Phase 2
Completed N=46
Study of Safety, Tolerability and Pharmacokinetics of Serelaxin in Japanese Acute Heart Failure (AHF) Patients
Source: ClinicalTrials.gov NCT02002702 ↗Enrolled (actual)
46
Serious AEs
8.7%
Results posted
Oct 2015
Primary outcomePrimary: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Due to AEs and SAEs, AEs Requiring Dose Adjustment or Interruption and Additional Therapy — 10; 11; 9; 1 participants
Summary
This is a multicenter, randomized, double-blind, placebo-controlled study to assess safety, tolerability and pharmacokinetics and to explore efficacy of IV infusion of 10 µg/kg/day and 30 µg/kg/day serelaxin for 48 hours compared to placebo, when added to the standard therapy, in approximately 45 Japanese AHF patients.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations Due to AEs and SAEs, AEs Requiring Dose Adjustment or Interruption and Additional Therapy |
10; 11; 9; 1; 3; 0 | — |
| PRIMARY Maximum Plasma Concentration (Cmax) of Serelaxin |
8.01; 19.2 | — |
| PRIMARY Weight Adjusted Clearance (CL) of Serelaxin |
56.8; 70.2 | — |
| PRIMARY Concentration at Steady-state (Css) of Serelaxin |
7.81; 19.1 | — |
| SECONDARY Change From Baseline in Area Under the Curve (AUC) for Systolic Blood Pressure (SBP) Through 48 Hours of Infusion at Day 5 |
-8.21; -18.6; -10.88; -8.79; -22.14; -14.77 | — |
| SECONDARY Change From Baseline in Aldosterone Levels Through Day 14 |
0.985; 0.816; 0.791; 0.975; 0.721; 0.911 | — |
| SECONDARY Change From Baseline in Cystatin-C Levels Through Day 14 |
0.921; 0.988; 0.985; 0.930; 0.852; 0.965 | — |
| SECONDARY Change From Baseline in High Sensitivity Troponin-T Levels Through Day 14 |
0.899; 1.060; 0.956; 0.856; 1.040; 0.894 | — |
| SECONDARY Change From Baseline in NT-proBNP Levels Through Day 14 |
0.585; 0.646; 0.673; 0.492; 0.451; 0.581 | — |
| SECONDARY Change From Baseline in Neutrophil Gelatinase-asc Lipocalin (NGAL) Levels Through Day 14 |
1.011; 1.083; 1.054; 0.929; 1.172; 1.099 | — |
Eligibility Criteria
Key Inclusion Criteria
- Written informed consent must be obtained before any study-specific assessment is performed.
- Male or female ≥20 years of age, with body weight ≥30 kg and ≤160 kg
- Hospitalized for AHF; AHF is defined as including all of the followings measured at any time between presentation (including the emergency department) and the end of screening:
- Dyspnea at rest or with minimal exertion
- Pulmonary congestion on chest radiograph
- BNP ≥350 pg/mL or NT-proBNP ≥1, 400 pg/mL
- SBP ≥125 mmHg at the start and at the end of screening
- Able to be randomized within 16 hours from presentation to the hospital, including the emergency department
- Received intravenous (IV) furosemide of at least 40 mg (or equivalent) at any time between presentation (this include outpatient clinic, ambulance, or hospital including emergency department) and the start of screening for the study for the treatment of the current acute heart failure (HF) episode.
- Impaired renal function defined as an estimated glomerular filtration rate (eGFR) between presentation and randomization of ≥ 25 and≤ 75 mL/min/1.73 m2, calculated using the Japanese formula
Key Exclusion Criteria
- Dyspnea primarily due to non-cardiac causes
- Temperature >38.5°C (oral or equivalent) or sepsis or active infection requiring IV anti-microbial treatment
- Clinical evidence of acute coronary syndrome currently or within 30 days prior to enrollment.
- AHF due to significant arrhythmias, which include any of the following: sustained ventricular tachycardia, bradycardia with sustained ventricular rate 130 beats per minute.
Data sourced from ClinicalTrials.gov (NCT02002702). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.