Phase III study of NEPA, a fixed-dose combination of netupitant (NETU) and palonosetron (PALO), versus PALO for prevention of chemotherapy-induced nausea and vomiting (CINV) following moderately emetogenic chemotherapy (MEC).

2013 ◽  
Vol 31 (18_suppl) ◽  
pp. LBA9514-LBA9514 ◽  
Author(s):  
Matti S. Aapro ◽  
Giorgia Rossi ◽  
Giada Rizzi ◽  
Marco Palmas ◽  
Steven Grunberg
Keyword(s):  
Adverse Events ◽  
Study Drug ◽  
Complete Response ◽  
Fixed Dose Combination ◽  
Phase Iii ◽  
Fixed Dose ◽  
Double Blind ◽  
Reported Study ◽  
Dose Combination

LBA9514 Background: Management of CINV has been refined over the past several decades and CINV can now be managed with targeted prophylactic medications aimed at inhibiting several molecular pathways involved in emesis. NEPA, a fixed-dose combination of netupitant (NETU), a new NK1 receptor antagonist (RA) and palonosetron (PALO), a pharmacologically distinct 5-HT3RA, targets these dual antiemetic pathways and has been shown to uniquely work synergistically in vitro. Methods: This was a multinational, randomized, double-blind, parallel group study assessing the efficacy and safety of a single oral dose of NEPA (NETU 300mg + PALO 0.50 mg) versus a single oral 0.50 mg dose of PALO in 1,455 chemotherapy-naive patients (pts) receiving anthracycline-based chemotherapy (all pts received oral dexamethasone (DEX) 12 mg (NEPA) or 20 mg (PALO) on Day 1). The primary efficacy endpoint was complete response (CR: no emesis, no rescue medication) during the delayed (25-120h) phase. Results: Treatment groups had comparable demographic characteristics with the majority of the population being female (98%) and white (80%), with a mean age of 54 yrs; 97% pts had breast cancer. NEPA showed superior CR rates compared to PALO during the delayed, acute, and overall phases. NEPA was also superior to PALO during the delayed/overall phases for complete protection, no emesis, and no significant nausea. Most frequently reported study drug-related adverse events (AEs) for NEPA included headache (3.3%) and constipation (2.1%). The majority of adverse events for NEPA-treated pts were mild/moderate and there were very few (0.7%) severe drug-related AEs. The type and frequency of AEs were comparable between NEPA and PALO. There was no evidence of any cardiac safety concerns for NEPA or PALO. Conclusions: NEPA, a novel single-day fixed-dose combination targeting dual antiemetic pathways, is superior to PALO (both associated with DEX) in preventing CINV in pts receiving MEC. Clinical trial information: NCT01339260. [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.

scholarly journals The novel bronchodilator navafenterol: a phase 2a, multi-centre, randomised, double-blind, placebo-controlled crossover trial in COPD

2021 ◽  
pp. 2100972
Author(s):  
Dave Singh ◽  
Jutta Beier ◽  
Carol Astbury ◽  
Maria G. Belvisi ◽  
Carla A. Da Silva ◽  
...  
Keyword(s):  
Adverse Events ◽  
Mean Difference ◽  
Beta Agonist ◽  
Fixed Dose Combination ◽  
Fixed Dose ◽  
Double Blind ◽  
Once Daily ◽  
Significant Difference ◽  
Dose Combination ◽  
Severe Copd

BackgroundNavafenterol (AZD8871) belongs to a new class of bronchodilator, the single-molecule muscarinic antagonist and beta agonist (MABA), being developed for the treatment of chronic obstructive pulmonary disease (COPD). This study aimed to evaluate the efficacy, pharmacokinetics and safety of navafenterol versus placebo and an active comparator treatment for moderate-to-severe COPD.MethodsThis phase 2a, randomised, multicentre (Germany and UK), double-blind, double-dummy, three-way complete crossover study (ClinicalTrials.gov identifier: NCT03645434) compared 2 weeks’ treatment of once-daily navafenterol 600 µg via inhalation with placebo and a fixed-dose combination bronchodilator (umeclidinium/vilanterol [UMEC/VI]; 62.5 µg/25 µg) in participants with moderate-to-severe COPD. The primary outcome was change from baseline in trough FEV1 on day 15. Secondary endpoints included: change from baseline in peak FEV1; change from baseline in breathlessness, cough and sputum scale (BCSS); change from baseline in COPD assessment tool (CAT); adverse events; and pharmacokinetics.ResultsSeventy-three participants were randomised. After 14 days, trough FEV1 was significantly improved with navafenterol compared with placebo (least-squares [LS] mean difference 0.202 L; p<0.0001). There was no significant difference in FEV1 between navafenterol and UMEC/VI (LS mean difference −0.046 L; p=0.075). COPD symptoms (CAT and BCSS) showed significantly greater improvements with both active treatments versus placebo (all p<0.005). Novel objective monitoring (VitaloJAK) showed that cough was reduced with both active treatments compared with placebo. Safety profiles were similar across the treatment groups and no serious adverse events were reported in the navafenterol treatment period.ConclusionOnce-daily navafenterol was well tolerated, improved lung function and reduced COPD-related symptoms, similar to an established once-daily fixed-dose combination bronchodilator.

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