distal renal tubular acidosis MedDRA version: 18.0 Level: PT Classification code 10038535 Term: Renal tubular acidosis System Organ Class: 10038359 - Renal and urinary disorders
Conditions
Interventions
Product Code: ADV7103
Pharmaceutical Form: Prolonged-release granules
INN or Proposed INN: potassium citrate
CAS Number: 6100-05-6
Other descriptive name: POTASSIUM CITRATE
Concentration unit: % (W/W)
Sponsors
Advicenne Pharma
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subject who has a diagnosis of distal renal tubular acidosis (acquired or inherited form) with metabolic acidosis 2. Subject male or female, including child aged between 6 months and 17 years old and adult aged = 18 years old and = 55 years old. Are the trial subjects under 18? yes Number of subjects for this age range: 18 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 6 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.,Subject who presents associated proximal tubular signs (i.e. presenting for example hypophoshoremia, urinary betamicroglobulin, hyponatremia). 2. Subject who presents a kalaemia > 5.0 mmol/L. 3. Subject who presents a severe or moderate renal impairment (creatinine clearance < 45 mL/min/1.73 m2 according to Schwartz formula for the children and both Cockcrauft & Gault and MDRD formulas for adults). 4. Subject who presents - barring the study disease - any previous or concurrent medical condition or any laboratory or clinical findings or any other condition that in the opinion of the investigator would be negatively affected by the study medication or that would affect the study medication or that precludes participation, e.g. uncontrolled diabetes mellitus, adrenal insufficiency, cardiac impairment, repeated infections, metabolic alkalosis, chronic diarrhea 5. Subject who takes or cannot stop (last dose on Day -1) potassium sparing diuretics (e.g. spironolactone, aldactone, amiloride, triamterene), angiotensin converting enzymes inhibitors, angiotensin II receptor antagonists, tacrolimus, potassium desodic salts
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the relative efficacy of ADV7103 and standard of care on correcting metabolic acidosis as measured on pre-morning dose blood bicarbonate levels during 3 days of treatment at steady state (Day 2 to Day 4);Secondary Objective: - To compare the efficacy of ADV7103 to standard of care on other blood bicarbonate-derived parameters given after 5 days of treatment at steady state - To evaluate the efficacy on the reduction of hypercalciuria of ADV7103 as compared to standard of care after 4 to 5 days of treatment at steady state - To evaluate the efficacy on the correction of hypocitraturia of ADV7103 as compared to standard of care after 4 to 5 days of treatment at steady state - To evaluate the safety and tolerability including the gastro-intestinal tolerability of ADV7103 as compared to standard of care during 5 days of treatment at steady state - To evaluate the acceptability (palatability, swallowing, easiness of administration) of ADV7103 as compared to standard of care for 5 days of treatment at steady state - To evaluate the compliance to ADV7103 as compared to standard of care during 5 days of treatment at steady state ;Primary end point(s): Average bicarbonate blood level during 3 days of treatment at steady state with ADV7103 and SoC. ;Timepoint(s) of evaluation of this end point: - At the end of the SoC steady state period SP I on Day 2 t0, Day 3 t0 and Day 4 t0 (before first daily dose) - At the end of the ADV7103 steady state period SP III on Day 2 t0, Day 3 t0 and Day 4 t0 (before first daily dose) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy endpoints: *Bicarbonate-derived endpoints after 5 days of treatment at steady state • For Sub-set 1, Sub-set 2, and Sub-set 3 and Sub-set 4 if feasible - AUC0-24h: Area under the curve on Day 5 from t0 to t24h - Cmin: Minimum concentration over 24 hours on Day 5 - Fluctuation: Maximum minus minimum concentrations over 24 hours on Day 5 • For the 4 Sub-sets - Percentage of values below the lower normal limit on SP I and SP III Day 2 t0, Day 3 t0 and Day 4 t0. - Number/proportion of subjets with abnormal bicarbonataemia values, i.e. patients with at least one value of bicarbonataemia below lower normal range on Day 2 t0, Day 3 t0 or Day 4 t0. - Number/proportion of non-responders i.e. patients with all three values of bicarbonataemia below lower normal range on Day 2 t0, Day 3 t0 and Day 4 t0. *Number of subjects presenting an hypercalciuria after 4 to 5 days of treatment at steady state *Number of subjects presenting an hypocitraturia after 4 to 5 days of treatment at steady state Safety endpoints: • Number/proportion of subjects presenting adverse events, incidence and severity of adverse events during the course of the study • Gastro-intestinal tolerability evaluated with appropriate scales (a facial hedonic scale for the youngest and a visual analogue scale (VAS) for the other subjects) at inclusion, on SP I Day 5 and on SP III Day 5 • Incidence of abnormal values on safety parameters after 5 days of treatment at steady state - Serum ionogram (Na+, Ca2+, Cl-, K+, Mg2+, HCO3-, phosphorus, proteins, creatinine, creatinine clearance, urea, uric acid) (Inclusion, SP I and SP III Day 5) - Kaliemia (SPII, with all bicarbonataemia samples ) - Urine ionogram (HCO3-, Na+, Cl-, K+, Mg2+, Ca2+, phosphates, proteins, urea, citrate, creatinine,) (Inclusion, SP I and SP III Day 5) - Urine pH at each urination during investigator site visit (Inclusion, SP I and SP III Day 5 from t0 to t24h post first morning dose for hospitalised su | — |
Countries
Belgium, France, Italy, Serbia, Slovakia, Spain, United Kingdom
Contacts
Public ContactDirector of Clinical Affairs
Advicenne Pharma
Outcome results
None listed