Efficacy and safety of rolapitant for prevention of chemotherapy-induced nausea and vomiting (CINV) in patients (pts) receiving anthracycline-cyclophosphamide (AC)-based chemotherapy.

2015 ◽  
Vol 33 (29_suppl) ◽  
pp. 208-208
Author(s):  
Daniel Powers ◽  
Ian D. Schnadig ◽  
Manuel R. Modiano ◽  
Sujata Arora ◽  
Lee Steven Schwartzberg
Keyword(s):  
Active Control ◽  
Rescue Medication ◽  
Complete Response ◽  
Controlled Study ◽  
Highly Emetogenic Chemotherapy ◽  
Double Blind ◽  
Post Hoc ◽  
And Control ◽  
Significant Nausea ◽  
Clinical Trial Information

208 Background: Rolapitant, a novel NK-1 receptor antagonist, demonstrated efficacy in the prevention of CINV in pts receiving moderately- or highly emetogenic chemotherapy (MEC; HEC). In this post-hoc analysis, we evaluated safety and efficacy outcomes in pts receiving AC-based therapy, now considered HEC. Methods: This double-blind, active-controlled study randomized pts to oral rolapitant 180 mg plus granisetron 2 mg and dexamethasone 20 mg or granisetron/dexamethasone alone (active control). Complete response (CR = no emesis and no use of rescue medication), no emesis, no significant nausea, and time to emesis or rescue medication during overall, acute, and delayed phases and treatment-emergent adverse events (AEs) are presented. Results: 703 pts received AC-based therapy, of which 97% had breast cancer. CR was significantly higher for rolapitant vs. active control for delayed and overall phases in pts receiving AC-based therapy (Table). Time to first emesis or use of rescue medication was significantly longer with rolapitant vs. active control (between-group comparison, p = 0.032); median was not reached in either treatment arm. A significantly greater proportion of pts on rolapitant (73.0%) vs. active control (60.2%) had no emesis during the overall phase (p < 0.001). Rates of no significant nausea were similar for rolapitant (63.7%) and active control (62.4%) in the overall phase (p = 0.728). Treatment-related AEs (TRAEs) during Cycle 1 occurred in 8.7% and 8.8% of pts on rolapitant vs. active control. Most frequent TRAEs were constipation (2.9% vs. 2.7%), fatigue (2.3% vs. 2.2%), and headache (2.3% vs. 3.3%). Conclusions: Rolapitant was superior to active control in preventing CINV during delayed and overall phases after AC-based chemotherapy. The safety profiles of the rolapitant and control arms were similar. These results are consistent with those of the overall pt population in this study. Clinical trial information: NCT01500226. [Table: see text]

Rolapitant for the prevention of nausea in patients receiving moderately or highly emetogenic chemotherapy.

2016 ◽  
Vol 34 (26_suppl) ◽  
pp. 224-224 ◽  
Author(s):  
Rudolph M. Navari ◽  
Cindy K Nagy ◽  
Sujata Arora ◽  
Daniel Powers ◽  
Rebecca Anne Clark-Snow
Keyword(s):  
Active Control ◽  
Unmet Need ◽  
Emetogenic Chemotherapy ◽  
Highly Emetogenic Chemotherapy ◽  
Phase 3 ◽  
Double Blind ◽  
Neurokinin 1 ◽  
Post Hoc ◽  
Significant Nausea ◽  
Clinical Trial Information

224 Background: Nausea control remains an unmet need for patients receiving moderately or highly emetogenic chemotherapy (MEC, HEC). The objective of this analysis was to determine the effect of the neurokinin-1 (NK-1) receptor antagonist rolapitant (VARUBI) on the prevention of nausea in patients receiving either MEC or HEC. Methods: Post hoc analyses of nausea from three randomized, double-blind, active-controlled, phase 3 clinical trials were performed for carboplatin-based MEC (n = 401), non-carboplatin-based MEC (n = 228), total MEC (n = 629), anthracycline/cyclophosphamide (AC)-based chemotherapy (n = 703), and cisplatin-based HEC (n = 1070). Patients were randomized 1:1 to oral rolapitant 180 mg or placebo ~1–2 h before chemotherapy. All patients received active control: granisetron 2 mg oral or 10 mcg/kg IV and oral dexamethasone 20 mg. Granisetron was continued on days 2 and 3 for patients receiving MEC or AC-based therapy and dexamethasone 8 mg twice daily on days 2–4 for patients receiving HEC. Patients self-assessed nausea on days 1–6 using a 100-mm visual analog scale (VAS). Percentage of patients with no nausea (NN; maximum VAS < 5 mm) or no significant nausea (NSN; maximum VAS < 25 mm) was determined for overall, delayed, and acute phases of CINV in cycle 1. Results: Rates of NN in the carboplatin-based MEC and total MEC subgroups were significantly higher (P < 0.05) with rolapitant than active control in the delayed and overall phases. In the cisplatin-based HEC subgroup, rates of NN and NSN were significantly higher (P < 0.05) with rolapitant than active control in the delayed, acute, and overall phases. Conclusions: Rolapitant prevents nausea during all CINV phases in patients receiving cisplatin-based HEC, and during the delayed and overall phases in patients receiving carboplatin-based MEC. Clinical trial information: NCT01500226, NCT01499849, NCT01500213.

