scholarly journals 700. Safety and Efficacy of Omadacycline in Patients with Diabetes in Phase 3 Clinical Studies

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S316-S317
Author(s):  
Manjunath P Pai ◽  
Mark H Wilcox ◽  
Marla Curran ◽  
Surya Chitra ◽  
Lynne Garrity-Ryan ◽  
...  
Keyword(s):  
Clinical Response ◽  
Medical History ◽  
Clinical Success ◽  
Oral Medication ◽  
Phase 3 ◽  
Safety And Efficacy ◽  
Skin Structure ◽  
Patients With Diabetes ◽  
Poor Treatment ◽  
History Of

Abstract Background The risk of serious infections and poor treatment outcomes is reported to be higher in patients with diabetes compared with the general population. Omadacycline (OMC) is an intravenous (IV) and oral aminomethylcycline antibiotic approved in the US to treat acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP) in adults. Here we assessed safety and efficacy results from OMC Phase 3 studies (ABSSSI: Omadacycline in Acute Skin and skin structure Infections Study [OASIS]-1 and OASIS-2; CABP: Omadacycline for Pneumonia Treatment In the Community study [OPTIC]), by diabetes history. Methods In OASIS-1 (IV to optional oral medication) and OASIS-2 (oral only), patients were randomized to OMC or linezolid (LZD) for 7–14 days. In OPTIC, patients were randomized to IV OMC or moxifloxacin (MOX) for 7–14 days, with optional transition to oral medication. Data from OASIS-1 and OASIS-2 were pooled, and patient subgroups were defined by any medical history of diabetes (type 1, type 2, or unspecified), or no medical history of diabetes. Efficacy outcomes were early clinical response (ECR) and investigator’s assessment of clinical response at post-treatment evaluation (PTE), as defined for each indication. Safety was assessed by treatment-emergent adverse events (TEAEs) and laboratory measures, and data were pooled across the three studies. Results A total of 2,150 patients were included, of whom 238 (11.1%) had any history of diabetes (n = 105 for ABSSSI, n = 133 for CABP). In the pooled ABSSSI studies and the CABP study, clinical success at ECR and PTE was similar between patients with or without diabetes, and between OMC and the respective comparator (figure). TEAEs and serious TEAEs, respectively, were reported in similar numbers of OMC-, LZD-, and MOX-treated patients with diabetes (41.8–49.3%, 4.5–7.0%) and without (41.2–48.3%, 1.6–6.9%). Rates of nausea and vomiting, respectively, in patients with diabetes were similar across treatment arms: OMC (5.0%, 5.0%), LZD (7.5%, 6.0%), MOX (7.0%, 2.8%). Conclusion Omadacycline efficacy and safety were similar and consistent in patients with or without diabetes. Disclosures All authors: No reported disclosures.

scholarly journals Ceftobiprole Compared With Vancomycin Plus Aztreonam in the Treatment of Acute Bacterial Skin and Skin Structure Infections: Results of a Phase 3, Randomized, Double-blind Trial (TARGET)

2020 ◽  
Author(s):  
J Scott Overcash ◽  
Charles Kim ◽  
Richard Keech ◽  
Illia Gumenchuk ◽  
Borislav Ninov ◽  
...  
Keyword(s):  
Clinical Response ◽  
Clinical Success ◽  
Laboratory Data ◽  
European Medicines Agency ◽  
Success Rates ◽  
Phase 3 ◽  
Gram Positive ◽  
Double Blind ◽  
Gram Negative ◽  
Skin Structure

Abstract Background The development of novel broad-spectrum antibiotics, with efficacy against both gram-positive and gram-negative bacteria, has the potential to enhance treatment options for acute bacterial skin and skin structure infections (ABSSSIs). Ceftobiprole is an advanced-generation intravenous cephalosporin with broad in vitro activity against gram-positive (including methicillin-resistant Staphylococcus aureus) and gram-negative pathogens. Methods TARGET was a randomized, double-blind, active-controlled, parallel-group, multicenter, phase 3 noninferiority study that compared ceftobiprole with vancomycin plus aztreonam. The Food and Drug Administration-defined primary efficacy endpoint was early clinical response 48–72 hours after treatment initiation in the intent-to-treat (ITT) population and the European Medicines Agency-defined primary endpoint was investigator-assessed clinical success at the test-of-cure (TOC) visit. Noninferiority was defined as the lower limit of the 95% CI for the difference in success rates (ceftobiprole minus vancomycin/aztreonam) >−10%. Safety was assessed through adverse event and laboratory data collection. Results In total, 679 patients were randomized to ceftobiprole (n = 335) or vancomycin/aztreonam (n = 344). Early clinical success rates were 91.3% and 88.1% in the ceftobiprole and vancomycin/aztreonam groups, respectively, and noninferiority was demonstrated (adjusted difference: 3.3%; 95% CI: −1.2, 7.8). Investigator-assessed clinical success at the TOC visit was similar between the 2 groups, and noninferiority was demonstrated for both the ITT (90.1% vs 89.0%) and clinically evaluable (97.9% vs 95.2%) populations. Both treatment groups displayed similar microbiological success and safety profiles. Conclusions TARGET demonstrated that ceftobiprole is noninferior to vancomycin/aztreonam in the treatment of ABSSSIs, in terms of early clinical response and investigator-assessed clinical success at the TOC visit. Clinical Trials Registration NCT03137173.

scholarly journals Telavancin for Acute Bacterial Skin and Skin Structure Infections, aPost HocAnalysis of the Phase 3 ATLAS Trials in Light of the 2013 FDA Guidance

2015 ◽  
Vol 59 (10) ◽  
pp. 6170-6174 ◽  
Author(s):  
Richard Pushkin ◽  
Steven L. Barriere ◽  
Whedy Wang ◽  
G. Ralph Corey ◽  
Martin E. Stryjewski
Keyword(s):  
Clinical Response ◽  
Lesion Size ◽  
Phase 3 ◽  
Two Phase ◽  
Skin Structure ◽  
Fda Guidance ◽  
Complicated Skin ◽  
Clinical Responses ◽  
Cure Rates ◽  
Post Hoc

ABSTRACTTwo phase 3 ATLAS trials demonstrated noninferiority of telavancin compared with vancomycin for complicated skin and skin structure infections. Data from these trials were retrospectively evaluated according to 2013 U.S. Food and Drug Administration (FDA) guidance on acute bacterial skin and skin structure infections. Thispost hocanalysis included patients with lesion sizes of ≥75 cm2and excluded patients with ulcers or burns (updated all-treated population;n= 1,127). Updated day 3 (early) clinical response was defined as a ≥20% reduction in lesion size from baseline and no rescue antibiotic. Updated test-of-cure (TOC) clinical response was defined as a ≥90% reduction in lesion size, no increase in lesion size since day 3, and no requirement for additional antibiotics or significant surgical procedures. Day 3 (early) clinical responses were achieved in 62.6% and 61.0% of patients receiving telavancin and vancomycin, respectively (difference, 1.7%, with a 95% confidence interval [CI] of −4.0% to 7.4%). Updated TOC visit cure rates were similar for telavancin (68.0%) and vancomycin (63.3%), with a difference of 4.8% (95% CI, −0.7% to 10.3%). Adopting current FDA guidance, this analysis corroborates previous noninferiority findings of the ATLAS trials of telavancin compared with vancomycin.

scholarly journals A pooled analysis of patients with wound infections in the Phase 3 REVIVE trials: randomized, double-blind studies to evaluate the safety and efficacy of iclaprim versus vancomycin for treatment of acute bacterial skin and skin structure infections

2020 ◽  
Vol 69 (4) ◽  
pp. 625-630
Author(s):  
Stephanie Noviello ◽  
G. Ralph Corey ◽  
Thomas L. Holland ◽  
Thomas Lodise ◽  
William O’Riordan ◽  
...  
Keyword(s):  
Clinical Response ◽  
Safety Profile ◽  
Wound Infections ◽  
Phase 3 ◽  
Gram Positive ◽  
Two Phase ◽  
Double Blind ◽  
Skin Structure ◽  
Treatment Difference ◽  
Vancomycin Treatment

Introduction. Iclaprim is a diaminopyrimidine antibiotic for the treatment of acute bacterial skin and skin structure infections (ABSSSI) due to Gram-positive pathogens. Aim. This analysis evaluates patients with wound infections from two Phase 3 trials of ABSSSI. Methodology. Six-hundred-two patients with wound infections from two Phase 3, double-blinded, randomized, multicenter, active controlled trials (REVIVE-1/–2) were evaluated in a post hoc analysis of iclaprim 80 mg compared with vancomycin 15 mg kg–1 administered intravenously every 12 h for 5–14 days. The primary endpoint was to determine whether iclaprim was non-inferior (10 % margin) to vancomycin in achieving a ≥20 % reduction from baseline in lesion size 48–72 h after starting study drug (early clinical response [ECR]). Safety was assessed. Results. In REVIVE-1, ECR was 83.5 % with iclaprim versus 79.7 % with vancomycin (treatment difference 3.77%, 95 % CI −4.50%, 12.04%). In REVIVE-2, ECR was 82.7 % with iclaprim versus 76.3 % with vancomycin (treatment difference 6.38%, 95 % CI −3.35%, 16.12%). In the pooled dataset, iclaprim had similar ECR rates compared with vancomycin among wound infection patients (83.2 % vs 78.2 %) with a treatment difference of 5.01 % (95 % CI −1.29%, 11.32%). The safety profile was similar in iclaprim- and vancomycin-treated patients, except for a higher incidence of diarrhea with vancomycin (n=17) compared with iclaprim (n=6) and fatigue with iclaprim (n=17) compared with vancomycin (n=8). Conclusion. Based on early clinical response, iclaprim achieved non-inferiority to vancomycin with a similar safety profile in patients with wound infections suspected or confirmed as caused by Gram-positive pathogens. Iclaprim may be a valuable treatment option for wound infections.

Safety and Efficacy of Various Intravenous Insulin Infusion Rates in Patients With and Without Diabetes Presenting With Hypertriglyceridemia

2022 ◽  
pp. 106002802110701
Author(s):  
Francisco Ibarra ◽  
Kaitlyn Loi ◽  
Ann W. Vu
Keyword(s):  
Medical History ◽  
Insulin Infusion ◽  
Case Reports ◽  
Retrospective Chart Review ◽  
Acute Management ◽  
Past Medical History ◽  
Safety And Efficacy ◽  
Intravenous Insulin ◽  
Number Of Patients ◽  
History Of

Background The use of IV insulin infusions in the acute management of hypertriglyceridemia has only been evaluated in small observational studies and case reports. Objective To evaluate the safety and efficacy of IV insulin infusions in the acute management of hypertriglyceridemia. Methods This was a retrospective chart review of adult patients who received an IV insulin infusion for the acute management of hypertriglyceridemia. The primary efficacy and safety outcomes were the number of patients who achieved a triglyceride level <500 mg/dL and experienced hypoglycemia (<70 mg/dL), respectively. A subgroup analysis was performed to compare outcomes between patients with and without diabetes, in addition to the IV insulin infusion rate received. Results In the total population (n = 51), there were no statistically significant differences between the insulin intensity groups in the number of patients who achieved TG levels <500 mg/dL. Compared to patients with a past medical history of diabetes, more patients without a past medical history of diabetes achieved triglyceride levels <500 mg/dL (14% vs 53%, respectively, P < 0.001). The number of hypoglycemic events observed in patients with and without a past medical history of diabetes were 5 (14%) and 4 (27%), respectively ( P = 0.023). Conclusion and Relevance Our findings suggest that patients who present with lower initial TG levels are more likely to achieve TG levels <500 mg/dL. To minimize the risk of hypoglycemia providers should consider prescribing a concomitant dextrose infusion and limiting IV insulin infusion rates ≤ 0.075 units/kg/h.

scholarly journals Tedizolid and Linezolid for Treatment of Acute Bacterial Skin and Skin Structure Infections of the Lower Extremity versus Non–Lower-Extremity Infections

2017 ◽  
Vol 107 (4) ◽  
pp. 264-271 ◽  
Author(s):  
Warren S. Joseph ◽  
Darren Culshaw ◽  
Steven Anuskiewicz ◽  
Carisa De Anda ◽  
Philippe Prokocimer
Keyword(s):  
Lower Extremity ◽  
Clinical Response ◽  
The United States ◽  
The European Union ◽  
Phase 3 ◽  
Two Phase ◽  
Once Daily ◽  
Therapy Evaluation ◽  
Skin Structure ◽  
Post Therapy

Background: Tedizolid phosphate, the prodrug of the oxazolidinone tedizolid, has been approved in a number of countries, including the United States, those in the European Union, and Canada, for treatment of patients with acute bacterial skin and skin structure infections (ABSSSI). Two phase 3 trials demonstrated the noninferior efficacy of tedizolid (200 mg once daily for 6 days) to linezolid (600 mg twice daily for 10 days) in patients with ABSSSI. Because of the challenges of treating lower-extremity ABSSSI, the efficacy and safety of tedizolid and linezolid for treating lower-extremity versus non–lower-extremity infections were compared. Methods: This was a post hoc analysis of pooled data from patients with lower-extremity infections enrolled in two phase 3 studies, ESTABLISH-1 (NCT01170221) and ESTABLISH-2 (NCT01421511), comparing tedizolid to linezolid in patients with ABSSSI. Results: Lower-extremity ABSSSI were present in 40.7% of tedizolid-treated and 42.2% of linezolid-treated patients. Methicillin-resistant Staphylococcus aureus (MRSA) was present in 34.7% of all patients with a baseline causative pathogen. Early clinical responses at 48 to 72 hours and investigator-assessed responses at the post-therapy evaluation were similar between tedizolid and linezolid, regardless of ABSSSI type. With both treatments, the early clinical response was slightly higher in patients with non–lower-extremity infection than in those with lower-extremity ABSSSI (tedizolid, 84.8% versus 77.0%; linezolid, 81.4% versus 76.6%, respectively); however, by the post-therapy evaluation visit, response rates were similar (tedizolid, 87.1% versus 86.3%; linezolid, 86.6% versus 87.2%, respectively). Gastrointestinal adverse events and low platelet counts were observed more frequently with linezolid treatment. Conclusions: Post-therapy evaluations showed that the clinical response of lower-extremity ABSSSI to tedizolid and linezolid was comparable to that of ABSSSI in other locations. A short 6-day course of once-daily tedizolid was as effective as a 10-day course of twice-daily linezolid in treating patients with lower-extremity ABSSSI.

scholarly journals 717. Lefamulin (LEF) vs. Moxifloxacin (MOX) in Patients With Community-Acquired Bacterial Pneumonia (CABP) at Risk for Poor Efficacy or Safety Outcomes: Pooled Subgroup Analyses From the Lefamulin Evaluation Against Pneumonia (LEAP) 1 and LEAP 2 Phase 3 Noninferiority Clinical Trials

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S322-S323
Author(s):  
Jennifer Schranz ◽  
Lisa Goldberg ◽  
Anita F Das ◽  
Elizabeth Alexander ◽  
Gregory J Moran ◽  
...  
Keyword(s):  
At Risk ◽  
Clinical Response ◽  
Study Drug ◽  
The United States ◽  
Chronic Obstructive ◽  
Phase 3 ◽  
Safety Concerns ◽  
Safety Outcomes ◽  
Patients At Risk ◽  
History Of

Abstract Background In the United States, CABP is the second most common cause of hospitalization and a leading cause of infectious death. Patients with chronic obstructive pulmonary disease (COPD)/asthma or diabetes are at risk for CABP and associated mortality. Similarly, patients with underlying cardiac or liver disease are at risk for potential cardiac or liver toxicities, respectively, associated with CABP antimicrobials, and patients aged ≥65 years are at risk for both efficacy/safety concerns. We report pooled efficacy/safety outcomes in at-risk subgroups from the LEAP 1 and 2 phase 3 trials. Methods In LEAP 1, patients with CABP (PORT III–V) received IV LEF 150 mg q12h for 5–7 days or MOX 400mg q24h for 7 days, with optional IV-to-oral switch (600 mg LEF q12h or 400 mg MOX q24h). In LEAP 2, patients with CABP (PORT II–IV) received oral LEF 600 mg q12h for 5 days or MOX 400 mg q24h for 7 days. Both studies assessed early clinical response (ECR; 96 ± 24 hours after first dose) in the intent-to-treat (ITT; all randomized patients) population (FDA primary endpoint) and investigator assessment of clinical response (IACR) at test-of-cure (TOC; 5–10 days after last dose) in the modified ITT (≥1 study drug dose) and clinically evaluable (met predefined evaluability criteria) populations (EMA coprimary endpoints). Pooled analyses used a 10% noninferiority margin. Safety was assessed in all randomized and treated patients. Results 1289 ITT patients were randomized to LEF (n = 646) or MOX (n = 643); of whom, 297 (23.0%) were aged 65–74 years and 220 (17.1%) were ≥75 years; 232 patients (18.0%) had COPD/asthma and 168 (13.0%) had diabetes mellitus (DM). At baseline, 501 patients (38.9%) had history of hypertension, 73 (5.7%) had history of arrhythmia, and 263 (20.4%) had transaminitis. The figure shows efficacy by age and in COPD/asthma and DM patients. Treatment-emergent adverse events, electrocardiogram assessments, and laboratory results in patients at risk for cardiac and hepatic safety concerns are shown in Tables 1 and 2. Conclusion In pooled analyses of LEAP 1 and 2, LEF efficacy was high and similar to MOX in patients at risk of efficacy concerns and LEF showed a safety profile similar to that of MOX in patients at risk of safety concerns. LEF is a promising new option for IV/oral monotherapy of CABP in patients at risk of poor outcomes due to CABP or to antimicrobial therapy for CABP. Disclosures All authors: No reported disclosures.

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