Study of Safety, Tolerability and Pharmacokinetics of Serelaxin in Japanese Acute Heart Failure (AHF) Patients

Novartis

Status and phase: Completed; Phase 2

Conditions: Acute Heart Failure

Treatments: Drug: Placebo; Drug: Serelaxin

Study type: Interventional

Funder types: Industry

Identifiers

NCT02002702

CRLX030A1201

Details and patient eligibility

About

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.

Enrollment: 46 patients

Sex: All

Ages: 20+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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 <45 beats per minute, or atrial fibrillation/flutter with sustained ventricular response of >130 beats per minute.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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46 participants in 3 patient groups, including a placebo group

Serelaxin 10 mcg/kg/Day

Experimental group

Description:

Participants received 10 mcg/kg/day serelaxin as continuous i.v. infusion for 48 hours.

Treatment:

Drug: Serelaxin

Serelaxin 30 mcg/kg/Day

Experimental group

Description:

Participants received 30 mcg/kg/day serelaxin as continuous i.v. infusion for 48 hours.

Treatment:

Drug: Serelaxin

Placebo

Placebo Comparator group

Description:

Participants received continuous i.v. infusion of placebo matched to serelaxin for 48 hours.

Treatment:

Drug: Placebo