PK of Serelaxin in Severe Renal Impairment and ESRD

End-Stage Renal Disease Clinical Trial

— CRLX030A2102  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01875523
• Other study ID #: CRLX030A2102
• Secondary ID: 2013-001875-18
• Status: Completed
• Phase: Phase 1
• Start date: August 2013
• Est. completion date: December 2013

Study information

• Verified date: April 2014
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• End-Stage Renal Disease
• Kidney Diseases
• Kidney Failure, Chronic
• Renal Failure, Chronic
• Renal Insufficiency

Intervention

Drug:
• Serelaxin

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Grunstadt

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	Percentage of patients with reported adverse events, serious adverse events and death.		From Day -21 to Day 15
Secondary	Percentage of patients developing anti-RLX030 antibodies		Day 1 (pre-treatment) and Day 15

External Links

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