This is a multicenter, randomized, controlled versus placebo, double-blinded, 4 parallel arms, dose-ranging main study, to evaluate the efficacy, safety and tolerability, and acceptability of repeated doses of ADV7103, after 7 days of treatment, in patients with cystinuria, and an efficacy and safety exploratory study in the youngest children.
The study will target enrolling at least 15 subjects in each of the following age groups: 6 months - 5 years (B13CS part only); 6-11 years; 12-17 years and adults\>18. Subjects will be in the study for up to 7 weeks. After screening and enrollment (up to 35 days), Eligible patients will be treated will alkalinizing treatment (SoC) at the well-adapted dose and regimen for 7 days. An in-patient visit is planned at the end of this period. The baseline evaluations, including urine pH and specific gravity, will be done during this inpatient visit, from Day -1 t0 to t24h. After this visit, patients are randomized in a balanced manner (1:1:1:1) to one of the 4 possible treatment arms, ADV7103 at a low dose, medium dose or high dose, or ADV7103 placebo. For patients in B13CS part, a period of titration is planned before the 7 days of treatment with ADV7103. No use of placebo in B13CS. Controls of urine pH will be done at the patient's home with a pocket glass electrode pH-meter on fresh urines, at least twice a day: before the administration of ADV7103, in the morning at t0 and in the evening at t12h (12hrs after last ADV7103 intake and before the next dose). Subjects will have the opportunity to subsequently enter a long-term, open-label extension.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Each dose of ADV7103 contains a fixed ratio of 1/3 of ADV7103-CK (potassium citrate) and 2/3 of ADV7103-BK (potassium bicarbonate) based on the mass of active substances.
Placebo is a combination of 2 mm green coated lactose granules and 2 mm white coated lactose granules. Each dose of placebo contains a fixed ratio of 1/3 of green granules and 2/3 of white granules.
Cliniques Universitaires Saint-Luc
Brussels, Brussels Capital, Belgium
UZ Leuven, Gasthuisberg Hospital
Leuven, Leuven, Belgium
CHU Grenoble
Grenoble, Grenoble Cedex, France
Percentage of urinary pH values ≥ 7.0 during 24h on Day 7 (after ADV7103 treatment period)
The primary endpoint is the comparison between the probability of having an urinary PH ≥ 7.0 based on all urinations during Day 7 in an ADV7103 dose versus the probability in the placebo group. All urinations on Day 7 with an evaluable pH measure will be included in the analysis. The study will be declared positive if the chance of having pH value ≥ 7.0 at each urination on D7 is superior with at least one ADV7103 treatment group than with placebo.
Time frame: 24 hours
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CHRU Lille
Lille, Lille, France
CHU Pitié-Salpétrière
Paris, Paris, France
Hôpital Necker AP-HP
Paris, Paris, France
Hôpital Necker Enfants Malades
Paris, Paris, France
Hôpital Ténon - Explorations fonctionnelles Mutlidisciplinaires et INSERM UMR S 1155
Paris, Paris, France
Hôpital Américain CHU de Reims
Reims, Reims, France
CHU Reims
Reims, Reims, France
...and 2 more locations