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]

Phase III study of sustained release granisetron (APF530) compared to palonosetron for the prevention of chemotherapy-induced nausea and vomiting (CINV)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9627-9627 ◽  
Author(s):  
J. J. Grous ◽  
E. Riegel ◽  
N. Gabrail ◽  
V. Charu ◽  
R. Arevalo-Araujo ◽  
...  
Keyword(s):  
Acute Phase ◽  
Complete Response ◽  
Phase Iii ◽  
Sustained Drug Release ◽  
Phase Iii Study ◽  
Multiple Cycles ◽  
The Difference ◽  
To Receive ◽  
Delayed Phase ◽  
Polymeric Formulation

9627 Background: APF530 is a polymeric formulation of granisetron providing sustained drug release over 5 days. Two doses (5 and 10 mg) of subcutaneous APF530 were evaluated in comparison to 0.25 mg intravenous palonosetron. Efficacy was evaluated in acute (0–24 hrs) and delayed (24–120 hrs) CINV among patients receiving moderate (MEC) or highly (HEC) emetogenic chemotherapy. Methods: Randomized, blinded patients (n=1,395) were stratified into MEC or HEC according to Hesketh et al 1999, and assigned to receive either dose of APF530 or palonosetron. Dexamethasone use was standardized based on the emetogenic strata. Patient diaries recorded emetic episodes, nausea and rescue medications over a 5-day period. Primary endpoint was Complete Response (CR), defined as no emetic episodes and no rescue medication. Non-inferiority to palonosetron was declared if the lower bound of the CI for the difference was above -15%. Results: APF530 was well tolerated. Adverse events were consistent with those previously reported for granisetron. For APF530 Tmax was observed about 24 hrs with sustained levels over 120 hrs. For MEC acute phase CR rates of 74.8% (n=214), 76.9% (n=212) and 75.0% (n=208) were observed for 5 mg, 10 mg APF530 and palonosetron, respectively. Delayed phase CR rates of 51.4%, 59.0% and 57.7% were observed for 5 mg, 10 mg APF530 and palonosetron, respectively. For HEC acute phase CR rates of 77.7% (n=229), 81.3% (n=240) and 80.7% (n=238) were observed for 5 mg, 10 mg APF530 and palonosetron, respectively. Delayed phase CR rates of 64.6%, 68.3% and 66.4% were observed for 5 mg, 10 mg APF530 and palonosetron, respectively. Efficacy was maintained with APF530 over multiple cycles (up to 4). Conclusions: Both doses of APF530 were non-inferior to palonosetron with respect to CR during the acute phase following MEC and HEC. Only the higher dose of APF530 (10 mg granisetron) was non-inferior to palonosetron during the delayed phase of MEC. Both doses of APF530 were comparable to the CR rates of palonosetron during the delayed phase of HEC. [Table: see text]

Clinical evaluation of the effects of a single oral dose of gabapentin on fear-based aggressive behaviors in cats during veterinary examinations

2021 ◽  
pp. 1-7
Author(s):  
Marie Kruszka ◽  
Edith Graff ◽  
Tiphaine Medam ◽  
Sylvia Masson
Keyword(s):  
Adverse Effects ◽  
Oral Dose ◽  
Single Oral Dose ◽  
Untreated Control ◽  
Control Group ◽  
Aggressive Behaviors ◽  
Untreated Control Group ◽  
Control Groups ◽  
Complete Evaluation ◽  
Double Blind

Abstract OBJECTIVE To investigate the effects of a single oral dose of gabapentin on fear-based aggressive behaviors (FABs) in cats during veterinary examinations. ANIMALS 55 healthy pet cats (26 with and 29 without a history of FAB during veterinary visits [FAB and untreated control groups, respectively]). PROCEDURES A standardized 9-step clinical examination protocol (with patient compliance scored from 0 to 9 according to the highest completed step) was tested on untreated control group cats. The protocol was then used in a double-blind, randomized, placebo-controlled, crossover-design trial in which FAB-group cats received owner-administered gabapentin (100 or 200 mg/cat) or placebo capsules 2 hours before the first of 2 veterinary visits and received the alternate treatment before the second visit ≥ 1 day later. Ease of administration (scored from 1 [very difficult] to 4 [very easy]) and adverse effects were recorded. Compliance scores were compared between treatments for the FAB group and between FAB and untreated control groups. Changes in scores between treatments for the FAB group were used to investigate associations between selected variables and the outcome of interest. RESULTS FAB group compliance scores after gabapentin administration (median, 9; range, 0 to 9) were significantly higher than scores after placebo administration (median 0.5; range, 0 to 7) and did not differ from scores for the untreated control group. Owner scores indicated capsule administration was easy. Adverse effects (most commonly drowsiness, myorelaxation, and ataxia) resolved ≤ 10 hours after detection. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested oral administration of gabapentin to cats 2 hours before a veterinary visit can reduce FAB during physical examination, enabling more complete evaluation.

The Effects of a Caffeine Placebo and Experimenter Expectation on Blood Pressure, Heart Rate, Well-Being, and Cognitive Performance

2001 ◽  
Vol 6 (1) ◽  
pp. 15-25 ◽  
Author(s):  
Harald Walach ◽  
Stefan Schmidt ◽  
Yvonne-Michelle Bihr ◽  
Susanne Wiesch
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Cognitive Task ◽  
Well Being ◽  
Control Group ◽  
Double Blind ◽  
Main Effect ◽  
The Difference ◽  
Being There ◽  
To Receive

We studied the effect of experimenter expectations and different instructions in a balanced placebo design. 157 subjects were randomized into a 2 × 4 factorial design. Two experimenters were led to expect placebos either to produce physiological effects or not (pro- vs. antiplacebo). All subjects except a control group received a caffeine placebo. They were either made to expect coffee, no coffee, or were in a double-blind condition. Dependent measures were blood pressure, heart rate, well-being, and a cognitive task. There was one main effect on the instruction factor (p = 0.03) with the group “told no caffeine” reporting significantly better well-being. There was one main effect on the experimenter factor with subjects instructed by experimenter “proplacebo” having higher systolic blood pressure (p = 0.008). There was one interaction with subjects instructed by experimenter “proplacebo” to receive coffee doing worse in the cognitive task than the rest. Subjects instructed by experimenter “antiplacebo” were significantly less likely to believe the experimental instruction, and that mostly if they had been instructed to receive coffee. Contrary to the literature we could not show an effect of instruction, but there was an effect of experimenters. It is likely, however, that these experimenter effects were not due to experimental manipulations, but to the difference in personalities.

Synthetic Food Colors and Hyperactivity in Children: A Double-Blind Challenge Experiment

PEDIATRICS ◽  
1978 ◽  
Vol 62 (6) ◽  
pp. 975-983
Author(s):  
J. Preston Harley ◽  
Charles G. Matthews ◽  
Peter Eichman
Keyword(s):  
Classroom Behavior ◽  
Matched Control ◽  
Neuropsychological Test ◽  
Control Group ◽  
Comparable Data ◽  
Double Blind ◽  
Multiple Trials ◽  
To Receive ◽  
Male Subjects ◽  
Comparison Measures

Nine hyperactive male subjects, selected on the basis of showing a favorable "response" to the Feingold diet in an earlier study, were maintained on a strict elimination (Feingold) diet for 11 weeks, and were given multiple trials of placebo and challenge food materials. Parental and teacher ratings, classroom behavior observations, and neuropsychological test scores obtained during baseline, placebo, and challenge conditions, in general, were not found to be adversely affected by the artificial color challenge materials. As expected, comparable data gathered on a matched control group showed them to receive substantially better ratings than the hyperactive subjects on the majority of the comparison measures employed. Possible explanations for the discrepancy between the dramatic clinical-anecdotal reports that have been given and the much more equivocal findings from format experimental projects are presented.

Thorough QT Study to Evaluate the Effect of Zoliflodacin, a Novel Therapeutic for Gonorrhea, on Cardiac Repolarization in Healthy Adults

2021 ◽  
Author(s):  
Lori M. Newman ◽  
Martin Kankam ◽  
Aya Nakamura ◽  
Tom Conrad ◽  
John Mueller ◽  
...  
Keyword(s):  
Oral Dose ◽  
Single Oral Dose ◽  
Cardiac Repolarization ◽  
Cardiac Safety ◽  
Double Blind ◽  
Thorough Qt Study ◽  
Regulatory Guidelines ◽  
Clinically Significant ◽  
The One ◽  
Global Threat

Zoliflodacin is a novel spiropyrimidinetrione antibiotic being developed as single oral dose treatment to address the growing global threat of Neisseria gonorrhoeae . To evaluate the cardiac safety of zoliflodacin, a thorough QT/QTc (TQT) study was performed in healthy subjects. In this randomized, double-blind, placebo-controlled, 4-period crossover study, 72 subjects in a fasted state received a single dose of zoliflodacin 2 g (therapeutic), zoliflodacin 4 g (supratherapeutic), placebo, and moxifloxacin 400 mg as a positive comparator. Cardiac repolarization was measured by duration of the corrected QT interval by Fridericia’s formula (QTcF). At each time point up to 24 hours after zoliflodacin administration, the upper limit of the one-sided 95% confidence interval (CI) for the placebo-corrected change from the pre-dose baseline in QTcF (ΔΔQTcF) was less than 10 ms, indicating an absence of a clinically meaningful increase in QT prolongation. The lower limit of the one-sided multiplicity-adjusted 95% CI of ΔΔQTcF for moxifloxacin was longer than 5 ms at four time points from 1-4 hours after dosing, demonstrating adequate sensitivity of the QTc measurement. There were no clinically significant effects on heart rate, PR and QRS intervals, ECG morphology, or laboratory values. Treatment-emergent adverse events (AEs) were mild or moderate in severity and transient. This was a negative TQT study according to regulatory guidelines (E14) and confirms that a single oral dose of zoliflodacin is safe and well-tolerated. These findings suggest zoliflodacin is not proarrhythmic and contribute to the favorable assessment of cardiac safety for a single oral dose of zoliflodacin.

scholarly journals Aspirin-Persantin Prophylaxis in Elective total hip Replacement

1977 ◽  
Author(s):  
A.J. Silvergleid ◽  
R. Bernstein ◽  
D.S. Burton ◽  
J.B. Tanner ◽  
J.F. Silverman ◽  
...  
Keyword(s):  
Total Hip Replacement ◽  
Hip Replacement ◽  
Treated Group ◽  
Control Group ◽  
Double Blind ◽  
Total Hip ◽  
Blind Area ◽  
Effective Prophylaxis ◽  
Clinically Significant ◽  
To Receive

A prospective, double-blind clinical study was performed to evaluate the combination of dipyridamole(Persantin)225 mg/day and acetyl salicyclic acid (ASA) 1 g/day prophylaxis of post-operative venous thromboembolism in elective total hip replacement. Patients were stratified according to age, and randomly assigned to receive drug or placebo. All patients were followed with 125I-labelledfibrinogen scanning for one week post-operatively, or until fully mobile. Venography was performed in 67/129 patients; in 27 patients the venogram was obtained to confirm a positive fibrinogen scan, in 40 patients an elective venogram was obtained on the 7th post-operative day to evaluate the operated thigh (a blind area for scanning). Thrombosis (by scan or venogram) was found in 16/66(24%) in the control group, and in 21/63(33%) in the treated group. Overall incidence was 37/129 (29%). Correlation of scan with venography was 90%. There were no clinically significant pulmonary emboli in either group. We conclude that the combination of ASA and dipridamole as given in this study is not effective prophylaxis in elective total hip replacement.

Analgesic Efficacy and Safety Comparison of Ketorolac Tromethamine and Doleron for the Alleviation of Orthopaedic Post-Operative Pain

1989 ◽  
Vol 17 (4) ◽  
pp. 324-332 ◽  
Author(s):  
S. Johansson ◽  
G. Josefsson ◽  
J. Malstam ◽  
A. Lindstrand ◽  
A. Stenstroem
Keyword(s):  
Treatment Group ◽  
Adverse Events ◽  
Oral Dose ◽  
Single Oral Dose ◽  
Analgesic Efficacy ◽  
Ketorolac Tromethamine ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Post Operative Pain ◽  
Parallel Group

The analgesic efficacy and safety of ketorolac tromethamine (ketorolac), a potent analgesic with anti-inflammatory and antipyretic activities, were evaluated and compared with Doleron, a combination analgesic, in 115 patients with moderate to severe orthopaedic post-operative pain. This was a randomized, double-blind (double-dummy), parallel-group comparison of a single oral dose of one capsule of 10 mg ketorolac with a single oral dose of two Doleron tablets (each tablet contained 150 mg dextropropoxyphene napsylate, 350 mg aspirin and 150 mg phenazone). During the 6 h following treatment, 80% of ketorolac treated patients and 82% of Doleron treated patients experienced adequate pain relief. There were no statistically significant differences in the overall analgesic efficacy between the treatment groups. Three patients (one on ketorolac, two on Doleron) withdrew because of adverse events (vomiting). Nausea (two patients in each treatment group), vertigo (none on ketorolac, three on Doleron) and sore throat (none on ketorolac, two on Doleron) were the only drug-related adverse events reported by more than one person in a treatment group during the trial. A total of 82% of patients given ketorolac and 76% given Doleron experienced no adverse events. A single oral dose of 10 mg ketorolac was shown to be as effective and safe as two Doleron tablets in the treatment of moderate to severe orthopaedic post-operative pain.

Sustainability of antiemetic responses with APF530 (sustained-release granisetron) during multiple cycles of moderately (MEC) and highly (HEC) emetogenic chemotherapy regimens: Results of a randomized phase III trial.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9626-9626
Author(s):  
Ralph V. Boccia ◽  
William Cooper ◽  
Erin O'Boyle
Keyword(s):  
Rescue Medication ◽  
Emetogenic Chemotherapy ◽  
Phase Iii ◽  
Sustained Delivery ◽  
Test Results ◽  
Phase Iii Trial ◽  
Multiple Cycles ◽  
To Receive ◽  
Delayed Phase ◽  
Clinical Trial Information

9626 Background: Patients receiving MEC or HEC were administered subcutaneous (SC) APF530 500 mg, a sustained delivery formulation of granisetron (10 mg). The complete antiemetic response rates (CR; no emetic episodes and no rescue medication) were non-inferior to those of palonosetron in preventing acute and delayed chemotherapy-induced nausea and vomiting (CINV) (Grous et al. ASCO 2009, #9627). We report on sustainability of CR with APF530 (10 mg) during multiple chemotherapy cycles in this study. Methods: 1428 patients scheduled to receive single doses of MEC or HEC were randomized to APF530 SC (5 or 10 mg granisetron) or 0.25 mg palonosetron intravenously (IV) prior to cycle 1 (C1). In C2-4, patients who received palonosetron in C1 were randomized to APF530 5 or 10 mg; those who received APF530 continued with their C1 APF530 dose. Treatment cycles were separated by 7-28 days. CR rates were compared between cycles using McNemar’s test. Results: No significant differences in within-cycle CR occurred between APF530 doses during acute and delayed phases in C2-4 for MEC and HEC, but a trend toward higher CR rates was seen in successive cycles. For the 2 doses, CR was sustained across all 4 cycles in 56.5-62.6% and 68.4-71.7% in acute phase, and 41.8-42.4% and 57.5-57.9% in delayed phase with MEC and HEC, respectively. Examination of CR rates in C2, C3, or C4 compared with the rate in C1 showed that CR rates were sustained and that the proportion of patients with no CR in C1 but CR in later cycles was consistently higher than that of patients with CR in C1 but no CR later. For illustration, the table shows C4 CR and C1 CR for patients who received APF530 10 mg in C1 and C4. Conclusions: CR rates achieved with APF530 during acute and delayed phases of CINV in MEC and HEC were maintained over multiple cycles. Clinical trial information: NCT00343460. [Table: see text]

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