Efficacy and safety of rolapitant for prevention of chemotherapy-induced nausea and vomiting (CINV) in non–anthracycline/cyclophosphamide (AC)-based moderately emetogenic therapy (MEC).

2015 ◽  
Vol 33 (29_suppl) ◽  
pp. 209-209
Author(s):  
Daniel Powers ◽  
Paul Joseph Hesketh ◽  
Lee Steven Schwartzberg ◽  
Manuel R. Modiano ◽  
Sujata Arora ◽  
...  
Keyword(s):  
Active Control ◽  
Complete Response ◽  
Controlled Study ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Double Blind ◽  
Oral Dexamethasone ◽  
Low Incidence ◽  
Post Hoc ◽  
Clinical Trial Information

209 Background: Rolapitant, a novel NK-1 receptor antagonist, showed efficacy in CINV prevention in patients (pts) receiving MEC (anthracycline/cyclophosphamide (AC) and other regimens) in a global phase 3 trial. Recent anti-emetic guidelines consider AC based regimens to be highly emetogenic. In this post hoc analysis, the efficacy and safety of rolapitant was assessed in Cycle 1 in pts receiving non-AC MEC, and in the subset of pts receiving carboplatin-based MEC. Methods: In a double-blind, active-controlled study, pts were randomized to oral rolapitant 180 mg or placebo 1–2 hours before MEC. All pts received granisetron 2 mg oral on days 1-3 and oral dexamethasone 20 mg on day 1. Complete response (CR = no emesis + no use of rescue medication), no emesis, and no nausea were assessed in overall (0-120 h), acute (0-24 h), and delayed ( > 24-120 h) phases. Results: CR was significantly (P < 0.01) higher with rolapitant than active control in overall and delayed phases in the carboplatin subset and in all 3 phases in the non-AC population (Table). No emesis rates were significantly (p < 0.05) higher with rolapitant in the carboplatin subset in the overall phase. No nausea rates were significantly (P < 0.05) higher with rolapitant in the overall and delayed phases in carboplatin-based MEC. Incidences of treatment-related AEs in Cycle 1 with rolapitant vs. active control were 11.3% vs. 6.7% in the carboplatin-based subset. Most common AEs with rolapitant and active control were constipation, fatigue, and headache. Conclusions: Rolapitant was superior to active control in preventing CINV in pts receiving non-AC MEC, including in the subgroup receiving carboplatin. Rolapitant was well tolerated with low incidence of AEs. Clinical trial information: NCT01500226. [Table: see text]

Rolapitant for control of chemotherapy-induced nausea and vomiting (CINV) in patients with gynecologic cancer.

2016 ◽  
Vol 34 (26_suppl) ◽  
pp. 223-223 ◽  
Author(s):  
Bernardo Leon Rapoport ◽  
Lee Steven Schwartzberg ◽  
Sujata Arora ◽  
Daniel Powers ◽  
Karin Jordan ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Receptor Antagonist ◽  
Rescue Medication ◽  
Gynecologic Cancer ◽  
Complete Response ◽  
Double Blind ◽  
Neurokinin 1 ◽  
Long Acting ◽  
Type 3 ◽  
And Control

