FP001REDUCTION OF THE NUMBER OF DAILY INTAKES AND IMPROVED BLOOD BICARBONATE LEVELS IN DISTAL RENAL TUBULAR ACIDOSIS (DRTA) PATIENTS: INTEREST OF ADV7103, A NEW PROLONGED RELEASE FORMULATION

Abstract Background Distal renal tubular acidosis (dRTA), due to impaired acid secretion in the urine, can lead to severe long-term consequences. Standard of care (SoC) oral alkalizers, requiring several daily intakes, are currently used to restore normal plasma bicarbonate levels. A new prolonged-release formulation, ADV7103, has been developed to achieve a sustained effect with an improved dosing scheme. Methods In a multicenter, open-label, non-inferiority trial (n = 37), patients with dRTA were switched from SoC to ADV7103. Mean plasma bicarbonate values and proportion of responders during steady state therapy with both treatments were compared, as were other blood and urine parameters, as well as acceptability, tolerability, and safety. Results When switching from SoC to ADV7103, the number of daily intakes was reduced from a median of three to twice daily. Mean plasma bicarbonate was increased and non-inferiority of ADV7103 was demonstrated (p < 0.0001, per protocol), as was statistical superiority (p = 0.0008, intention to treat [ITT]), and the response rate increased from 43 to 90% with ADV7103 (p < 0.001, ITT). Urine calcium/citrate ratio was reduced below the threshold for risk of lithogenesis with ADV7103 in 56% of previously non-responders with SoC (p = 0.021, ITT). Palatability was improved (difference [95% CI] of 25 [10.7, 39.2] mm) and gastrointestinal discomfort was reduced (difference [95% CI] of − 14.2 [− 25.9, − 2.6] mm) with ADV7103. Conclusions Plasma bicarbonate levels and response rate were significantly higher with ADV7103 than with SoC. Urine calcium/citrate ratio, palatability, and gastrointestinal safety were significantly improved, supporting the use of ADV7103 as first-line treatment for dRTA. Trial registration Registered as EudraCT 2013-002988-25 on the 1st July 2013

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Correction to: Efficacy and safety of an innovative prolonged-release combination drug in patients with distal renal tubular acidosis: an open-label comparative trial versus standard of care treatments

Pediatric Nephrology ◽

10.1007/s00467-020-04776-0 ◽

2020 ◽

Vol 36 (1) ◽

pp. 215-215

Author(s):

Aurélia Bertholet-Thomas ◽

Catherine Guittet ◽

Maria A. Manso-Silván ◽

Arnaud Castang ◽

Véronique Baudouin ◽

...

Keyword(s):

Renal Tubular Acidosis ◽

Comparative Trial ◽

Standard Of Care ◽

Distal Renal Tubular Acidosis ◽

Prolonged Release ◽

Efficacy And Safety ◽

Open Label ◽

Combination Drug ◽

Renal Tubular

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

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0003 ◽

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.

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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

Pediatric Nephrology ◽

10.1007/s00467-020-04873-0 ◽

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

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