ESPN 50th Annual Meeting

ESPN 2017


 
EFFICACY AND ACCEPTABILITY OF ADV7103, AN INNOVATIVE PROLONGED-RELEASE ORAL ALKALISING FORMULATION IN DISTAL RENAL TUBULAR ACIDOSIS (DRTA) PATIENTS
AURELIA BERTHOLET-THOMAS 1 CATHERINE GUITTET 2 MARIA A. MANSO 2 FRANÇOIS VANDENHENDE 3 MATHILDE CAILLIEZ 4 VERONIQUE BAUDOIN 5 MASSIMO DI MAIO 6 OLIVIA GILLION-BOYER 7 EMILIJA GOLUBOVIC 8 JERÔME HARAMBAT 9 ALEXANDRE KLEIN 10 BERTRAND KNEBELMANN 11 FRANÇOIS NOBILI 12 ROBERT NOVO 13 LUDMILA PODRACKA 14 GWENAELLE ROUSSEY-KESLER 15 LUC-ANDRE GRANIER 2 PIERRE COCHAT 1

1- Centre de référence des Maladies rénales rares, Néphrogones, Hôpital Femme Mère Enfant, Bron, France - Filière ORKiD
2- Advicenne, Nîmes, France
3- ClinBay SPRL, Genappe, Belgium
4- Service de Néphrologie Pédiatrique, CHU Timone enfants, Marseille, France
5- Service de Néphrologie Pédiatrique, Hôpital Robert Debré, Paris, France
6- Service de Réanimation Néonatale et Néonatologie, CHU de Nîmes, France
7- Service de Néphrologie Pédiatrique, Hôpital Necker-Enfants Malades, Paris, France
8- Klinički Centar Niš, Klinika za dečije interne bolesti – Odeljenje za nefrologiju, Niš, Serbia
9- Service de Pédiatrie, CHU de Bordeaux - Hôpital Pellegrin, Bordeaux, France
10- Service de Néphrologie, Pôle DIACOR, Hôpitaux Civils de Colmar, France
11- Service de Néphrologie adultes Hôpital Necker, Paris, France
12- Service de Pédiatrie 2, Hôpital Jean Minjoz, CHU de Besançon, France
13- Service de Néphrologie Pédiatrique, Hôpital Jeanne de Flandre, CHRU de Lille, France
14- Detská fakultná nemocnica s poliklinikou, Bratislava, Slovakia
15- Unité de Néphrologie et Hémomodialyse Pédiatrique, Clinique Médicale Pédiatrique Hôpital Mère-Enfant, CHU de Nantes, France
 
Introduction:

A new prolonged-release granule formulation, ADV7103, has been developed in order to obtain an age-adaptable form achieving sustained physiological blood pH (blood bicarbonate levels ≥22 mM) with a 2-daily intake. Improvement of palatability and gastro-intestinal (GI) tolerability were also targeted as they are critical factors affecting compliance. The objective of this study was to evaluate the efficacy and acceptability of ADV7103 with two daily doses (morning and evening) in dRTA patients, in comparison with their current standard of care (SoC), frequently requiring several daily administrations. 

Material and methods:

Adult and paediatric dRTA patients (n=37, 30 evaluable for first evaluation criterion) were included in a multicentre (N=13), open-label, non-inferiority, sequential study. They received their SoC and then ADV7103 at appropriate doses, both during 5-day periods. Bicarbonataemia and kalaemia were measured. Palatability, easiness of administration and swallowing, and GI tolerability were evaluated using 100-mm visual analogue scales or 5-point facial hedonic scales. Descriptive analyses were performed overall and by age-subset for both products.

Results:

The efficacy of ADV7103 was shown through its ability to correct metabolic acidosis (Fig.1). Normal blood bicarbonate levels were attained in most patients with doses of ADV7103 ranging from 0.75 to 8.45 mEq/kg/day. Mean doses of 1.7, 2.3, 3.8 and 6.1 mEq/kg/day ADV7103 were given, respectively, in adults, adolescents, children, and infants. Non-inferiority of ADV7103 vs. SoC or baseline literature data was consistently demonstrated (per protocol, intention-to-treat, and sensitivity analyses), which also allowed demonstrating superiority (p<0.0047). Kalaemia was normal with both treatments. Palatability, easiness of administration and GI tolerability were improved with ADV7103, as compared to the SoC. Easiness of swallowing features were maintained with ADV7103.


Conclusions:

These results support ADV7103, a prolonged-release combination of potassium citrate and potassium bicarbonate, for registration as the first alkalising product ever for first-line treatment of dRTA.