223 Background: Rolapitant, a long-acting neurokinin-1 receptor antagonist, protected against CINV in patients receiving highly or moderately emetogenic chemotherapy (HEC or MEC). Methods: In 3 double-blind phase 3 studies, patients were randomized to receive oral rolapitant 180 mg or placebo before administration of HEC or MEC. All patients received a 5-hydroxytryptamine type 3 receptor antagonist and dexamethasone. In a post hoc analysis of 3 pooled studies (2 HEC and 1 MEC), we assessed the efficacy and safety of rolapitant in patients with gynecologic (ovarian, uterine, or cervical) cancer. Endpoints included complete response (CR; no emesis and no use of rescue medication), no emesis, no nausea (maximum visual analogue scale [VAS] < 5 mm), and complete protection (CP; no emesis, no use of rescue medication, and no significant nausea [maximum VAS < 25 mm]) in the overall (0–120 h), acute (≤ 24 h), and delayed (> 24–120 h) phases. Results: Of 201 patients with gynecologic cancer (60% ovarian, 28% uterine, and 12% cervical cancer), 55% received cisplatin-based HEC and 44% received MEC (99% of whom received carboplatin-based therapy). In the overall and delayed phases, improved rates of CR, no emesis, no nausea, and CP were observed with rolapitant compared with control (Table). The overall incidence of treatment-emergent adverse events was similar in the rolapitant and control groups (45% vs 54%). Conclusions: Rolapitant protected against overall and delayed CINV in patients with gynecologic cancer receiving HEC or MEC. Clinical trial information: NCT01500226, NCT01499849, NCT01500213. [Table: see text]

Efficacy of rolapitant for prevention of chemotherapy-induced nausea and vomiting (CINV) in patients with gastrointestinal and colorectal cancers.

2016 ◽  
Vol 34 (26_suppl) ◽  
pp. 222-222
Author(s):  
Rudolph M. Navari ◽  
Karin Jordan ◽  
Bernardo Leon Rapoport ◽  
Ian D. Schnadig ◽  
Martin Chasen ◽  
...  
Keyword(s):  
Active Control ◽  
Rescue Medication ◽  
Complete Response ◽  
Emetogenic Chemotherapy ◽  
Colorectal Cancers ◽  
Dexamethasone Therapy ◽  
Neurokinin 1 ◽  
Long Acting ◽  
Type 3 ◽  
Significant Nausea

222 Background: Rolapitant (VARUBI) is a selective, long-acting neurokinin-1 receptor antagonist (RA) for the prevention of CINV. Rolapitant effectively prevented CINV in phase 3 trials of patients (pts) receiving highly or moderately emetogenic chemotherapy (HEC, MEC). While MEC and HEC regimens are commonly used to treat pts with gastrointestinal and colorectal cancers (GI/CRC), very few studies have evaluated the effectiveness of a neurokinin-1 RA regimen in these pts. We assessed the incidence of CINV and efficacy of rolapitant in a subset of pts with GI/CRC. Methods: This is a post hoc analysis of 3 similarly-designed, randomized, placebo-controlled trials. Pts with cancer of the esophagus, stomach, colon/rectum, or anus received a single oral dose of 180 mg oral rolapitant or placebo prior to HEC or MEC. All pts received a 5-hydroxytryptamine type 3 (5-HT3) RA and dexamethasone (active control). The HEC studies included cisplatin, and the MEC study carboplatin, oxaliplatin, irinotecan, epirubicin, and doxorubicin. Endpoints included complete response (CR; no emesis and no use of rescue medication), no emesis, no nausea (maximum visual analogue scale [VAS] < 5 mm), no significant nausea (maximum VAS < 25mm) and complete protection (CP; no emesis, no use of rescue medication, and no significant nausea) in the overall (0-120 h), acute (≤ 24 h), and delayed (> 24-120 h) phases. Results: Out of 188 GI/CRC pts, 101 pts received rolapitant and 87 received active control. Pts treated with rolapitant had significantly higher rates of CR, no nausea, no emesis, and CP in the overall phase (P < 0.05). Rolapitant was well-tolerated and overall incidence of treatment-emergent adverse events comparable in both groups. Conclusions: Addition of rolapitant to 5-HT3RA and dexamethasone therapy significantly improved CR, no nausea, no emesis, and CP in pts with GI/CRC receiving emetogenic chemotherapy. Clinical trial information: NCT01500226, NCT01499849, NCT01500213. [Table: see text]

Efficacy of NEPA, a novel combination of netupitant (NETU) and palonosetron (PALO), for prevention of chemotherapy-induced nausea and vomiting (CINV) following highly emetogenic chemotherapy (HEC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9512-9512 ◽  
Author(s):  
Paul Joseph Hesketh ◽  
Giorgia Rossi ◽  
Giada Rizzi ◽  
Marco Palmas ◽  
Anna Alyasova ◽  
...  
Keyword(s):  
Complete Response ◽  
Complete Protection ◽  
Ecg Changes ◽  
Highly Emetogenic Chemotherapy ◽  
Double Blind ◽  
Oral Dexamethasone ◽  
Parallel Group ◽  
Dose Combination ◽  
Oral Doses ◽  
Significant Nausea

