PK of Serelaxin in Severe Renal Impairment and ESRD

NCT01875523 | Completed Phase 1

• 2 other identifiers: CRLX030A21022013-001875-18
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Renal Failure, Chronic; End-Stage Renal Disease

Keywords

Renal disease; renal impairment; End stage renal disease; Healthy volunteer; Pharmacokinetics

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (2)

• 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

Study Arms (4)

Group 1 Treatment with serelaxin

EXPERIMENTAL

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

Drug: Serelaxin

Group 2 Treatment with serelaxin

EXPERIMENTAL

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

Group 3 Treatment with serelaxin

EXPERIMENTAL

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

Group 4 Treatment with serelaxin

EXPERIMENTAL

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

Interventions

Serelaxin DRUG

Also known as: RLX030

Group 1 Treatment with serelaxin; Group 2 Treatment with serelaxin; Group 3 Treatment with serelaxin; Group 4 Treatment with serelaxin

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (1)

Novartis Investigative Site

Grünstadt, D-67269, Germany

Location

Related Links

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

MeSH Terms

Conditions

Kidney Failure, Chronic; Kidney Diseases; Renal Insufficiency

Interventions

serelaxin protein, human

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2013
• First Posted: June 12, 2013
• Study Start: August 1, 2013
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: December 21, 2020

Record last verified: 2014-04

Locations

DE (1)