Efficacy and Safety of Plecanatide in Patients With Irritable Bowel Syndrome With Constipation: Pooled Analysis of 2 Randomized Clinical Trials 2017 Presidential Poster Award

2017 ◽  
Vol 112 ◽  
pp. S254
Author(s):  
Richard Krause ◽  
Jennifer Christie ◽  
Robert Kirshoff ◽  
Anhthu Nguyen ◽  
Patrick Griffin
Keyword(s):  
Clinical Trials ◽  
Irritable Bowel Syndrome ◽  
Randomized Clinical Trials ◽  
Pooled Analysis ◽  
Efficacy And Safety ◽  
Poster Award ◽  
Irritable Bowel

Efficacy, safety, and tolerability of plecanatide in patients with irritable bowel syndrome with constipation: results of two phase 3 randomized clinical trials

2018 ◽  
Vol 113 (5) ◽  
pp. 735-745 ◽  
Author(s):  
Darren M. Brenner ◽  
Ronald Fogel ◽  
Spencer D. Dorn ◽  
Richard Krause ◽  
Paul Eng ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Irritable Bowel Syndrome ◽  
Randomized Clinical Trials ◽  
Phase 3 ◽  
Two Phase ◽  
Irritable Bowel

Efficacy and Safety of Plecanatide in Patients with Irritable Bowel Syndrome with Constipation: Results from 2 Randomized, Double-Blind, Placebo-Controlled Clinical Trials

2017 ◽  
Vol 152 (5) ◽  
pp. S1309-S1310 ◽  
Author(s):  
Ronald Fogel ◽  
Spencer D. Dorn ◽  
Richard Krause ◽  
Paul Eng ◽  
Robert Kirshoff ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Irritable Bowel Syndrome ◽  
Efficacy And Safety ◽  
Controlled Clinical Trials ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Irritable Bowel

P190 ABROCITINIB EFFICACY AND SAFETY BY BODY WEIGHT: POOLED ANALYSIS OF 3 RANDOMIZED CLINICAL TRIALS

2021 ◽  
Vol 127 (5) ◽  
pp. S53-S54
Author(s):  
J. Thyssen ◽  
J. Silverberg ◽  
M. Cork ◽  
A. Taieb ◽  
B. Malhotra ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Body Weight ◽  
Randomized Clinical Trials ◽  
Pooled Analysis ◽  
Efficacy And Safety

Efficacy and Safety of Ixabepilone and Capecitabine in Patients With Advanced Triple-negative Breast Cancer: a Pooled Analysis From Two Large Phase III, Randomized Clinical Trials

2018 ◽  
Vol 18 (6) ◽  
pp. 489-497 ◽  
Author(s):  
Hope S. Rugo ◽  
Henri Roche ◽  
Eva Thomas ◽  
Hyun C. Chung ◽  
Guillermo L. Lerzo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Triple Negative Breast Cancer ◽  
Randomized Clinical Trials ◽  
Triple Negative ◽  
Pooled Analysis ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Large Phase

scholarly journals Efficacy and Safety Profile of Ixazomib Based Regimens in Relapsed/Refractory Multiple Myeloma: A Meta-Analysis of Clinical Trials

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 20-21
Author(s):  
Ahmad Iftikhar ◽  
Muhammad Ashar Ali ◽  
Anum Javaid ◽  
Muhammad Abu Zar ◽  
Atif Sohail ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Safety Profile ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Case Series ◽  
Pooled Analysis ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Grade 3

