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

Primary Purpose

Patients With Moderate Knee Osteoarthritis (30 - 65 Years)

Status

Completed

Phase

Phase 1

Locations

Netherlands

Study Type

Interventional

Intervention

LRX712

Placebo

About this trial

This is an interventional treatment trial for Patients With Moderate Knee Osteoarthritis (30 - 65 Years) focused on measuring Osteoarthritic patients, Cartilage, Safety

Eligibility Criteria

30 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

LRX712

Placebo

Arm Description

LRX712 given intra-articularly

Placebo given intra-articularly

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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)

Maximum Observed Plasma Concentration (Cmax)

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)

To evaluate LRX712 and metabolite MAE344 pharmacokinetics in plasma - Area Under the Plasma Concentration-time Curve From 0 to the Last Measurable Concentration (AUClast)

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)

Half-life (T1/2)

To evaluate LRX712 and metabolite MAE344 pharmacokinetics in plasma - Half-life (T1/2)

CL/F - Total clearance

To evaluate LRX712 and metabolite MAE344 pharmacokinetics in plasma - CL/F - Total clearance

Vz/F - Volume of Distribution

To evaluate LRX712 and metabolite MAE344 pharmacokinetics in plasma - Vz/F - Volume of Distribution

Full Information

NCT ID

NCT03355196

First Posted

November 17, 2017

Last Updated

December 9, 2020

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT03355196

Brief Title

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

2. Study Status

Record Verification Date

May 2020

Overall Recruitment Status

Completed

Study Start Date

November 20, 2017 (Actual)

Primary Completion Date

March 26, 2019 (Actual)

Study Completion Date

March 26, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Patients With Moderate Knee Osteoarthritis (30 - 65 Years)

Keywords

Osteoarthritic patients, Cartilage, Safety

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

N/A

Enrollment

42 (Actual)

8. Arms, Groups, and Interventions

Arm Title

LRX712

Arm Type

Experimental

Arm Description

LRX712 given intra-articularly

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo given intra-articularly

Intervention Type

Drug

Intervention Name(s)

LRX712

Intervention Description

Ascending single dose on Day 1

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Ascending single dose on Day 1

Primary Outcome Measure Information:

Title

Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) of LRX712 after a single intra-articular (i.a.) injection in Osteoarthritic (OA) patients

Description

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

Secondary Outcome Measure Information:

Title

Time to Reach the Maximum Plasma Concentration (Tmax)

Description

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

Title

Maximum Observed Plasma Concentration (Cmax)

Description

To evaluate LRX712 and metabolite MAE344 pharmacokinetics in plasma - Maximum Observed Plasma Concentration (Cmax)

Time Frame

pre-dose to 29 days post-dose

Title

Area Under the Plasma Concentration-time Curve From 0 to the Last Measurable Concentration (AUClast)

Description

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

Title

Area under the plasma concentration-time curve from time zero to infinity (AUCinf)

Description

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

Title

Half-life (T1/2)

Description

To evaluate LRX712 and metabolite MAE344 pharmacokinetics in plasma - Half-life (T1/2)

Time Frame

pre-dose to 29 days post-dose

Title

CL/F - Total clearance

Description

To evaluate LRX712 and metabolite MAE344 pharmacokinetics in plasma - CL/F - Total clearance

Time Frame

pre-dose to 29 days post-dose

Title

Vz/F - Volume of Distribution

Description

To evaluate LRX712 and metabolite MAE344 pharmacokinetics in plasma - Vz/F - Volume of Distribution

Time Frame

pre-dose to 29 days post-dose

10. Eligibility

Sex

All

Minimum Age & Unit of Time

30 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

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

Facility Information:

Facility Name

Novartis Investigative Site

City

Leiden

ZIP/Postal Code

2333 CL

Country

Netherlands

12. IPD Sharing Statement

Plan to Share IPD

Links:

URL

https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17606

Description

Results for CLRX712X2101 can be found on the Novartis Clinical Trial Results Website

URL

https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=381

Description

A Plain Language Trial Summary is available on novartisclinicatrials.com

Learn more about this trial

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

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