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

NCT01433458 | Completed Phase 1

• 2 other identifiers: CRLX030A21012011-001596-39
• Study Type: interventional
• Target: 55
• Locations: 2 countries
• Sites: 2

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.

Conditions

Hepatic Impairment

Keywords

Hepatic impairment; healthy volunteers; RLX030; pharmacokinetics

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (6)

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

  Day 15

• Determination of the presence and quantification of anti-RLX030 antibodies

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

• Mean residence time [MRT] of RLX030

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

• Terminal elimination half life (T ½) of RLX030

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

• Systemic clearance of RLX030 from serum (CL)

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

Study Arms (4)

RLX030: Group 1 mild hepatic impairment

EXPERIMENTAL

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

Drug: RLX030A

RLX030: Group 2 moderate hepatic impairment

EXPERIMENTAL

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

Drug: RLX030A

RLX030: Group 3 severe hepatic impairment

EXPERIMENTAL

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

Drug: RLX030A

RLX030: Group 4 - healthy volunteers

ACTIVE COMPARATOR

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

Interventions

RLX030A DRUG

RLX030 is administered as a continuous 24 hour infusion

RLX030: Group 1 mild hepatic impairment; RLX030: Group 2 moderate hepatic impairment; RLX030: Group 3 severe hepatic impairment; RLX030: Group 4 - healthy volunteers

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (2)

Novartis Investigative Site

Grünstadt, D-67269, Germany

Location

Novartis Investigative Site

Moscow, 115419, Russia

Location

Related Publications (1)

• 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.

  PMID: 25511105 DERIVED

Related Links

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

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 9, 2011
• First Posted: September 14, 2011
• Study Start: July 1, 2011
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: December 21, 2020

Record last verified: 2013-01

Locations

DE (1); RU (1)