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
  Purpose

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.


Condition Intervention Phase
Hepatic Impairment
Drug: RLX030A
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
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

Further study details as provided by Novartis:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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


Enrollment: 55
Study Start Date: July 2011
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01433458

Locations
Germany
Novartis Investigative Site
Grunstadt, Germany, D-67269
Russian Federation
Novartis Investigative Site
Moscow, Russian Federation, 115419
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01433458     History of Changes
Other Study ID Numbers: CRLX030A2101, 2011-001596-39
Study First Received: August 9, 2011
Last Updated: January 20, 2013
Health Authority: United States: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices
Russia: Ministry of Health of the Russian Federation

Keywords provided by Novartis:
Hepatic impairment
healthy volunteers
RLX030
pharmacokinetics

Additional relevant MeSH terms:
Liver Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on September 16, 2014