Kidney Stones
Conditions
Keywords
oxalate, glycolate oxidase
Brief summary
This is a Phase 2a study of glycolate oxidase inhibitor LLX-424 in patients with a history of kidney stones. Eligible subjects with a history of kidney stones will be randomized to receive study drug (LLX-424 or placebo) for 8 weeks.
Detailed description
This is a Phase 2a, randomized, double-blind, placebo-controlled study designed to assess the safety, tolerability, PK, and PD effects of LLX-424 in patients with a history of kidney stones. Following completion of screening procedures, on Study Day 1, eligible subjects will be randomized in a 2:1 ratio to receive either LLX-424 or matching placebo, respectively. An outpatient safety Follow-up Visit will be scheduled on Day 63 or 7 days after the last dose (end of study visit).
Interventions
DRUGLLX-424
Tablets for oral administration
Sponsors
Lilac Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* History of kidney stones documented in medical records * 24-hour urine oxalate excretion * Body mass index 18.5 to 38 kg/m2 inclusive * Estimated glomerular filtration rate ≥ 60 mL/min/1.73m2
Exclusion criteria
* History or medical record evidence of kidney stones that are not calcium oxalate * Unstable kidney function * Spot urine protein to creatinine ratio ≥ 1 mg/mg at screening * History of kidney transplantation * Hemoglobin A1c \> 9.5% at screening * History of enteric hyperoxaluria, intestinal malabsorption, bariatric surgery, intestinal surgery, inflammatory bowel disease * History or evidence of cirrhosis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment-emergent adverse events (TEAEs) | From the first dose and for up to 9 weeks | Percentage of subjects with TEAEs |
| Percentage of subjects with study drug-related severe laboratory-based AEs | From the first dose and for up to 9 weeks | Laboratory-based adverse events |
| QT interval on ECG | From the first dose and for up to 9 weeks | Percentage of subjects with an increase from baseline in the QTcF by \> 60 milliseconds |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peak plasma concentration (Cmax) of glycolate | From pre-dose to Study Day 56 | Cmax of plasma glycolate |
| Mean change from baseline in 24-hour urine oxalate excretion rate | From pre-dose to Study Day 56 | Comparison between LLX-424 group and the placebo group |
| Area under the curve (AUC) of plasma glycolate concentration versus time after dosage | From pre-dose to Study Day 56 | AUC of plasma glycolate |
| Peak plasma concentration (Cmax) of LLX-424 | From pre-dose to Study Day 56 | Cmax of plasma LLX-424 |
| Area under the curve (AUC) of plasma LLX-424 concentration versus time after dosage | From pre-dose to Study Day 56 | AUC of plasma LLX-424 |
Countries
United States
Outcome results
None listed