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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01433458
First received: August 9, 2011
Last updated: January 20, 2013
Last verified: January 2013

August 9, 2011
January 20, 2013
July 2011
December 2011   (final data collection date for primary outcome measure)
  • Area under the serum concentration-time curve from time zero to infinity (AUCinf) [ Time Frame: Up to Day 15 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Up to Day 15 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Upto Day 15 ] [ Designated as safety issue: No ]
    Blood samples will be collected during screening, days 1 through 4 and then on Day 15 for the determination of serum concentrations of RLX030
Measure: Relaxin pharmacokinetic profile (Composite of Pharmacokinetics: AUCinf, AUClast, C24h, T1/2, MRT, CL, Vss) [ Time Frame: Day 1 (prior to administration and 6x after administration) and Days 2 (9x), 3, 4 and 15. ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01433458 on ClinicalTrials.gov Archive Site
  • Number of patients with adverse events, serious adverse events and death [ Time Frame: Day 15 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Day 1 (prior to administration) and Day 15 end of study ] [ Designated as safety issue: No ]
    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 [ Time Frame: screening, days 1, 2, 3, 4 and 15 ] [ Designated as safety issue: No ]
    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 [ Time Frame: screening, days 1, 2, 3, 4 and 15 ] [ Designated as safety issue: No ]
    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) [ Time Frame: screening, days 1, 2, 3, 4 and 15 ] [ Designated as safety issue: No ]
    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) [ Time Frame: screening, days 1, 2, 3, 4 and 15 ] [ Designated as safety issue: No ]
    Blood samples will be collected during screening, days 1 through 4 and then on Day 15 for the determination of serum concentrations of RLX030
  • Measure: Safety and tolerability (composite outcome: vital signs, 12 lead ECG, safety laboratory, [serious] adverse events) [ Time Frame: Days 1, 2, 3, 4, 15 ] [ Designated as safety issue: Yes ]
  • Measure: Immunogenicity (number of subjects with anti-RLX030 antibodies) [ Time Frame: Day 1 (prior to administration) and Day 15 end of study ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
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.

Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Hepatic Impairment
Drug: RLX030A
RLX030 is administered as a continuous 24 hour infusion
  • Experimental: RLX030: Group 1 mild hepatic impairment
    Patients with mild hepatic impairment will receive a single IV 24 hour infusion of RLX030
    Intervention: Drug: RLX030A
  • Experimental: RLX030: Group 2 moderate hepatic impairment
    Patients with moderate hepatic impairment will receive a single IV 24 hour infusion of RLX030
    Intervention: Drug: RLX030A
  • Experimental: RLX030: Group 3 severe hepatic impairment
    Patients with severe hepatic impairment will receive a single IV 24 hour infusion of RLX030
    Intervention: Drug: RLX030A
  • 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.
    Intervention: Drug: RLX030A
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
55
December 2011
December 2011   (final data collection date for primary outcome measure)

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.

Both
18 Years to 70 Years
Yes
Contact information is only displayed when the study is recruiting subjects
Germany,   Russian Federation
 
NCT01433458
CRLX030A2101, 2011-001596-39
Not Provided
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
January 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP