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]

Antiemetic efficacy of intravenous (IV) NEPA in patients with breast cancer (BC) receiving anthracycline/cyclophosphamide (AC) chemotherapy.

2019 ◽  
Vol 37 (31_suppl) ◽  
pp. 115-115
Author(s):  
Lee S. Schwartzberg ◽  
Matti S. Aapro
Keyword(s):  
Single Dose ◽  
Complete Response ◽  
Hypersensitivity Reactions ◽  
Infusion Site ◽  
Double Blind ◽  
Multi Agent ◽  
Presentation Methods ◽  
Chemotherapy Patients ◽  
Favorable Safety ◽  
To Receive

115 Background: The complexity of administering multi-agent prophylactic antiemetic combinations required to prevent chemotherapy-induced nausea and vomiting (CINV) may contribute to poor guideline adherence seen in multiple studies. NEPA, a combination antiemetic of an NK1 receptor antagonist (RA) [netupitant (oral)/fosnetupitant (IV)] and 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, thereby minimizing infusion-related toxicities that have been reported with other NK1RAs. This study previously reported the safety of IV NEPA in BC patients receiving repeat cycles of AC; there were no infusion-site or hypersensitivity reactions related to IV NEPA reported. The efficacy results of this study are the focus of this presentation. Methods: This was a Phase 3b, double-blind safety study in females with BC naïve to highly/moderately emetogenic chemotherapy. Patients 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 AC on Day 1 only. Complete response (CR: no emesis, no rescue) and no significant nausea (NSN: < 25mm on 100mm VAS scale) rates were calculated daily during the 5 days (0-120 h) post-AC in Cycle 1. No formal statistical comparison between groups was planned. Results: 402 total patients were included in the analysis. Most patients were white (93%) with ECOG status of 0 (75%); the mean age was 55 years. Comparable CR and NSN rates were seen for IV and oral NEPA during each of the 5 days post-AC. Conclusions: As a simplified single-dose formulation, IV NEPA showed high response rates in BC patients receiving AC, with favorable safety as no treatment-related infusion-site/hypersensitivity reactions were reported. Clinical trial information: NCT03403712. [Table: see text]

Mono- and diglycerides improve lutein absorption in healthy adults: a randomised, double-blind, cross-over, single-dose study

2017 ◽  
Vol 118 (10) ◽  
pp. 813-821 ◽  
Author(s):  
Barbara J. Marriage ◽  
Jennifer A. Williams ◽  
Yong S. Choe ◽  
Kevin C. Maki ◽  
Mustafa Vurma ◽  
...  
Keyword(s):  
Single Dose ◽  
Peak Level ◽  
Study Data ◽  
Primary Objective ◽  
Healthy Adults ◽  
Double Blind Study ◽  
Double Blind ◽  
Single Dose Study ◽  
High Oleic ◽  
Time To Peak

AbstractWith the association between increased carotenoid intake and lower risk of chronic diseases, the absorption of lutein from the diet becomes an important factor in its delivery and physiological action. The primary objective of this study was to gain an understanding of how a new formulation technology (mixture of mono- and diglycerides (MDG)), affected lutein absorption. Subjects (n24) were randomised in a cross-over, double-blind study to receive a single dose of 6 mg lutein (FloraGLO 20 %) provided as capsules containing either high-oleic safflower (SAF) oil or a MDG oil. Subjects receiving a single dose of lutein in MDG showed a significantly greater change from baseline (0 h) to 4, 6, 8, 12, 24, 48 and 336 h (P<0·05) and baseline adjusted AUC for plasma lutein at 48 and 336 h (P<0·001) as compared with subjects given lutein in SAF. Analysis of the 48 h absorption kinetics of lutein showed that the time to peak level of lutein (12 h) was the same for SAF and MDG groups, but the change in plasma lutein at 12 and 48 h were 129 and 320 % higher, respectively, for MDG compared with SAF. This difference continued as the adjusted AUC 0–48 and 0–336 h for the MDG group was 232 and 900 % higher, respectively, v. SAF. The study data show that by changing the lipid that is combined with a lutein supplement results in significant increases in lutein absorption in healthy adults.

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.

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

Olanzapine for Prevention of Vomiting in Children and Adolescents Receiving Highly Emetogenic Chemotherapy: Investigator-Initiated, Randomized, Open-Label Trial

2020 ◽  
Vol 38 (32) ◽  
pp. 3785-3793 ◽  
Author(s):  
Ramavath D. Naik ◽  
Sreenivas V ◽  
Vishwajeet Singh ◽  
Ashwati S. Pillai ◽  
Deepa Dhawan ◽  
...  
Keyword(s):  
Safety Evaluation ◽  
Complete Response ◽  
Primary Objective ◽  
Emetogenic Chemotherapy ◽  
Control Group ◽  
Study Group ◽  
Open Label ◽  
Highly Emetogenic Chemotherapy ◽  
Acute Period ◽  
Open Label Trial

PURPOSE Chemotherapy-induced nausea and vomiting (CINV) is a significant toxicity of chemotherapy. Olanzapine is recommended in adult patients for the prevention of CINV but has not been prospectively investigated in children. METHODS This investigator-initiated, randomized, open-label trial evaluated olanzapine in children (ages 5-18 years) scheduled to receive the first cycle of highly emetogenic chemotherapy (HEC). All participants received aprepitant, ondansetron, and dexamethasone during and 2 days after chemotherapy. Participants in the study group additionally received oral olanzapine 0.14 mg/kg/day (rounded to the nearest 2.5 mg; maximum, 10 mg) during the chemotherapy block and 3 days postchemotherapy. The primary objective was to compare complete response (CR) rates (no vomiting and no rescue medication) between the groups in the acute, delayed, and overall periods. Nausea comparison and safety evaluation were secondary and additional objectives, respectively. The collection of outcomes and adverse events was performed daily until the completion of the overall period. RESULTS A total of 240 patients underwent randomization. We performed a modified intention-to-treat analysis on 231 patients (116 in the control group and 115 in the study group). A higher proportion of patients in the olanzapine group achieved CR in the acute period (78% v 59%; P = .001), delayed period (74% v 47%; P < .001) and overall period (64% v 38%; P < .001) than in the control group. The proportion of patients with no nausea was significantly higher in the olanzapine group in the acute period (74% v 52%; P < .001), delayed period (74% v 47%; P < .001), and overall period (64% v 37%; P < .001). Grade 1/2 somnolence was greater in the olanzapine group (35% v 11%; P < .001). There was no grade 3/4 somnolence reported. CONCLUSION Olanzapine significantly improved CR rates for vomiting in children receiving the first cycle of HEC.

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.

scholarly journals An Integrated Efficacy and Safety Analysis of Single-Dose Secnidazole 2 g in the Treatment of Bacterial Vaginosis

2020 ◽  
Vol 27 (2) ◽  
pp. 523-528
Author(s):  
Helen Pentikis ◽  
Nikki Adetoro ◽  
Diane Tipping ◽  
Sharon Levy
Keyword(s):  
Single Dose ◽  
Bacterial Vaginosis ◽  
Integrated Analysis ◽  
Adult Women ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Study Visit ◽  
Pivotal Study ◽  
The Us ◽  
Dose Oral

AbstractBacterial vaginosis (BV) is the most common gynecologic infection in women aged 14 to 49 years. Currently recommended treatments require extended dosing and are thus associated with poor adherence. A single-dose oral granule formulation of secnidazole 2 g (SOLOSEC™ [secnidazole], Symbiomix Therapeutics, a Lupin company, Baltimore, MD), a 5-nitroimidazole antibiotic with antimicrobial activity, has been approved by the US Food and Drug Administration for the treatment of BV in adult women. As part of the US registration package, two randomized, double-blind, placebo-controlled clinical studies were conducted to confirm the efficacy and safety of a novel single-dose oral formulation of secnidazole 2 g. This is an integrated analysis of efficacy and safety results from these studies, pivotal study 1 and pivotal study 2. By combining the results of the two studies, relevant information is presented especially when considering the effect of secnidazole on patients with recurrent episodes of BV and the difference in effect on patients of black race. Single-dose secnidazole 2 g was statistically superior to placebo on all primary and secondary efficacy outcomes in both trials, including clinical outcome responder rate (P < 0.001), achievement of Nugent scores in the normal range of 0 to 3 (P < 0.001), greater numbers of patients as therapeutic outcome responders at the test of cure/end of study visit on days 21–30 (P < 0.001), and fewer patients requiring additional treatment at the test of cure/end of study visit (P < 0.001), supporting the role for single oral dose secnidazole 2 g granules as treatment for women with BV.

Interaction between Paracetamol and Warfarin: A Double-Blind Placebo-Controlled Randomised Study.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4153-4153
Author(s):  
Isabelle Mahe ◽  
Nathalie Bertrand ◽  
Ludovic Drouet ◽  
Guy Simoneau ◽  
Claire Bal dit Sollier ◽  
...  
Keyword(s):  
Oral Anticoagulants ◽  
Primary Objective ◽  
Double Blind Study ◽  
Factor V ◽  
Clotting Factors ◽  
Double Blind ◽  
Randomised Study ◽  
Factor Ii ◽  
The Mean ◽  
Clinically Significant

Abstract Background: Paracetamol is the gold standard antalgic and antipyretic therapy for patients receiving oral anticoagulants. Paracetamol and anticoagulant are therefore often concomitantly prescribed. The literature reports conflicting data about this association, concluding sometimes to the existence of an interaction and sometimes not. The primary objective of the study is to assess the effect of paracetamol on the anticoagulant effect of warfarin in usual conditions. Methods: Patients on stable oral anticoagulation (warfarin with a target INR between 2 and 3) for at least 1 month have been included in a prospective randomised double blind study, cross-over controlled versus placebo. They randomsuccessively received for a 14 days-period paracetamol (at 1g four times daily) and placebo. Both periods were separated by a wash-out period lasting at least 2 weeks. INR, factors II, V, VII, X were measured during each period before the intake of the study-treatment and 12h after the intake at day 2, 4, 7, 9, 11 and 14. Results: 20 patients were included. On paracetamol, the mean maximal INR increase observed was 1.01 ± 0.45 versus 0.27 ± 0.28 on placebo, p=0.003. The mean maximal INR was higher on paracetamol than on placebo (3.45 vs 2.66, p=0.01). A clinically significant increase of INR (above 0.5) was observed in 17 out of 19 patients on paracetamol as compared to 3 out of 19 patients on placebo. Factor II, VII, X levels were significantly decreased on paracetamol while there was no difference in factor V levels. Discussion: Paracetamol at 4g/d induced a significant increase in INR in patients on a stable anticoagulation with warfarin. It results in an increase in the risk of bleeding of the warfarin. The mechanism of the interaction may be a metabolit of the paracetamol, inhibiting of enzymes involved in the synthesis of the vitamino-K dependent clotting factors.

Efficacy and tolerability of bevacizumab (BEV) plus capecitabine and cisplatin (XP) in Chinese patients (pts) with locally advanced or metastatic gastric/gastroesophageal junction cancer (AGC): Results from the AVATAR study.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 73-73 ◽  
Author(s):  
Lin Shen ◽  
Jin Li ◽  
Jian-Ming Xu ◽  
Hong-Ming Pan ◽  
Guanghai Dai ◽  
...  
Keyword(s):  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Chinese Patients ◽  
Double Blind Study ◽  
Double Blind ◽  
Gastroesophageal Junction Cancer ◽  
The Difference ◽  
Grade 3

73 Background: In the AVAGAST study, chemotherapy (fluoropyrimidine and cisplatin) + BEV did not significantly improve overall survival (OS) vs. chemotherapy + placebo. Geographic differences in efficacy were observed, but only 12 Chinese pts were included. AVATAR, a study similar in design to AVAGAST, is a randomized double-blind study conducted exclusively in China in pts with AGC. Methods: Pts aged >18 years with gastric adenocarcinoma were randomized 1:1 to XP + BEV 7.5 mg/kg or placebo + XP. The primary objective was OS; secondary objectives included progression-free survival (PFS) and safety. Results: Baseline characteristics of the 202 pts were well balanced. The primary efficacy endpoint of improved OS in the BEV arm was not met (HR 1.11, 95% CI 0.79–1.56; p=0.5567; see table ). BEV + XP was well tolerated. Grade 3–5 adverse events (AEs) and serious AEs were 60% and 19% for BEV and 68% vs. 21% for placebo, respectively. Grade 3–5 AEs of special interest with BEV occurred in 8% of BEV pts and 15% of placebo pts; the difference was mainly due to grade 3–5 haemorrhage (BEV 4%, placebo 12%). Conclusions: Addition of BEV to XP in Chinese pts with AGC did not significantly improve outcomes in AVATAR. The results from AVATAR are consistent with the findings seen in the Asian sub-population of the previous AVAGAST study. [Table: see text]

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