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
Overview
- Phase
- Phase 1
- Intervention
- Serelaxin
- Conditions
- Renal Failure, Chronic
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 36
- Locations
- 1
- Primary Endpoint
- The observed maximum serum concentration following drug administration (Cmax)
- Status
- Completed
- Last Updated
- 5 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
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.
Arms & Interventions
Group 1 Treatment with serelaxin
Patients with severe renal impairment will receive a single 4 hour i.v. infusion of serelaxin
Intervention: Serelaxin
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
Intervention: Serelaxin
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
Intervention: Serelaxin
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
Intervention: Serelaxin
Outcomes
Primary Outcomes
The observed maximum serum concentration following drug administration (Cmax)
Time Frame: 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
Blood samples will be collected on days 1 through 3 and then on Day 15 for the determination of serum concentrations of serelaxin
The area under the serum concentration-time curve from time zero to 28 hours after administration (AUC 0-28hr)
Time Frame: 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
Blood samples will be collected on days 1 through 3 and then on Day 15 for the determination of serum concentrations of serelaxin
Area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast)
Time Frame: 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
Blood samples will be collected on days 1 through 3 and then on Day 15 for the determination of serum concentrations of serelaxin
The area under the serum concentration-time curve from time zero to infinity (AUCinf)
Time Frame: 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
Blood samples will be collected on days 1 through 3 and then on Day 15 for the determination of serum concentrations of serelaxin
Secondary Outcomes
- Percentage of patients developing anti-RLX030 antibodies(Day 1 (pre-treatment) and Day 15)
- Percentage of patients with reported adverse events, serious adverse events and death.(From Day -21 to Day 15)