Patients With Moderate Knee Osteoarthritis (30 - 65 Years)
Conditions
Keywords
Osteoarthritic patients, Cartilage, Safety
Brief summary
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.
Interventions
DRUGLRX712
Ascending single dose on Day 1
DRUGPlacebo
Ascending single dose on Day 1
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
30 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Male and female patients, 30 to 65 years of age inclusive, and in good health as determined by medical history, physical examination, vital signs, electrocardiogram, and laboratory tests at screening. * At screening, and at baseline vital signs (systolic and diastolic blood pressure and pulse rate) will be assessed in the sitting position after the subject has rested for at least three minutes, and again (when required) after three minutes in the standing position as outlined in the SOM. Sitting vital signs should be guided by the following ranges: * body temperature between 35.0-37.5 °C * systolic blood pressure 90-139 mm Hg * diastolic blood pressure 50-89 mm Hg * pulse rate, 40 - 90 bpm • Subjects must weigh at least 50 kg to participate in the study, and must have a body mass index (BMI) within the range of 18 - 32 kg/m2. BMI = Body weight (kg) / \[Height (m)\]
Exclusion criteria
* Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant. * Pregnant or nursing (lactating) women * Use of other investigational drugs at the time of enrollment, or within 5 half-lives of enrollment, or within 30 days, whichever is longer; or longer if required by local regulations * A history of clinically significant ECG abnormalities, or any of the following ECG abnormalities at screening and baseline * PR \> 200 msec * QRS complex \> 120 msec * QTcF \> 450 msec (males) * QTcF \> 460 msec (females) * Known family history or known presence of long QT syndrome
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) of LRX712 after a single intra-articular (i.a.) injection in Osteoarthritic (OA) patients | Day 29 | To evaluate Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) of LRX712 after a single i.a. injection in osteoarthritic patients |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Vz/F - Volume of Distribution | pre-dose to 29 days post-dose | To evaluate LRX712 and metabolite MAE344 pharmacokinetics in plasma - Vz/F - Volume of Distribution |
| Time to Reach the Maximum Plasma Concentration (Tmax) | pre-dose to 29 days post-dose | To evaluate LRX712 and metabolite MAE344 pharmacokinetics in plasma - Time to Reach the Maximum Plasma Concentration (Tmax) |
| Maximum Observed Plasma Concentration (Cmax) | pre-dose to 29 days post-dose | To evaluate LRX712 and metabolite MAE344 pharmacokinetics in plasma - Maximum Observed Plasma Concentration (Cmax) |
| CL/F - Total clearance | pre-dose to 29 days post-dose | To evaluate LRX712 and metabolite MAE344 pharmacokinetics in plasma - CL/F - Total clearance |
| Area under the plasma concentration-time curve from time zero to infinity (AUCinf) | pre-dose to 29 days post-dose | To evaluate LRX712 and metabolite MAE344 pharmacokinetics in plasma - Area under the plasma concentration-time curve from time zero to infinity (AUCinf) |
| Half-life (T1/2) | pre-dose to 29 days post-dose | To evaluate LRX712 and metabolite MAE344 pharmacokinetics in plasma - Half-life (T1/2) |
| Area Under the Plasma Concentration-time Curve From 0 to the Last Measurable Concentration (AUClast) | pre-dose to 29 days post-dose | To evaluate LRX712 and metabolite MAE344 pharmacokinetics in plasma - Area Under the Plasma Concentration-time Curve From 0 to the Last Measurable Concentration (AUClast) |
Countries
Netherlands
Outcome results
None listed