Evidence map›Paper›PMID 27083930›Full record

Trial reportEuropean journal of clinical pharmacology2016

Single therapeutic and supratherapeutic doses of sacubitril/valsartan (LCZ696) do not affect cardiac repolarization.

Thomas H Langenickel, Pierre Jordaan, Jesika Petruck, Kiran Kode, Parasar Pal, Soniya Vaidya, Priya Chandra, Iris Rajman

Open access · hybridAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in European journal of clinical pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
2.7field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 25 citations in OpenAlex.

  1. Vericiguat: A Randomized, Phase Ib, Placebo-Controlled, Double-Blind, QTc Interval Study in Patients with Chronic Coronary Syndromes.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2023
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 2 countries.

Thomas H LangenickelTranslational Medicine, Clinical Pharmacology and Profiling, Novartis Pharma AG, Basel, CH-4002, Switzerland. thomas.langenickel@novartis.com.
Pierre JordaanTranslational Medicine, Clinical Pharmacology and Profiling, Novartis Pharma AG, Basel, CH-4002, Switzerland.
Jesika PetruckTranslational Medicine, Clinical Sciences and Innovation, Novartis Institutes for Biomedical Research, Cambridge, MA, USA.
Kiran KodeIntegrated Quantitative Sciences, Novartis Healthcare Private Limited, Hyderabad, India.
Parasar PalIntegrated Quantitative Sciences, Novartis Healthcare Private Limited, Hyderabad, India.
Soniya VaidyaTranslational Medicine, Drug Metabolism and Pharmacokinetics, Novartis Institutes for Biomedical Research, Cambridge, MA, USA.
Priya ChandraTranslational Medicine, Drug Metabolism and Pharmacokinetics, Novartis Institutes for Biomedical Research, East Hanover, NJ, USA.
Iris RajmanTranslational Medicine, Clinical Pharmacology and Profiling, Novartis Pharma AG, Basel, CH-4002, Switzerland.
Novartis (Switzerland) · CHNovartis (India) · IN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeSacubitril/valsartan (LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor (ARNI) indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA class II-IV) and reduced ejection fraction. This study was aimed to evaluate the effect of single oral therapeutic (400 mg) and supratherapeutic (1200 mg) doses of LCZ696 on cardiac repolarization.

methodThis randomized double-blind crossover study in healthy male subjects compared the effect of therapeutic and supratherapeutic doses of LCZ696 with placebo and moxifloxacin 400 mg (open-label treatment) as positive control. The primary assessment was mean baseline- and placebo-corrected QTcF (∆∆QTcF; Fridericia correction). Additional assessments included the ∆∆QTcB (Bazett's correction), PR interval, QRS duration, heart rate (HR), LCZ696 pharmacokinetics, pharmacokinetic/pharmacodynamic relationships, and safety.

resultsOf the 84 subjects enrolled, 81 completed the study. The maximum upper bound of the two-sided 90 % confidence interval for ∆∆QTcF for LCZ696 400 mg and 1200 mg were <10 ms, and assay sensitivity was confirmed with moxifloxacin. No relevant treatment-emergent changes were observed in any of the ECG-derived parameters with LCZ696 or placebo, and the incidence of adverse events was comparable among the treatment groups.

conclusionSingle therapeutic and supratherapeutic doses of LCZ696 did not affect cardiac repolarization as defined by the E14 ICH guidelines.

Indexed as

AdolescentAdultAminobutyratesAngiotensin Receptor AntagonistsBiphenyl CompoundsCross-Over StudiesDouble-Blind MethodDrug CombinationsElectrocardiographyHeartHeart RateHumansMaleMiddle AgedTetrazolesValsartanAminobutyratesAngiotensin Receptor AntagonistsBiphenyl CompoundsDrug CombinationsLBQ657sacubitril and valsartan sodium hydrate drug combinationTetrazolesValsartanAngiotensin receptor neprilysin inhibitorCardiac repolarizationHeart failureLCZ696QT prolongationSacubitril/valsartan

Identifiers

PMID27083930
PMCPMC4942489
OpenAlexW2338387536

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.