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

Phase 1

Completed

• Conditions: Patients With Moderate Knee Osteoarthritis (30 - 65 Years)
• Interventions: Drug: LRX712; Drug: Placebo

• Registration Number: NCT03355196
• Lead Sponsor: Novartis Pharmaceuticals

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-11-17
• Study Start: 2017-11-20
• Study First Submitted QC: 2017-11-27
• Study First Posted: 2017-11-28
• Primary Completion: 2019-03-26
• Study Completion: 2019-03-26
• Status Verified: 2020-05
• Last Update Submitted: 2020-12-09
• Last Update Posted: 2020-12-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 42

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)]

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
LRX712	LRX712	LRX712 given intra-articularly
Placebo	Placebo	Placebo given intra-articularly

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
CL/F - Total clearance	pre-dose to 29 days post-dose	To evaluate LRX712 and metabolite MAE344 pharmacokinetics in plasma - CL/F - Total clearance
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)
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)
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 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)
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

Trial Locations

Locations (1)

Novartis Investigative Site; 🇳🇱 Leiden, Netherlands