Background: Multiple myeloma (MM) is an incurable disease, and clinical trials with newer agents have shown improved patient outcomes. There is a need for effective and tolerable treatment for patients with relapsed/refractory MM (RRMM). Proteasome inhibitors (bortezomib, carfilzomib, ixazomib) remain an integral part of regimens used in RRMM or newly diagnosed (ND) MM. This meta-analysis aims to assess the efficacy and safety of ixazomib (Ixa) based regimens in RRMM. Methods: A comprehensive literature search was performed on PubMed, Cochrane, Embase, Web of Science, and clinicaltrials.gov. We used MeSH and Emtree terms, "ixazomib" AND "multiple myeloma" from the inception of literature till 06/01/2020. We screened 1529 articles and included 3 randomized clinical trials (RCT, N=907) and 8 non-randomized clinical trials (NRCT, N=321). We excluded case reports, case series, review articles, meta-analysis, observational studies, and clinical trials that didn't provide data about the efficacy and safety of Ixa in RRMM. We used the R programming language (version 4.0.2) to conduct a meta-analysis. Results: In 11 clinical trials (N=1228), the age range of patients was 30-91 years. In Phase III RCTs (N=837) comparing Ixa + Lenalidomide (Len) + dexamethasone (Dex) vs. placebo + Len + Dex, risk ratio of overall response rate (ORR), complete response (CR), and very good partial response (VGPR) were 1.14 (95% CI=1.05-1.24, I2=80%), 1.87 (95% CI=1.17-2.99, I2=0), and 1.15 (95% CI=0.95-1.40, I2=0), respectively in favor of Ixa + Len + Dex. (Fig 1-3) Grade 3 or higher treatment-related adverse events (TRAEs) thrombocytopenia, diarrhea, and rash were reported in 20%, 5.7% and 6.4% of the patients in the Ixa group vs. 10%, 2.1%, and 2.8% in the placebo group, respectively. In a Phase II RCT by Kumar et al (N=70) comparing the Ixa dosage, 4 mg Ixa + Dex yielded an ORR of 31%, CR 2.8%, and VGPR 17.1%, while 5.5 mg Ixa yielded improved ORR of 54%, CR 2.8%, and VGPR 25.7%. In a NRCT by Costello et al. (N=6), Ixa + daratumumab (Dara) + Pom + Dex yielded 100% ORR, CR 5% (95% CI=0.17-0.83), and VGPR 50% (95% CI=0.17-0.83). ≥Grade 3 TRAEs were hypertension (16%), and hematological (33%). Among 417 patients from two RCT in single arm who received Ixa + Len + Dex, pooled ORR was 70% (95% CI=0.53-0.82, I2=84%), pooled CR 11% (95% CI=0.8-0.14, I2=0), and pooled VGPR was 29% (95% CI=0.18-0.43, I2=66%). In a NRCT by Dhakal et al. (N=19), Ixa + bendamustine + Dex yielded an ORR 58% (95% CI=0.36-0.77), CR 0, and VGPR 11% (95% CI =0.03-0.34). ≥Grade 3 TRAEs were neutropenia 31%, thrombocytopenia 52%, and diarrhea 10%. In 2 NRCT (N=106), Ixa + cyclophosphamide (Cyc) + Dex yielded a pooled ORR 52% (95% CI=0.42-0.61, I2=0), CR 4% (95% CI=0.01-0.10, I2=0), and VGPR 17% (95% CI=0.11-0.25, I2=0). ≥Grade 3 TRAEs were thrombocytopenia (15%), and upper abdominal pain (4%). In a NRCT by Ludwig et al. (N=90), Ixa + thalidomide (Thal) + Dex yielded an ORR 51% (95% CI=0.41-0.61), CR 9% (95% CI=0.5-0.17), and VGPR 14% (95% CI=0.09-0.23). ≥Grade 3 TRAEs were anemia (17.8%), and infections (16.1%). In a NRCT by Krishnan et al. (N=31), Ixa + Pomalidomide (Pom) + Dex yielded an ORR 48% (95% CI=0.32-0.65) and VGPR 16% (95% CI=0.07-0.33). (Fig 4-6) ≥Grade 3 TRAEs were neutropenia (10%), and lymphopenia (35%). In 2 NRCT by Kumar et al. (N=70) of two drugs combination, Ixa + Dex yielded a pooled ORR 43% (95% CI=0.28-0.59, I2=47%), pooled CR 1% (95% CI=0-0.09, I2=0), and pooled VGPR 24% (95% CI=0.16-0.36, I2=0). ≥Grade 3 TRAEs were hematological (28%), and non-hematological (22.8%). In 2 NRCT of Ixa monotherapy (N=69), pooled ORR was 17% (95% CI=0.10-0.28, I2=0), and pooled CR 6% (95% CI=0.2-0.22, I2=0). (Fig 4-6) ≥Grade 3 TRAEs were anemia (11%), thrombocytopenia (5.4%), and neutropenia (2.7%). Conclusion: Our study provides useful insight into relative efficacy of various Ixa regimens for the treatment of RRMM. The pooled analysis of RCT showed that the combination of Ixa + Len + Dex yielded better response as compared to placebo. In the pooled analysis of outcomes in single arm NRCT, Ixa + Dara + Pom + Dex and Ixa + Len + Dex showed better efficacy outcomes as compared to Ixa + Dex in combination with Thal, Cyc, or Bendamustin. Three drugs Ixa combination regimens had better efficacy as compared to two drugs combination of Ixa + Dex and Ixa monotherapy. Ixa was well tolerated with acceptable safety profile. Additional multicenter, double-blind clinical trials are needed to confirm these results. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

929d Eluxadoline for the Treatment of Diarrhea-Predominant Irritable Bowel Syndrome: Results of 2 Randomized, Double-blind, Placebo-Controlled Phase 3 Clinical Trials of Efficacy and Safety

2014 ◽  
Vol 146 (5) ◽  
pp. S-159 ◽  
Author(s):  
Anthony Lembo ◽  
Scott Dove ◽  
David Andrae ◽  
J. Michael Davenport ◽  
Gail McIntyre ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Irritable Bowel Syndrome ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Irritable Bowel

scholarly journals Efficacy of otilonium bromide in irritable bowel syndrome: a pooled analysis

2017 ◽  
Vol 10 (3) ◽  
pp. 311-322 ◽  
Author(s):  
Pere Clavé ◽  
Jan Tack
Keyword(s):  
Clinical Trials ◽  
Irritable Bowel Syndrome ◽  
Pooled Analysis ◽  
Stool Frequency ◽  
Global Response ◽  
Intention To Treat ◽  
Therapeutic Benefits ◽  
Irritable Bowel ◽  
To Receive ◽  
Significant Therapeutic Effect

Background: Otilonium bromide (OB) is a spasmolytic agent acting as an L-type calcium channel antagonist in intestinal and colonic smooth muscle cells (SMCs). We analyzed three independent clinical trials with homogeneous design on patients with irritable bowel syndrome (IBS). After 2 weeks receiving placebo, patients were randomized to receive OB (3 × 40 mg daily) or placebo for 15 weeks. We aimed to perform a pooled analysis of the data from these homogeneous clinical trials to evaluate the efficacy of OB treatment on symptoms and global response of patients. Methods: A total of 883 patients with IBS (69.8% women, mean age 46.2 years, 43.8% mixed type) were included, 442 treated with OB and 441 with placebo. The efficacy results from the three studies at weeks 5, 10 and 15 were pooled in an intention-to-treat (ITT) strategy, analyzed with a logistic regression model and described by forest plots. Results: Despite a placebo effect in all efficacy variables, a significant therapeutic effect of OB was observed at weeks 10 and 15 with reference to: (a) intensity and frequency of abdominal pain; (b) rate of responders as evaluated by patients (71.8% at week 10 and 77.2% at week 15); (c) severity of bloating; (d) rate of responders as evaluated by physicians (55% at week 10 and 63.9% at week 15). No significant OB effect was observed in stool frequency and consistency. Conclusions: OB is more effective than placebo in IBS treatment. Therapeutic benefits are significant after 10 weeks and are maximal after 15 weeks of treatment.

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