9512 Background: Further progress in preventing CINV will require the introduction of novel agents providing maximal convenience and with efficacy for nausea as well as vomiting. NEPA is a single dose combination of NETU, a novel NK1 receptor antagonist (RA) and PALO, a pharmacologically distinct 5-HT3RA. This study was designed to determine the proper dose of NETU to combine with PALO. Methods: This was a randomized, double-blind, parallel group study in chemotherapy-naïve patients (pts) undergoing cisplatin-based HEC. Four study arms compared 3 oral doses of NEPA (NETU 100, 200, 300mg + PALO 0.50 mg) with oral PALO 0.50 mg, all given on day 1. All pts received oral dexamethasone (DEX) days 1-4. An exploratory aprepitant (APREP) + ondansetron/DEX arm was included. The primary endpoint was complete response (CR: no emesis, no rescue) in the overall (0-120h) phase. Results: 694 pts were enrolled with comparable characteristics across groups: males (57%), median age 55. Common cancers: lung (27%), head and neck (21%). Median cisplatin dose: 75 mg/m2. All NEPA groups showed superior CR rates compared with PALO during the overall and delayed phases, with NEPA300also superior to PALO during the acute phase. NEPA300was also superior to PALO during all phases for no emesis, no significant nausea and complete protection with incremental benefits over lower NEPA doses. AEs were comparable across groups with no dose-response. The % of pts developing ECG changes was comparable across groups. Conclusions: Each NEPA dose resulted in superior CR rates compared with PALO. NEPA300was the best dose studied, with an advantage over lower doses for all efficacy endpoints (including nausea). NEPA doses were well tolerated with similar safety profiles to PALO and APREP. NEPA combined with DEX is superior to PALO plus DEX in prevention of CINV following HEC. [Table: see text]

Evaluation of nausea control with NEPA, a novel oral combination antiemetic.

2014 ◽  
Vol 32 (31_suppl) ◽  
pp. 169-169 ◽  
Author(s):  
Snezana Bosnjak ◽  
Lee Steven Schwartzberg ◽  
Giada Rizzi ◽  
Maria Elisa Borroni
Keyword(s):  
Single Dose ◽  
Development Program ◽  
Complete Response ◽  
Chemotherapeutic Agents ◽  
Fixed Dose ◽  
Double Blind ◽  
Clinical Development Program ◽  
Dose Oral ◽  
Significant Nausea ◽  
Clinical Trial Information

169 Background: The introduction of NK1 receptor antagonists (RAs) improved the control of chemotherapy-induced nausea and vomiting. However, prevention of nausea, particularly in the delayed phase remains suboptimal, with no consistent superiority seen with the addition of aprepitant over 5-HT3 RAs + dexamethasone (DEX). NEPA, a fixed-dose oral combination of the new NK1RA, netupitant (NETU 300 mg) plus palonosetron (PALO 0.50 mg) targets two main antiemetic pathways with a convenient single dose. NEPA has shown superior complete response rates (no vomiting and no rescue use) compared with PALO in pivotal trials. This analysis summarizes the nausea control seen with NEPA in all 3 pivotal trials in the clinical development program. Methods: Patients in 3 randomized, double-blind trials received a single dose of NEPA + DEX prior to a variety of either highly emetogenic (HEC) (Studies 1 and 3) or moderately emetogenic (MEC) (Studies 2 and 3) chemotherapeutic agents. Patients receiving HEC also received additional DEX on Days 2–4. Nausea was measured daily with a 100 mm visual analog scale (VAS). The proportion of patients with no significant nausea (VAS <25 mm) were summarized (Table). Results: In Studies 1 and 2, NEPA was significantly more effective in controlling delayed and overall nausea compared with PALO (Table). The greatest nausea control with NEPA was seen in the non-AC MEC and HEC settings. Conclusions: This summary suggests that NEPA + DEX improves control of nausea during the delayed and overall periods following chemotherapy. High levels of nausea control were seen and were most noteworthy in patients receiving HEC or non-AC MEC. Clinical trial information: NCT01339260; NCT01376297. [Table: see text]

scholarly journals Early and sustained symptom improvement with umeclidinium/vilanterol versus monotherapy in COPD: a post hoc analysis of the EMAX randomised controlled trial

