Jia Hu ◽  
Gwo-Chin Lee
Keyword(s):  
Postoperative Pain ◽  
Local Anesthetic ◽  
Immediate Release ◽  
Opioid Consumption ◽  
Phase Iii ◽  
Opioid Use ◽  
Double Blind ◽  
Registration Number ◽  
Secondary Endpoints ◽  
Phase Iii Study

Background and objectivesThere is a need for local anesthetics that provide consistent analgesia through 72 hours after surgery. This study evaluates the use of HTX-011 (bupivacaine and meloxicam in Biochronomerpolymer technology), an extended-release, dual-acting local anesthetic, in reducing both postoperative pain over 72 hours and postoperative opioid use when compared with bupivacaine hydrochloride (HCl) and saline placebo. Inclusion of low-dose meloxicam in HTX-011 is designed to reduce local inflammation caused by surgery, potentiating the analgesic effect of bupivacaine. Previously, significant synergy has been observed with bupivacaine and meloxicam with both given locally together.MethodsEPOCH 1 was a randomized, double-blind, placebo-controlled and active-controlled phase III study in subjects undergoing a primary unilateral, distal, first metatarsal bunionectomy in which subjects received either a single intraoperative dose of HTX-011, immediate-release bupivacaine HCl or saline placebo.ResultsA total of 412 subjects were dosed. The results for the primary and all four key secondary endpoints were statistically significant in favor of HTX-011. HTX-011 demonstrated superior, sustained pain reduction through 72 hours, significantly reduced opioid consumption and resulted in significantly more opioid-free subjects compared with saline placebo and bupivacaine HCl. Safety was similar across groups with fewer opioid-related adverse events observed in the HTX-011 group.ConclusionsHTX-011 demonstrated significant reduction in postoperative pain through 72 hours with significant reduction in opioid consumption and a significant increase in the proportion of opioid-free subjects compared with saline placebo and the most widely used local anesthetic, bupivacaine HCl.Trial registration numberNCT03295721.

scholarly journals HTX-011 reduced pain intensity and opioid consumption versus bupivacaine HCl in herniorrhaphy: results from the phase 3 EPOCH 2 study

Hernia ◽  
2019 ◽  
Vol 23 (6) ◽  
pp. 1071-1080 ◽  
Author(s):  
E. Viscusi ◽  
H. Minkowitz ◽  
P. Winkle ◽  
S. Ramamoorthy ◽  
J. Hu ◽  
...  
Keyword(s):  
Postoperative Pain ◽  
Pain Intensity ◽  
Local Anesthetic ◽  
Immediate Release ◽  
Opioid Consumption ◽  
Opioid Use ◽  
Phase 3 ◽  
Double Blind ◽  
Mesh Placement ◽  
Number Of Patients

Abstract Purpose Currently available local anesthetics have not demonstrated sufficient analgesia beyond 12–24 h postoperatively. The purpose of the study was to assess the safety and efficacy of HTX-011 (bupivacaine and meloxicam in Biochronomer® polymer technology), a long-acting investigational anesthetic, in reducing both postoperative pain over 72 h and postoperative opioid use compared to bupivacaine hydrochloride (HCl). Methods A phase 3, randomized, double-blind, active-controlled multi-center study (EPOCH 2; NCT03237481) in subjects undergoing unilateral open inguinal herniorrhaphy with mesh placement was performed. Subjects randomly received a single intraoperative dose of HTX-011, immediate-release bupivacaine HCl, or saline placebo prior to closure. Results The study evaluated 418 subjects, and the primary and all key secondary efficacy endpoints were in favor of HTX-011. HTX-011 reduced mean pain intensity by 23% versus placebo (primary endpoint; p < 0.001) and by 21% versus bupivacaine HCl (p < 0.001) with significant reductions in the number of patients experiencing severe pain. Opioid consumption over 72 h was reduced by 38% versus placebo (p < 0.001) and 25% versus bupivacaine HCl (p = 0.024). Overall, 51% of HTX-011 subjects were opioid-free through 72 h (versus 22% for placebo [p < 0.001] and 40% for bupivacaine HCl [p = 0.049]). HTX-011 was generally well-tolerated with fewer opioid-related adverse events reported compared to the bupivacaine HCl and placebo and no evidence of local anesthetic systemic toxicity. Conclusions HTX-011 demonstrated significant improvement in postoperative pain control and a clinically meaningful reduction in opioid consumption when compared to the most widely used local anesthetic, bupivacaine HCl.

scholarly journals Safety, immunogenicity and efficacy after switching from reference infliximab to biosimilar SB2 compared with continuing reference infliximab and SB2 in patients with rheumatoid arthritis: results of a randomised, double-blind, phase III transition study

2017 ◽  
Vol 77 (2) ◽  
pp. 234-240 ◽  
Author(s):  
Josef S Smolen ◽  
Jung-Yoon Choe ◽  
Nenad Prodanovic ◽  
Jaroslaw Niebrzydowski ◽  
Ivan Staykov ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Transition Period ◽  
Phase Iii ◽  
Double Blind ◽  
Treatment Groups ◽  
American College Of Rheumatology ◽  
Registration Number ◽  
Phase Iii Study ◽  
Transition Study ◽  
To Receive

ObjectivesEfficacy, safety and immunogenicity results from the phase III study of SB2, a biosimilar of reference infliximab (INF), were previously reported through 54 weeks. This transition period compared results in patients with rheumatoid arthritis (RA) who switched from INF to SB2 with those in patients who maintained treatment with INF or SB2.MethodsPatients with moderate to severe RA despite methotrexate treatment were randomised (1:1) to receive SB2 or INF at weeks 0, 2 and 6 and every 8 weeks thereafter until week 46. At week 54, patients previously receiving INF were rerandomised (1:1) to switch to SB2 (INF/SB2 (n=94)) or to continue on INF (INF/INF (n=101)) up to week 70. Patients previously receiving SB2 continued on SB2 (SB2/SB2 (n=201)) up to week 70. Efficacy, safety and immunogenicity were assessed up to week 78.ResultsEfficacy was sustained and comparable across treatment groups. American College of Rheumatology (ACR) 20 responses between weeks 54 and 78 ranged from 63.5% to 72.3% with INF/SB2, 66.3%%–69.4% with INF/INF and 65.6%–68.3% with SB2/SB2. Treatment-emergent adverse events during this time occurred in 36.2%, 35.6% and 40.3%, respectively, and infusion-related reactions in 3.2%, 2.0% and 3.5%. Among patients who were negative for antidrug antibodies (ADA) up to week 54, newly developed ADAs were reported in 14.6%, 14.9% and 14.1% of the INF/SB2, INF/INF and SB2/SB2 groups, respectively.ConclusionsThe efficacy, safety and immunogenicity profiles remained comparable among the INF/SB2, INF/INF and SB2/SB2 groups up to week 78, with no treatment-emergent issues or clinically relevant immunogenicity after switching from INF to SB2.Trial registration numberNCT01936181; EudraCT number: 2012-005733-37.

Phase III study of androgen deprivation therapy (ADT) with enzalutamide (ENZA) or placebo (PBO) in metastatic hormone-sensitive prostate cancer (mHSPC): The ARCHES trial.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 687-687 ◽  
Author(s):  
Andrew J. Armstrong ◽  
Russell Zelig Szmulewitz ◽  
Daniel Peter Petrylak ◽  
Arnauld Villers ◽  
Arun Azad ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
High Volume ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
Secondary Endpoints ◽  
Phase Iii Study ◽  
Grade 3

687 Background: ENZA, a potent androgen receptor inhibitor, has demonstrated benefit in men with metastatic and nonmetastatic castration-resistant prostate cancer (CRPC). Efficacy of ENZA with ADT in men with mHSPC is unknown. Methods: ARCHES is a multinational, double-blind, phase 3 study (NCT02677896). Patients (pts) with mHSPC were randomized 1:1 to ENZA (160 mg/day) + ADT or PBO + ADT, stratified by disease volume (CHAARTED criteria) and prior docetaxel therapy. Primary endpoint was radiographic progression-free survival (rPFS) assessed centrally or death within 24 weeks of treatment discontinuation. Secondary endpoints included time to prostate-specific antigen (PSA) progression, PSA and radiographic responses and overall survival (OS). Treatment continued until disease progression or unacceptable toxicity. Results: 1150 men were randomized to ENZA (n=574) or PBO (n=576); baseline characteristics were balanced between groups. Overall, 67% had distant metastasis at initial diagnosis; 63% had high volume disease, 18% had prior docetaxel. Median follow-up was 14.4 mo. ENZA + ADT significantly improved rPFS (Table); similar significant improvements in rPFS were reported in prespecified subgroups of disease volume, pattern of spread, region and prior docetaxel (HRs 0.24–0.53). Secondary endpoints improved with ENZA + ADT (Table); OS data are immature. Grade 3–4 adverse events (AEs) were reported in 23.6% of ENZA pts vs 24.7% of PBO pts with no unexpected AEs. Conclusions: ENZA + ADT significantly improved rPFS and other efficacy endpoints vs PBO + ADT in men with mHSPC, with a preliminary safety analysis that appears consistent with the safety profile of ENZA in previous CRPC clinical trials. Acknowledgements: Medical writing and editing assistance was provided by Stephanie Rippon, MBio, and Lauren Smith from Complete HealthVizion, funded by the study sponsors. This study was funded by Astellas Pharma Inc. and Medivation LLC, a Pfizer Company, the co-developers of enzalutamide. Clinical trial information: NCT02677896. [Table: see text]

scholarly journals HTX-011 effectively reduces postoperative pain intensity and opioid use in the elderly

2021 ◽  
Author(s):  
Tina Yip ◽  
Jia Hu ◽  
Pamela S Hawn ◽  
Amy Yamamoto ◽  
Gary Oderda
Keyword(s):  
Clinical Trial ◽  
Postoperative Pain ◽  
Elderly Patients ◽  
Pain Intensity ◽  
Local Anesthetic ◽  
Extended Release ◽  
The Elderly ◽  
Opioid Consumption ◽  
Opioid Use ◽  
Clinical Trial Registration

Aim: HTX-011 (ZYNRELEF™) is an extended-release, dual-acting local anesthetic containing bupivacaine and meloxicam. In bunionectomy and herniorrhaphy studies, HTX-011 resulted in less postoperative pain and less opioid consumption versus bupivacaine HCl. Here we evaluate HTX-011 in patients aged ≥65 years. Materials & methods: Patients received placebo, bupivacaine HCl or HTX-011 following surgery. End points included pain intensity, total opioid consumption, opioid-free patients and safety. Results: HTX-011-treated patients reported lower postoperative pain through 72 h versus bupivacaine HCl and placebo. Elderly patients administered HTX-011 used fewer opioids versus bupivacaine HCl, and a greater proportion remained opioid-free through 72 h. HTX-011 was well tolerated with a safety profile similar to bupivacaine HCl and placebo. Conclusion: HTX-011 maintained effectiveness and was well tolerated in elderly patients. Clinical Trial Registration: NCT03295721 and NCT03237481

Prospective, Double-blind Evaluation of Perioperative Intravenous Acetaminophen and Ketorolac for Postoperative Pain and Opioid Consumption After Endoscopic Carpal Tunnel Release

Hand ◽  
2020 ◽  
pp. 155894472090650
Author(s):  
Elizabeth C. Truelove ◽  
Eva Urrechaga ◽  
Carmella Fernandez ◽  
John R. Fowler
Keyword(s):  
Pain Management ◽  
Postoperative Pain ◽  
Carpal Tunnel ◽  
Carpal Tunnel Release ◽  
Opioid Consumption ◽  
Controlled Study ◽  
Opioid Use ◽  
Double Blind ◽  
Pain Scores ◽  
Endoscopic Carpal Tunnel Release

Background: The current opioid epidemic highlights the need for pain management strategies to decrease or eliminate postoperative use of opioid medications. The purpose of this study was to determine if perioperative administration of intravenous (IV) acetaminophen and/or IV ketorolac decreases postoperative pain and opioid consumption after endoscopic carpal tunnel release. Methods: In all, 44 subjects were enrolled in this randomized, double-blind, placebo-controlled study from October 2015 to April 2017 and divided into 4 treatment arms: placebo, IV acetaminophen, IV ketorolac, or both IV acetaminophen and IV ketorolac. Patients recorded pain at 8-hour intervals on an 11-point scale and daily opioid use for 7 days after surgery. Analysis of variance and Kruskal-Wallis tests were used to compare mean pain scores and opioid consumption. Results: Mean pain scores over the 7-day study period were lower in the placebo and IV acetaminophen groups. Patients in the placebo and acetaminophen groups reported less pain than those in the ketorolac and combination groups on postoperative days 6 and 7. Patients administered IV acetaminophen had lower daily mean opioid usage. In all, 50% of the patients did not take any opioids after surgery. Conclusions: There are small, statistically significant differences in postoperative pain and opioid consumption supporting the use of IV acetaminophen for pain control after endoscopic carpal tunnel release, though these results are likely not clinically relevant. We recommend continued investigation into multimodal pain management in upper extremity surgery as well as limiting the number and quantity of opioid prescriptions provided to patients postoperatively.

scholarly journals A randomised, double-blind, placebo-controlled, 24-week, phase II, proof-of-concept study of romilkimab (SAR156597) in early diffuse cutaneous systemic sclerosis

2020 ◽  
Vol 79 (12) ◽  
pp. 1600-1607 ◽  
Author(s):  
Yannick Allanore ◽  
Peter Wung ◽  
Christina Soubrane ◽  
Corinne Esperet ◽  
Frederic Marrache ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Phase Ii ◽  
Phase Iii ◽  
Scleroderma Renal Crisis ◽  
Proof Of Concept ◽  
Double Blind ◽  
Immunoglobulin G4 ◽  
Background Therapy ◽  
Registration Number ◽  
Phase Iii Study

ObjectivesRecent advances in systemic sclerosis (SSc) show that it involves a T-helper type-2-oriented immune response with interleukin (IL)-4 and IL-13. Romilkimab is an engineered, humanised, bispecific immunoglobulin-G4 antibody that binds and neutralises IL-4/IL-13 making it ideal for exploration in fibrosis.MethodsPatients aged ≥18 years diagnosed with diffuse cutaneous SSc (dcSSc), and with or without immunosuppressive background therapy, were randomised (1:1) to subcutaneous romilkimab 200 mg or placebo one time per week for 24 weeks in this double-blind, proof-of-concept, phase II study. The primary endpoint was change in modified Rodnan skin score (mRSS) from baseline to week 24.ResultsNinety-seven patients were randomised to romilkimab (n=48) or placebo (n=49) for 24 weeks. Least-squares mean (SE) change in mRSS was –4.76 (0.86) for romilkimab versus –2.45 (0.85) for placebo yielding a mean (SE) (90% CI) difference of –2.31 (1.21) (–4.32 to –0.31; p=0.0291, one-sided). Treatment-emergent AEs were balanced between placebo (n=41; 84%) and romilkimab (n=40; 80%). Most were mild-to-moderate and discontinuations were low (three overall). There were two deaths (one scleroderma renal crisis (romilkimab) and one cardiomyopathy (placebo)), neither were considered treatment related. Two patients in the placebo group had a cardiovascular treatment-emergent SAE (one cardiac failure, one cardiomyopathy), but there were no cardiac safety signals with romilkimab.ConclusionThis study demonstrated significant effects on skin changes with romilkimab in early dcSSc that require confirmation with a longer and more comprehensive phase III study to determine clinical relevance.Trial registration numberNCT02921971.

Double-blind, randomized phase III study to compare the efficacy and safety of CT-P6, trastuzumab biosimilar candidate versus trastuzumab as neoadjuvant treatment in HER2 positive early breast cancer (EBC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 510-510 ◽  
Author(s):  
Justin Stebbing ◽  
Yauheni Valerievich Baranau ◽  
Valery Baryash ◽  
Alexey Manikhas ◽  
Vladimir Moiseyenko ◽  
...  
Keyword(s):  
Neoadjuvant Treatment ◽  
Complete Response ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Her2 Positive ◽  
Double Blind ◽  
Secondary Endpoints ◽  
Phase Iii Study ◽  
To Receive ◽  
Related Reaction

510 Background: CT-P6 (C) is a proposed biosimilar to trastuzumab. This trial (NCT02162667) evaluated the similarity of C and trastuzumab in efficacy and safety for HER2+ EBC. Methods: 549 patients with HER2+ EBC were randomized to receive C (n=271) or trastuzumab (n=278) in combination with docetaxel (Cycles 1-4) and 5-fluorouracil, epirubicin, and cyclophosphamide (Cycles 5-8). C or trastuzumab was administered at 8 mg/kg (Cycle 1 only) followed by 6 mg/kg every 3 weeks. The primary endpoint was pathological complete response (pCR) rate at surgery. Secondary endpoints were overall response rate (ORR), PK, PD and safety. After surgery, patients received adjuvant C or trastuzumab to complete a total of 1-year treatment. Results: The pCR rate was 46.8% for C and 50.4% for trastuzumab. The 95% CIs for the risk ratio estimate were within the equivalence margin (0.74, 1.35) in PPS and ITT analyses. Other efficacy endpoints were similar between C and trastuzumab. The proportion of patients with at least 1 treatment-emergent SAE was 6.6% for C and 7.6% for trastuzumab. Only 1 patient in each group withdrew treatment due to significant LVEF decrease. Infusion-related reaction was reported for 8.5% of patients in C and 9.0% of patients in trastuzumab. Conclusions: This study demonstrated the similarity of efficacy in terms of pCR between CT-P6 and trastuzumab in EBC patients. Secondary efficacy endpoints also supported the similarity between CT-P6 and trastuzumab. CT-P6 was well tolerated with a similar safety profile to that of trastuzumab during the neoadjuvant period. Clinical trial information: NCT02162667. [Table: see text]

scholarly journals A multicenter, double-blind, randomized trial on the bleeding profile of a drospirenone-only pill 4 mg over nine cycles in comparison with desogestrel 0.075 mg

2019 ◽  
Vol 300 (6) ◽  
pp. 1805-1812 ◽  
Author(s):  
Santiago Palacios ◽  
Enrico Colli ◽  
Pedro-Antonio Regidor
Keyword(s):  
Daily Intake ◽  
Phase Iii ◽  
Chi Square ◽  
Double Blind ◽  
Registration Number ◽  
Chi Square Test ◽  
Phase Iii Study ◽  
Compliance Problem ◽  
Unscheduled Bleeding

Abstract Purpose A typical compliance problem in the use of traditional progestin-only pills is the irregular bleeding pattern and the strict daily intake. Desogestrel 75 mg has a 12-h missed-pill window; however, its poor cycle control limits a more common use. Methods A drospirenone (DRSP)-only pill was developed to improve the bleeding profile. Setting A phase III study in healthy women aged 18–45 years was performed to compare the bleeding profile and safety of a DRSP-only pill in a regime of 24 days of 4 mg of DRSP tablets followed by 4 days of placebo versus desogestrel 0.075 mg per day continuously over nine cycles. Population A total of 858 women with 6691 drospirenone and 332 women with 2487 desogestrel treatment cycles were analyzed. Main outcome measures The primary end point was the proportion of women with unscheduled bleeding/spotting in each cycle from cycles 2 to 9 and cumulative in cycles 2–4 and cycles 7–9. Results In each cycle, up to cycle 7, the proportion of women with unscheduled bleeding was statistically significantly lower in the DRSP group than in the DSG group (p = 0.0001, Chi-square test). Conclusions This report describes the improvement in bleeding profile of women using the new DRSP-only oral contraceptive in comparison to DSG, providing a better quality of live and adherence to the contraceptive method. EudraCT Registration Number: 2011-002396-42.

scholarly journals Phase III, randomised, double-blind, multicentre study to evaluate the efficacy and safety of vonoprazan compared with lansoprazole in Asian patients with erosive oesophagitis

Gut ◽  
2019 ◽  
Vol 69 (2) ◽  
pp. 224-230 ◽  
Author(s):  
Yinglian Xiao ◽  
Shutian Zhang ◽  
Ning Dai ◽  
Guijun Fei ◽  
Khean-Lee Goh ◽  
...  
Keyword(s):  
Los Angeles ◽  
Multicentre Study ◽  
Healing Rate ◽  
Erosive Oesophagitis ◽  
Phase Iii ◽  
Double Blind ◽  
Los Angeles Classification ◽  
Asian Patients ◽  
Registration Number ◽  
Secondary Endpoints

ObjectiveTo establish the non-inferior efficacy of vonoprazan versus lansoprazole in the treatment of Asian patients with erosive oesophagitis (EO).DesignIn this phase III, double-blind, multicentre study, patients with endoscopically confirmed EO were randomised 1:1 to receive vonoprazan 20 mg or lansoprazole 30 mg, once daily for up to 8 weeks. The primary endpoint was EO healing rate at 8 weeks. The secondary endpoints were EO healing rates at 2 and 4 weeks. Safety endpoints included treatment-emergent adverse events (TEAEs).ResultsIn the vonoprazan (n=238) and lansoprazole (n=230) arms, 8-week EO healing rates were 92.4% and 91.3%, respectively (difference 1.1% (95% CI –3.822% to 6.087%)). The respective 2-week EO healing rates were 75.0% and 67.8% (difference 7.2% (95% CI –1.054% to 15.371%)), and the respective 4-week EO healing rates were 85.3% and 83.5% (difference 1.8% (95% CI –4.763% to 8.395%)). In patients with baseline Los Angeles classification grade C/D, 2-week, 4-week and 8-week EO healing rates were higher with vonoprazan versus lansoprazole (2 weeks: 62.2% vs 51.5%, difference 10.6% (95% CI –5.708% to 27.002%); 4 weeks: 73.3% vs 67.2%, difference 6.2% (95% CI –8.884 to 21.223); and 8 weeks: 84.0% vs 80.6%, difference 3.4% (95% CI –9.187% to 15.993%)). Overall, EO healing rates appeared higher with vonoprazan versus lansoprazole. TEAE rates were 38.1% and 36.6% in the vonoprazan and lansoprazole group, respectively.ConclusionOur findings demonstrate the non-inferior efficacy of vonoprazan versus lansoprazole in terms of EO healing rate at 8 weeks in this population. Safety outcomes were similar in the two treatment arms.Trial registration numberNCT02388724.

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