This study is designed to evaluate, for the first time in humans, safety and tolerability of single ascending doses of intra-articular (i.a.) injections of LRX712 into the knee of patients with moderate osteoarthritis (OA), in order to support the further clinical development. This study will also allow establishment of the systemic and local pharmacokinetics (PK) of LRX712 and the exploration of biomarkers of cartilage breakdown and regeneration in OA patients.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
42
Novartis Investigative Site
Leiden, Netherlands
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) of LRX712 after a single intra-articular (i.a.) injection in Osteoarthritic (OA) patients
To evaluate Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) of LRX712 after a single i.a. injection in osteoarthritic patients
Time frame: Day 29
Time to Reach the Maximum Plasma Concentration (Tmax)
To evaluate LRX712 and metabolite MAE344 pharmacokinetics in plasma - Time to Reach the Maximum Plasma Concentration (Tmax)
Time frame: pre-dose to 29 days post-dose
Maximum Observed Plasma Concentration (Cmax)
To evaluate LRX712 and metabolite MAE344 pharmacokinetics in plasma - Maximum Observed Plasma Concentration (Cmax)
Time frame: pre-dose to 29 days post-dose
Area Under the Plasma Concentration-time Curve From 0 to the Last Measurable Concentration (AUClast)
To evaluate LRX712 and metabolite MAE344 pharmacokinetics in plasma - Area Under the Plasma Concentration-time Curve From 0 to the Last Measurable Concentration (AUClast)
Time frame: pre-dose to 29 days post-dose
Area under the plasma concentration-time curve from time zero to infinity (AUCinf)
To evaluate LRX712 and metabolite MAE344 pharmacokinetics in plasma - Area under the plasma concentration-time curve from time zero to infinity (AUCinf)
Time frame: pre-dose to 29 days post-dose
Half-life (T1/2)
To evaluate LRX712 and metabolite MAE344 pharmacokinetics in plasma - Half-life (T1/2)
Time frame: pre-dose to 29 days post-dose
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CL/F - Total clearance
To evaluate LRX712 and metabolite MAE344 pharmacokinetics in plasma - CL/F - Total clearance
Time frame: pre-dose to 29 days post-dose
Vz/F - Volume of Distribution
To evaluate LRX712 and metabolite MAE344 pharmacokinetics in plasma - Vz/F - Volume of Distribution
Time frame: pre-dose to 29 days post-dose