The purpose of this study was to assess the safety of repeat doses of serelaxin in chronic heart failure.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Masking
QUADRUPLE
Enrollment
321
RLX030 (serelaxin) was administered according to a weight-range adjusted dosing regimen at a nominal dose of 30 μg/kg/day as a continuous IV infusion for 48 hours.
Matching placebo of serelaxin was administered as a continuous IV infusion for 48 hours.
Percentage of Participants With Chronic Heart Failure (CHF) Who Develop Anti-serelaxin Antibodies at Any Time Following Repeat Administration of IV Continuous Infusions of Serelaxin Administered for up to 48 Hours in 16 Weeks
A patient is considered antibody positive during the study if he/she had at least two infusions and had at least one evaluable measurement to test for anti-serelaxin antibodies after each infusion and all evaluable antibody test results were positive. A patient is considered antibody negative during the study if he/she had at least two infusions and had at least one evaluable measurement to test for anti-serelaxin antibodies after each infusion and all evaluable antibody test results were negative. A patient's antibody status is considered to be undetermined during the study if it is not defined as positive or negative.
Time frame: 16 weeks
Percentage of Participants With Chronic Heart Failure Who Develop Positive Anti-serelaxin Antibodies After a Single Infusion of Serelaxin Over Time up to Week 16
A patient is considered antibody positive during the study if he/she had at least two infusions and had at least one evaluable measurement to test for anti-serelaxin antibodies after each infusion and all evaluable antibody test results were positive. Each time period is defined as the time frame from study drug initiation (or the visit if there is no infusion) to prior to study drug initiation of the next period (or the visit if no there is no infusion). n= The total number of subjects with evaluable antibody status during the defined period.
Time frame: Randomization to Week 4, Week 4 to Week 8, Week 8 to Week 12, week 12 to week 16
Antibody Titers in Participants With Chronic Heart Failure Who Develop Positive Anti-serelaxin Antibodies (Neutralizing, Non-neutralizing or Both) at Any Time Following 3 Repeated Infusions and at Week 4, Week 8 and Week 12
Time frame: Week 4, Week 8, Week 12
Percentage of Participants With Chronic Heart Failure With Positive Antibody Status Who Develop Non-neutralizing Anti-serelaxin Antibodies Following 3 Repeated Infusions (i.e. at Week 4, Week 8, and Week 12)
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A patient is considered antibody positive during the study if he/she had at least two infusions and had at least one evaluable measurement to test for anti-serelaxin antibodies after each infusion and all evaluable antibody test results were positive. n = the total number of subjects with evaluable antibody status after specified number of infusions
Time frame: At Week 4, Week 8, Week 12
Number of Participants With Adverse Events Such as Adjudicated Potential Hypersensitivity or Infusion Reactions
Incidence rate of special interest, indicative of hypersensitivity reactions which occur during and after administration of repeated infusions of serelaxin relative to placebo in subjects with chronic heart failure is reported. Hypersensitivity reactions or infusion reactions can be headache, nausea, fever, chills, dizziness, flush, pruritus, chest and/or back pain.
Time frame: 16 weeks
Pharmacokinetics of RLX030: Area Under the Plasma Concentration Time Curve From Time Zero up to 48 Hours Post Dose (AUC 0-48)
Due to sparse PK sampling, AUC 0-48 hours was not analyzed.
Time frame: pre-infusion and 8, 24 and 48 hours post each infusion.
Pharmacokinetics of RLXL030: Actual Concentrations at Steady State (Css)
Concentration at steady state (Css) was estimated using C48 or C24 for patients who received the intended rate of infusion for at least 24hours. n: Number of patients with valid PK parameters available
Time frame: pre-infusion and 24, 48 hours post each infusion
Pharmacokinetics of RLX030: Cmax Steady State (Cmaxss) Concentration at 48 Hours
This analysis was not done due to sparse PK sampling.
Time frame: 48 hours post each infusion
Pharmacokinetics of RLX030: Clearance of Serelaxin (CL)
Clearance (CL) was calculated using concentration at steady state (Css) and the actual delivered dose rate. n: Number of patients with valid PK parameters available within 48 hours post each infusion.
Time frame: 48 hours post each infusion