scholarly journals Efficacy and safety of switching from rituximab to biosimilar CT-P10 in rheumatoid arthritis: 72-week data from a randomized Phase 3 trial

Rheumatology ◽  
2019 ◽  
Vol 58 (12) ◽  
pp. 2193-2202 ◽  
Author(s):  
Seung Cheol Shim ◽  
Ljubinka Božić-Majstorović ◽  
Alfredo Berrocal Kasay ◽  
Elias Chalouhi El-Khouri ◽  
Fedra Irazoque-Palazuelos ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Disease Activity ◽  
Study Drug ◽  
Efficacy And Safety ◽  
Drug Infusion ◽  
Phase 3 ◽  
Double Blind ◽  
American College Of Rheumatology ◽  
Extension Period

Abstract Objective To evaluate the efficacy and safety of CT-P10, a rituximab biosimilar after a single switch, during a multinational, randomized, double-blind Phase 3 trial involving patients with RA. Methods Patients received 48 weeks’ treatment with CT-P10 or United States- or European Union-sourced reference rituximab (US-RTX and EU-RTX, respectively). Patients entering the extension period (weeks 48–72) remained on CT-P10 (CT-P10/CT-P10; n = 122) or US-RTX (US-RTX/US-RTX; n = 64), or switched to CT-P10 from US-RTX (US-RTX/CT-P10; n = 62) or EU-RTX (EU-RTX/CT-P10; n = 47) for an additional course. Efficacy endpoints included Disease Activity Score using 28 joints (DAS28), American College of Rheumatology (ACR) response rates, and quality of life-related parameters. Pharmacodynamics, immunogenicity and safety were also assessed. Results At week 72, similar improvements were observed by disease activity parameters including DAS28 and ACR response rate in the four extension period treatment groups. Quality of life improvements at week 72 vs baseline were similarly shown during the extension period in all groups. Newly developed anti-drug antibodies were detected in two patients following study drug infusion in the extension period. Similar pharmacodynamic and safety profiles were observed across groups. Conclusion Long-term use of CT-P10 up to 72 weeks was effective and well tolerated. Furthermore, switching from reference rituximab to CT-P10 in RA was well tolerated and did not result in any clinically meaningful differences in terms of efficacy, pharmacodynamics, immunogenicity and safety. Trail registration ClinicalTrials.gov, http://clinicaltrials.gov, NCT02149121.

scholarly journals OR11-03 NT-814, a Non-Hormonal Dual Neurokinin 1,3 Receptor Antagonist Markedly Improves Vasomotor Symptoms in Post-Menopausal Women; Results of a Randomised, Double-Blind, Placebo-Controlled, Dose-Finding Study (SWITCH-1)

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
James Simon ◽  
Richard A Anderson ◽  
Elizabeth Ballantyne ◽  
Hadine Joffe ◽  
Mary Kerr ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Dose Finding ◽  
Vasomotor Symptoms ◽  
Phase 3 ◽  
Double Blind ◽  
Once Daily ◽  
Double Blind Placebo ◽  
Menopausal Women ◽  
Post Menopausal

