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

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

Lived experiences of patients with distal renal tubular acidosis treated with ADV7103 and of their caregivers: a qualitative study

“…The present qualitative research investigated the disease burden and treatment experience of 19 paediatric and adult patients with dRTA, who had been switched from previous SoC treatments to ADV7103 in the framework of a pivotal phase II/III clinical trial [ 12 ] and were followed up for at least 5 years during a phase III study [ 13 ]. This is the first time the impact of dRTA and its treatment on QoL, as described by the patients and their families, has been reported.…”

“…This study was conducted between June and November 2020 and involved qualitative in-depth interviews with patients with a confirmed diagnosis of dRTA and caregivers of paediatric patients. All patients included in a multicentre, single-arm, open-label, follow-up study (EudraCT 2013-003828-36) [ 13 ], proposed after a pivotal study (EudraCT 2013-002988-25) [ 12 ], and remaining in the follow-up study under treatment with ADV7103 at the time of the interviews, were invited to participate.…”

“…ADV7103 (Sibnayal) is a new alternative treatment for dRTA consisting of a combination of potassium citrate and potassium bicarbonate prolonged-release granules [ 11 ]. Comparatively, ADV7103 has the advantages of requiring only two doses per day (morning and evening), of being tasteless and easy to take, and of reducing gastrointestinal side effects, resulting in an adequate adherence to treatment and control of plasma bicarbonate and calciuria [ 12 , 13 ].…”

Improved growth of a child with primary distal renal tubular acidosis after switching from a conventional alkalizing treatment to a new prolonged-release formulation containing potassium citrate and potassium bicarbonate: lessons for the clinical nephrologist

“…This could allow sustained control of metabolic acidosis, thus minimizing the periods of activation of bone regulatory mechanisms with twice daily administration. ADV7103 is well-tolerated and reported adherence to treatment is excellent [1], [2].…”

“…She also presented low bone mineral density (BMD) (spine densitometry z-score = − 3.2). At 4.5 years of age, the girl entered a phase II/III study [1] and was switched to treatment with ADV7103 (Sibnayal), a new product consisting of a combination of potassium citrate and potassium bicarbonate prolonged-release granules and she continued with this treatment throughout a phase III follow-up trial [2]. Dosing was established at 16 mEq b.i.d.…”