PMID- 33635379 OWN - NLM STAT- MEDLINE DCOM- 20211221 LR - 20211221 IS - 1432-198X (Electronic) IS - 0931-041X (Print) IS - 0931-041X (Linking) VI - 36 IP - 7 DP - 2021 Jul TI - 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. PG - 1765-1774 LID - 10.1007/s00467-020-04873-0 [doi] AB - 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. FAU - Bertholet-Thomas, Aurelia AU - Bertholet-Thomas A AUID- ORCID: 0000-0002-4207-824X AD - Centre de Reference des Maladies Renales Rares-Nephrogones-Hopital Femme Mere Enfant, Hospices Civils de Lyon-Filiere ORKiD, Bron, France. aurelia.bertholet-thomas@chu-lyon.fr. FAU - Guittet, Catherine AU - Guittet C AD - Advicenne, Nimes, France. FAU - Manso-Silvan, Maria A AU - Manso-Silvan MA AUID- ORCID: 0000-0002-5056-9065 AD - Advicenne, Nimes, France. FAU - Joukoff, Sophie AU - Joukoff S AD - Advicenne, Nimes, France. FAU - Navas-Serrano, Victor AU - Navas-Serrano V AD - Advicenne, Nimes, France. FAU - Baudouin, Veronique AU - Baudouin V AD - Service de Nephrologie Pediatrique, Hopital Robert Debre, Paris, France. FAU - Cailliez, Mathilde AU - Cailliez M AD - Service de Pediatrie Multidisciplinaire, Hopital de la Timone, AP-HM, Marseille, France. FAU - Di Maio, Massimo AU - Di Maio M AD - Service de Reanimation Neonatale et Neonatologie, CHU de Nimes, Nimes, France. FAU - Gillion-Boyer, Olivia AU - Gillion-Boyer O AD - Service de Nephrologie Pediatrique, Centre de Reference des Maladies Renales Hereditaires de l'Enfant et de l'Adulte (MARHEA), Institut Imagine, Hopital Necker-Enfants Malades, Universite de Paris, Paris, France. FAU - Golubovic, Emilija AU - Golubovic E AD - Klinika za decije interne bolesti-Odeljenje za nefrologiju, Klinicki Centar Nis, Nis, Serbia. FAU - Harambat, Jerome AU - Harambat J AD - Service de Pediatrie, Centre de Reference Maladies Renales Rares du Sud-ouest (SoRare), CHU de Bordeaux, Hopital Pellegrin-Enfants, Bordeaux, France. FAU - Knebelmann, Bertrand AU - Knebelmann B AD - Service de Nephrologie adultes Hopital Necker, Paris, France. FAU - Nobili, Francois AU - Nobili F AD - Service de Pediatrie 2, Hopital Jean Minjoz, CHU de Besancon, Besancon, France. FAU - Novo, Robert AU - Novo R AD - Service de Nephrologie Pediatrique, Hopital Jeanne de Flandre, CHRU de Lille, Lille, France. FAU - Podracka, Ludmila AU - Podracka L AD - Department of Pediatrics, National Institute of Children's Health, Bratislava, Slovakia. FAU - Roussey-Kesler, Gwenaelle AU - Roussey-Kesler G AD - Unite de Nephrologie et Hemodialyse Pediatrique, Clinique Medicale Pediatrique Hopital Mere-Enfant, CHU de Nantes, Nantes, France. FAU - Granier, Luc-Andre AU - Granier LA AUID- ORCID: 0000-0002-4174-2487 AD - Advicenne, Nimes, France. LA - eng SI - EudraCT/2013-003828-36 PT - Clinical Trial PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210226 PL - Germany TA - Pediatr Nephrol JT - Pediatric nephrology (Berlin, Germany) JID - 8708728 RN - 0 (Bicarbonates) RN - 0 (Potassium Compounds) RN - EE90ONI6FF (Potassium Citrate) RN - HM5Z15LEBN (potassium bicarbonate) RN - RWP5GA015D (Potassium) SB - IM MH - *Acidosis, Renal Tubular/drug therapy MH - Adult MH - *Bicarbonates/adverse effects/therapeutic use MH - Child MH - Humans MH - Potassium MH - *Potassium Citrate/adverse effects/therapeutic use MH - *Potassium Compounds/adverse effects/therapeutic use MH - Quality of Life PMC - PMC8172410 OTO - NOTNLM OT - Acceptability OT - Adherence to treatment OT - Plasma bicarbonate OT - Safety OT - dRTA COIS- C. Guittet, M.A. Manso-Silvan and L.A. Granier are employees of Advicenne and hold stock options or shares in the company. S. Joukoff and V. Navas-Serrano are also employees of Advicenne. A. Bertholet received support from Advicenne for traveling to meetings and/or funding for lectures. EDAT- 2021/02/27 06:00 MHDA- 2021/12/22 06:00 PMCR- 2021/02/26 CRDT- 2021/02/26 12:12 PHST- 2020/07/06 00:00 [received] PHST- 2020/11/23 00:00 [accepted] PHST- 2020/10/21 00:00 [revised] PHST- 2021/02/27 06:00 [pubmed] PHST- 2021/12/22 06:00 [medline] PHST- 2021/02/26 12:12 [entrez] PHST- 2021/02/26 00:00 [pmc-release] AID - 10.1007/s00467-020-04873-0 [pii] AID - 4873 [pii] AID - 10.1007/s00467-020-04873-0 [doi] PST - ppublish SO - Pediatr Nephrol. 2021 Jul;36(7):1765-1774. doi: 10.1007/s00467-020-04873-0. Epub 2021 Feb 26.