Abstract Introduction: Vasomotor symptoms (VMS), caused by declining estrogen in menopausal women, are common and debilitating. Hormone therapy is effective in many women but carries risks and may be contraindicated. Biological and clinical evidence shows a modulatory role for neurokinin (NK) receptor antagonists acting primarily via hypothalamic KNDy (kisspeptin, NK, dynorphin) neurons on VMS. NT-814 is an oral non-hormonal dual NK1,3 receptor antagonist which has previously been shown to cause rapid and marked improvements in VMS in post-menopausal women. This Phase-2b trial (SWITCH-1) was undertaken to further evaluate efficacy and safety and to establish the optimum dose(s) for Phase 3 studies. Methods: SWITCH-1 was a double-blind, placebo-controlled, adaptive-randomization, dose-finding trial in 199 post-menopausal women. After a 2-week single-blind placebo run-in to establish symptom stability, women (40 to 65 years) with ≥7 moderate and/or severe VMS per day at baseline were randomized to 12 weeks of once daily treatment with placebo or one of 4 doses of NT-814: 40 mg, 80 mg, 120 mg, 160 mg. Subjects recorded the frequency and severity of VMS in electronic diaries twice daily throughout the study. Patient-reported measures of quality-of-life, sleep and mood were collected periodically. Adverse events (AEs) were recorded at each clinic visit. Results: VMS frequency was reduced in all treatment groups, including placebo. VMS reductions were significantly greater with the 2 higher NT-814 doses at most time-points, as early as the first week of treatment. Least squares mean reductions from baseline in moderate/severe VMS per day at week 4 were: placebo, 2.7; 40 mg, 4.3 (p=0.161 vs placebo); 80 mg, 4.1 (p=0.326); 120 mg, 6.7 (p<0.0001); 160 mg, 5.5 (p=0.007). In week 12 the reductions were: placebo, 4.7; 40 mg, 6.5 (p=0.185); 80 mg, 5.6 (p=0.599); 120 mg, 7.8 (p=0.009); 160 mg, 6.6 (p=0.109). At the 160 mg dose the median reduction in week 12 was significantly greater than placebo (6.9 vs 4.4, p=0.0023), indicating an effect of high outliers on the mean. Average HF severity was also improved in a dose-related manner, with greater reductions compared to placebo with the 2 higher NT-814 doses. Improvements in HF were accompanied by statistically significant benefits on sleep (assessed using the Insomnia Severity Index and Pittsburgh Sleep Quality Index), mood (measured using the Beck Depression Inventory), and all four domains of the MenQoL menopause-specific quality-of-life instrument. NT-814 was well-tolerated; most AEs were mild or moderate and there were no serious AEs related to treatment. Conclusions: NT-814, a once daily non-hormonal NK antagonist, at doses of 120 & 160 mg reduced the frequency and severity of VMS and significantly improved quality of life, mood and sleep, in postmenopausal women. NT-814 was well tolerated, with a safety profile that supports further evaluation in Phase 3 trials.

scholarly journals 2477 Targeting pulsatile load to increase exercise capacity and quality of life after TAVR for severe aortic stenosis

2018 ◽  
Vol 2 (S1) ◽  
pp. 48-48
Author(s):  
Anupam Kumar ◽  
Julio Chirinos
Keyword(s):  
Quality Of Life ◽  
Aortic Stenosis ◽  
Exercise Capacity ◽  
Severe Aortic Stenosis ◽  
Myocardial Strain ◽  
Study Drug ◽  
Potassium Nitrate ◽  
Exercise Intolerance ◽  
Double Blind

OBJECTIVES/SPECIFIC AIMS: The objective of the study is to test the effect of oral inorganic nitrate on the primary outcomes of exercise capacity and quality of life in patients who have undergone TAVR for severe aortic stenosis. We will also test the effect of the study drug on various physiology endpoints, including systemic vasodilator response to exercise, LV diastolic function and myocardial strain, late systolic LV load and pulsatile arterial wave reflections. METHODS/STUDY POPULATION: This is a randomized double-blind crossover clinical trial, in which 24 subjects who underwent TAVR for severe AS 3 or more months before enrollment will receive the following 2 interventions, in randomized order: (1) Potassium nitrate (KNO3), at a dose of 12–18 mmol/day by mouth for ~4 weeks, or (2) Potassium chloride (KCl), at a dose of 12–18 mmol/day by mouth for ~4 weeks. A 1-week washout period will be introduced between the 2 interventions. RESULTS/ANTICIPATED RESULTS: We hypothesize that sustained oral administration of potassium nitrate will lead to improvement of exercise capacity and quality of life in this population.DISCUSSION/SIGNIFICANCE OF IMPACT: His study will have a significant impact on assessment and management of patients after TAVR. We will gain a better understanding of physiologic abnormalities leading to exercise intolerance after TAVR. In addition, there are currently no proven therapies that improve exercise capacity in this population.

Health-Related Quality of Life (HRQoL) in Patients (Pts) with Chronic Immune Thrombocytopenic Purpura (ITP): Results from Two Placebo-Controlled Phase 3 Studies of AMG 531.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1314-1314
Author(s):  
James N. George ◽  
Roger Lyons ◽  
Francis J. Cuevas ◽  
Ronald S. Go ◽  
David H. Henry ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Reproductive Health ◽  
Social Activity ◽  
Phase 3 ◽  
Double Blind ◽  
Chronic Itp ◽  
Women’S Reproductive Health ◽  
Women's Reproductive Health ◽  
Disease Specific

Abstract Pt-reported outcomes (PROs) are important tools for understanding the effects of treatment for various diseases. We developed the ITP Pt Assessment Questionnaire (ITP-PAQ) as the first disease-specific PRO instrument for adult chronic ITP. Further evaluation of its validity was assessed in ITP pts receiving AMG 531. AMG 531 is a novel thrombopoiesis-stimulating peptibody that is being studied for its ability to increase platelet production by stimulating the thrombopoietin receptor. The ITP-PAQ was used to examine HRQoL changes in both splenectomized and nonsplenectomized pts from 2 randomized, double blind, placebo-controlled Phase 3 studies of AMG 531 in adult pts with chronic ITP. It contains 44 items and 10 scales including Symptoms, Bother, Fatigue, Activity, Fear, Psychological, Work, Social Activity, Women’s Reproductive Health, and Overall Quality of Life. Pts were blinded to their platelet counts before completing the ITP-PAQ. Changes in mean scores from baseline to week 24 were calculated for each ITP-PAQ scale by treatment arm, with positive values indicating improvement in HRQoL. Independent two-tailed t-tests were used to test differences. Specific items within each scale were also analyzed to provide further insights into the disease-specific areas of most concern for pts. Of the 125 pts enrolled, 63 were splenectomized (placebo, 21; AMG 531, 42), and 62 were nonsplenectomized (placebo, 21; AMG 531, 41). At baseline, splenectomized pts had lower scores on all ITP-PAQ scales than nonsplenectomized pts, especially Bother (51.0 vs 66.7), Fear (69.4 vs 81.3), Work (62.4 vs 77.5), and Overall Quality of Life (40.3 vs 56.5). Over the 24-week study, AMG 531-treated pts reported significantly greater improvement relative to placebo on 5 of 10 scales. Among splenectomized pts, significantly greater improvements in mean scores from baseline were found in the AMG 531 arm for Symptoms (placebo vs AMG 531; 0.2 vs 10.8, p=0.02), Bother (4.5 vs 24.6, p=0.009), Social Activity (−2.1 vs 16.9, p=0.017), and Women’s Reproductive Health (−11.9 vs 10.1, p=0.027). Among nonsplenectomized pts, significantly greater improvement was found in AMG 531 pts for Activity (−1.8 vs 23.7, p=0.016). Particular improvements in items shown by both splenectomized and nonsplenectomized AMG 531-treated pts included bleeding (Symptoms), bruising (Symptoms), feeling unattractive due to bruising (Bother), and fear of infections (Fear). In summary, lower HRQoL was reported in splenectomized compared to nonsplenectomized pts with ITP, reflecting potentially different clinical needs for these 2 pt populations. Pts treated with AMG 531 showed greater improvement in HRQoL relative to placebo pts on most ITP-PAQ scales, and significant improvements were more common in splenectomized pts. Results from these 2 trials have provided further validation of the ITP-PAQ and can inform selection of key endpoints for future studies.

T1209 Twice-Daily Balsalazide Tablets Improve Patient Quality of Life After 2, 6, or 8 Weeks of Treatment: Results of Two Phase 3, Randomized, Double-Blind Multicenter Studies

2009 ◽  
Vol 136 (5) ◽  
pp. A-522
Author(s):  
Alana A. Rosen ◽  
Shahriar Sedghi ◽  
Roland D. Shepard ◽  
Shadreck M. Mareya ◽  
Shirley Huang ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Treatment Results ◽  
Phase 3 ◽  
Multicenter Studies ◽  
Two Phase ◽  
Double Blind ◽  
Improve Patient

scholarly journals Preventive Efficacy and Safety of Yiqi-Wenjing-Fang Granules on Oxaliplatin-Induced Peripheral Neuropathy: A Protocol for a Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Zhancheng Gu ◽  
Guoli Wei ◽  
Liangjun Zhu ◽  
Lingjun Zhu ◽  
Jing Hu ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Peripheral Neuropathy ◽  
Intervention Group ◽  
Secondary Outcome ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Group I ◽  
Preventive Efficacy

Background. Oxaliplatin-induced peripheral neuropathy (OIPN) is one of the most common side effects of oxaliplatin, which can cause reduction and cessation of oxaliplatin-based chemotherapy and significantly affect patients’ quality of life. However, no drug has got recognition to prevent or treat OIPN. Yiqi-Wenjing-Fang (YWF) is a joint name of Chinese medicine prescriptions with similar effects of tonifying qi and warming meridians, represented by Huangqi Guizhi Wuwu decoction (HGWD) and Danggui Sini decoction (DSD), both from “Treatise on Cold Pathogenic and Miscellaneous Diseases.” YWF granules, including HGWD granules and DSD granules, have been, respectively, demonstrated to be effective in preventing OIPN in previous small-sample observations. The purpose of this study is to enlarge the sample size for further evaluation of the preventive efficacy and safety of YWF granules on OIPN. Methods and Analysis. This study is a randomized, double-blind, placebo-controlled, and multicenter clinical trial. 360 postoperative patients with stage IIa-IIIc colorectal cancer will be randomly assigned into placebo-control group, intervention group I, and intervention group II, taking the mimetic granules of YWF as placebo, HGWD granules and DSD granules, respectively. All subjects will receive oxaliplatin-based chemotherapy regimen at the same time. EORTC QLQ-CIPN20 will be used to assess the degree of OIPN as the primary outcome measure. The grades of OIPN, quality of life, chemotherapeutic efficacy, and the number of completed chemotherapy cycles are selected as the secondary outcome measures. Discussion. Based on the condition of no recognized effective drugs in preventing OIPN, evidence-based medical study will be conducted for seeking a breakthrough in the field of Chinese herb medicine. This protocol could provide reliable and systemic research basis about the efficacy of YWF granules and the differentiation of two classical prescriptions of YWF on preventing OIPN objectively. Trial Registration. This study was registered at ClinicalTrials.gov on 26 December 2020 (ID: https://clinicaltrials.gov/ct2/show/NCT04690283).

scholarly journals Effect of a rescue or recurrence dose of lasmiditan on efficacy and safety in the acute treatment of migraine: Findings from the Phase 3 trials (SAMURAI and SPARTAN)

2019 ◽  
Author(s):  
Li Shen Loo ◽  
Brian Plato ◽  
Ira Turner ◽  
Michael Case ◽  
Joel Raskin ◽  
...  
Keyword(s):  
Acute Treatment ◽  
Study Drug ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Double Blind ◽  
Rescue Treatment ◽  
Patient Pain ◽  
Bothersome Symptom ◽  
Severe Migraine ◽  
Headache Recurrence

Abstract Background We studied the efficacy and safety of a second dose of lasmiditan for acute treatment of migraine. Methods SAMURAI and SPARTAN were double-blind, placebo-controlled Phase 3 studies in which individuals with migraine were randomized to oral lasmiditan 50mg (SPARTAN only), 100mg, 200mg, or placebo. Study drug was to be taken within 4 hours (h) of onset of a migraine attack (moderate or severe pain). A second dose of study drug was provided for rescue (patient not pain-free at 2h and took a second dose 2-24h post-first dose) or recurrence (patient pain-free at 2h, but experienced recurrence of mild, moderate, or severe migraine pain and took a second dose 2-24h after first dose). Randomization to second dose occurred at baseline; patients originally assigned lasmiditan were randomized to the same lasmiditan dose or placebo (2:1 ratio), and those originally assigned placebo received placebo. Data from SAMURAI and SPARTAN were pooled for efficacy and safety assessment of a second dose of lasmiditan. Results The proportion of patients taking a second dose was lower with lasmiditan versus placebo, and decreased with increasing lasmiditan dose; the majority who took a second dose did so for rescue. In patients taking lasmiditan as first dose, outcomes (pain free, most bothersome symptom [MBS] free) at 2h after a second dose for rescue were similar whether the second dose was lasmiditan or placebo (p>0.05 in all cases). In patients taking lasmiditan for first dose, outcomes at 2h after a second dose for recurrence were as follows: lasmiditan pooled versus placebo - pain free, 50% vs 32% (p>0.05); MBS free, 71% vs 41% (p=0.02); pain relief, 77% vs 52% (p=0.03). In patients whose first dose was lasmiditan, the incidence of treatment emergent adverse events (TEAEs) reported after the second dose was similar whether second dose was lasmiditan or placebo. Conclusions A second dose of lasmiditan showed some evidence of efficacy when taken for headache recurrence. There was no clear benefit of a second dose of lasmiditan for rescue treatment. The incidences of TEAEs were similar whether the second dose was lasmiditan or placebo.

scholarly journals Effect of a rescue or recurrence dose of lasmiditan on efficacy and safety in the acute treatment of migraine: Findings from the Phase 3 trials (SAMURAI and SPARTAN)

2019 ◽  
Author(s):  
Li Shen Loo ◽  
Brian Plato ◽  
Ira Turner ◽  
Michael Case ◽  
Joel Raskin ◽  
...  
Keyword(s):  
Acute Treatment ◽  
Study Drug ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Double Blind ◽  
Rescue Treatment ◽  
Patient Pain ◽  
Bothersome Symptom ◽  
Severe Migraine ◽  
Headache Recurrence

Abstract Background We studied the efficacy and safety of a second dose of lasmiditan for acute treatment of migraine. Methods SAMURAI and SPARTAN were double-blind, placebo-controlled Phase 3 studies in which individuals with migraine were randomized to oral lasmiditan 50mg (SPARTAN only), 100mg, 200mg, or placebo. Study drug was to be taken within 4 hours (h) of onset of a migraine attack (moderate or severe pain). A second dose of study drug was provided for rescue (patient not pain-free at 2h and took a second dose 2-24h post-first dose) or recurrence (patient pain-free at 2h, but experienced recurrence of mild, moderate, or severe migraine pain and took a second dose 2-24h after first dose). Randomization to second dose occurred at baseline; patients originally assigned lasmiditan were randomized to the same lasmiditan dose or placebo (2:1 ratio), and those originally assigned placebo received placebo. Data from SAMURAI and SPARTAN were pooled for efficacy and safety assessment of a second dose of lasmiditan. Results The proportion of patients taking a second dose was lower with lasmiditan versus placebo, and decreased with increasing lasmiditan dose; the majority who took a second dose did so for rescue. In patients taking lasmiditan as first dose, outcomes (pain free, most bothersome symptom [MBS] free) at 2h after a second dose for rescue were similar whether the second dose was lasmiditan or placebo (p>0.05 in all cases). In patients taking lasmiditan for first dose, outcomes at 2h after a second dose for recurrence were as follows: lasmiditan pooled versus placebo - pain free, 50% vs 32% (p>0.05); MBS free, 71% vs 41% (p=0.02); pain relief, 77% vs 52% (p=0.03). In patients whose first dose was lasmiditan, the incidence of treatment emergent adverse events (TEAEs) reported after the second dose was similar whether second dose was lasmiditan or placebo. Conclusions A second dose of lasmiditan showed some evidence of efficacy when taken for headache recurrence. There was no clear benefit of a second dose of lasmiditan for rescue treatment. The incidences of TEAEs were similar whether the second dose was lasmiditan or placebo.

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