Open-label Extension Study for CLCZ696G2301 (PARADISE-MI)

A Multicenter Study to Evaluate the Long-term Safety and Tolerability of Open-label LCZ696 in Patients With Acute Myocardial Infarction Who Previously Participated in CLCZ696G2301 (PARADISE-MI)

The purpose of this study is to collect long-term safety and tolerability data of LCZ696 and to provide open-label LCZ696 to eligible participants who completed CLCZ696G2301 study (PARADISE-MI) if LCZ696 is shown to have a positive benefit-risk profile in comparison to ramipril in reducing risk of cardiovascular (CV) mortality and development of heart failure in participants enrolled in the PARADISE-MI study.

Study Overview

• Status: Withdrawn
• Conditions: Post Myocardial Infarction
• Intervention / Treatment: Drug: sacubitril/valsartan

• Study Type: Interventional
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Written informed consent must be obtained before any assessment is performed.
2. Participant received study treatment (either in LCZ696 or ramipril treatment arm) in PARADISE-MI.
3. Participant is safe to be enrolled in the extension study and may benefit from the treatment of LCZ696 per investigator's clinical judgement.

Exclusion Criteria:

1. Participant with a known history of angioedema
2. History of hypersensitivity to the study drug or drugs of similar chemical classes or known intolerance or contraindications to study drug or drugs of similar chemical classes including ACE inhibitors, ARB or NEP inhibitors
3. Symptomatic hypotension at screening
4. Serum potassium > 5.2 mmol /L (or equivalent plasma potassium value) at screening
5. Known hepatic impairment (as evidenced by total bilirubin > 3.0 mg/dL or increased ammonia levels, if performed), or history of cirrhosis with evidence of portal hypertension such as esophageal varices
6. Pregnant or nursing women or women of child-bearing potential unless they are using highly effective methods of contraception
7. Other protocol-defined inclusion/exclusion criteria 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 (sacubitril/valsartan); Following start of treatment, patients will receive LCZ696. Possible doses are level 1, 2, and 3 (50, 100 and 200 mg twice daily respectively)	Drug: sacubitril/valsartan; LCZ696 (sacubitril/valsartan) tablet will be available in 24/26 mg, 49/51 mg and 97/103 mg, respectively; Other Names: LCZ696

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with AE(s) leading to permanent study drug discontinuation, temporary study drug interruption, or study drug dose adjustment will be reported and summarized	Adverse events (AEs) leading to treatment changes including treatment discontinuation, interruption, and dose adjustment	Up to 24 months
Number of participants with Serious Adverse Events (SAEs)	SAE(s) will be reported, and the number of participants with SAE(s) will be summarized	Up to 24 months
Vital signs (Blood Pressure and pulse)	BP and pulse will be measured at every visit. The test values of Systolic Blood Pressure (mmHg), Diastolic Blood Pressure (mmHg) and heart rate (rate/minute) as well as change from the baseline will be summarized by parameter, using number of observations, mean, standard deviation, median, minimum, and maximum	Baseline and up to 24 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Anticipated): May 26, 2021
• Primary Completion (Anticipated): June 1, 2023
• Study Completion (Anticipated): June 1, 2023

Study Registration Dates

• First Submitted: November 4, 2020
• First Submitted That Met QC Criteria: November 17, 2020
• First Posted (Actual): November 19, 2020

Study Record Updates

• Last Update Posted (Actual): November 26, 2021
• Last Update Submitted That Met QC Criteria: November 16, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: LCZ696; Open-Label Extension; PARADISE-MI; Post Myocardial Infarction; Post Heart Attack; CLCZ696G2301
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; 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: CLCZ696G2301E1; 2020-003906-29 (EudraCT Number)

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