Safety and tolerability during open-label treatment with LCZ696 in patients with chronic heart failure and reduced ejection fraction

• Register: EUCTR
• Last refreshed on: 13 March 2017
• Main ID: EUCTR2014-001971-30-SK
• Date of registration: 12/11/2014
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: Safety and tolerability during open-label treatment with LCZ696 in patients with chronic heart failure and reduced ejection fraction
• Scientific title: A multicenter study to evaluate safety and tolerability in patients with chronic heart failure and reduced ejection fraction from PARADIGM-HF receiving open label LCZ696
• Date of first enrolment: 10/12/2014
• Target sample size: 5000
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-001971-30
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Belgium, Brazil, Bulgaria, Canada, Chile, China, Colombia, Czech Republic, Denmark, Dominican Republic, Ecuador, Estonia, Finland, France, Germany, Guatemala, Hong Kong, Hungary, Iceland, India, Israel, Italy, Korea, Republic of, Latvia, Lithuania, Malaysia, Mexico, Netherlands, Panama, Peru, Philippines, Poland, Portugal, Romania, Russian Federation, Singapore, Slovakia, South Africa, Spain, Sweden, Taiwan, Thailand, Turkey, United Kingdom, United States, Venezuela, Bolivarian Republic of

Contacts

• Name: DRA Department
• Affiliation: Novartis Slovakia s.r.o.

• Name: DRA Department
• Affiliation: Novartis Slovakia s.r.o.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Written informed consent for the extension must be obtained before any assessment is performed.
2. Patients who have been enrolled and treated with double-blind study medication in the PARADIGM-HF study (protocol CLCZ696B2314) and are able to be safely enrolled into the open-label trial as judged by the investigator.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 2400
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2600

Exclusion criteria:
1. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is
longer
2. History of hypersensitivity or allergy to any of the study drugs, drugs of similar chemical classes, ACEIs, ARBs, or NEP inhibitors as well as known or suspected contraindications to LCZ696
3. Known history of angioedema
4. Requirement of simultaneous treatment with both ACEIs and ARBs 5. Current acute decompensated HF (exacerbation of chronic HF manifested by signs and symptoms that may require intravenous therapy)
6. Symptomatic hypotension and/or a SBP < 100 mmHg at Visit 1 (screening)
7. Estimated GFR < 30 mL/min/1.73m2 as measured by the simplified MDRD formula at Visit 1 (screening)
8. Presence of bilateral renal artery stenosis
9. Serum potassium > 5.2mmol/L at Visit 1 (screening)
10. Evidence of hepatic disease as determined by any one of the following: AST or ALT values exceeding 3 x ULN at Visit 1, history of hepatic encephalopathy, history of esophageal varices, or history of portacaval shunt
11. Pregnant or nursing (lactating) women
12. Women of childbearing potential
13. Any condition, not identified in the protocol, 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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Heart failure with reduced ejection fraction
MedDRA version: 19.1 Level: LLT Classification code 10019279 Term: Heart failure System Organ Class: 100000004849

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Intervention(s)

Product Name: LCZ696 50mg
Product Code: LCZ696
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: sacubitril/valsartan
Other descriptive name: LCZ696
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Product Name: LCZ696 100mg
Product Code: LCZ696
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: sacubitril/valsartan
Other descriptive name: LCZ696
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Product Name: LCZ696 200mg
Product Code: LCZ696
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: sacubitril/valsartan
Other descriptive name: LCZ696
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Primary Outcome(s)

Primary end point(s): The primary assessments for safety are the reporting of angioedema, AEs that are suspected to be related to LCZ696, AEs leading to study drug discontinuation and serious adverse events (SAE) including death. The assessment of safety will be based primarily on the frequency of adverse events of special interest, sitting systolic and diastolic blood pressure, heart rate, and serious adverse events suspected by the investigators to be related to LCZ696 for the Safety set.

Timepoint(s) of evaluation of this end point: Total follow up time (up to 30 months)

Main Objective: The primary objective of this study is to continue to evaluate the safety and tolerability of LCZ696 in heart failure patients from PARADIGM-HF receiving open-label investigational drug.

Secondary Objective: Not applicable

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Not applicable

Secondary end point(s): Not applicable

Secondary ID(s)

2014-001971-30-LV

CLCZ696B2317

Source(s) of Monetary Support

Novartis Pharma Services AG