An Open-label Extension Study Evaluating Safety and Tolerability of LCZ696 in Subjects Who Completed PARAGON-HF in Japan.

A Multicenter, Open-label Study to Evaluate the Safety and Tolerability of LCZ696 Treatment in Japanese Heart Failure Patients (NYHA Class II-IV) With Preserved Ejection Fraction After CLCZ696D2301 (PARAGON-HF)

This study evaluated the safety and tolerability of LCZ696 treatment in Japanese heart failure patients (NYHA Class II-IV) with preserved ejection fraction after CLCZ696D2301 (PARAGON-HF).

Study Overview

• Status: Terminated
• Conditions: Heart Failure With Preserved Ejection Fraction (HFpEF)
• Intervention / Treatment: Drug: LCZ696

Detailed Description

This study was an open-label extension study following the PARAGON-HF. Patients who have completed the PARAGON-HF were eligible to participate. During the study, open-label LCZ696 was taken in addition to background treatments of comorbidities. All subjects were treated with LCZ696 (sacubitril/valsartan) at maximally tolerated dosed with a target dose of 200 mg b.i.d (twice a day).

The subject were to continue to receive LCZ696 until it became commercially available, or for a period up to 24 months from the first patient enrolled in this study whichever came first. However, this study was terminated early based on the pre-defined early termination criteria of "the primary endpoint of PARAGONHF was not met" in the protocol.

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Aichi
    • Seto-city, Aichi, Japan, 489-8642
      • Novartis Investigative Site
  • Fukuoka
    • Chikushino-city, Fukuoka, Japan, 818-8516
      • Novartis Investigative Site
  • Gifu
    • Ogaki-city, Gifu, Japan, 503-8502
      • Novartis Investigative Site
  • Gunma
    • Maebashi city, Gunma, Japan, 371 8511
      • Novartis Investigative Site
  • Ishikawa
    • Kanazawa, Ishikawa, Japan, 920 8650
      • Novartis Investigative Site
  • Iwate
    • Morioka, Iwate, Japan, 020 0066
      • Novartis Investigative Site
  • Kagawa
    • Kanonji-city, Kagawa, Japan, 769-1695
      • Novartis Investigative Site
    • Takamatsu city, Kagawa, Japan, 760 8557
      • Novartis Investigative Site
  • Kanagawa
    • Yokohama-city, Kanagawa, Japan, 236 0051
      • Novartis Investigative Site
    • Yokohama-city, Kanagawa, Japan, 227-8501
      • Novartis Investigative Site
  • Miyagi
    • Sendai city, Miyagi, Japan, 980 8574
      • Novartis Investigative Site
  • Nara
    • Kashihara city, Nara, Japan, 634 8522
      • Novartis Investigative Site
  • Saitama
    • Sayama-city, Saitama, Japan, 350-1305
      • Novartis Investigative Site
  • Shiga
    • Kusatsu city, Shiga, Japan, 525 8585
      • Novartis Investigative Site
  • Tokyo
    • Hachioji-city, Tokyo, Japan, 192-0918
      • Novartis Investigative Site
    • Itabashi-ku, Tokyo, Japan, 173-8610
      • Novartis Investigative Site
    • Shinagawa-ku, Tokyo, Japan, 142-8666
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed informed consent must be obtained before any assessment is performed.
• Patients who have completed LCZ696D2301 and are able to be safely enrolled into this study as judged by the investigator.

Exclusion Criteria:

• Patients who discontinued study drug treatment during LCZ696D2301 due to an event or intercurrent illness. Eligibility can be re-considered if the event has resolved and no longer represents a risk to the patient and the patient can safely tolerate the administration of LCZ696 per the investigator's assessment.
• Any medical condition that in the opinion of the investigator is likely to prevent the patient from safely tolerating LCZ696 or complying with the requirements of the study.
• Patients who have experience of angioedema event(s) which occurred and reported by the investigator during LCZ696D2301.
• Pregnant or nursing (lactating) women.
• Women of childbearing potential unless they are using highly effective methods of contraception.

Other protocol-defined inclusion/exclusion may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LCZ696; Starting dose was either 50 mg b.i.d. or 100 mg b.i.d. largely depending on the last dose level taken by the patient at the time of completing PARAGON-HF and patient condition. The dose level was gradually up-titrated with the goal of reaching the target dose of 200 mg b.i.d. as soon as tolerated by the patient	Drug: LCZ696; Starting dose was either 50 mg b.i.d. or 100 mg b.i.d. largely depending on the last dose level taken by the patient at the time of completing PARAGON-HF and patient condition. The dose level was gradually up-titrated with the goal of reaching the target dose of 200 mg b.i.d. as soon as tolerated by the patient; Other Names: Sacubitril/valsartan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events and Serious Adverse Events	An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a subject or clinical investigation subject after providing written informed consent for participation in the study. Any sign or symptom that occured from first dose of study treatment until end of study treatment.	Up to 27 weeks

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• A Plain Language Trial Summary is available on novartisclinicaltrials.com

Study record dates

Study Major Dates

• Study Start (Actual): May 7, 2019
• Primary Completion (Actual): November 19, 2019
• Study Completion (Actual): November 19, 2019

Study Registration Dates

• First Submitted: April 8, 2019
• First Submitted That Met QC Criteria: April 8, 2019
• First Posted (Actual): April 10, 2019

Study Record Updates

• Last Update Posted (Actual): October 8, 2021
• Last Update Submitted That Met QC Criteria: October 7, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: heart failure with preserved ejection fraction, Japanese patients, extension study, long-term safety and tolerability, open-label
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Valsartan; Sacubitril and valsartan sodium hydrate drug combination
• Other Study ID Numbers: CLCZ696D1301E1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No