2020 ◽  
Vol 14 ◽  
pp. 175346662092694
Author(s):  
Edward M Kerwin ◽  
Isabelle H Boucot ◽  
Claus F Vogelmeier ◽  
Francois Maltais ◽  
Ian P Naya ◽  
...  
Keyword(s):  
Rescue Medication ◽  
Controlled Trial ◽  
Medication Use ◽  
Symptom Improvement ◽  
Chronic Obstructive ◽  
Electronic Diary ◽  
Double Blind ◽  
Clinical Trial Registration ◽  
Bronchodilator Therapy ◽  
Post Hoc

Background: In chronic obstructive pulmonary disease (COPD), both the time needed for patients to gain symptom improvement with long-acting bronchodilator therapy and whether an early response is predictive of a sustained response is unknown. This study aimed to investigate how quickly meaningful symptom responses are seen in patients with COPD with bronchodilator therapy and whether these responses are sustained. Methods: Early MAXimisation of bronchodilation for improving COPD stability (EMAX) was a 24-week, double-blind, double-dummy, parallel-group trial that randomised patients to umeclidinium/vilanterol (UMEC/VI), umeclidinium or salmeterol. Daily Evaluating Respiratory Symptoms in COPD (E-RS:COPD) score and rescue salbutamol use were captured via an electronic diary and analysed initially in 4-weekly periods. Post hoc analyses assessed change from baseline in daily E-RS:COPD score and rescue medication use weekly (Weeks 1–8), and association between E-RS:COPD responder status at Weeks 1–4 and later time points. Results: In the intent-to-treat population ( n = 2425), reductions from baseline in E-RS:COPD scores and rescue medication use were apparent from Day 2 with all treatments. Treatment differences for UMEC/VI versus either monotherapy plateaued by Week 4–8 and were sustained at Weeks 21–24; improvements were consistently greater with UMEC/VI. For all treatments, most patients (60–85%) retained their Weeks 1–4 E-RS:COPD responder/non-responder status at Weeks 21−24. Among patients receiving UMEC/VI who were E-RS:COPD responders at Weeks 1–4, 70% were responders at Weeks 21–24. Conclusion: Patients with symptomatic COPD had greater potential for early symptom improvements with UMEC/VI versus either monotherapy. This benefit was generally maintained for 24 weeks. Early monitoring of treatment response can provide clinicians with an early indication of a patient’s likely longer-term response to prescribed bronchodilator treatment and will facilitate appropriate early adjustments in care. Clinical Trial Registration: NCT03034915, 2016-002513-22 (EudraCT Number). The reviews of this paper are available via the supplemental material section.

scholarly journals Randomized, Double-Blind, Placebo-Controlled Study of Modified Erzhi Granules in the Treatment of Menopause-Related Vulvovaginal Atrophy

2018 ◽  
Vol 2018 ◽  
pp. 1-15
Author(s):  
Ranran Chen ◽  
Dianrong Song ◽  
Wei Zhang ◽  
Guanwei Fan ◽  
Yingqiang Zhao ◽  
...  
Keyword(s):  
Drug Withdrawal ◽  
Endometrial Thickness ◽  
Vaginal Epithelium ◽  
Controlled Study ◽  
Control Group ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Vulvovaginal Atrophy ◽  
Normal Ranges ◽  
And Control

Objective. To evaluate the clinical therapeutic efficacy and safety of modified Erzhi granules (MEG) in patients with menopause-related vulvovaginal atrophy (VVA). Methods. This randomized, double-blind, placebo-controlled study comprised two groups, including the treatment and control groups. Patients receive MEG and placebo for 12 weeks, respectively. Vaginal health score (VHS), vaginitis score, vaginal maturation index (VMI), female sexual function index (FSFI), and modified Kupperman Index (modified KI) were used as efficacy endpoints and assessed at baseline, 4, 8, and 12 weeks during administration, and 4 weeks after drug withdrawal. At baseline and 12 weeks, serum estradiol (E2), follicle stimulating hormone (FSH), pelvic ultrasound, breast ultrasound, and other safety parameters were measured, recording adverse events. Results. At 12 weeks, VHS, percentage of superficial cells in the vaginal epithelium and FSFI were significantly increased, while vaginitis score, percentage of basal cells in the vaginal epithelium, and modified KI were significantly decreased in comparison with baseline and control group (all P<0.05); these differences persisted for up to 4 weeks after drug withdrawal. The placebo group showed no significant change during treatment compared with baseline values (p>0.05). Serum E2 and FSH levels, endometrial thickness, and breast thickness in all patients were within the normal ranges before and after treatment, with no serious adverse reactions observed. Conclusion. MEG significantly alleviates menopause-related vulvovaginal atrophy, with no overt adverse effects on the endometrium, breast, hepatic, and renal functions.

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