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

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

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.

Study Overview

• Status: Completed
• Conditions: Hepatic Impairment
• Intervention / Treatment: Drug: RLX030A

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Grunstadt, Germany, D-67269
    • Novartis Investigative Site
• Russian Federation
  • Moscow, Russian Federation, 115419
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RLX030: Group 1 mild hepatic impairment; Patients with mild hepatic impairment will receive a single IV 24 hour infusion of RLX030	Drug: RLX030A; RLX030 is administered as a continuous 24 hour infusion
Experimental: RLX030: Group 2 moderate hepatic impairment; Patients with moderate hepatic impairment will receive a single IV 24 hour infusion of RLX030	Drug: RLX030A; RLX030 is administered as a continuous 24 hour infusion
Experimental: RLX030: Group 3 severe hepatic impairment; Patients with severe hepatic impairment will receive a single IV 24 hour infusion of RLX030	Drug: RLX030A; RLX030 is administered as a continuous 24 hour infusion
Active Comparator: RLX030: Group 4 - healthy volunteers; 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.	Drug: RLX030A; RLX030 is administered as a continuous 24 hour infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Up to Day 15
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	Up to Day 15
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	Upto Day 15

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Day 15
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	Day 1 (prior to administration) and Day 15 end of study
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	screening, days 1, 2, 3, 4 and 15
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	screening, days 1, 2, 3, 4 and 15
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	screening, days 1, 2, 3, 4 and 15
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	screening, days 1, 2, 3, 4 and 15

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• 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.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: August 9, 2011
• First Submitted That Met QC Criteria: September 12, 2011
• First Posted (Estimate): September 14, 2011

Study Record Updates

• Last Update Posted (Actual): December 21, 2020
• Last Update Submitted That Met QC Criteria: December 17, 2020
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: pharmacokinetics; healthy volunteers; Hepatic impairment; RLX030
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases
• Other Study ID Numbers: CRLX030A2101; 2011-001596-39 (EudraCT Number)