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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Hepatic Impairment

Intervention / Treatment
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* Drug: RLX030A


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatic impairment, healthy volunteers, RLX030, pharmacokinetics