E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Heart failure with reduced ejection fraction |
Hartfalen met lage ejectiefractie |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019279 |
E.1.2 | Term | Heart failure |
E.1.2 | System Organ Class | 100000004849 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
De primaire doelstelling van dit onderzoek is het blijven evalueren van de veiligheid en verdraagbaarheid van LCZ696 bij patiënten uit PARADIGM-HF met hartfalen die open-label onderzoeksgeneesmiddel ontvangen. |
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E.2.2 | Secondary objectives of the trial |
Not applicable |
Niet van toepassing |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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. |
1. Schriftelijke toestemming voor het extensie onderzoek voordat ook maar enige onderzoeksprocedure plaatsvindt.
2. Patiënten die in het PARADIGM-HF-onderzoek zijn behandeld met dubbelblind onderzoeksmedicatie en naar het oordeel van de onderzoeker veilig kunnen overgaan naar het open-label onderzoek.
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E.4 | Principal 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. |
1. Het gebruik van andere experimentele geneesmiddelen op het moment van inclusie, of in de periode 30 dagen of 5 halfwaardetijden, welke maar het langste is, voorafgaand aan de inclusie.
2. Geschiedenis van overgevoeligheid of allergie voor LCZ696, medicatie van vergelijkbare klassen, ACEIs, ARBs, of Neutral Endopeptidase-remmers als ook een bekende of vermoede contra-indicatie voor LCZ696.
3. Bekende voorgeschiedenis van angio-oedeem.
4. Benodigde gelijktijdige behandeling met zowel ACEIs en ARB's.
5. Huidig acuut gedecompenseerd HF (exacerbatie van chronische HF gemanifesteerd door symptomen die intraveneuze therapie vereisen).
6. Symptomatische hypotensie en / of een SBP <100 mmHg op moment van visite 1 (screening).
7. eGFR <30 ml / min / 1.73m2, zoals gemeten door de vereenvoudigde MDRD formule op visite 1 (screening).
8. Aanwezigheid van een bilaterale nierarteriestenose.
9. Serum kalium > 5,2 mmol / L op visite 1 (screening).
10. Leveraandoening zoals bepaald door een van de volgende: AST of ALT-waarden meer dan 3 x ULN op visite 1, geschiedenis van hepatische encefalopathie, geschiedenis van oesofagiale varices, of een voorgeschiedenis van portacaval shunt.
11. Zwangere of zogende vrouwen.
12. Vrouwen in de vruchtbare leeftijd, tenzij 2 anticonceptie methoden.
13. Elke aandoening, niet gespecificeerd in het protocol, waardoor LCZ696 niet wordt verdragen of patiënt niet aan studie procedures kan worden voldaan, dit naar oordeel van de onderzoeker. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary assessments for safety are the reporting of all (S)AEs. 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. |
Rapportage van alle (S)AEs. De beoordeling van de veiligheid wordt voornamelijk gebaseerd op de frequentie van specifieke bijwerkingen, zittende systolische en diastolische bloeddruk, hartslag, en ernstige bijwerkingen gerelateerd aan LCZ696. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Total follow up time (up to 30 months) |
Gedurende gehele follow-up tijd (maximaal 30 maanden). |
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E.5.2 | Secondary end point(s) |
Not applicable |
Niet van toepassing |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Not applicable |
Niet van toepassing |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability of LCZ696 in patients with chronic heart failure |
Verdraagbaarheid van LCZ696 bij patiënten met chronisch hartfalen |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 15 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 429 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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 |
Romania |
Russian Federation |
Singapore |
Slovakia |
South Africa |
Spain |
Sweden |
Taiwan |
Thailand |
Turkey |
United Kingdom |
United States |
Venezuela, Bolivarian Republic of |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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LVLS (Expected: 2017-03-31). |
LVLS (naar verwachting: 31-03-2017). |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 15 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |