Single-Dose Fosaprepitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting Associated With Cisplatin Therapy: Randomized, Double-Blind Study Protocol—EASE

2011 ◽  
Vol 29 (11) ◽  
pp. 1495-1501 ◽  
Author(s):  
Steven Grunberg ◽  
Daniel Chua ◽  
Anish Maru ◽  
José Dinis ◽  
Suzanne DeVandry ◽  
...  
Keyword(s):  
Single Dose ◽  
Complete Response ◽  
Double Blind Study ◽  
Double Blind ◽  
Neurokinin 1 ◽  
First Time ◽  
Delayed Phase ◽  
Cisplatin Therapy ◽  
Noninferiority Margin ◽  
Site Pain

Purpose Addition of aprepitant, a neurokinin-1 receptor antagonist (NK1RA), to an ondansetron and dexamethasone regimen improves prevention of chemotherapy-induced nausea/vomiting (CINV), particularly during the delayed phase (DP; 25 to 120 hours). Therefore, recommended antiemetic regimens include multiple-day NK1RA administration. Preliminary data suggested that single-dose aprepitant before chemotherapy could provide CINV protection throughout the overall risk phase (OP; 0 to 120 hours). This study compared a 3-day oral aprepitant schedule to a regimen containing a single dose of the intravenous NK1RA fosaprepitant. Patients and Methods A randomized, double-blind, active-control design was used to test whether fosaprepitant is noninferior to aprepitant. Patients receiving cisplatin ≥ 70 mg/m2 for the first time received ondansetron and dexamethasone with a standard aprepitant regimen (125 mg on day 1, 80 mg on day 2, 80 mg on day 3) or a single-dose fosaprepitant regimen (150 mg on day 1). The primary end point was complete response (CR; no vomiting, no rescue medication) during OP. Secondary end points were CR during DP and no vomiting during OP. Accrual of 1,113 evaluable patients per treatment arm was planned to confirm noninferiority with expected CR of 67.7% and noninferiority margin of minus 7 percentage points. Results A total of 2,322 patients were randomly assigned, and 2,247 were evaluable for efficacy. Antiemetic protection with aprepitant and fosaprepitant was equivalent within predefined bounds for noninferiority. Both regimens were well tolerated, although more frequent infusion site pain/erythema/thrombophlebitis was seen with fosaprepitant relative to aprepitant (2.7% v 0.3%, respectively). Conclusion Given with ondansetron and dexamethasone, single-dose intravenous fosaprepitant (150 mg) was noninferior to standard 3-day oral aprepitant in preventing CINV during OP and DP.

Safety of intravenous (IV) NEPA and oral NEPA for prevention of CINV in patients (pts) with breast cancer (BC) receiving anthracycline/cyclophosphamide (AC) chemotherapy (CT).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 11594-11594
Author(s):  
Lee S. Schwartzberg ◽  
Daniel Voisin ◽  
Giada Rizzi ◽  
Kamal Patel ◽  
Matti S. Aapro
Keyword(s):  
Single Dose ◽  
Safety Evaluation ◽  
Complete Response ◽  
Primary Objective ◽  
Double Blind Study ◽  
Infusion Site ◽  
Double Blind ◽  
Antiemetic Agent ◽  
Pivotal Study ◽  
Safety Population

11594 Background: NEPA, a combination antiemetic agent [NK1 receptor antagonist (RA) netupitant (oral) or fosnetupitant (IV) + 5-HT3RA palonosetron] offers 5-day CINV prevention with a single-dose. Unlike other IV NK1RAs, the fosnetupitant solution does not require a surfactant, emulsifier, or solubility enhancer and contains no allergenic excipients. In a Phase 3 study in pts receiving cisplatin-based CT, there were no infusion site or anaphylactic reactions related to IV NEPA. In contrast, hypersensitivity reactions and anaphylaxis have been reported with IV aprepitant, fosaprepitant and rolapitant, with the highest rate (35%) for fosaprepitant in the AC setting. This study (NCT03403712) evaluates the safety of IV NEPA in BC pts receiving repeat cycles of AC CT. Methods: This was a Phase 3b, double-blind study in females with BC naïve to highly/moderately emetogenic CT. Pts were randomized 1:1 to receive a single 30-min infusion of IV NEPA or a single oral NEPA capsule on Day 1, prior to AC. Oral dexamethasone was also given to all patients before CT. The primary objective was a safety evaluation of IV NEPA based primarily on treatment-emergent adverse events (TEAEs). No formal between groups statistical comparison was planned. Results: 402 pts were treated with IV NEPA or oral NEPA and included in the safety population. The AE profiles were similar for the two groups; cycle 1 results are reported (Table). Comparable complete response (no emesis, no rescue) rates were seen during the cycle 1 overall phase (0-120h) (73.0% IV NEPA, 77.2% oral NEPA). Conclusions: There were no infusion-site AEs related to IV NEPA and no anaphylaxis reported for either formulation. Consistent with the pivotal study, IV NEPA is safe and effective in pts receiving AC. As a simplified single-dose formulation, IV NEPA may be better tolerated than other NK1 RAs. Clinical trial information: NCT03403712. [Table: see text]

Evaluation of daily breakthrough chemotherapy-induced nausea and vomiting (CINV) rates in a phase III study of NEPA versus an aprepitant (APR)/granisetron (GRAN) regimen.

2017 ◽  
Vol 35 (31_suppl) ◽  
pp. 120-120 ◽  
Author(s):  
Eric Roeland ◽  
Gary Binder ◽  
Joseph Ma ◽  
Corinna Lanzarotti ◽  
Li Zhang
Keyword(s):  
Statistical Significance ◽  
Secondary Analysis ◽  
Complete Response ◽  
Phase Iii ◽  
Double Blind Study ◽  
Close Monitoring ◽  
Double Blind ◽  
Treatment Groups ◽  
The Difference ◽  
Delayed Phase

120 Background: Antiemetic trials typically evaluate CINV control during acute (Day 1), delayed (Days 2-5), and overall (Days 1-5) phases post-chemotherapy; the daily course of events is often unstudied in the delayed phase. In a head-to-head study evaluating NK1RA-containing regimens, a single dose of NEPA, an oral fixed combination of the NK1RA netupitant and 5-HT3RA palonosetron, was non-inferior to a 3-day regimen of APR and GRAN for overall complete response (no emesis/no rescue use) rates (74% NEPA vs 72% APR/GRAN) in 828 patients receiving cisplatin-based highly emetogenic chemotherapy (HEC). This secondary analysis explores daily rates of breakthrough CINV in this study. Methods: This was a double-blind study in chemotherapy-naïve patients with solid tumors. Daily rates of breakthrough CINV, defined as the % of patients with emesis and/or rescue use were calculated with differences between treatment groups evaluated by the Cochran-Mantel-Haenszel method stratified by sex. Results: While daily rates of patients with breakthrough CINV remained stable between 13%-15.1% for APR/GRAN, they declined from 15.5% to 8% over the 5 days for NEPA, with the difference between groups reaching statistical significance on Day 5 (Table). Percent of total patient days with CINV events were 11.7% [NEPA] and 14.0% [APR/GRAN]. The % of patients with ≥ 3 days of breakthrough CINV were 8.5% and 12.3%, respectively. Conclusions: In this study evaluating guideline-recommended antiemetic regimens for HEC, CINV was prevented in most patients during the overall phase yet breakthrough CINV on individual days differed between treatment groups. APR/GRAN showed a relatively constant rate over time, while NEPA rates decreased and patients had fewer total days with breakthrough. This suggests the need for close monitoring of CINV events during the delayed phase. [Table: see text]

scholarly journals A Phase 3, Randomized, Double-Blind Study Comparing Tedizolid Phosphate and Linezolid for Treatment of Ventilated Gram-Positive Hospital-Acquired or Ventilator-Associated Bacterial Pneumonia

2021 ◽  
Author(s):  
Richard G Wunderink ◽  
Antoine Roquilly ◽  
Martin Croce ◽  
Daniel Rodriguez Gonzalez ◽  
Satoshi Fujimi ◽  
...  
Keyword(s):  
Clinical Response ◽  
Bacterial Pneumonia ◽  
Double Blind Study ◽  
Phase 3 ◽  
Gram Positive ◽  
Double Blind ◽  
Intention To Treat ◽  
The Difference ◽  
Hospital Acquired ◽  
Noninferiority Margin

Abstract Background Hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP) are associated with high mortality rates. We evaluated the efficacy and safety of tedizolid (administered as tedizolid phosphate) for treatment of gram-positive ventilated HABP/VABP. Methods In this randomized, noninferiority, double-blind, double-dummy, global phase 3 trial, patients were randomized 1:1 to receive intravenous tedizolid phosphate 200 mg once daily for 7 days or intravenous linezolid 600 mg every 12 hours for 10 days. Treatment was 14 days in patients with concurrent gram-positive bacteremia. The primary efficacy end points were day 28 all-cause mortality (ACM; noninferiority margin, 10%) and investigator-assessed clinical response at test of cure (TOC; noninferiority margin, 12.5%) in the intention-to-treat population. Results Overall, 726 patients were randomized (tedizolid, n = 366; linezolid, n = 360). Baseline characteristics, including incidence of methicillin-resistant Staphylococcus aureus (31.3% overall), were well balanced. Tedizolid was noninferior to linezolid for day 28 ACM rate: 28.1% and 26.4%, respectively (difference, –1.8%; 95% confidence interval [CI]: –8.2 to 4.7). Noninferiority of tedizolid was not demonstrated for investigator-assessed clinical cure at TOC (tedizolid, 56.3% vs linezolid, 63.9%; difference, –7.6%; 97.5% CI: –15.7 to 0.5). In post hoc analyses, no single factor accounted for the difference in clinical response between treatment groups. Drug-related adverse events occurred in 8.1% and 11.9% of patients who received tedizolid and linezolid, respectively. Conclusions Tedizolid was noninferior to linezolid for day 28 ACM in the treatment of gram-positive ventilated HABP/VABP. Noninferiority of tedizolid for investigator-assessed clinical response at TOC was not demonstrated. Both drugs were well tolerated. Clinical Trials Registration NCT02019420.

Single dose oral ranitidine improves MRCP image quality: a double-blind study

2007 ◽  
Vol 62 (1) ◽  
pp. 53-57 ◽  
Author(s):  
M.T. Bowes ◽  
D.F. Martin ◽  
A. Melling ◽  
D. Roberts ◽  
H.-U. Laasch ◽  
...  
Keyword(s):  
Single Dose ◽  
Image Quality ◽  
Blind Study ◽  
Double Blind Study ◽  
Double Blind ◽  
Dose Oral

scholarly journals Comparison of Ondansetron with Gabapentin for prevention of intrathecal morphine induced pruritus

2019 ◽  
Vol 2 (3) ◽  
pp. 142-148
Author(s):  
Rohini Sigdel ◽  
Anil Shrestha ◽  
Roshana Amatya
Keyword(s):  
Single Dose ◽  
Intrathecal Morphine ◽  
Double Blind Study ◽  
Physical Status ◽  
Hyperbaric Bupivacaine ◽  
Double Blind ◽  
Subarachnoid Block ◽  
Significant Difference ◽  
Group 2 ◽  
To Receive

Background: Ondansetron has been used successfully for prophylaxis and treatment of intrathecal morphine induced pruritus. Gabapentin has anxiolytic, antiemetic, antipruritic effects and has also been shown to potentiate the analgesic effect of intrathecally or epidurally administered opioids. Materials and method: We compared the effectiveness of oral gabapentin with intravenous ondansetron to prevent incidence of intrathecal morphine induced pruritus. In a prospective, double-blind study, sixty patients aged 18-65 years with ASA physical status I and II undergoing surgery under subarachnoid block were randomized to receive placebo tablets (ondansetron group) or gabapentin 1200 mg (gabapentin group) 2 hours before surgery. Patients receiving placebo tablets received 8 mg of intravenous ondansetron and those receiving gabapentin received 4 ml of intravenous normal saline just prior to subarachnoid block with 3 ml of 0.5% hyperbaric bupivacaine plus 0.2 mg morphine. The incidence, onset, severity, location of pruritus and incidence of side effects were studied for next 24 hours. Results: The overall incidence of pruritus was 48.3%. The incidence, severity, location of pruritus was comparable between the two groups. There was significant difference between the onset of pruritus between groups (p=0.009). The incidence and grade of nausea vomiting, requirement of intraoperative sedation was comparable between groups. The incidence of urinary retention was significantly high in gabapentin group (p=0.020). Respiratory depression was observed in one patient. Conclusion: A single dose of 1200 mg oral gabapentin 2 hours before, is as effective as prophylactic intravenous ondansetron 8 mg for prevention of intrathecal morphine induced pruritus.

Randomized phase II trial of the neurokinin-1 receptor antagonist (NK-1 RA) casopitant mesylate with ondansetron (ond)/dexamethasone (dex) for chemotherapy-induced nausea/vomiting (CINV) in patients (pts) receiving highly emetogenic chemotherapy (HEC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 8513-8513 ◽  
Author(s):  
J. Rolski ◽  
R. Ramlau ◽  
M. Dediu ◽  
M. W. Russo ◽  
G. A. Ross ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Complete Response ◽  
Trend Test ◽  
Placebo Control ◽  
Double Blind ◽  
Therapy Regimen ◽  
Armitage Trend Test ◽  
Neurokinin 1 ◽  
Intent To Treat ◽  
Future Evaluation

8513 Background: A combination of a 5-HT3 receptor antagonist (5-HT3 RA) + dex is standard for prevention of CINV due to HEC. However, NK-1 RAs are now also of interest. The current trial evaluated casopitant mesylate, a potent, oral, selective NK-1 RA, in a triple therapy regimen with a 5-HT3 RA and dex in pts receiving HEC. Methods: In this multicenter, randomized, double-blind, placebo-controlled, dose-ranging, parallel group study, pts receiving HEC were stratified by gender and randomized among six arms. HEC consisted of regimens including cisplatin ≥ 70 mg/m2 IV over 1–4 hours (h) day 1 (D1). All pts received ond 32mg IV D1 and dex PO D1–4 with either placebo control, casopitant 50mg QD D1–3, casopitant 100mg QD D1–3, or casopitant 150mg QD D1–3. Pts on exploratory arms received ond/dex plus either casopitant 150 mg D1 only or aprepitant 125mg D1 and 80mg D2–3. The primary endpoint was complete response (CR) rate (no vomiting, retching, rescue medications or premature withdrawals) during the first 120 h following initiation of HEC. Target intent-to-treat (ITT) group enrollment was 82 pts per arm. Results: 493 enrolled patients comprised the ITT group. CR rate was 60% in the control arm; 76% for casopitant 50mg; 86% for 100mg; and 77% for 150mg (p=.0036, Cochran-Armitage trend test). CR rate was 75% with casopitant 150 mg D1 and 72% for 3-day aprepitant. CR rates at 24 h were similar in all groups (86%-96%). Casopitant prolonged time to emesis (p=.0029) and increased the proportion of pts without vomiting (p=.0122) relative to control. There were no differences in rates of nausea or use of rescue medication among groups. Adverse events were similar across all arms, with neutropenia, nausea, and hiccups (≤ 17%) as most common. All casopitant doses were generally well tolerated. Conclusions: The addition of casopitant to ond/dex at all doses tested and in 1- or 3-day administration regimens was well tolerated and significantly reduced CINV rates over a 5-day period in pts receiving HEC. The results of the exploratory 1-day regimen are of particular interest for future evaluation. [Table: see text]

Impact on patients’ daily life activities of NEPA, the oral fixed-dose combination of netupitant, a new NK1 receptor antagonist (RA), and palonosetron (PALO) plus dexamethasone (DEX) versus PALO plus DEX for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately emetogenic chemotherapy (MEC).

2013 ◽  
Vol 31 (31_suppl) ◽  
pp. 66-66 ◽  
Author(s):  
Matti S. Aapro ◽  
Giorgia Rossi ◽  
Giada Rizzi ◽  
Maria Elisa Borroni ◽  
Norman G. Nagl
Keyword(s):  
Complete Response ◽  
Emetogenic Chemotherapy ◽  
Fixed Dose Combination ◽  
Phase Iii ◽  
Fixed Dose ◽  
Double Blind ◽  
Efficacy Analysis ◽  
Daily Life Activities ◽  
Dose Combination ◽  
Delayed Phase

66 Background: Certain antiemesis guidelines recommend combining a 5-HT3 RA, a NK1RA and DEX for prevention of CINV associated with highly emetogenic chemotherapy (HEC) and with anthracycline + cyclophosphamide (AC)-based MEC. The objective of this analysis was to determine if using the oral fixed-dose combination NEPA prior to initiating AC-based chemotherapy resulted in no impact on daily living (NIDL) for patients. Methods: This phase III, multinational, randomized, double-blind, double-dummy, active-controlled, parallel group trial enrolled patients with solid tumors who were naïve to cytotoxics and scheduled to initiate AC-based chemotherapy. Patients received oral NEPA (netupitant 300 mg + PALO 0.5 mg) + oral DEX 12 mg on Day 1, or oral PALO 0.5 mg + oral DEX 20 mg on Day 1. The primary efficacy endpoint was Complete Response (CR: no emesis/no rescue medication) in the delayed phase (25-120 hours after chemotherapy) in cycle 1. Secondary endpoints including NIDL for patients was assessed using the Functional Living Index—Emesis (FLIE) during the first 120 hours. Results: 1,455 patients were randomized; 1,449 were included in the efficacy analysis. Significantly more patients achieved CR during the delayed phase in the NEPA arm compared with the PALO arm (76.9% vs 69.5%, respectively: p = 0.001). Significantly more patients in the NEPA arm reported NIDL via the FLIE (78.5% vs 72.1%: p = 0.005). A greater proportion of NEPA-treated patients reported no personal hardship imposed and no daily functioning affected (75.3% vs 70.5% and 77.1% vs 71.6%, respectively, as scored by the nausea domain of the FLIE; 95.2% vs 89.2% and 95.6% vs 89.2%, respectively, as scored by the vomiting domain of the FLIE). Adverse events were similar for both groups. Conclusions: NEPA significantly improved efficacy vs PALO for prevention of CINV in AC MEC and significantly more patients experienced NIDL compared to PALO. Both regimens were generally well tolerated.

Netupitant/palonosetron (NEPA) for prevention of delayed chemotherapy-induced nausea and vomiting (CINV) in multiple cycles of chemotherapy.

2015 ◽  
Vol 33 (29_suppl) ◽  
pp. 211-211
Author(s):  
Lee Steven Schwartzberg ◽  
Richard J. Gralla ◽  
Kimia Kashef ◽  
Hope Rugo
Keyword(s):  
Oral Dose ◽  
Single Oral Dose ◽  
Complete Response ◽  
Control Group ◽  
Double Blind ◽  
Report Data ◽  
Multiple Cycles ◽  
To Receive ◽  
Delayed Phase ◽  
Significant Nausea

211 Background: Prevention of CINV in the delayed phase (24-120 h post-chemotherapy) and over multiple cycles of chemotherapy remains a challenge. NEPA, a fixed combination of the NK1 receptor antagonist (RA) netupitant (300 mg) and the 5-HT3 RA palonosetron (PALO; 0.5 mg), has demonstrated efficacy in multiple studies, in both acute and delayed phases, during the first cycle of moderately or highly emetogenic chemotherapy (MEC and HEC, respectively) regimens. Two clinical trials evaluated NEPA over multiple cycles of chemotherapy. We report data for the delayed phase for each cycle. Methods: Both studies were Phase 3, double-blind, active-controlled studies. In study 1 (MEC), patients were randomized 1:1 to receive a single oral dose of NEPA (n = 724) or PALO 0.5 mg (n = 725) on Day 1; following cycle 1, patients could participate in a multi-cycle extension phase. In study 2 (MEC or HEC), patients were randomized 3:1 to receive a single oral dose of NEPA on Day 1 (n = 309) or oral aprepitant (APR) 125 mg plus oral PALO 0.5 mg on Day 1, then APR 80 mg/d on days 2 and 3 of each cycle (n = 103). In both studies, all patients also received dexamethasone. Efficacy endpoints included complete response (CR; no emesis, no rescue medication) and no significant nausea. Results: In both studies, CR rates were consistently numerically higher with NEPA (Study 1 range: 77%-89%; Study 2 range: 83%-93%) than with PALO (Study 1; range: 69%-83%) or APR/PALO (Study 2; range: 78%-88%) in each cycle up to cycle 6 (Table). In both studies, rates of no significant nausea in the NEPA group were similar to or higher than in the control group. NEPA was well tolerated in both studies; treatment-related adverse events included constipation and headache. Conclusions: These studies demonstrate sustained efficacy of NEPA (administered as a single dose on Day 1) across multiple cycles of MEC or HEC for prevention of CINV in the delayed phase. Clinical trial information: 2009-016775-30; 2010-023297-39. [Table: see text]

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