Relief of bowel-related symptoms with telotristat etiprate in octreotide refractory carcinoid syndrome: Preliminary results of a placebo-controlled, multicenter study.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 312-312 ◽  
Author(s):  
Thomas M. O'Dorisio ◽  
Alexandria T. Phan ◽  
Robert M. Langdon ◽  
Billie J. Marek ◽  
Nadeem Ikhlaque ◽  
...  
Keyword(s):  
Carcinoid Syndrome ◽  
Bowel Movement ◽  
Biochemical Response ◽  
Categorical Variables ◽  
Open Label ◽  
The Past ◽  
Day Range ◽  
Bowel Movements ◽  
Expansion Cohort ◽  
To Receive

312 Background: Diarrhea associated with carcinoid syndrome (CS) has been attributed to tumor production of serotonin. Telotristat etiprate, (LX1032, LX1606), is an oral inhibitor of peripheral serotonin synthesis. This study explored the safety, tolerability, and efficacy of telotristat etiprate in carcinoid patients with octreotide-refractory diarrhea. Methods: Carcinoid patients with >4 bowel movements (BM)/day on octreotide were randomized 3:1 to receive telotristat etiprate or placebo. Patients enrolled in sequential, escalating dose cohorts of 150, 250, 350, or 500 mg tid, followed by a 500 mg tid expansion cohort. Patients were followed for toxicity, 24-hr urinary 5-HIAA (u5-HIAA) secretion, BM frequency, and self-reported relief of bowel-related symptoms. Subjects were asked “In the past 7 days, have you had adequate relief of your carcinoid syndrome bowel complaints such as diarrhea, urgent need to have a bowel movement, abdominal pain or discomfort?” Responses (yes or no) were analyzed as categorical variables. Results: 16 patients enrolled in the 4 escalating dose cohorts and 7 in the expansion cohort; 18 on telotristat etiprate and 5 on placebo. Median age was 62 yrs with a mean 6.2 BMs/day (range 4-10). AEs included primarily mild-moderate diarrhea, nausea, and abdominal discomfort. In treated subjects, adequate relief was reported as follows: Week 1 – 6/18 (33.3%), Week 2 – 5/16 (31.3%), Week 3 - 5/15 (33.3%), and Week 4 – 6/12 (50.0%). No placebo subjects reported improvement at any timepoint. Biochemical response (>50%reduction in u5-HIAA) and BM response (>30% reduction in daily BM for 2 weeks) were associated with reporting of adequate relief. For evaluable telotristat etiprate-treated patients, 9/16 (56%) experienced a biochemical response and 5/18 (28%) experienced a clinical (BM) response; no placebo subjects achieved either biochemical or clinical response. Conclusions: Treatment with telotristat etiprate was associated with decreases in u5-HIAA and BM frequency, and with self-reported relief of bowel related symptoms. Treatment in an extension phase with open-label telotristat etiprate is ongoing.

Relief of bowel-related symptoms with telotristat etiprate in octreotide refractory carcinoid syndrome: Preliminary results of a double-blind, placebo-controlled multicenter study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4085-4085
Author(s):  
Thomas M. O'Dorisio ◽  
Alexandria T. Phan ◽  
Robert M. Langdon ◽  
Billie J. Marek ◽  
Nadeem Ikhlaque ◽  
...  
Keyword(s):  
Carcinoid Syndrome ◽  
Biochemical Response ◽  
Categorical Variables ◽  
Open Label ◽  
Double Blind ◽  
The Past ◽  
Day Range ◽  
Bowel Movements ◽  
Expansion Cohort ◽  
To Receive

4085 Background: Diarrhea associated with carcinoid syndrome has been attributed to tumor production of serotonin. Telotristat etiprate, (LX1032, LX1606), is an oral inhibitor of peripheral serotonin synthesis. This study explored the safety, tolerability, and efficacy of telotristat etiprate in carcinoid patients with octreotide-refractory diarrhea. Methods: Carcinoid patients with ≥4 bowel movements (BMs)/day on octreotide were randomized 3:1 to receive telotristat etiprate or placebo as double-blind treatment. Patients enrolled in sequential, escalating dose cohorts of 150, 250, 350, or 500 mg tid, followed by a 500 mg tid expansion cohort. Patients were followed for toxicity, 24-hr urinary 5-HIAA (u5-HIAA), BM frequency, and self-reported bowel-related symptoms. Subjects were asked “In the past 7 days, have you had adequate relief of your carcinoid syndrome bowel complaints such as diarrhea, urgent need to have a bowel movement, abdominal pain or discomfort?” Responses (yes or no) were analyzed as categorical variables. Results: 16 patients enrolled in the 4 escalating dose cohorts and 7 in the expansion cohort; 18 on telotristat etiprate and 5 on placebo. Median age: 62 yrs; mean 6.3 BMs/day (range, 4-10). AEs included primarily mild-moderate diarrhea, nausea, and abdominal discomfort. In treated subjects, adequate relief was reported as: Week 1 - 6/18 (33.3%), Week 2 - 5/16 (31.3%), Week 3 - 5/15 (33.3%), and Week 4 - 6/13 (46.0%). No placebo subjects reported improvement at any timepoint. Biochemical response (≥50%reduction in u5-HIAA) and BM response (≥30% reduction in daily BMs for 2 weeks) were associated with reporting of adequate relief. For evaluable telotristat etiprate-treated patients, 9/16 (56%) experienced a biochemical response and 5/18 (28%) experienced a clinical (BM) response; no placebo subjects achieved either biochemical or clinical response. Conclusions: Treatment with telotristat etiprate was associated with decreases in u5-HIAA and BM frequency, and with self-reported relief of bowel related symptoms. Treatment in an extension phase with open-label telotristat etiprate is ongoing.

scholarly journals Evaluation of meaningful change in bowel movement frequency for patients with carcinoid syndrome

2019 ◽  
Vol 3 (1) ◽  
Author(s):  
Stacie Hudgens ◽  
John Ramage ◽  
Matthew Kulke ◽  
Emily Bergsland ◽  
Lowell Anthony ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Effect Size ◽  
Carcinoid Syndrome ◽  
Bowel Movement ◽  
Life Questionnaire ◽  
Meaningful Change ◽  
Movement Frequency ◽  
Bowel Movements ◽  
Bowel Movement Frequency

Abstract Background Carcinoid syndrome is associated with a reduced quality of life that can be attributed to symptoms such as diarrhea and fatigue as well as social and financial issues. This study was conducted to psychometrically assess meaningful change in bowel movement frequency among carcinoid syndrome patients using data from the TELESTAR clinical study. Methods An anchor-based approach for deriving meaningful change thresholds consisted of mapping change from baseline bowel movement frequency to other patient-reported assessments of change. These included the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core Questionnaire (QLQ-C30) Diarrhea Symptom responders, the EORTC Gastrointestinal NET questionnaire (GI.NET21) GI Symptom responders, and reported adequate relief at Week 12 (≥ 10-point score decrease from Day 1 to Week 12). Parameters included within-group mean change from baseline to Week 12, t-tests of the change (Wilcoxon rank sum for adequate relief), and effect size. Results There were 135 carcinoid syndrome patients with a mean baseline frequency of 5.7 bowel movements a day. A distribution-based method yielded meaningful change estimates of 0.62 bowel movements a day for overall frequency and 0.83 bowel movements a day at Week 12. Anchor-based analysis indicated a large effect size among patients who reported adequate relief at Week 12 (− 1.58; n = 18; P = 0.014), the QLQ-C30 Diarrhea domain responders (− 1.24; n = 40; P < 0.001), and the GI.NET21 GI Symptoms Domain responders (− 1.49; n = 25; P = 0.005). Exit interview data for meaningful change yielded effect size estimates of − 1.57 for overall change during the Double-blind Treatment Period and − 1.97 for change between Baseline and Week 12. Conclusions Meaningful change derivation is critical to interpret patient outcomes for evaluating treatment efficacy. In this study, carcinoid syndrome patients experienced clinically meaningful reductions in bowel movement frequency of ≥30% over 12 weeks with telotristat ethyl treatment. Trial registration NCT01677910.

scholarly journals Telotristat ethyl in carcinoid syndrome: safety and efficacy in the TELECAST phase 3 trial

2018 ◽  
Vol 25 (3) ◽  
pp. 309-322 ◽  
Author(s):  
Marianne Pavel ◽  
David J Gross ◽  
Marta Benavent ◽  
Petros Perros ◽  
Raj Srirajaskanthan ◽  
...  
Keyword(s):  
Carcinoid Syndrome ◽  
Tryptophan Hydroxylase ◽  
Somatostatin Analogs ◽  
Confidence Limits ◽  
Open Label ◽  
Phase 3 ◽  
Double Blind ◽  
Safety And Efficacy ◽  
Bowel Movements ◽  
Hydroxyindoleacetic Acid

Telotristat ethyl, a tryptophan hydroxylase inhibitor, was efficacious and well tolerated in the phase 3 TELESTAR study in patients with carcinoid syndrome (CS) experiencing ≥4 bowel movements per day (BMs/day) while on somatostatin analogs (SSAs). TELECAST, a phase 3 companion study, assessed the safety and efficacy of telotristat ethyl in patients with CS (diarrhea, flushing, abdominal pain, nausea or elevated urinary 5-hydroxyindoleacetic acid (u5-HIAA)) with <4 BMs/day on SSAs (or ≥1 symptom or ≥4 BMs/day if not on SSAs) during a 12-week double-blind treatment period followed by a 36-week open-label extension (OLE). The primary safety and efficacy endpoints were incidence of treatment-emergent adverse events (TEAEs) and percent change from baseline in 24-h u5-HIAA at week 12. Patients (N = 76) were randomly assigned (1:1:1) to receive placebo or telotristat ethyl 250 mg or 500 mg 3 times per day (tid); 67 continued receiving telotristat ethyl 500 mg tid during the OLE. Through week 12, TEAEs were generally mild to moderate in severity; 5 (placebo), 1 (telotristat ethyl 250 mg) and 3 (telotristat ethyl 500 mg) patients experienced serious events, and the rate of TEAEs in the OLE was comparable. At week 12, significant reductions in u5-HIAA from baseline were observed, with Hodges–Lehmann estimators of median treatment differences from placebo of −54.0% (95% confidence limits, −85.0%, −25.1%, P < 0.001) and −89.7% (95% confidence limits, −113.1%, −63.9%, P < 0.001) for telotristat ethyl 250 mg and 500 mg. These results support the safety and efficacy of telotristat ethyl when added to SSAs in patients with CS diarrhea (ClinicalTrials.gov identifier: Nbib2063659).

Provision of Remedies for Violation of Economic, Social and Cultural Rights: A Comparative Study of the United Nations, Inter-American and African Human Rights Systems

2020 ◽  
Vol 28 (2) ◽  
pp. 298-318
Author(s):  
Roman Girma Teshome
Keyword(s):  
Human Rights ◽  
United Nations ◽  
Comparative Study ◽  
Economic Rights ◽  
Regional Monitoring ◽  
Cultural Rights ◽  
The Past ◽  
The United Nations ◽  
To Receive

The effectiveness of human rights adjudicative procedures partly, if not most importantly, hinges upon the adequacy of the remedies they grant and the implementation of those remedies. This assertion also holds water with regard to the international and regional monitoring bodies established to receive individual complaints related to economic, social and cultural rights (hereinafter ‘ESC rights’ or ‘socio-economic rights’). Remedies can serve two major functions: they are meant, first, to rectify the pecuniary and non-pecuniary damage sustained by the particular victim, and second, to resolve systematic problems existing in the state machinery in order to ensure the non-repetition of the act. Hence, the role of remedies is not confined to correcting the past but also shaping the future by providing reforming measures a state has to undertake. The adequacy of remedies awarded by international and regional human rights bodies is also assessed based on these two benchmarks. The present article examines these issues in relation to individual complaint procedures that deal with the violation of ESC rights, with particular reference to the case laws of the three jurisdictions selected for this work, i.e. the United Nations, Inter-American and African Human Rights Systems.

Impact of Temperature on Injection-Related Pain Caused by Subcutaneous Administration of Ustekinumab: A Three-arm Crossover Open-label Randomized Controlled Trial

2017 ◽  
Vol 1 (3) ◽  
pp. 117-127
Author(s):  
Yasaman Mansouri ◽  
Yasmin Amir ◽  
Michelle Min ◽  
Raveena Khanna ◽  
Ruiqi Huang ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Subcutaneous Administration ◽  
Open Label ◽  
Post Dose ◽  
Subcutaneous Injections ◽  
Pain Scores ◽  
Observational Cohort ◽  
Vas Scores ◽  
Pre Treatment ◽  
To Receive

Background: Adherence to subcutaneous biologic agents for the treatment of psoriasis can be negatively influenced by injection pain.Objective: To explore the differences in injection site pain when patients are pre-treated with heat or cold, versus no pre-treatment prior to administration of a subcutaneous biologic agent.Methods: In an observational cohort study, patients receiving subcutaneous injections of ustekinumab were randomly assigned to receive pretreatment with ice, heat, or no intervention over three visits. Post-dose, patients rated pain on a 100 mm visual analogue scale (VAS).Results: There was an increase in the VAS score for both heat (2.51, P=0.30) and ice (3.33, P=0.16), compared to no intervention. No differences were found between the two intervention groups (-0.83, P=0.73). On average, females had the same VAS scores with ice compared to that of no intervention (-0.12, P=0.97) and a non–significant decrease of 3.29 points (P=0.38) with heat. Males had increased pain scores by 5.65 points (P=0.07) with ice and by 6.39 points (P=0.04) with heat.Limitations: Pain is a subjective measurement and objective quantification is difficult.Conclusions: On average, neither heat nor cold application reliably reduced pain. Our results do not support the application of heat or cold prior to ustekinumab injection.

scholarly journals Further improvement in glycemic control after switching from exenatide two times per day to exenatide once-weekly autoinjected suspension in patients with type 2 diabetes: 52-week results from the DURATION-NEO-1 study

2020 ◽  
Vol 8 (1) ◽  
pp. e000773
Author(s):  
Carol H Wysham ◽  
Julio Rosenstock ◽  
Marion L Vetter ◽  
Hui Wang ◽  
Elise Hardy ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Weight ◽  
Phase Iii ◽  
Open Label ◽  
Open Label Study ◽  
Registration Number ◽  
Efficacy Measures ◽  
Design And Methods ◽  
To Receive

IntroductionInvestigate the effects of switching from two times per day exenatide to once-weekly exenatide administered by autoinjector (exenatide once-weekly suspension by autoinjector (QWS-AI)) or treatment with exenatide QWS-AI for 1 year.Research design and methodsIn this phase III open-label study, adults with type 2 diabetes were randomized to receive exenatide QWS-AI (2 mg) or exenatide two times per day (5 mcg for 4 weeks, followed by 10 mcg) for 28 weeks. During a subsequent non-randomized 24-week extension, patients who received exenatide two times per day were switched to exenatide QWS-AI and those randomized to exenatide QWS-AI continued this treatment. Efficacy measures included changes from baseline in glycated hemoglobin (A1C), fasting plasma glucose (FPG), and body weight.ResultsIn total, 315 patients (mean baseline A1C of 8.5%) completed the initial 28 weeks of randomized treatment with exenatide QWS-AI (n=197) or exenatide two times per day (n=118) and were included in the 24-week extension (mean A1C of 7.0% and 7.3%, respectively, at week 28). From weeks 28–52, patients who switched from exenatide two times per day to exenatide QWS-AI had additional A1C reductions of approximately 0.5% (mean A1C change from baseline of –1.4% at week 52) and further reductions from baseline in FPG. Patients who continued exenatide QWS-AI treatment for 52 weeks showed clinically relevant A1C reductions (mean A1C change from baseline of –1.3% at week 52). Body-weight reductions achieved through week 28 were sustained at week 52 in both groups. There were no unexpected safety concerns or changes in the safety profile among patients who switched from exenatide two times per day to exenatide QWS-AI or those who continued exenatide QWS-AI treatment for 52 weeks.ConclusionsSwitching from exenatide two times per day to exenatide QWS-AI resulted in further A1C reductions and maintenance of earlier decreases in body weight, while continued therapy with exenatide QWS-AI for 52 weeks maintained A1C and body-weight reductions, without additional safety or tolerability concerns.Trial registration numberNCT01652716.

scholarly journals Oxygen saturation improved with nitrate-based nutritional formula in patients with COVID-19

2021 ◽  
Vol 49 (4) ◽  
pp. 030006052110123
Author(s):  
Sergej M. Ostojic ◽  
Aleksandra Milovancev ◽  
Patrik Drid ◽  
Alexandros Nikolaidis
Keyword(s):  
Oxygen Saturation ◽  
Patient Reported Outcomes ◽  
Case Series ◽  
Potassium Nitrate ◽  
Open Label ◽  
Patient Reported ◽  
Baseline Values ◽  
Study Participants ◽  
To Receive ◽  
Test Result

In this open-label case series trial, we evaluated the effects of a nitrate-based nutritional formula on oxygen saturation (SpO2) and patient-reported outcomes in individuals with coronavirus disease 2019 (COVID-19). Five adult patients (three men and two women, age 39.6 ± 6.9 years) with a positive COVID-19 test result, breathing difficulties, and SpO2 ≤95%, who were free from other pulmonary and cardiovascular conditions, were recruited for this study. Participants were assigned to receive a multi-component nutritional formula (containing 1200 mg of potassium nitrate, 200 mg of magnesium, 50 mg of zinc, and 1000 mg of citric acid) every 4 hours during the 48-hour monitoring period. In all participants, SpO2 improved immediately after administration of the nutritional formula, from 1 to 7 percentage points (mean increase 3.6 ± 2.7 points; 95% confidence interval 0.3 to 7.0). SpO2 remained above baseline values throughout the monitoring interval, with values persisting over threshold values (>92%) for all patients and at each time point during the 48 hours. No patients reported any side effects of the intervention. These promising and rather unexpected results call for immediate, well-sampled, mechanistic randomized controlled trials to validate our findings.

Industry Payments to Plastic Surgeons: What Has Changed Over the Last Six-Years Following Implementation of the Physician Payment Sunshine Act?

2021 ◽  
Author(s):  
Rowland W Pettit ◽  
Jordan Kaplan ◽  
Matthew M Delancy ◽  
Edward Reece ◽  
Sebastian Winocour ◽  
...  
Keyword(s):  
United States ◽  
User Interface ◽  
Stock Options ◽  
Data Interpretation ◽  
The United States ◽  
Inclusion Criteria ◽  
Physician Payment ◽  
The Past ◽  
To Receive ◽  
Open Payments

Abstract Background The Open Payments Program, as designated by the Physician Payments Sunshine Act is the single largest repository of industry payments made to licensed physicians within the United States. Though sizeable in its dataset, the database and user interface are limited in their ability to permit expansive data interpretation and summarization. Objectives We sought to comprehensively compare industry payments made to plastic surgeons with payments made to all surgeons and all physicians to elucidate industry relationships since implementation. Methods The Open Payments Database was queried between 2014 and 2019, and inclusion criteria were applied. These data were evaluated in aggregate and for yearly totals, payment type, and geographic distribution. Results 61,000,728 unique payments totaling $11,815,248,549 were identified over the six-year study period. 9,089 plastic surgeons, 121,151 surgeons, and 796,260 total physicians received these payments. Plastic surgeons annually received significantly less payment than all surgeons (p=0.0005). However, plastic surgeons did not receive significantly more payment than all physicians (p = 0.0840). Cash and cash equivalents proved to be the most common form of payment; Stock and stock options were least commonly transferred. Plastic surgeons in Tennessee received the most in payments between 2014-2019 (mean $ 76,420.75). California had the greatest number of plastic surgeons to receive payments (1,452 surgeons). Conclusions Plastic surgeons received more in industry payments than the average of all physicians but received less than all surgeons. The most common payment was cash transactions. Over the past six years, geographic trends in industry payments have remained stable.

scholarly journals Kaleidoscope

2017 ◽  
Vol 210 (4) ◽  
pp. 307-308 ◽  
Author(s):  
Derek K. Tracy ◽  
Dan W. Joyce ◽  
Sukhwinder S. Shergill
Keyword(s):  
Smoking Prevalence ◽  
Health Belief ◽  
Proactive Approach ◽  
The Past ◽  
Quitting Smoking ◽  
Stop Smoking Services ◽  
General Practices ◽  
Belief Model ◽  
To Receive ◽  
The Health Belief Model

Quitting smoking isn't easy, even with the advent of e-cigarettes. The NHS Stop Smoking Services (SSSs) were established in 2000, and have shown superior results to nicotine replacement alone, but are characterised by low, and dropping, attendance rates. Beneath the highlight figure of a halving of UK smoking prevalence over the past 40 years lies a direct £6 billion cost to the NHS and 80000 deaths each year, as well as recent concern that clinical commissioning groups are not renewing service funding. Given that the ‘health belief model’ is based upon a trigger changing behaviour, what will encourage attendance at SSSs, especially with evidence that smokers underestimate their own personal risk? Gilbert et al randomised over 4000 smokers across almost 100 general practices to receive either a standard generic advertisement of the SSS clinic, or an individually tailored risk letter and invitation to a no-commitment introductory SSS session. The hosting general practitioners (GPs) and SSS advisors were masked to the allocation. The personalised letter more than doubled the odds of attending the SSS, showing that a more proactive approach can help engagement. Interestingly, the intervention was more effective with men, who are typically less likely to attend and set quit dates.

Semiannual Treatment of Albendazole Alone is Efficacious for Treatment of Lymphatic Filariasis: A Randomized Open-label Trial in Cote d'Ivoire

2021 ◽  
Author(s):  
Allassane F Ouattara ◽  
Catherine M Bjerum ◽  
Méité Aboulaye ◽  
Olivier Kouadio ◽  
Vanga K Marius ◽  
...  
Keyword(s):  
Lymphatic Filariasis ◽  
Primary Outcome ◽  
Central Africa ◽  
Wuchereria Bancrofti ◽  
Bancroftian Filariasis ◽  
Loa Loa ◽  
Open Label ◽  
Treatment Groups ◽  
Open Label Trial ◽  
To Receive

Abstract Background Ivermectin (IVM) plus albendazole (ALB), or IA, is widely used in mass drug administration (MDA) programs that aim to eliminate lymphatic filariasis (LF) in Africa. However, IVM can cause severe adverse events in persons with heavy Loa loa infections that are common in Central Africa. ALB is safe in loiasis, but more information is needed on its efficacy for LF. This study compared the efficacy and safety of three years of semiannual treatment with ALB to annual IA in persons with bancroftian filariasis. Methods Adults with Wuchereria bancrofti microfilaremia (Mf) were randomized to receive either three annual doses of IA (N=52), six semiannual doses of ALB 400mg (N=45), or six semiannual doses of ALB 800mg (N=47). The primary outcome amicrofilaremia at 36 months. Findings IA was more effective for completely clearing Mf than ALB 400mg or ALB 800mg (79%, CI 67-91; vs. 48%, CI 32-66 and 57%, CI 41-73, respectively). Mean % reductions in Mf counts at 36 months relative to baseline tended to be greater after IA (98%, CI 88-100) than after ALB 400mg (88%, CI 78-98) and ALB 800mg (89%, CI 79-99) (P=0.07 and P=0.06, respectively). Adult worm nest numbers (assessed by ultrasound) were reduced in all treatment groups. Treatments were well tolerated. Interpretation Repeated semiannual treatment with ALB is macrofilaricidal for W. bancrofti and leads to sustained reductions in Mf counts. This is a safe and effective regimen that could be used as MDA to eliminate LF in areas ivermectin cannot be used.

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