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

Novartis

Status and phase: Completed; Phase 1

Conditions: End-Stage Renal Disease; Renal Failure, Chronic

Treatments: Drug: Serelaxin

Study type: Interventional

Funder types: Industry

Identifiers

NCT01875523

2013-001875-18 (EudraCT Number)

CRLX030A2102

Details and patient eligibility

About

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.

Enrollment: 36 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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36 participants in 4 patient groups

Group 1 Treatment with serelaxin

Experimental group

Description:

Patients with severe renal impairment will receive a single 4 hour i.v. infusion of serelaxin

Treatment:

Drug: Serelaxin

Group 2 Treatment with serelaxin

Experimental group

Description:

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

Treatment:

Drug: Serelaxin

Group 3 Treatment with serelaxin

Experimental group

Description:

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

Treatment:

Drug: Serelaxin

Group 4 Treatment with serelaxin

Experimental group

Description:

Healthy volunteers will receive a single 4 hour i.v. infusion of serelaxin and dialysis will be done on the day of treatment

Treatment:

Drug: Serelaxin