Cystinuria MedDRA version: 20.0 Level: PT Classification code 10011778 Term: Cystinuria System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: ADV7103
Pharmaceutical Form: Prolonged-release granules
INN or Proposed INN: potassium citrate monohydrate
CAS Number: 6100-05-6
Current Sponsor code: ADV7103-CK
Other descriptive name:
Sponsors
Advicenne
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: To be eligible for inclusion into the study, the subjects must fulfil all of the following criteria: 1. Patient who has a diagnosis of cystinuria based on medical diagnosis (at least one previous or current episode of calculus of cystine, and/or one previous or current episode of cystine crystalluria) or on genetic diagnosis (only for patients enrolled in B13CS study). 2. Patient treated with an alkalising treatment at a well-adapted dose (defined as a daily dose deemed by the investigator aiming to maintain overtime urinary pH value = 7.0 and/or compatible with an acceptable safety profile and/or patient's constraints or compliance). 3. Patient who, when treated with a second line therapy (chelator agent), presents a disease status enabling interruption of the chelator agent during the course of the B12CS-B13CS research. 4. Patient male or female, including child aged between 6 months and 17 years old and adult aged = 18 years old up to 70 years old. 5. For patient with mild to moderate renal impairment (45= estimated glomerular filtration rate (eGFR) =65 years) yes F.1.3.1 Number of subjects for this age range 2
Exclusion criteria
Exclusion criteria: To be eligible for inclusion into the study, the subjects must not meet any of the following criteria: 1. Patient treated with the second line therapy and who cannot stop cystine chelating agents (sulfhydryl compounds) during the B12CSB13CS study. 2. Patient who presents kalaemia > 5.0 mmol/L. 3. Patient who presents a renal impairment as following: - severe renal impairment (eGFR < 45 mL/min/1.73 m2 according to Schwartz formula for children and CKD-EPI for adults), XML File Identifier: 5req015GVN6Ni+SmfMfA1eCEbog= Page 12/29 - mild to moderate renal impairment not stabilised (45 = eGFR < 60 mL/min/1.73 m2, according to Schwartz formula for children and CKDEPI for adults), AND a BMI =.30 Kg/m² 4. Patient 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 diarrhoea. 5. Female patient who is pregnant or breast-feeding. 6. Patient who cannot stop potassium sparing diuretics (e.g. antagonists of aldosterone as such spironolactone, canrenoate and eplerenone, amiloride, triamterene), angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists, tacrolimus, ciclosporine, potassium desodic salts, nonsteroidal anti-inflammatory drugs and cardiac glycosides. 7. Patient who received any medication that could interfere with the study treatment within 4 weeks before the inclusion in the study, including angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists, tacrolimus, potassium desodic salts, antibiotics limited to sulfamides, quinolones and azithromycine. 8. Patient who received potassium sparing diuretics 6 weeks before the inclusion in the study. 9. Patient who presents contra indications to the administration of the study treatment such like known allergic reactions or hypersensitivity to the active pharmaceutical ingredients or other excipients of the formulations of the study treatment (such as lactose), history of difficult access to the oral administration route and/or conditions that may hamper compliance and/or absorption of the study treatment (e.g. any difficulty of swallowing, mal-absorption, delayed gastric emptying, oesophageal compression, intestinal obstruction or other chronic gastrointestinal disease). 10. Patient who is admitted to hospital in emergency settings. 11. Patient who participated in a clinical trial within the last 3 months before enrolment. 12. Patient who is at risk of non-compliance in the judgment of the investigator. 13. Patient who could present any other condition, which in the opinion of the investigator, would preclude participation in the study. 14. Patient who cannot be contacted in case of emergency. 15. Patient under any administrative or legal supervision.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary objective of B12CS - To evaluate the effect of ADV7103 at three different doses compared to placebo on the probability of having urinary pH values = 7.0 at each urination over 24h on Day 7, after a 7-day treatment, in patients of at least 6 years of age and toilet trained. Primary objective of B13CS - To evaluate the effect of ADV7103 at the individual optimal dose on the probability of having urinary pH values = 7.0 at each urination over 24h on Day 7 after a 7-day treatment, in patients aged from 6 months to < 6 years old or not yet toilet trained.;Secondary Objective: Efficacy - To evaluate the effect of ADV7103 (including 3 doses of ADV7103 and placebo in B12CS) on secondary urine pH parameters over 24 hours, with day and night periods on Day 7, after a 7-day treatment - To evaluate the dose-response relationship of ADV7103 on urine mean 24-h pH on Day 7, after a 7 day-treatment (B12CS only). - To evaluate the effect of ADV7103 (including 3 doses of ADV7103 and placebo) on cystine crystalluria, in the first and second morning urine, on Day 7, after a 7 day-treatment. - To evaluate the dose-response relationship of ADV7103 on cystine crystalluria, other crystalluria types, other cystinuria parameters, and other urine metabolic markers of crystalluria in the first and second morning urine, on Day 7, after a 7 day-treatment (B12CS only). Safety - To evaluate the safety and tolerability of the study products, over a 7 day-treatment. Acceptability - To evaluate the acceptability of the study products on Day 7, after a 7 day-treatment;Primary end point(s): Main Study B12CS The primary endpoint is the comparison between the probability of having a urinary pH = 7.0 based on each urination over 24 hours on Day 7 in an ADV7103 dose versus the probability in the placebo group. All urinations on Day 7 from t0 to t24h with evaluable pH measures will be included in the analysis. Exploratory Study B13CS The primary endpoint is the evaluation of the prob | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy endpoints . Presence of cystine crystals defined as the number/proportion of patients with at least one cystine crystal, (baseline, Day 7 and change from baseline) by urine sample and overall on Day 7 . Absence / presence of crystals defined as the number/proportion of patients with crystals, by urine sample, by crystal type, (baseline, Day 7 and change from baseline) . Number of crystals by urine sample, by crystal type (baseline, Day 7 and change from baseline) . Number of aggregates of crystals (baseline, Day 7 and change from baseline) . Urine free cystine concentration (mmol/L) (baseline, Day 7 and change from baseline) . Urine free cystine excretion (mmol/day) (baseline, Day 7 and change from baseline) . Urine free cystine to creatinine ratio (mmol/mmol) . Other urine metabolic markers of crystalluria . Presence /absence cystine free or precipitate Safety and tolerability endpoints . Adverse events throughout the study. . Standard safety measures, according to the investigator site normal ranges, at screening, in baseline (Day -1) and on Day 7/end of study . Number of patients with hyperkaliemia (defined as plasma potassium = 5.5 mmol/L at least once) throughout the study. . Number of patients with ACCP granulations to be measured in the first and second morning urines collected both before the first morning dose (in baseline i.e. on Day -1 t24h and approximately 2 hours later, on Day 7 t24h and approximately 2 hours later) . Number of patients with urine tract infections . Number/proportion of patients with plasma levels of potassium by normality status, over the study periods . Blood levels of potassium (kinetics) on Day 7 . Gastro-intestinal tolerability on Day 7 t24h. Acceptability endpoints . Palatability, to be evaluated by the patient her/himself, and with the support of her/his parents when necessary, (baseline i.e. on Day -1 t24h, Day 7 t24h) . Ease of swallowing, to be evaluated | — |
Countries
Belgium, France
Contacts
Public ContactClinical Project Manager
Advicenne
Outcome results
None listed