PK of Serelaxin in Severe Renal Impairment and ESRD (CRLX030A2102)

A Single Dose, Open-label, Parallel-group Study to Assess the Pharmacokinetics of Serelaxin in Patients With Severe Renal Impairment or End-Stage Renal Disease on Hemodialysis Compared to Matched Healthy Control Subjects

The study is designed to evaluate the pharmacokinetics, safety and tolerability, immunogenicity and pharmacogenetics of a single dose of serelaxin/RLX030 in patients with severe renal impairment and end-stage-renal-disease (ESRD) compared to healthy volunteers.

Study Overview

• Status: Completed
• Conditions: End-Stage Renal Disease; Renal Failure, Chronic
• Intervention / Treatment: Drug: Serelaxin

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Grunstadt, Germany, D-67269
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion criteria:

All subjects

- at least 50 years; body mass index (BMI) within the range of 18 - 35 kg/m2.

Patients with severe renal impairment / ESRD

• Severe renal impairment (clinically significantly abnormal creatinine and creatinine clearance (15mL/min/1.73m2≤eGFR<30mL/min/1.73m2) or ESRD on hemodialysis.
• Sitting vital signs should be within the following ranges:
• oral body temperature between 35.0-37.5 °C
• systolic blood pressure, 110 to 170 mm Hg
• diastolic blood pressure, 60 to 105 mm Hg
• pulse rate, 45 - 100 bpm

Healthy subjects

• eGFR > 90mL/min/1.73m2;
• matching in race, age (±10 years), gender, BMI (±15%) to a subject with renal impairment
• Subject must be in good health.
• Sitting vital signs should be within the following ranges:
• oral body temperature between 35.0-37.5 °C
• systolic blood pressure, 100 to 150 mm Hg
• diastolic blood pressure, 60 to 95 mm Hg
• pulse rate, 50 to 100 bpm

Exclusion Criteria:

All subjects

• History of clinically significant ECG abnormalities at Screening or Baseline.
• Pregnant or nursing (lactating) women
• Women of child-bearing potential unless they are using highly effective methods of contraception during dosing of study treatment.
• Sexually active males (incl. vasectomized men) must use a condom during intercourse while taking drug and for 2 weeks after stopping study medication.
• Recent (within the last three years) and/or recurrent history of autonomic dysfunction (e.g., recurrent episodes of fainting, palpitations, etc.).

Patients with severe renal impairment / ESRD:

• Presence of any non-controlled and clinically significant disease, surgical or medical condition that could affect the study outcome or that would place the patient at undue risk as judged by the investigator.
• Hemoglobin levels below 9.0 g/dL at screening and baseline, other laboratory parameters at screening and baseline outside acceptable limits .
• Treatment with any cytostatic drug or autonomic alpha blocker.

Healthy subjects:

• Use of any prescription drugs (other than hormonal contraception, herbal supplements, within four (4) weeks prior to initial dosing, and/or over-the-counter (OTC) medication, dietary supplements (vitamins included) within two (2) weeks prior to initial dosing.
• History or presence of any disease, surgical or medical condition of any major system organ class considered clinically significant by the investigator.
• Laboratory parameter at screening and baseline outside of normal limits. For small deviations which could be attributed to the characteristics of the subjects (e.g. age) it will be to the discretion of the investigator to consider them as exclusive or not.
• A positive Hepatitis B surface antigen or Hepatitis C test result.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1 Treatment with serelaxin; Patients with severe renal impairment will receive a single 4 hour i.v. infusion of serelaxin	Drug: Serelaxin; Other Names: RLX030
Experimental: Group 2 Treatment with serelaxin; Patients with end stage renal disease will receive a single 4 hour i.v. infusion of serelaxin and dialysis will be done on the day of treatment	Drug: Serelaxin; Other Names: RLX030
Experimental: Group 3 Treatment with serelaxin; Patients with end stage renal disease will receive a single 4 hour i.v. infusion of serelaxin and treatment and PK will be done in dialysis-free interval	Drug: Serelaxin; Other Names: RLX030
Experimental: Group 4 Treatment with serelaxin; Healthy volunteers will receive a single 4 hour i.v. infusion of serelaxin and dialysis will be done on the day of treatment	Drug: Serelaxin; Other Names: RLX030

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast)	Blood samples will be collected on days 1 through 3 and then on Day 15 for the determination of serum concentrations of serelaxin	pre-treatment, 15 min, 1, 2, 3, 4, 4:15, 5, 6, 7, 8, 9, 10, 12, 24, 28, 36, 48 hours and day 15
The area under the serum concentration-time curve from time zero to 28 hours after administration (AUC 0-28hr)	Blood samples will be collected on days 1 through 3 and then on Day 15 for the determination of serum concentrations of serelaxin	pre-treatment, 15 min, 1, 2, 3, 4, 4:15, 5, 6, 7, 8, 9, 10, 12, 24, 28, 36, 48 hours and day 15
The area under the serum concentration-time curve from time zero to infinity (AUCinf)	Blood samples will be collected on days 1 through 3 and then on Day 15 for the determination of serum concentrations of serelaxin	pre-treatment, 15 min, 1, 2, 3, 4, 4:15, 5, 6, 7, 8, 9, 10, 12, 24, 28, 36, 48 hours and day 15
The observed maximum serum concentration following drug administration (Cmax)	Blood samples will be collected on days 1 through 3 and then on Day 15 for the determination of serum concentrations of serelaxin	pre-treatment, 15 min, 1, 2, 3, 4, 4:15, 5, 6, 7, 8, 9, 10, 12, 24, 28, 36, 48 hours and day 15

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of patients with reported adverse events, serious adverse events and death.	From Day -21 to Day 15
Percentage of patients developing anti-RLX030 antibodies	Day 1 (pre-treatment) and Day 15

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• Results for CRLX030A2102 can be found on the Novartis Clinical Trial Results Website

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: June 7, 2013
• First Submitted That Met QC Criteria: June 7, 2013
• First Posted (Estimate): June 12, 2013

Study Record Updates

• Last Update Posted (Actual): December 21, 2020
• Last Update Submitted That Met QC Criteria: December 17, 2020
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: Pharmacokinetics; End stage renal disease; renal impairment; Healthy volunteer; Renal disease
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency, Chronic; Kidney Diseases; Kidney Failure, Chronic; Renal Insufficiency
• Other Study ID Numbers: CRLX030A2102; 2013-001875-18 (EudraCT Number)