Clinical trial NCT03355196: First-in-human, Safety, Tolerability and Pharmacokinetics Study of LRX712 in Osteoarthritic Patients
Official title: A Randomized, Placebo Controlled, Subject and Investigator Blinded, first-in- Human, Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics After Intra-articular Injection of LRX712 Into the Knee of Osteoarthritic Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Patients With Moderate Knee Osteoarthritis (30 - 65 Years)
Keywords: Osteoarthritic patients
Cartilage
Safety
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2017-11-28
Enrollment: 42
Sex: ALL
Minimum age (years): 30
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) of LRX712 after a single intra-articular (i.a.) injection in Osteoarthritic (OA) patients
timeFrame: Day 29
Secondary outcomes:
measure: Time to Reach the Maximum Plasma Concentration (Tmax)
timeFrame: pre-dose to 29 days post-dose
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: pre-dose to 29 days post-dose
measure: Area Under the Plasma Concentration-time Curve From 0 to the Last Measurable Concentration (AUClast)
timeFrame: pre-dose to 29 days post-dose
measure: Area under the plasma concentration-time curve from time zero to infinity (AUCinf)
timeFrame: pre-dose to 29 days post-dose
measure: Half-life (T1/2)
timeFrame: pre-dose to 29 days post-dose
measure: CL/F - Total clearance
timeFrame: pre-dose to 29 days post-dose
measure: Vz/F - Volume of Distribution
timeFrame: pre-dose to 29 days post-dose
Other outcomes:
Locations:
city: Leiden
country: Netherlands
facility: Novartis Investigative Site
Study officials:
References: