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NCT02992288: PANTHEON

A Trial to Study Neladenoson Bialanate Over 20 Weeks in Patients With Chronic Heart Failure With Reduced Ejection Fraction

Completed Phase 2 Results posted Last updated 23 April 2019
What this trial tests

Phase 2 trial testing Neladenoson bialanate (BAY1067197) in Heart Failure in 427 participants. Completed in 16 May 2018.

Timeline
22 February 2017
Primary endpoint
28 March 2018
16 May 2018

Quick facts

Lead sponsorBayer
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment427
Start date22 February 2017
Primary completion28 March 2018
Estimated completion16 May 2018
Sites75 locations across Italy, Japan, Netherlands, Greece, Belgium, Germany, Israel, Poland

Drugs / interventions tested

Conditions studied

Sponsor

Bayer — full company profile →

Who can join

18 and older, any sex, with Heart Failure. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Absolute Change From Baseline in Left Ventricular Ejection Fraction (LVEF) (%) at Week 20 Measured by Echocardiography Primary · Baseline, Week 20

Left ventricular ejection fraction (LVEF) was measured by echocardiography. Mean and standard deviation were reported.

GroupValue95% CI
Placebo-2.19± 8.39
Neladenoson Bialanate 5 mg2.59± 8.48
Neladenoson Bialanate 10 mg-3.01± 10.43
Neladenoson Bialanate 20 mg0.13± 8.74
Neladenoson Bialanate 30 mg-2.45± 10.54
Neladenoson Bialanate 40 mg1.53± 10.01
Absolute Change From Baseline in Log-transformed NT-pro B-type Natriuretic Peptide (BNP) at Week 20 Primary · Baseline, Week 20

NT-pro b-type Natriuretic Peptide (BNP) was measured. Mean and standard deviation were reported.

GroupValue95% CI
Placebo-0.07± 0.70
Neladenoson Bialanate 5 mg-0.24± 0.90
Neladenoson Bialanate 10 mg-0.07± 0.52
Neladenoson Bialanate 20 mg-0.07± 0.56
Neladenoson Bialanate 30 mg0.07± 0.55
Neladenoson Bialanate 40 mg-0.08± 0.79
Change From Baseline in Left Ventricular End-Systolic Volume (LVESV) at Week 20 Secondary · Baseline, Week 20

LVESV was defined as the volume of blood in the left ventricle at the end of contraction, or systole and the beginning of filling or diastole. Mean and standard deviation were reported.

GroupValue95% CI
Placebo-5.44± 33.29
Neladenoson Bialanate 5 mg-21.41± 48.13
Neladenoson Bialanate 10 mg-2.82± 35.12
Neladenoson Bialanate 20 mg-4.32± 29.73
Neladenoson Bialanate 30 mg-3.12± 33.96
Neladenoson Bialanate 40 mg-15.16± 39.65
Change From Baseline in Left Ventricular End-Diastolic Volume (LVEDV) at Week 20 Secondary · Baseline, Week 20

LVEDV was defined as the volume of blood in the left ventricle at end load or filling in diastole or the amount of blood in the ventricles just before systole. Mean and standard deviation were reported.

GroupValue95% CI
Placebo-13.16± 40.23
Neladenoson Bialanate 5 mg-21.65± 61.96
Neladenoson Bialanate 10 mg-12.44± 39.84
Neladenoson Bialanate 20 mg-5.92± 30.89
Neladenoson Bialanate 30 mg-11.17± 42.32
Neladenoson Bialanate 40 mg-19.69± 48.38
Change From Baseline in High Sensitivity Troponin T (Hs-TNT) at Week 20 Secondary · Baseline, Week 20

High sensitivity troponin T (hs-TNT) was measured. Mean and standard deviation were reported.

GroupValue95% CI
Placebo0.13± 9.98
Neladenoson Bialanate 5 mg6.46± 33.04
Neladenoson Bialanate 10 mg3.77± 22.32
Neladenoson Bialanate 20 mg7.43± 37.79
Neladenoson Bialanate 30 mg2.59± 12.90
Neladenoson Bialanate 40 mg7.03± 24.81
Number of Participants With Composite Efficacy Outcome Secondary · Baseline up to Week 26

Composite efficacy outcome was the first occurrence of CV death, HF hospitalization or urgent visit for HF. Number of participants with composite efficacy outcome were reported.

GroupValue95% CI
Placebo10
Neladenoson Bialanate 5 mg4
Neladenoson Bialanate 10 mg10
Neladenoson Bialanate 20 mg9
Neladenoson Bialanate 30 mg7
Neladenoson Bialanate 40 mg8
Number of Participants With Cardiovascular (CV) Mortality Secondary · Baseline up to Week 26

Cardiovascular (CV) mortality was assessed. Number of participants with CV mortality were reported.

GroupValue95% CI
Placebo1
Neladenoson Bialanate 5 mg1
Neladenoson Bialanate 10 mg3
Neladenoson Bialanate 20 mg1
Neladenoson Bialanate 30 mg2
Neladenoson Bialanate 40 mg1
Number of Participants With Heart Failure (HF) Hospitalization and Urgent Visits for Heart Failure (HF) Secondary · Baseline up to Week 26

Number of participants with HF hospitalization and urgent visits for HF were reported.

GroupValue95% CI
Placebo10
Neladenoson Bialanate 5 mg4
Neladenoson Bialanate 10 mg9
Neladenoson Bialanate 20 mg8
Neladenoson Bialanate 30 mg5
Neladenoson Bialanate 40 mg8

Adverse events — posted to ClinicalTrials.gov

Time frame: From start of study drug administration up to 26 weeks. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo
Serious: 31/106 (29%)
Deaths: 8/106
Neladenoson Bialanate 5mg
Serious: 13/37 (35%)
Deaths: 1/37
Neladenoson Bialanate 10mg
Serious: 28/70 (40%)
Deaths: 5/70
Neladenoson Bialanate 20mg
Serious: 22/72 (31%)
Deaths: 1/72
Neladenoson Bialanate 30mg
Serious: 28/69 (41%)
Deaths: 2/69
Neladenoson Bialanate 40mg
Serious: 26/72 (36%)
Deaths: 2/72

Serious adverse events (99 terms)

ReactionSystemPlaceboNeladenoson Bialanate 5mgNeladenoson Bialanate 10mgNeladenoson Bialanate 20mgNeladenoson Bialanate 30mgNeladenoson Bialanate 40mg
Cardiac failureCardiac disorders
Cardiac failure chronicCardiac disorders
Atrial fibrillationCardiac disorders
Cardiogenic shockCardiac disorders
Renal impairmentRenal and urinary disorders
AnaemiaBlood and lymphatic system disorders
Atrial flutterCardiac disorders
Atrioventricular block completeCardiac disorders
Ventricular tachycardiaCardiac disorders
PneumoniaInfections and infestations
HypokalaemiaMetabolism and nutrition disorders
Renal failureRenal and urinary disorders
Chronic kidney diseaseRenal and urinary disorders
Acute kidney injuryRenal and urinary disorders
Implantable defibrillator insertionSurgical and medical procedures
Acute myocardial infarctionCardiac disorders
Angina pectorisCardiac disorders
Angina unstableCardiac disorders
Atrial tachycardiaCardiac disorders
Cardiac arrestCardiac disorders
Cardiac failure acuteCardiac disorders
Cardiac failure congestiveCardiac disorders
Cardio-respiratory arrestCardiac disorders
Coronary artery diseaseCardiac disorders
Low cardiac output syndromeCardiac disorders
Other adverse events (12 terms — click to expand)

ReactionSystemPlaceboNeladenoson Bialanate 5mgNeladenoson Bialanate 10mgNeladenoson Bialanate 20mgNeladenoson Bialanate 30mgNeladenoson Bialanate 40mg
Cardiac failureCardiac disorders
Renal impairmentRenal and urinary disorders
HeadacheNervous system disorders
NauseaGastrointestinal disorders
HypotensionVascular disorders
AstheniaGeneral disorders
Urinary tract infectionInfections and infestations
DizzinessNervous system disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Abdominal painGastrointestinal disorders
FatigueGeneral disorders
HyperglycaemiaMetabolism and nutrition disorders

Most-reported serious reactions: Cardiac failure, Cardiac failure chronic, Atrial fibrillation, Cardiogenic shock, Renal impairment, Anaemia, Atrial flutter, Atrioventricular block complete.

Data from ClinicalTrials.gov NCT02992288 adverse events section.

Sponsor's own description

The objective of the study is to find the optimal dose of once daily oral neladenoson bialanate (BAY 1067197) when given in addition to standard therapy for heart failure with reduced ejection fraction (HFrEF).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Hypoxia signaling in human diseases and therapeutic targets.
    Lee JW, Ko J, Ju C, Eltzschig HK. · · 2019 · cited 272× · PMID 31221962 · DOI 10.1038/s12276-019-0235-1
  2. Targeting the Mitochondria in Heart Failure: A Translational Perspective.
    Sabbah HN. · · 2020 · cited 98× · PMID 32043022 · DOI 10.1016/j.jacbts.2019.07.009
  3. The hypoxia-adenosine link during inflammation.
    Bowser JL, Lee JW, Yuan X, Eltzschig HK. · · 2017 · cited 90× · PMID 28798196 · DOI 10.1152/japplphysiol.00101.2017
  4. Safety and efficacy of the partial adenosine A1 receptor agonist neladenoson bialanate in patients with chronic heart failure with reduced ejection fraction: a phase IIb, randomized, double-blind, placebo-controlled trial.
    Voors AA, Bax JJ, Hernandez AF, Wirtz AB, et al · · 2019 · cited 24× · PMID 31523892 · DOI 10.1002/ejhf.1591
  5. The Adenosinergic System as a Therapeutic Target in the Vasculature: New Ligands and Challenges.
    Sousa JB, Diniz C. · · 2017 · cited 17× · PMID 28481238 · DOI 10.3390/molecules22050752
  6. Clinical Validation of Novel Digital Measures: Statistical Methods for Reliability Evaluation.
    Ratitch B, Trigg A, Majumder M, Vlajnic V, et al · · 2023 · cited 10× · PMID 37588480 · DOI 10.1159/000531054
  7. The developmental journey of therapies targeting purine receptors: from basic science to clinical trials.
    Han S, Suzuki-Kerr H, Vlajkovic SM, Thorne PR. · · 2022 · cited 9× · PMID 36173587 · DOI 10.1007/s11302-022-09896-w
  8. Pharmacological Insights Into Safety and Efficacy Determinants for the Development of Adenosine Receptor Biased Agonists in the Treatment of Heart Failure.
    Rueda P, Merlin J, Chimenti S, Feletou M, et al · · 2021 · cited 4× · PMID 33776771 · DOI 10.3389/fphar.2021.628060

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02992288.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing