scholarly journals P0003ADHERENCE BENEFITS OF ADV7103, AN INNOVATIVE PROLONGED-RELEASE ORAL COMBINATION PRODUCT, IN PATIENTS WITH DISTAL RENAL TUBULAR ACIDOSIS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Aurélia Bertholet-Thomas ◽  
Catherine Guittet ◽  
Maria Asunción Manso-Silván ◽  
Victor Navas Serrano ◽  
Luc André Granier ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Renal Tubular Acidosis ◽  
Potassium Citrate ◽  
Distal Renal Tubular Acidosis ◽  
Prolonged Release ◽  
Open Label ◽  
Advanced Therapy ◽  
Renal Tubular

Abstract Background and Aims Distal renal tubular acidosis (dRTA) is a rare disorder leading to impaired net acid excretion by the kidney inducing hyperchloremic metabolic acidosis and hypokalemia. The therapeutic effect of the standard of care is of short duration and requires multiple day and night administrations; it is also often accompanied by gastrointestinal discomfort and poor palatability impacting medication adherence. ADV7103, the first advanced therapy for dRTA, consists of a combination of prolonged-release potassium citrate and prolonged-release potassium bicarbonate granules providing round-the-clock alkali and potassium coverage with twice daily administration. Long-term adherence with ADV7103 is reported, along with acceptability of the product. Method B22CS is a multicentre, open-label long-term extension study, evaluating safety, tolerability, acceptability and efficacy of ADV7103 in adult and paediatric patients with dRTA. Adherence was assessed at each study visit up to 24 months, based on accountability of study drug retrieval, laboratory results, and interview of the patients in a diary and expressed as the proportion of patients that presented adherence lower than 50%, between 50% and 74%, between 75 and 90%, and higher than to 90%. Treatment acceptability as well as quality of life of the patients and their parents were assessed using a 100-mm visual analogue scales (VAS). Results Table 1 shows the evolution of compliance between Month 6 and Month 24. Overall, of the 29 patients remaining in the study after 24 months, 18 (62%) had adherence rates >90%, 5 (17%) had adherence rates of 75-90%, 6 (21%) had adherence rates of 50-74%, and there were no patients with adherence <50%. Adherence was good in all age groups, with rates of ≥75% in 100% of adults, 63% of adolescents 85% of children, and 67% of infants and toddlers. Compared to the alkalising treatments they had before the study, more than 80% of the patients perceived both the improvement of the formulation and of the number of daily doses at scores ≥ 75 mm. The overall improvement of quality of life reported by the patients was of 89 ± 19 mm and that reported by their parents was of 90 ± 14 mm after 24 months of treatment. Conclusion Adherence to treatment was maintained at a high level throughout the 24 months of the study confirming the good acceptance of ADV7103 therapy.

scholarly journals Safety, efficacy, and acceptability of ADV7103 during 24 months of treatment: an open-label study in pediatric and adult patients with distal renal tubular acidosis

2021 ◽  
Author(s):  
Aurélia Bertholet-Thomas ◽  
Catherine Guittet ◽  
Maria A. Manso-Silván ◽  
Sophie Joukoff ◽  
Victor Navas-Serrano ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Renal Tubular Acidosis ◽  
Distal Renal Tubular Acidosis ◽  
Adult Patients ◽  
Prolonged Release ◽  
Open Label ◽  
Plasma Bicarbonate ◽  
Normal Ranges ◽  
Renal Tubular

Abstract Background A new prolonged-release formulation of potassium citrate and potassium bicarbonate, ADV7103, has been shown to improve metabolic control, palatability, and gastrointestinal safety in patients with distal renal tubular acidosis (dRTA) when compared to standard of care (SoC) treatments. The present work evaluates safety and efficacy of ADV7103 during 24 months. Methods Thirty pediatric and adult patients were included in an open-label extension study after a phase II/III trial. Safety and tolerability were assessed. Plasma bicarbonate and potassium levels, as well as urine parameters, were evaluated over time. Acceptability, adherence, and quality of life were also assessed. The evolution of clinical consequences of dRTA in the cohort was explored. Results There were 104 adverse events (AEs) reported, but only 9 gastrointestinal events observed in five patients (17%) were considered to be related to ADV7103 treatment. There were no AEs leading to treatment discontinuation. Plasma bicarbonate and potassium levels were in the normal ranges at the different visits, respectively, in 69–86% and 83–93% of patients. Overall adherence rates were ≥ 75% throughout the whole study in 79% patients. An average improvement of quality of life of 89% was reported at 24 months of study. Conclusions Common AEs concerned metabolism and gastrointestinal disorders; the former being related to the disease. Less than half of the gastrointestinal AEs were related to ADV7103 treatment and they were mostly mild in severity. Metabolic parameters were maintained in the normal ranges in most patients. Patient satisfaction was high and adherence to treatment was good and remained stable. Trial registration number Registered as EudraCT 2013-003828-36 on the 3rd of September 2013. Graphical Abstract

scholarly journals Long-Term Effectiveness and Tolerability of Pain Treatment with Tapentadol Prolonged Release

2020 ◽  
Vol 1;24 (1;1) ◽  
pp. E75-E85
Keyword(s):  
Quality Of Life ◽  
Chronic Pain ◽  
Neuropathic Pain ◽  
Knee Pain ◽  
Prolonged Release ◽  
Low Back ◽  
State Of Health ◽  
Open Label

BACKGROUND: The central analgesic tapentadol prolonged release (PR) has proven effective and generally well tolerated in a broad range of chronic pain conditions. Long-term data of its use are still scarce. OBJECTIVES: To evaluate long-term effectiveness, tolerability, and safety of tapentadol PR in patients with severe chronic osteoarthritis (OA) knee pain or low back pain (LBP) who responded to tapentadol in 1 of 4 preceding 12-week phase 3b clinical trials. STUDY DESIGN: Open-label, uncontrolled, observational extension study of up to 72 weeks. SETTING: Fourteen centers in Spain. Protocol approval by the reference ethics committee for all the participating centers. METHODS: Eligible patients started the extension trial on the tapentadol PR dosage optimized for them in the preceding trial; dose adjustments were permitted throughout the extension. Treatment effectiveness outcomes included changes in pain intensity, sleep, state of health, quality of life, patient and clinician global impression of change, and patients’ satisfaction with treatment. Patients with OA knee pain also answered the Western Ontario and McMaster Universities OA index, and patients with LBP with a possible neuropathic pain component completed neuropathic pain-related questionnaires. RESULTS: Eighty-three patients were enrolled: 40 with OA knee pain, 43 with LBP. The full analysis set consisted of 81 patients. Mean pain intensity remained relatively stable over the 72-week extension period with mean increases from baseline of 0.44 (95% confidence interval [CI], -0.1,1.0; Numeric Rating Scale) for all patients, 0.2 (95% CI, -0.5, 0.9) for patients with OA, and 0.68 (95% CI, -0.2, 1.6) for patients with LBP. State of health and quality of life baseline ratings were maintained; overall impression of change was “improved.” Most patients (88.9%) reported at least good treatment satisfaction at the end of treatment. Mean daily tapentadol PR doses slightly increased from 313.3 ± 139.5 mg at baseline to 315.7 ± 140.1 mg at end of study. Uptitration was required for 8.4% of the patients, 4.8% had a dose reduction during the trial. Adverse events considered probably/likely or certainly related to tapentadol PR treatment by the investigator were documented for 18.1% of all patients, most commonly constipation (7.2%). Seven patients (8.4%) experienced adverse events leading to premature discontinuation. LIMITATIONS: An open-label design, stable concomitant analgesics (World Health Organization step I), and dose adjustments were allowed during the study. All patients had benefitted from tapentadol PR in preceding trials. CONCLUSIONS: Sustained pain relief and quality of life for up to 72 treatment weeks under relatively stable dosing, as well as the good safety profile, indicate the usefulness of tapentadol PR for patients who suffer from severe chronic OA knee pain and LBP with limited risk for tolerance development. KEY WORDS: Tapentadol prolonged release, extension study, long-term, chronic pain, osteoarthritis, low back pain, efficacy, safety

PUK22 Treatment Adherence and Quality of Life in UK Distal Renal Tubular Acidosis Patients

2021 ◽  
Vol 24 ◽  
pp. S237
Author(s):  
D. Sudusinghe ◽  
I. Dunnett ◽  
J. Mumford ◽  
A. Chrysos ◽  
S. Donald ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Treatment Adherence ◽  
Renal Tubular Acidosis ◽  
Distal Renal Tubular Acidosis ◽  
Renal Tubular

scholarly journals Nine-year prospective efficacy and safety of brain-responsive neurostimulation for focal epilepsy

Neurology ◽  
2020 ◽  
Vol 95 (9) ◽  
pp. e1244-e1256 ◽  
Author(s):  
Dileep R. Nair ◽  
Kenneth D. Laxer ◽  
Peter B. Weber ◽  
Anthony M. Murro ◽  
Yong D. Park ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Seizure Frequency ◽  
Focal Epilepsy ◽  
Responder Rate ◽  
Seizure Freedom ◽  
Open Label ◽  
Cognitive Domains ◽  
Signed Rank

ObjectiveTo prospectively evaluate safety and efficacy of brain-responsive neurostimulation in adults with medically intractable focal onset seizures (FOS) over 9 years.MethodsAdults treated with brain-responsive neurostimulation in 2-year feasibility or randomized controlled trials were enrolled in a long-term prospective open label trial (LTT) to assess safety, efficacy, and quality of life (QOL) over an additional 7 years. Safety was assessed as adverse events (AEs), efficacy as median percent change in seizure frequency and responder rate, and QOL with the Quality of Life in Epilepsy (QOLIE-89) inventory.ResultsOf 256 patients treated in the initial trials, 230 participated in the LTT. At 9 years, the median percent reduction in seizure frequency was 75% (p < 0.0001, Wilcoxon signed rank), responder rate was 73%, and 35% had a ≥90% reduction in seizure frequency. We found that 18.4% (47 of 256) experienced ≥1 year of seizure freedom, with 62% (29 of 47) seizure-free at the last follow-up and an average seizure-free period of 3.2 years (range 1.04–9.6 years). Overall QOL and epilepsy-targeted and cognitive domains of QOLIE-89 remained significantly improved (p < 0.05). There were no serious AEs related to stimulation, and the sudden unexplained death in epilepsy (SUDEP) rate was significantly lower than predefined comparators (p < 0.05, 1-tailed χ2).ConclusionsAdjunctive brain-responsive neurostimulation provides significant and sustained reductions in the frequency of FOS with improved QOL. Stimulation was well tolerated; implantation-related AEs were typical of other neurostimulation devices; and SUDEP rates were low.ClinicalTrials.gov identifierNCT00572195.Classification of evidenceThis study provides Class IV evidence that brain-responsive neurostimulation significantly reduces focal seizures with acceptable safety over 9 years.

scholarly journals Treatment and long-term outcome in primary distal renal tubular acidosis

2019 ◽  
Vol 34 (6) ◽  
pp. 981-991 ◽  
Author(s):  
Sergio Camilo Lopez-Garcia ◽  
Francesco Emma ◽  
Stephen B Walsh ◽  
Marc Fila ◽  
Nakysa Hooman ◽  
...  
Keyword(s):  
Renal Tubular Acidosis ◽  
Distal Renal Tubular Acidosis ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Renal Tubular

scholarly journals Long-Term Prolonged-Release Fampridine Treatment and Health-Related Quality of Life Outcomes: Interim Results of the Enable Study

2013 ◽  
Vol 16 (7) ◽  
pp. A627
Author(s):  
G. Nagels ◽  
R. Macdonell ◽  
P. Soelberg Sorensen ◽  
C. Pozzilli ◽  
D. Laplaud ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Prolonged Release ◽  
Health Related Quality ◽  
Life Outcomes ◽  
Quality Of Life Outcomes ◽  
Related Quality ◽  
Health Related

scholarly journals Sustained Improvement in Health-Related Quality of Life in Patients with Hemophilia A with or without Inhibitors Treated with Fitusiran Prophylaxis

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3197-3197
Author(s):  
Viridiana Cano ◽  
José Bartelt-Hofer ◽  
Wenruo Hu ◽  
Shauna R. Andersson ◽  
Pronabesh Dasmahapatra ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Board Of Directors ◽  
Phase 1 ◽  
Publicly Traded ◽  
Open Label ◽  
Advisory Committees ◽  
Open Label Extension ◽  
Related Quality

Abstract BACKGROUND Fitusiran is an investigational, subcutaneous (SC), prophylactically administered small interfering RNA (siRNA) therapeutic. It targets antithrombin and restores thrombin generation sufficient to rebalance hemostasis in people with hemophilia A or B, with or without inhibitors. Long-term exposure to fitusiran is being studied in a Phase 1/2, 6-year open-label extension study (NCT02554773) in patients with hemophilia (PwH) A or B with or without inhibitors. Improvement in the health-related quality of life (HRQoL) as measured by Haemophilia Quality of Life Questionnaire for Adults (Haem-A-QoL) total score, and specifically in the physical health domain was previously reported by von Mackensen et al. for PwHA with inhibitors (NCT02554773, N=17, von Mackensen et al. Blood 2020;136(1):23-24). This analysis aimed to present HRQoL changes from baseline to last available measure (LAM), as measured by the Haem-A-QoL total score and domains (filtered by actual treatment exposure following 2 voluntary dosing holds) in PwHA, with or without inhibitors, who continued into the Phase 2 open-label extension study. METHODS Participants who completed the Phase 1 study (NCT02035605) were eligible to participate in Phase 2 long-term exposure study (NCT02554773). All participants received fixed monthly doses of 50 mg (N=9) or 80 mg (N=18) of fitusiran. HRQoL data were collected in 3-month lapse periods. Mean changes from baseline to LAM were calculated for the Haem-A-QoL (total score and domains). RESULTS As of February 2021, 26 severe and 1 moderate PwHA (13 with, 14 without inhibitors) with mean baseline age (SD) 37.3 (9.7) were treated for up to mean (SD) 33.32 (17.06) months. For the total Haem-A-QoL score and each of 10 domains, mean improvements from baseline to LAM (lower scores denoting better HRQoL) were consistently observed in PwHA (except for the sport & leisure domain that was higher in the non-inhibitor group). Mean estimated reductions (SD) in the Haem-A-QoL total score were -8.33 (13.84) and -9.16 (14.55) while that in the physical health domain score were -13.21 (25.07) and -7.14 (22.80), for PwHA with and without inhibitors respectively (Table 1). When comparing Haem-A-QoL domains in inhibitor to non-inhibitor participants, results suggest a modest favorable trend for non-inhibitor patients (greater reductions in 4 vs 6 domains, respectively). CONCLUSIONS Mean improvements in the Haem-A-QoL total scores and 9 out of 10 domains suggest sustained HRQoL improvements in PwHA. Small sample size and outlying results might limit the interpretation. Further research in HRQoL for fitusiran will include a larger population on the new 50 mg every other month dose regimen, and notably Phase III results from NCT03549871 (open-label study in patients switching to fitusiran from previous prophylaxis or bypassing agents) and NCT03754790 (open-label, long-term safety and efficacy study of fitusiran) in various subpopulations. Figure 1 Figure 1. Disclosures Cano: Sanofi Genzyme: Current Employment, Current equity holder in publicly-traded company; Takeda: Ended employment in the past 24 months. Bartelt-Hofer: Sanofi: Current Employment, Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company. Hu: Sanofi: Current Employment. Andersson: Sanofi: Current Employment, Current equity holder in publicly-traded company; WEST advisory committee member: Membership on an entity's Board of Directors or advisory committees. Dasmahapatra: Sanofi: Current Employment, Current equity holder in publicly-traded company. Von Mackensen: Biomarin: Speakers Bureau; Novo Nordisk: Consultancy; Sanofi: Consultancy; Sobi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; University Medical Centre Hamburg-Eppendorf: Current Employment; CSL Behring: Speakers Bureau; Chugai/Roche: Membership on an entity's Board of Directors or advisory committees.

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