Clinical trial NCT02002702: Study of Safety, Tolerability and Pharmacokinetics of Serelaxin in Japanese Acute Heart Failure (AHF) Patients
Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled Phase II Study to Assess the Safety, Tolerability and Pharmacokinetics of Serelaxin When Added to Standard Therapy in Japanese Acute Heart Failure Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Heart Failure
Keywords: Acute heart failure (AHF),
Japanese,
Safety and tolerability, Pharmacokinetics,
Renal Impairment
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2013-12-06
Enrollment: 46
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


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

Primary outcomes:
measure: 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
timeFrame: From start of study treatment up to Day 5 (for AEs); From start of study treatment up to Day 14 (for SAEs)
measure: Maximum Plasma Concentration (Cmax) of Serelaxin
timeFrame: Baseline (pre-dose), 1, 2, 24, 48, 49, 52 and 56 hours (post-dose)
measure: Weight Adjusted Clearance (CL) of Serelaxin
timeFrame: Baseline (pre-dose), 1, 2, 24, 48, 49, 52 and 56 hours (post-dose)
measure: Concentration at Steady-state (Css) of Serelaxin
timeFrame: Baseline (pre-dose), 1, 2, 24, 48, 49, 52 and 56 hours (post-dose)
Secondary outcomes:
measure: Change From Baseline in Area Under the Curve (AUC) for Systolic Blood Pressure (SBP) Through 48 Hours of Infusion at Day 5
timeFrame: Baseline, 48 hours, Day 5
measure: Change From Baseline in Aldosterone Levels Through Day 14
timeFrame: Baseline, Day 1, Day 2, Day 5, Day 14
measure: Change From Baseline in Cystatin-C Levels Through Day 14
timeFrame: Baseline, Day 1, Day 2, Day 5, Day 14
measure: Change From Baseline in High Sensitivity Troponin-T Levels Through Day 14
timeFrame: Baseline, Day 1, Day 2, Day 5, Day 14
measure: Change From Baseline in NT-proBNP Levels Through Day 14
timeFrame: Baseline, Day 1, Day 2, Day 5, Day 14
measure: Change From Baseline in Neutrophil Gelatinase-asc Lipocalin (NGAL) Levels Through Day 14
timeFrame: Baseline, Day 1, Day 2, Day 5, Day 14
Other outcomes:
Locations:
city: Seto-city
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Fukuoka-city
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Iizuka-city
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Hiroshima-city
country: Japan
facility: Novartis Investigative Site
state: Hiroshima
city: Amagasaki-city
country: Japan
facility: Novartis Investigative Site
state: Hyogo
city: Higashiibaraki-gun
country: Japan
facility: Novartis Investigative Site
state: Ibaraki
city: Kanazawa
country: Japan
facility: Novartis Investigative Site
state: Ishikawa
city: Kawasaki-city
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Yokohama-city
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Sendai-city
country: Japan
facility: Novartis Investigative Site
state: Miyagi
city: Ueda-city
country: Japan
facility: Novartis Investigative Site
state: Nagano
city: Osaka-city
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Sayama-city
country: Japan
facility: Novartis Investigative Site
state: Saitama
city: Komatsushima-city
country: Japan
facility: Novartis Investigative Site
state: Tokushima
city: Itabashi-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: