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

NCT02002702 | Completed Phase 2 Results

• 1 other identifier: CRLX030A1201
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 15

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.

Conditions

Acute Heart Failure

Keywords

Acute heart failure (AHF),; Japanese,; Safety and tolerability, Pharmacokinetics,; Renal Impairment

Outcome Measures

Primary Outcomes (4)

• 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

  AEs were defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. SAEs were defined as any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgement of investigators represent significant hazards. AEs leading to discontinuations, or requiring dose adjustment or interruptions and additional therapy were assessed.

  From start of study treatment up to Day 5 (for AEs); From start of study treatment up to Day 14 (for SAEs)

• Maximum Plasma Concentration (Cmax) of Serelaxin

  Maximum plasma concentration (Cmax) was defined as the peak level of serelaxin, derived from plasma concentration-time data, using a non-compartmental model approach.

  Baseline (pre-dose), 1, 2, 24, 48, 49, 52 and 56 hours (post-dose)

• Weight Adjusted Clearance (CL) of Serelaxin

  Weight adjusted clearance (CL) was defined as the total body clearance of serelaxin after drug administration. CL was calculated as nominal infusion rate divided by Css, using a non-compartmental model approach.

  Baseline (pre-dose), 1, 2, 24, 48, 49, 52 and 56 hours (post-dose)

• Concentration at Steady-state (Css) of Serelaxin

  Concentration at steady-state (Css) was defined as concentration at the state of equilibrium obtained at the end of a certain number of administrations. Css of serelaxin in plasma was calculated by using a non-compartmental model approach.

  Baseline (pre-dose), 1, 2, 24, 48, 49, 52 and 56 hours (post-dose)

Secondary Outcomes (6)

• Change From Baseline in Area Under the Curve (AUC) for Systolic Blood Pressure (SBP) Through 48 Hours of Infusion at Day 5

  Baseline, 48 hours, Day 5

• Change From Baseline in Aldosterone Levels Through Day 14

  Baseline, Day 1, Day 2, Day 5, Day 14

• Change From Baseline in Cystatin-C Levels Through Day 14

  Baseline, Day 1, Day 2, Day 5, Day 14

• Change From Baseline in High Sensitivity Troponin-T Levels Through Day 14

  Baseline, Day 1, Day 2, Day 5, Day 14

• Change From Baseline in NT-proBNP Levels Through Day 14

  Baseline, Day 1, Day 2, Day 5, Day 14

Study Arms (3)

Serelaxin 10 mcg/kg/Day

EXPERIMENTAL

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

Drug: Serelaxin

Serelaxin 30 mcg/kg/Day

EXPERIMENTAL

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

Drug: Serelaxin

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Serelaxin DRUG

Intravenous infusion

Serelaxin 10 mcg/kg/Day; Serelaxin 30 mcg/kg/Day

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (15)

Novartis Investigative Site

Seto, Aichi-ken, 489-8642, Japan

Location

Novartis Investigative Site

Fukuoka, Fukuoka, 810-0001, Japan

Location

Novartis Investigative Site

Iizuka, Fukuoka, 820-8505, Japan

Location

Novartis Investigative Site

Hiroshima, Hiroshima, 730-8518, Japan

Location

Novartis Investigative Site

Amagasaki, Hyōgo, 660-8550, Japan

Location

Novartis Investigative Site

Higashiibaraki-gun, Ibaraki, 311-3193, Japan

Location

Novartis Investigative Site

Kanazawa, Ishikawa-ken, 920-8650, Japan

Location

Novartis Investigative Site

Kawasaki, Kanagawa, 211-8533, Japan

Location

Novartis Investigative Site

Yokohama, Kanagawa, 231-8682, Japan

Location

Novartis Investigative Site

Sendai, Miyagi, 981-3107, Japan

Location

Novartis Investigative Site

Ueda, Nagano, 386-8610, Japan

Location

Novartis Investigative Site

Osaka, Osaka, 534-0021, Japan

Location

Novartis Investigative Site

Sayama, Saitama, 350-1323, Japan

Location

Novartis Investigative Site

Komatsushimachō, Tokushima, 773-8502, Japan

Location

Novartis Investigative Site

Itabashi-ku, Tokyo, 173-8610, Japan

Location

MeSH Terms

Conditions

Hemophilia A; Renal Insufficiency

Interventions

serelaxin protein, human

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862 -778 -8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2013
• First Posted: December 6, 2013
• Study Start: January 1, 2014
• Primary Completion: August 1, 2014
• Study Completion: August 1, 2014
• Last Updated: October 12, 2015
• Results First Posted: October 12, 2015

Record last verified: 2015-09

Locations

JP (15)