Back to results

Pharmacokinetics of RLX030 in Subjects With Mild, Moderate and Severe Hepatic Impairment Compared to Healthy Subjects

Primary Purpose

Hepatic Impairment

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

RLX030A

About this trial

This is an interventional other trial for Hepatic Impairment focused on measuring Hepatic impairment, healthy volunteers, RLX030, pharmacokinetics

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion criteria:

All subjects:
• Female subjects must be of non-child bearing potential OR use an effective method of contraception and sexually active males must use a condom during intercourse while taking the drug and for 5 half-lives after stopping treatment
Subjects with hepatic impairment:
- Subjects must have either mild, moderate or severe hepatic impairment

Exclusion criteria:

All subjects
- Hepatic impairment due to non-liver disease
- Use of other investigational drugs at time of enrollment
- History of malignancy of any organ system
- Donation or loss of 400 mL or more of blood or plasma within 8 weeks prior to initial dosing
- Hemoglobin levels below 10.0 g/dL at screening or baseline
Subjects with hepatic impairment:
- Presence of any non-controlled and clinically significant disease that could affect the study outcome or that would place the patient at undue risk
- Treatment with any cytostatic drug, vasodilator, autonomic alpha blocker or B2 agonist
- Any surgical or medical condition other than hepatic impairment which might significantly alter the distribution or excretion of drugs

Other protocol-defined inclusion/exclusion criteria may apply.

Sites / Locations

Novartis Investigative Site
Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Active Comparator

Arm Label

RLX030: Group 1 mild hepatic impairment

RLX030: Group 2 moderate hepatic impairment

RLX030: Group 3 severe hepatic impairment

RLX030: Group 4 - healthy volunteers

Arm Description

Patients with mild hepatic impairment will receive a single IV 24 hour infusion of RLX030

Patients with moderate hepatic impairment will receive a single IV 24 hour infusion of RLX030

Patients with severe hepatic impairment will receive a single IV 24 hour infusion of RLX030

Participants will receive a single IV 24 hour infusion of RLX030. This group will consist of 3 sub-groups to match patients of groups 1, 2and 3.

Outcomes

Primary Outcome Measures

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

Blood samples will be collected during screening, days 1 through 4 and then on Day 15 for the determination of serum concentrations of RLX030

Area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast)

Blood samples will be collected during screening, days 1 through 4 and then on Day 15 for the determination of serum concentrations of RLX030

Serum concentration at 24 hour (C24h) after administration

Blood samples will be collected during screening, days 1 through 4 and then on Day 15 for the determination of serum concentrations of RLX030

Secondary Outcome Measures

Number of patients with adverse events, serious adverse events and death

Monitoring of adverse events, serious adverse events and death from screening to end of study

Determination of the presence and quantification of anti-RLX030 antibodies

Blood will be collected and serum analyzed for the presence of antiRLX030 antibodies. Anti-RLX030 antibodies will be evaluated in serum in a validated four-tiered assay approach

Mean residence time [MRT] of RLX030

Blood samples will be collected during screening, days 1 through 4 and then on Day 15 for the determination of serum concentrations of RLX030

Terminal elimination half life (T ½) of RLX030

Blood samples will be collected during screening, days 1 through 4 and then on Day 15 for the determination of serum concentrations of RLX030

Systemic clearance of RLX030 from serum (CL)

Blood samples will be collected during screening, days 1 through 4 and then on Day 15 for the determination of serum concentrations of RLX030

Volume of distribution at steady state (Vss)

Blood samples will be collected during screening, days 1 through 4 and then on Day 15 for the determination of serum concentrations of RLX030

Full Information

NCT ID

NCT01433458

First Posted

August 9, 2011

Last Updated

December 17, 2020

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT01433458

Brief Title

Pharmacokinetics of RLX030 in Subjects With Mild, Moderate and Severe Hepatic Impairment Compared to Healthy Subjects

Official Title

A Single-dose, Open-label Parallel Study to Assess the Pharmacokinetics of RLX030 in Subjects With Mild, Moderate and Severe Hepatic Impairment Compared to Healthy Control Subjects

Study Type

Interventional

2. Study Status

Record Verification Date

January 2013

Overall Recruitment Status

Completed

Study Start Date

July 2011 (undefined)

Primary Completion Date

December 2011 (Actual)

Study Completion Date

December 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

5. Study Description

Brief Summary

This study will assess the pharmacokinetics of RLX030 during and after administration in subjects with mild to severe hepatic impairment and matched healthy control subjects. 20 to 24 patients and 20 to 24 healthy subjects will be enrolled.

6. Conditions and Keywords

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

Hepatic Impairment

Keywords

Hepatic impairment, healthy volunteers, RLX030, pharmacokinetics

7. Study Design

Primary Purpose

Other

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

55 (Actual)

8. Arms, Groups, and Interventions

Arm Title

RLX030: Group 1 mild hepatic impairment

Arm Type

Experimental

Arm Description

Patients with mild hepatic impairment will receive a single IV 24 hour infusion of RLX030

Arm Title

RLX030: Group 2 moderate hepatic impairment

Arm Type

Experimental

Arm Description

Patients with moderate hepatic impairment will receive a single IV 24 hour infusion of RLX030

Arm Title

RLX030: Group 3 severe hepatic impairment

Arm Type

Experimental

Arm Description

Patients with severe hepatic impairment will receive a single IV 24 hour infusion of RLX030

Arm Title

RLX030: Group 4 - healthy volunteers

Arm Type

Active Comparator

Arm Description

Participants will receive a single IV 24 hour infusion of RLX030. This group will consist of 3 sub-groups to match patients of groups 1, 2and 3.

Intervention Type

Drug

Intervention Name(s)

RLX030A

Intervention Description

RLX030 is administered as a continuous 24 hour infusion

Primary Outcome Measure Information:

Title

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

Description

Blood samples will be collected during screening, days 1 through 4 and then on Day 15 for the determination of serum concentrations of RLX030

Time Frame

Up to Day 15

Title

Area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast)

Description

Blood samples will be collected during screening, days 1 through 4 and then on Day 15 for the determination of serum concentrations of RLX030

Time Frame

Up to Day 15

Title

Serum concentration at 24 hour (C24h) after administration

Description

Blood samples will be collected during screening, days 1 through 4 and then on Day 15 for the determination of serum concentrations of RLX030

Time Frame

Upto Day 15

Secondary Outcome Measure Information:

Title

Number of patients with adverse events, serious adverse events and death

Description

Monitoring of adverse events, serious adverse events and death from screening to end of study

Time Frame

Day 15

Title

Determination of the presence and quantification of anti-RLX030 antibodies

Description

Blood will be collected and serum analyzed for the presence of antiRLX030 antibodies. Anti-RLX030 antibodies will be evaluated in serum in a validated four-tiered assay approach

Time Frame

Day 1 (prior to administration) and Day 15 end of study

Title

Mean residence time [MRT] of RLX030

Description

Blood samples will be collected during screening, days 1 through 4 and then on Day 15 for the determination of serum concentrations of RLX030

Time Frame

screening, days 1, 2, 3, 4 and 15

Title

Terminal elimination half life (T ½) of RLX030

Description

Blood samples will be collected during screening, days 1 through 4 and then on Day 15 for the determination of serum concentrations of RLX030

Time Frame

screening, days 1, 2, 3, 4 and 15

Title

Systemic clearance of RLX030 from serum (CL)

Description

Blood samples will be collected during screening, days 1 through 4 and then on Day 15 for the determination of serum concentrations of RLX030

Time Frame

screening, days 1, 2, 3, 4 and 15

Title

Volume of distribution at steady state (Vss)

Description

Blood samples will be collected during screening, days 1 through 4 and then on Day 15 for the determination of serum concentrations of RLX030

Time Frame

screening, days 1, 2, 3, 4 and 15

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion criteria: All subjects: • Female subjects must be of non-child bearing potential OR use an effective method of contraception and sexually active males must use a condom during intercourse while taking the drug and for 5 half-lives after stopping treatment Subjects with hepatic impairment: Subjects must have either mild, moderate or severe hepatic impairment Exclusion criteria: All subjects Hepatic impairment due to non-liver disease Use of other investigational drugs at time of enrollment History of malignancy of any organ system Donation or loss of 400 mL or more of blood or plasma within 8 weeks prior to initial dosing Hemoglobin levels below 10.0 g/dL at screening or baseline Subjects with hepatic impairment: Presence of any non-controlled and clinically significant disease that could affect the study outcome or that would place the patient at undue risk Treatment with any cytostatic drug, vasodilator, autonomic alpha blocker or B2 agonist Any surgical or medical condition other than hepatic impairment which might significantly alter the distribution or excretion of drugs Other protocol-defined inclusion/exclusion criteria may apply.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Novartis Pharmaceuticals

Organizational Affiliation

Novartis Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Novartis Investigative Site

City

Grunstadt

ZIP/Postal Code

D-67269

Country

Germany

Facility Name

Novartis Investigative Site

City

Moscow

ZIP/Postal Code

115419

Country

Russian Federation

12. IPD Sharing Statement

Citations:

PubMed Identifier

25511105

Citation

Kobalava Z, Villevalde S, Kotovskaya Y, Hinrichsen H, Petersen-Sylla M, Zaehringer A, Pang Y, Rajman I, Canadi J, Dahlke M, Lloyd P, Halabi A. Pharmacokinetics of serelaxin in patients with hepatic impairment: a single-dose, open-label, parallel group study. Br J Clin Pharmacol. 2015 Jun;79(6):937-45. doi: 10.1111/bcp.12572.

Results Reference

derived

Links:

URL

https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=7565

Description

Results for CRLX030A2101 can be found on the Novartis Clinical Trial Results Website

Learn more about this trial

Pharmacokinetics of RLX030 in Subjects With Mild, Moderate and Severe Hepatic Impairment Compared to Healthy Subjects

We'll reach out to this number within 24 hrs