First-in-human, Safety, Tolerability and Pharmacokinetics Study of LRX712 in Osteoarthritic Patients
First-in-human, Safety, Tolerability and Pharmacokinetics Study of LRX712 in Osteoarthritic Patients
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.
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