Clinical trial NCT01433458: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatic Impairment
Keywords: Hepatic impairment
healthy volunteers
RLX030
pharmacokinetics
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2011-09-14
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.


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.

Primary outcomes:
measure: Area under the serum concentration-time curve from time zero to infinity (AUCinf)
timeFrame: Up to Day 15
measure: Area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast)
timeFrame: Up to Day 15
measure: Serum concentration at 24 hour (C24h) after administration
timeFrame: Upto Day 15
Secondary outcomes:
measure: Number of patients with adverse events, serious adverse events and death
timeFrame: Day 15
measure: Determination of the presence and quantification of anti-RLX030 antibodies
timeFrame: Day 1 (prior to administration) and Day 15 end of study
measure: Mean residence time [MRT] of RLX030
timeFrame: screening, days 1, 2, 3, 4 and 15
measure: Terminal elimination half life (T ½) of RLX030
timeFrame: screening, days 1, 2, 3, 4 and 15
measure: Systemic clearance of RLX030 from serum (CL)
timeFrame: screening, days 1, 2, 3, 4 and 15
measure: Volume of distribution at steady state (Vss)
timeFrame: screening, days 1, 2, 3, 4 and 15
Other outcomes:
Locations:
city: Grunstadt
country: Germany
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
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.